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Sample records for high-fat diet-induced hypertension

  1. Maternal Melatonin Therapy Rescues Prenatal Dexamethasone and Postnatal High-Fat Diet Induced Programmed Hypertension in Male Rat Offspring

    PubMed Central

    Tain, You-Lin; Sheen, Jiunn-Ming; Yu, Hong-Ren; Chen, Chih-Cheng; Tiao, Mao-Meng; Hsu, Chien-Ning; Lin, Yu-Ju; Kuo, Kuang-Che; Huang, Li-Tung

    2015-01-01

    Prenatal dexamethasone (DEX) exposure and high-fat (HF) intake are linked to hypertension. We examined whether maternal melatonin therapy prevents programmed hypertension synergistically induced by prenatal DEX plus postnatal HF in adult offspring. We also examined whether DEX and melatonin causes renal programming using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received intraperitoneal dexamethasone (0.1 mg/kg) or vehicle from gestational day 16 to 22. In the melatonin-treatment groups (M), rats received 0.01% melatonin in drinking water during their entire pregnancy and lactation. Male offspring were assigned to five groups: control, DEX, HF, DEX+HF, and DEX+HF+M. Male offspring in the HF group were fed a HF diet from weaning to 4 months of age. Prenatal DEX and postnatal HF diet synergistically induced programmed hypertension in adult offspring, which melatonin prevented. Maternal melatonin treatment modified over 3000 renal transcripts in the developing offspring kidney. Our NGS data indicate that PPAR signaling and fatty acid metabolism are two significantly regulated pathways. In addition, maternal melatonin therapy elicits longstanding alterations on renal programming, including regulation of the melatonin signaling pathway and upregulation of Agtr1b and Mas1 expression in the renin-angiotensin system (RAS), to protect male offspring against programmed hypertension. Postnatal HF aggravates prenatal DEX induced programmed hypertension in adult offspring, which melatonin prevented. The protective effects of melatonin on programmed hypertension is associated with regulation of the RAS and melatonin receptors. The long-term effects of maternal melatonin therapy on renal transcriptome require further clarification. PMID:26696906

  2. Serotonin Improves High Fat Diet Induced Obesity in Mice.

    PubMed

    Watanabe, Hitoshi; Nakano, Tatsuya; Saito, Ryo; Akasaka, Daisuke; Saito, Kazuki; Ogasawara, Hideki; Minashima, Takeshi; Miyazawa, Kohtaro; Kanaya, Takashi; Takakura, Ikuro; Inoue, Nao; Ikeda, Ikuo; Chen, Xiangning; Miyake, Masato; Kitazawa, Haruki; Shirakawa, Hitoshi; Sato, Kan; Tahara, Kohji; Nagasawa, Yuya; Rose, Michael T; Ohwada, Shyuichi; Watanabe, Kouichi; Aso, Hisashi

    2016-01-01

    There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle. PMID:26766570

  3. High-carbohydrate, high-fat diet-induced metabolic syndrome and cardiovascular remodeling in rats.

    PubMed

    Panchal, Sunil K; Poudyal, Hemant; Iyer, Abishek; Nazer, Reeza; Alam, Md Ashraful; Diwan, Vishal; Kauter, Kathleen; Sernia, Conrad; Campbell, Fiona; Ward, Leigh; Gobe, Glenda; Fenning, Andrew; Brown, Lindsay

    2011-05-01

    The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome. PMID:21572266

  4. Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

    PubMed

    Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

    2016-04-01

    Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. PMID:26740595

  5. Chlorella Protein Hydrolysate Attenuates Glucose Metabolic Disorder and Fatty Liver in High-fat Diet-induced Obese Mice.

    PubMed

    Noguchi, Naoto; Yanagita, Teruyoshi; Rahman, Shaikh Mizanoor; Ando, Yotaro

    2016-07-01

    Chlorella (Parachlorella beijerinckii) powder is reported to show a preventive effect against metabolic syndromes such as arteriosclerosis, hyperlipidemia, and hypertension. Approximately 60% of the chlorella content is protein. In order to understand the role of chlorella protein, we prepared a chlorella protein hydrolysate (CPH) by protease treatment. Male C57BL/6 mice were divided into three groups: a normal diet group, high-fat diet (HFD) group, and high-fat diet supplemented with CPH (HFD+CPH) group. The CPH administration improved glucose intolerance, insulin sensitivity, and adipose tissue hypertrophy in the high-fat diet-fed mice. In addition, the HFD+CPH group had significantly decreased liver total cholesterol and triglyceride levels compared with those in the HFD group. Furthermore, the HFD+CPH group had a decreased level of monocyte chemotactic protein-1 (MCP-1) in serum and a lower MCP-1 mRNA expression level in adipose tissue compared with the HFD group. The present study suggests that chlorella protein hydrolysate can prevent a high-fat diet-induced glucose disorder and fatty liver by inhibiting adipocyte hypertrophy and reducing the MCP-1 protein and gene expression. PMID:27321121

  6. Antihyperlipidemic and Antioxidant Potential of Paeonia emodi Royle against High-Fat Diet Induced Oxidative Stress

    PubMed Central

    Zargar, Bilal A.; Masoodi, Mubashir H.; Ahmed, Bahar; Ganie, Showkat A.

    2014-01-01

    The present study was intended to evaluate the effects of Paeonia emodi rhizome extracts on serum triglycerides (TGs), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c), high density lipoprotein cholesterol (HDL-c), atherogenic index (AI), superoxide dismutase (SOD), and glutathione peroxidase (GPx). The plant was extensively examined for its in vitro antioxidant activity, and the preliminary phytochemical screening was carried out using standard protocols. Male Wistar rats were induced with hyperlipidemia using high-fat diet and were treated orally with hydroalcoholic and aqueous extracts at the dose of 200 mg/kg bw for 30 days. TGs, TC, LDL-c, and AI were significantly reduced while HDL-c, SOD, and GPx levels rose to a considerable extent. After subjecting to acute toxicity testing, the extracts were found to be safe. The observations suggest antihyperlipidemic and antioxidant potential of P. emodi in high-fat diet induced hyperlipidemic/oxidative stressed rats. PMID:24734192

  7. Sirt1 protects against high-fat diet-induced metabolic damage

    PubMed Central

    Pfluger, Paul T.; Herranz, Daniel; Velasco-Miguel, Susana; Serrano, Manuel; Tschöp, Matthias H.

    2008-01-01

    The identification of new pharmacological approaches to effectively prevent, treat, and cure the metabolic syndrome is of crucial importance. Excessive exposure to dietary lipids causes inflammatory responses, deranges the homeostasis of cellular metabolism, and is believed to constitute a key initiator of the metabolic syndrome. Mammalian Sirt1 is a protein deacetylase that has been involved in resveratrol-mediated protection from high-fat diet-induced metabolic damage, but direct proof for the implication of Sirt1 has remained elusive. Here, we report that mice with moderate overexpression of Sirt1 under the control of its natural promoter exhibit fat mass gain similar to wild-type controls when exposed to a high-fat diet. Higher energy expenditure appears to be compensated by a parallel increase in food intake. Interestingly, transgenic Sirt1 mice under a high-fat diet show lower lipid-induced inflammation along with better glucose tolerance, and are almost entirely protected from hepatic steatosis. We present data indicating that such beneficial effects of Sirt1 are due to at least two mechanisms: induction of antioxidant proteins MnSOD and Nrf1, possibly via stimulation of PGC1α, and lower activation of proinflammatory cytokines, such as TNFα and IL-6, via down-modulation of NFκB activity. Together, these results provide direct proof of the protective potential of Sirt1 against the metabolic consequences of chronic exposure to a high-fat diet. PMID:18599449

  8. Apelin administration ameliorates high fat diet-induced cardiac hypertrophy and contractile dysfunction.

    PubMed

    Ceylan-Isik, Asli F; Kandadi, Machender R; Xu, Xihui; Hua, Yinan; Chicco, Adam J; Ren, Jun; Nair, Sreejayan

    2013-10-01

    Apelin has been recognized as an adipokine that plays an important role in regulating energy metabolism and is credited with antiobesity and antidiabetic properties. This study was designed to examine the effect of exogenous apelin on obesity-associated cardiac dysfunction. Oral glucose tolerance test, echocardiography, cardiomyocyte contractile and intracellular Ca(2+) properties were assessed in adult C57BL/6J mice fed - low or a - high-fat diet for 24weeks followed by apelin treatment (100nmol/kg, i.p. for 2weeks). High-fat diet resulted in increased left ventricular diastolic and systolic diameters, and wall thickness, compromised fractional shortening, impaired cardiomyocyte mechanics (peak-shortening, maximal velocity of shortening/relengthening, and duration of shortening and relengthening) and compromised intracellular Ca(2+) handling, all of which were reconciled by apelin. Apelin treatment also reversed high fat diet-induced changes in intracellular Ca(2+) regulatory proteins, ER stress, and autophagy. In addition, microRNAs (miR) -133a, miR-208 and miR-1 which were elevated following high-fat feeding were attenuated by apelin treatment. In cultured cardiomyocytes apelin reconciled palmitic acid-induced cardiomyocyte contractile anomalies. Collectively, these data depict a pivotal role of apelin in obesity-associated cardiac contractile dysfunction, suggesting a therapeutic potential of apelin in the management of cardiac dysfunction associated with obesity. PMID:23859766

  9. Prior exercise training blunts short-term high-fat diet-induced weight gain.

    PubMed

    Snook, Laelie A; MacPherson, Rebecca E K; Monaco, Cynthia M F; Frendo-Cumbo, Scott; Castellani, Laura; Peppler, Willem T; Anderson, Zachary G; Buzelle, Samyra L; LeBlanc, Paul J; Holloway, Graham P; Wright, David C

    2016-08-01

    High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (-30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet. PMID:27101294

  10. Effect of Morinda citrifolia (Noni) Fruit Juice on High Fat Diet Induced Dyslipidemia in Rats

    PubMed Central

    Shoeb, Ahsan; Alwar, M.C.; Gokul, P.

    2016-01-01

    Introduction The medicinal value of Morinda citrifolia L. (commonly known as Noni) has been explored in ancient folk remedies with a wide range of therapeutic utility, including antibacterial, antiviral, antifungal, antitumour, analgesic, hypotensive, anti-inflammatory and immune enhancing effects. Aim The present study was designed to evaluate the effects of Noni fruit juice on serum lipid profile in high fat diet induced murine model of dyslipidemia. Materials and Methods Hyperlipidemia was induced by feeding a cholesterol rich high fat diet for 45 days in wistar albino rats of either sex (n=8). Noni fruit juice administered at 50mg/kg/day and 100mg/kg/day, per oral, was compared with the standard drug Atorvastatin (10mg/kg/day, oral) fed for the latter 30 days. The blood samples were then sent for complete blood lipid profile, after 30 days of treatment. The data presented as mean ± SEM was analyzed using one-way ANOVA followed by Tukey’s post-hoc test. The p <0.05 was considered as statistically significant. Results The Noni fruit juice treated group showed a significant decrease in the total cholesterol, triglycerides and very low density lipoprotein - Cholesterol at both the doses when compared to the disease control (p<0.05). However, the decrease in the TC (102.75±9.79 mg/dL) and LDL-C (47.87±7.47 mg/dL) levels observed with the noni fruit juice at the 50mg/kg dose employed, failed to show a statistical significance when compared to atorvastatin. Conclusion The present study provides evidence for the hypolipidemic activity of Noni fruit juice in high fat diet induced hyperlipidemia in rats. PMID:27190827

  11. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats.

    PubMed

    Kumar, V; Bhandari, Uma; Tripathi, C D; Khanna, Geetika

    2014-07-01

    Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na(+)/K(+) ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na(+)/K(+) ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus. PMID:25284929

  12. Protective Effect of Gymnema sylvestre Ethanol Extract on High Fat Diet-induced Obese Diabetic Wistar Rats

    PubMed Central

    Kumar, V.; Bhandari, Uma; Tripathi, C. D.; Khanna, Geetika

    2014-01-01

    Obesity is associated with numerous co-morbidities such as cardiovascular diseases, type 2 diabetes, hypertension and others. Therefore, the present study was planned to investigate the effect of water- soluble fraction of Gymnema sylvestre ethanol extract on biochemical and molecular alterations in obese diabetic rats. Diabetes was induced by single i.v. injection of streptozotocin (45 mg/kg) via tail vein. Obesity was induced by oral feeding of high fat diet for a period of 28 days in diabetic rats. Body weight gain, food intake, water intake, hemodynamic parameters (systolic, diastolic, mean arterial blood pressures and heart rate), serum biochemical parameters (leptin, insulin, lipid levels, apolipoprotein B and glucose), cardiomyocyte apoptosis (cardiac caspase-3, Na+/K+ ATPase activity and DNA fragmentation) organs and visceral fat pad weight and oxidative stress parameters were measured. Oral treatment with water soluble fraction of Gymnema sylvestre ethanol extracts (120 mg/kg/p.o.) for a period of 21 days, resulted in significant reduction in heart rate, mean arterial pressure, serum leptin, insulin, apolipoprotein B, lipids, glucose, cardiac caspase-3 levels, Na+/K+ ATPase activity and DNA laddering, visceral fat pad and organ's weight and improved the antioxidant enzymes levels in the high fat diet induced obesity in diabetic rats. The results of present study reveal that water soluble fraction of Gymnema sylvestre ethanol extract could be useful intervention in the treatment of obesity and type-2 diabetes mellitus. PMID:25284929

  13. Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance.

    PubMed

    Amine, Hamza; Benomar, Yacir; Haimeur, Adil; Messaouri, Hafida; Meskini, Nadia; Taouis, Mohammed

    2016-01-01

    The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurita overcomes HFD-induced insulin resistance through the inhibition of TLR4/JNK/p38 MAP kinase signaling pathways. PMID:26459640

  14. Obesity Takes Its Toll on Visceral Pain: High-Fat Diet Induces Toll-Like Receptor 4-Dependent Visceral Hypersensitivity

    PubMed Central

    Dinan, Timothy G.; Cryan, John F.

    2016-01-01

    Exposure to high-fat diet induces both, peripheral and central alterations in TLR4 expression. Moreover, functional TLR4 is required for the development of high-fat diet-induced obesity. Recently, central alterations in TLR4 expression have been associated with the modulation of visceral pain. However, it remains unknown whether there is a functional interaction between the role of TLR4 in diet-induced obesity and in visceral pain. In the present study we investigated the impact of long-term exposure to high-fat diet on visceral pain perception and on the levels of TLR4 and Cd11b (a microglial cell marker) protein expression in the prefrontal cortex (PFC) and hippocampus. Peripheral alterations in TLR4 were assessed following the stimulation of spleenocytes with the TLR4-agonist LPS. Finally, we evaluated the effect of blocking TLR4 on visceral nociception, by administering TAK-242, a selective TLR4-antagonist. Our results demonstrated that exposure to high-fat diet induced visceral hypersensitivity. In parallel, enhanced TLR4 expression and microglia activation were found in brain areas related to visceral pain, the PFC and the hippocampus. Likewise, peripheral TLR4 activity was increased following long-term exposure to high-fat diet, resulting in an increased level of pro-inflammatory cytokines. Finally, TLR4 blockage counteracted the hyperalgesic phenotype present in mice fed on high-fat diet. Our data reveal a role for TLR4 in visceral pain modulation in a model of diet-induced obesity, and point to TLR4 as a potential therapeutic target for the development of drugs to treat visceral hypersensitivity present in pathologies associated to fat diet consumption. PMID:27159520

  15. Eicosapentaenoic acid reduces high-fat diet-induced insulin resistance by altering adipose tissue glycolytic and inflammatory function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously reported Eicosapentaenoic Acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity, insulin resistance, and inflammation. In this study, we dissected mechanisms mediating anti-inflammatory and anti-lipogenic actions of EPA, using histology/ immunohistochemistry, transcriptomi...

  16. Eicosapentaenoic acid prevents high fat diet-induced metabolic disorders: Genomic and metabolomic analyses of underlying mechanism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously our lab demonstrated eicosapenaenoic acid (EPA)'s ability to prevent high-fat (HF) diet-induced obesity by decreasing insulin resistance, glucose intolerance and inflammation. In the current study, we used genomic and metabolomic approaches to further investigate the molecular basis for t...

  17. Lamp-2 deficiency prevents high-fat diet-induced obese diabetes via enhancing energy expenditure

    SciTech Connect

    Yasuda-Yamahara, Mako; Kume, Shinji; Yamahara, Kosuke; Nakazawa, Jun; Chin-Kanasaki, Masami; Araki, Hisazumi; Araki, Shin-ichi; Koya, Daisuke; Haneda, Masakzu; Ugi, Satoshi; Maegawa, Hiroshi; Uzu, Takashi

    2015-09-18

    Autophagy process is essential for maintaining intracellular homeostasis and consists of autophagosome formation and subsequent fusion with lysosome for degradation. Although the role of autophagosome formation in the pathogenesis of diabetes has been recently documented, the role of the latter process remains unclear. This study analyzed high-fat diet (HFD)-fed mice lacking lysosome-associated membrane protein-2 (lamp-2), which is essential for the fusion with lysosome and subsequent degradation of autophagosomes. Although lamp-2 deficient mice showed little alteration in glucose metabolism under normal diet feeding, they showed a resistance against high-fat diet (HFD)-induced obesity, hyperinsulinemic hyperglycemia and tissues lipid accumulation, accompanied with higher energy expenditure. The expression levels of thermogenic genes in brown adipose tissue were significantly increased in HFD-fed lamp-2-deficient mice. Of some serum factors related to energy expenditure, the serum level of fibroblast growth factor (FGF) 21 and its mRNA expression level in the liver were significantly higher in HFD-fed lamp-2-deficient mice in an ER stress-, but not PPARα-, dependent manner. In conclusion, a lamp-2-depenedent fusion and degradation process of autophagosomes is involved in the pathogenesis of obese diabetes, providing a novel insight into autophagy and diabetes. - Highlights: • Lamp-2 is essential for autophagosome fusion with lysosome and its degradation. • Lamp-2 deficiency lead to a resistance to diet-induced obese diabetes in mice. • Lamp-2 deficiency increased whole body energy expenditure under HFD-feeding. • Lamp-2 deficiency elevated the serum level of FGF21 under HFD-feeding.

  18. Unaltered Prion Pathogenesis in a Mouse Model of High-Fat Diet-Induced Insulin Resistance

    PubMed Central

    Zhu, Caihong; Schwarz, Petra; Abakumova, Irina; Aguzzi, Adriano

    2015-01-01

    Epidemiological, clinical, and experimental animal studies suggest a strong correlation between insulin resistance and Alzheimer’s disease. In fact, type-2 diabetes is considered an important risk factor of developing Alzheimer’s disease. In addition, impaired insulin signaling in the Alzheimer’s disease brain may promote Aβ production, impair Aβ clearance and induce tau hyperphosphorylation, thereby leading to deterioration of the disease. The pathological prion protein, PrPSc, deposits in the form of extracellular aggregates and leads to dementia, raising the question as to whether prion pathogenesis may also be affected by insulin resistance. We therefore established high-fat diet-induced insulin resistance in tga20 mice, which overexpress the prion protein. We then inoculated the insulin-resistant mice with prions. We found that insulin resistance in tga20 mice did not affect prion disease progression, PrPSc deposition, astrogliosis or microglial activation, and had no effect on survival. Our study demonstrates that in a mouse model, insulin resistance does not significantly contribute to prion pathogenesis. PMID:26658276

  19. High Fat Diet Induces Adhesion of Platelets to Endothelium in Two Models of Dyslipidemia

    PubMed Central

    Gonzalez, Jaime; Donoso, Wendy; Díaz, Natalia; Albornoz, María Eliana; Huilcaman, Ricardo; Morales, Erik

    2014-01-01

    Cardiovascular diseases (CVD) represent about 30% of all global deaths. It is currently accepted that, in the atherogenic process, platelets play an important role, contributing to endothelial activation and modulation of the inflammatory phenomenon, promoting the beginning and formation of lesions and their subsequent thrombotic complications. The objective of the present work was to study using immunohistochemistry, the presence of platelets, monocytes/macrophages, and cell adhesion molecules (CD61, CD163, and CD54), in two stages of the atheromatous process. CF-1 mice fed a fat diet were used to obtain early stages of atheromatous process, denominated early stage of atherosclerosis, and ApoE−/− mice fed a fat diet were used to observe advanced stages of atherosclerosis. The CF-1 mice model presented immunostaining on endothelial surface for all three markers studied; the advanced atherosclerosis model in ApoE−/− mice also presented granular immunostaining on lesion thickness, for the same markers. These results suggest that platelets participate in atheromatous process from early stages to advance d stages. High fat diet induces adhesion of platelets to endothelial cells in vivo. These findings support studying the participation of platelets in the formation of atheromatous plate. PMID:25328689

  20. Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet-induced Metabolic Disorder

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals’ access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity. PMID:27189661

  1. Alternating Diet as a Preventive and Therapeutic Intervention for High Fat Diet-induced Metabolic Disorder.

    PubMed

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    This study presents the alternating diet as a new strategy in combating obesity and metabolic diseases. Lean or obese mice were fed a high-fat diet (HFD) for five days and switched to a regular diet for one (5 + 1), two (5 + 2), or five (5 + 5) days before switching back to HFD to start the second cycle, for a total of eight weeks (for prevention) or five weeks (for treatment) without limiting animals' access to food. Our results showed that animals with 5 + 2 and 5 + 5 diet alternations significantly inhibited body weight and fat mass gain compared to animals fed an HFD continuously. The dietary switch changed the pattern of daily caloric intake and suppressed HFD-induced adipose macrophage infiltration and chronic inflammation, resulting in improved insulin sensitivity and alleviated fatty liver. Alternating diet inhibited HFD-induced hepatic Pparγ-mediated lipid accumulation and activated the expression of Pparα and its target genes. Alternating diet in the 5 + 5 schedule induced weight loss in obese mice and reversed the progression of metabolic disorders, including hepatic steatosis, glucose intolerance, and inflammation. The results provide direct evidence to support that alternating diet represents a new intervention in dealing with the prevalence of diet-induced obesity. PMID:27189661

  2. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  3. Preventing High Fat Diet-induced Obesity and Improving Insulin Sensitivity through Neuregulin 4 Gene Transfer.

    PubMed

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

    Neuregulin 4 (NRG4), an epidermal growth factor-like signaling molecule, plays an important role in cell-to-cell communication during tissue development. Its function to regulate energy metabolism has recently been reported. This current study was designed to assess the preventive and therapeutic effects of NRG4 overexpression on high fat diet (HFD)-induced obesity. Using the hydrodynamic gene transfer method, we demonstrate that Nrg4 gene transfer in mice suppressed the development of diet-induced obesity, but did not affect pre-existing adiposity and body weight in obese mice. Nrg4 gene transfer curbed HFD-induced hepatic steatosis by inhibiting lipogenesis and PPARγ-mediated lipid storage. Concurrently, overexpression of NRG4 reduced chronic inflammation in both preventive and treatment studies, evidenced by lower mRNA levels of macrophage marker genes including F4/80, Cd68, Cd11b, Cd11c, and macrophage chemokine Mcp1, resulting in improved insulin sensitivity. Collectively, these results demonstrate that overexpression of the Nrg4 gene by hydrodynamic gene delivery prevents HFD-induced weight gain and fatty liver, alleviates obesity-induced chronic inflammation and insulin resistance, and supports the health benefits of NRG4 in managing obesity and obesity-associated metabolic disorders. PMID:27184920

  4. Antihyperlipidemic and antiatherogenic activities of Terminalia pallida Linn. fruits in high fat diet-induced hyperlipidemic rats.

    PubMed

    Sampathkumar, M T; Kasetti, R B; Nabi, S A; Sudarshan, P Renuka; Swapna, S; Apparao, C

    2011-07-01

    Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and coronary heart disease (CHD). Although synthetic lipid-lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. So the current interest has stimulated the search for new lipid-lowering agents with minimal side effects from natural sources. The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Terminalia pallida fruits in high fat diet-induced hyperlipidemic rats. T. pallida fruits ethanolic extract (TPEt) was prepared using Soxhlet apparatus. Sprague-Dawley male rats were made hyperlipidemic by giving high fat diet, supplied by NIN (National Institute of Nutrition), Hyderabad, India. TPEt was administered in a dose of 100 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The body weights, plasma lipid, and lipoprotein levels were measured before and after the treatment. TPEt showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels coupled together with elevation of high-density lipoprotein cholesterol levels and diminution of atherogenic index in high fat diet-induced hyperlipidemic rats. There was a significantly reduced body weight gain in TPEt-treated hyperlipidemic rats than in the control group. The present study demonstrates that TPEt possesses significant antihyperlipidemic and antiatherogenic properties, thus suggesting its beneficial effect in the treatment of cardiovascular diseases. PMID:21966168

  5. Antihyperlipidemic and antiatherogenic activities of Terminalia pallida Linn. fruits in high fat diet-induced hyperlipidemic rats

    PubMed Central

    Sampathkumar, M. T.; Kasetti, R. B.; Nabi, S. A.; Sudarshan, P. Renuka; Swapna, S.; Apparao, C.

    2011-01-01

    Hyperlipidemia contributes significantly in the manifestation and development of atherosclerosis and coronary heart disease (CHD). Although synthetic lipid-lowering drugs are useful in treating hyperlipidemia, there are number of adverse effects. So the current interest has stimulated the search for new lipid-lowering agents with minimal side effects from natural sources. The present study was designed to investigate the antihyperlipidemic and antiatherogenic potentiality of ethanolic extract of Terminalia pallida fruits in high fat diet-induced hyperlipidemic rats. T. pallida fruits ethanolic extract (TPEt) was prepared using Soxhlet apparatus. Sprague-Dawley male rats were made hyperlipidemic by giving high fat diet, supplied by NIN (National Institute of Nutrition), Hyderabad, India. TPEt was administered in a dose of 100 mg/kg.b.w./day for 30 days in high fat diet-induced hyperlipidemic rats. The body weights, plasma lipid, and lipoprotein levels were measured before and after the treatment. TPEt showed significant antihyperlipidemic and antiatherogenic activities as evidenced by significant decrease in plasma total cholesterol, triglycerides, low-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol levels coupled together with elevation of high-density lipoprotein cholesterol levels and diminution of atherogenic index in high fat diet-induced hyperlipidemic rats. There was a significantly reduced body weight gain in TPEt-treated hyperlipidemic rats than in the control group. The present study demonstrates that TPEt possesses significant antihyperlipidemic and antiatherogenic properties, thus suggesting its beneficial effect in the treatment of cardiovascular diseases. PMID:21966168

  6. Mediobasal hypothalamic overexpression of DEPTOR protects against high-fat diet-induced obesity

    PubMed Central

    Caron, Alexandre; Labbé, Sébastien M.; Lanfray, Damien; Blanchard, Pierre-Gilles; Villot, Romain; Roy, Christian; Sabatini, David M.; Richard, Denis; Laplante, Mathieu

    2015-01-01

    Background/Objective The mechanistic target of rapamycin (mTOR) is a serine–threonine kinase that functions into distinct protein complexes (mTORC1 and mTORC2) that regulate energy homeostasis. DEP-domain containing mTOR-interacting protein (DEPTOR) is part of these complexes and is known to dampen mTORC1 function, consequently reducing mTORC1 negative feedbacks and promoting insulin signaling and Akt/PKB activation in several models. Recently, we observed that DEPTOR is expressed in several structures of the brain including the mediobasal hypothalamus (MBH), a region that regulates energy balance. Whether DEPTOR in the MBH plays a functional role in regulating energy balance and hypothalamic insulin signaling has never been tested. Methods We have generated a novel conditional transgenic mouse model based on the Cre-LoxP system allowing targeted overexpression of DEPTOR. Mice overexpressing DEPTOR in the MBH were subjected to a metabolic phenotyping and MBH insulin signaling was evaluated. Results We first report that systemic (brain and periphery) overexpression of DEPTOR prevents high-fat diet-induced obesity, improves glucose metabolism and protects against hepatic steatosis. These phenotypes were associated with a reduction in food intake and feed efficiency and an elevation in oxygen consumption. Strikingly, specific overexpression of DEPTOR in the MBH completely recapitulated these phenotypes. DEPTOR overexpression was associated with an increase in hypothalamic insulin signaling, as illustrated by elevated Akt/PKB activation. Conclusion Altogether, these results support a role for MBH DEPTOR in the regulation of energy balance and metabolism. PMID:26909318

  7. Clostridium ramosum Promotes High-Fat Diet-Induced Obesity in Gnotobiotic Mouse Models

    PubMed Central

    Woting, Anni; Pfeiffer, Nora; Loh, Gunnar; Klaus, Susanne

    2014-01-01

    ABSTRACT The intestines of obese humans and mice are enriched with Erysipelotrichi, a class within the Firmicutes. Clostridium ramosum, a member of the Erysipelotrichi, is associated with symptoms of the metabolic syndrome in humans. To clarify the possible obesogenic potential of this bacterial species and to unravel the underlying mechanism, we investigated the role of C. ramosum in obesity development in gnotobiotic mice. Mice were associated with a simplified human intestinal (SIHUMI) microbiota of eight bacterial species, including C. ramosum, with the SIHUMI microbiota except C. ramosum (SIHUMIw/oCra), or with C. ramosum only (Cra) and fed a high-fat diet (HFD) or a low-fat diet (LFD). Parameters related to the development of obesity and metabolic diseases were compared. After 4 weeks of HFD feeding, the mouse groups did not differ in energy intake, diet digestibility, gut permeability, and parameters of low-grade inflammation. However, SIHUMI and Cra mice fed the HFD gained significantly more body weight and body fat and displayed higher food efficiency than SIHUMIw/oCra mice fed the HFD. Gene expression of glucose transporter 2 (Glut2) in jejunal mucosa and of fatty acid translocase (CD36) in ileal mucosa was significantly increased in the obese SIHUMI and Cra mice compared with the less obese SIHUMIw/oCra mice. The data demonstrate that the presence of C. ramosum in SIHUMI and Cra mice enhanced diet-induced obesity. Upregulation of small intestinal glucose and fat transporters in these animals may contribute to their increased body fat deposition. PMID:25271283

  8. Beneficial effects of neomangiferin on high fat diet-induced nonalcoholic fatty liver disease in rats.

    PubMed

    Zhou, Chengyan; Zhou, Jingjing; Han, Na; Liu, Zhihui; Xiao, Bin; Yin, Jun

    2015-03-01

    This study was carried out to determine the effect and mechanism of action of neomangiferin (NG) on high-fat diet-induced nonalcoholic fatty liver disease (NAFLD) in rats. NAFLD rats were randomly assigned into several groups of equal number. NG (50, 25mg/kg·day(-1) BW) and lipanthyl (PT, 5mg/kg·day(-1) BW) were given to the NAFLD rats, respectively. In the study, serum lipids, metabolic rate, liver fat, liver lipids and histology were examined. To further investigate the molecular mechanism of the effect of NG on NAFLD, expression levels of mRNA and protein for peroxisome proliferator-activated receptor α (PPARα), fatty acid transport protein 2 (FATP2), long-chain-fatty-acid - CoA ligase 1 (ACSL1) and carnitine palmitoyltransferase 1a (CPT1a) in the liver were determined by Real Time-PCR and western blot analysis, respectively. NG administration significantly reduced the final body weight, liver fat accumulation, and serum triglyceride (TG), total cholesterol (TC) concentrations, low-density lipoprotein cholesterol (LDL-C), glucose (GLU) levels, and hepatic TG, TC, malondialdehyde (MDA) levels, but increased serum high-density lipoprotein cholesterol (HDL-C) and hepatic superoxide dismutase (SOD) levels. NG upregulated the mRNA and protein expression of PPARα and CPT1a, but downregulated the mRNA and protein expression of FATP2 and ACSL1 in the liver. These results suggested that NG can regulate NAFLD partly by modulating the expression levels of genes involved in FFA uptake and lipid oxidation. PMID:25661699

  9. Resveratrol Protects against High-Fat Diet Induced Renal Pathological Damage and Cell Senescence by Activating SIRT1.

    PubMed

    Zhang, Nannan; Li, Zhongchi; Xu, Kang; Wang, Yanying; Wang, Zhao

    2016-01-01

    Obesity-related renal diseases have been a worldwide issue. Effective strategy that prevents high fat-diet induced renal damage is of great significance. Resveratrol, a natural plant polyphenol, is famous for its antioxidant activity, cardioprotective effects and anticancer properties. However whether resveratrol can play a role in the treatment of renal diseases is unknown. In this study, we added resveratrol in normal glucose or high glucose medium and provide evidences that resveratrol protects against high-glucose triggered oxidative stress and cell senescence. Moreover, mice were fed with standard diet, standard diet plus resveratrol, high-fat diet or high-fat diet plus resveratrol for 3 months, and results show that resveratrol treatment prevents high-fat diet induced renal pathological damage by activating SIRT1, a key member in the mammalian sirtuin family that response to calorie restriction life-extension method. This research confirms the potential role of resveratrol in the treatment of renal diseases and may provide an effective and convenient method to mimic the beneficial effects of calorie restriction. PMID:27582325

  10. Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.

    PubMed

    Liang, Lei; Shou, Xi-Ling; Zhao, Hai-Kang; Ren, Gu-Qun; Wang, Jian-Bang; Wang, Xi-Hui; Ai, Wen-Ting; Maris, Jackie R; Hueckstaedt, Lindsay K; Ma, Ai-Qun; Zhang, Yingmei

    2015-02-01

    Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial

  11. Effects of chronic exercise on the endocannabinoid system in Wistar rats with high-fat diet-induced obesity.

    PubMed

    Gamelin, François-Xavier; Aucouturier, Julien; Iannotti, Fabio Arturo; Piscitelli, Fabiana; Mazzarella, Enrico; Aveta, Teresa; Leriche, Melissa; Dupont, Erwan; Cieniewski-Bernard, Caroline; Montel, Valérie; Bastide, Bruno; Di Marzo, Vincenzo; Heyman, Elsa

    2016-06-01

    The endocannabinoid system is dysregulated during obesity in tissues involved in the control of food intake and energy metabolism. We examined the effect of chronic exercise on the tissue levels of endocannabinoids (eCBs) and on the expression of genes coding for cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) (Cnr1 and Cnr2, respectively) in the subcutaneous (SAT) and visceral adipose tissues and in the soleus and extensor digitorim longus (EDL) muscles, in rats fed with standard or high-fat diet. Twenty-eight male Wistar rats were placed on high-fat diet or standard diet (HFD and Ctl groups, respectively) during 12 weeks whereafter half of each group was submitted to an exercise training period of 12 weeks (HFD + training and Ctl + training). Tissue levels of eCBs were measured by LC-MS while expressions of genes coding for CB1 and CB2 receptors were investigated by qPCR. High-fat diet induced an increase in anandamide (AEA) levels in soleus and EDL (p < 0.02). In soleus of the HFD group, these changes were accompanied by elevated Cnr1 messenger RNA (mRNA) levels (p < 0.05). In EDL, exercise training allowed to reduce significantly this diet-induced AEA increase (p < 0.005). 2-Arachidonoylglycerol (2-AG) levels were decreased and increased by high-fat diet in SAT and EDL, respectively (p < 0.04), but not affected by exercise training. Unlike the HFD + training group, 2-AG levels in soleus were also decreased in the HFD group compared to Ctl (p < 0.04). The levels of eCBs and Cnr1 expression are altered in a tissue-specific manner following a high-fat diet, and chronic exercise reverses some of these alterations. PMID:26880264

  12. Transgenic Rescue of Adipocyte Glucose-dependent Insulinotropic Polypeptide Receptor Expression Restores High Fat Diet-induced Body Weight Gain*

    PubMed Central

    Ugleholdt, Randi; Pedersen, Jens; Bassi, Maria Rosaria; Füchtbauer, Ernst-Martin; Jørgensen, Signe Marie; Kissow, Hanne-Louise; Nytofte, Nikolaj; Poulsen, Steen Seier; Rosenkilde, Mette Marie; Seino, Yutaka; Thams, Peter; Holst, Peter Johannes; Holst, Jens Juul

    2011-01-01

    The glucose-dependent insulinotropic polypeptide receptor (GIPr) has been implicated in high fat diet-induced obesity and is proposed as an anti-obesity target despite an uncertainty regarding the mechanism of action. To independently investigate the contribution of the insulinotropic effects and the direct effects on adipose tissue, we generated transgenic mice with targeted expression of the human GIPr to white adipose tissue or beta-cells, respectively. These mice were then cross-bred with the GIPr knock-out strain. The central findings of the study are that mice with GIPr expression targeted to adipose tissue have a similar high fat diet -induced body weight gain as control mice, significantly greater than the weight gain in mice with a general ablation of the receptor. Surprisingly, this difference was due to an increase in total lean body mass rather than a gain in total fat mass that was similar between the groups. In contrast, glucose-dependent insulinotropic polypeptide-mediated insulin secretion does not seem to be important for regulation of body weight after high fat feeding. The study supports a role of the adipocyte GIPr in nutrient-dependent regulation of body weight and lean mass, but it does not support a direct and independent role for the adipocyte or beta-cell GIPr in promoting adipogenesis. PMID:22027838

  13. Anti-obesity and cardioprotective effects of cinnamic acid in high fat diet- induced obese rats.

    PubMed

    Mnafgui, Kais; Derbali, Amal; Sayadi, Sami; Gharsallah, Neji; Elfeki, Abdelfattah; Allouche, Noureddine

    2015-07-01

    Obesity is a chronic metabolic disorder that is associated with numerous diseases including hyperlipidemia, diabetes mellitus, hypertension, atherosclerosis, cardiovascular disease, and cancer. Cinnamic acid is a phytochemical compound having many biological effects and could be considered for the management of obesity. This study is aimed to assess the possible anti-obesity and cardioprotective properties of cinnamic acid (CA) in high fat diet-fed rats (HFD). Male Wistar rats were divided into 4 groups. They received normal diet, HFD diet, HFD supplemented with fluvastatin (2 mg/kg/day) or cinnamic acid (30 mg/kg/day) for 7 weeks. The results showed an increase in body weight of HFD rats by ~27 % as compared to control group. Moreover, serum lipase activity underwent a significant rise by 103 % which led to an increase in the levels of total cholesterol (T-Ch), triglycerides (TG), LDL-cholesterol in serum of untreated HFD-fed rats. Furthermore, the concentration of leptin and angiotensin-converting enzyme (ACE) activity exhibited remarkable increases in serum of HFD-fed rats as compared to controls. Whereas, the administration of CA to HFD-fed rats improved the body weight gain and serum lipid profile and reverted back near to normal the activities of lipase and ACE. In addition, the echocardiography evidenced that CA is able to protect the aorta and aortic arch and avoided vasoconstriction by increasing their diameters and improved liver steatosis and kidney indices of toxicity. Overall, these results suggest that cinnamic acid exerts anti-obesity and antihypertensive effects through inhibition of lipid digestive enzymes and ACE. PMID:26139902

  14. High Fat and High Sucrose (Western) Diet Induce Steatohepatitis that is Dependent on Fructokinase

    PubMed Central

    Ishimoto, Takuji; Lanaspa, Miguel A.; Rivard, Christopher J.; Roncal-Jimenez, Carlos A.; Orlicky, David J.; Cicerchi, Christina; McMahan, Rachel H.; Abdelmalek, Manal F.; Rosen, Hugo R.; Jackman, Matthew R.; MacLean, Paul S.; Diggle, Christine P.; Asipu, Aruna; Inaba, Shinichiro; Kosugi, Tomoki; Sato, Waichi; Maruyama, Shoichi; Sánchez-Lozada, Laura G.; Sautin, Yuri Y.; Hill, James O.; Bonthron, David T.; Johnson, Richard J.

    2013-01-01

    Fructose intake from added sugars has been implicated as a cause of nonalcoholic fatty liver disease. Here we tested the hypothesis that fructose may interact with high fat diet to induce fatty liver, and to determine if this was dependent on a key enzyme in fructose metabolism, fructokinase. Wild type or fructokinase knockout mice were fed a low fat (11%), high fat (36%) or high fat (36%) and high sucrose (30%) diet for 15 weeks. Both wild type and fructokinase knockout mice developed obesity with mild hepatic steatosis and no evidence for hepatic inflammation on a high fat diet compared to a low fat diet. In contrast, wild type mice fed a high fat and high sucrose diet developed more severe hepatic steatosis with low grade inflammation and fibrosis, as noted by increased CD68, TNF-alpha, MCP-1, alpha-smooth muscle actin, and collagen I and TIMP1 expression. These changes were prevented in the fructokinase knockout mice. Conclusion An additive effect of high fat and high sucrose diet on the development of hepatic steatosis exists. Further, the combination of sucrose with high fat diet may induce steatohepatitis. The protection in fructokinase knockout mice suggests a key role for fructose (from sucrose) in this development of steatohepatitis. These studies emphasize the important role of fructose in the development of fatty liver and nonalcoholic steatohepatitis (NASH). PMID:23813872

  15. High-fat diet induced adiposity and insulin resistance in mice lacking the myotonic dystrophy protein kinase.

    PubMed

    Llagostera, Esther; Carmona, Mari Carmen; Vicente, Meritxell; Escorihuela, Rosa María; Kaliman, Perla

    2009-06-18

    Myotonic dystrophy 1 (MD1) is caused by a CTG expansion in the 3'-unstranslated region of the myotonic dystrophy protein kinase (DMPK) gene. MD1 patients frequently present insulin resistance and increased visceral adiposity. We examined whether DMPK deficiency is a genetic risk factor for high-fat diet-induced adiposity and insulin resistance using the DMPK knockout mouse model. We found that high-fat fed DMPK knockout mice had significantly increased body weights, hypertrophic adipocytes and whole-body insulin resistance compared with wild-type mice. This nutrient-genome interaction should be considered by physicians given the cardiometabolic risks and sedentary lifestyle associated with MD1 patients. PMID:19482024

  16. Gut carbohydrate metabolism instead of fat metabolism regulated by gut microbes mediates high-fat diet-induced obesity.

    PubMed

    Li, M; Gu, D; Xu, N; Lei, F; Du, L; Zhang, Y; Xie, W

    2014-09-01

    The aim of this study was to investigate the mechanisms underlying the involvement of gut microbes in body weight gain of high-fat diet-fed obesity-prone (obese) and obesity-resistant (lean) mice. C57BL/6 mice were grouped into an obese group, a lean group and a normal control group. Both obese and lean mice were fed a high-fat diet while normal control mice were fed a normal diet; they were observed for six weeks. The results showed that lean mice had lower serum lipid levels, body fat and weight gain than obese mice. The ATPase, succinate dehydrogenase and malate dehydrogenase activities in liver as well as oxygen expenditure and rectal temperature of lean mice were significantly lower than in obese mice. As compared with obese mice, the absorption of intestinal carbohydrates but not of fats or proteins was significantly attenuated in lean mice. Furthermore, 16S rRNA abundances of faecal Firmicutes and Bacteroidetes were significantly reduced in lean mice. In addition, faecal β-D-galactosidase activity and short chain fatty acid levels were significantly decreased in lean mice. Expressions of peroxisome proliferator-activated receptor gamma 2 and CCAAT/enhancer binding protein-β in visceral adipose tissues were significantly downregulated in lean mice as compared with obese mice. Resistance to dyslipidaemia and high-fat diet-induced obesity was mediated by ineffective absorption of intestinal carbohydrates but not of fats or proteins, probably through reducing gut Bacteroidetes and Firmicutes contents and lowering of gut carbohydrate metabolism. The regulation of intestinal carbohydrates instead of fat absorption by gut microbes might be a potential treatment strategy for high-fat diet-induced obesity. PMID:24675232

  17. TRPV1 Channels and Gastric Vagal Afferent Signalling in Lean and High Fat Diet Induced Obese Mice

    PubMed Central

    Kentish, Stephen J.; Frisby, Claudine L.; Kritas, Stamatiki; Li, Hui; Hatzinikolas, George; O’Donnell, Tracey A.; Wittert, Gary A.; Page, Amanda J.

    2015-01-01

    Aim Within the gastrointestinal tract vagal afferents play a role in control of food intake and satiety signalling. Activation of mechanosensitive gastric vagal afferents induces satiety. However, gastric vagal afferent responses to mechanical stretch are reduced in high fat diet mice. Transient receptor potential vanilloid 1 channels (TRPV1) are expressed in vagal afferents and knockout of TRPV1 reduces gastro-oesophageal vagal afferent responses to stretch. We aimed to determine the role of TRPV1 on gastric vagal afferent mechanosensitivity and food intake in lean and HFD-induced obese mice. Methods TRPV1+/+ and -/- mice were fed either a standard laboratory diet or high fat diet for 20wks. Gastric emptying of a solid meal and gastric vagal afferent mechanosensitivity was determined. Results Gastric emptying was delayed in high fat diet mice but there was no difference between TRPV1+/+ and -/- mice on either diet. TRPV1 mRNA expression in whole nodose ganglia of TRPV1+/+ mice was similar in both dietary groups. The TRPV1 agonist N-oleoyldopamine potentiated the response of tension receptors in standard laboratory diet but not high fat diet mice. Food intake was greater in the standard laboratory diet TRPV1-/- compared to TRPV1+/+ mice. This was associated with reduced response of tension receptors to stretch in standard laboratory diet TRPV1-/- mice. Tension receptor responses to stretch were decreased in high fat diet compared to standard laboratory diet TRPV1+/+ mice; an effect not observed in TRPV1-/- mice. Disruption of TRPV1 had no effect on the response of mucosal receptors to mucosal stroking in mice on either diet. Conclusion TRPV1 channels selectively modulate gastric vagal afferent tension receptor mechanosensitivity and may mediate the reduction in gastric vagal afferent mechanosensitivity in high fat diet-induced obesity. PMID:26285043

  18. High-Fat Diet-Induced IL-17A Exacerbates Psoriasiform Dermatitis in a Mouse Model of Steatohepatitis.

    PubMed

    Vasseur, Philippe; Serres, Laura; Jégou, Jean-François; Pohin, Mathilde; Delwail, Adriana; Petit-Paris, Isabelle; Levillain, Pierre; Favot, Laure; Samson, Michel; Yssel, Hans; Morel, Franck; Silvain, Christine; Lecron, Jean-Claude

    2016-09-01

    Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermal infiltrates of CD45(+) leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1β. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet-induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients. PMID:27423696

  19. Ameliorating effect of Allium Sativum on high-fat diet induced fatty liver in albino rats

    PubMed Central

    Qamar, Aisha; Usmani, Ambreen; Waqar, Humera; Siddiqui, Asma; Kumar, Hemant

    2016-01-01

    Objective: To assess the hepatoprotective effect provided by fresh garlic on fatty liver induced by high-fat diet. Methods: This experimental study was carried out at BMSI, JPMC from October to November 2008. Thirty adult albino rats, 200-240 gram weight, were divided into three groups. Group A received control diet, Group B received high-fat diet (20 mg butter/100 gm diet) and Group C received high-fat diet with fresh garlic (20 mg butter with 6 gm fresh garlic/100 gm diet). The groups were further divided on the basis of duration of treatment, four weeks and eight weeks respectively. The rats were sacrificed, liver removed, weighed and relative liver weight calculated. Hepatic tissue was processed and tissue slides stained with haematoxylin and eosin. Results: There was significant increase in relative liver weight in group B animals as compared to the control animals, which decreased significantly in group C. Haematoxylin and eosin stained sections revealed ballooned hepatocytes having vesicular appearance with pyknotic nuclei in high-fat group which were preserved to a great extent in group C animals. Conclusion: This study has shown that use of fresh garlic along with high-fat diet prevents its damaging effects on liver to a great extent. PMID:27182249

  20. High fat diet-induced diabetes in mice exacerbates cognitive deficit due to chronic hypoperfusion.

    PubMed

    Zuloaga, Kristen L; Johnson, Lance A; Roese, Natalie E; Marzulla, Tessa; Zhang, Wenri; Nie, Xiao; Alkayed, Farah N; Hong, Christine; Grafe, Marjorie R; Pike, Martin M; Raber, Jacob; Alkayed, Nabil J

    2016-07-01

    Diabetes causes endothelial dysfunction and increases the risk of vascular cognitive impairment. However, it is unknown whether diabetes causes cognitive impairment due to reductions in cerebral blood flow or through independent effects on neuronal function and cognition. We addressed this using right unilateral common carotid artery occlusion to model vascular cognitive impairment and long-term high-fat diet to model type 2 diabetes in mice. Cognition was assessed using novel object recognition task, Morris water maze, and contextual and cued fear conditioning. Cerebral blood flow was assessed using arterial spin labeling magnetic resonance imaging. Vascular cognitive impairment mice showed cognitive deficit in the novel object recognition task, decreased cerebral blood flow in the right hemisphere, and increased glial activation in white matter and hippocampus. Mice fed a high-fat diet displayed deficits in the novel object recognition task, Morris water maze and fear conditioning tasks and neuronal loss, but no impairments in cerebral blood flow. Compared to vascular cognitive impairment mice fed a low fat diet, vascular cognitive impairment mice fed a high-fat diet exhibited reduced cued fear memory, increased deficit in the Morris water maze, neuronal loss, glial activation, and global decrease in cerebral blood flow. We conclude that high-fat diet and chronic hypoperfusion impair cognitive function by different mechanisms, although they share commons features, and that high-fat diet exacerbates vascular cognitive impairment pathology. PMID:26661233

  1. DSS colitis promotes tumorigenesis and fibrogenesis in a choline-deficient high-fat diet-induced NASH mouse model.

    PubMed

    Achiwa, Koichi; Ishigami, Masatoshi; Ishizu, Yoji; Kuzuya, Teiji; Honda, Takashi; Hayashi, Kazuhiko; Hirooka, Yoshiki; Katano, Yoshiaki; Goto, Hidemi

    2016-01-29

    Nonalcoholic steatohepatitis (NASH) patients progress to liver cirrhosis and even hepatocellular carcinoma (HCC). Several lines of evidence indicate that accumulation of lipopolysaccharide (LPS) and disruption of gut microbiota play contributory roles in HCC. Moreover, in a dextran sodium sulfate (DSS)-induced colitis model in mice, a high-fat diet increases portal LPS level and promotes hepatic inflammation and fibrosis. However, this diet-induced NASH model requires at least 50 weeks for carcinogenesis. In this study, we sought to determine whether increased intestinal permeability would aggravate liver inflammation and fibrosis and accelerate tumorigenesis in a diet-induced NASH model. Mice were fed a choline-deficient high-fat (CDHF) diet for 4 or 12 weeks. The DSS group was fed CDHF and intermittently received 1% DSS in the drinking water. Exposure to DSS promoted mucosal changes such as crypt loss and increased the number of inflammatory cells in the colon. In the DSS group, portal LPS levels were elevated at 4 weeks, and the proportions of Clostridium cluster XI in the fecal microbiota were elevated. In addition, levels of serum transaminase, number of lobular inflammatory cells, F4/80 staining-positive area, and levels of inflammatory cytokines were all elevated in the DSS group. Liver histology in the DSS group revealed severe fibrosis at 12 weeks. Liver tumors were detected in the DSS group at 12 weeks, but not in the other groups. Thus, DSS administration promoted liver tumors in a CDHF diet-induced NASH mouse over the short term, suggesting that the induction of intestinal inflammation and gut disruption of microbiota in NASH promote hepatic tumorigenesis. PMID:26682925

  2. Antiobesity Effects of the Ethanol Extract of Laminaria japonica Areshoung in High-Fat-Diet-Induced Obese Rat

    PubMed Central

    Jang, Woong Sun; Choung, Se Young

    2013-01-01

    Laminaria japonica Areshoung, a widely consumed marine vegetable, has traditionally been used in Korean maternal health. The present study investigated the antiobesity effects of Laminaria japonica Areshoung ethanol extract (LE) and its molecular mechanism in high-fat-diet-induced obese rats. Six-week-old Sprague-Dawley male rats were separately fed a normal diet or a high-calorie high-fat diet for 6 weeks; then they were treated with LE or tea catechin for another 6 weeks. LE administration significantly decreased the body weight gain, fat-pad weights, and serum and hepatic lipid levels in HD-induced obese rats. The histological analysis revealed that LE-treated group showed a significantly decreased number of lipid droplets and size of adipocytes compared to the HD group. To elucidate the mechanism of action of LE, the levels of genes and proteins involved in obesity were measured in the liver and skeletal muscle. LE treatment resulted in an increased expression of fatty acid oxidation and thermogenesis-related genes in obese rats. Conversely, the expression of the fat intake-related gene (ACC2) and lipogenesis-related genes was reduced by LE treatment. Additionally, LE treatment increased the phosphorylation of AMP-activated protein kinase and its direct downstream protein, acetyl coenzyme A carboxylase, which is one of the rate-limiting enzymes in fatty acid synthesis pathway. These findings demonstrate that LE treatment has a protective effect against a high-fat-diet-induced obesity in rats through regulation of expression of genes and proteins involved in lipolysis and lipogenesis. PMID:23365609

  3. Luteolin protects against high fat diet-induced cognitive deficits in obesity mice.

    PubMed

    Liu, Yi; Fu, Xiaobin; Lan, Nuo; Li, Sai; Zhang, Jingzheng; Wang, Shuaishuai; Li, Cheng; Shang, Yanguo; Huang, Tonghui; Zhang, Ling

    2014-07-01

    The epidemic and experimental studies have confirmed that the obesity can lead to neuroinflammation, neurodegenerative diseases and adversely affect cognition. Despite the numerous elucidations on the impact of obesity on cognition decline, the contributors to the impairments in obesity remain unclear. Male C57BL/6J mice were fed either a control or high-fat diet (HFD) for 16 weeks and then randomized into four groups treated with their respective diets for 4 weeks including control diet (CD); control diet+luteolin (CDL); high-fat diet (HFD), high-fat diet+luteolin (HFDL). The dose of luteolin was 10mg/kg, oral. We showed that adding luteolin in high-fat diet can significantly reduce body weight gain, food intake and plasma cytokines as well as improving glucose metabolism of mice on HFD. Importantly, we showed that luteolin treatment had the effects of alleviating neuroinflammation, oxidative stress and neuronal insulin resistance in the mouse brain, restored blood adipocytokines level to normal. Furthermore, luteolin increased the level of brain-derived neurotrophic factor (BDNF), the action of synapsin I (SYP) and postsynaptic density protein 95 (PSD-95) in the cortex and hippocampus as to that the behavioral performance in Morris water maze (MWM) and step-through task were significantly improved. These results indicate a previously unrecognized potential of luteolin in alleviating obesity-induced cognitive impairment for type-2 diabetes mellitus and Alzheimer disease (AD). PMID:24667364

  4. High-fat diet induced isoform changes of the Parkinson's disease protein DJ-1.

    PubMed

    Poschmann, Gereon; Seyfarth, Katrin; Besong Agbo, Daniela; Klafki, Hans-Wolfgang; Rozman, Jan; Wurst, Wolfgang; Wiltfang, Jens; Meyer, Helmut E; Klingenspor, Martin; Stühler, Kai

    2014-05-01

    Genetic and environmental factors mediate via different physiological and molecular processes a shifted energy balance leading to overweight and obesity. To get insights into the underlying processes involved in energy intake and weight gain, we compared hypothalamic tissue of mice kept on a high-fat or control diet for 10 days by a proteomic approach. Using two-dimensional difference gel electrophoresis in combination with LC-MS/MS, we observed significant abundance changes in 15 protein spots. One isoform of the protein DJ-1 was elevated in the high-fat diet group in three different mouse strains SWR/J, C57BL/6N, and AKR/J analyzed. Large-scale validation of DJ-1 isoforms in individual samples and tissues confirmed a shift in the pattern of DJ-1 isoforms toward more acidic isoforms in several brain and peripheral tissues after feeding a high-fat diet for 10 days. The identification of oxidation of cysteine 106 as well as 2-succinyl modification of the same residue by mass spectrometry not only explains the isoelectric shift of DJ-1 but also links our results to similar shifts of DJ-1 observed in neurodegenerative disease states under oxidative stress. We hypothesize that DJ-1 is a common physiological sensor involved in both nutrition-induced effects and neurodegenerative disease states. PMID:24646099

  5. Antiobesity effects of yerba maté extract (Ilex paraguariensis) in high-fat diet-induced obese mice.

    PubMed

    Arçari, Demétrius P; Bartchewsky, Waldemar; dos Santos, Tanila W; Oliveira, Karim A; Funck, Alexandre; Pedrazzoli, José; de Souza, Marina F F; Saad, Mario J; Bastos, Deborah H M; Gambero, Alessandra; Carvalho, Patricia de O; Ribeiro, Marcelo L

    2009-12-01

    Because the potential of yerba maté (Ilex paraguariensis) has been suggested in the management of obesity, the aim of the present study was to evaluate the effects of yerba maté extract on weight loss, obesity-related biochemical parameters, and the regulation of adipose tissue gene expression in high-fat diet-induced obesity in mice. Thirty animals were randomly assigned to three groups. The mice were introduced to standard or high-fat diets. After 12 weeks on a high-fat diet, mice were randomly assigned according to the treatment (water or yerba maté extract 1.0 g/kg). After treatment intervention, plasma concentrations of total cholesterol, high-density lipoprotein cholesterol, triglyceride, low-density lipoprotein (LDL) cholesterol, and glucose were evaluated. Adipose tissue was examined to determine the mRNA levels of several genes such as tumor necrosis factor-alpha (TNF-alpha), leptin, interleukin-6 (IL-6), C-C motif chemokine ligand-2 (CCL2), CCL receptor-2 (CCR2), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin, peroxisome proliferator-activated receptor-gamma(2) (PPAR-gamma(2)), uncoupling protein-1 (UCP1), and PPAR-gamma coactivator-1 alpha (PGC-1 alpha). The F4/80 levels were determined by immunoblotting. We found that obese mice treated with yerba maté exhibited marked attenuation of weight gain, adiposity, a decrease in epididymal fat-pad weight, and restoration of the serum levels of cholesterol, triglycerides, LDL cholesterol, and glucose. The gene and protein expression levels were directly regulated by the high-fat diet. After treatment with yerba maté extract, we observed a recovery of the expression levels. In conclusion, our data show that yerba maté extract has potent antiobesity activity in vivo. Additionally, we observed that the treatment had a modulatory effect on the expression of several genes related to obesity. PMID:19444227

  6. Antiobesity effect of Tamarindus indica L. pulp aqueous extract in high-fat diet-induced obese rats.

    PubMed

    Azman, Khairunnuur Fairuz; Amom, Zulkhairi; Azlan, Azrina; Esa, Norhaizan Mohd; Ali, Rasadah Mat; Shah, Zamree Md; Kadir, Khairul Kamilah Abdul

    2012-04-01

    Obesity and overweight are associated with atherosclerosis, fatty liver, hyperlipemia, diabetes mellitus, and various types of cancer. The global prevalence of overweight and obesity has reached epidemic proportions. Here, we investigated the effect of Tamarindus indica pulp aqueous extract (TIE) in diet-induced obese Sprague-Dawley rats. The animals were divided into five groups and labeled as follows: the normal control (NC) group received normal diet; the positive control (PC) group received high-fat diet; and the TIE 5, 25, and 50 groups, after the induction of obesity via a high-fat diet, received TIE at 5, 25, or 50 mg/kg orally for 10 weeks. It was observed that TIE decreased the levels of plasma total cholesterol, low-density lipoprotein (LDL), and triglyceride, and increased high-density lipoprotein (HDL), with the concomitant reduction of body weight. Moreover, TIE decreased plasma leptin and reduced fatty acid synthase (FAS) activity and enhanced the efficiency of the antioxidant defense system. TIE exhibits antiobesity effects, as indicated by a significant reduction in adipose tissue weights, as well as lowering the degree of hepatic steatosis in the obesity-induced rats. The extract possesses hepatoprotective activity, as it reversed the plasma liver enzymes level elevation prior to the high-fat diet. In conclusion, TIE improved obesity-related parameters in blood, liver, and adipose tissue in a rat model and suppressed obesity induced by a high-fat diet, possibly by regulating lipid metabolism and lowering plasma leptin and FAS levels. A dose-dependant effect of TIE is detected, where TIE at 50 mg/kg showed the most prominent effect, followed by TIE at 25 mg/kg and, subsequently, 5 mg/kg. PMID:21989999

  7. High fat diet induced obesity alters ovarian phosphatidylinositol-3 kinase signaling gene expression

    PubMed Central

    Nteeba, J.; Ross, J.W.; Perfield, J.W.; Keating, A.F.

    2013-01-01

    Insulin regulates ovarian phosphatidylinositol-3-kinase (PI3K) signaling, important for primordial follicle viability and growth activation. This study investigated diet-induced obesity impacts on: 1) insulin receptor (Insr) and insulin receptor substrate 1 (Irs1); 2) PI3K components (Kit ligand (Kitlg), kit (c-Kit), protein kinase B alpha (Akt1) and forkhead transcription factor subfamily 3 (Foxo3a)); 3) xenobiotic biotransformation (microsomal epoxide hydrolase (Ephx1), Cytochrome P450 isoform 2E1 (Cyp2e1), Glutathione S-transferase (Gst) isoforms mu (Gstm) and pi (Gstp)) and 4) microRNA’s 184, 205, 103 and 21 gene expression. INSR, GSTM and GSTP protein levels were also measured. Obese mouse ovaries had decreased Irs1, Foxo3a, Cyp2e1, MiR-103, and MiR-21 but increased Kitlg, Akt1, and miR-184 levels relative to lean littermates. These results support that diet-induced obesity potentially impairs ovarian function through aberrant gene expression. PMID:23954404

  8. Improvement for high fat diet-induced hepatic injuries and oxidative stress by flavonoid-enriched extract from Nelumbo nucifera leaf.

    PubMed

    Lin, Ming-Cheng; Kao, Shao-Hsuan; Chung, Pei-Jun; Chan, Kuei-Chuan; Yang, Mon-Yuan; Wang, Chau-Jong

    2009-07-01

    Nelumbo nucifera Gaertn is widespread and a popular food in central and southern Taiwan. It has also been reported to possess different therapeutic effects, but the effects of N. nucifera leaf on lipid metabolism and liver function remain unclear. In this study, a high fat diet was used to induce hyperlipidemia, hypercholesterolemia, and fatty liver in hamster. The effects of flavonoid-enriched N. nucifera leaf extract supplement and two lipid-lowing drugs, silymarin and simvastatin, on the disorders induced by high fat diet were investigated. The results showed that a 10-week application of a high fat diet to hamsters led to significant increases of body weight, plasma lipid derivatives (triglyceride, total cholesterol, and lipoproteins), lipid peroxidation, and liver damage markers (plasma aspartate aminotransferase and alanine aminotransferase). Interestingly, flavonoid-enriched N. nucifera leaf extract supplement effectively ameliorated the high fat diet-induced lipid metabolic disorders as significantly as silymarin and simvastatin did. Moreover, the flavonoid-enriched supplement alleviated the high fat diet-induced accumulation of lipids in liver, the findings showing distinguishing mechanisms from the effects of silymarin and simvastatin. These results suggested that the flavonoid-enriched N. nucifera leaf extract supplement may significantly improve the high fat diet-induced abnormal blood lipids and liver damage as significantly as the common drugs. Consequently, it is suggested that the flavonoid-enriched N. nucifera leaf extract supplement is beneficial for the improvement of lipid metabolisms and the alleviation of liver damage in high fat diet treatment. PMID:19499892

  9. Anti-obesity effects of traditional and standardized meju in high-fat diet-induced obese C57BL/6J mice

    PubMed Central

    Bae, Cho-Rong; Kwon, Dae-Young; Cha, Youn-Soo

    2014-01-01

    The aim of the study was to evaluate the anti-obesity effects of two types of meju in diet induced obese C57BL/6J mice. Animals were randomly divided into 4 dietary group (n = 10); normal diet, high fat diet with 30% soybean, high fat diet with 30% traditional meju, high fat diet with 30% standardized meju. After 16 weeks, after animals were sacrificed. It was observed that the high fat diet with 30% traditional meju and high fat diet with 30% standardized meju significantly reduced body weight gain, epididymal fat weight, serum triglyceride along with serum insulin and leptin levels compared to the high fat diet with 30% soybean. And also, the expression levels of hepatic lipid anabolic genes were significantly decreased in the high fat diet with 30% traditional meju and high fat diet with 30% standardized meju compared to the high fat diet with 30% soybean. In conclusion, the assessment of all the obesity markers strongly advocate the anti-obesity effect of traditional as well as standardized meju in diet induce obesity conditions. PMID:24426190

  10. Psoralea corylifolia L. Seed Extract Attenuates Nonalcoholic Fatty Liver Disease in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Seo, Eunhui; Oh, Yoon Sin; Jun, Hee-Sook

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), along with obesity, is increasing world-wide and is one of the major causes of chronic hepatic disease. The present study evaluated the ameliorative effect of extract of Psoralea corylifolia L. seed (PCS) on high fat diet-induced NAFLD in C57BL/6 mice after daily administration at 300 or 500 mg/kg for 12 weeks. Treatment with PCS extract significantly reduced body weight and blood glucose levels and improved glucose tolerance and insulin sensitivity. In addition, PCS extract treatment significantly attenuated lipid accumulation in liver and adipose tissue and reduced serum lipid and hepatic triglyceride levels. Furthermore, the expression of lipogenic genes and inflammatory genes were reduced, and the expression of fat oxidation-related genes was increased in the liver of PCS extract-treated mice compared with control mice. Our study suggests the therapeutic potential of PCS extract for NAFLD by inhibiting lipid accumulation and inflammation in liver. PMID:26861390

  11. Dehydrozingerone exerts beneficial metabolic effects in high-fat diet-induced obese mice via AMPK activation in skeletal muscle.

    PubMed

    Kim, Su Jin; Kim, Hong Min; Lee, Eun Soo; Kim, Nami; Lee, Jung Ok; Lee, Hye Jeong; Park, Na Yeon; Jo, Joo Yeon; Ham, Bo Young; Han, Si Hyun; Park, Sun Hwa; Chung, Choon Hee; Kim, Hyeon Soo

    2015-03-01

    Dehydrozingerone (DHZ) exerts beneficial effects on human health; however, its mechanism of action remains unclear. Here, we found that DHZ suppressed high-fat diet-induced weight gain, lipid accumulation and hyperglycaemia in C57BL/6 mice and increased AMP-activated protein kinase (AMPK) phosphorylation and stimulated glucose uptake in C2C12 skeletal muscle cells. DHZ activated p38 mitogen-activated protein kinase (MAPK) signalling in an AMPK-dependent manner. Inhibiting AMPK or p38 MAPK blocked DHZ-induced glucose uptake. DHZ increased GLUT4 (major transporter for glucose uptake) expression in skeletal muscle. Glucose clearance and insulin-induced glucose uptake increased in DHZ-fed animals, suggesting that DHZ increases systemic insulin sensitivity in vivo. Thus, the beneficial health effects of DHZ could possibly be explained by its ability to activate the AMPK pathway in skeletal muscle. PMID:25582026

  12. High-fat diet-induced obesity Rat model: a comparison between Wistar and Sprague-Dawley Rat

    PubMed Central

    Marques, Cláudia; Meireles, Manuela; Norberto, Sónia; Leite, Joana; Freitas, Joana; Pestana, Diogo; Faria, Ana; Calhau, Conceição

    2016-01-01

    ABSTRACT In the past decades, obesity and associated metabolic complications have reached epidemic proportions. For the study of these pathologies, a number of animal models have been developed. However, a direct comparison between Wistar and Sprague-Dawley (SD) Rat as models of high-fat (HF) diet-induced obesity has not been adequately evaluated so far. Wistar and SD rats were assigned for 2 experimental groups for 17 weeks: standard (St) and high-fat (HF) diet groups. To assess some of the features of the metabolic syndrome, oral glucose tolerance tests, systolic blood pressure measurements and blood biochemical analysis were performed throughout the study. The gut microbiota composition of the animals of each group was evaluated at the end of the study by real-time PCR. HF diet increased weight gain, body fat mass, mesenteric adipocyte's size, adiponectin and leptin plasma levels and decreased oral glucose tolerance in both Wistar and SD rats. However, the majority of these effects were more pronounced or earlier detected in Wistar rats. The gut microbiota of SD rats was less abundant in Bacteroides and Prevotella but richer in Bifidobacterium and Lactobacillus comparatively to the gut microbiota of Wistar rats. Nevertheless, the modulation of the gut microbiota by HF diet was similar in both strains, except for Clostridium leptum that was only reduced in Wistar rats fed with HF diet. In conclusion, both Wistar and SD Rat can be used as models of HF diet-induced obesity although the metabolic effects caused by HF diet seemed to be more pronounced in Wistar Rat. Differences in the gut microbial ecology may account for the worsened metabolic scenario observed in Wistar Rat. PMID:27144092

  13. Effects of Nano-sized Carbon Black on the Lungs of High Fat-diet Induced Overweight Rats

    PubMed Central

    Kang, Mingu; Han, Jeong-Hee; Yun, Hyo-In

    2013-01-01

    Objectives This study was conducted to determine whether nano-sized carbon black exposure results in greater damage in high fat diet-induced overweight rats than normal weight ones and to identify the possible causes of any differences. Methods Two groups of Sprague-Dawley rats allocated by body weight (normal and overweight) were exposed to aerosolized nano-sized carbon black for 6 hours a day, 5 days per week over a 4-week period. Differential cell counts, lactate dehydrogenase (LDH) activities and albumin concentrations were measured in bronchoalveolar lavage (BAL) fluid, and histopathological findings in the lungs were evaluated. Tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were measured in BAL fluid and supernatants of lipopolysaccharide(LPS)-stimulated lymphocyte culture. Results Rats exposed to high concentrations of nano-sized carbon black showed significantly increased (p<0.05) polymorphonuclear leukocyte number and LDH activity in the BAL fluid from both overweight and normal rats. Mild histopathological changes were observed in normal rats irrespective of carbon black concentrations. However, severe histological scores were found in overweight rats (1.75±0.46, 2.25±0.46, and 2.88±0.35 after low, medium, and high concentration exposures). Proinflammatory cytokine levels of TNF-α and IL-6 were significantly higher in the supernatant of LPS-stimulated lymphocytes of overweight rats, whereas there was no significant difference in the BAL fluid between normal and overweight rats. Conclusions Inflammation and damage to lungs exposed to nano-sized carbon black was more severe in high fat diet-induced overweight rats compared to normal rats. PMID:24303350

  14. Endoplasmic reticulum membrane potassium channel dysfunction in high fat diet induced stress in rat hepatocytes

    PubMed Central

    Khodaee, Naser; Ghasemi, Maedeh; Saghiri, Reza; Eliassi, Afsaneh

    2014-01-01

    In a previous study we reported the presence of a large conductance K+ channel in the membrane of endoplasmic reticulum (ER) from rat hepatocytes. The channel open probability (Po) appeared voltage dependent and reached to a minimum 0.2 at +50 mV. Channel activity in this case was found to be totally inhibited at ATP concentration 2.5 mM, glibenclamide 100 µM and tolbutamide 400 µM. Existing evidence indicates an impairment of endoplasmic reticulum functions in ER stress condition. Because ER potassium channels have been involved in several ER functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the ER potassium channel function is altered in a high fat diet model of ER stress. Male Wistar rats were made ER stress for 2 weeks with a high fat diet. Ion channel incorporation of ER stress model into the bilayer lipid membrane allowed the characterization of K+ channel. Our results indicate that the channel Po was significantly increased at voltages above +30 mV. Interestingly, addition of ATP 7.5 mM, glibenclamide 400 µM and tolbutamide 2400 µM totally inhibited the channel activities, 3-fold, 4-fold and 6-fold higher than that in the control groups, respectively. Our results thus demonstrate a modification in the ER K+ channel gating properties and decreased sensitivity to drugs in membrane preparations coming from ER high fat model of ER stress, an effect potentially linked to a change in ER K+ channel subunits in ER stress condition. Our results may provide new insights into the cellular mechanisms underlying ER dysfunctions in ER stress. PMID:26417322

  15. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice.

    PubMed

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-06-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment. PMID:27419109

  16. Treadmill exercise alleviates impairment of cognitive function by enhancing hippocampal neuroplasticity in the high-fat diet-induced obese mice

    PubMed Central

    Kim, Tae-Woon; Choi, Hyun-Hee; Chung, Yong-Rak

    2016-01-01

    Physical exercise is one of the most effective methods for managing obesity, and exercise exerts positive effects on various brain functions. Excessive weight gain is known to be related to the impairment of cognitive function. High-fat diet-induced obesity impairs hippocampal neuroplasticity, which impedes cognitive function, such as learning ability and memory function. In this study, we investigated the effect of treadmill exercise on impairment of cognitive function in relation with hippocampal neuroplasticity using high-fat diet-induced obese mice. After obesity was induced by a 20-week high-fat (60%) diet, treadmill exercise was performed for 12 weeks. In the present results, cognitive function was impaired in the high-fat diet-induced obese mice. Brain-derived neurotrophic factor (BDNF) and tyrosin kinase B (TrkB) expression and cell proliferation were decreased in the high-fat diet-induced obese mice. Treadmill exercise improved cognitive function through enhancing neuroplasticity, including increased expression of BDNF and TrkB and enhanced cell proliferation. The present results suggest that treadmill exercise enhances hippocampal neuroplasticity, and then potentially plays a protective role against obesity-induced cognitive impairment. PMID:27419109

  17. High fat diet induced alterations of atrial electrical activities in mice

    PubMed Central

    Zhang, Fan; Hartnett, Sigurd; Sample, Alex; Schnack, Sabrina; Li, Yifan

    2016-01-01

    Obesity is a well-known risk factor for various cardiovascular diseases. Recent clinical data showed that overweight and obese patients have higher incidence of atrial fibrillation (AF) compared with individuals with normal body weights, but the underlying mechanisms remain to be elucidated. In this study, we investigated the effects of a high fat diet on atrial activities in mice. ICR male mice were fed a regular diet (RD) or a high fat diet (HFD) for 8 weeks. Mice fed HFD showed significantly greater body weight gains and visceral fat accumulation compared with RD mice. Under anesthetic condition, baseline arterial blood pressure and heart rate were not significantly different between RD and HFD groups. Although no spontaneous or atrial stimulation-induced atrial fibrillation was observed, this study revealed several alterations in the activities and protein levels in the atria in HFD mice. Surface electrocardiogram (ECG) revealed significantly shortened PR interval in HFD mice. In the atrial stimulation experiments, the sinoatrial (SA) node recovery time was significantly prolonged whereas the atrial effective refractory period was significantly reduced in HFD mice as compared with RD mice. Western blot showed protein levels of two major potassium channels, Kv1.5 and Kv4.2/3, were significantly increased in atria of HFD mice. These data indicate that HFD induces atrial electrophysiological remodeling in mice, which may be a potential mechanism underlying the increased risk for atrial arrhythmias in obesity and metabolic disorders. PMID:27073731

  18. Plasma carnosine, but not muscle carnosine, attenuates high-fat diet-induced metabolic stress.

    PubMed

    Stegen, Sanne; Stegen, Bram; Aldini, Giancarlo; Altomare, Alessandra; Cannizzaro, Luca; Orioli, Marica; Gerlo, Sarah; Deldicque, Louise; Ramaekers, Monique; Hespel, Peter; Derave, Wim

    2015-09-01

    There is growing in vivo evidence that the dipeptide carnosine has protective effects in metabolic diseases. A critical unanswered question is whether its site of action is tissues or plasma. This was investigated using oral carnosine versus β-alanine supplementation in a high-fat diet rat model. Thirty-six male Sprague-Dawley rats received a control diet (CON), a high-fat diet (HF; 60% of energy from fat), the HF diet with 1.8% carnosine (HFcar), or the HF diet with 1% β-alanine (HFba), as β-alanine can increase muscle carnosine without increasing plasma carnosine. Insulin sensitivity, inflammatory signaling, and lipoxidative stress were determined in skeletal muscle and blood. In a pilot study, urine was collected. The 3 HF groups were significantly heavier than the CON group. Muscle carnosine concentrations increased equally in the HFcar and HFba groups, while elevated plasma carnosine levels and carnosine-4-hydroxy-2-nonenal adducts were detected only in the HFcar group. Elevated plasma and urine N(ε)-(carboxymethyl)lysine in HF rats was reduced by ∼50% in the HFcar group but not in the HFba group. Likewise, inducible nitric oxide synthase mRNA was decreased by 47% (p < 0.05) in the HFcar group, but not in the HFba group, compared with HF rats. We conclude that plasma carnosine, but not muscle carnosine, is involved in preventing early-stage lipoxidation in the circulation and inflammatory signaling in the muscle of rats. PMID:26307517

  19. A high-fat, ketogenic diet induces a unique metabolic state in mice.

    PubMed

    Kennedy, Adam R; Pissios, Pavlos; Otu, Hasan; Roberson, Russell; Xue, Bingzhong; Asakura, Kenji; Furukawa, Noburu; Marino, Frank E; Liu, Fen-Fen; Kahn, Barbara B; Libermann, Towia A; Maratos-Flier, Eleftheria

    2007-06-01

    Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss. PMID:17299079

  20. Consumption of Clarified Grapefruit Juice Ameliorates High-Fat Diet Induced Insulin Resistance and Weight Gain in Mice

    PubMed Central

    Chudnovskiy, Rostislav; Thompson, Airlia; Tharp, Kevin; Hellerstein, Marc; Napoli, Joseph L.; Stahl, Andreas

    2014-01-01

    To determine the metabolic effects of grapefruit juice consumption we established a model in which C57Bl/6 mice drank 25–50% sweetened GFJ, clarified of larger insoluble particles by centrifugation (cGFJ), ad libitum as their sole source of liquid or isocaloric and sweetened water. cGFJ and control groups consumed similar amounts of liquids and calories. Mice fed a high-fat diet and cGFJ experienced a 18.4% decrease in weight, a 13–17% decrease in fasting blood glucose, a three-fold decrease in fasting serum insulin, and a 38% decrease in liver triacylglycerol values, compared to controls. Mice fed a low-fat diet that drank cGFJ experienced a two-fold decrease in fasting insulin, but not the other outcomes observed with the high-fat diet. cGFJ consumption decreased blood glucose to a similar extent as the commonly used anti-diabetic drug metformin. Introduction of cGFJ after onset of diet-induced obesity also reduced weight and blood glucose. A bioactive compound in cGFJ, naringin, reduced blood glucose and improved insulin tolerance, but did not ameliorate weight gain. These data from a well-controlled animal study indicate that GFJ contains more than one health-promoting neutraceutical, and warrant further studies of GFJ effects in the context of obesity and/or the western diet. PMID:25296035

  1. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity

    PubMed Central

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-01-01

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese. PMID:27271106

  2. Cholesterol 7α-hydroxylase-deficient mice are protected from high-fat/high-cholesterol diet-induced metabolic disorders.

    PubMed

    Ferrell, Jessica M; Boehme, Shannon; Li, Feng; Chiang, John Y L

    2016-07-01

    Cholesterol 7α-hydroxylase (CYP7A1) is the first and rate-limiting enzyme in the conversion of cholesterol to bile acids in the liver. In addition to absorption and digestion of nutrients, bile acids play a critical role in the regulation of lipid, glucose, and energy homeostasis. We have backcrossed Cyp7a1(-/-) mice in a mixed B6/129Sv genetic background to C57BL/6J mice to generate Cyp7a1(-/-) mice in a near-pure C57BL/6J background. These mice survive well and have normal growth and a bile acid pool size ∼60% of WT mice. The expression of the genes in the alternative bile acid synthesis pathway are upregulated, resulting in a more hydrophilic bile acid composition with reduced cholic acid (CA). Surprisingly, Cyp7a1(-/-) mice have improved glucose sensitivity with reduced liver triglycerides and fecal bile acid excretion, but increased fecal fatty acid excretion and respiratory exchange ratio (RER) when fed a high-fat/high-cholesterol diet. Supplementing chow and Western diets with CA restored bile acid composition, reversed the glucose tolerant phenotype, and reduced the RER. Our current study points to a critical role of bile acid composition, rather than bile acid pool size, in regulation of glucose, lipid, and energy metabolism to improve glucose and insulin tolerance, maintain metabolic homeostasis, and prevent high-fat diet-induced metabolic disorders. PMID:27146480

  3. Naringenin suppresses macrophage infiltration into adipose tissue in an early phase of high-fat diet-induced obesity.

    PubMed

    Yoshida, Hiroki; Watanabe, Hideaki; Ishida, Akiko; Watanabe, Wataru; Narumi, Keiko; Atsumi, Toshiyuki; Sugita, Chihiro; Kurokawa, Masahiko

    2014-11-01

    Obese adipose tissue is characterized by increased macrophage infiltration, which results in chronic inflammation in adipose tissue and leads to obesity-related diseases such as type 2 diabetes mellitus and atherosclerosis. The regulation of macrophage infiltration into adipose tissue is an important strategy for preventing and treating obesity-related diseases. In this study, we report that naringenin, a citrus flavonoid, suppressed macrophage infiltration into adipose tissue induced by short-term (14 days) feeding of a high-fat diet in mice; although naringenin did not show any differences in high-fat diet-induced changes of serum biochemical parameters in this short administration period. Naringenin suppressed monocyte chemoattractant protein-1 (MCP-1) in adipose tissue, and this effect was mediated in part through inhibition of c-Jun NH2-terminal kinase pathway. Naringenin also inhibited MCP-1 expression in adipocytes, macrophages, and a co-culture of adipocytes and macrophages. Our results suggest a mechanism by which daily consumption of naringenin may exhibit preventive effects on obesity-related diseases. PMID:25450363

  4. Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity.

    PubMed

    Auffret, Julien; Viengchareun, Say; Carré, Nadège; Denis, Raphaël G P; Magnan, Christophe; Marie, Pierre-Yves; Muscat, Adeline; Fève, Bruno; Lombès, Marc; Binart, Nadine

    2012-09-01

    Stimulating conversion of white fat to metabolically active adipocytes (beige fat) constitutes a promising strategy against weight gain and its deleterious associated-disorders. We provide direct evidence that prolactin (PRL), best known for its actions on the mammary gland, plays a pivotal role in energy balance through the control of adipocyte differentiation and fate. Here we show that lack of prolactin receptor (PRLR) causes resistance to high-fat-diet-induced obesity due to enhanced energy expenditure and increased metabolic rate. Mutant mice displayed reduced fat mass associated with appearance of massive brown-like adipocyte foci in perirenal and subcutaneous but not in gonadal fat depots under a high-fat diet. Positron emission tomography imaging further demonstrated the occurrence of these thermogenic brown fat depots in adult mice, providing additional support for recruitable brown-like adipocytes (beigeing) in white fat depots. Consistent with the activation of brown adipose tissue, PRLR inactivation increases expression of master genes controlling brown adipocyte fate (PRDM16) and mitochondrial function (PGC1α, UCP1). Altered pRb/Foxc2 expression suggests that this PRL-regulated pathway may contribute to beige cell commitment. Together, these results provide direct genetic evidence that PRLR affects energy balance and metabolic adaptation in rodents via effects on brown adipose tissue differentiation and function. PMID:22637534

  5. Consumption of clarified grapefruit juice ameliorates high-fat diet induced insulin resistance and weight gain in mice.

    PubMed

    Chudnovskiy, Rostislav; Thompson, Airlia; Tharp, Kevin; Hellerstein, Marc; Napoli, Joseph L; Stahl, Andreas

    2014-01-01

    To determine the metabolic effects of grapefruit juice consumption we established a model in which C57Bl/6 mice drank 25-50% sweetened GFJ, clarified of larger insoluble particles by centrifugation (cGFJ), ad libitum as their sole source of liquid or isocaloric and sweetened water. cGFJ and control groups consumed similar amounts of liquids and calories. Mice fed a high-fat diet and cGFJ experienced a 18.4% decrease in weight, a 13-17% decrease in fasting blood glucose, a three-fold decrease in fasting serum insulin, and a 38% decrease in liver triacylglycerol values, compared to controls. Mice fed a low-fat diet that drank cGFJ experienced a two-fold decrease in fasting insulin, but not the other outcomes observed with the high-fat diet. cGFJ consumption decreased blood glucose to a similar extent as the commonly used anti-diabetic drug metformin. Introduction of cGFJ after onset of diet-induced obesity also reduced weight and blood glucose. A bioactive compound in cGFJ, naringin, reduced blood glucose and improved insulin tolerance, but did not ameliorate weight gain. These data from a well-controlled animal study indicate that GFJ contains more than one health-promoting neutraceutical, and warrant further studies of GFJ effects in the context of obesity and/or the western diet. PMID:25296035

  6. Chemical chaperones reduce ER stress and adipose tissue inflammation in high fat diet-induced mouse model of obesity.

    PubMed

    Chen, Yaqin; Wu, Zhihong; Zhao, Shuiping; Xiang, Rong

    2016-01-01

    Obesity, which is characteristic by chronic inflammation, is defined as abnormal or excessive fat accumulation in adipose tissues. Endoplasmic reticulum (ER) stress is increased in adipose tissue of obese state and is known to be strongly associated with chronic inflammation. The aim of this study was to investigate the effect of ER stress on adipokine secretion in obese mice and explore the potential mechanisms. In this study, we found high-fat diet induced-obesity contributed to strengthened ER stress and triggered chronic inflammation in adipose tissue. Chemical chaperones, 4-PBA and TUDCA, modified metabolic disorders and decreased the levels of inflammatory cytokines in obese mice fed a high-fat diet. The alleviation of ER stress is in accordance with the decrease of free cholesterol in adipose tissue. Furthermore chemical chaperones suppress NF-κB activity in adipose tissue of obese mice in vivo. In vitro studies showed IKK/NF-κB may be involved in the signal transduction of adipokine secretion dysfunction induced by ER stress. The present study revealed the possibility that inhibition of ER stress may be a novel drug target for metabolic abnormalities associated with obesity. Further studies are now needed to characterize the initial incentive of sustained ER stress in obese. PMID:27271106

  7. White adipose tissue re-growth after partial lipectomy in high fat diet induced obese wistar rats.

    PubMed

    Bueno, Allain Amador; Habitante, Carlos Alexandre; Oyama, Lila Missae; Estadella, Débora; Ribeiro, Eliane Beraldi; Oller do Nascimento, Cláudia Maria

    2011-01-01

    The effects of partial removal of epididymal (EPI) and retroperitoneal (RET) adipose tissues (partial lipectomy) on the triacylglycerol deposition of high fat diet induced obese rats were analyzed, aiming to challenge the hypothesized body fat regulatory system. Male 28-day-old wistar rats received a diet enriched with peanuts, milk chocolate and sweet biscuits during the experimental period. At the 90th day of life, rats were submitted to either lipectomy (L) or sham surgery. After 7 or 30 days, RET, EPI, liver, brown adipose tissue (BAT), blood and carcass were obtained and analyzed. Seven days following surgery, liver lipogenesis rate and EPI relative weight were increased in L. After 30 days, L, RET and EPI presented increased lipogenesis, lipolysis and percentage of small area adipocytes. L rats also presented increased liver malic enzyme activity, BAT lipogenesis, and triacylglycerol and corticosterone serum levels. The partial removal of visceral fat pads affected the metabolism of high fat diet obese rats, which leads to excised tissue re-growth and possibly compensatory growth of non-excised depots at a later time. PMID:21140253

  8. Extracts of Rhizoma Polygonati Odorati Prevent High-Fat Diet-Induced Metabolic Disorders in C57BL/6 Mice

    PubMed Central

    Fan, Shengjie; Ding, Xiaobo; Ji, Guang; Huang, Cheng

    2013-01-01

    Polygonatum odoratum (Mill.) Druce belongs to the genus Polygonatum family of plants. In traditional Chinese medicine, the root of Polygonatum odoratum, Rhizoma Polygonati Odorati, is used both for food and medicine to prevent and treat metabolic disorders such as hyperlipidemia, hyperglycemia, obesity and cardiovascular disease. However, there is no solid experimental evidence to support these applications, and the underlying mechanism is also needed to be elucidated. Here, we examined the effect of the extract of Rhizoma Polygonati Odorati (ER) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, the ER blocked body weight gain, and lowered serum total cholesterol (TC), triglyceride (TG) and fasting blood glucose, improved glucose tolerance test (GTT) and insulin tolerance test (ITT), reduced the levels of serum insulin and leptin, and increased serum adiponectin levels in mice fed with a high-fat diet significantly. In the therapeutic study, we induced obesity in the mice and treated the obese mice with ER for two weeks. We found that ER treatments reduced serum TG and fasting blood glucose, and improved glucose tolerance in the mice. Gene expression analysis showed that ER increased the mRNA levels of peroxisome proliferator-activated receptors (PPAR) γ and α and their downstream target genes in mice livers, adipose tissues and HepG2 cells. Our data suggest that ER ameliorates metabolic disorders and enhances the mRNA expression of PPARs in obese C57BL/6 mice induced by high-fat diet. PMID:24312343

  9. Ameliorative potential of Tamarindus indica on high fat diet induced nonalcoholic fatty liver disease in rats.

    PubMed

    Sasidharan, Suja Rani; Joseph, Joshua Allan; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Madhavan, Chandrasekharan Nair Ariyattu; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  10. Ameliorative Potential of Tamarindus indica on High Fat Diet Induced Nonalcoholic Fatty Liver Disease in Rats

    PubMed Central

    Sasidharan, Suja Rani; Anandakumar, Senthilkumar; Venkatesan, Vijayabalaji; Ariyattu Madhavan, Chandrasekharan Nair; Agarwal, Amit

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD), the prevalence of which is rising globally with current upsurge in obesity, is one of the most frequent causes of chronic liver diseases. The present study evaluated the ameliorative effect of extract of Tamarindus indica seed coat (ETS) on high fat diet (HFD) induced NAFLD, after daily administration at 45, 90, and 180 mg/kg body weight dose levels for a period of 6 weeks, in albino Wistar rats. Treatment with ETS at all tested dose levels significantly attenuated the pathological alterations associated with HFD induced NAFLD viz. hepatomegaly, elevated hepatic lipid and lipid peroxides, serum alanine aminotransferase, and free fatty acid levels as well as micro-/macrohepatic steatosis. Moreover, extract treatment markedly reduced body weight and adiposity along with an improvement in insulin resistance index. The study findings, therefore suggested the therapeutic potential of ETS against NAFLD, acting in part through antiobesity, insulin sensitizing, and antioxidant mechanisms. PMID:24688399

  11. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia.

    PubMed

    Baufeld, Caroline; Osterloh, Anja; Prokop, Stefan; Miller, Kelly R; Heppner, Frank L

    2016-09-01

    Diets high in fat (HFD) are known to cause an immune response in the periphery as well as the central nervous system. In peripheral adipose tissue, this immune response is primarily mediated by macrophages that are recruited to the tissue. Similarly, reactivity of microglia, the innate immune cells of the brain, has been shown to occur in the hypothalamus of mice fed a high-fat diet. To characterize the nature of the microglial response to diets high in fat in a temporal fashion, we studied the phenotypic spectrum of hypothalamic microglia of mice fed high-fat diet for 3 days and 8 weeks by assessing their tissue reaction and inflammatory signature. While we observed a significant increase in Iba1+ myeloid cells and a reaction of GFAP+ astrocytes in the hypothalamus after 8 weeks of HFD feeding, we found the hypothalamic myeloid cell reaction to be limited to endogenous microglia and not mediated by infiltrating myeloid cells. Moreover, obese humans were found to present with signs of hypothalamic gliosis and exacerbated microglia dystrophy, suggesting a targeted microglia response to diet in humans as well. Notably, the glial reaction occurring in the mouse hypothalamus was not accompanied by an increase in pro-inflammatory cytokines, but rather by an anti-inflammatory reaction. Gene expression analyses of isolated microglia not only confirmed this observation, but also revealed a downregulation of microglia genes important for sensing signals in the microenvironment. Finally, we demonstrate that long-term exposure of microglia to HFD in vivo does not impair the cell's ability to respond to additional stimuli, like lipopolysaccharide. Taken together, our findings support the notion that microglia react to diets high in fat in a region-specific manner in rodents as well as in humans; however, this response changes over time as it is not exclusively pro-inflammatory nor does exposure to HFD prime microglia in the hypothalamus. PMID:27393312

  12. Effect of tomato extract supplementation against high-fat diet-induced hepatic lesions.

    PubMed

    Melendez-Martinez, Antonio J; Nascimento, Andre F; Wang, Yan; Liu, Chun; Mao, Yilei; Wang, Xiang-Dong

    2013-08-01

    Higher intake of tomatoes or tomato-based products has been associated with lower risk for liver cancer. In this study, we investigated the effects of supplementing tomato extract (TE), which contains mainly lycopene (LY) and less amounts of its precursors, phytoene (PT) and phytofluene (PTF) against high-fat-diet related hepatic inflammation and lipid profiles, and carcinogenesis. Four groups of rats were injected with a hepatic carcinogen, diethylnitrosamine (DEN) and then fed either Lieber-DeCarli control diet (35% fat, CD) or high fat diet (71% fat, HFD) with or without TE supplementation for 6 weeks. Results showed that the supplementation of TE significantly decreased the multiplicity of both inflammatory foci and altered hepatic foci (AHF) expressing placental form glutathione-S transferase (p-GST) in the liver of HFD-fed rats. High-performance liquid chromatography (HPLC) analysis showed that TE supplementation results in a significantly higher accumulation of both PT and PTF than LY in livers of rats. In addition, the TE supplementation led to a decrease of plasma cholesterol levels but an overall increase in hepatic lipids which is associated with changes in the genes on lipid metabolism, including the peroxisome proliferator-activated receptor gamma (PPARγ) and the sterol-regulatory element binding protein (SREBP-1). These data suggest that TE supplementation decreases hepatic inflammation and plasma total cholesterol associated with high dietary fat intake. Moreover, TE supplementation results in an accumulation of hepatic PT and PTF as well as increased lipogenesis suggesting further investigation into their biological function(s). PMID:24273751

  13. Gallic Acid Ameliorated Impaired Glucose and Lipid Homeostasis in High Fat Diet-Induced NAFLD Mice

    PubMed Central

    Chao, Jung; Huo, Teh-Ia; Cheng, Hao-Yuan; Tsai, Jen-Chieh; Liao, Jiunn-Wang; Lee, Meng-Shiou; Qin, Xue-Mei; Hsieh, Ming-Tsuen; Pao, Li-Heng; Peng, Wen-Huang

    2014-01-01

    Gallic acid (GA), a naturally abundant plant phenolic compound in vegetables and fruits, has been shown to have potent anti-oxidative and anti-obesity activity. However, the effects of GA on nonalcoholic fatty liver disease (NAFLD) are poorly understood. In this study, we investigated the beneficial effects of GA administration on nutritional hepatosteatosis model by a more “holistic view” approach, namely 1H NMR-based metabolomics, in order to prove efficacy and to obtain information that might lead to a better understanding of the mode of action of GA. Male C57BL/6 mice were placed for 16 weeks on either a normal chow diet, a high fat diet (HFD, 60%), or a high fat diet supplemented with GA (50 and 100 mg/kg/day, orally). Liver histopathology and serum biochemical examinations indicated that the daily administration of GA protects against hepatic steatosis, obesity, hypercholesterolemia, and insulin resistance among the HFD-induced NAFLD mice. In addition, partial least squares discriminant analysis scores plots demonstrated that the cluster of HFD fed mice is clearly separated from the normal group mice plots, indicating that the metabolic characteristics of these two groups are distinctively different. Specifically, the GA-treated mice are located closer to the normal group of mice, indicating that the HFD-induced disturbances to the metabolic profile were partially reversed by GA treatment. Our results show that the hepatoprotective effect of GA occurs in part through a reversing of the HFD caused disturbances to a range of metabolic pathways, including lipid metabolism, glucose metabolism (glycolysis and gluconeogenesis), amino acids metabolism, choline metabolism and gut-microbiota-associated metabolism. Taken together, this study suggested that a 1H NMR-based metabolomics approach is a useful platform for natural product functional evaluation. The selected metabolites are potentially useful as preventive action biomarkers and could also be used to help

  14. Soluble Fermentable Dietary Fibre (Pectin) Decreases Caloric Intake, Adiposity and Lipidaemia in High-Fat Diet-Induced Obese Rats

    PubMed Central

    Adam, Clare L.; Thomson, Lynn M.; Williams, Patricia A.; Ross, Alexander W.

    2015-01-01

    Consumption of a high fat diet promotes obesity and poor metabolic health, both of which may be improved by decreasing caloric intake. Satiety-inducing ingredients such as dietary fibre may be beneficial and this study investigates in diet-induced obese (DIO) rats the effects of high or low fat diet with or without soluble fermentable fibre (pectin). In two independently replicated experiments, young adult male DIO rats that had been reared on high fat diet (HF; 45% energy from fat) were given HF, low fat diet (LF; 10% energy from fat), HF with 10% w/w pectin (HF+P), or LF with 10% w/w pectin (LF+P) ad libitum for 4 weeks (n = 8/group/experiment). Food intake, body weight, body composition (by magnetic resonance imaging), plasma hormones, and plasma and liver lipid concentrations were measured. Caloric intake and body weight gain were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Body fat mass increased in HF, was maintained in LF, but decreased significantly in LF+P and HF+P groups. Final plasma leptin, insulin, total cholesterol and triglycerides were lower, and plasma satiety hormone PYY concentrations were higher, in LF+P and HF+P than in LF and HF groups, respectively. Total fat and triglyceride concentrations in liver were greatest in HF, lower in LF and HF+P, and lowest in the LF+P group. Therefore, the inclusion of soluble fibre in a high fat (or low fat) diet promoted increased satiety and decreased caloric intake, weight gain, adiposity, lipidaemia, leptinaemia and insulinaemia. These data support the potential of fermentable dietary fibre for weight loss and improving metabolic health in obesity. PMID:26447990

  15. Anti-Obese Effect of Glucosamine and Chitosan Oligosaccharide in High-Fat Diet-Induced Obese Rats

    PubMed Central

    Huang, Lanlan; Chen, Jian; Cao, Peiqiu; Pan, Haitao; Ding, Chen; Xiao, Tiancun; Zhang, Pengfei; Guo, Jiao; Su, Zhengquan

    2015-01-01

    Objective: This study is to evaluate the anti-obese effects of glucosamine (GLC) and chitosan oligosaccharide (COS) on high-fat diet-induced obese rats. Methods: The rats were randomly divided into twelve groups: a normal diet group (NF), a high-fat diet group (HF), Orlistat group, GLC high-, middle-, and low-dose groups (GLC-H, GLC-M, GLC-L), COS1 (COS, number-average molecular weight ≤1000) high-, middle-, and low-dose groups (COS1-H, COS1-M, COS1-L), and COS2 (COS, number-average molecular weight ≤3000) high-, middle-, and low-dose groups (COS2-H, COS2-M, COS2-L). All groups received oral treatment by gavage once daily for a period of six weeks. Results: Rats fed with COS1 gained the least weight among all the groups (P < 0.01), and these rats lost more weight than those treated with Orlistat. In addition to the COS2-H and Orlistat groups, the serum total cholesterol (CHO) and low-density lipoprotein cholesterol (LDL-C) levels were significantly reduced in all treatment groups compared to the HF group (P < 0.01). The various doses of GLC, COS1 and COS2 reduced the expression levels of PPARγ and LXRα mRNA in the white adipose tissue. Conclusions: The results above demonstrated that GLC, COS1, and COS2 improved dyslipidemia and prevented body weight gains by inhibiting the adipocyte differentiation in obese rats induced by a high-fat diet. Thus, these agents may potentially be used to treat obesity. PMID:25942093

  16. Mori Folium and Mori Fructus Mixture Attenuates High-Fat Diet-Induced Cognitive Deficits in Mice

    PubMed Central

    Jeong, Hyun Uk; Park, Gunhyuk; Kim, Hocheol; Lim, Yunsook; Oh, Myung Sook

    2015-01-01

    Obesity has become a global health problem, contributing to various diseases including diabetes, hypertension, cancer, and dementia. Increasing evidence suggests that obesity can also cause neuronal damage, long-term memory loss, and cognitive impairment. The leaves and the fruits of Morus alba L., containing active phytochemicals, have been shown to possess antiobesity and hypolipidemic properties. Thus, in the present study, we assessed their effects on cognitive functioning in mice fed a high-fat diet by performing immunohistochemistry, using antibodies against c-Fos, synaptophysin, and postsynaptic density protein 95 and a behavioral test. C57BL/6 mice fed a high-fat diet for 21 weeks exhibited increased body weight, but mice coadministered an optimized Mori Folium and Mori Fructus extract mixture (2 : 1; MFE) for the final 12 weeks exhibited significant body weight loss. Additionally, obese mice exhibited not only reduced neural activity, but also decreased presynaptic and postsynaptic activities, while MFE-treated mice exhibited recovery of these activities. Finally, cognitive deficits induced by the high-fat diet were recovered by cotreatment with MFE in the novel object recognition test. Our findings suggest that the antiobesity effects of MFE resulted in recovery of the cognitive deficits induced by the high-fat diet by regulation of neural and synaptic activities. PMID:25945108

  17. Effect of Dietary Cocoa Tea (Camellia ptilophylla) Supplementation on High-Fat Diet-Induced Obesity, Hepatic Steatosis, and Hyperlipidemia in Mice

    PubMed Central

    Yang, Xiao Rong; Wat, Elaine; Wang, Yan Ping; Ko, Chun Hay; Koon, Chi Man; Siu, Wing Sum; Gao, Si; Cheung, David Wing Shing; Lau, Clara Bik San; Ye, Chuang Xing; Leung, Ping Chung

    2013-01-01

    Recent studies suggested that green tea has the potential to protect against diet-induced obesity. The presence of caffeine within green tea has caused limitations. Cocoa tea (Camellia ptilophylla) is a naturally decaffeinated tea plant. To determine whether cocoa tea supplementation results in an improvement in high-fat diet-induced obesity, hyperlipidemia and hepatic steatosis, and whether such effects would be comparable to those of green tea extract, we studied six groups (n = 10) of C57BL/6 mice that were fed with (1) normal chow (N); (2) high-fat diet (21% butterfat + 0.15% cholesterol, wt/wt) (HF); (3) a high-fat diet supplemented with 2% green tea extract (HFLG); (4) a high-fat diet supplemented with 4% green tea extract (HFHG); (5) a high-fat diet supplemented with 2% cocoa tea extract (HFLC); and (6) a high-fat diet supplemented with 4% cocoa tea extract (HFHC). From the results, 2% and 4% dietary cocoa tea supplementation caused a dose-dependent decrease in (a) body weight, (b) fat pad mass, (c) liver weight, (d) total liver lipid, (e) liver triglyceride and cholesterol, and (f) plasma lipids (triglyceride and cholesterol). These data indicate that dietary cocoa tea, being naturally decaffeinated, has a beneficial effect on high-fat diet-induced obesity, hepatomegaly, hepatic steatosis, and elevated plasma lipid levels in mice, which are comparable to green tea. The present findings have provided the proof of concept that dietary cocoa tea might be of therapeutic value and could therefore provide a safer and cost effective option for patients with diet-induced metabolic syndrome. PMID:23935682

  18. Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ooi, Der-Jiun; Sarega, Nadarajan; Azmi, Nur Hanisah; Ismail, Norsharina; Chan, Kim Wei; Hou, Zhiping; Yusuf, Norhayati Binti

    2015-01-01

    Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. PMID:26273674

  19. Mast cell stabilizers obviate high fat diet-induced renal dysfunction in rats.

    PubMed

    Reena; Kaur, Tajpreet; Kaur, Anudeep; Singh, Manjinder; Buttar, Harpal Singh; Pathak, Devendra; Singh, Amrit Pal

    2016-04-15

    The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats. PMID:26944217

  20. High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22.

    PubMed

    Gulhane, Max; Murray, Lydia; Lourie, Rohan; Tong, Hui; Sheng, Yong H; Wang, Ran; Kang, Alicia; Schreiber, Veronika; Wong, Kuan Yau; Magor, Graham; Denman, Stuart; Begun, Jakob; Florin, Timothy H; Perkins, Andrew; Cuív, Páraic Ó; McGuckin, Michael A; Hasnain, Sumaira Z

    2016-01-01

    Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy. PMID:27350069

  1. Bardoxolone Methyl Prevents High-Fat Diet-Induced Colon Inflammation in Mice.

    PubMed

    Dinh, Chi H L; Yu, Yinghua; Szabo, Alexander; Zhang, Qingsheng; Zhang, Peng; Huang, Xu-Feng

    2016-04-01

    Obesity induces chronic, low-grade inflammation, which increases the risk of colon cancer. We investigated the preventive effects of Bardoxolone methyl (BARD) on high-fat diet (HFD)-induced inflammation in a mouse colon. Male C57BL/6J mice (n=7) were fed a HFD (HFD group), HFD plus BARD (10 mg/kg) in drinking water (HFD/BARD group), or normal laboratory chow diet (LFD group) for 21 weeks. In HFD mice, BARD reduced colon thickness and decreased colon weight per length. This was associated with an increase in colon crypt depth and the number of goblet cells per crypt. BARD reduced the expression of F4/80 and CD11c but increased CD206 and IL-10, indicating an anti-inflammatory effect. BARD prevented an increase of the intracellular pro-inflammatory biomarkers (NF-қB, p NF-қB, IL-6, TNF-α) and cell proliferation markers (Cox2 and Ki67). BARD prevented fat deposition in the colon wall and prevented microbial population changes. Overall, we report the preventive effects of BARD on colon inflammation in HFD-fed mice through its regulation of macrophages, NF-қB, cytokines, Cox2 and Ki67, fat deposition and microflora. PMID:26920068

  2. Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice

    PubMed Central

    Wu, Dongdong; Gao, Biao; Li, Mengling; Yao, Ling; Wang, Shuaiwei; Chen, Mingliang; Li, Hui; Ma, Chunyan

    2016-01-01

    Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury. PMID:27413418

  3. Geldanamycin Derivative Ameliorates High Fat Diet-Induced Renal Failure in Diabetes

    PubMed Central

    Zhang, Hong-Mei; Dang, Howard; Kamat, Amrita; Yeh, Chih-Ko; Zhang, Bin-Xian

    2012-01-01

    Diabetic nephropathy is a serious complication of longstanding diabetes and its pathogenesis remains unclear. Oxidative stress may play a critical role in the pathogenesis and progression of diabetic nephropathy. Our previous studies have demonstrated that polyunsaturated fatty acids (PUFA) induce peroxynitrite generation in primary human kidney mesangial cells and heat shock protein 90β1 (hsp90β1) is indispensable for the PUFA action. Here we investigated the effects of high fat diet (HFD) on kidney function and structure of db/db mice, a widely used rodent model of type 2 diabetes. Our results indicated that HFD dramatically increased the 24 h-urine output and worsened albuminuria in db/db mice. Discontinuation of HFD reversed the exacerbated albuminuria but not the increased urine output. Prolonged HFD feeding resulted in early death of db/db mice, which was associated with oliguria and anuria. Treatment with the geldanamycin derivative, 17-(dimethylaminoehtylamino)-17-demethoxygeldanamycin (17-DMAG), an hsp90 inhibitor, preserved kidney function, and ameliorated glomerular and tubular damage by HFD. 17-DMAG also significantly extended survival of the animals and protected them from the high mortality associated with renal failure. The benefit effect of 17-DMAG on renal function and structure was associated with a decreased level of kidney nitrotyrosine and a diminished kidney mitochondrial Ca2+ efflux in HFD-fed db/db mice. These results suggest that hsp90β1 is a potential target for the treatment of nephropathy and renal failure in diabetes. PMID:22412919

  4. Sasa borealis Stem Extract Attenuates Hepatic Steatosis in High-Fat Diet-induced Obese Rats

    PubMed Central

    Song, Yuno; Lee, Soo-Jung; Jang, Sun-Hee; Ha, Ji Hee; Song, Young Min; Ko, Yeoung-Gyu; Kim, Hong-Duck; Min, Wongi; Kang, Suk Nam; Cho, Jae-Hyeon

    2014-01-01

    The aim of the current study is to examine the improving effect of Sasa borealis stem (SBS) extract extracts on high-fat diet (HFD)-induced hepatic steatosis in rats. To determine the hepatoprotective effect of SBS, we fed rats a normal regular diet (ND), HFD, and HFD supplemented with 150 mg/kg body weight (BW) SBS extracts for five weeks. We found that the body weight and liver weight of rats in the HFD + SBS group were significantly lower than those in the HFD group. Significantly lower serum total cholesterol (TC) and triglyceride (TG) concentrations were observed in the SBS-supplemented group compared with the HFD group. We also found that the HFD supplemented with SBS group showed dramatically reduced hepatic lipid accumulation compared to the HFD alone group, and administration of SBS resulted in dramatic suppression of TG, TC in the HFD-induced fatty liver. In liver gene expression within the SBS treated group, PPARα was significantly increased and SREBP-1c was significantly suppressed. SBS induced a significant decrease in the hepatic mRNA levels of PPARγ, FAS, ACC1, and DGAT2. In conclusion, SBS improved cholesterol metabolism, decreased lipogenesis, and increased lipid oxidation in HFD-induced hepatic steatosis in rats, implying a potential application in treatment of non-alcoholic fatty liver disease. PMID:24905748

  5. Sasa borealis stem extract attenuates hepatic steatosis in high-fat diet-induced obese rats.

    PubMed

    Song, Yuno; Lee, Soo-Jung; Jang, Sun-Hee; Ha, Ji Hee; Song, Young Min; Ko, Yeoung-Gyu; Kim, Hong-Duck; Min, Wongi; Kang, Suk Nam; Cho, Jae-Hyeon

    2014-06-01

    The aim of the current study is to examine the improving effect of Sasa borealis stem (SBS) extract extracts on high-fat diet (HFD)-induced hepatic steatosis in rats. To determine the hepatoprotective effect of SBS, we fed rats a normal regular diet (ND), HFD, and HFD supplemented with 150 mg/kg body weight (BW) SBS extracts for five weeks. We found that the body weight and liver weight of rats in the HFD + SBS group were significantly lower than those in the HFD group. Significantly lower serum total cholesterol (TC) and triglyceride (TG) concentrations were observed in the SBS-supplemented group compared with the HFD group. We also found that the HFD supplemented with SBS group showed dramatically reduced hepatic lipid accumulation compared to the HFD alone group, and administration of SBS resulted in dramatic suppression of TG, TC in the HFD-induced fatty liver. In liver gene expression within the SBS treated group, PPARα was significantly increased and SREBP-1c was significantly suppressed. SBS induced a significant decrease in the hepatic mRNA levels of PPARγ, FAS, ACC1, and DGAT2. In conclusion, SBS improved cholesterol metabolism, decreased lipogenesis, and increased lipid oxidation in HFD-induced hepatic steatosis in rats, implying a potential application in treatment of non-alcoholic fatty liver disease. PMID:24905748

  6. Deepure Tea Improves High Fat Diet-Induced Insulin Resistance and Nonalcoholic Fatty Liver Disease

    PubMed Central

    Deng, Jing-Na; Li, Juan; Mu, Hong-Na; Liu, Yu-Ying; Wang, Ming-Xia; Pan, Chun-Shui; Fan, Jing-Yu; Ye, Fei; Han, Jing-Yan

    2015-01-01

    This study was to explore the protective effects of Deepure tea against insulin resistance and hepatic steatosis and elucidate the potential underlying molecular mechanisms. C57BL/6 mice were fed with a high fat diet (HFD) for 8 weeks to induce the metabolic syndrome. In the Deepure tea group, HFD mice were administrated with Deepure tea at 160 mg/kg/day by gavage for 14 days. The mice in HFD group received water in the same way over the same period. The age-matched C57BL/6 mice fed with standard chow were used as normal control. Compared to the mice in HFD group, mice that received Deepure tea showed significantly reduced plasma insulin and improved insulin sensitivity. Deepure tea increased the expression of insulin receptor substrate 2 (IRS-2), which plays an important role in hepatic insulin signaling pathway. Deepure tea also led to a decrease in hepatic fatty acid synthesis and lipid accumulation, which were mediated by the downregulation of sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthesis (FAS), and acetyl-CoA carboxylase (ACC) proteins that are involved in liver lipogenesis. These results suggest that Deepure tea may be effective for protecting against insulin resistance and hepatic steatosis via modulating IRS-2 and downstream signaling SREBP-1c, FAS, and ACC. PMID:26504484

  7. Edible Bird's Nest Prevents High Fat Diet-Induced Insulin Resistance in Rats.

    PubMed

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ooi, Der-Jiun; Sarega, Nadarajan; Azmi, Nur Hanisah; Ismail, Norsharina; Chan, Kim Wei; Hou, Zhiping; Yusuf, Norhayati Binti

    2015-01-01

    Edible bird's nest (EBN) is used traditionally in many parts of Asia to improve wellbeing, but there are limited studies on its efficacy. We explored the potential use of EBN for prevention of high fat diet- (HFD-) induced insulin resistance in rats. HFD was given to rats with or without simvastatin or EBN for 12 weeks. During the intervention period, weight measurements were recorded weekly. Blood samples were collected at the end of the intervention and oral glucose tolerance test conducted, after which the rats were sacrificed and their liver and adipose tissues collected for further studies. Serum adiponectin, leptin, F2-isoprostane, insulin, and lipid profile were estimated, and homeostatic model assessment of insulin resistance computed. Effects of the different interventions on transcriptional regulation of insulin signaling genes were also evaluated. The results showed that HFD worsened metabolic indices and induced insulin resistance partly through transcriptional regulation of the insulin signaling genes. Additionally, simvastatin was able to prevent hypercholesterolemia but promoted insulin resistance similar to HFD. EBN, on the other hand, prevented the worsening of metabolic indices and transcriptional changes in insulin signaling genes due to HFD. The results suggest that EBN may be used as functional food to prevent insulin resistance. PMID:26273674

  8. Intrinsic aerobic capacity impacts susceptibility to acute high-fat diet-induced hepatic steatosis

    PubMed Central

    Matthew Morris, E.; Jackman, Matthew R.; Johnson, Ginger C.; Liu, Tzu-Wen; Lopez, Jordan L.; Kearney, Monica L.; Fletcher, Justin A.; Meers, Grace M. E.; Koch, Lauren G.; Britton, Stephen L.; Scott Rector, R.; Ibdah, Jamal A.; MacLean, Paul S.

    2014-01-01

    Aerobic capacity/fitness significantly impacts susceptibility for fatty liver and diabetes, but the mechanisms remain unknown. Herein, we utilized rats selectively bred for high (HCR) and low (LCR) intrinsic aerobic capacity to examine the mechanisms by which aerobic capacity impacts metabolic vulnerability for fatty liver following a 3-day high-fat diet (HFD). Indirect calorimetry assessment of energy metabolism combined with radiolabeled dietary food was employed to examine systemic metabolism in combination with ex vivo measurements of hepatic lipid oxidation. The LCR, but not HCR, displayed increased hepatic lipid accumulation in response to the HFD despite both groups increasing energy intake. However, LCR rats had a greater increase in energy intake and demonstrated greater daily weight gain and percent body fat due to HFD compared with HCR. Additionally, total energy expenditure was higher in the larger LCR. However, controlling for the difference in body weight, the LCR has lower resting energy expenditure compared with HCR. Importantly, respiratory quotient was significantly higher during the HFD in the LCR compared with HCR, suggesting reduced whole body lipid utilization in the LCR. This was confirmed by the observed lower whole body dietary fatty acid oxidation in LCR compared with HCR. Furthermore, LCR liver homogenate and isolated mitochondria showed lower complete fatty acid oxidation compared with HCR. We conclude that rats bred for low intrinsic aerobic capacity show greater susceptibility for dietary-induced hepatic steatosis, which is associated with a lower energy expenditure and reduced whole body and hepatic mitochondrial lipid oxidation. PMID:24961240

  9. Hydrogen Sulfide Mitigates Kidney Injury in High Fat Diet-Induced Obese Mice.

    PubMed

    Wu, Dongdong; Gao, Biao; Li, Mengling; Yao, Ling; Wang, Shuaiwei; Chen, Mingliang; Li, Hui; Ma, Chunyan; Ji, Ailing; Li, Yanzhang

    2016-01-01

    Obesity is prevalent worldwide and is a major risk factor for the development and progression of kidney disease. Hydrogen sulfide (H2S) plays an important role in renal physiological and pathophysiological processes. However, whether H2S is able to mitigate kidney injury induced by obesity in mice remains unclear. In this study, we demonstrated that H2S significantly reduced the accumulation of lipids in the kidneys of high fat diet- (HFD-) induced obese mice. The results of hematoxylin and eosin, periodic acid-Schiff, and Masson's trichrome staining showed that H2S ameliorated the kidney structure, decreased the extent of interstitial injury, and reduced the degree of kidney fibrosis in HFD-induced obese mice. We found that H2S decreased the expression levels of tumor necrosis factor-α, interleukin- (IL-) 6, and monocyte chemoattractant protein-1 but increased the expression level of IL-10. Furthermore, H2S treatment decreased the protein expression of p50, p65, and p-p65 in the kidney of HFD-induced obese mice. In conclusion, H2S is able to mitigate renal injury in HFD-induced obese mice through the reduction of kidney inflammation by downregulating the expression of nuclear factor-kappa B. H2S or its releasing compounds may serve as a potential therapeutic molecule for obesity-induced kidney injury. PMID:27413418

  10. Sesamin Ameliorates High-Fat Diet-Induced Dyslipidemia and Kidney Injury by Reducing Oxidative Stress.

    PubMed

    Zhang, Ruijuan; Yu, Yan; Deng, Jianjun; Zhang, Chao; Zhang, Jinghua; Cheng, Yue; Luo, Xiaoqin; Han, Bei; Yang, Haixia

    2016-01-01

    The study explored the protective effect of sesamin against lipid-induced renal injury and hyperlipidemia in a rat model. An animal model of hyperlipidemia was established in Sprague-Dawley rats. Fifty-five adult Sprague-Dawley rats were divided into five groups. The control group was fed a standard diet, while the other four groups were fed a high-fat diet for 5 weeks to induce hyperlipidemia. Three groups received oral sesamin in doses of 40, 80, or 160 mg/(kg·day). Seven weeks later, the blood lipids, renal function, antioxidant enzyme activities, and hyperoxide levels in kidney tissues were measured. The renal pathological changes and expression levels of collagen type IV (Col-IV) and α-smooth muscle actin (α-SMA) were analyzed. The administration of sesamin improved the serum total cholesterol, triglyceride, low-density lipoprotein cholesterol, apolipoprotein-B, oxidized-low-density lipoprotein, and serum creatinine levels in hyperlipidemic rats, while it increased the high-density lipoprotein cholesterol and apolipoprotein-A levels. Sesamin reduced the excretion of 24-h urinary protein and urinary albumin and downregulated α-SMA and Col-IV expression. Moreover, sesamin ameliorated the superoxide dismutase activity and reduced malondialdehyde levels in kidney tissue. Sesamin could mediate lipid metabolism and ameliorate renal injury caused by lipid metabolism disorders in a rat model of hyperlipidemia. PMID:27171111

  11. High Fat Diets Induce Colonic Epithelial Cell Stress and Inflammation that is Reversed by IL-22

    PubMed Central

    Gulhane, Max; Murray, Lydia; Lourie, Rohan; Tong, Hui; Sheng, Yong H.; Wang, Ran; Kang, Alicia; Schreiber, Veronika; Wong, Kuan Yau; Magor, Graham; Denman, Stuart; Begun, Jakob; Florin, Timothy H.; Perkins, Andrew; Cuív, Páraic Ó.; McGuckin, Michael A.; Hasnain, Sumaira Z.

    2016-01-01

    Prolonged high fat diets (HFD) induce low-grade chronic intestinal inflammation in mice, and diets high in saturated fat are a risk factor for the development of human inflammatory bowel diseases. We hypothesized that HFD-induced endoplasmic reticulum (ER)/oxidative stress occur in intestinal secretory goblet cells, triggering inflammatory signaling and reducing synthesis/secretion of proteins that form the protective mucus barrier. In cultured intestinal cells non-esterified long-chain saturated fatty acids directly increased oxidative/ER stress leading to protein misfolding. A prolonged HFD elevated the intestinal inflammatory cytokine signature, alongside compromised mucosal barrier integrity with a decrease in goblet cell differentiation and Muc2, a loss in the tight junction protein, claudin-1 and increased serum endotoxin levels. In Winnie mice, that develop spontaneous colitis, HFD-feeding increased ER stress, further compromised the mucosal barrier and increased the severity of colitis. In obese mice IL-22 reduced ER/oxidative stress and improved the integrity of the mucosal barrier, and reversed microbial changes associated with obesity with an increase in Akkermansia muciniphila. Consistent with epidemiological studies, our experiments suggest that HFDs are likely to impair intestinal barrier function, particularly in early life, which partially involves direct effects of free-fatty acids on intestinal cells, and this can be reversed by IL-22 therapy. PMID:27350069

  12. Germinated Waxy Black Rice Suppresses Weight Gain in High-Fat Diet-Induced Obese Mice.

    PubMed

    Lim, Won-Chul; Ho, Jin-Nyoung; Lee, Hee-Seop; Cho, Hong-Yon

    2016-04-01

    This study was performed to investigate the antiobesity effect of germinated waxy black rice (GWBR) in high-fat diet (HFD)-induced obese mice. The mice were divided into a normal diet (ND) group, HFD group, and 2 test groups for 8 weeks: 2.5% GWBR-supplemented (GWBR-2.5) group and 5% GWBR-supplemented (GWBR-5) group. Supplementing with GWBR significantly reduced body weight gain and lipid accumulation in the liver and adipose tissue compared to the HFD control group. Triglyceride (TG), total cholesterol, and low-density lipoprotein-cholesterol levels in serum were decreased by GWBR supplementation, whereas high-density lipoprotein-cholesterol level significantly increased. In addition, mRNA levels of transcriptional factors, such as peroxisome proliferator-activated receptor-γ, CCAAT enhancer-binding protein (C/EBP)-α, C/EBP-β, sterol regulatory element-binding protein-1c, and related genes, including adipocyte fatty acid-binding protein, fatty acid synthase, and lipoprotein lipase, were significantly lower in the GWBR groups. However, lipolytic enzymes, such as hormone-sensitive lipase, adipose TG lipase, and carnitine palmitoyltransferase-1, and uncoupling protein 2 mRNA levels were significantly higher in GWBR-supplemented mice. These results suggest that GWBR exerts antiobesity effects by decreasing lipid accumulation and promoting lipolysis in HFD-induced obese mice. PMID:27022689

  13. High fat diet induces obesity in British Angora rabbit: a model for experimental obesity.

    PubMed

    Dhungel, S; Sinha, R; Sinha, M; Paudel, B H; Bhattacharya, N; Mandal, M B

    2009-01-01

    A reliable and cost-effective animal model for human obesity with its manifested disorders is yet to be established in the context of increased morbidity and mortality due to obesity and its related problems. Therefore, an attempt was made to produce obesity in locally available British Angora Rabbits (BAR) and examine the effect on metabolic and cardiovascular parameters. Adult male BARs weighing nearly 2 kg were randomly divided into two groups, one of the groups was fed with high fat diet (HFD) ad libitum for 10 weeks and the control group received standard normal rabbit chow for same period. Body weight, skinfold thickness, serum cholesterol, serum glucose and resting heart rate were measured before and after the dietary regimens. After 10 weeks, HFD group of rabbits demonstrated significant (P < 0.05) increase in body weight (+24%) and skinfold thickness (+37%). The gain in body weight was positively correlated to skinfold thickness (r = 0.61). Serum cholesterol, serum glucose and resting heart rate were also increased by 46%, 52% and 15%, respectively. Whereas no such increases in any of these parameters were observed in control group of rabbits. Our results suggest that obesity can be produced in BARs by feeding HFD. The obesity manifests with cardiovascular and metabolic changes. It is proposed that this may serve as a valid and reliable model of experimental obesity. PMID:19810577

  14. Protective effect of lycopene on high-fat diet-induced cognitive impairment in rats.

    PubMed

    Wang, Zhiqiang; Fan, Jin; Wang, Jian; Li, Yuxia; Xiao, Li; Duan, Dan; Wang, Qingsong

    2016-08-01

    A Western diet, high in saturated fats, has been linked to the development of cognitive impairment. Lycopene has recently received considerable attention for its potent protective properties demonstrated in several models of nervous system dysfunction. However, it remains unclear whether lycopene exerts protective effects on cognition. The present study aimed to investigate the protective effects of lycopene on learning and memory impairment and the potential underlying mechanism in rats fed a high-fat diet (HFD). One-month-old male rats were fed different diets for 16 weeks (n=12 per group), including a standard chow diet (CD), a HFD, or a HFD plus lycopene (4mg/kg, oral gavage in the last three weeks). Behavioral testing, including the Morris water maze (MWM), object recognition task (ORT), and anxiety-like behavior in an open field (OF), were assessed at week 16. The dendritic spine density and neuronal density in the hippocampal CA1 subfield were subsequently measured. The results indicate that HFD consumption for 16 weeks significantly impaired spatial memory (P<0.001), working memory (P<0.01), and object recognition memory (P<0.01), decreased the dendritic spine density (P<0.001), damaged pyramidal neurons in the CA1 subfield (P<0.001) compared with the CD group. However, lycopene significantly attenuated learning and memory impairments and prevented the reduction in dendritic spine density (P<0.001). Thus, this study indicated that lycopene helps to protect HFD induced cognitive dysfunction. PMID:27177726

  15. High-Fat Diet Induced Anxiety and Anhedonia: Impact on Brain Homeostasis and Inflammation.

    PubMed

    Dutheil, Sophie; Ota, Kristie T; Wohleb, Eric S; Rasmussen, Kurt; Duman, Ronald S

    2016-06-01

    Depression and type 2 diabetes (T2D) are highly comorbid disorders that carry a large public health burden. However, there is a clear lack of knowledge of the neural pathological pathways underlying these illnesses. The present study aims to elucidate the molecular mechanisms by which a diet rich in fat can cause multiple complications in the brain, thereby affecting intracellular signaling and gene expression that underlie anxiety and depressive behaviors. The results show that a high-fat diet (HFD; ~16 weeks) causes anxiety and anhedonic behaviors. Importantly, the results also show that 4 months of HFD causes disruption of intracellular cascades involved in synaptic plasticity and insulin signaling/glucose homeostasis (ie, Akt, extracellular signal-regulated kinase (ERK), P70S6K), as well as increased corticosterone levels and activation of the innate immune system, including elevation of inflammatory cytokines (ie, IL-6, IL-1β, TNFα). Interestingly, the rapid acting antidepressant ketamine reverses the behavioral deficits caused by HFD and activates ERK and P70S6 kinase signaling in the prefrontal cortex. In addition, we found that pharmacological blockade of the innate immune inflammasome system by repeated administration of an inhibitor of the purinergic P2X7 receptor blocks the anxiety caused by HFD. Together these studies further elucidate the signaling pathways that underlie chronic HFD exposure on anxiety and depressive behaviors, and identify novel therapeutic targets for patients with metabolic disorder or T2D who suffer from anxiety and depression. PMID:26658303

  16. CARD9 knockout ameliorates myocardial dysfunction associated with high fat diet-induced obesity.

    PubMed

    Cao, Li; Qin, Xing; Peterson, Matthew R; Haller, Samantha E; Wilson, Kayla A; Hu, Nan; Lin, Xin; Nair, Sreejayan; Ren, Jun; He, Guanglong

    2016-03-01

    Obesity is associated with chronic inflammation which plays a critical role in the development of cardiovascular dysfunction. Because the adaptor protein caspase recruitment domain-containing protein 9 (CARD9) in macrophages regulates innate immune responses via activation of pro-inflammatory cytokines, we hypothesize that CARD9 mediates the pro-inflammatory signaling associated with obesity en route to myocardial dysfunction. C57BL/6 wild-type (WT) and CARD9(-/-) mice were fed normal diet (ND, 12% fat) or a high fat diet (HFD, 45% fat) for 5months. At the end of 5-month HFD feeding, cardiac function was evaluated using echocardiography. Cardiomyocytes were isolated and contractile properties were measured. Immunofluorescence was performed to detect macrophage infiltration in the heart. Heart tissue homogenates, plasma, and supernatants from isolated macrophages were collected to measure the concentrations of pro-inflammatory cytokines using ELISA kits. Western immunoblotting analyses were performed on heart tissue homogenates and isolated macrophages to explore the underlying signaling mechanism(s). CARD9 knockout alleviated HFD-induced insulin resistance and glucose intolerance, prevented myocardial dysfunction with preserved cardiac fractional shortening and cardiomyocyte contractile properties. CARD9 knockout also significantly decreased the number of infiltrated macrophages in the heart with reduced myocardium-, plasma-, and macrophage-derived cytokines including IL-6, IL-1β and TNFα. Finally, CARD9 knockout abrogated the increase of p38 MAPK phosphorylation, the decrease of LC3BII/LC3BI ratio and the up-regulation of p62 expression in the heart induced by HFD feeding and restored cardiac autophagy signaling. In conclusion, CARD9 knockout ameliorates myocardial dysfunction associated with HFD-induced obesity, potentially through reduction of macrophage infiltration, suppression of p38 MAPK phosphorylation, and preservation of autophagy in the heart. PMID

  17. Hsp70 plays an important role in high-fat diet induced gestational hyperglycemia in mice.

    PubMed

    Xing, Baoheng; Wang, Lili; Li, Qin; Cao, Yalei; Dong, Xiujuan; Liang, Jun; Wu, Xiaohua

    2015-12-01

    Gestational diabetes mellitus (GDM) has emerged as an epidemic disease during the last decade, affecting about 2 to 5% pregnant women. Even among women who have gestational hyperglycemia may also be positively related to adverse outcomes as GDM. Since heat shock protein (Hsp) 70 has been reported to be associated with diabetes and insulin resistance and its expression was reported to be negatively regulated by the membrane-permeable Hsp70 inhibitor MAL3-101 while positively regulated by the Hsp70 activator BGP-15, we investigated whether Hsp70 played a role in a gestational hyperglycemia mouse model. Mice were divided into non-pregnant and pregnant groups, and each comprised three subgroups: control, high-fat diet (HFD) + MAL3-101, and HFD + BGP-15. We examined the serum levels of triglycerides, total cholesterol, glucose, and insulin, as well as conducted thermal detection of brown adipose tissue (BAT). The role of Hsp70 in BAT apoptosis was also investigated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and caspase-3 staining. Higher serum level of Hsp70 was associated with increased bodyweight gain after pregnancy in mice fed HFD. Circulating Hsp70 was elevated in control pregnant mice compared to control non-pregnant mice. BGP-induced serum Hsp70 expression reduced triglycerides, total cholesterol, glucose, and insulin levels in the serum. Additionally, thermal detection of BAT, TUNEL, and caspase-3 staining revealed relationship correlation between Hsp70 and BAT functions. Hsp70 level is associated with hyperglycemia during pregnancy. Our results support the role of Hsp70 in facilitating BAT activities and protecting BAT cells from apoptosis via caspase-3 pathway. PMID:26318018

  18. Morin attenuates hepatic insulin resistance in high-fat-diet-induced obese mice.

    PubMed

    Naowaboot, Jarinyaporn; Wannasiri, Supaporn; Pannangpetch, Patchareewan

    2016-06-01

    Morin is a natural bioflavonoid that exhibits antioxidant and anti-inflammatory properties. The present study was designed to evaluate the effect of morin on insulin resistance, oxidative stress, and inflammation in a high-fat-diet (HFD)-induced obese mice. Obesity was induced in ICR mice by feeding a HFD (60 % kcal from fat) for 12 weeks. After the first 6 weeks, obese mice were treated with morin (50 or 100 mg/kg/day) once daily for further 6 weeks. Blood glucose, lipid profile, insulin, leptin, adiponectin, and markers of oxidative stress and inflammation were then measured. Liver was excised, subjected to histopathology, glycogen determination, and gene and protein expression analysis. Morin administration reduced blood glucose, serum insulin, leptin, malondialdehyde, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) levels and increased serum adiponectin levels. Moreover, there was a reduction in serum lipid and liver triglyceride levels. Liver histology indicated that morin limited accumulation of lipid droplets. Interestingly, morin reduced expression of hepatic sterol regulatory element binding protein 1c (SREBP1c), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) and up-regulated hepatic carnitine palmitoyltransferase 1a (CPT1a) expression. Morin also stimulated glycogen storage and suppressed phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) protein expression. Furthermore, hepatic superoxide dismutase (SOD) and catalase (CAT) expression were increased after morin treatment. These findings indicate that morin has a positive effect in the HFD-induced obesity condition by suppressing lipogenesis, gluconeogenesis, inflammation, and oxidative stress activities. PMID:26976296

  19. Exenatide reverses dysregulated microRNAs in high-fat diet-induced obese mice.

    PubMed

    Lee, Ihn Suk; Park, Ki Cheol; Yang, Keum-Jin; Choi, Hyunsu; Jang, Yi Sun; Lee, Jong Min; Kim, Hye Soo

    2016-01-01

    Exenatide has beneficial effects on insulin sensitivity in several animal models; however, its mechanism of action remains unclear. Furthermore, the relationship between the effect of exenatide on the changes in the relative abundance of microRNAs (miRNAs), which play a role in regulating glucose and lipid metabolism, is not fully understood. Therefore, we assessed the effect of exenatide on miRNA expression in a high-fat diet (HFD)-induced mouse model of obesity. Both HFD control and exenatide-treated HFD mice showed similar body weight gain and increase in β-cell mass. Insulin levels were significantly lower in exenatide-treated mice than in HFD control mice. The levels of miRNA-15a, 29c, 124a, and 375 in the pancreas were significantly increased in HFD control mice. Furthermore, the levels of miRNA-29c, 124a, and 146a in the liver and miRNA-15a, 29c, 124a, and 146a in the muscle were significantly increased. In contrast, the levels of miRNA-15a, 29c, 124a, and 375 in the serum were significantly decreased. These effects were reversed by treatment with exenatide. Our results provide experimental evidence that exenatide-mediated amelioration of insulin sensitivity is associated with antagonistic changes in the relative abundance of miRNA-15a, 29c, 124a, and 375 in tissues and serum, thus highlighting their usefulness as biomarkers for monitoring insulin sensitivity and response to exenatide treatment in experimental diabetes. PMID:26314504

  20. Androgen Deficiency Exacerbates High-Fat Diet-Induced Metabolic Alterations in Male Mice.

    PubMed

    Dubois, Vanessa; Laurent, Michaël R; Jardi, Ferran; Antonio, Leen; Lemaire, Katleen; Goyvaerts, Lotte; Deldicque, Louise; Carmeliet, Geert; Decallonne, Brigitte; Vanderschueren, Dirk; Claessens, Frank

    2016-02-01

    Androgen deficiency is associated with obesity, metabolic syndrome, and type 2 diabetes mellitus in men, but the mechanisms behind these associations remain unclear. In this study, we investigated the combined effects of androgen deficiency and high-fat diet (HFD) on body composition and glucose homeostasis in C57BL/6J male mice. Two models of androgen deficiency were used: orchidectomy (ORX) and androgen receptor knockout mice. Both models displayed higher adiposity and serum leptin levels upon HFD, whereas no differences were seen on a regular diet. Fat accumulation in HFD ORX animals was accompanied by increased sedentary behavior and occurred in spite of reduced food intake. HFD ORX mice showed white adipocyte hypertrophy, correlated with decreased mitochondrial content but not function as well as increased lipogenesis and decreased lipolysis suggested by the up-regulation of fatty acid synthase and the down-regulation of hormone-sensitive lipase. Both ORX and androgen receptor knockout exacerbated HFD-induced glucose intolerance by impairing insulin action in liver and skeletal muscle, as evidenced by the increased triglyceride and decreased glycogen content in these tissues. In addition, serum IL-1β levels were elevated, and pancreatic insulin secretion was impaired after ORX. Testosterone but not dihydrotestosterone supplementation restored the castration effects on body composition and glucose homeostasis. We conclude that sex steroid deficiency in combination with HFD exacerbates adiposity, insulin resistance, and β-cell failure in 2 preclinical male mouse models. Our findings stress the importance of a healthy diet in a clinical context of androgen deficiency and may have implications for the prevention of metabolic alterations in hypogonadal men. PMID:26562264

  1. Megalin-Mediated Tubuloglomerular Alterations in High-Fat Diet-Induced Kidney Disease.

    PubMed

    Kuwahara, Shoji; Hosojima, Michihiro; Kaneko, Reika; Aoki, Hiroyuki; Nakano, Daisuke; Sasagawa, Taiji; Kabasawa, Hideyuki; Kaseda, Ryohei; Yasukawa, Ryota; Ishikawa, Tomomi; Suzuki, Akiyo; Sato, Hiroyoshi; Kageyama, Shun; Tanaka, Takahiro; Kitamura, Nobutaka; Narita, Ichiei; Komatsu, Masaaki; Nishiyama, Akira; Saito, Akihiko

    2016-07-01

    Obesity, an important risk factor for metabolic syndrome (MetS) and cardiovascular disease, is often complicated by CKD, which further increases cardiovascular risk and causes ESRD. To elucidate the mechanism underlying this relationship, we investigated the role of the endocytic receptor megalin in proximal tubule epithelial cells (PTECs). We studied a high-fat diet (HFD)-induced obesity/MetS model using kidney-specific mosaic megalin knockout (KO) mice. Compared with control littermates fed a normal-fat diet, control littermates fed an HFD for 12 weeks showed autolysosomal dysfunction with autophagy impairment and increased expression of hypertrophy, lipid peroxidation, and senescence markers in PTECs of the S2 segment, peritubular capillary rarefaction with localized interstitial fibrosis, and glomerular hypertrophy with mesangial expansion. These were ameliorated in HFD-fed megalin KO mice, even though these mice had the same levels of obesity, dyslipidemia, and hyperglycemia as HFD-fed control mice. Intravital renal imaging of HFD-fed wild-type mice also demonstrated the accumulation of autofluorescent lipofuscin-like substances in PTECs of the S2 segment, accompanied by focal narrowing of tubular lumens and peritubular capillaries. In cultured PTECs, fatty acid-rich albumin induced the increased expression of genes encoding PDGF-B and monocyte chemoattractant protein-1 via megalin, with large (auto)lysosome formation, compared with fatty acid-depleted albumin. Collectively, the megalin-mediated endocytic handling of glomerular-filtered (lipo)toxic substances appears to be involved primarily in hypertrophic and senescent PTEC injury with autophagy impairment, causing peritubular capillary damage and retrograde glomerular alterations in HFD-induced kidney disease. Megalin could be a therapeutic target for obesity/MetS-related CKD, independently of weight, dyslipidemia, and hyperglycemia modification. PMID:26534923

  2. A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance.

    PubMed

    Jun, Lucy S; Siddall, C Parker; Rosen, Evan D

    2011-11-01

    Adipose tissue controls energy homeostasis and systemic insulin sensitivity through the elaboration of a series of cytokines and hormones, collectively termed "adipokines." We and others have identified Lcn2 as a novel adipokine, but its exact role in obesity-induced insulin resistance remains controversial. The aim of this study was to examine the metabolic phenotype of Lcn2(-/-) mice to clarify the role of Lcn2 in metabolism. Male and female Lcn2(-/-) and wild-type (WT) littermates were placed on either chow or high-fat diet (HFD) to characterize their metabolic phenotype. Studies included body weight and body composition, glucose and insulin tolerance tests, and adipokine expression studies in serum and in white adipose tissue (WAT). Neither chow nor HFD cohorts showed any differences in body weight or body composition. Chow-fed Lcn2(-/-) mice did not exhibit any difference in glucose homeostasis compared with WT mice. Fasting serum glucose levels were lower in the chow-fed Lcn2(-/-) mice, but this finding was not seen in the HFD cohort. Serum adiponectin, leptin, resistin, and RBP4 levels were not different between WT and Lcn2(-/-) on chow diet. HFD-fed male Lcn2(-/-) mice did display a small improvement in glucose tolerance, but no difference in insulin sensitivity was seen in either male or female Lcn2(-/-) mice on HFD. We conclude that the global ablation of Lcn2 has a minimal effect on obesity-associated glucose intolerance but does not appear to affect either age- or obesity-mediated insulin resistance in vivo. PMID:21771968

  3. A minor role for lipocalin 2 in high-fat diet-induced glucose intolerance

    PubMed Central

    Jun, Lucy S.; Siddall, C. Parker

    2011-01-01

    Adipose tissue controls energy homeostasis and systemic insulin sensitivity through the elaboration of a series of cytokines and hormones, collectively termed “adipokines.” We and others have identified Lcn2 as a novel adipokine, but its exact role in obesity-induced insulin resistance remains controversial. The aim of this study was to examine the metabolic phenotype of Lcn2−/− mice to clarify the role of Lcn2 in metabolism. Male and female Lcn2−/− and wild-type (WT) littermates were placed on either chow or high-fat diet (HFD) to characterize their metabolic phenotype. Studies included body weight and body composition, glucose and insulin tolerance tests, and adipokine expression studies in serum and in white adipose tissue (WAT). Neither chow nor HFD cohorts showed any differences in body weight or body composition. Chow-fed Lcn2−/− mice did not exhibit any difference in glucose homeostasis compared with WT mice. Fasting serum glucose levels were lower in the chow-fed Lcn2−/− mice, but this finding was not seen in the HFD cohort. Serum adiponectin, leptin, resistin, and RBP4 levels were not different between WT and Lcn2−/− on chow diet. HFD-fed male Lcn2−/− mice did display a small improvement in glucose tolerance, but no difference in insulin sensitivity was seen in either male or female Lcn2−/− mice on HFD. We conclude that the global ablation of Lcn2 has a minimal effect on obesity-associated glucose intolerance but does not appear to affect either age- or obesity-mediated insulin resistance in vivo. PMID:21771968

  4. N-Acetylneuraminic acid attenuates hypercoagulation on high fat diet-induced hyperlipidemic rats

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Wong, WaiTeng; Abdullah, Maizaton Atmadini; Ideris, Aini; Ismail, Norsharina

    2015-01-01

    Background and objective N-Acetylneuraminic acid (Neu5Ac), a type of sialic acid, has close links with cholesterol metabolism and is often used as a biomarker in evaluating the risk of cardiovascular diseases. However, most studies on the health implications of Neu5Ac have focused on its effects on the nervous system, while its effects on cardiovascular risk factors have largely been unreported. Thus, the effects of Neu5Ac on coagulation status in high fat diet (HFD)-induced hyperlipidemic rats were evaluated in this study. Methods Sprague Dawley male rats were divided into five different groups and fed with HFD alone, HFD low-dose Neu5Ac, HFD high-dose Neu5Ac, HFD simvastatin (10 mg/kg day), and normal pellet alone. Food was given ad libitum while body weight of rats was measured weekly. After 12 weeks of intervention, rats were sacrificed and serum and tissue samples were collected for biochemistry and gene expression analysis, respectively. Results The results showed that Neu5Ac could improve lipid metabolism and hyperlipidemia-associated coagulation. Neu5Ac exerted comparable or sometimes better physiological effects than simvastatin, at biochemical and gene expression levels. Conclusions The data indicated that Neu5Ac prevented HFD-induced hyperlipidemia and associated hypercoagulation in rats through regulation of lipid-related and coagulation-related genes and, by extension, induced metabolite and protein changes. The implications of the present findings are that Neu5Ac may be used to prevent coagulation-related cardiovascular events in hyperlipidemic conditions. These findings are worth studying further. PMID:26642300

  5. Exercise ameliorates high fat diet induced cardiac dysfunction by increasing interleukin 10

    PubMed Central

    Kesherwani, Varun; Chavali, Vishalakshi; Hackfort, Bryan T.; Tyagi, Suresh C.; Mishra, Paras K.

    2015-01-01

    Increasing evidence suggests that a sedentary lifestyle and a high fat diet (HFD) leads to cardiomyopathy. Moderate exercise ameliorates cardiac dysfunction, however underlying molecular mechanisms are poorly understood. Increased inflammation due to induction of pro-inflammatory cytokine such as tumor necrosis factor-alpha (TNF-α) and attenuation of anti-inflammatory cytokine such as interleukin 10 (IL-10) contributes to cardiac dysfunction in obese and diabetics. We hypothesized that exercise training ameliorates HFD- induced cardiac dysfunction by mitigating obesity and inflammation through upregulation of IL-10 and downregulation of TNF-α. To test this hypothesis, 8 week old, female C57BL/6J mice were fed with HFD and exercised (swimming 1 h/day for 5 days/week for 8 weeks). The four treatment groups: normal diet (ND), HFD, HFD + exercise (HFD + Ex) and ND + Ex were analyzed for mean body weight, blood glucose level, TNF-α, IL-10, cardiac fibrosis by Masson Trichrome, and cardiac dysfunction by echocardiography. Mean body weights were increased in HFD but comparatively less in HFD + Ex. The level of TNF-α was elevated and IL-10 was downregulated in HFD but ameliorated in HFD + Ex. Cardiac fibrosis increased in HFD and was attenuated by exercise in the HFD + Ex group. The percentage ejection fraction and fractional shortening were decreased in HFD but comparatively increased in HFD + Ex. There was no difference between ND and ND + Ex for the above parameters except an increase in IL-10 level following exercise. Based on these results, we conclude that exercise mitigates HFD- induced cardiomyopathy by decreasing obesity, inducing IL-10, and reducing TNF-α in mice. PMID:25954207

  6. Effect of Ginseng (Panax ginseng) Berry EtOAc Fraction on Cognitive Impairment in C57BL/6 Mice under High-Fat Diet Inducement.

    PubMed

    Park, Chang Hyeon; Park, Seon Kyeong; Seung, Tae Wan; Jin, Dong Eun; Guo, Tianjiao; Heo, Ho Jin

    2015-01-01

    High-fat diet-induced obesity leads to type 2 diabetes. Recently, there has been growing apprehension about diabetes-associated cognitive impairment (DACM). The effect of ginseng (Panax ginseng) berry ethyl acetate fraction (GBEF) on mice with high-fat diet-induced cognitive impairment was investigated to confirm its physiological function. C57BL/6 mice were fed a high-fat diet for 5 weeks and then a high-fat diet with GBEF (20 and 50 mg/kg of body weight) for 4 weeks. After three in vivo behavioral tests (Y-maze, passive avoidance, and Morris water maze tests), blood samples were collected from the postcaval vein for biochemical analysis, and whole brains were prepared for an ex vivo test. A method based on ultra-performance liquid chromatography (UPLC) accurate-mass quadrupole time-of-flight mass spectrometry (Q-TOF/MS) was used to determine major ginsenosides. GBEF decreased the fasting blood glucose levels of high-fat diet-induced diabetes mellitus (DM) mice and improved hyperglycemia. Cognitive behavior tests were examined after setting up the DM mice. The in vivo experiments showed that mice treated with GBEF exhibited more improved cognitive behavior than DM mice. In addition, GBEF effectively inhibited the acetylcholinesterase (AChE) activity and malondialdehyde (MDA) levels of DM mice brain tissues. Q-TOF UPLC/MS analyses of GBEF showed that ginsenoside Re was the major ginsenoside. PMID:26161118

  7. Anti-inflammatory and antiobesity effects of mulberry leaf and fruit extract on high fat diet-induced obesity.

    PubMed

    Lim, Hyun Hwa; Lee, Sung Ok; Kim, Sun Yeou; Yang, Soo Jin; Lim, Yunsook

    2013-10-01

    The purpose of this study was to investigate the anti-inflammatory and antiobesity effect of combinational mulberry leaf extract (MLE) and mulberry fruit extract (MFE) in a high-fat (HF) diet-induced obese mice. Mice were fed a control diet or a HF diet for nine weeks. After obesity was induced, the mice were administered with single MLE at low dose (133 mg/kg/day, LMLE) and high dose (333 mg/kg/day, HMLE) or combinational MLE and MFE (MLFE) at low dose (133 mg MLE and 67 mg MFE/kg/day, LMLFE) and high dose (333 mg MLE and 167 mg MFE/kg/day, HMLFE) by stomach gavage for 12 weeks. The mulberry leaf and fruit extract treatment for 12 weeks did not show liver toxicity. The single MLE and combinational MLFE treatments significantly decreased plasma triglyceride, liver lipid peroxidation levels and adipocyte size and improved hepatic steatosis as compared with the HF group. The combinational MLFE treatment significantly decreased body weight gain, fasting plasma glucose and insulin, and homeostasis model assessment of insulin resistance. HMLFE treatment significantly improved glucose control during intraperitoneal glucose tolerance test compared with the HF group. Moreover, HMLFE treatment reduced protein levels of oxidative stress markers (manganese superoxide dismutase) and inflammatory markers (monocyte chemoattractant protein-1, inducible nitric oxide synthase, C-reactive protein, tumour necrosis factor-α and interleukin-1) in liver and adipose tissue. Taken together, combinational MLFE treatment has potential antiobesity and antidiabetic effects through modulation of obesity-induced inflammation and oxidative stress in HF diet-induced obesity. PMID:24000381

  8. Neuroprotective Effects of Endurance Exercise Against High-Fat Diet-Induced Hippocampal Neuroinflammation.

    PubMed

    Kang, E-B; Koo, J-H; Jang, Y-C; Yang, C-H; Lee, Y; Cosio-Lima, L M; Cho, J-Y

    2016-05-01

    Obesity contributes to systemic inflammation, which is associated with the varied pathogenesis of neurodegenerative diseases. Growing evidence has demonstrated that endurance exercise (EE) mitigates obesity-induced brain inflammation. However, exercise-mediated anti-inflammatory mechanisms remain largely unknown. We investigated how treadmill exercise (TE) reverses obesity-induced brain inflammation, mainly focusing on toll-like receptor-4 (TLR-4)-dependent neuroinflammation in the obese rat brain after 20 weeks of a high-fat diet (HFD). TE in HFD-fed rats resulted in a significant lowering in the homeostasis model assessment of insulin resistance index, the area under the curve for glucose and abdominal visceral fat, and also improved working memory ability in a passive avoidance task relative to sedentary behaviour in HFD-fed rats, with the exception of body weight. More importantly, TE revoked the increase in HFD-induced proinflammatory cytokines (tumour necrosis factor α and interleukin-1β) and cyclooxygenase-2, which is in parallel with a reduction in TLR-4 and its downstream proteins, myeloid differentiation 88 and tumour necrosis factor receptor associated factor 6, and phosphorylation of transforming growth factor β-activated kinase 1, IkBα and nuclear factor-κB. Moreover, TE reduced an indicator of microglia activation, ionised calcium-binding adapter molecule-1, and also decreased glial fibrillary acidic protein, an indicator of gliosis formed by activated astrocytes in the cerebral cortex and the hippocampal dentate gyrus, compared to HFD-fed sedentary rats. Finally, EE up-regulated the expression of anti-apoptotic protein, Bcl-2, and suppressed the expression of pro-apoptotic protein, Bax, in the hippocampus compared to HFD-fed sedentary rats. Taken together, these data suggest that TE may exert neuroprotective effects as a result of mitigating the production of proinflammatory cytokines by inhibiting the TLR4 signalling pathways. The results of

  9. An obligatory role for neurotensin in high-fat-diet-induced obesity.

    PubMed

    Li, Jing; Song, Jun; Zaytseva, Yekaterina Y; Liu, Yajuan; Rychahou, Piotr; Jiang, Kai; Starr, Marlene E; Kim, Ji Tae; Harris, Jennifer W; Yiannikouris, Frederique B; Katz, Wendy S; Nilsson, Peter M; Orho-Melander, Marju; Chen, Jing; Zhu, Haining; Fahrenholz, Timothy; Higashi, Richard M; Gao, Tianyan; Morris, Andrew J; Cassis, Lisa A; Fan, Teresa W-M; Weiss, Heidi L; Dobner, Paul R; Melander, Olle; Jia, Jianhang; Evers, B Mark

    2016-05-19

    Obesity and its associated comorbidities (for example, diabetes mellitus and hepatic steatosis) contribute to approximately 2.5 million deaths annually and are among the most prevalent and challenging conditions confronting the medical profession. Neurotensin (NT; also known as NTS), a 13-amino-acid peptide predominantly localized in specialized enteroendocrine cells of the small intestine and released by fat ingestion, facilitates fatty acid translocation in rat intestine, and stimulates the growth of various cancers. The effects of NT are mediated through three known NT receptors (NTR1, 2 and 3; also known as NTSR1, 2, and NTSR3, respectively). Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with increased risk of diabetes, cardiovascular disease and mortality; however, a role for NT as a causative factor in these diseases is unknown. Here we show that NT-deficient mice demonstrate significantly reduced intestinal fat absorption and are protected from obesity, hepatic steatosis and insulin resistance associated with high fat consumption. We further demonstrate that NT attenuates the activation of AMP-activated protein kinase (AMPK) and stimulates fatty acid absorption in mice and in cultured intestinal cells, and that this occurs through a mechanism involving NTR1 and NTR3 (also known as sortilin). Consistent with the findings in mice, expression of NT in Drosophila midgut enteroendocrine cells results in increased lipid accumulation in the midgut, fat body, and oenocytes (specialized hepatocyte-like cells) and decreased AMPK activation. Remarkably, in humans, we show that both obese and insulin-resistant subjects have elevated plasma concentrations of pro-NT, and in longitudinal studies among non-obese subjects, high levels of pro-NT denote a doubling of the risk of developing obesity later in life. Our findings directly link NT with increased fat absorption and obesity and

  10. High-fat diet induces hepatic insulin resistance and impairment of synaptic plasticity.

    PubMed

    Liu, Zhigang; Patil, Ishan Y; Jiang, Tianyi; Sancheti, Harsh; Walsh, John P; Stiles, Bangyan L; Yin, Fei; Cadenas, Enrique

    2015-01-01

    High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consisted of 3 month-old C57BL/6J mice fed either a normal chow diet (control group) or a HFD (60% of calorie from fat; HFD group) for 12 weeks. This model was characterized as a function of time in terms of body weight, fasting blood glucose and insulin levels, HOMA-IR values, and plasma triglycerides. IRS-1/Akt pathway was assessed in primary hepatocytes and brain homogenates. The effect of HFD in brain was assessed by electrophysiology, input/output responses and long-term potentiation. HFD-fed mice exhibited a significant increase in body weight, higher fasting glucose- and insulin levels in plasma, lower glucose tolerance, and higher HOMA-IR values. In liver, HFD elicited (a) a significant decrease of insulin receptor substrate (IRS-1) phosphorylation on Tyr608 and increase of Ser307 phosphorylation, indicative of IRS-1 inactivation; (b) these changes were accompanied by inflammatory responses in terms of increases in the expression of NFκB and iNOS and activation of the MAP kinases p38 and JNK; (c) primary hepatocytes from mice fed a HFD showed decreased cellular oxygen consumption rates (indicative of mitochondrial functional impairment); this can be ascribed partly to a decreased expression of PGC1α and mitochondrial biogenesis. In brain, HFD feeding elicited (a) an inactivation of the IRS-1 and, consequentially, (b) a decreased expression and plasma membrane localization of the insulin-sensitive neuronal glucose transporters GLUT3/GLUT4; (c) a suppression of the ERK/CREB pathway, and (d) a substantial decrease in long-term potentiation in the CA1 region of hippocampus (indicative of impaired synaptic plasticity). It may be surmised that 12 weeks fed with HFD induce a systemic insulin resistance that impacts

  11. Emodin improves lipid and glucose metabolism in high fat diet-induced obese mice through regulating SREBP pathway.

    PubMed

    Li, Jinmei; Ding, Lili; Song, Baoliang; Xiao, Xu; Qi, Meng; Yang, Qiaoling; Yang, Qiming; Tang, Xiaowen; Wang, Zhengtao; Yang, Li

    2016-01-01

    Currently, obesity has become a worldwide epidemic associated with Type 2 diabetes, dyslipidemia, cardiovascular disease and chronic metabolic diseases. Emodin is one of the active anthraquinone derivatives from Rheum palmatum and some other Chinese herbs with anti-inflammatory, anticancer and hepatoprotective properties. In the present study, we investigated the anti-obesity effects of emodin in obese mice and explore its potential pharmacological mechanisms. Male C57BL/6 mice were fed with high-fat diet for 12 weeks to induce obesity. Then the obese mice were divided into four groups randomly, HFD or emodin (40mg/kg/day and 80mg/kg/day) or lovastatin (30mg/kg/ day) for another 6 weeks. Body weight and food intake were recorded every week. At the end of the treatment, the fasting blood glucose, glucose and insulin tolerance test, serum and hepatic lipid levels were assayed. The gene expressions of liver and adipose tissues were analyzed with a quantitative PCR assay. Here, we found that emodin inhibited sterol regulatory element-binding proteins (SREBPs) transactivity in huh7 cell line. Furthermore, emodin (80mg/kg/day) treatment blocked body weight gain, decreased blood lipids, hepatic cholesterol and triglyceride content, ameliorated insulin sensitivity, and reduced the size of white and brown adipocytes. Consistently, SREBP-1 and SREBP-2 mRNA levels were significantly reduced in the liver and adipose tissue after emodin treatment. These data demonstrated that emodin could improve high-fat diet-induced obesity and associated metabolic disturbances. The underlying mechanism is probably associated with regulating SREBP pathway. PMID:26626587

  12. Anti-inflammatory and anti-diabetic effects of brown seaweeds in high-fat diet-induced obese mice

    PubMed Central

    Oh, Ji-Hyun; Kim, Jaehoon

    2016-01-01

    BACKGROUND/OBJECTIVES Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ appeared to show improved insulin sensitivity compared to mice fed HFD. Consistently, we observed significantly reduced blood glucose concentrations in mice fed HFD + LJ compared with those of mice fed HFD. Although no significant differences in adipocyte size were detected among the HFD-fed groups, consumption of seaweeds decreased formation of HFD-induced crown-like structures in gonadal adipose tissue as well as plasma inflammatory cytokines. BMDM from mice fed HFDs with seaweeds showed differential regulation of pro-inflammatory cytokines such as IL-1β and IL-6 compared with BMDM from mice fed HFD by LPS stimulation. CONCLUSION Although seaweed consumption did not prevent long-term HFD-induced obesity in C57BL/6N mice, it reduced insulin resistance (IR) and circulation of pro-inflammatory cytokines. Therefore, seaweeds may ameliorate systemic inflammation and IR in obesity partially due to inhibition of inflammatory signaling in adipose tissue cells as well as bone marrow-derived immune cells. PMID:26865915

  13. Skeletal Muscle Mitochondrial Bioenergetics and Morphology in High Fat Diet Induced Obesity and Insulin Resistance: Focus on Dietary Fat Source.

    PubMed

    Putti, Rosalba; Migliaccio, Vincenzo; Sica, Raffaella; Lionetti, Lillà

    2015-01-01

    It has been suggested that skeletal muscle mitochondria play a key role in high fat (HF) diet induced insulin resistance (IR). Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle IR. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to IR. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of IR. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift toward mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and IR development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle IR and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle IR, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance. PMID:26834644

  14. Thrombospondin 1 Mediates High-Fat Diet-Induced Muscle Fibrosis and Insulin Resistance in Male Mice

    PubMed Central

    Jiang, Yibin; Barnes, Richard H.; Tokunaga, Masakuni; Martinez-Santibañez, Gabriel; Geletka, Lynn; Lumeng, Carey N.; Buchner, David A.

    2013-01-01

    Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression. PMID:24140711

  15. Thrombospondin 1 mediates high-fat diet-induced muscle fibrosis and insulin resistance in male mice.

    PubMed

    Inoue, Mayumi; Jiang, Yibin; Barnes, Richard H; Tokunaga, Masakuni; Martinez-Santibañez, Gabriel; Geletka, Lynn; Lumeng, Carey N; Buchner, David A; Chun, Tae-Hwa

    2013-12-01

    Thrombospondin 1 (THBS1 or TSP-1) is a circulating glycoprotein highly expressed in hypertrophic visceral adipose tissues of humans and mice. High-fat diet (HFD) feeding induces the robust increase of circulating THBS1 in the early stages of HFD challenge. The loss of Thbs1 protects male mice from diet-induced weight gain and adipocyte hypertrophy. Hyperinsulinemic euglycemic clamp study has demonstrated that Thbs1-null mice are protected from HFD-induced insulin resistance. Tissue-specific glucose uptake study has revealed that the insulin-sensitive phenotype of Thbs1-null mice is mostly mediated by skeletal muscles. Further assessments of the muscle phenotype using RNA sequencing, quantitative PCR, and histological studies have demonstrated that Thbs1-null skeletal muscles are protected from the HFD-dependent induction of Col3a1 and Col6a1, coupled with a new collagen deposition. At the same time, the Thbs1-null mice display a better circadian rhythm and higher amplitude of energy expenditure with a browning phenotype in sc adipose tissues. These results suggest that THBS1, which circulates in response to a HFD, may induce insulin resistance and fibrotic tissue damage in skeletal muscles as well as the de-browning of sc adipose tissues in the early stages of a HFD challenge. Our study may shed new light on the pathogenic role played by a circulating extracellular matrix protein in the cross talk between adipose tissues and skeletal muscles during obesity progression. PMID:24140711

  16. Rutin Increases Muscle Mitochondrial Biogenesis with AMPK Activation in High-Fat Diet-Induced Obese Rats

    PubMed Central

    Seo, Sangjin; Lee, Mak-Soon; Chang, Eugene; Shin, Yoonjin; Oh, Soojung; Kim, In-Hwan; Kim, Yangha

    2015-01-01

    Decreased mitochondrial number and dysfunction in skeletal muscle are associated with obesity and the progression of obesity-associated metabolic disorders. The specific aim of the current study was to investigate the effects of rutin on mitochondrial biogenesis in skeletal muscle of high-fat diet-induced obese rats. Supplementation with rutin reduced body weight and adipose tissue mass, despite equivalent energy intake (p < 0.05). Rutin significantly increased mitochondrial size and mitochondrial DNA (mtDNA) content as well as gene expression related to mitochondrial biogenesis, such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), nuclear respiratory factor-1 (NRF-1), transcription factor A (Tfam), and nicotinamide adenine dinucleotide (NAD)-dependent deacetylase, sirtulin1 (SIRT1) in skeletal muscle (p < 0.05). Moreover, rutin consumption increased muscle adenosine monophosphate-activated protein kinase (AMPK) activity by 40% (p < 0.05). Taken together, these results suggested at least partial involvement of muscle mitochondria and AMPK activation in the rutin-mediated beneficial effect on obesity. PMID:26402699

  17. The NAD+ precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet induced obesity

    PubMed Central

    Cantó, Carles; Houtkooper, Riekelt H.; Pirinen, Eija; Youn, Dou Y.; Oosterveer, Maaike H.; Cen, Yana; Fernandez-Marcos, Pablo J.; Yamamoto, Hiroyasu; Andreux, Pénélope A.; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A.; Auwerx, Johan

    2013-01-01

    SUMMARY As NAD+ is a rate-limiting co-substrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38 —both NAD+ consumers— increases NAD+ bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD+ precursor with the ability to increase NAD+ levels, Sir2-dependent gene silencing and replicative lifespan in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD+ levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin, NR, could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. PMID:22682224

  18. The NAD(+) precursor nicotinamide riboside enhances oxidative metabolism and protects against high-fat diet-induced obesity.

    PubMed

    Cantó, Carles; Houtkooper, Riekelt H; Pirinen, Eija; Youn, Dou Y; Oosterveer, Maaike H; Cen, Yana; Fernandez-Marcos, Pablo J; Yamamoto, Hiroyasu; Andreux, Pénélope A; Cettour-Rose, Philippe; Gademann, Karl; Rinsch, Chris; Schoonjans, Kristina; Sauve, Anthony A; Auwerx, Johan

    2012-06-01

    As NAD(+) is a rate-limiting cosubstrate for the sirtuin enzymes, its modulation is emerging as a valuable tool to regulate sirtuin function and, consequently, oxidative metabolism. In line with this premise, decreased activity of PARP-1 or CD38-both NAD(+) consumers-increases NAD(+) bioavailability, resulting in SIRT1 activation and protection against metabolic disease. Here we evaluated whether similar effects could be achieved by increasing the supply of nicotinamide riboside (NR), a recently described natural NAD(+) precursor with the ability to increase NAD(+) levels, Sir2-dependent gene silencing, and replicative life span in yeast. We show that NR supplementation in mammalian cells and mouse tissues increases NAD(+) levels and activates SIRT1 and SIRT3, culminating in enhanced oxidative metabolism and protection against high-fat diet-induced metabolic abnormalities. Consequently, our results indicate that the natural vitamin NR could be used as a nutritional supplement to ameliorate metabolic and age-related disorders characterized by defective mitochondrial function. PMID:22682224

  19. Skeletal Muscle Mitochondrial Bioenergetics and Morphology in High Fat Diet Induced Obesity and Insulin Resistance: Focus on Dietary Fat Source

    PubMed Central

    Putti, Rosalba; Migliaccio, Vincenzo; Sica, Raffaella; Lionetti, Lillà

    2016-01-01

    It has been suggested that skeletal muscle mitochondria play a key role in high fat (HF) diet induced insulin resistance (IR). Two opposite views are debated on mechanisms by which mitochondrial function could be involved in skeletal muscle IR. In one theory, mitochondrial dysfunction is suggested to cause intramyocellular lipid accumulation leading to IR. In the second theory, excess fuel within mitochondria in the absence of increased energy demand stimulates mitochondrial oxidant production and emission, ultimately leading to the development of IR. Noteworthy, mitochondrial bioenergetics is strictly associated with the maintenance of normal mitochondrial morphology by maintaining the balance between the fusion and fission processes. A shift toward mitochondrial fission with reduction of fusion protein, mainly mitofusin 2, has been associated with reduced insulin sensitivity and inflammation in obesity and IR development. However, dietary fat source during chronic overfeeding differently affects mitochondrial morphology. Saturated fatty acids induce skeletal muscle IR and inflammation associated with fission phenotype, whereas ω-3 polyunsaturated fatty acids improve skeletal muscle insulin sensitivity and inflammation, associated with a shift toward mitochondrial fusion phenotype. The present minireview focuses on mitochondrial bioenergetics and morphology in skeletal muscle IR, with particular attention to the effect of different dietary fat sources on skeletal muscle mitochondria morphology and fusion/fission balance. PMID:26834644

  20. Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation.

    PubMed

    Liu, Chang; Rajapakse, Angana G; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II(-/-) mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II(-/-) mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II(-/-) mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II(-/-)-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity. PMID:26846206

  1. Targeting arginase-II protects mice from high-fat-diet-induced hepatic steatosis through suppression of macrophage inflammation

    PubMed Central

    Liu, Chang; Rajapakse, Angana G.; Riedo, Erwin; Fellay, Benoit; Bernhard, Marie-Claire; Montani, Jean-Pierre; Yang, Zhihong; Ming, Xiu-Fen

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) associates with obesity and type 2 diabetes. Hypoactive AMP-activated protein kinase (AMPK), hyperactive mammalian target of rapamycin (mTOR) signaling, and macrophage-mediated inflammation are mechanistically linked to NAFLD. Studies investigating roles of arginase particularly the extrahepatic isoform arginase-II (Arg-II) in obesity-associated NAFLD showed contradictory results. Here we demonstrate that Arg-II−/− mice reveal decreased hepatic steatosis, macrophage infiltration, TNF-α and IL-6 as compared to the wild type (WT) littermates fed high fat diet (HFD). A higher AMPK activation (no difference in mTOR signaling), lower levels of lipogenic transcription factor SREBP-1c and activity/expression of lipogenic enzymes were observed in the Arg-II−/− mice liver. Moreover, release of TNF-α and IL-6 from bone marrow-derived macrophages (BMM) of Arg-II−/− mice is decreased as compared to WT-BMM. Conditioned medium from Arg-II−/−-BMM exhibits weaker activity to facilitate triglyceride synthesis paralleled with lower expression of SREBP-1c and SCD-1 and higher AMPK activation in hepatocytes as compared to that from WT-BMM. These effects of BMM conditioned medium can be neutralized by neutralizing antibodies against TNF-α and IL-6. Thus, Arg-II-expressing macrophages facilitate diet-induced NAFLD through TNF-α and IL-6 in obesity. PMID:26846206

  2. High Hydrostatic Pressure Extract of Red Ginseng Attenuates Inflammation in Rats with High-fat Diet Induced Obesity

    PubMed Central

    Jung, Sunyoon; Lee, Mak-Soon; Shin, Yoonjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2015-01-01

    Chronic low-grade inflammation is associated with obesity. This study investigated effect of high hydrostatic pressure extract of red ginseng (HRG) on inflammation in rats with high-fat (HF) diet induced obesity. Male, Sprague-Dawley rats (80~110 g) were randomly divided into two groups, and fed a 45% HF diet (HF) and a 45% HF diet containing 1.5% HRG (HF+HRG) for 14 weeks. At the end of the experiment, the serum leptin level was reduced by the HRG supplementation. The mRNA expression of genes related to adipogenesis including peroxisome proliferator-activated receptor-gamma and adipocyte protein 2 was down-regulated in the white adipose tissue (WAT). The mRNA levels of major inflammatory cytokines such as tumor necrosis factor-α, monocyte chemoattractant protein 1, and interleukin-6 were remarkably down-regulated by the HRG in WAT. These results suggest that HRG might be beneficial in ameliorating the inflammation-associated health complications by suppressing adipogenic and pro-inflammatory gene expression. PMID:26770912

  3. Critical role of the C5a-activated neutrophils in high-fat diet-induced vascular inflammation

    PubMed Central

    Osaka, Mizuko; Ito, Shunsuke; Honda, Masaki; Inomata, Yukihiro; Egashira, Kensuke; Yoshida, Masayuki

    2016-01-01

    Exceed and chronic high-fat diet (HFD) contributes to the diagnosis and development of atherosclerosis, obesity, and metabolic syndrome. However, the key molecular component(s) triggered by HFD responsible for initiating vascular inflammation remain unknown. We observed that feeding HFD for 4 weeks is sufficient to induce leukocyte recruitment in the femoral artery of wild-type mice. Neutrophil- and monocyte-depletion analyses confirmed the preferential recruitment of neutrophils in these mice. Protein analysis of sera from HFD-fed mice revealed a marked elevation of complement component C5a levels. Exogenous C5a alone induced leukocyte recruitment, which was abolished by a C5a-receptor antagonist. We also examined the role of neutrophil-derived MCP-1 in accumulation of leukocytes in the artery. These results demonstrated a previously unrecognized role for C5a and neutrophils in the early onset of HFD-induced vascular inflammation. Further study may help in elucidating a novel regulatory pathway to control diet-induced inflammation such as that in case of atherosclerosis. PMID:26893238

  4. Dietary Polyphenols Promote Growth of the Gut Bacterium Akkermansia muciniphila and Attenuate High-Fat Diet-Induced Metabolic Syndrome.

    PubMed

    Roopchand, Diana E; Carmody, Rachel N; Kuhn, Peter; Moskal, Kristin; Rojas-Silva, Patricio; Turnbaugh, Peter J; Raskin, Ilya

    2015-08-01

    Dietary polyphenols protect against metabolic syndrome, despite limited absorption and digestion, raising questions about their mechanism of action. We hypothesized that one mechanism may involve the gut microbiota. To test this hypothesis, C57BL/6J mice were fed a high-fat diet (HFD) containing 1% Concord grape polyphenols (GP). Relative to vehicle controls, GP attenuated several effects of HFD feeding, including weight gain, adiposity, serum inflammatory markers (tumor necrosis factor [TNF]α, interleukin [IL]-6, and lipopolysaccharide), and glucose intolerance. GP lowered intestinal expression of inflammatory markers (TNFα, IL-6, inducible nitric oxide synthase) and a gene for glucose absorption (Glut2). GP increased intestinal expression of genes involved in barrier function (occludin) and limiting triglyceride storage (fasting-induced adipocyte factor). GP also increased intestinal gene expression of proglucagon, a precursor of proteins that promote insulin production and gut barrier integrity. 16S rRNA gene sequencing and quantitative PCR of cecal and fecal samples demonstrated that GP dramatically increased the growth of Akkermansia muciniphila and decreased the proportion of Firmicutes to Bacteroidetes, consistent with prior reports that similar changes in microbial community structure can protect from diet-induced obesity and metabolic disease. These data suggest that GP act in the intestine to modify gut microbial community structure, resulting in lower intestinal and systemic inflammation and improved metabolic outcomes. The gut microbiota may thus provide the missing link in the mechanism of action of poorly absorbed dietary polyphenols. PMID:25845659

  5. Skeletal Muscle TRIB3 Mediates Glucose Toxicity in Diabetes and High- Fat Diet-Induced Insulin Resistance.

    PubMed

    Zhang, Wei; Wu, Mengrui; Kim, Teayoun; Jariwala, Ravi H; Garvey, W John; Luo, Nanlan; Kang, Minsung; Ma, Elizabeth; Tian, Ling; Steverson, Dennis; Yang, Qinglin; Fu, Yuchang; Garvey, W Timothy

    2016-08-01

    In the current study, we used muscle-specific TRIB3 overexpressing (MOE) and knockout (MKO) mice to determine whether TRIB3 mediates glucose-induced insulin resistance in diabetes and whether alterations in TRIB3 expression as a function of nutrient availability have a regulatory role in metabolism. In streptozotocin diabetic mice, TRIB3 MOE exacerbated, whereas MKO prevented, glucose-induced insulin resistance and impaired glucose oxidation and defects in insulin signal transduction compared with wild-type (WT) mice, indicating that glucose-induced insulin resistance was dependent on TRIB3. In response to a high-fat diet, TRIB3 MOE mice exhibited greater weight gain and worse insulin resistance in vivo compared with WT mice, coupled with decreased AKT phosphorylation, increased inflammation and oxidative stress, and upregulation of lipid metabolic genes coupled with downregulation of glucose metabolic genes in skeletal muscle. These effects were prevented in the TRIB3 MKO mice relative to WT mice. In conclusion, TRIB3 has a pathophysiological role in diabetes and a physiological role in metabolism. Glucose-induced insulin resistance and insulin resistance due to diet-induced obesity both depend on muscle TRIB3. Under physiological conditions, muscle TRIB3 also influences energy expenditure and substrate metabolism, indicating that the decrease and increase in muscle TRIB3 under fasting and nutrient excess, respectively, are critical for metabolic homeostasis. PMID:27207527

  6. High Hydrostatic Pressure Extract of Red Ginseng Attenuates Inflammation in Rats with High-fat Diet Induced Obesity.

    PubMed

    Jung, Sunyoon; Lee, Mak-Soon; Shin, Yoonjin; Kim, Chong-Tai; Kim, In-Hwan; Kim, Yangha

    2015-12-01

    Chronic low-grade inflammation is associated with obesity. This study investigated effect of high hydrostatic pressure extract of red ginseng (HRG) on inflammation in rats with high-fat (HF) diet induced obesity. Male, Sprague-Dawley rats (80~110 g) were randomly divided into two groups, and fed a 45% HF diet (HF) and a 45% HF diet containing 1.5% HRG (HF+HRG) for 14 weeks. At the end of the experiment, the serum leptin level was reduced by the HRG supplementation. The mRNA expression of genes related to adipogenesis including peroxisome proliferator-activated receptor-gamma and adipocyte protein 2 was down-regulated in the white adipose tissue (WAT). The mRNA levels of major inflammatory cytokines such as tumor necrosis factor-α, monocyte chemoattractant protein 1, and interleukin-6 were remarkably down-regulated by the HRG in WAT. These results suggest that HRG might be beneficial in ameliorating the inflammation-associated health complications by suppressing adipogenic and pro-inflammatory gene expression. PMID:26770912

  7. Quercetin Alleviates High-Fat Diet-Induced Oxidized Low-Density Lipoprotein Accumulation in the Liver: Implication for Autophagy Regulation

    PubMed Central

    Liu, Liang; Gao, Chao; Yao, Ping; Gong, Zhiyong

    2015-01-01

    A growing body of evidence has indicated that high-fat diet-induced nonalcoholic fatty liver disease is usually accompanied by oxidized low-density lipoprotein (ox-LDL) deposited in the liver. The current study aimed to investigate the effect of quercetin on high-fat diet-induced ox-LDL accumulation in the liver and to explore the potential underlying mechanisms. The results demonstrate that quercetin supplementation for 24 weeks significantly alleviated high-fat diet-induced liver damage and reduced hepatic cholesterol and ox-LDL level. Quercetin notably inhibited both mRNA and protein expression of CD36 (reduced by 53% and 71%, resp.) and MSR1 (reduced by 25% and 45%, resp.), which were upregulated by high-fat diet. The expression of LC3II was upregulated by 2.4 times whereas that of p62 and mTOR was downregulated by 57% and 63% by quercetin treatment. Therefore, the significantly improved autophagy lysosomal degradation capacity for ox-LDL may be implicated in the hepatoprotective effect of quercetin; scavenger receptors mediated ox-LDL uptake might also be involved. PMID:26697490

  8. Anti-obesity effect of extract from fermented Curcuma longa L. through regulation of adipogenesis and lipolysis pathway in high-fat diet-induced obese rats

    PubMed Central

    Kim, Ji Hye; Kim, Ok-Kyung; Yoon, Ho-Geun; Park, Jeongjin; You, Yanghee; Kim, Kyungmi; Lee, Yoo-Hyun; Choi, Kyung-Chul; Lee, Jeongmin; Jun, Woojin

    2016-01-01

    Background Even though Curcuma longa L. possesses various biological activities, it has strong flavor and taste, which decrease consumer palatability and limit industrial applications in food. Objective The present study investigates the effects of C. longa L. fermented with Aspergillus oryzae supplementation in 60% high-fat diet-induced obese rats measured by the activation of adipogenesis and lipolysis. Design Rats were divided into four groups (n=6 per group) after 1 week of acclimatization: a normal diet group comprised rats fed the AIN76A rodent diet; a high-fat diet-induced obese group with rats fed a 60% high-fat diet; a Garcinia cambogia treated group (positive control) with rats fed a 60% high-fat diet with G. cambogia 500 g/kg body weight (b.w.)/day; and an fermented C. longa L. 50% ethanolic extract treated group (FCE50) with rats fed a 60% high-fat diet with FCE50 500 g/kg b.w./day. Each group received the appropriate vehicle or sample daily by gastric intubation for 12 weeks. Results We found that FCE50 administration suppressed b.w. gain and reduced white adipose tissue weight, serum triglyceride (TG), and cholesterol in high-fat diet-induced obese rats. These results can be associated with the suppression of adipocyte differentiation and lipogenesis with a decrease in the mRNA expressions of fatty acid synthase, acetyl-CoA carboxylase, adipocyte protein 2, and lipoprotein lipase induced by FCE50 administration. In addition, FCE50 increased lipolysis and β-oxidation by up-regulating the expression of lipases such as adipose triglyceride lipase, hormone-sensitive lipase, adiponectin, and AMP-activated protein kinase. Conclusions These results suggest that FCE50 can be a candidate for the prevention of obesity via suppressing adipogenesis and promoting lipolysis. PMID:26822962

  9. Novel PPAR Pan Agonist, ZBH Ameliorates Hyperlipidemia and Insulin Resistance in High Fat Diet Induced Hyperlipidemic Hamster

    PubMed Central

    Xie, Xinni; Xue, Nina; Jin, Xueyuan; Wang, Lili

    2014-01-01

    Effective and safe pharmacological interventions for hyperlipidemia remains badly needed. By incorporating the key pharmacophore of fibrates into the natural scaffold of resveratrol, a novel structural compound ZBH was constructed. In present study, we found ZBH reserved approximately one third of the sirtuin 1 (SIRT1) activation produced by resveratrol at in-vitro enzyme activity assay, directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. Moreover, ZBH (EC50, 1.75 µM) activate PPARα 21 fold more efficiently than the well-known PPAR pan agonist bezafibrate (EC50, 37.37 µM) in the cellular transactivation assays. In the high fat diet induced hyperlipidemic hamsters, 5-week treatment with ZBH significantly lowered serum triglyceride, total cholesterol, LDL-C, FFA, hyperinsulinemia, and improved insulin sensitivity more potently than bezafibrate. Meanwhile, serum transaminases, creatine phosphokinase and CREA levels were found not altered by ZBH intervention. Mechanism study indicated ZBH promoted the expression of PPARα target genes and SIRT1 mRNA. Hepatic lipogenesis was markedly decreased via down-regulation of lipogenic genes, and fatty acid uptake and oxidation was simultaneously increased in the liver and skeletal muscle via up-regulation of lipolysis genes. Glucose uptake and utilization was also significantly promoted in skeletal muscle. These results suggested that ZBH significantly lowered hyperlipidemia and ameliorated insulin resistance more efficiently than bezafibrate in the hyperlipidemic hamsters primarily by activating of PPARα, and SIRT1 promotion and activation. ZBH thus presents a potential new agent to combat hyperlipidemia. PMID:24759758

  10. Antihyperlipidemic and Antioxidant Activities of Edible Tunisian Ficus carica L. Fruits in High Fat Diet-Induced Hyperlipidemic Rats.

    PubMed

    Belguith-Hadriche, Olfa; Ammar, Sonda; Contreras, Maria Del Mar; Turki, Mouna; Segura-Carretero, Antonio; El Feki, Abdelfattah; Makni-Ayedi, Fatma; Bouaziz, Mohamed

    2016-06-01

    The phenolic constituents of the aqueous-ethanolic extract of Tunisian Ficus carica (F. carica) fruit (FE) and its antihyperlipidemic and antioxidant activities in high-fat diet-induced hyperlipidemic rats (HFD) were evaluated. The obtained results demonstrated that the FE improved the lipid profile by decreasing the total cholesterol, triglyceride, low-density lipoprotein cholesterol and increasing high-density lipoprotein cholesterol levels. It also reduced the content of thiobarbituric acid-reactive substances and increased the antioxidant enzymes in liver, heart and kidney in HFD-fed rats. These antihyperlipidemic effects and in vivo antioxidative effects correlated with the in vitro phenolic content scavenging ability. Thus, the major phenolic compounds were identified using reversed-phase ultra-high-performance liquid chromatography (RP-UHPLC) coupled with two detection systems: diode-array detection (DAD) and quadrupole time-of-flight (QTOF) mass spectrometry (MS). Therefore, in the negative ionization mode, 28 phenolic compounds, including hydroxybenzoic acids, hydroxycinnamic acids, flavanoids and hydroxycoumarins were characterized. Dihydroxybenzoic acid di-pentoside, the flavonol quercetin 3-O-rutinoside and the flavone assigned as apigenin 8-C-glucoside were the main representative compounds in 'Tounsi' fruits. This work was complemented by the detection of seven other phenolic compounds in the positive ionization mode, including anthocyanins and furanocoumarins. Overall, these results have shown that the FE has a significant hypocholesterolemic effect and antioxidant activity in HFD-fed rats. This beneficial effect may be partly due to these phenolic constituents, especially vitexin, dihydroxybenzoic acid di-pentoside as well as rutin. PMID:27086310

  11. Vitis thunbergii var. taiwaniana Extracts and Purified Compounds Ameliorate Obesity in High-Fat Diet-Induced Obese Mice.

    PubMed

    Lin, Shyr-Yi; Huang, Guan-Cheng; Hsieh, Ying-Ying; Lin, Yin-Shiou; Han, Chuan-Hsiao; Wen, Chi-Luan; Chang, Chi-I; Hou, Wen-Chi

    2015-10-28

    The increasing prevalence of obesity continues to gain more attention worldwide. In this study, diet-induced obese mice were used to evaluate the antiobesity effects of extracts, fractions, and purified compounds from Vitis thunbergii var. taiwaniana (VTT). The C57BL/6J mice were fed a 5-week high-fat diet (HF) concurrently with ethanol extracts (Et-ext, 80 mg/kg) from roots (R), stems (S), and leaves (L) by oral gavage daily. Only R-Et-ext interventions showed significant weight reduction in mice compared with those in the HF group; however, mouse plasma contents of total cholesterols (TC), total triglycerides (TG) and low-density lipoproteins (LDL) of all three Et-ext intervened groups showed significant reductions compared with those in the HF group. Furthermore, intervention with the ethyl acetate-partitioned fraction (EA-fra, 60 mg/kg) from R-Et-ext but not the n-butanol-partitioned fraction or water fraction from R-Et-ext showed significant weight reduction in mice compared with those in the HF group. The same molecular weights of three resveratrol tetramers, (+)-hopeaphenol, (+)-vitisin A, and (-)-vitisin B, were isolated from the EA-fra of VTT-R. The (+)-vitisin A and fenofibrate (25 mg/kg) but not the (+)-hopeaphenol and (-)-vitisin B interventions showed significant weight reduction in mice compared with those in the HF group. The total feed intake among the HF groups with or without interventions showed no significant differences. The mouse plasma contents of TC, TG, LDL, free fatty acid, and plasma lipase activity of the three resveratrol tetramer-intervened groups showed reductions in the mice compared with those in the HF group. It was proposed that the lipase inhibitory activities of VTT extracts and purified resveratrol tetramers might contribute in part to the antiobesity effect, and these results suggested that VTT may be developed as functional food for achieving antiobesity objectives and requires further investigation. PMID:26448517

  12. Curcuma longa Extract Associated with White Pepper Lessens High Fat Diet-Induced Inflammation in Subcutaneous Adipose Tissue

    PubMed Central

    Memvanga, Patrick B.; Névraumont, Elodie; Larondelle, Yvan; Préat, Véronique; Cani, Patrice D.; Delzenne, Nathalie M.

    2013-01-01

    Background Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity. Methodology/Principal Findings Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation. Conclusions/Significance These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition. PMID:24260564

  13. Novel PPAR pan agonist, ZBH ameliorates hyperlipidemia and insulin resistance in high fat diet induced hyperlipidemic hamster.

    PubMed

    Chen, Wei; Fan, Shiyong; Xie, Xinni; Xue, Nina; Jin, Xueyuan; Wang, Lili

    2014-01-01

    Effective and safe pharmacological interventions for hyperlipidemia remains badly needed. By incorporating the key pharmacophore of fibrates into the natural scaffold of resveratrol, a novel structural compound ZBH was constructed. In present study, we found ZBH reserved approximately one third of the sirtuin 1 (SIRT1) activation produced by resveratrol at in-vitro enzyme activity assay, directly bound to and activated all three peroxisome proliferator-activated receptor (PPAR) subtypes respectively in PPAR binding and transactivation assays. Moreover, ZBH (EC₅₀, 1.75 µM) activate PPARα 21 fold more efficiently than the well-known PPAR pan agonist bezafibrate (EC₅₀ 37.37 µM) in the cellular transactivation assays. In the high fat diet induced hyperlipidemic hamsters, 5-week treatment with ZBH significantly lowered serum triglyceride, total cholesterol, LDL-C, FFA, hyperinsulinemia, and improved insulin sensitivity more potently than bezafibrate. Meanwhile, serum transaminases, creatine phosphokinase and CREA levels were found not altered by ZBH intervention. Mechanism study indicated ZBH promoted the expression of PPARα target genes and SIRT1 mRNA. Hepatic lipogenesis was markedly decreased via down-regulation of lipogenic genes, and fatty acid uptake and oxidation was simultaneously increased in the liver and skeletal muscle via up-regulation of lipolysis genes. Glucose uptake and utilization was also significantly promoted in skeletal muscle. These results suggested that ZBH significantly lowered hyperlipidemia and ameliorated insulin resistance more efficiently than bezafibrate in the hyperlipidemic hamsters primarily by activating of PPARα, and SIRT1 promotion and activation. ZBH thus presents a potential new agent to combat hyperlipidemia. PMID:24759758

  14. Beneficial effects of natural Jeju groundwaters on lipid metabolism in high-fat diet-induced hyperlipidemic rats

    PubMed Central

    Wang, Yan-chao; Lu, Jin-miao; Jin, Hui-zi; Ma, Ai-niu; Zhang, Jin-yang; Gong, Nian; Xiao, Qi; Zhu, Bin; Lv, Ying-fang; Yu, Na; Zhang, Wei-dong

    2014-01-01

    BACKGROUND Groundwater is believed to possess many beneficial effects due to its natural source of various minerals. In this study, we examined the effects of natural Jeju groundwater S1 (Samdasoo™), S2 and S3 pumped up from different locations of Jeju Island, Korea, along with local tap water, on body weight gain, serum lipids and lipoproteins, and liver histopathology in high-fat diet-induced hyperlipidemic rats. MATERIALS/METHODS Rats were randomly and equally divided into 6 groups. Different water samples were supplied to the hyperlipidemic rats as their daily drinking water and the widely-used anti-hyperlipidemic drug simvastatin was used as a positive control. Body weight, serum lipids and lipoproteins were measured weekly. Liver weight, liver index and liver histopathology were examined after the execution of the rats. RESULTS After drinking Jeju groundwaters for two months, S2 but not S3 significantly reduced weight growth and serum triglycerides levels and increased high density lipoprotein-C (HDL-C) without affecting total cholesterol or LDL-C. S1 and particularly S2 significantly reduced the severity of liver hypertrophy and steatosis. All Groundwaters had much higher contents of vanadium (S3>S2>S1>>tap water) whereas S1 and S2 but not S3 markedly blocked autoxidation of ferrous ions. CONCLUSION Jeju Groundwater S1 and particularly S2 exhibit protective effects against hyperlipidemia and fatty liver and hypothesize that the beneficial effect of Jeju Groundwaters may be contributed from blockade of autoxidation of ferrous ions rather than their high contents of vanadium. PMID:24741400

  15. Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates high-fat diet-induced myocardial stress.

    PubMed

    Prasad, Vikram; Lorenz, John N; Miller, Marian L; Vairamani, Kanimozhi; Nieman, Michelle L; Wang, Yigang; Shull, Gary E

    2013-12-01

    Acute inhibition of the NHE1 Na(+)/H(+) exchanger protects against ischemia-reperfusion injury and chronic inhibition attenuates development of cardiac hypertrophy and failure. To determine the cardiac effects of chronic inhibition of NHE1 under non-pathological conditions we used NHE1-null mice as a model of long-term NHE1 inhibition. Cardiovascular performance was relatively normal in Nhe1(-/-) mice although cardiac contractility and relaxation were slightly improved in mutant mice of the FVB/N background. GSH levels and GSH:GSSG ratios were elevated in Nhe1(-/-) hearts indicating an enhanced redox potential. Consistent with a reduced need for antioxidant protection, expression of heat shock proteins Hsp60 and Hsp25 was lower in Nhe1(-/-) hearts. Similarly, expression of mitochondrial superoxide dismutase 2 was reduced, with no increase in expression of other ROS scavenging enzymes. GLUT1 levels were increased in Nhe1(-/-) hearts, the number of lipid droplets in myocytes was reduced, and PDK4 expression was refractory to high-fat diet-induced upregulation observed in wild-type hearts. High-fat diet-induced stress was attenuated in Nhe1(-/-) hearts, as indicated by smaller increases in phosphorylation of Hsp25 and α-B crystallin, and there was better preservation of insulin sensitivity, as evidenced by PKB/Akt phosphorylation. Plasma glucose and insulin levels were lower and high-fat diet-induced hepatic lipid accumulation was reduced in Nhe1(-/-) mice, demonstrating extracardiac effects of NHE1 ablation. These data indicate that long-term ablation of NHE1 activity increases the redox potential, mitigates high-fat diet-induced myocardial stress and fatty liver disease, leads to better preservation of insulin sensitivity, and may alter both cardiac and systemic metabolic substrate handling in mice. PMID:24080184

  16. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis.

    PubMed

    Abrigo, Johanna; Rivera, Juan Carlos; Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando; Ezquer, Marcelo; Cabello-Verrugio, Claudio

    2016-01-01

    Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes. PMID:27579157

  17. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis

    PubMed Central

    Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando

    2016-01-01

    Obesity can lead to skeletal muscle atrophy, a pathological condition characterized by the loss of strength and muscle mass. A feature of muscle atrophy is a decrease of myofibrillar proteins as a result of ubiquitin proteasome pathway overactivation, as evidenced by increased expression of the muscle-specific ubiquitin ligases atrogin-1 and MuRF-1. Additionally, other mechanisms are related to muscle wasting, including oxidative stress, myonuclear apoptosis, and autophagy. Stem cells are an emerging therapy in the treatment of chronic diseases such as high fat diet-induced obesity. Mesenchymal stem cells (MSCs) are a population of self-renewable and undifferentiated cells present in the bone marrow and other mesenchymal tissues of adult individuals. The present study is the first to analyze the effects of systemic MSC administration on high fat diet-induced skeletal muscle atrophy in the tibialis anterior of mice. Treatment with MSCs reduced losses of muscle strength and mass, decreases of fiber diameter and myosin heavy chain protein levels, and fiber type transitions. Underlying these antiatrophic effects, MSC administration also decreased ubiquitin proteasome pathway activation, oxidative stress, and myonuclear apoptosis. These results are the first to indicate that systemically administered MSCs could prevent muscle wasting associated with high fat diet-induced obesity and diabetes. PMID:27579157

  18. Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle

    PubMed Central

    Li, Xi; Higashida, Kazuhiko; Kawamura, Takuji; Higuchi, Mitsuru

    2016-01-01

    Long-term high-fat diet increases muscle mitochondrial enzyme activity and endurance performance. However, excessive calorie intake causes intra-abdominal fat accumulation and metabolic syndrome. The purpose of this study was to investigate the effect of an alternating day high-fat diet on muscle mitochondrial enzyme activities, protein content, and intra-abdominal fat mass in rats. Male Wistar rats were given a standard chow diet (CON), high-fat diet (HFD), or alternate-day high-fat diet (ALT) for 4 weeks. Rats in the ALT group were fed a high-fat diet and standard chow every other day for 4 weeks. After the dietary intervention, mitochondrial enzyme activities and protein content in skeletal muscle were measured. Although body weight did not differ among groups, the epididymal fat mass in the HFD group was higher than those of the CON and ALT groups. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities in the plantaris muscle of rats in HFD and ALT were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT groups. No significant difference was observed in muscle glycogen concentration or glucose transporter-4 protein content among the three groups. These results suggest that an alternate-day high-fat diet induces increases in mitochondrial enzyme activities and protein content in rat skeletal muscle without intra-abdominal fat accumulation. PMID:27058555

  19. Alternate-Day High-Fat Diet Induces an Increase in Mitochondrial Enzyme Activities and Protein Content in Rat Skeletal Muscle.

    PubMed

    Li, Xi; Higashida, Kazuhiko; Kawamura, Takuji; Higuchi, Mitsuru

    2016-01-01

    Long-term high-fat diet increases muscle mitochondrial enzyme activity and endurance performance. However, excessive calorie intake causes intra-abdominal fat accumulation and metabolic syndrome. The purpose of this study was to investigate the effect of an alternating day high-fat diet on muscle mitochondrial enzyme activities, protein content, and intra-abdominal fat mass in rats. Male Wistar rats were given a standard chow diet (CON), high-fat diet (HFD), or alternate-day high-fat diet (ALT) for 4 weeks. Rats in the ALT group were fed a high-fat diet and standard chow every other day for 4 weeks. After the dietary intervention, mitochondrial enzyme activities and protein content in skeletal muscle were measured. Although body weight did not differ among groups, the epididymal fat mass in the HFD group was higher than those of the CON and ALT groups. Citrate synthase and beta-hydroxyacyl CoA dehydrogenase activities in the plantaris muscle of rats in HFD and ALT were significantly higher than that in CON rats, whereas there was no difference between HFD and ALT groups. No significant difference was observed in muscle glycogen concentration or glucose transporter-4 protein content among the three groups. These results suggest that an alternate-day high-fat diet induces increases in mitochondrial enzyme activities and protein content in rat skeletal muscle without intra-abdominal fat accumulation. PMID:27058555

  20. Gamma delta T cells promote inflammation and insulin resistance during high fat diet-induced obesity in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gamma delta T cells are resident in adipose tissue and increase during diet-induced obesity. Their possible contribution to the inflammatory response that accompanies diet-induced obesity was investigated in mice after a 5-10 week high milk fat diet. The high milk fat diet resulted in significant in...

  1. Efficacy of Dietary Lipid Control in Healing High-Fat and High-Cholesterol Diet-Induced Fibrotic Steatohepatitis in Rats

    PubMed Central

    Tamada, Hazuki; Naito, Hisao; Kitamori, Kazuya; Hayashi, Yumi; Yamagishi, Nozomi; Kato, Masashi; Nakajima, Tamie

    2016-01-01

    Nonalcoholic steatohepatitis is related to lifestyle, particularly to dietary habits. We developed diet-induced fibrotic steatohepatitis model stroke-prone spontaneously hypertensive 5/Dmcr (SHRSP5/Dmcr) rats showing steatosis, hepatic inflammation, and severe fibrosis induced by high-fat and -cholesterol (HFC) diet feeding. We aimed to clarify the efficacy of dietary intervention on the disease before and after the appearance of fibrosis. Male SHRSP5/Dmcr rats were divided into 9 groups; of these, 6 groups were fed control or HFC diet for several weeks and the remaining 3 groups represented the dietary intervention groups, which were fed the control diet after HFC diet feeding for 2 (before the appearance of fibrosis) or 8 (after the appearance of fibrosis) weeks. Dietary intervention before the appearance of fibrosis significantly improved the steatosis and reset the increased serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and serum total cholesterol (TC) levels. However, dietary intervention after the appearance of fibrosis was unable to reset the levels of hepatic TC, serum ALT, and fibrogenesis-related markers and had only a minor influence on hepatic fibrosis, although it reset the increased expression of transforming growth factor (TGF)-β1 and α-smooth muscle actin (SMA). It was noted that dietary intervention improved the increased AST levels; however, aggregated CD68-positive cells were still observed around the fibrosis area, which may be related to the findings of inflammatory cytokine mRNAs. Taken together, dietary intervention for fibrotic steatohepatitis improved steatosis, although it could not completely improve fibrosis. PMID:26727365

  2. Sea cucumber cerebrosides and long-chain bases from Acaudina molpadioides protect against high fat diet-induced metabolic disorders in mice.

    PubMed

    Liu, Xiaofang; Xu, Jie; Xue, Yong; Gao, Zhuang; Li, Zhaojie; Leng, Kailiang; Wang, Jingfeng; Xue, Changhu; Wang, Yuming

    2015-11-01

    Metabolic syndrome (MS) is a cluster of metabolic disorders such as abdominal obesity, hypertension, glucose intolerance, dyslipidemia and hepatic steatosis that contribute to increased cardiovascular morbidity and mortality. There is an urgent need for strategies to prevent this emerging global epidemic. Recently, growing interest in discovering food functional nutrients for the prevention and treatment of MS has generated. In the present study, sea cucumber cerebrosides (SCC) and the main structural units, long-chain bases (LCB), were prepared from Acaudina molpadioides and then administered to high fat (HF) diet-induced obese C57BL/6J mice at a diet supplement dosage of 0.025% for 5 weeks to evaluate their effects on obesity-related metabolic disorders. SCC and LCB significantly decreased epididymal adipose tissue weights, lowered hepatic triacylglycerol levels, and reduced serum glucose, insulin levels and HOMA-IR index in mice. The activities of hepatic lipogenetic enzymes including FAS, ME and the mRNA levels of SREBP-1c and FAS were reduced by SCC and LCB treatment. However, SCC and LCB showed no effect on the hepatic lipolysis pathway. Besides, SCC and LCB also efficiently up-regulated the gene expression of SREBP-1c, FAS, ACC, ATGL and HSL, and down-regulated the gene expression of LPL and VLDL-r in the adipose tissue. These results demonstrated that SCC and LCB were efficacious in suppressing hepatic SREBP-1c mediated lipogenesis, inhibiting lipid uptake and increasing TG catabolism in the adipose tissue. The ameliorative degree and regulatory mechanisms of these two compounds were basically the same, suggesting that LCB are the key active structural units. Such findings would offer new insight into the application of SCC or LCB in the development of functional foods for preventing MS in humans. PMID:26399628

  3. Loss of NHE1 activity leads to reduced oxidative stress in heart and mitigates high-fat diet-induced myocardial stress

    PubMed Central

    Prasad, Vikram; Lorenz, John N.; Miller, Marian L.; Vairamani, Kanimozhi; Nieman, Michelle L.; Wang, Yigang; Shull, Gary E.

    2013-01-01

    Acute inhibition of the NHE1 Na+/H+ exchanger protects against ischemia-reperfusion injury and chronic inhibition attenuates development of cardiac hypertrophy and failure. To determine the cardiac effects of chronic inhibition of NHE1 under non-pathological conditions we used NHE1-null mice as a model of long-term NHE1 inhibition. Cardiovascular performance was relatively normal in Nhe1−/− mice although cardiac contractility and relaxation were slightly improved in mutant mice of the FVB/N background. GSH levels and GSH:GSSG ratios were elevated in Nhe1−/− hearts indicating an enhanced redox potential. Consistent with a reduced need for antioxidant protection, expression of heat shock proteins Hsp60 and Hsp25 was lower in Nhe1−/− hearts. Similarly, expression of mitochondrial superoxide dismutase 2 was reduced, with no increase in expression of other ROS scavenging enzymes. GLUT1 levels were increased in Nhe1−/− hearts, the number of lipid droplets in myocytes was reduced, and PDK4 expression was refractory to high-fat diet-induced upregulation observed in wild-type hearts. High-fat dietinduced stress was attenuated in Nhe1−/− hearts, as indicated by smaller increases in phosphorylation of Hsp25 and α-B crystallin, and there was better preservation of insulin sensitivity, as evidenced by PKB/Akt phosphorylation. Plasma glucose and insulin levels were lower and high-fat diet-induced hepatic lipid accumulation was reduced in Nhe1−/− mice, demonstrating extracardiac effects of NHE1 ablation. These data indicate that long-term ablation of NHE1 activity increases the redox potential, mitigates high-fat diet-induced myocardial stress and fatty liver disease, leads to better preservation of insulin sensitivity, and may alter both cardiac and systemic metabolic substrate handling in mice. PMID:24080184

  4. Saturated high-fat diet-induced obesity increases adenylate cyclase of myocardial β-adrenergic system and does not compromise cardiac function.

    PubMed

    Vileigas, Danielle F; de Deus, Adriana F; da Silva, Danielle C T; de Tomasi, Loreta C; de Campos, Dijon H S; Adorni, Caroline S; de Oliveira, Scarlet M; Sant'Ana, Paula G; Okoshi, Katashi; Padovani, Carlos R; Cicogna, Antonio C

    2016-09-01

    Obesity is a worldwide pandemic associated with high incidence of cardiovascular disease. The mechanisms by which the obesity leads cardiac dysfunction are not fully elucidated and few studies have evaluated the relationship between obesity and proteins involved in myocardial β-adrenergic (βA) system. The purpose of this study was to evaluate the cardiac function and βA pathway components in myocardium of obese rats. Male Wistar rats were distributed into two groups: control (n = 17; standard diet) and obese (n = 17; saturated high-fat diet) fed for 33 weeks. Nutritional profile and comorbidities were assessed. Cardiac structure and function was evaluated by macroscopic postmortem, echocardiographic and isolated papillary muscle analyzes. Myocardial protein expression of β1- and β2-adrenergic receptors, Gαs protein, adenylate cyclase (AC) and protein kinase A (PKA) was performed by Western blot. Cardiac cyclic adenosine monophosphate (cAMP) levels and PKA activity were assessed by ELISA Obese rats showed increased adiposity index (P < 0.001) and several comorbidities as hypertension, glucose intolerance, insulin resistance, and dyslipidemia compared with control rats. Echocardiographic assessment revealed increased left atrium diameter (C: 4.98 ± 0.38 vs. Ob: 5.47 ± 0.53, P = 0.024) and posterior wall shortening velocity (C: 37.1 ± 3.6 vs. Ob: 41.8 ± 3.8, P = 0.007) in obese group. Papillary muscle evaluation indicated that baseline data and myocardial responsiveness to isoproterenol stimulation were similar between the groups. Protein expression of myocardial AC was higher in obese group than in the control (C: 1.00 ± 0.21 vs. Ob: 1.25 ± 0.10, P = 0.025), whereas the other components were unchanged. These results suggest that saturated high-fat diet-induced obesity was not effective in triggering cardiac dysfunction and impair the beta-adrenergic signaling. PMID:27582064

  5. Anti-obesity effect of Triticum aestivum sprout extract in high-fat-diet-induced obese mice.

    PubMed

    Im, Ji-Young; Ki, Hyeon-Hui; Xin, Mingjie; Kwon, Se-Uk; Kim, Young Ho; Kim, Dae-Ki; Hong, Sun-Pyo; Jin, Jong-Sik; Lee, Young-Mi

    2015-01-01

    Obesity is a common disease worldwide that often results in serious conditions including hypertension, diabetes, and hyperlipidemia. Many herbal medicines have been examined with regard to ameliorating obesity. We investigated the anti-obesity effects of 50% EtOH extract of Triticum aestivum sprout (TAEE) in high-fat-diet (HFD)-induced obese mice. TAEE administration (10, 50, or 200 mg/kg) for 6 weeks significantly decreased the body weights, serum total cholesterol (TC), and low-density lipoprotein cholesterol levels in HFD-fed mice. TAEE treatment reduced lipid accumulation in epididymal white adipose tissue (EWAT) and liver. Moreover, TC and lipid levels were decreased by TAEE treatment in liver. Serum leptin and adiponectin concentrations were reduced by TAEE treatment. TAEE-treated mice showed decreases in peroxisome proliferator-activated receptor γ (PPARγ) and fatty acid synthase expression in EWAT. Furthermore, TAEE administration elevated levels of PPARα protein in the liver of HFD-induced obese mice. These results suggest that TAEE supplementation might be beneficial for the treatment and prevention of obesity and related diseases. PMID:25925980

  6. Tyrosol Attenuates High Fat Diet-Induced Hepatic Oxidative Stress: Potential Involvement of Cystathionine β-Synthase and Cystathionine γ-Lyase.

    PubMed

    Sarna, Lindsei K; Sid, Victoria; Wang, Pengqi; Siow, Yaw L; House, James D; O, Karmin

    2016-05-01

    The Mediterranean diet is known for its cardioprotective effects. Recently, its protective qualities have also been reported in patients with non-alcoholic fatty liver disease (NAFLD). Oxidative stress is one of the important factors responsible for the development and progression of NAFLD. Hydrogen sulfide (H2S), a multifaceted gasotransmitter, has emerged as a potential therapeutic target in NAFLD. Cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) are major enzymes responsible for endogenous H2S synthesis. Since oxidative stress contributes to NAFLD pathogenesis, the objective of this study was to investigate the effect of tyrosol, a major compound in olive oil and white wine, on high fat diet-induced hepatic oxidative stress and the mechanisms involved. Mice (C57BL/6) were fed for 5 weeks with a control diet (10 % kcal fat), a high fat diet (60 % kcal fat, HFD) or a HFD supplemented with tyrosol. High fat diet feeding induced hepatic oxidative stress, as indicated by the significant increase in lipid peroxidation and NADPH oxidase activity. Tyrosol supplementation significantly increased hepatic CBS and CSE expression and H2S synthesis in high fat diet-fed mice. Such effects were associated with the attenuation of high fat diet-induced hepatic lipid peroxidation and the restoration of the redox equilibrium of the antioxidant glutathione. Tyrosol also inhibited palmitic acid-induced oxidative stress in hepatocytes (HepG2 cells). These results suggest that the antioxidant properties of tyrosol may be mediated through functional changes in CBS and CSE activity, which might contribute to the hepatoprotective effect of the Mediterranean diet. PMID:26518313

  7. Cheonggukjang, a soybean paste fermented with B. licheniformis-67 prevents weight gain and improves glycemic control in high fat diet induced obese mice

    PubMed Central

    Choi, Joo-Hee; Pichiah, P.B.Tirupathi; Kim, Min-Jung; Cha, Youn-Soo

    2016-01-01

    In this study, we investigated the anti-obesity effects of soybean paste—Cheonggukjang, fermented with poly gamma glutamic acid producing Bacillus licheniformis-67 in diet induced obese C57BL/6J mice. Forty male C57BL/6J mice aged 4 weeks were divided into four dietary groups; normal diet control, high fat diet control, high fat diet containing 30% of unfermented soybean and high fat diet containing 30% Cheonggukjang fermented with Bacillus licheniformis-67. After 13 weeks of dietary intervention the mice were sacrificed; serum and tissue samples were examined. Serum and hepatic lipid profile, blood glucose, insulin, leptin level were lower (<0.05) along with the body weight and epididymal fat pad weight in the 30% Cheonggukjang supplemented group compared with the high fat diet control group. The expression level of lipid anabolic gene was significantly decreased; whereas the expression level of lipid catabolic genes were significantly increased in the 30% Cheonggukjang supplemented group compared to the high fat diet control group. Collectively, these results suggested that intake of Cheonggukjang fermented with Bacillus licheniformis-67 significantly prevents obesity related parameters. PMID:27499576

  8. Mitigating efficacy of piperine in the physiological derangements of high fat diet induced obesity in Sprague Dawley rats.

    PubMed

    BrahmaNaidu, Parim; Nemani, Harishankar; Meriga, Balaji; Mehar, Santosh Kumar; Potana, Sailaja; Ramgopalrao, Sajjalaguddam

    2014-09-25

    An increased risk of obesity has become a common public health concern as it is associated with hypertension, diabetes, osteoarthritis, heart diseases, liver steatosis etc. Pharmacological intervention with natural product-based drugs is considered a healthier alternative to treat obesity. This study was aimed to evaluate anti-obesity effects of piperine on high fat diet (HFD) induced obesity in rats. Piperine was isolated from methanolic extract of Piper nigrum by using column chromatography and confirmed by LC-MS analysis. Male SD rats were fed HFD initially for 15weeks to induce obesity. After induction of obesity, piperine was supplemented in different doses (20, 30 and 40mg/kgb.wt) through HFD for 42days to experimental rats. HFD induced changes in body weight, body composition, fat percentage, adiposity index, blood pressure, plasma levels of glucose, insulin resistance, leptin, adiponectin, plasma and tissue lipid profiles, liver antioxidants were explained. The activities of lipase, amylase and lipid metabolic marker enzymes such as HMG-CoA reductase, carnitine palmitoyl transferase (CPT), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), lecithin-cholesterol acyl transferase (LCAT) and lipoprotein lipase (LPL) were assessed in experimental rats. Supplementation of piperine at a dose of 40mg/kgb.wt has significantly (p<0.05) reversed the HFD-induced alterations in experimental rats in a dose dependant manner, the maximum therapeutic effect being noted at a dose of 40mg/kgb.wt. Our study concludes that piperine can be well considered as an effective bioactive molecule to suppress of body weight, improve insulin and leptin sensitivity, ultimately leading to regulate obesity. PMID:25087745

  9. Dopamine transporter and D2 receptor binding densities in mice prone or resistant to chronic high fat diet-induced obesity.

    PubMed

    Huang, Xu-Feng; Zavitsanou, Katerina; Huang, Xin; Yu, Yinghua; Wang, HongQin; Chen, Feng; Lawrence, Andrew J; Deng, Chao

    2006-12-15

    This study examined the density of dopamine transporter (DAT) and D2 receptors in the brains of chronic high-fat diet-induced obese (cDIO), obese-resistant (cDR) and low-fat-fed (LF) control mice. Significantly decreased DAT densities were observed in cDR mice compared to cDIO and LF mice, primarily in the nucleus accumbens, striatal and hypothalamic regions. D2 receptor density was significantly lower in the rostral part of caudate putamen in cDIO mice compared to cDR and LF mice. PMID:17000016

  10. Direct infusion MS-based lipid profiling reveals the pharmacological effects of compound K-reinforced ginsenosides in high-fat diet induced obese mice.

    PubMed

    Shon, Jong Cheol; Shin, Hwa-Soo; Seo, Yong Ki; Yoon, Young-Ran; Shin, Heungsop; Liu, Kwang-Hyeon

    2015-03-25

    The serum lipid metabolites of lean and obese mice fed normal or high-fat diets were analyzed via direct infusion nanoelectrospray-ion trap mass spectrometry followed by multivariate analysis. In addition, lipidomic biomarkers responsible for the pharmacological effects of compound K-reinforced ginsenosides (CK), thus the CK fraction, were evaluated in mice fed high-fat diets. The obese and lean groups were clearly discriminated upon principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) score plot, and the major metabolites contributing to such discrimination were triglycerides (TGs), cholesteryl esters (CEs), phosphatidylcholines (PCs), and lysophosphatidylcholines (LPCs). TGs with high total carbon number (>50) and low total carbon number (<50) were negatively and positively associated with high-fat diet induced obesity in mice, respectively. When the CK fraction was fed to obese mice that consumed a high-fat diet, the levels of certain lipids including LPCs and CEs became similar to those of mice fed a normal diet. Such metabolic markers can be used to better understand obesity and related diseases induced by a hyperlipidic diet. Furthermore, changes in the levels of such metabolites can be employed to assess the risk of obesity and the therapeutic effects of obesity management. PMID:25744175

  11. Chrysobalanus icaco L. Leaves Normalizes Insulin Sensitivity and Blood Glucose and Inhibits Weight Gain in High-Fat Diet-Induced Obese Mice.

    PubMed

    White, Pollyanna A S; Araújo, Jessica M D; Cercato, Luana M; Souza, Lucas A; Barbosa, Ana Paula Oliveira; Quintans-Junior, Lucindo José; Machado, Ubiratan F; Camargo, Enilton A; Brito, Luciana C; Santos, Marcio Roberto V

    2016-02-01

    Chrysobalanus icaco L. is a medicinal plant present in the Brazilian coastline and known for its hypoglicemic and antioxidant properties. Here, we assessed the beneficial metabolic effects of the aqueous extract of C. icaco (AECI) leaves in diet-induced obese mice. Swiss mice were fed standard chow (SC used as controls) or high-fat diet (HFD) to induce obesity. After 10 weeks, mice on each diet were divided into two groups with one group used as control while the other group treated with AECI for 4 weeks resulting in four groups of mice: SC; SC treated with AECI (SC + AECI); HFD; and HFD treated with AECI (HFD + AECI). AECI was administered drinking water at about 200 mg/kg. AECI was able to normalize insulin (13,682 ± 1090 vs. 9828 ± 485 AU, P < .05) and fasting blood glucose (192.8 ± 14.2 vs. 132.3 ± 6.4 mg/dL, P < .05) and inhibit weight gain (39 ± 5.7%) and fat storage in liver (72.60 ± 3.83%, P < .0001), despite the high-fat intake. These findings reinforce the use of AECI in hyperglycemia and highlight the potential extract's effect in preventing weight gain and fat accumulation in liver of diet-induced obese mice. PMID:26854845

  12. Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.

    PubMed

    Suzuki-Kemuriyama, Noriko; Matsuzaka, Takashi; Kuba, Motoko; Ohno, Hiroshi; Han, Song-Iee; Takeuchi, Yoshinori; Isaka, Masaaki; Kobayashi, Kazuto; Iwasaki, Hitoshi; Yatoh, Shigeru; Suzuki, Hiroaki; Miyajima, Katsuhiro; Nakae, Dai; Yahagi, Naoya; Nakagawa, Yoshimi; Sone, Hirohito; Yamada, Nobuhiro; Shimano, Hitoshi

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs-eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)-in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis. PMID:27333187

  13. Different Effects of Eicosapentaenoic and Docosahexaenoic Acids on Atherogenic High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

    PubMed Central

    Suzuki-Kemuriyama, Noriko; Matsuzaka, Takashi; Kuba, Motoko; Ohno, Hiroshi; Han, Song-iee; Takeuchi, Yoshinori; Isaka, Masaaki; Kobayashi, Kazuto; Iwasaki, Hitoshi; Yatoh, Shigeru; Suzuki, Hiroaki; Miyajima, Katsuhiro; Nakae, Dai; Yahagi, Naoya; Nakagawa, Yoshimi; Sone, Hirohito; Yamada, Nobuhiro; Shimano, Hitoshi

    2016-01-01

    Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of metabolic syndrome, can progress to steatohepatitis (NASH) and advanced liver damage, such as that from liver cirrhosis and cancer. Recent studies have shown the benefits of consuming n-3 polyunsaturated fatty acids (PUFAs) for the treatment of NAFLD. In the present study, we investigated and compared the effects of the major n-3 PUFAs—eicosapentaenoic acid (EPA, C20:5) and docosahexaenoic acid (DHA, C22:6)—in preventing atherogenic high-fat (AHF) diet-induced NAFLD. Mice were fed the AHF diet supplemented with or without EPA or DHA for four weeks. Both EPA and DHA reduced the pathological features of AHF diet-induced NASH pathologies such as hepatic lobular inflammation and elevated serum transaminase activity. Intriguingly, EPA had a greater hepatic triacylglycerol (TG)-reducing effect than DHA. In contrast, DHA had a greater suppressive effect than EPA on AHF diet-induced hepatic inflammation and ROS generation, but no difference in fibrosis. Both EPA and DHA could be effective for treatment of NAFLD and NASH. Meanwhile, the two major n-3 polyunsaturated fatty acids might differ in a relative contribution to pathological intermediate steps towards liver fibrosis. PMID:27333187

  14. Effects of exercise and L-arginine intake on inflammation in aorta of high-fat diet induced obese rats

    PubMed Central

    Kim, Hee-jae; Son, Junseok; Jin, Eunhee; Lee, Jin; Park, Sok

    2016-01-01

    [Purpose] In the present study, we investigated the effect of exercise and arginine on the inflammatory makers and Cu-Mn superoxide dismutase (SOD) expression in the aortas of high-fat-induced obese rats. [Methods] Fifty 6-month-old male Sprague-Dawley rats were randomly assigned as follows: HF-Con: high-fat diet, HF-Ex: high-fat diet and exercise, HF-Ex+A: high-fat diet and combined exercise and arginine, HF-A: high-fat diet and arginine. The high-fat diet was fed for 12 weeks following 1 week of environmental adaptation with mixed solid chow. The rats performed treadmill exercise 6 times per week for 12 weeks at20 m/min for 60 min. L-argininewas mixed with saline and orally administered at 150 mg/kg once a day. Expressions of inflammatory markers (including NF- κB, TNF-α, COX-2) and SOD were evaluated using western blotting. [Results] NF-κB expression decreased significantly (p<0.05) in the HF-Ex group compared with HF-Con group, and we found additional effects(p<0.01) on NF-κB expression in HF-EX+A compared withHF-Ex. TNF-α expression decreased significantly (p<0.01) in HF-Ex, FH-Ex+A, and FH-A compared with HF-Con. In a similar trend with NF-κB expression, COX-2 expression decreased significantly in HF-Ex compared withHF-Con. In Cu-Mn SOD expression, there was no difference between HF and HF-Ex, but significant increases (p<0.01) inCu-Mn SOD werefound in HF-Ex+A and HF-A. [Conclusion] Based on our results, treatment that combines exercise and arginine might be effective for modulatingvascular inflammation and oxidative stress in obesity PMID:27298811

  15. Compensatory hyperinsulinemia in high-fat diet-induced obese mice is associated with enhanced insulin translation in islets

    SciTech Connect

    Kanno, Ayumi; Asahara, Shun-ichiro; Masuda, Katsuhisa; Matsuda, Tomokazu; Kimura-Koyanagi, Maki; Seino, Susumu; Ogawa, Wataru; Kido, Yoshiaki

    2015-03-13

    A high-fat diet (HF) is associated with obesity, insulin resistance, and hyperglycemia. Animal studies have shown compensatory mechanisms in pancreatic β-cells after high fat load, such as increased pancreatic β-cell mass, enhanced insulin secretion, and exocytosis. However, the effects of high fat intake on insulin synthesis are obscure. Here, we investigated whether insulin synthesis was altered in correlation with an HF diet, for the purpose of obtaining further understanding of the compensatory mechanisms in pancreatic β-cells. Mice fed an HF diet are obese, insulin resistant, hyperinsulinemic, and glucose intolerant. In islets of mice fed an HF diet, more storage of insulin was identified. We analyzed insulin translation in mouse islets, as well as in INS-1 cells, using non-radioisotope chemicals. We found that insulin translational levels were significantly increased in islets of mice fed an HF diet to meet systemic demand, without altering its transcriptional levels. Our data showed that not only increased pancreatic β-cell mass and insulin secretion but also elevated insulin translation is the major compensatory mechanism of pancreatic β-cells. - Highlights: • More stored insulin was recognized in islets of mice fed a high-fat diet. • Insulin translation was not enhanced by fatty acids, but by insulin demand. • Insulin transcription was not altered in islets of mice fed a high-fat diet. • Insulin translation was markedly enhanced in islets of mice fed a high-fat diet. • Non-radioisotope chemicals were used to measure insulin translation in mouse islets.

  16. Nordihydroguaiaretic acid protects against high-fat diet-induced fatty liver by activating AMP-activated protein kinase in obese mice

    SciTech Connect

    Lee, Myoung-Su; Kim, Daeyoung; Jo, Keunae; Hwang, Jae-Kwan

    2010-10-08

    Research highlights: {yields} NDGA decreases high-fat diet-induced body weight gain and adiposity. {yields} NDGA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} NDGA improves lipid storage in vitro through altering lipid regulatory proteins. {yields} Inhibition of lipid storage in vivo and in vitro is mediated by AMPK activation. -- Abstract: Nonalcoholic fatty liver disease, one of the most common causes of chronic liver disease, is strongly associated with metabolic syndrome. Nordihydroguaiaretic acid (NDGA) has been reported to inhibit lipoprotein lipase; however, the effect of NDGA on hepatic lipid metabolism remains unclear. We evaluated body weight, adiposity, liver histology, and hepatic triglyceride content in high-fat diet (HFD)-fed C57BL/6J mice treated with NDGA. In addition, we characterized the underlying mechanism of NDGA's effects in HepG2 hepatocytes by Western blot and RT-PCR analysis. NDGA (100 or 200 mg/kg/day) reduced weight gain, fat pad mass, and hepatic triglyceride accumulation, and improved serum lipid parameters in mice fed a HFD for 8 weeks. NDGA significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the liver and in HepG2 hepatocytes. NDGA downregulated the level of mature SREBP-1 and its target genes (acetyl-CoA carboxylase and fatty acid synthase), but, it upregulated expression of genes involved in fatty acid oxidation, such as peroxisome proliferator-activated receptor (PPAR){alpha}, PPAR{gamma} coactivator-1, carnitine palmitoyl transferase-1, and uncoupling protein-2. The specific AMPK inhibitor compound C attenuated the effects of NDGA on expression of lipid metabolism-related proteins in HepG2 hepatocytes. The beneficial effects of NDGA on HFD-induced hepatic triglyceride accumulation are mediated through AMPK signaling pathways, suggesting a potential target for preventing NAFLD.

  17. Effect of combined mulberry leaf and fruit extract on liver and skin cholesterol transporters in high fat diet-induced obese mice

    PubMed Central

    Valacchi, Giuseppe; Belmonte, Giuseppe; Miracco, Clelia; Eo, Hyeyoon

    2014-01-01

    Obesity is an epidemic disease characterized by an increased inflammatory state and chronic oxidative stress with high levels of pro-inflammatory cytokines and lipid peroxidation. Moreover, obesity alters cholesterol metabolism with increases in low-density lipoprotein (LDL) cholesterols and triglycerides and decreases in high-density lipoprotein (HDL) cholesterols. It has been shown that mulberry leaf and fruit ameliorated hyperglycemic and hyperlipidemic conditions in obese and diabetic subjects. We hypothesized that supplementation with mulberry leaf combined with mulberry fruit (MLFE) ameliorate cholesterol transfer proteins accompanied by reduction of oxidative stress in the high fat diet induced obesity. Mice were fed control diet (CON) or high fat diet (HF) for 9 weeks. After obesity was induced, the mice were administered either the HF or the HF with combination of equal amount of mulberry leaf and fruit extract (MLFE) at 500mg/kg/day by gavage for 12 weeks. MLFE treatment ameliorated HF induced oxidative stress demonstrated by 4-hydroxynonenal (4-HNE) and modulated the expression of 2 key proteins involved in cholesterol transfer such as scavenger receptor class B type 1 (SR-B1) and ATP-binding cassette transporter A1 (ABCA1) in the HF treated animals. This effect was mainly noted in liver tissue rather than in cutaneous tissue. Collectively, this study demonstrated that MLFE treatment has beneficial effects on the modulation of high fat diet-induced oxidative stress and on the regulation of cholesterol transporters. These results suggest that MLFE might be a beneficial substance for conventional therapies to treat obesity and its complications. PMID:24611101

  18. Lipid-Lowering Effects of Pediococcus acidilactici M76 Isolated from Korean Traditional Makgeolli in High Fat Diet-Induced Obese Mice

    PubMed Central

    Moon, Yeon-Jeong; Baik, Sang-Ho; Cha, Youn-Soo

    2014-01-01

    The effect of Pediococcus acidilactici M76 (lactic acid bacteria) isolated from makgeolli on mice fed a high fat diet was investigated to clarify the lipid lowering function. C57BL/6J male mice were randomly divided into a normal diet (ND) group, high fat diet (HD) group, HD plus Pediococcus acidilactici DSM 20284 reference strain (PR) group, and HD plus Pediococcus acidilactici M76 strain (PA) groups. The lyophilized PA and PR strain were dissolved in distilled water at a final concentration of 1.25 × 109 cfu/mL and was given orally to animals at a dose of 4 mL/kg body weight for 12 weeks. The PA group had a lower final body weight, adipose tissue weight, and lipid profile than those in the HD group. Additionally, level of ACC, FAS and PPAR-γ, a key lipid synthesis enzyme, was markedly suppressed in the PA compared to those in the HD group. These data suggest that P. acidilactici M76 may exert a lipid-lowering effect in high fat diet- induced obese mice. PMID:24609135

  19. Preventive and ameliorating effects of citrus D-limonene on dyslipidemia and hyperglycemia in mice with high-fat diet-induced obesity.

    PubMed

    Jing, Li; Zhang, Yu; Fan, Shengjie; Gu, Ming; Guan, Yu; Lu, Xiong; Huang, Cheng; Zhou, Zhiqin

    2013-09-01

    D-limonene is a major constituent in citrus essential oil, which is used in various foods as a flavoring agent. Recently, d-limonene has been reported to alleviate fatty liver induced by a high-fat diet. Here we determined the preventive and therapeutic effects of d-limonene on metabolic disorders in mice with high-fat diet-induced obesity. In the preventive treatment, d-limonene decreased the size of white and brown adipocytes, lowered serum triglyceride (TG) and fasting blood glucose levels, and prevented liver lipid accumulations in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, d-limonene reduced serum TG, low-density lipoprotein cholesterol (LDL-c) and fasting blood glucose levels and glucose tolerance, and increased serum high-density lipoprotein cholesterol (HDL-c) in obese mice. Using a reporter assay and gene expression analysis, we found that d-limonene activated peroxisome proliferator-activated receptor (PPAR)-α signaling, and inhibited liver X receptor (LXR)-β signaling. Our data suggest that the intake of d-limonene may benefit patients with dyslipidemia and hyperglycemia and is a potential dietary supplement for preventing and ameliorating metabolic disorders. PMID:23838456

  20. GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance.

    PubMed

    Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

    2016-01-01

    Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice. PMID:27081476

  1. Probiotic mixture VSL#3 reduce high fat diet induced vascular inflammation and atherosclerosis in ApoE(-/-) mice.

    PubMed

    Chan, Yee Kwan; El-Nezami, Hani; Chen, Yan; Kinnunen, Kristiina; Kirjavainen, Pirkka V

    2016-12-01

    Atherosclerosis results from chronic inflammation potentially caused by translocation of bacterial components from the oro-gastrointestinal tract to circulation. Specific probiotics have anti-inflammatory effects and may reduce bacterial translocation. We thereby tested whether a probiotic mixture with documented anti-inflammatory potential could reduce atherosclerosis. ApoE(-/-) mice were fed high fat diet alone or with VSL#3 or a positive control treatment, telmisartan or both for 12 weeks. All treatments reduced atherosclerotic plaques significantly compared to high fat diet alone. VSL#3 significantly reduced proinflammatory adhesion molecules and risk factors of plaque rupture, reduced vascular inflammation and atherosclerosis to a comparable extent to telmisartan; and VSL#3 treated mice had the most distinctly different intestinal microbiota composition from the control groups. Combining the VSL#3 and telmisartan brought no further benefits. Our findings showed the therapeutic potential of VSL#3 in reducing atherosclerosis and vascular inflammation. PMID:27576894

  2. GPR21 KO mice demonstrate no resistance to high fat diet induced obesity or improved glucose tolerance

    PubMed Central

    Wang, Jinghong; Pan, Zheng; Baribault, Helene; Chui, Danny; Gundel, Caroline; Véniant, Murielle

    2016-01-01

    Gpr21 KO mice generated with Gpr21 KO ES cells obtained from Deltagen showed improved glucose tolerance and insulin sensitivity when fed a high fat diet. Further mRNA expression analysis revealed changes in Rabgap1 levels and raised the possibility that Rabgap1 gene may have been modified. To assess this hypothesis a new Gpr21 KO mouse line using TALENS technology was generated. Gpr21 gene deletion was confirmed by PCR and Gpr21 and Rabgap1 mRNA expression levels were determined by RT-PCR. The newly generated Gpr21 KO mice when fed a normal or high fat diet chow did not maintain their improved metabolic phenotype. In conclusion, Rabgap1 disturbance mRNA expression levels may have contributed to the phenotype of the originally designed Gpr21 KO mice. PMID:27081476

  3. Sasa quelpaertensis leaf extract improves high fat diet-induced lipid abnormalities and regulation of lipid metabolism genes in rats.

    PubMed

    Kim, Jina; Kim, Yoo-Sun; Lee, Hyun Ah; Lim, Ji Ye; Kim, Mina; Kwon, Oran; Ko, Hee-Chul; Kim, Se-Jae; Shin, Jae-Ho; Kim, Yuri

    2014-05-01

    Sasa quelpaertensis is a bamboo leaf that is only grown on Jeju Island in South Korea. It is used as a bamboo tea that is consumed for therapeutic purposes, particularly for its anti-diabetic, diuretic, and anti-inflammatory effects. This study investigated the effect of S. quelpaertensis leaf extract (SQE) on high fat-induced lipid abnormalities and regulation of lipid metabolism-related gene expressions in rats. SQE supplementation significantly decreased the levels of plasma triglycerides, total cholesterol, and low-density lipoprotein cholesterol as well as the atherogenic index. SQE restored levels of plasma high-density lipoprotein cholesterol, which were lowered by a high fat diet. Plasma and cardiac resistin levels were also significantly decreased by SQE supplementation. In adipose tissue, mRNA levels of CAAT/enhancer-binding protein β (C/EBPβ) were suppressed in the SQE group. SQE supplementation decreased the accumulation of lipid droplets, inflammatory cell infiltrations, levels of triglycerides, and total lipids in the liver and effectively down-regulated expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), and uncoupling protein 2 (UCP-2). These results suggest that SQE may be a potential treatment for high fat-related disorders by improving lipid profiles and modulating lipid metabolism. PMID:24738745

  4. Anti-obesity Effect of Dioscorea oppositifolia Extract in High-Fat Diet-Induced Obese Mice and Its Chemical Characterization.

    PubMed

    Jeong, Eun Ju; Jegal, Jonghwan; Ahn, Jongmin; Kim, Jinwoong; Yang, Min Hye

    2016-01-01

    Dioscorea oppositifolia is a well-known edible and traditional medicine for the treatment of gastrointestinal diseases. In our previous study, D. oppositifolia exhibited both pancreatic lipase inhibition and an anti-adipogenesis effect in vitro. This study was performed to investigate the anti-obesity effect of D. oppositifolia on high-fat diet-induced obese mice. Female ICR mice were fed a high-fat diet with the 100 mg/kg of D. oppositifolia n-BuOH extract for 8 weeks. The high-fat diet mice received the 15 mg/kg Orlistat orally as a positive control. The body weight, parametrial adipose tissue weight, and the levels of triglyceride (TG), total cholesterol (TC), and low density lipoprotein (LDL)-cholesterol in blood serum of female ICR mice were significantly decreased by feeding a high-fat diet with the n-BuOH extract of D. oppositifolia. An inhibitory effect of D. oppositifolia extract on dietary fat absorption was also clearly shown. The D. oppositifolia sample was found to contain 3,5-dimethoxy-2,7-phenanthrenediol and (3R,5R)-3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)-3,5-heptanediol as main components based on its phytochemical analysis. The present study is the first report of the anti-obesity effect by D. oppositifolia n-BuOH extract using an established disease model. The increase in fecal fat excretion by treatment of D. oppositifolia may be an effective approach for treating obesity and related diseases. PMID:26700066

  5. Linoleate-rich high-fat diet decreases mortality in hypertensive heart failure rats compared with lard and low-fat diets.

    PubMed

    Chicco, Adam J; Sparagna, Genevieve C; McCune, Sylvia A; Johnson, Christopher A; Murphy, Robert C; Bolden, David A; Rees, Meredith L; Gardner, Ryan T; Moore, Russell L

    2008-09-01

    Recent studies indicate that high-fat diets may attenuate cardiac hypertrophy and contractile dysfunction in chronic hypertension. However, it is unclear whether consuming a high-fat diet improves prognosis in aged individuals with advanced hypertensive heart disease or the extent to which differences in its fatty acid composition modulate its effects in this setting. In this study, aged spontaneously hypertensive heart failure rats were administered a standard high-carbohydrate diet or high-fat diet (42% of kilocalories) supplemented with high-linoleate safflower oil or lard until death to determine their effects on disease progression and mortality. Both high-fat diets attenuated cardiac hypertrophy, left ventricular chamber dilation, and systolic dysfunction observed in rats consuming the high-carbohydrate diet. However, the lard diet significantly hastened heart failure mortality compared with the high-carbohydrate diet, whereas the linoleate diet significantly delayed mortality. Both high-fat diets elicited changes in the myocardial fatty acid profile, but neither had any effect on thromboxane excretion or blood pressure. The prosurvival effect of the linoleate diet was associated with a greater myocardial content and linoleate-enrichment of cardiolipin, an essential mitochondrial phospholipid known to be deficient in the failing heart. This study demonstrates that, despite having favorable effects on cardiac morphology and function in hypertension, a high-fat diet may accelerate or attenuate mortality in advanced hypertensive heart disease depending on its fatty acid composition. The precise mechanisms responsible for the divergent effects of the lard and linoleate-enriched diets merit further investigation but may involve diet-induced changes in the content and/or composition of cardiolipin in the heart. PMID:18663155

  6. The saponin-rich fraction of a Gymnema sylvestre R. Br. aqueous leaf extract reduces cafeteria and high-fat diet-induced obesity.

    PubMed

    Reddy, Rama Manohar I; Latha, Pushpa B; Vijaya, Tartte; Rao, Dattatreya S

    2012-01-01

    We examined the antiobesity effect of a saponin-rich fraction of a Gymnema sylvestre R. Br. aqueous leaf extract (SGE) using cafeteria and high-fat diet-induced obese rats for a period of eight weeks. SGE was orally administered at a dose of 100 mg/kg body weight once a day to the treatment group. It significantly decreased the body weight, food consumption, visceral organs weight, and the levels of triglycerides, total cholesterol, low-density lipoproteins, very low-density lipoproteins, atherogenic index, glucose, and increased the levels of high-density lipoproteins. There was no significant difference with respect to all parameters of the study in case of normal (N) diet and N diet + SGE rats. In vitro, SGE inhibited the pancreatic lipase activity. The present study gave clear evidence that the SGE has a significant antiobese action, supporting its use in traditional medicine, and can be used as a substitute for synthetic drugs. PMID:22486040

  7. Dehydrozingerone exerts beneficial metabolic effects in high-fat diet-induced obese mice viaAMPK activation in skeletal muscle

    PubMed Central

    Kim, Su Jin; Kim, Hong Min; Lee, Eun Soo; Kim, Nami; Lee, Jung Ok; Lee, Hye Jeong; Park, Na Yeon; Jo, Joo Yeon; Ham, Bo Young; Han, Si Hyun; Park, Sun Hwa; Chung, Choon Hee; Kim, Hyeon Soo

    2015-01-01

    Dehydrozingerone (DHZ) exerts beneficial effects on human health; however, its mechanism of action remains unclear. Here, we found that DHZ suppressed high-fat diet-induced weight gain, lipid accumulation and hyperglycaemia in C57BL/6 mice and increased AMP-activated protein kinase (AMPK) phosphorylation and stimulated glucose uptake in C2C12 skeletal muscle cells. DHZ activated p38 mitogen-activated protein kinase (MAPK) signalling in an AMPK-dependent manner. Inhibiting AMPK or p38 MAPK blocked DHZ-induced glucose uptake. DHZ increased GLUT4 (major transporter for glucose uptake) expression in skeletal muscle. Glucose clearance and insulin-induced glucose uptake increased in DHZ-fed animals, suggesting that DHZ increases systemic insulin sensitivity in vivo. Thus, the beneficial health effects of DHZ could possibly be explained by its ability to activate the AMPK pathway in skeletal muscle. PMID:25582026

  8. Black tea polyphenols and polysaccharides improve body composition, increase fecal fatty acid, and regulate fat metabolism in high-fat diet-induced obese rats.

    PubMed

    Wu, Tao; Guo, Yu; Liu, Rui; Wang, Kuan; Zhang, Min

    2016-05-18

    With the current changes in diet and living habits, obesity has become a global health problem. Thus, the weight-reducing function of tea has attracted considerable attention. This study investigated the anti-obesity effect and the mechanism of black tea (BT) polyphenols and polysaccharides in male Sprague-Dawley rats. The BT polyphenols and polysaccharides reduced the body weight, Lee's index, visceral fat weight, and fat cell size but improved the biochemical profile and increased the fecal fatty acid content, thereby preventing high-fat diet-induced obesity. A gene expression profile array was used to screen eight upregulated and five downregulated differentially expressed genes that affect fat metabolic pathways, such as glycerolipid and glycerophospholipid metabolism, fatty acid degradation, glycolysis and gluconeogenesis, bile and pancreatic secretion, the insulin signaling pathway, and steroid hormone secretion. The BT polyphenols and polysaccharides suppressed the formation and accumulation of fat and promoted its decomposition to prevent obesity. PMID:27161951

  9. The Hypolipidemic Effect of Total Saponins from Kuding Tea in High-Fat Diet-Induced Hyperlipidemic Mice and Its Composition Characterized by UPLC-QTOF-MS/MS.

    PubMed

    Song, Chengwu; Yu, Qingsong; Li, Xiaohua; Jin, Shuna; Li, Sen; Zhang, Yang; Jia, Shuailong; Chen, Cheng; Xiang, Yi; Jiang, Hongliang

    2016-05-01

    Kuding tea are used as a traditional tea material and widely consumed in China. In this study, total saponins (TS) from water extract of Kuding tea was prepared by D101 macroporous resins and analyzed by UPLC-QTOF-MS/MS. Then the hypolipidemic effect of TS extract was investigated in high-fat diet-induced hyperlipidemic mice. For comprehensive identification or characterization of saponins in TS extract, 3 major saponins of Kudinoside A, Kudinoside F, and Kudinoside D were isolated and used as standards to investigate the MS/MS fragmentation pattern. As a result, 52 saponins were identified or characterized in TS extract from Kuding tea. In addition, the increased levels of mice serum TC, LDL-C, HDL-C, and atherogenic index (AI) were significantly reduced after the treatment of TS extract. Also, the liver protective effect of TS extract was obviously judged from the photographs stained with oil red-O staining. Meanwhile, TS extract significantly upregulated the expression of hepatic scavenger receptors including SR-AI, SR-BI, and CD36. Therefore, it is reasonable to assume that the overexpression of hepatic scavenger receptors was involved in the hypolipidemic effect of Kuding tea on the high-fat diet-induced hyperlipidemic mice. The TS extract could influence these scavenger receptors, and this could be the potential mechanism of TS extract from Kuding tea in the treatment of lipid disorders. These results give the evidence that the saponins in Kuding tea could provide benefits in managing hypercholesterolemia and may be a good candidate for development as a functional food and nutraceutical. PMID:27074384

  10. Relationship of p53 accumulation in peripheral tissues of high-fat diet-induced obese rats with decrease in metabolic and oncogenic signaling of insulin.

    PubMed

    Homayounfar, Reza; Jeddi-Tehrani, Mahmood; Cheraghpour, Makan; Ghorbani, Asghar; Zand, Hamid

    2015-04-01

    This paper aimed to explore the role of p53 in adipose and some other peripheral tissues of a diet-induced obese model and targeted it using pharmacological approach to ameliorate diet-induced insulin resistance. Five week old male Wistar rats were randomly divided into three groups and fed on low-fat diet (13% control lean group), high-fat diet (41% obese group), or high-fat diet plus a single dose of pifithrin-α in the end of experiments (PFT group). Insulin, glucose, and other serum parameters were analyzed by standard colorimetric kits. Protein levels were evaluated by immunoblotting and immunofluorescence methods. After 12weeks, both body weight and insulin resistance were significantly higher in obese rats than in the control ones. P53 and PTEN protein levels were markedly elevated in peripheral tissues in addition to adipose tissues. AKT activation was decreased in the peripheral tissues of obese rats and was in correlation with the increase of p53 and PTEN level. Systemic pifithrin-α administration considerably diminished p53 levels and ameliorated AKT phosphorylation in all peripheral tissues including adipose tissues. Interestingly, the systemic inhibition of p53 was in correlation with improving insulin glucose at serum level. The present results clearly showed that p53 activation in peripheral tissues was in correlation with decreased insulin action. These results indicated p53 activation in the peripheral tissues of obese subjects as a protective mechanism against chronic insulin elevation, suggested that p53 could be a new target for the treatment of type 2 diabetes. PMID:25016051

  11. Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning.

    PubMed

    Franco, J G; Fernandes, T P; Rocha, C P D; Calviño, C; Pazos-Moura, C C; Lisboa, P C; Moura, E G; Trevenzoli, I H

    2012-11-01

    Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3-adrenoreceptor content in adipose tissue (-40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (-40%, P < 0.05) and SOCS3 (-55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases

  12. Maternal high-fat diet induces obesity and adrenal and thyroid dysfunction in male rat offspring at weaning

    PubMed Central

    Franco, J G; Fernandes, T P; Rocha, C P D; Calviño, C; Pazos-Moura, C C; Lisboa, P C; Moura, E G; Trevenzoli, I H

    2012-01-01

    Maternal nutritional status affects the future development of offspring. Both undernutrition and overnutrition in critical periods of life (gestation or lactation) may cause several hormonal changes in the pups and programme obesity in the adult offspring. We have shown that hyperleptinaemia during lactation results in central leptin resistance, higher adrenal catecholamine secretion, hyperthyroidism, and higher blood pressure and heart rate in the adult rats. Here, we evaluated the effect of a maternal isocaloric high-fat diet on breast milk composition and its impact on leptinaemia, energy metabolism, and adrenal and thyroid function of the offspring at weaning. We hypothesised that the altered source of fat in the maternal diet even under normal calorie intake would disturb the metabolism of the offspring. Female Wistar rats were fed a normal (9% fat; C group) or high-fat diet (29% fat as lard; HF group) for 8 weeks before mating and during pregnancy and lactation. HF mothers presented increased total body fat content after 8 weeks (+27%, P < 0.05) and a similar fat content at the end of lactation. In consequence, the breast milk from the HF group had higher concentration of protein (+18%, P < 0.05), cholesterol (+52%, P < 0.05) and triglycerides (+86%, P < 0.05). At weaning, HF offspring had increased body weight (+53%, P < 0.05) and adiposity (2 fold, P < 0.05), which was associated with lower β3-adrenoreceptor content in adipose tissue (−40%, P < 0.05). The offspring also presented hyperglycaemia (+30%, P < 0.05) and hyperleptinaemia (+62%, P < 0.05). In the leptin signalling pathway in the hypothalamus, we found lower p-STAT3/STAT3 (−40%, P < 0.05) and SOCS3 (−55%, P < 0.05) content in the arcuate nucleus, suggesting leptin resistance. HF offspring also had higher adrenal catecholamine content (+17%, P < 0.05), liver glycogen content (+50%, P < 0.05) and hyperactivity of the thyroid axis at weaning. Our results suggest that a high fat diet increases

  13. Okra polysaccharide improves metabolic disorders in high-fat diet-induced obese C57BL/6 mice.

    PubMed

    Fan, Shengjie; Guo, Lu; Zhang, Yu; Sun, Qinhu; Yang, Baican; Huang, Cheng

    2013-11-01

    Okra is a tropical vegetable that is rich in polysaccharides. Here, we investigated the effects of okra polysaccharide (OP) on metabolic disorders in mice. We found that OP lowered body weight and glucose levels, improved glucose tolerance, and decreased serum total cholesterol levels in high-fat diet-fed C57BL/6 mice. OP regulated the gene expression of liver X receptors (LXRs) and peroxisome proliferator-activated receptors (PPARs) and their target genes in the liver and the adipose tissue of the mice. These results suggest that OP may have therapeutic effects on metabolic diseases via the inhibition of LXR and PPAR signaling. PMID:23894043

  14. Naringin Improves Neuronal Insulin Signaling, Brain Mitochondrial Function, and Cognitive Function in High-Fat Diet-Induced Obese Mice.

    PubMed

    Wang, Dongmei; Yan, Junqiang; Chen, Jing; Wu, Wenlan; Zhu, Xiaoying; Wang, Yong

    2015-10-01

    The epidemic and experimental studies have confirmed that the obesity induced by high-fat diet not only caused neuronal insulin resistance, but also induced brain mitochondrial dysfunction as well as learning impairment in mice. Naringin has been reported to posses biological functions which are beneficial to human cognitions, but its protective effects on HFD-induced cognitive deficits and underlying mechanisms have not been well characterized. In the present study Male C57BL/6 J mice were fed either a control or high-fat diet for 20 weeks and then randomized into four groups treated with their respective diets including control diet, control diet + naringin, high-fat diet (HFD), and high-fat diet + naringin (HFDN). The behavioral performance was assessed by using novel object recognition test and Morris water maze test. Hippocampal mitochondrial parameters were analyzed. Then the protein levels of insulin signaling pathway and the AMP-activated protein kinase (AMPK) in the hippocampus were detected by Western blot method. Our results showed that oral administration of naringin significantly improved the learning and memory abilities as evidenced by increasing recognition index by 52.5% in the novel object recognition test and inducing a 1.05-fold increase in the crossing-target number in the probe test, and ameliorated mitochondrial dysfunction in mice caused by HFD consumption. Moreover, naringin significantly enhanced insulin signaling pathway as indicated by a 34.5% increase in the expression levels of IRS-1, a 47.8% decrease in the p-IRS-1, a 1.43-fold increase in the p-Akt, and a 1.89-fold increase in the p-GSK-3β in the hippocampus of the HFDN mice versus HFD mice. Furthermore, the AMPK activity significantly increased in the naringin-treated (100 mg kg(-1) d(-1)) group. These findings suggest that an enhancement in insulin signaling and a decrease in mitochondrial dysfunction through the activation of AMPK may be one of the mechanisms that naringin

  15. Tissue Inhibitor Of Matrix Metalloproteinase-1 Is Required for High-Fat Diet-Induced Glucose Intolerance and Hepatic Steatosis in Mice

    PubMed Central

    Myrmel, Lene Secher; Petersen, Rasmus Koefoed; Hansen, Jakob Bondo; Tastesen, Hanne Sørup; Mandrup-Poulsen, Thomas; Brünner, Nils; Kristiansen, Karsten

    2015-01-01

    Background Plasma levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are elevated in obesity and obesity-related disorders, such as steatosis, but the metabolic role of TIMP-1 is unclear. Here we investigated how the presence or absence of TIMP-1 affected the development of diet-induced glucose intolerance and hepatic steatosis using the Timp1 null mice. Methods Timp1 knockout (TKO) and wild type (TWT) mice were fed chow, high-fat diet (HFD) or intermediate fat and sucrose diet (IFSD). We determined body weight, body composition, lipid content of the liver, energy intake, energy expenditure, oral glucose tolerance, as well as insulin tolerance. In addition, the histology of liver and adipose tissues was examined and expression of selected genes involved in lipid metabolism and inflammation in liver and adipose tissues was determined by RT-qPCR. Results TKO mice gained less weight and had lower energy efficiency than TWT mice when fed HFD, but not when fed chow or IFSD. Importantly, TKO mice were protected from development of HFD- as well as IFSD-induced glucose intolerance, hepatic steatosis, and altered expression of genes involved in hepatic lipid metabolism and inflammation. Conclusion Collectively, our results indicate that TIMP-1 contributes to the development of diet-induced hepatic steatosis and glucose intolerance and may be a potential therapeutic target. PMID:26168159

  16. Mice Deficient in the Respiratory Chain Gene Cox6a2 Are Protected against High-Fat Diet-Induced Obesity and Insulin Resistance

    PubMed Central

    Quintens, Roel; Singh, Sarvjeet; Lemaire, Katleen; De Bock, Katrien; Granvik, Mikaela; Schraenen, Anica; Vroegrijk, Irene Olga Cornelia Maria; Costa, Veronica; Van Noten, Pieter; Lambrechts, Dennis; Lehnert, Stefan; Van Lommel, Leentje; Thorrez, Lieven; De Faudeur, Geoffroy; Romijn, Johannes Anthonius; Shelton, John Michael; Scorrano, Luca; Lijnen, Henri Roger; Voshol, Peter Jacobus; Carmeliet, Peter; Mammen, Pradeep Puthenveetil Abraham; Schuit, Frans

    2013-01-01

    Oxidative phosphorylation in mitochondria is responsible for 90% of ATP synthesis in most cells. This essential housekeeping function is mediated by nuclear and mitochondrial genes encoding subunits of complex I to V of the respiratory chain. Although complex IV is the best studied of these complexes, the exact function of the striated muscle-specific subunit COX6A2 is still poorly understood. In this study, we show that Cox6a2-deficient mice are protected against high-fat diet-induced obesity, insulin resistance and glucose intolerance. This phenotype results from elevated energy expenditure and a skeletal muscle fiber type switch towards more oxidative fibers. At the molecular level we observe increased formation of reactive oxygen species, constitutive activation of AMP-activated protein kinase, and enhanced expression of uncoupling proteins. Our data indicate that COX6A2 is a regulator of respiratory uncoupling in muscle and we demonstrate that a novel and direct link exists between muscle respiratory chain activity and diet-induced obesity/insulin resistance. PMID:23460811

  17. Cynanchum wilfordii ameliorates hypertension and endothelial dysfunction in rats fed with high fat/cholesterol diets.

    PubMed

    Choi, Deok Ho; Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

    2012-02-01

    Hypercholesterolemia increases the incidence of atherosclerosis and its pathologic complications. This study was performed to test the effect of an ethanol extract of Cynanchum wilfordii (ECW) on vascular dysfunction in rats fed with high fat/cholesterol diets (HFCD). Male rats were fed a HFCD consisting of 7.5% cocoa butter and 1.25% cholesterol, with or without 100, 200 mg/day/kg ECW. Rats fed with HFCD increased body weight associated with an increase in plasma low-density lipoprotein (LDL) cholesterol level. Chronic ECW treatment in HFCD-fed rats lessened LDL cholesterol and triglyceride levels as well as elevated high-density lipoprotein (HDL) cholesterol. Chronic ECW treatment recovered the HFCD-induced increase in systolic blood pressure, maintained smooth and soft intima endothelial layers by the decrease of intima-media thickness. ECW significantly recovered the diet-induced decrease in vasorelaxation to acetylcholine, high-dose ECW apparently increased vasorelaxation response to sodium nitroprusside in rats fed with HFCD. ECW clearly restored the HFCD-induced reduction in endothelial nitric oxide (NO) synthase expression and Akt expression levels in aortic tissue, leading to improve endothelial function through an increase in endothelium-derived NO production. Furthermore, treatment of ECW significantly recovered the HFCD-induced decrease in aortic cGMP levels in rats. These findings suggest that ECW ameliorates hypertension and endothelial dysfunction via improvement of NO/cGMP signaling pathway in aortic tissue of rats fed with HFCD, suggesting a vascular protective role for this herb in the treatment and prevention of atherosclerotic vascular disease. PMID:22176675

  18. Protective Effects of Tamarillo (Cyphomandra betacea) Extract against High Fat Diet Induced Obesity in Sprague-Dawley Rats

    PubMed Central

    Abdul Kadir, Noor Atiqah Aizan; Rahmat, Asmah; Jaafar, Hawa Z. E.

    2015-01-01

    This study aims to investigate the protective effect of Cyphomandra betacea in adult male Sprague-Dawley rats fed with high fat diet. Rats were fed on either normal chow or high fat diet for 10 weeks for obesity induction phase and subsequently received C. betacea extract at low dose (150 mg kg−1), medium dose (200 mg kg−1), or high dose (300 mg kg−1) or placebo via oral gavages for another 7 weeks for treatment phase. Treatment of obese rats with C. betacea extracts led to a significant decrease in total cholesterol and significant increase in HDL-C (p < 0.05). Also there was a trend of positive reduction in blood glucose, triglyceride, and LDL-C with positive reduction of body weight detected in medium and high dosage of C. betacea extract. Interestingly, C. betacea treated rats showed positive improvement of superoxide dismutase (SOD) activity and glutathione peroxidase (GPx) activity along with a significant increase of total antioxidant status (TAS) (p < 0.05). Further, rats treated with C. betacea show significantly lower in TNF-α and IL-6 activities (p < 0.05). This study demonstrates the potential use of Cyphomandra betacea extract for weight maintenance and complimentary therapy to suppress some obesity complication signs. PMID:26171246

  19. Endurance and Resistance Training Affect High Fat Diet-Induced Increase of Ceramides, Inflammasome Expression, and Systemic Inflammation in Mice.

    PubMed

    Mardare, Cornelia; Krüger, Karsten; Liebisch, Gerhard; Seimetz, Michael; Couturier, Aline; Ringseis, Robert; Wilhelm, Jochen; Weissmann, Norbert; Eder, Klaus; Mooren, Frank-Christoph

    2016-01-01

    The study aimed to investigate the effects of differentiated exercise regimes on high fat-induced metabolic and inflammatory pathways. Mice were fed a standard diet (ST) or a high fat diet (HFD) and subjected to regular endurance training (ET) or resistance training (RT). After 10 weeks body weight, glucose tolerance, fatty acids (FAs), circulating ceramides, cytokines, and immunological mediators were determined. The HFD induced a significant increase in body weight and a disturbed glucose tolerance (p < 0.05). An increase of plasma FA, ceramides, and inflammatory mediators in adipose tissue and serum was found (p < 0.05). Both endurance and resistance training decreased body weight (p < 0.05) and reduced serum ceramides (p < 0.005). While RT attenuated the increase of NLRP-3 (RT) expression in adipose tissue, ET was effective in reducing TNF-α and IL-18 expression. Furthermore, ET reduced levels of MIP-1γ, while RT decreased levels of IL-18, MIP-1γ, Timp-1, and CD40 in serum (p < 0.001), respectively. Although both exercise regimes improved glucose tolerance (p < 0.001), ET was more effective than RT. These results suggest that exercise improves HFD-induced complications possibly through a reduction of ceramides, the reduction of inflammasome activation in adipose tissues, and a systemic downregulation of inflammatory cytokines. PMID:26788518

  20. Effects of Compound Dan-shen Root Dropping Pill on hemorheology in high-fat diet induced hyperlipidemia in dogs.

    PubMed

    Guo, Jun; Zhang, Lei; Jiang, Yuhui; Zeng, Zhu; Sun, Dagong; Ka, Weibo; Zheng, Jun; Guo, Zhixin; Wen, Zongyao

    2005-01-01

    The purpose of this study was to examine the effects of Compound Dan-shen Root Dropping Pill (CDRDP) (Tasly Group, Tianjing, China) on hemorheology and biorheology of dogs suffering from hyperlipidemia induced by high-fat diet. Eighteen dogs were randomly divided into two groups: the high-fat diet group (H group); the control group (C group), fed with a standard laboratory diet. Six month later, six dogs in the H group were chosen as the drug-taking group (D group), to which CDRDP was administered, fed with the same diet as H group. In the 4th month, blood was taken from the veins of the dogs, and blood triglyceride (TG), total cholesterol (TC), RBC hemorheological indexes as well as malondialdehyde (MDA), glutathione transferase (GSH-ST) and superoxide dismutase (SOD) activities in plasma and erythrocytes were measured. Compared with H group, TC, TG, plasma MDA levels, the whole blood viscosity, RBC osmotic fragility and the value of CHOL (cholesterol)/PL (phospholipid) of the membrane of D group decreased, however, erythrocyte GSH-ST, histopathological changes in liver, deformation index (DI), orientation index (DI)or, small deformation index (DI)d, electrophoresis ratio and microfluidity of the membrane lipid bilayer of RBCs, increased distinctly. CDRDP can improve micro-hemorheological characteristics, therefore has a significant therapy application of hyperlipidemia. PMID:15665423

  1. Extract of Wax Gourd Peel Prevents High-Fat Diet-Induced Hyperlipidemia in C57BL/6 Mice via the Inhibition of the PPARγ Pathway

    PubMed Central

    Gu, Ming; Fan, Shengjie; Liu, Gaigai; Guo, Lu; Ding, Xiaobo; Lu, Yan; Zhang, Yu; Huang, Cheng

    2013-01-01

    Wax gourd is a popular vegetable in East Asia. In traditional Chinese medicine, wax gourd peel is used to prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, and cardiovascular disease. However, there is no experimental evidence to support these applications. Here, we examined the effect of the extract of wax gourd peel (EWGP) on metabolic disorders in diet-induced C57BL/6 obese mice. In the preventive experiment, EWGP blocked body weight gain and lowered serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), liver TG and TC contents, and fasting blood glucose in mice fed with a high-fat diet. In the therapeutic study, we induced obesity in the mice and treated with EWGP for two weeks. We found that EWGP treatment reduced serum and liver triglyceride (TG) contents and fasting blood glucose and improved glucose tolerance in the mice. Reporter assay and gene expression analysis showed that EWGP could inhibit peroxisome proliferator-activated receptor γ (PPARγ) transactivities and could decrease mRNA levels of PPARγ and its target genes. We also found that HMG-CoA reductase (HMGCR) was downregulated in the mouse liver by EWGP. Our data suggest that EWGP lowers hyperlipidemia of C57BL/6 mice induced by high-fat diet via the inhibition of PPARγ and HMGCR signaling. PMID:23533476

  2. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

    SciTech Connect

    Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong; Ma, Qinyun

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

  3. Early metabolic adaptation in C57BL/6 mice resistant to high fat diet induced weight gain involves an activation of mitochondrial oxidative pathways.

    PubMed

    Boulangé, Claire L; Claus, Sandrine P; Chou, Chieh J; Collino, Sebastiano; Montoliu, Ivan; Kochhar, Sunil; Holmes, Elaine; Rezzi, Serge; Nicholson, Jeremy K; Dumas, Marc E; Martin, François-Pierre J

    2013-04-01

    We investigated the short-term (7 days) and long-term (60 days) metabolic effect of high fat diet induced obesity (DIO) and weight gain in isogenic C57BL/6 mice and examined the specific metabolic differentiation between mice that were either strong-responders (SR), or non-responders (NR) to weight gain. Mice (n = 80) were fed a standard chow diet for 7 days prior to randomization into a high-fat (HF) (n = 56) or a low-fat (LF) (n = 24) diet group. The (1)H NMR urinary metabolic profiles of LF and HF mice were recorded 7 and 60 days after the diet switch. On the basis of the body weight gain (BWG) distribution of HF group, we identified NR mice (n = 10) and SR mice (n = 14) to DIO. Compared with LF, HF feeding increased urinary excretion of glycine conjugates of β-oxidation intermediate (hexanoylglycine), branched chain amino acid (BCAA) catabolism intermediates (isovalerylglycine, α-keto-β-methylvalerate and α-ketoisovalerate) and end-products of nicotinamide adenine dinucleotide (NAD) metabolism (N1-methyl-2-pyridone-5-carboxamide, N1-methyl-4-pyridone-3-carboxamide) suggesting up-regulation of mitochondrial oxidative pathways. In the HF group, NR mice excreted relatively more hexanoylglycine, isovalerylglycine, and fewer tricarboxylic acid (TCA) cycle intermediate (succinate) in comparison to SR mice. Thus, subtle regulation of ketogenic pathways in DIO may alleviate the saturation of the TCA cycle and mitochondrial oxidative metabolism. PMID:23473242

  4. Anti-obesity potential of enzymatic fragments of hyaluronan on high-fat diet-induced obesity in C57BL/6 mice.

    PubMed

    Park, Byong-Gon; Park, Yoon-Sun; Park, Joo Woong; Shin, Eunji; Shin, Woon-Seob

    2016-04-22

    Hyaluronan has diverse biological activities depending on its molecular size. The hyaluronan fragments (50 kDa) can decrease adipogenic differentiation in vitro. However, in vivo anti-obesitic effects of hyaluronan fragments have not been elucidated. Therefore, we examined the anti-obesity effects of hyaluronan fragments on high-fat diet induced obesity in C57BL/6 mice. Oral administration of hyaluronan fragments (200 mg/kg for 8 weeks) decreased body weight, adipose tissues, serum lipid (low-density lipoprotein cholesterol, triglyceride), and leptin level. Hyaluronan fragments decreased the hypertrophy of adipose tissue and ameliorated liver steatosis. The mRNA expression of leptin was reduced in adipocyte by treatment with hyaluronan fragments. Additionally, hyaluronan fragments enhanced the mRNA expression of PPAR-α and its target genes UCP-2 and decreased mRNA expression of PPAR- γ and fatty acid synthase in liver. In conclusions, hyaluronan fragments had marked effects on inhibiting the development of obesity in obese mice fed the high-fat diet. It suggested that enhancing PPAR-α and suppressing PPAR-γ expression are two possible mechanisms for the anti-obesitic effect of hyaluronan fragments. PMID:27012203

  5. Protective effects of aerobic swimming training on high-fat diet induced nonalcoholic fatty liver disease: regulation of lipid metabolism via PANDER-AKT pathway.

    PubMed

    Wu, Hao; Jin, Meihua; Han, Donghe; Zhou, Mingsheng; Mei, Xifan; Guan, Youfei; Liu, Chang

    2015-03-20

    This study aimed to investigate the mechanism by which aerobic swimming training prevents high-fat-diet-induced nonalcoholic fatty liver disease (NAFLD). Forty-two male C57BL/6 mice were randomized into normal-diet sedentary (ND; n = 8), ND exercised (n = 8), high-fat diet sedentary (HFD; n = 13), and HFD exercised groups (n = 13). After 2 weeks of training adaptation, the mice were subjected to an aerobic swimming protocol (60 min/day) 5 days/week for 10 weeks. The HFD group exhibited significantly higher mRNA levels of fatty acid transport-, lipogenesis-, and β-oxidation-associated gene expressions than the ND group. PANDER and FOXO1 expressions increased, whereas AKT expression decreased in the HFD group. The aerobic swimming program with the HFD reversed the effects of the HFD on the expressions of thrombospondin-1 receptor, liver fatty acid-binding protein, long-chain fatty-acid elongase-6, Fas cell surface death receptor, and stearoyl-coenzyme A desaturase-1, as well as PANDER, FOXO1, and AKT. In the HFD exercised group, PPARα and AOX expressions were much higher. Our findings suggest that aerobic swimming training can prevent NAFLD via the regulation of fatty acid transport-, lipogenesis-, and β-oxidation-associated genes. In addition, the benefits from aerobic swimming training were achieved partly through the PANDER-AKT-FOXO1 pathway. PMID:25701781

  6. Effects of Berberine on Amelioration of Hyperglycemia and Oxidative Stress in High Glucose and High Fat Diet-Induced Diabetic Hamsters In Vivo

    PubMed Central

    Liu, Cong; Wang, Zhuo; Song, Yulong; Wu, Dan; Zheng, Xuan; Li, Ping; Jin, Jin; Xu, Nannan; Li, Ling

    2015-01-01

    This study investigated the effects of berberine on amelioration of hyperglycemia and hyperlipidemia and the mechanism involved in high glucose and high fat diet-induced diabetic hamsters. Golden hamsters fed with high glucose and high fat diet were medicated with metformin, simvastatin, and low or high dose of berberine (50 and 100 mg·kg−1) for 6 weeks. The results showed that the body weights were significantly lower in berberine-treated groups than control group. Histological analyses revealed that the treatment of berberine inhibited hepatic fat accumulation. Berberine significantly reduced plasma total cholesterol, triglyceride, free fatty acid, low density lipoprotein cholesterol, malondialdehyde, thiobarbituric acid-reactive substance, and 8-isoprostane level but significantly increased plasma superoxide dismutase activity. Glucose and insulin levels were significantly reduced in metformin and berberine-treated groups. Glucose tolerance tests documented that berberine-treated mice were more glucose tolerant. Berberine treatment increased expression of skeletal muscle glucose transporter 4 mRNA and significantly decreased liver low density lipoprotein receptor mRNA expression. The study suggested that berberine was effective in lowering blood glucose and lipids levels, reducing the body weight, and alleviating the oxidative stress in diabetic hamsters, which might be beneficial in reducing the cardiovascular risk factors in diabetes. PMID:25705654

  7. A Fomitopsis pinicola Jeseng Formulation Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity

    PubMed Central

    Jung, Hoe-Yune; Ji, Yosep; Kim, Na-Ri; Kim, Do-Young; Kim, Kyong-Tai; Choi, Bo-Hwa

    2016-01-01

    This study investigated the antiobesity effect of an extract of the Fomitopsis pinicola Jeseng-containing formulation (FAVA), which is a combination of four natural components: Fomitopsis pinicola Jeseng; Acanthopanax senticosus; Viscum album coloratum; and Allium tuberosum. High-fat diet- (HFD-) fed male C57BL/6J mice were treated with FAVA (200 mg/kg/day) for 12 weeks to monitor the antiobesity effect and amelioration of nonalcoholic fatty liver diseases (NAFLD). Body and white adipose tissue (WAT) weights were reduced in FAVA-treated mice, and a histological examination showed an amelioration of fatty liver in FAVA-treated mice without decreasing food consumption. Additionally, FAVA reduced serum lipid profiles, leptin, and insulin levels compared with the HFD control group. The FAVA extract suppressed lipogenic mRNA expression levels from WAT concomitantly with the cholesterol biosynthesis level in the liver. These results demonstrate the inhibitory effects of FAVA on obesity and NAFLD in the diet-induced obese (DIO) mouse model. Therefore, FAVA may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet. PMID:27200103

  8. Sasa borealis leaves extract improves insulin resistance by modulating inflammatory cytokine secretion in high fat diet-induced obese C57/BL6J mice.

    PubMed

    Yang, Jung-Hwa; Lim, Hyeon-Sook; Heo, Young-Ran

    2010-04-01

    Obesity is considered a mild inflammatory state, and the secretion of inflammation-related cytokines rises as adipose tissue expands. Inflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha), interlukin 6 (IL-6) and monocyte-chemoattractant protein 1 (MCP-1), are modulated by adipose tissue and known to play an important role in insulin resistance which is the common characteristics of obesity related disorders. In this study we analyzed the effects of Sasa borealis leaves extract on inflammatory cytokines and insulin resistance in diet induced obese C57/BL6J mice. The obese state was induced by a high fat diet for 20 weeks and then the mice were divided into two groups; obese control group (OBC, n = 7) and experimental group (OB-SBE, n = 7). The OBC group was fed a high fat diet and the OB-SBE group was fed a high fat diet containing 5% Sasa borealis leaves extract (SBE) for 12 weeks. We also used mice fed a standard diet as a normal control (NC, n = 7). The body weight and adipose tissue weight in the OB group were significantly higher than those in the NC group. The effects of the high fat diet were reduced by SBE treatments, and the body weight and adipose tissue deposition in the OB-SBE group were significantly decreased compared to the OBC group. The OBC group showed higher serum glucose and insulin levels which resulted in a significant increase of incremental area under the curve (IAUC) and HOMA-IR than the NC group. Also, serum leptin, TNF-alpha, and IL-6 levels were significantly higher in the OBC group than in the NC group. In contrast, the OB-SBE group showed a reversal in the metabolic defects, including a decrease in glucose, insulin, IAUC, HOMA-IR, TNF-alpha, IL-6 and leptin levels. These results suggest that BSE can suppress increased weight gain and/or fat deposition induced by a high fat diet and theses effects are accompanied by modulation of the inflammatory cytokines, TNF-alpha and IL-6 secretion resulting in improved insulin

  9. Sasa borealis leaves extract improves insulin resistance by modulating inflammatory cytokine secretion in high fat diet-induced obese C57/BL6J mice

    PubMed Central

    Yang, Jung-Hwa; Lim, Hyeon-Sook

    2010-01-01

    Obesity is considered a mild inflammatory state, and the secretion of inflammation-related cytokines rises as adipose tissue expands. Inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interlukin 6 (IL-6) and monocyte-chemoattractant protein 1 (MCP-1), are modulated by adipose tissue and known to play an important role in insulin resistance which is the common characteristics of obesity related disorders. In this study we analyzed the effects of Sasa borealis leaves extract on inflammatory cytokines and insulin resistance in diet induced obese C57/BL6J mice. The obese state was induced by a high fat diet for 20 weeks and then the mice were divided into two groups; obese control group (OBC, n = 7) and experimental group (OB-SBE, n = 7). The OBC group was fed a high fat diet and the OB-SBE group was fed a high fat diet containing 5% Sasa borealis leaves extract (SBE) for 12 weeks. We also used mice fed a standard diet as a normal control (NC, n = 7). The body weight and adipose tissue weight in the OB group were significantly higher than those in the NC group. The effects of the high fat diet were reduced by SBE treatments, and the body weight and adipose tissue deposition in the OB-SBE group were significantly decreased compared to the OBC group. The OBC group showed higher serum glucose and insulin levels which resulted in a significant increase of incremental area under the curve (IAUC) and HOMA-IR than the NC group. Also, serum leptin, TNF-α, and IL-6 levels were significantly higher in the OBC group than in the NC group. In contrast, the OB-SBE group showed a reversal in the metabolic defects, including a decrease in glucose, insulin, IAUC, HOMA-IR, TNF-α, IL-6 and leptin levels. These results suggest that BSE can suppress increased weight gain and/or fat deposition induced by a high fat diet and theses effects are accompanied by modulation of the inflammatory cytokines, TNF-α and IL-6 secretion resulting in improved insulin resistance. PMID

  10. Effects of Fortunella margarita Fruit Extract on Metabolic Disorders in High-Fat Diet-Induced Obese C57BL/6 Mice

    PubMed Central

    Ding, Xiaobo; Fan, Shengjie; Guo, Lu; Gu, Ming; Zhang, Yu; Feng, Li; Jiang, Dong; Li, Yiming; Xi, Wanpeng; Huang, Cheng; Zhou, Zhiqin

    2014-01-01

    Introduction Obesity is a nutritional disorder associated with many health problems such as dyslipidemia, type 2 diabetes and cardiovascular diseases. In the present study, we investigated the anti-metabolic disorder effects of kumquat (Fortunella margarita Swingle) fruit extract (FME) on high-fat diet-induced C57BL/6 obese mice. Methods The kumquat fruit was extracted with ethanol and the main flavonoids of this extract were analyzed by HPLC. For the preventive experiment, female C57BL/6 mice were fed with a normal diet (Chow), high-fat diet (HF), and high-fat diet with 1% (w/w) extract of kumquat (HF+FME) for 8 weeks. For the therapeutic experiment, female C57BL/6 mice were fed with high-fat diet for 3 months to induce obesity. Then the obese mice were divided into two groups randomly, and fed with HF or HF+FME for another 2 weeks. Body weight and daily food intake amounts were recorded. Fasting blood glucose, glucose tolerance test, insulin tolerance test, serum and liver lipid levels were assayed and the white adipose tissues were imaged. The gene expression in mice liver and brown adipose tissues were analyzed with a quantitative PCR assay. Results In the preventive treatment, FME controlled the body weight gain and the size of white adipocytes, lowered the fasting blood glucose, serum total cholesterol (TC), serum low density lipoprotein cholesterol (LDL-c) levels as well as liver lipid contents in high-fat diet-fed C57BL/6 mice. In the therapeutic treatment, FME decreased the serum triglyceride (TG), serum TC, serum LDL-c, fasting blood glucose levels and liver lipid contents, improved glucose tolerance and insulin tolerance. Compared with the HF group, FME significantly increased the mRNA expression of PPARα and its target genes. Conclusion Our study suggests that FME may be a potential dietary supplement for preventing and ameliorating the obesity and obesity-related metabolic disturbances. PMID:24705395

  11. PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications.

    PubMed

    Lancaster, G I; Kammoun, H L; Kraakman, M J; Kowalski, G M; Bruce, C R; Febbraio, M A

    2016-01-01

    Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation. PMID:26838266

  12. PKR is not obligatory for high-fat diet-induced obesity and its associated metabolic and inflammatory complications

    PubMed Central

    Lancaster, G. I.; Kammoun, H. L.; Kraakman, M. J.; Kowalski, G. M.; Bruce, C. R.; Febbraio, M. A.

    2016-01-01

    Protein kinase R (PKR) has previously been suggested to mediate many of the deleterious consequences of a high-fat diet (HFD). However, previous studies have observed substantial phenotypic variability when examining the metabolic consequences of PKR deletion. Accordingly, herein, we have re-examined the role of PKR in the development of obesity and its associated metabolic complications in vivo as well as its putative lipid-sensing role in vitro. Here we show that the deletion of PKR does not affect HFD-induced obesity, hepatic steatosis or glucose metabolism, and only modestly affects adipose tissue inflammation. Treatment with the saturated fatty acid palmitate in vitro induced comparable levels of inflammation in WT and PKR KO macrophages, demonstrating that PKR is not necessary for the sensing of pro-inflammatory lipids. These results challenge the proposed role for PKR in obesity, its associated metabolic complications and its role in lipid-induced inflammation. PMID:26838266

  13. High-Fat Diet-Induced Insulin Resistance Does Not Increase Plasma Anandamide Levels or Potentiate Anandamide Insulinotropic Effect in Isolated Canine Islets

    PubMed Central

    Woolcott, Orison O.; Richey, Joyce M.; Kabir, Morvarid; Chow, Robert H.; Iyer, Malini S.; Kirkman, Erlinda L.; Stefanovski, Darko; Lottati, Maya; Kim, Stella P.; Harrison, L. Nicole; Ionut, Viorica; Zheng, Dan; Hsu, Isabel R.; Catalano, Karyn J.; Chiu, Jenny D.; Bradshaw, Heather; Wu, Qiang; Bergman, Richard N.

    2015-01-01

    Background Obesity has been associated with elevated plasma anandamide levels. In addition, anandamide has been shown to stimulate insulin secretion in vitro, suggesting that anandamide might be linked to hyperinsulinemia. Objective To determine whether high-fat diet-induced insulin resistance increases anandamide levels and potentiates the insulinotropic effect of anandamide in isolated pancreatic islets. Design and Methods Dogs were fed a high-fat diet (n = 9) for 22 weeks. Abdominal fat depot was quantified by MRI. Insulin sensitivity was assessed by the euglycemic-hyperinsulinemic clamp. Fasting plasma endocannabinoid levels were analyzed by liquid chromatography-mass spectrometry. All metabolic assessments were performed before and after fat diet regimen. At the end of the study, pancreatic islets were isolated prior to euthanasia to test the in vitro effect of anandamide on islet hormones. mRNA expression of cannabinoid receptors was determined in intact islets. The findings in vitro were compared with those from animals fed a control diet (n = 7). Results Prolonged fat feeding increased abdominal fat content by 81.3±21.6% (mean±S.E.M, P<0.01). In vivo insulin sensitivity decreased by 31.3±12.1% (P<0.05), concomitant with a decrease in plasma 2-arachidonoyl glycerol (from 39.1±5.2 to 15.7±2.0 nmol/L) but not anandamide, oleoyl ethanolamide, linoleoyl ethanolamide, or palmitoyl ethanolamide. In control-diet animals (body weight: 28.8±1.0 kg), islets incubated with anandamide had a higher basal and glucose-stimulated insulin secretion as compared with no treatment. Islets from fat-fed animals (34.5±1.3 kg; P<0.05 versus control) did not exhibit further potentiation of anandamide-induced insulin secretion as compared with control-diet animals. Glucagon but not somatostatin secretion in vitro was also increased in response to anandamide, but there was no difference between groups (P = 0.705). No differences in gene expression of CB1R or CB2R between groups

  14. Exercise and dietary change ameliorate high fat diet induced obesity and insulin resistance via mTOR signaling pathway

    PubMed Central

    Bae, Ju Yong; Shin, Ki Ok; Woo, Jinhee; Woo, Sang Heon; Jang, Ki Soeng; Lee, Yul Hyo; Kang, Sunghwun

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effect of exercise and dietary change on obesity and insulin resistance and mTOR signaling protein levels in skeletal muscles of obese rats. [Methods] Sixty male Sprague-Dawley rats were divided into CO (Normal diet) and HF (High Fat diet) groups in order to induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO + Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND + Training) groups (10 rats / group). The training groups underwent moderate-intensity treadmill exercise for 8 weeks, after which soleus muscles were excised and analyzed. Data was statistically analyzed by independent t-test and One-way ANOVA tests with a 0.05 significance level. [Results] Fasting blood glucose, plasma insulin, and HOMA-IR in the HF group were significantly higher, as compared with other groups (p <.05). Protein levels of insulin receptor subunit-1 (IRS-1), IRS-2, and p-Akt were significantly higher in the HFT, HFND, and HFNDT groups, as compared with HF group. In addition, the protein levels of the mammalian target of rapamycin complex 1 (mTORC1) and ribosomal S6 protein kinase 1 were significantly decreased by exercise and dietary change (p <.05). However, mTORC2 and phosphoinositide 3-kinase were significantly increased (p <.05). [Conclusion] In summary, despite the negative impact of continuous high fat intake, regular exercise and dietary change showed a positive effect on insulin resistance and mTOR signaling protein levels. PMID:27508151

  15. Emodin ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    PubMed

    Cao, Yanni; Chang, Shufang; Dong, Jie; Zhu, Shenyin; Zheng, Xiaoying; Li, Juan; Long, Rui; Zhou, Yuanda; Cui, Jianyu; Zhang, Ye

    2016-06-01

    Emodin, an anthraquinone derivative isolated from root and rhizome of Rheum palmatum, has been reported to have promising anti-diabetic activity. The present study was to explore the possible mechanism of emodin to ameliorate insulin resistance. Insulin resistance was induced by feeding a high fat diet to Sprague-Dawley rats. The blood glucose and lipid profiles in serum were measured by an enzymatic method, and a hyperinsulinaemic-euglycaemic clamp was used to evaluate insulin resistance. L6 cells were cultured and treated with palmitic acid and emodin. The lipid content was assayed in the soleus muscle and L6 cells by Oil Red O staining. Western blot, qRT-PCR, and immunohistochemical staining were used to detect the following in the rat soleus muscle and L6 cells: protein levels, mRNA levels of FATP1, FATP4, transporter fatty acid translocase (FAT/CD36), and plasma membrane-associated fatty acid protein (FABPpm). We found that blood glucose, triglyceride (TG), total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were significantly decreased in the emodin group. Oil Red O staining and the level of TG in skeletal muscle and L6 cells confirmed that lipid deposition decreased after treatment with emodin. Furthermore, the protein levels and mRNA levels of FATP1 in skeletal muscle and in L6 cells of rats were significantly decreased, yet the protein levels and mRNA levels of FATP4, FAT/CD36 and FABPpm did not drop off significantly. The study suggest that emodin ameliorates insulin resistance by reducing FATP1-mediated skeletal muscle lipid accumulation in rats fed a high fat diet. PMID:27020550

  16. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    PubMed Central

    2012-01-01

    Background There is a high prevalence of diabetes mellitus (DM) and dyslipidemia in women with polycystic ovary syndrome (PCOS). The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C), n = 10; the andronate-treated group (Andronate), n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks); and the andronate-treated and high-fat diet group (Andronate+HFD), n = 10. The rate of glucose appearance (Ra of glucose), gluconeogenesis (GNG), and the rate of glycerol appearance (Ra of glycerol) were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P < 0.05) but similar blood glucose concentrations. Of the two andronate-treated groups, the andronate+HFD group had the most serious insulin resistance (IR). Estrus cycles were completely acyclic, with polycystic ovaries and elevated serum lipid profiles in the andronate+HFD group (P < 0.05). Ra of glucose and GNG increased significantly in the andronate+HFD rats. However, the Ra of glycerol was similar in the three groups. Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS. PMID:22276997

  17. The treatment combination of vitamins E and C and astaxanthin prevents high-fat diet induced memory deficits in rats.

    PubMed

    Komaki, Alireza; Karimi, Seyed Asaad; Salehi, Iraj; Sarihi, Abdolrahman; Shahidi, Siamak; Zarei, Mohammad

    2015-04-01

    Cognitive function is impaired by imbalanced diet consumption. High-fat diet (HFD) induces oxidative stress and metabolic disorders, which results in neuronal damage and interferes with synaptic transmission and neurogenesis; hence, a decline in learning and memory. Antioxidants are believed to have positive effects on cognitive function. The objective of this study was to determine the relation between the chronic consumption of a HFD and antioxidants on passive avoidance learning (PAL) in male rats. Wistar rats were randomly assigned into the following five groups (N=6-8): Control group-consumed an ordinary diet; HFD group-received high-fat diets only; ANO group-received HFD plus antioxidants (vitamins C and E and astaxanthin (ASX)); RHFD group-received the restricted HFD (30% less than the HFD group); and RANO group-received restricted HFD plus antioxidants (30% less than the ANO group). Following 6months of controlled dietary condition as mentioned above, in each experimental group, the PAL was assessed using shuttle box apparatus. Our results showed that HFD caused a decrease in step through latency in the retention test (STLr) and increased the time spent in the dark compartment in the retention test (TDC) when compared to the control group. Antioxidant supplementation caused an increase in STLr and decrease in TDC when compared to the control group. Furthermore, RHFD and RANO had no significant effect on STLr and TDC compared with the control group. According to our results, HFD impairs PAL and the combination of vitamins C and E and astaxanthin improves PAL deficits in the HFD group. PMID:25687375

  18. Effects of treadmill exercise on skeletal muscle mTOR signaling pathway in high-fat diet-induced obese mice.

    PubMed

    Woo, Jin Hee; Shin, Ki Ok; Lee, Yul Hyo; Jang, Ki Soeng; Bae, Ju Yong; Roh, Hee Tae

    2016-04-01

    [Purpose] The aim of this study was to investigate the effects of regular treadmill exercise on skeletal muscle Rictor-Akt and mTOR-Raptor-S6K1 signaling pathway in high-fat diet-induced obese mice. [Subjects and Methods] Four- week-old C57BL/6 mice were adopted and classified into normal diet group (ND, n = 10), normal diet and training group (NDT, n = 10), high-fat diet group (HF, n = 10), and high-fat diet and training group (HFT, n = 10). The exercise program consisted of a treadmill exercise provided at low intensity for 1-4 weeks, and moderate intensity for 5-8 weeks. [Results] The Western blot method was used to measure the expression of mTOR, Raptor, S6K1, Rictor, and Akt proteins in the soleus muscle. mTOR levels were significantly higher in the HF group than in the ND and NDT groups. Raptor/mTORC1 and S6K1 levels were significantly higher in the HF group than in all the other groups. Akt levels were significantly lower in the HF group than in the NDT group. The risk of obesity may be associated with the overactivation of the mTOR-Raptor-S6K1 signaling pathway and a decrease in Akt levels. [Conclusion] This study also indicates that performing aerobic exercise may be associated with the downregulation of the mTOR-Raptor-S6K1 pathway. PMID:27190464

  19. Effects of treadmill exercise on skeletal muscle mTOR signaling pathway in high-fat diet-induced obese mice

    PubMed Central

    Woo, Jin Hee; Shin, Ki Ok; Lee, Yul Hyo; Jang, Ki Soeng; Bae, Ju Yong; Roh, Hee Tae

    2016-01-01

    [Purpose] The aim of this study was to investigate the effects of regular treadmill exercise on skeletal muscle Rictor-Akt and mTOR-Raptor-S6K1 signaling pathway in high-fat diet-induced obese mice. [Subjects and Methods] Four- week-old C57BL/6 mice were adopted and classified into normal diet group (ND, n = 10), normal diet and training group (NDT, n = 10), high-fat diet group (HF, n = 10), and high-fat diet and training group (HFT, n = 10). The exercise program consisted of a treadmill exercise provided at low intensity for 1–4 weeks, and moderate intensity for 5–8 weeks. [Results] The Western blot method was used to measure the expression of mTOR, Raptor, S6K1, Rictor, and Akt proteins in the soleus muscle. mTOR levels were significantly higher in the HF group than in the ND and NDT groups. Raptor/mTORC1 and S6K1 levels were significantly higher in the HF group than in all the other groups. Akt levels were significantly lower in the HF group than in the NDT group. The risk of obesity may be associated with the overactivation of the mTOR-Raptor-S6K1 signaling pathway and a decrease in Akt levels. [Conclusion] This study also indicates that performing aerobic exercise may be associated with the downregulation of the mTOR-Raptor-S6K1 pathway. PMID:27190464

  20. Carnosic acid as a major bioactive component in rosemary extract ameliorates high-fat-diet-induced obesity and metabolic syndrome in mice.

    PubMed

    Zhao, Yantao; Sedighi, Rashin; Wang, Pei; Chen, Huadong; Zhu, Yingdong; Sang, Shengmin

    2015-05-20

    In this study, we investigated the preventive effects of carnosic acid (CA) as a major bioactive component in rosemary extract (RE) on high-fat-diet-induced obesity and metabolic syndrome in mice. The mice were given a low-fat diet, a high-fat diet or a high-fat diet supplemented with either 0.14% or 0.28% (w/w) CA-enriched RE (containing 80% CA, RE#1L and RE#1H), or 0.5% (w/w) RE (containing 45% CA, RE#2), for a period of 16 weeks. There was the same CA content in the RE#1H and RE#2 diets and half of this amount in the RE#1L diet. The dietary RE supplementation significantly reduced body weight gain, percent of fat, plasma ALT, AST, glucose, insulin levels, liver weight, liver triglyceride, and free fatty acid levels in comparison with the mice fed with a HF diet without RE treatment. RE administration also decreased the levels of plasma and liver malondialdehyde, advanced glycation end products (AGEs), and the liver expression of receptor for AGE (RAGE) in comparison with those for mice of the HF group. Histological analyses of liver samples showed decreased lipid accumulation in hepatocytes in mice administrated with RE in comparison with that of HF-diet-fed mice. Meanwhile, RE administration enhanced fecal lipid excretion to inhibit lipid absorption and increased the liver GSH/GSSG ratio to perform antioxidant activity compared with HF group. Our results demonstrate that rosemary is a promising dietary agent to reduce the risk of obesity and metabolic syndrome. PMID:25929334

  1. IL-17A is proatherogenic in high-fat diet-induced and Chlamydia pneumoniae-infection accelerated atherosclerosis in mice

    PubMed Central

    Chen, Shuang; Shimada, Kenichi; Zhang, Wenxuan; Huang, Ganghua; Crother, Timothy R.; Arditi, Moshe

    2011-01-01

    The role of IL-17 in atherogenesis remains controversial. We previously reported that the TLR/MyD88 signaling pathway plays an important role in high–fat diet, as well as Chlamydophila pneumoniae (Cpn) infection-mediated acceleration of atherosclerosis in ApoE deficient mice. Here we investigated the role of the IL-17A in high-fat diet and Cpn-induced acceleration of atherosclerosis. The aortic sinus plaque and aortic lesion size and lipid composition as well as macrophage accumulation in the lesions were significantly diminished in IL-17A−/− mice fed high-fat diet compared to wild-type C57Bl/6 control mice. As expected, Cpn infection led to a significant increase in size and lipid content of the atherosclerotic lesions in wild-type mice. However, IL-17A−/− mice developed significantly less acceleration of lesion size following Cpn infection compared to wild-type control despite similar levels of blood cholesterol levels. Furthermore, Cpn infection in wild-type but not in IL-17A−/− mice was associated with significant increases in serum concentrations of IL-12p40, CCL2, INFγ and numbers of macrophages in their plaques. Additionally, in vitro studies suggest that IL-17A activates vascular endothelial cells, which secrete cytokines that in turn enhance foam cell formation in bone marrow macrophages. Taken together, our data suggest that IL-17A is pro-atherogenic and that it plays an important role in both diet-induced atherosclerotic lesion development, and Cpn infection-mediated acceleration of atherosclerotic lesions in the presence of high fat diet. PMID:20935201

  2. High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia.

    PubMed

    Carabelli, Julieta; Burgueño, Adriana L; Rosselli, Maria Soledad; Gianotti, Tomas Fernández; Lago, Nestor R; Pirola, Carlos J; Sookoian, Silvia

    2011-06-01

    Mitochondrial DNA (mtDNA) copy number plays a key role in the pathophysiology of metabolic syndrome-related phenotypes, but its role in non-alcoholic fatty liver disease (NAFLD) is not well understood. We evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of HIF-1α. Rats were given either standard chow diet (SCD, n = 10) or high-fat diet (HFD, n = 15) for 20 weeks. Subsequently, mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out using real time quantitative PCR. HFD induced a significant increase in liver mtDNA/nDNA ratio, which significantly correlated with the liver triglyceride content (R: 0.29, P < 0.05). The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1α mRNA (R: 0.37, P < 0.001); liver HIF-1α mRNA was significantly higher in the HFD group. In addition, liver cytochrome c oxidase subunit IV isoform 1 (COX4I1) mRNA expression was also positively correlated with liver mtDNA content. The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PGC-1β, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor δ and Tfam, was not associated with the liver mtDNA content. Neither hepatocyte apoptosis nor oxidative stress was involved in the HIF-1α-mediated increase in mtDNA copy number. In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1α, probably to enhance the mitochondrial function as well as to accommodate the metabolic load. PMID:20629985

  3. High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia

    PubMed Central

    Carabelli, Julieta; Burgueño, Adriana L; Rosselli, Maria Soledad; Gianotti, Tomas Fernández; Lago, Nestor R; Pirola, Carlos J; Sookoian, Silvia

    2011-01-01

    Abstract Mitochondrial DNA (mtDNA) copy number plays a key role in the pathophysiology of metabolic syndrome-related phenotypes, but its role in non-alcoholic fatty liver disease (NAFLD) is not well understood. We evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of HIF-1α. Rats were given either standard chow diet (SCD, n= 10) or high-fat diet (HFD, n= 15) for 20 weeks. Subsequently, mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out using real time quantitative PCR. HFD induced a significant increase in liver mtDNA/nDNA ratio, which significantly correlated with the liver triglyceride content (R: 0.29, P < 0.05). The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1α mRNA (R: 0.37, P < 0.001); liver HIF-1α mRNA was significantly higher in the HFD group. In addition, liver cytochrome c oxidase subunit IV isoform 1 (COX4I1) mRNA expression was also positively correlated with liver mtDNA content. The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) and PGC-1β, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor δ and Tfam, was not associated with the liver mtDNA content. Neither hepatocyte apoptosis nor oxidative stress was involved in the HIF-1α-mediated increase in mtDNA copy number. In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1α, probably to enhance the mitochondrial function as well as to accommodate the metabolic load. PMID:20629985

  4. Protective effect of thymol on high fat diet induced diabetic nephropathy in C57BL/6J mice.

    PubMed

    Saravanan, Settu; Pari, Leelevinothan

    2016-02-01

    Obesity is one of several factors implicated in chronic kidney disease (CKD). Thymol, a monoterpene phenolic compound found in the oils of thyme with multiple biological properties especially antidiabetic activity. The present study was undertaken to evaluate the thymol against diabetic nephropathy by high fat diet (HFD)-induced diabetic C57BL/6J mice. After 10 weeks of continuous dietary intervention, HFD (fat- 35.2%) to mice presented characteristic features of progressive nephropathy by significant increased in kidney weight, blood, and urinary parameters, glomerulosclerosis, oxidative stress, hyperlipidemia and subsequent renal injuries. After intragastric administration of thymol (40 mg/kg BW) daily for the subsequent 5 weeks significantly decreased the blood, urinary parameters and kidney weight. Thymol inhibited the activation of transforming growth factor-β1 (TGF-β1) and vascular endothelial growth factor (VEGF). Also, significantly increased the antioxidants and suppresses the lipid peroxidation markers in erythrocytes and kidney tissue compared to the diabetic mice. Thymol downregulated the expression level of sterol regulatory element binding protein-1c (SREBP-1c) and reduced the lipid accumulation in renal. Histopathological study of kidney tissues showed that extracellular mesangial matrix expansion, glomerulosclerosis in diabetic mice were suppressed by thymol. Further, our results indicate that administration of thymol afforded remarkable protection against HFD-induced diabetic nephropathy. PMID:26680107

  5. Fibroblast Growth Factor 21 (FGF21) Protects against High Fat Diet Induced Inflammation and Islet Hyperplasia in Pancreas

    PubMed Central

    Singhal, Garima; Fisher, ffolliott Martin; Chee, Melissa J.; Tan, Tze Guan; El Ouaamari, Abdelfattah; Adams, Andrew C.; Najarian, Robert; Kulkarni, Rohit N.; Benoist, Christophe; Flier, Jeffrey S.; Maratos-Flier, Eleftheria

    2016-01-01

    Fibroblast growth factor 21 (FGF21) is an important endocrine metabolic regulator expressed in multiple tissues including liver and adipose tissue. Although highest levels of expression are in pancreas, little is known about the function of FGF21 in this tissue. In order to understand the physiology of FGF21 in the pancreas, we analyzed its expression and regulation in both acinar and islet tissues. We found that acinar tissue express 20-fold higher levels than that observed in islets. We also observed that pancreatic FGF21 is nutritionally regulated; a marked reduction in FGF21 expression was noted with fasting while obesity is associated with 3–4 fold higher expression. Acinar and islet cells are targets of FGF21, which when systemically administered, leads to phosphorylation of the downstream target ERK 1/2 in about half of acinar cells and a small subset of islet cells. Chronic, systemic FGF21 infusion down-regulates its own expression in the pancreas. Mice lacking FGF21 develop significant islet hyperplasia and periductal lymphocytic inflammation when fed with a high fat obesogenic diet. Inflammatory infiltrates consist of TCRb+ Thy1+ T lymphocytes with increased levels of Foxp3+ regulatory T cells. Increased levels of inflammatory cells were coupled with elevated expression of cytokines such as TNFα, IFNγ and IL1β. We conclude that FGF21 acts to limit islet hyperplasia and may also prevent pancreatic inflammation. PMID:26872145

  6. High-fat Diet-induced Intestinal Hyperpermeability is Associated with Increased Bile Acids in the Large Intestine of Mice.

    PubMed

    Murakami, Yuki; Tanabe, Soichi; Suzuki, Takuya

    2016-01-01

    Metabolic syndrome is characterized by low-grade chronic systemic inflammation, which is associated with intestinal hyperpermeability. This study examined the effects of 3 high-fat diets (HFDs) composed of different fat sources (soybean oil and lard) on the intestinal permeability, tight junction (TJ) protein expression, and cecal bile acid (BA) concentrations in mice, and then analyzed their interrelations. C57/BL6 mice were fed the control diet, HFD (soybean oil), HFD (lard), and HFD (mix; containing equal concentrations of soybean oil and lard) for 8 wk. Glucose tolerance, intestinal permeability, TJ protein expression, and cecal BA concentration were evaluated. Feeding with the 3 HDFs similarly increased body weight, liver weight, and fat pad weight, and induced glucose intolerance and intestinal hyperpermeability. The expression of TJ proteins, zonula occludens-2 and junctional adhesion molecule-A, were lower in the colons of the 3 HFD groups than in the control group (P < 0.05), and these changes appeared to be related to intestinal hyperpermeability. Feeding with HFDs increased total secondary BA (SBA) and total BA concentrations along with increases in some individual BAs in the cecum. Significant positive correlations between intestinal permeability and the concentrations of most SBAs, such as deoxycholic acid and ω-muricholic acids, were detected (P < 0.05). These results suggest that the HFD-induced intestinal hyperpermeability is associated with increased BA secretion. The abundance of SBAs in the large intestine may be responsible for the hyperpermeability. PMID:26595891

  7. Hepatic Gene Expression Profiling in Nrf2 Knockout Mice after Long-Term High-Fat Diet-Induced Obesity

    PubMed Central

    Chartoumpekis, Dionysios V.; Ziros, Panos G.; Zaravinos, Apostolos; Iskrenova, Ralitsa P.; Psyrogiannis, Agathoklis I.; Kyriazopoulou, Venetsana E.; Sykiotis, Gerasimos P.; Habeos, Ioannis G.

    2013-01-01

    Introduction. The transcription factor NFE2-related factor 2 (Nrf2) is a central regulator of antioxidant and detoxification gene expression in response to electrophilic or oxidative stress. Nrf2 has recently been shown to cross-talk with metabolic pathways, and its gene deletion protected mice from high-fat-diet-(HFD-) induced obesity and insulin resistance. This study aimed to identify potential Nrf2-regulated genes of metabolic interest by comparing gene expression profiles of livers of wild-type (WT) versus Nrf2 knockout (Nrf2-KO) mice after a long-term HFD. Methods. WT and Nrf2-KO mice were fed an HFD for 180 days; total RNA was prepared from liver and used for microarray analysis and quantitative real-time RT-PCR (qRT-PCR). Results. The microarray analysis identified 601 genes that were differentially expressed between WT and Nrf2-KO mice after long-term HFD. Selected genes, including ones known to be involved in metabolic regulation, were prioritized for verification by qRT-PCR: Cyp7a1 and Fabp5 were significantly overexpressed in Nrf2-KO mice; in contrast, Car, Cyp2b10, Lipocalin 13, Aquaporin 8, Cbr3, Me1, and Nqo1 were significantly underexpressed in Nrf2-KO mice. Conclusion. Transcriptome profiling after HFD-induced obesity confirms that Nrf2 is implicated in liver metabolic gene networks. The specific genes identified here may provide insights into Nrf2-dependent mechanisms of metabolic regulation. PMID:23710285

  8. Fenugreek seed extract inhibit fat accumulation and ameliorates dyslipidemia in high fat diet-induced obese rats.

    PubMed

    Kumar, Parveen; Bhandari, Uma; Jamadagni, Shrirang

    2014-01-01

    This study investigated the inhibitory effect of aqueous extract of Trigonella foenum-graecum seeds (AqE-TFG) on fat accumulation and dyslipidemia in high fat diet- (HFD-) induced obese rats. Female Wistar rats were fed with HFD ad libitum, and the rats on HFD were treated orally with AqE-TFG or orlistat ((HFD for 28 days+AqE-TFG (0.5 and 1.0 g/kg) or orlistat (10 mg/kg) from day 8 to 28), respectively. Treatment with AqE-TFG produced significant reduction in body weight gain, body mass index (BMI), white adipose tissue (WAT) weights, blood glucose, serum insulin, lipids, leptin, lipase, and apolipoprotein-B levels and elevation in adiponectin levels. AqE-TFG improved serum aspartate amino transferase (AST), alanine amino transferase (ALT), and lactate dehydrogenase (LDH) levels. AqE-TFG treatment reduced the hepatic and cardiac thiobarbituric acid reactive substances (TBARS) and elevated the antioxidant enzyme (glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT)) levels. In addition, liver and uterine WAT lipogenic enzyme (fatty acid synthetase (FAS) and glucose-6-phosphate dehydrogenase (G6PD)) activities were restored towards normal levels. These findings demonstrated the preventive effect of AqE-TFG on fat accumulation and dyslipidemia, due to inhibition of impaired lipid digestion and absorption, in addition to improvement in glucose and lipid metabolism, enhancement of insulin sensitivity, increased antioxidant defense, and downregulation of lipogenic enzymes. PMID:24868532

  9. Anti-obesity effect of Gymnema sylvestre extract on high fat diet-induced obesity in Wistar rats.

    PubMed

    Kumar, V; Bhandari, U; Tripathi, C D; Khanna, G

    2013-12-01

    Gymnema sylvestre R. BR. (Asclepiadaceae) has been used frequently in traditional Indian folk medicine for the treatment of diabetes. Study was performed in high fat diet (HFD)-induced obesity in murine model. Obesity was induced by oral feeding of HFD for 28 days. The anti obesity effect of water soluble fraction of Gymnema sylvestre extract (120 mg/kg, p.o. for 21 days) in HFD fed rats was evaluated by the measurement of body weight gain, food intake, hemodynamic changes (systolic, diastolic, mean blood pressure and heart rate), serum lipid profiles (triglycerides, total cholesterol, LDL-cholesterol, HDL-cholesterol), leptin, insulin, glucose, apolipoproteins A1 and B, lactate dehydrogenase (LDH) and antioxidant enzymes such as reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S transferase (GST), superoxide dismutase (SOD) and catalase (CAT) levels in liver tissues. Organs and visceral fat pad weight were measured. Histopathological studies were also carried out. Water soluble fraction of G. sylvestre ethanolic extract and rimonabant significantly reduced serum lipids, leptin, insulin, glucose, apolipoprotein B and LDH levels while it significantly increased the HDL-cholesterol, apolipoprotein A1 and antioxidant enzymes levels in liver tissue as compared to the HFD fed rats. Histopathological studies of tissues showed no pathological changes. The results of this study show that water soluble fraction of G. sylvestre extract possess antiobesity effect. PMID:23842942

  10. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice.

    PubMed

    Park, Soyoung; Shin, Sunhye; Lim, Yeseo; Shin, Jae Hoon; Seong, Je Kyung; Han, Sung Nim

    2016-01-01

    Korean pine nut oil (PNO) has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD) can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO) (PC, SC) or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD), for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively) compared with SHFD. Hepatic triacylglycerol (TG) level was significantly lower in PHFD than the SHFD (26% lower). PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT) 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR) and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response. PMID:26805879

  11. Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

    PubMed

    Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

    2016-09-01

    Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc. PMID:26852013

  12. Inhibition of ROS and inflammation by an imidazopyridine derivative X22 attenuate high fat diet-induced arterial injuries.

    PubMed

    Li, Weixin; Wang, Lintao; Huang, Weijian; Skibba, Melissa; Fang, Qilu; Xie, Longteng; Wei, Tiemin; Feng, Zhiguo; Liang, Guang

    2015-09-01

    Obesity is strongly associated with the cause of structural and functional changes of the artery. Oxidative stress and inflammation play a critical role in the development of obesity-induced cardiovascular disorders. Our group previously found that an imidazopyridine derivative X22 showed excellent anti-inflammatory activity in LPS-stimulated macrophages. This study was designed to investigate the protective effects of X22 on high fat diet (HFD)-induced arterial injury and its underlying mechanisms. We observed that palmitate (PA) treatment in HUVECs induced a marked increase in reactive oxygen species, inflammation, apoptosis, and fibrosis. All of these changes were effectively suppressed by X22 treatment in a dose-dependent manner, associated with NF-κB inactivation and Nrf-2 activation. In HFD-fed rats, administration of X22 at 10mg/kg significantly decreased the arterial inflammation and oxidative stress, and eventually improved the arterial matrix remodeling and apoptosis. X22 at 10mg/kg showed a comparable bioactivity with the positive control, curcumin at 50mg/kg. The in vivo beneficial effects of X22 are also associated with its ability to increase Nrf2 expression and inhibit NF-κB activation in the artery of HFD-fed rats. Overall, these results suggest that X22 may have therapeutic potential in the treatment of obesity-induced artery injury via regulation of Nrf2-mediated oxidative stress and NF-κB-mediated inflammation. PMID:25989105

  13. High fat diet-induced TGF-β/Gbb signaling provokes insulin resistance through the tribbles expression.

    PubMed

    Hong, Seung-Hyun; Kang, Moonyoung; Lee, Kyu-Sun; Yu, Kweon

    2016-01-01

    Hyperglycemia, hyperlipidemia, and insulin resistance are hallmarks of obesity-induced type 2 diabetes, which is often caused by a high-fat diet (HFD). However, the molecular mechanisms underlying HFD-induced insulin resistance have not been elucidated in detail. In this study, we established a Drosophila model to investigate the molecular mechanisms of HFD-induced diabetes. HFD model flies recapitulate mammalian diabetic phenotypes including elevated triglyceride and circulating glucose levels, as well as insulin resistance. Expression of glass bottom boat (gbb), a Drosophila homolog of mammalian transforming growth factor-β (TGF-β), is elevated under HFD conditions. Furthermore, overexpression of gbb in the fat body produced obese and insulin-resistant phenotypes similar to those of HFD-fed flies, whereas inhibition of Gbb signaling significantly ameliorated HFD-induced metabolic phenotypes. We also discovered that tribbles, a negative regulator of AKT, is a target gene of Gbb signaling in the fat body. Overexpression of tribbles in flies in the fat body phenocopied the metabolic defects associated with HFD conditions or Gbb overexpression, whereas tribbles knockdown rescued these metabolic phenotypes. These results indicate that HFD-induced TGF-β/Gbb signaling provokes insulin resistance by increasing tribbles expression. PMID:27484164

  14. The Resin from Protium heptaphyllum Prevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms.

    PubMed

    Carvalho, Karine Maria Martins Bezerra; Marinho Filho, José Delano Barreto; de Melo, Tiago Sousa; Araújo, Ana Jérsia; Quetz, Josiane da Silva; da Cunha, Maria do Perpétuo Socorro Saldanha; de Melo, Karina Moura; da Silva, Armenio Andre de Carvalho Almeida; Tomé, Adriana Rocha; Havt, Alexandre; Fonseca, Said Gonçalves da Cruz; Brito, Gerly Anne de Castro; Chaves, Mariana Helena; Rao, Vietla Satyanarayana; Santos, Flávia Almeida

    2015-01-01

    Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH) and the possible mechanisms in mice fed a high-fat diet (HFD) for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-α, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining) at concentrations up to 50 μg/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation. PMID:25709707

  15. The Resin from Protium heptaphyllum Prevents High-Fat Diet-Induced Obesity in Mice: Scientific Evidence and Potential Mechanisms

    PubMed Central

    Carvalho, Karine Maria Martins Bezerra; Marinho Filho, José Delano Barreto; de Melo, Tiago Sousa; Araújo, Ana Jérsia; Quetz, Josiane da Silva; da Cunha, Maria do Perpétuo Socorro Saldanha; de Melo, Karina Moura; da Silva, Armenio Andre de Carvalho Almeida; Tomé, Adriana Rocha; Havt, Alexandre; Fonseca, Said Gonçalves da Cruz; Brito, Gerly Anne de Castro; Chaves, Mariana Helena; Rao, Vietla Satyanarayana; Santos, Flávia Almeida

    2015-01-01

    Herbal compounds rich in triterpenes are well known to regulate glucose and lipid metabolism and to have beneficial effects on metabolic disorders. The present study investigated the antiobesity properties of resin from Protium heptaphyllum (RPH) and the possible mechanisms in mice fed a high-fat diet (HFD) for 15 weeks. Mice treated with RPH showed decreases in body weight, net energy intake, abdominal fat accumulation, plasma glucose, amylase, lipase, triglycerides, and total cholesterol relative to their respective controls, which were RPH unfed. Additionally, RPH treatment, while significantly elevating the plasma level of ghrelin hormone, decreased the levels of insulin, leptin, and resistin. Besides, HFD-induced increases in plasma levels of proinflammatory mediators TNF-α, IL-6, and MCP-1 were significantly lowered by RPH. Furthermore, in vitro studies revealed that RPH could significantly inhibit the lipid accumulation in 3T3-L1 adipocytes (measured by Oil-Red O staining) at concentrations up to 50 μg/mL. These findings suggest that the antiobese potential of RPH is largely due to its modulatory effects on various hormonal and enzymatic secretions related to fat and carbohydrate metabolism and to the regulation of obesity-associated inflammation. PMID:25709707

  16. Protective effects of L-arabinose in high-carbohydrate, high-fat diet-induced metabolic syndrome in rats

    PubMed Central

    Hao, Lei; Lu, Xiaoling; Sun, Min; Li, Kai; Shen, Lingmin; Wu, Tao

    2015-01-01

    Background L-Arabinose is a non-caloric sugar, which could affect glucose and lipid metabolism and suppress obesity. However, few reports have described the effect of L-arabinose in metabolic syndrome, a combination of medical disorders that increase the risk of diabetes and cardiovascular disease. Objective This study was conducted to explore the effects of L-arabinose in rats with metabolic syndrome induced by a high-carbohydrate, high-fat (HCHF) diet. Methods After the rat model for metabolic syndrome was successfully established, L-arabinose was administrated by oral gavage for 6 weeks. The biochemical index and histological analysis were measured, and the expression levels of genes related to fatty acid metabolism were analyzed using real-time PCR. Results Following treatment with L-arabinose, metabolic syndrome rats had an obvious reduction in body weight, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triglycerides, total cholesterol, serum insulin, TNF-α, and leptin. Further study showed that treatment with L-arabinose significantly increased the expression of mRNA for hepatic CPT-1α and PDK4, but the expression of mRNA for hepatic ACCα was reduced. Conclusions This work suggests that L-arabinose could lower body weight, Lee's index, and visceral index and improve dyslipidemia, insulin resistance, inflammation, and viscera function, which indicate that it might be a promising candidate for therapies combating metabolic syndrome. PMID:26652604

  17. High-fat diet-induced adiposity, adipose inflammation, hepatic steatosis and hyperinsulinemia in outbred CD-1 mice.

    PubMed

    Gao, Mingming; Ma, Yongjie; Liu, Dexi

    2015-01-01

    High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population. PMID:25768847

  18. Matrix metalloproteinase 12 modulates high-fat-diet induced glomerular fibrogenesis and inflammation in a mouse model of obesity

    PubMed Central

    Niu, Honglin; Li, Ying; Li, Haibin; Chi, Yanqing; Zhuang, Minghui; Zhang, Tao; Liu, Maodong; Nie, Lei

    2016-01-01

    Obesity-induced kidney injury contributes to albuminuria, which is characterized by a progressive decline in renal function leading to glomerulosclerosis and renal fibrosis. Matrix metalloproteinases (MMPs) modulate inflammation and fibrosis by degrading a variety of extracellular matrix and regulating the activities of effector proteins. Abnormal regulation of MMP-12 expression has been implicated in abdominal aortic aneurysm, atherosclerosis, and emphysema, but the underlying mechanisms remain unclear. The present study examined the function of MMP-12 in glomerular fibrogenesis and inflammation using apo E−/− or apo E−/−MMP-12−/− mice and maintained on a high-fat-diet (HFD) for 3, 6, or 9 months. MMP-12 deletion reduced glomerular matrix accumulation, and downregulated the expression of NADPH oxidase 4 and the subunit-p67phox, indicating the inhibition of renal oxidative stress. In addition, the expression of the inflammation-associated molecule MCP-1 and macrophage marker-CD11b was decreased in glomeruli of apo E−/−MMP-12−/− mice fed HFD. MMP-12 produced by macrophages infiltrating into glomeruli contributed to the degradation of collagen type IV and fibronectin. Crescent formation due to renal oxidative stress in Bowman’s space was a major factor in the development of fibrogenesis and inflammation. These results suggest that regulating MMP-12 activity could be a therapeutic strategy for the treatment of crescentic glomerulonephritis and fibrogenesis. PMID:26822129

  19. High-Fat Diet Induces Oxidative Stress and MPK2 and HSP83 Gene Expression in Drosophila melanogaster

    PubMed Central

    Trindade de Paula, Mariane; Poetini Silva, Márcia Rósula; Machado Araujo, Stífani; Cardoso Bortolotto, Vandreza; Barreto Meichtry, Luana; Zemolin, Ana Paula Pegoraro; Wallau, Gabriel L.; Jesse, Cristiano Ricardo; Posser, Thaís

    2016-01-01

    The consumption of a high-fat diet (HFD) causes alteration in normal metabolism affecting lifespan of flies; however molecular mechanism associated with this damage in flies is not well known. This study evaluates the effects of ingestion of a diet supplemented with 10% and 20% of coconut oil, which is rich in saturated fatty acids, on oxidative stress and cells stress signaling pathways. After exposure to the diet for seven days, cellular and mitochondrial viability, lipid peroxidation and antioxidant enzymes SOD and CAT activity, and mRNA expression of antioxidant enzymes HSP83 and MPK2 were analyzed. To confirm the damage effect of diet on flies, survival and lifespan were investigated. The results revealed that the HFD augmented the rate of lipid peroxidation and SOD and CAT activity and induced a higher expression of HSP83 and MPK2 mRNA. In parallel, levels of enzymes involved in lipid metabolism (ACSL1 and ACeCS1) were increased. Our data demonstrate that association among metabolic changes, oxidative stress, and protein signalization might be involved in shortening the lifespan of flies fed with a HFD. PMID:27579152

  20. Protective effects of Lactobacillus rhamnosus GG against dyslipidemia in high-fat diet-induced obese mice.

    PubMed

    Kim, Bobae; Park, Kun-Young; Ji, Yosep; Park, Soyoung; Holzapfel, Wilhelm; Hyun, Chang-Kee

    2016-04-29

    Recent reports suggest that gut microbiota can be a major determinant of dyslipidemia and non-alcoholic fatty liver disease (NAFLD) and its modulation by treating probiotics is a valid strategy to exert a protective effect. In this study, high-fat diet (HFD)-fed mice were orally administrated with Lactobacillus rhamnosus GG (LGG) for 13 weeks. Significant reductions in the weights of the liver, mesenteric and subcutaneous adipose tissues were observed in LGG-treated HFD-fed mice compared to LGG-non-treated controls. The serum levels of triglyceride and cholesterol were also significantly reduced in LGG-treated mice. Gut microbial composition analysis showed that shifts in the diversity of dominant gut bacteria were caused by HFD and restored by LGG treatment. A remarkable decrease of hepatic fat content was also observed in LGG-treated mice, accompanied by downregulated expressions of lipogenic and pro-inflammatory genes in the liver. LGG-treated mice had lower expression levels of genes involved in cholesterol synthesis, but conversely, higher expression levels of cholesterol efflux-related genes compared to LGG-non-treated controls. The cholesterol-lowering effect of LGG was also found to be mediated by suppression of FXR and FGF15 signaling, resulting in the upregulation of hepatic CYP7A1. Our findings confirm a therapeutic potential of probiotics for ameliorating dyslipidemia and NAFLD. PMID:27018382

  1. High fat diet-induced TGF-β/Gbb signaling provokes insulin resistance through the tribbles expression

    PubMed Central

    Hong, Seung-Hyun; Kang, Moonyoung; Lee, Kyu-Sun; Yu, Kweon

    2016-01-01

    Hyperglycemia, hyperlipidemia, and insulin resistance are hallmarks of obesity-induced type 2 diabetes, which is often caused by a high-fat diet (HFD). However, the molecular mechanisms underlying HFD-induced insulin resistance have not been elucidated in detail. In this study, we established a Drosophila model to investigate the molecular mechanisms of HFD-induced diabetes. HFD model flies recapitulate mammalian diabetic phenotypes including elevated triglyceride and circulating glucose levels, as well as insulin resistance. Expression of glass bottom boat (gbb), a Drosophila homolog of mammalian transforming growth factor-β (TGF-β), is elevated under HFD conditions. Furthermore, overexpression of gbb in the fat body produced obese and insulin-resistant phenotypes similar to those of HFD-fed flies, whereas inhibition of Gbb signaling significantly ameliorated HFD-induced metabolic phenotypes. We also discovered that tribbles, a negative regulator of AKT, is a target gene of Gbb signaling in the fat body. Overexpression of tribbles in flies in the fat body phenocopied the metabolic defects associated with HFD conditions or Gbb overexpression, whereas tribbles knockdown rescued these metabolic phenotypes. These results indicate that HFD-induced TGF-β/Gbb signaling provokes insulin resistance by increasing tribbles expression. PMID:27484164

  2. High-Fat Diet Induces Oxidative Stress and MPK2 and HSP83 Gene Expression in Drosophila melanogaster.

    PubMed

    Trindade de Paula, Mariane; Poetini Silva, Márcia Rósula; Machado Araujo, Stífani; Cardoso Bortolotto, Vandreza; Barreto Meichtry, Luana; Zemolin, Ana Paula Pegoraro; Wallau, Gabriel L; Jesse, Cristiano Ricardo; Franco, Jeferson Luís; Posser, Thaís; Prigol, Marina

    2016-01-01

    The consumption of a high-fat diet (HFD) causes alteration in normal metabolism affecting lifespan of flies; however molecular mechanism associated with this damage in flies is not well known. This study evaluates the effects of ingestion of a diet supplemented with 10% and 20% of coconut oil, which is rich in saturated fatty acids, on oxidative stress and cells stress signaling pathways. After exposure to the diet for seven days, cellular and mitochondrial viability, lipid peroxidation and antioxidant enzymes SOD and CAT activity, and mRNA expression of antioxidant enzymes HSP83 and MPK2 were analyzed. To confirm the damage effect of diet on flies, survival and lifespan were investigated. The results revealed that the HFD augmented the rate of lipid peroxidation and SOD and CAT activity and induced a higher expression of HSP83 and MPK2 mRNA. In parallel, levels of enzymes involved in lipid metabolism (ACSL1 and ACeCS1) were increased. Our data demonstrate that association among metabolic changes, oxidative stress, and protein signalization might be involved in shortening the lifespan of flies fed with a HFD. PMID:27579152

  3. N-Acetylneuraminic Acid Supplementation Prevents High Fat Diet-Induced Insulin Resistance in Rats through Transcriptional and Nontranscriptional Mechanisms.

    PubMed

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Azmi, Nur Hanisah; Wong, Waiteng; Altine Adamu, Hadiza; Md Zamri, Nur Diyana; Ideris, Aini; Abdullah, Maizaton Atmadini

    2015-01-01

    N-Acetylneuraminic acid (Neu5Ac) is a biomarker of cardiometabolic diseases. In the present study, we tested the hypothesis that dietary Neu5Ac may improve cardiometabolic indices. A high fat diet (HFD) + Neu5Ac (50 or 400 mg/kg BW/day) was fed to rats and compared with HFD + simvastatin (10 mg/kg BW/day) or HFD alone for 12 weeks. Weights and serum biochemicals (lipid profile, oral glucose tolerance test, leptin, adiponectin, and insulin) were measured, and mRNA levels of insulin signaling genes were determined. The results indicated that low and high doses of sialic acid (SA) improved metabolic indices, although only the oral glucose tolerance test, serum triglycerides, leptin, and adiponectin were significantly better than those in the HFD and HFD + simvastatin groups (P < 0.05). Furthermore, the results showed that only high-dose SA significantly affected the transcription of hepatic and adipose tissue insulin signaling genes. The data suggested that SA prevented HFD-induced insulin resistance in rats after 12 weeks of administration through nontranscriptionally mediated biochemical changes that may have differentially sialylated glycoprotein structures at a low dose. At higher doses, SA induced transcriptional regulation of insulin signaling genes. These effects suggest that low and high doses of SA may produce similar metabolic outcomes in relation to insulin sensitivity through multiple mechanisms. These findings are worth studying further. PMID:26688813

  4. Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Park, Soyoung; Shin, Sunhye; Lim, Yeseo; Shin, Jae Hoon; Seong, Je Kyung; Han, Sung Nim

    2016-01-01

    Korean pine nut oil (PNO) has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD) can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO) (PC, SC) or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD), for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively) compared with SHFD. Hepatic triacylglycerol (TG) level was significantly lower in PHFD than the SHFD (26% lower). PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT) 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR) and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response. PMID:26805879

  5. Ablation of Elovl6 protects pancreatic islets from high-fat diet-induced impairment of insulin secretion.

    PubMed

    Tang, Nie; Matsuzaka, Takashi; Suzuki, Marii; Nakano, Yuta; Zao, Hui; Yokoo, Tomotaka; Suzuki-Kemuriyama, Noriko; Kuba, Motoko; Okajima, Yuka; Takeuchi, Yoshinori; Kobayashi, Kazuto; Iwasaki, Hitoshi; Yatoh, Shigeru; Takahashi, Akimitsu; Suzuki, Hiroaki; Sone, Hirohito; Shimada, Masako; Nakagawa, Yoshimi; Yahagi, Naoya; Yamada, Nobuhiro; Shimano, Hitoshi

    2014-07-18

    ELOVL family member 6, elongation of very long-chain fatty acids (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids and is related to the development of obesity-induced insulin resistance via the modification of the fatty acid composition. In this study, we investigated the role of systemic Elovl6 in the pancreatic islet and β-cell function. Elovl6 is expressed in both islets and β-cell lines. In mice fed with chow, islets of the Elovl6(-/-) mice displayed normal architecture and β-cell mass compared with those of the wild-type mice. However, when fed a high-fat, high-sucrose (HFHS) diet, the islet hypertrophy in response to insulin resistance observed in normal mice was attenuated and glucose-stimulated insulin secretion (GSIS) increased in the islets of Elovl6(-/-) mice compared with those of the wild-type mice. Enhanced GSIS in the HFHS Elovl6(-/-) islets was associated with an increased ATP/ADP ratio and the suppression of ATF-3 expression. Our findings suggest that Elovl6 could be involved in insulin secretory capacity per β-cell and diabetes. PMID:24938128

  6. High-Fat Diet-Induced Adiposity, Adipose Inflammation, Hepatic Steatosis and Hyperinsulinemia in Outbred CD-1 Mice

    PubMed Central

    Gao, Mingming; Ma, Yongjie; Liu, Dexi

    2015-01-01

    High-fat diet (HFD) has been applied to a variety of inbred mouse strains to induce obesity and obesity related metabolic complications. In this study, we determined HFD induced development of metabolic disorders on outbred female CD-1 mice in a time dependent manner. Compared to mice on regular chow, HFD-fed CD-1 mice gradually gained more fat mass and consequently exhibited accelerated body weight gain, which was associated with adipocyte hypertrophy and up-regulated expression of adipose inflammatory chemokines and cytokines such as Mcp-1 and Tnf-α. Increased fat accumulation in white adipose tissue subsequently led to ectopic fat deposition in brown adipose tissue, giving rise to whitening of brown adipose tissue without altering plasma level of triglyceride. Ectopic fat deposition was also observed in the liver, which was associated with elevated expression of key genes involved in hepatic lipid sequestration, including Ppar-γ2, Cd36 and Mgat1. Notably, adipose chronic inflammation and ectopic lipid deposition in the liver and brown fat were accompanied by glucose intolerance and insulin resistance, which was correlated with hyperinsulinemia and pancreatic islet hypertrophy. Collectively, these results demonstrate sequentially the events that HFD induces physiological changes leading to metabolic disorders in an outbred mouse model more closely resembling heterogeneity of the human population. PMID:25768847

  7. Chronic inflammation aggravates metabolic disorders of hepatic fatty acids in high-fat diet-induced obese mice

    PubMed Central

    Zhao, Lei; Zhong, Shan; Qu, Haiyang; Xie, Yunxia; Cao, Zhennan; Li, Qing; Yang, Ping; Varghese, Zac; Moorhead, John F.; Chen, Yaxi; Ruan, Xiong Z.

    2015-01-01

    The prevalence of nonalcoholic fatty liver disease (NAFLD) increases with increasing body mass index (BMI). However, approximately 40–50% of obese adults do not develop hepatic steatosis. The level of inflammatory biomarkers is higher in obese subjects with NAFLD compared to BMI-matched subjects without hepatic steatosis. We used a casein injection in high-fat diet (HFD)-fed C57BL/6J mice to induce inflammatory stress. Although mice on a HFD exhibited apparent phenotypes of obesity and hyperlipidemia regardless of exposure to casein injection, only the HFD+Casein mice showed increased hepatic vacuolar degeneration accompanied with elevated inflammatory cytokines in the liver and serum, compared to mice on a normal chow diet. The expression of genes related to hepatic fatty acid synthesis and oxidation were upregulated in the HFD-only mice. The casein injection further increased baseline levels of lipogenic genes and decreased the levels of oxidative genes in HFD-only mice. Inflammatory stress induced both oxidative stress and endoplasmic reticulum stress in HFD-fed mice livers. We conclude that chronic inflammation precedes hepatic steatosis by disrupting the balance between fatty acid synthesis and oxidation in the livers of HFD-fed obese mice. This mechanism may operate in obese individuals with chronic inflammation, thus making them more prone to NAFLD. PMID:25974206

  8. Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin

    PubMed Central

    Jang, Hyun-Ju; Kim, Hae-Suk; Hwang, Daniel H.; Quon, Michael J.

    2013-01-01

    Obesity is characterized by a chronic proinflammatory state that leads to endothelial dysfunction. Saturated fatty acids (SFA) stimulate Toll-like receptors (TLR) that promote metabolic insulin resistance. However, it is not known whether TLR2 mediates impairment of vascular actions of insulin in response to high-fat diet (HFD) to cause endothelial dysfunction. siRNA knockdown of TLR2 in primary endothelial cells opposed palmitate-stimulated expression of proinflammatory cytokines and splicing of X box protein 1 (XBP-1). Inhibition of unfolding protein response (UPR) reduced SFA-stimulated expression of TNFα. Thus, SFA stimulates UPR and proinflammatory response through activation of TLR2 in endothelial cells. Knockdown of TLR2 also opposed impairment of insulin-stimulated phosphorylation of eNOS and subsequent production of NO. Importantly, insulin-stimulated vasorelaxation of mesenteric arteries from TLR2 knockout mice was preserved even on HFD (in contrast with results from arteries examined in wild-type mice on HFD). We conclude that TLR2 in vascular endothelium mediates HFD-stimulated proinflammatory responses and UPR that accompany impairment of vasodilator actions of insulin, leading to endothelial dysfunction. These results are relevant to understanding the pathophysiology of the cardiovascular complications of diabetes and obesity. PMID:23531618

  9. N-Acetylneuraminic Acid Supplementation Prevents High Fat Diet-Induced Insulin Resistance in Rats through Transcriptional and Nontranscriptional Mechanisms

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Azmi, Nur Hanisah; Wong, Waiteng; Altine Adamu, Hadiza; Md Zamri, Nur Diyana; Ideris, Aini; Abdullah, Maizaton Atmadini

    2015-01-01

    N-Acetylneuraminic acid (Neu5Ac) is a biomarker of cardiometabolic diseases. In the present study, we tested the hypothesis that dietary Neu5Ac may improve cardiometabolic indices. A high fat diet (HFD) + Neu5Ac (50 or 400 mg/kg BW/day) was fed to rats and compared with HFD + simvastatin (10 mg/kg BW/day) or HFD alone for 12 weeks. Weights and serum biochemicals (lipid profile, oral glucose tolerance test, leptin, adiponectin, and insulin) were measured, and mRNA levels of insulin signaling genes were determined. The results indicated that low and high doses of sialic acid (SA) improved metabolic indices, although only the oral glucose tolerance test, serum triglycerides, leptin, and adiponectin were significantly better than those in the HFD and HFD + simvastatin groups (P < 0.05). Furthermore, the results showed that only high-dose SA significantly affected the transcription of hepatic and adipose tissue insulin signaling genes. The data suggested that SA prevented HFD-induced insulin resistance in rats after 12 weeks of administration through nontranscriptionally mediated biochemical changes that may have differentially sialylated glycoprotein structures at a low dose. At higher doses, SA induced transcriptional regulation of insulin signaling genes. These effects suggest that low and high doses of SA may produce similar metabolic outcomes in relation to insulin sensitivity through multiple mechanisms. These findings are worth studying further. PMID:26688813

  10. Dioscorea batatas Extract Attenuates High-Fat Diet-Induced Obesity in Mice by Decreasing Expression of Inflammatory Cytokines

    PubMed Central

    Gil, Hyo-Wook; Lee, Eun-Young; Lee, Ji-Hye; Kim, Yong-Sik; Lee, Byung-Eui; Suk, Jeong Woo; Song, Ho-Yeon

    2015-01-01

    Background The objective of the present study was to determine whether Dioscorea batatas (DB) extract reduces visceral fat accumulation and obesity-related biomarkers in mice fed a high-fat diet (HFD) and whether genes associated with adipogenesis and inflammation could be modulated by a diet containing DB extract. Material/Methods Male C57BL/6J mice were divided into 4 groups (n=10 per group): normal diet (ND), HFD, 100 mg/kg DB extract-gavage with HFD, and 200 mg/kg DB extract-gavage with HFD. The mice were fed the experimental diets for 14 weeks. At 12 weeks, micro-computed X-ray tomography (micro-CT) was performed. Results Supplementation of the diet with DB extract for 14 weeks significantly prevented HFD-induced increases in body weight, visceral adipose tissue, plasma lipid levels, and leptins. The area of visceral fat was reduced by DB extract supplementation when examined by micro-CT. Supplementation with DB extract resulted in the downregulation of the adipogenic transcription factor (C/ERBα) and its target gene (CD36) in epididymal adipose tissue, compared to HFD alone. DB extract decreased the expression of proinflammatory cytokines (TNF-α, MCP-1, and IL-6) in epididymal adipose tissue. Conclusions Our results suggest that DB extract may prevent HFD-induced obesity by downregulating the expression of genes related to adipogenesis and inflammation in visceral adipose tissue. PMID:25681821

  11. Silymarin ameliorates memory deficits and neuropathological changes in mouse model of high-fat-diet-induced experimental dementia.

    PubMed

    Neha; Kumar, Amit; Jaggi, Amteshwar S; Sodhi, Rupinder K; Singh, Nirmal

    2014-08-01

    A huge body evidences suggest that obesity is the single great risk factor for the development of dementia. Recently, silymarin, a flavonoid, clinically in use as a hepatoprotectant, has been reported to prevent amyloid beta-induced memory impairment by reducing oxidative stress and inflammation in mice brain. However, its potential in high-fat-diet (HFD)-induced dementia has not yet been investigated. Therefore, the present study is designed to explore the role of silymarin in HFD-induced experimental dementia in mice. Morris water maze test was employed to assess learning and memory. Various biochemical estimations including brain acetylcholinerstarse activity (AchE), thiobarbituric acid-reactive species (TBARS) level, reduced glutathione level (GSH), nirate/nitrite, and myeloperoxidase (MPO) activity were measured. Serum cholesterol level was also determined. HFD significantly impaired the cognitive abilities, along with increasing brain AchE, TBARS, MPO, nitrate/nitrite, and serum cholesterol levels. Marked reduction of brain GSH levels was observed. On the contrary, silymarin significantly reversed HFD-induced cognitive deficits and the biochemical changes. The present study indicates strong potential of silymarin in HFD-induced experimental dementia. PMID:24866499

  12. A comparison of effects of lard and hydrogenated vegetable shortening on the development of high-fat diet-induced obesity in rats

    PubMed Central

    Kubant, R; Poon, A N; Sánchez-Hernández, D; Domenichiello, A F; Huot, P S P; Pannia, E; Cho, C E; Hunschede, S; Bazinet, R P; Anderson, G H

    2015-01-01

    Background: Obesity is associated with increased consumption and preference for dietary fat. Experimental models of fat-induced obesity use either lard or vegetable shortening. Yet, there are no direct comparisons of these commonly used fat sources, or the influence of their fatty acid composition, on the development of diet-induced obesity. Objective: To compare the effects of lard and hydrogenated vegetable-shortening diets, which differ in their fatty acid composition, on weight gain and the development of obesity and insulin resistance in rats. Methods and design: Male Wistar rats were fed ad libitum for 14 weeks high-fat diets containing either (1) high vegetable fat (HVF, 60 kcal% from vegetable shortening) or (2) high lard fat (HLF, 60 kcal% from lard). Rats fed normal-fat (NF, 16 kcal% from vegetable shortening) diet served as control. Body weight, food intake, adipose tissue mass, serum 25[OH]D3, glucose, insulin and fatty acid composition of diets were measured. Results: Rats fed either of the two high-fat diets had higher energy intake, weight gain and fat accretion than rats fed normal-fat diet. However, rats fed the HLF diet consumed more calories and gained more weight and body fat with greater increases of 32% in total (158.5±8.2 vs 120.2±6.6 g, P<0.05), 30% in visceral (104.4±5.2 vs 80.3±4.2 g, P<0.05) and 36% in subcutaneous fat mass (54.1±3.6 vs 39.9±3.1 g, P<0.05), compared with rats fed the HVF diet. Higher visceral adiposity was positively correlated with serum insulin (r=0.376, P<0.05) and homeostatic model assessment insulin resistance (r=0.391, P<0.05). Conclusion: We conclude that lard-based high-fat diets accentuate the increase in weight gain and the development of obesity and insulin resistance more than hydrogenated vegetable-shortening diets. These results further point to the importance of standardizing fatty acid composition and type of fat used in determining outcomes of consuming high-fat diets. PMID:26657014

  13. Electronegative LDL is linked to high-fat, high-cholesterol diet-induced nonalcoholic steatohepatitis in hamsters.

    PubMed

    Lai, Yu-Sheng; Yang, Tzu-Ching; Chang, Po-Yuan; Chang, Shwu-Fen; Ho, Shu-Li; Chen, Hui-Ling; Lu, Shao-Chun

    2016-04-01

    The pathogenesis of nonalcoholic steatohepatitis (NASH), like that of atherosclerosis, involves lipid accumulation, inflammation and fibrosis. Recent studies suggest that oxidized LDL (oxLDL) may be a risk factor for NASH, but oxLDL levels were not directly measured in these studies. The aim of this study was to examine whether there was an association between electronegative LDL [LDL(-)], a mildly oxLDL found in the blood, and the development of NASH using two animal models. Golden Syrian hamsters and C57BL/6 mice were fed a high-fat, high-cholesterol (HFC) diet for 6 or 12weeks, then liver lipid and histopathology, plasma lipoprotein profile and LDL(-) levels were examined. The HFC-diet-fed hamsters and mice had similar levels of hepatic lipid but different histopathological changes, with microvesicular steatosis, hepatocellular hypertrophy, inflammation and bridging fibrosis in the hamsters, but only in mild steatohepatitis with low inflammatory cell infiltration in the mice. It also resulted in a significant increase in plasma levels of LDL cholesterol and LDL(-) in hamsters, but only a slight increase in mice. Moreover, enlarged Kupffer cells, LDL(-) and accumulation of unesterified cholesterol were detected in the portal area of HFC-diet-fed hamsters, but not HFC-diet-fed mice. An in vitro study showed that LDL(-) from HFC-diet-fed hamsters induced TNF-α secretion in rat Kupffer cell through a LOX-1-dependent pathway. Our results strongly suggest that LDL(-) is one of the underlying causes of hepatic inflammation and plays a critical role in the development of NASH. PMID:27012620

  14. Antioxidative Activity of Blueberry Leaf Extract Prevents High-fat Diet-induced Obesity in C57BL/6 Mice

    PubMed Central

    Lee, In-Chul; Kim, Dae Yong; Choi, Bu Young

    2014-01-01

    Background: Health beneficial effects of blueberry have been well documented. Obesity is health hazard that is associated with metabolic abnormalities. We investigated the effect of blueberry leaf extract (BBLE) on high-fat diet (HFD)-induced obesity in C57BL/6J mice. Methods: C57BL/6 mice were fed HFD with or without BBLE for 10 weeks. Body weight, serum parameter, and adipose tissues morphology were assessed. The expression of mRNA associated with adipogenesis was measured using real-time polymerase chain reaction (RT-PCR) analysis. Results: Administration of BBLE to mice challenged with HFD significantly decreased the body weight gain, the levels of plasma triglyceride (TG) and liver lipid peroxidation, and reduced the adipocyte size and improved hepatic status compared with the group treated with HFD only. BBLE treatment significantly improved glucose control compared with the HFD group. Moreover, BBLE showed an inhibitory effect on adipocyte differentiation in obese mice together with significant decrease in the lipid accumulation by downregulating gene expression of adipocyte-specific transcription factors, such as peroxisome proliferation-activity receptor and acetyl coenzyme A carboxylase and upregulating the mRNA expression of adiponectin, which are critical for adipogenesis. Conclusion: BBLE suppressed the body weight gain in the HFD-fed C57BL/6 mice. Intake of BBLE reduced body weight in HFD-fed mice by 20%. Furthermore, BBLE supplementation significantly decreased the TG level in the liver and inhibited leptin secretion. BBLE supplementation also improved insulin resistance. Therefore, BBLE is a possible agent to prevent obesity. PMID:25337590

  15. Deletion of miR-150 Exacerbates Retinal Vascular Overgrowth in High-Fat-Diet Induced Diabetic Mice

    PubMed Central

    Shi, Liheng; Kim, Andy Jeesu; Chang, Richard Cheng-An; Chang, Janet Ya-An; Ying, Wei; Ko, Michael L.; Zhou, Beiyan; Ko, Gladys Yi-Ping

    2016-01-01

    Diabetic retinopathy (DR) is the leading cause of blindness among American adults above 40 years old. The vascular complication in DR is a major cause of visual impairment, making finding therapeutic targets to block pathological angiogenesis a primary goal for developing DR treatments. MicroRNAs (miRs) have been proposed as diagnostic biomarkers and potential therapeutic targets for various ocular diseases including DR. In diabetic animals, the expression levels of several miRs, including miR-150, are altered. The expression of miR-150 is significantly suppressed in pathological neovascularization in mice with hyperoxia-induced retinopathy. The purpose of this study was to investigate the functional role of miR-150 in the development of retinal microvasculature complications in high-fat-diet (HFD) induced type 2 diabetic mice. Wild type (WT) and miR-150 null mutant (miR-150-/-) male mice were given a HFD (59% fat calories) or normal chow diet. Chronic HFD caused a decrease of serum miR-150 in WT mice. Mice on HFD for 7 months (both WT and miR-150-/-) had significant decreases in retinal light responses measured by electroretinograms (ERGs). The retinal neovascularization in miR-150-/--HFD mice was significantly higher compared to their age matched WT-HFD mice, which indicates that miR-150 null mutation exacerbates chronic HFD-induced neovascularization in the retina. Overexpression of miR-150 in cultured endothelial cells caused a significant reduction of vascular endothelial growth factor receptor 2 (VEGFR2) protein levels. Hence, deletion of miR-150 significantly increased the retinal pathological angiogenesis in HFD induced type 2 diabetic mice, which was in part through VEGFR2. PMID:27304911

  16. Vitamin d deficiency attenuates high-fat diet-induced hyperinsulinemia and hepatic lipid accumulation in male mice.

    PubMed

    Liu, Xiao-Jing; Wang, Bi-Wei; Zhang, Cheng; Xia, Mi-Zhen; Chen, Yuan-Hua; Hu, Chun-Qiu; Wang, Hua; Chen, Xi; Xu, De-Xiang

    2015-06-01

    It is increasingly recognized that vitamin D deficiency is associated with increased risks of metabolic disorders among overweight children. A recent study showed that vitamin D deficiency exacerbated inflammation in nonalcoholic fatty liver disease through activating toll-like receptor 4 in a high-fat diet (HFD) rat model. The present study aimed to further investigate the effects of vitamin D deficiency on HFD-induced insulin resistance and hepatic lipid accumulation. Male ICR mice (35 d old) were randomly assigned into 4 groups as follows. In control diet and vitamin D deficiency diet (VDD) groups, mice were fed with purified diets. In HFD and VDD+HFD groups, mice were fed with HFD. In VDD and VDD+HFD groups, vitamin D in feed was depleted. Feeding mice with vitamin D deficiency diet did not induce obesity, insulin resistance, and hepatic lipid accumulation. By contrary, vitamin D deficiency markedly alleviated HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation. Moreover, vitamin D deficiency significantly attenuated HFD-induced up-regulation of hepatic peroxisome proliferator-activated receptor γ, which promoted hepatic lipid uptake and lipid droplet formation, and its target gene cluster of differentiation 36. In addition, vitamin D deficiency up-regulated carnitine palmitoyltrans 2, the key enzyme for fatty acid β-oxidation, and uncoupling protein 3, which separated oxidative phosphorylation from ATP production, in adipose tissue. These data suggest that vitamin D deficiency is not a direct risk factor for obesity, insulin resistance, and hepatic lipid accumulation. Vitamin D deficiency alleviates HFD-induced overweight, hyperinsulinemia, and hepatic lipid accumulation through promoting fatty acid β-oxidation and elevating energy expenditure in adipose tissue. PMID:25774554

  17. High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus.

    PubMed

    Borges, Beatriz de Carvalho; Rorato, Rodrigo; Uchoa, Ernane Torres; Marangon, Paula; da Silva, Glauber S F; de Paula, Francisco José; Branco, Luiz G S; Antunes-Rodrigues, José; Elias, Lucila Leico Kagohara

    2014-01-01

    Hypophagia induced by inflammation is associated with Janus kinase (JAK)-2/signal transducer and activator of transcription (STAT) 3 signaling pathway, and leptin-mediated hypophagia is also mediated by JAK2-STAT3 pathway. We have previously reported that lipopolysaccharide (LPS) did not reduce food intake in leptin-resistant high-fat diet (HFD) rats but maintained body weight loss. We investigated whether changes in p-STAT3 expression in the hypothalamus and brain stem could account for the desensitization of hypophagia in HFD animals after a low LPS dose (100 μg/kg). Wistar rats fed standard diet (3.95 kcal/g) or HFD (6.3 kcal/g) for 8 wk were assigned into control diet-saline, control diet-LPS, HFD-saline, and HFD-LPS groups. LPS reduced feeding in the control diet but not HFD. This group showed no p-STAT3 expression in the paraventricular nucleus (PVN) and ventromedial hypothalamic nucleus (VMH), but sustained, though lower than control, p-STAT3 in the nucleus of the solitary tract (NTS) and raphe pallidus (RPa). LPS decreased body weight in HFD rats and increased Fos expression in the NTS. LPS increased body temperature, oxygen consumption, and energy expenditure in both control diet and HFD rats, and this response was more pronounced in HFD-LPS group. Brown adipose tissue (BAT) thermogenesis and increased energy expenditure seem to contribute to body weight loss in HFD-LPS. This response might be related with increased brain stem activation. In conclusion, LPS activates STAT3-mediated pathway in the hypothalamus and brain stem, leading to hypophagia, however, LPS effects on food intake, but not body weight loss, are abolished by leptin resistance induced by HFD. The preserved STAT3 phosphorylation in the brain stem suggests that unresponsiveness to LPS on STAT3 activation under HFD might be selective to the hypothalamus. PMID:24226027

  18. The absence of GH signaling affects the susceptibility to high-fat diet-induced hypothalamic inflammation in male mice.

    PubMed

    Baquedano, Eva; Ruiz-Lopez, Ana M; Sustarsic, Elahu G; Herpy, James; List, Edward O; Chowen, Julie A; Frago, Laura M; Kopchick, John J; Argente, Jesús

    2014-12-01

    GH is important in metabolic control, and mice with disruption of the gene encoding the GH receptor (GHR) and GH binding protein (GHR-/- mice) are dwarf with low serum IGF-1 and insulin levels, high GH levels, and increased longevity, despite their obesity and altered lipid and metabolic profiles. Secondary complications of high-fat diet (HFD)-induced obesity are reported to be associated with hypothalamic inflammation and gliosis. Because GH and IGF-1 can modulate inflammatory processes, our objective was to evaluate the effect of HFD on hypothalamic inflammation/gliosis in the absence of GH signaling and determine how this correlates with changes in systemic metabolism. On normal chow, GHR-/- mice had a higher percentage of fat mass and increased circulating nonesterified free fatty acids levels compared with wild type (WT), and this was associated with increased hypothalamic TNF-α and phospho-JNK levels. After 7 weeks on a HFD, both WT and GHR-/- mice had increased weight gain, with GHR-/- mice having a greater rise in their percentage of body fat. In WT mice, HFD-induced weight gain was associated with increased hypothalamic levels of phospho-JNK and the microglial marker Iba-1 (ionized calcium-binding adapter molecule 1) but decreased cytokine production. Moreover, in GHR-/- mice, the HFD decreased hypothalamic inflammatory markers to WT levels with no indication of gliosis. Thus, the GH/IGF-1 axis is important in determining not only adipose tissue accrual but also the inflammatory response to HFD. However, how hypothalamic inflammation/gliosis is defined will determine whether it can be considered a common feature of HFD-induced obesity. PMID:25237935

  19. Ginger Essential Oil Ameliorates Hepatic Injury and Lipid Accumulation in High Fat Diet-Induced Nonalcoholic Fatty Liver Disease.

    PubMed

    Lai, Yi-Syuan; Lee, Wan-Ching; Lin, Yu-En; Ho, Chi-Tang; Lu, Kuan-Hung; Lin, Shih-Hang; Panyod, Suraphan; Chu, Yung-Lin; Sheen, Lee-Yan

    2016-03-16

    The objective of this study was to investigate the hepatoprotective efficacy and mechanism of action of ginger essential oil (GEO) against the development of nonalcoholic fatty liver disease (NAFLD). Mice were maintained on either a control diet or high-fat diet (HFD) supplemented with GEO (12.5, 62.5, and 125 mg/kg) or citral (2.5 and 25 mg/kg) for 12 weeks. We demonstrated that GEO and its major component (citral) lowered HFD-induced obesity in a dose-dependent manner, accompanied by anti-hyperlipidemic effects by reducing serum free fatty acid, triglyceride, and total cholesterol levels. Moreover, liver histological results showed that administration of 62.5 and 125 mg/kg GEO and 25 mg/kg citral significantly reduced hepatic lipid accumulation. Further assessment by Western blotting and investigation of the lipid metabolism revealed that hepatic protein expression of sterol regulatory element-binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), and cytochrome P450 2E1 (CYP2E1) were down-regulated by GEO and citral, indicating that GEO and citral suppressed HFD-stimulated lipid biosynthesis and oxidative stress. Furthermore, GEO and citral effectively enhanced the antioxidant capacities and reduced inflammatory response in mouse liver, which exerted protective effects against steatohepatitis. Collectively, GEO and citral exhibited potent hepatoprotective effects against NAFLD induced by HFD in obese mice. Thus, GEO might be an effective dietary supplement to ameliorate NAFLD-related metabolic diseases, and citral could play a vital role in its management. PMID:26900108

  20. Anti-Obesity Effects of Aster spathulifolius Extract in High-Fat Diet-Induced Obese Rats.

    PubMed

    Kim, Sa-Jic; Bang, Chae-Young; Guo, Yuan-Ri; Choung, Se-Young

    2016-04-01

    The aim of this study was to investigate the anti-obesity and antihyperlipidemic efficacy and molecular mechanisms of Aster spathulifolius Maxim extract (ASE) in rats with high-fat diet (HFD)-induced obesity. Rats were separately fed a normal diet or a HFD for 8 weeks, then they were treated with ASE (62.5, 125, or 250 mg/kg) for another 4.5 weeks. The ASE supplementation significantly lowered body weight gain, visceral fat pad weights, serum lipid levels, as well as hepatic lipid levels in HFD-induced obese rats. Histological analysis showed that the ASE-treated group showed lowered numbers of lipid droplets and smaller size of adipocytes compared to the HFD group. To understand the mechanism of action of ASE, the expression of genes and proteins involved in obesity were measured in liver and skeletal muscle. The expression of fatty acid oxidation and thermogenesis-related genes (e.g., PPAR-α, ACO, CPT1, UCP2, and UCP3) of HFD-induced obese rats were increased by ASE treatment. On the other hand, ASE treatment resulted in decreased expression of fat intake-related gene ACC2 and lipogenesis-related genes (e.g., SREBP-1c, ACC1, FAS, SCD1, GPATR, AGPAT, and DGAT). Furthermore, ASE treatment increased the level of phosphorylated AMPKα in obese rats. Similarly, the level of phosphorylated ACC, a target protein of AMPKα in ASE groups, was increased by ASE treatment compared with the HFD group. These results suggest that ASE attenuated visceral fat accumulation and improved hyperlipidemia in HFD-induced obese rats by increasing lipid metabolism through the regulation of AMPK activity and the expression of genes and proteins involved in lipolysis and lipogenesis. PMID:26908215

  1. A high fat diet induces sex-specific differences in hepatic lipid metabolism and nitrite/nitrate in rats.

    PubMed

    Stanimirovic, Julijana; Obradovic, Milan; Jovanovic, Aleksandra; Sudar-Milovanovic, Emina; Zafirovic, Sonja; Pitt, Samantha J; Stewart, Alan J; Isenovic, Esma R

    2016-04-01

    Men and women differ substantially with regard to the severity of insulin resistance (IR) but the underlying mechanism(s) of how this occurs is poorly characterized. We investigated whether a high fat (HF) diet resulted in sex-specific differences in nitrite/nitrate production and lipid metabolism and whether these variances may contribute to altered obesity-induced IR. Male and female Wistar rats were fed a standard laboratory diet or a HF diet for 10 weeks. The level of plasma nitrite/nitrate, as well as free fatty acid (FFA), in both plasma and liver lysates were assessed. The levels of inducible nitric oxide (NO) synthase (iNOS), p65 subunit of NFκB, total and phosphorylated forms of Akt, mTOR and PDK-1 in lysates, and the levels of glucose transporter 2 (Glut-2) and fatty acid translocase/cluster of differentiation 36 (FAT/CD36) in plasma membrane fractions of liver were assessed. HF-fed male rats exhibited a significant increase in plasma nitrite/nitrate, and hepatic FFA and FAT/CD36 levels compared with controls. They also displayed a relative decrease in iNOS and Glut-2 levels in the liver. Phosphorylation of Akt (at Ser(473) and Thr(308)), mTOR and PDK-1 was also reduced. HF-fed female rats exhibited increased levels of NFκB-p65 in liver compared with controls, while levels of Glut-2, FAT/CD36 and Akt phosphorylation at Thr(308) and PDK-1 were decreased. Our results reveal that altered lipid and glucose metabolism in obesity, lead to altered iNOS expression and nitrite/nitrate production. It is likely that this mechanism contributes to sex-specific differences in the development of IR. PMID:26924725

  2. Combined treatment of mulberry leaf and fruit extract ameliorates obesity-related inflammation and oxidative stress in high fat diet-induced obese mice.

    PubMed

    Lim, Hyun Hwa; Yang, Soo Jin; Kim, Yuri; Lee, Myoungsook; Lim, Yunsook

    2013-08-01

    The aim of this study was to investigate whether a combined treatment of mulberry leaf extract (MLE) and mulberry fruit extract (MFE) was effective for improving obesity and obesity-related inflammation and oxidative stress in high fat (HF) diet-induced obese mice. After obesity was induced by HF diet for 9 weeks, the mice were divided into eight groups: (1) lean control, (2) HF diet-induced obese control, (3) 1:1 ratio of MLE and MFE at doses of 200 (L1:1), (4) 500 (M1:1), and (5) 1000 (H1:1) mg/kg per day, and (6) 2:1 ratio of MLE and MFE at doses of 200 (L2:1), (7) 500 (M2:1), and (8) 1000 (H2:1) mg/kg per day. All six combined treatments significantly lowered body weight gain, plasma triglycerides, and lipid peroxidation levels after the 12-week treatment period. Additionally, all combined treatments suppressed hepatic fat accumulation and reduced epididymal adipocyte size. These improvements were accompanied by decreases in protein levels of proinflammatory markers (tumor necrosis factor-alpha, C-reactive protein, interleukin-1, inducible nitric oxide synthase, and phospho-nuclear factor-kappa B inhibitor alpha) and oxidative stress markers (heme oxygenase-1 and manganese superoxide dismutase). M2:1 was the most effective ratio and dose for the improvements in obesity, inflammation, and oxidative stress. These results demonstrate that a combined MLE and MFE treatment ameliorated obesity and obesity-related metabolic stressors and suggest that it can be used as a means to prevent and/or treat obesity. PMID:23957352

  3. The anti-obesity effects of Lactobacillus casei strain Shirota versus Orlistat on high fat diet-induced obese rats

    PubMed Central

    Karimi, Golgis; Sabran, Mohd Redzwan; Jamaluddin, Rosita; Parvaneh, Kolsoom; Mohtarrudin, Norhafizah; Ahmad, Zuraini; Khazaai, Huzwah; Khodavandi, Alireza

    2015-01-01

    Background Obesity and overweight are major public health problems. Various factors, such as daily nutritional habits, physical inactivity, and genetic, are related to the prevalence of obesity. Recently, it was revealed that the gut microflora may also play an important role in weight management. Thus, this study aimed to determine the anti-obesity effects of Lactobacillus casei strain Shirota (LcS) compared with those of orlistat in an animal model fed a high-fat diet (HFD). Design Thirty-two male Sprague-Dawley rats were assigned to four groups fed various diets as follows: a standard diet group, HFD group, HFD supplemented with LcS (108109 colony-forming units (HFD-LcS) group, and HFD group treated with Orlistat (10 mg/kg body weight)). After 15 weeks, the weights of organs, body weight, body fat mass and serological biomarkers were measured. In addition, histological analysis of the liver and adipose tissue was performed. Results Body weight, body mass index, fat mass, leptin and glucose levels were lower, and high-density lipoprotein and adiponectin levels were higher in the HFD-LcS and HFD-orlistat groups than in the HFD group. In addition a significant difference in body fat mass was observed between HFD-LcS group with HFD-orlistat group (19.19±5.76 g vs. 30.19±7.98 g). Although the interleukin-6 level was significantly decreased in the HFD-LcS and HFD-orlistat groups compared with the HFD group, no significant change was observed in other inflammatory biomarkers. Conclusion The results of the present study show that LcS supplementation improves body weight management and the levels of some related biomarkers. In addition, LcS supplementation showed a better result in fat mass and alanine aminotransferase reduction than Orlistat. Further studies are needed to elucidate the anti-obesity effects of LcS, with a longer period of supplementation. PMID:26699936

  4. Transgenic mice overexpressing nesfatin/nucleobindin-2 are susceptible to high-fat diet-induced obesity

    PubMed Central

    Shimizu, H; Tanaka, M; Osaki, A

    2016-01-01

    Background: Nesfatin/Nucleobindin-2 (Nesf/NUCB2), a precursor of nesfatin-1, an anorexigenic protein, is ubiquitously expressed in peripheral tissues in addition to the hypothalamus. However, the role of intracellular Nesf/NUCB2 has not been established in the periphery. Methods: Nesf/NUCB2-transgenic (Tg) mice were generated, and chronological changes of body weight and daily food intake were measured in Nesf/NUCB2-Tg mice fed normal laboratory chow or 45% high-fat diet (HFD). In addition, changes of metabolic markers were evaluated in those mice. Results: No differences were observed in daily food intake and body weight between Nesf/NUCB2-Tg mice (n=11) and their non-Tg littermates (n=11) fed normal chow. Nesf/NUCB2-Tg mice showed increased mRNA expression of oxytocin and corticotropin-releasing hormone and decreased mRNA expression of cocaine- and amphetamine-related transcript in the hypothalamus. Nesf/NUCB2-Tg mice fed 45% HFD (n=6) showed significantly higher increase in body weight than their non-Tg littermates fed the same diet (n=8); however, no difference was observed in daily food intake between these two groups. Further, Nesf/NUCB2-Tg mice fed 45% HFD showed a significant increase in the weight of the liver, subcutaneous fat, and brown adipose tissue and decrease in the expression of uncoupling protein-1 in the subcutaneous fat. Blood glucose levels of Nesf/NUCB2-Tg mice fed 45% HFD were not different from those of their non-Tg littermates fed the same diet. Insulin levels of these Tg mice were significantly higher than those of their non-Tg littermates. Histological analysis showed marked fat deposition in the hepatocytes surrounding the hepatic central veins in Nesf/NUCB2-Tg mice fed 45% HFD. Conclusions: Overexpression of Nesf/NUCB2 did not change food intake, but increased body weight only in Nesf/NUCB2-Tg mice fed HFD. The results of this study indicate that Nesf/NUCB2 was involved in the development of insulin resistance and fat deposition in the

  5. Hypolipidemic potential of perillaldehyde-loaded self-nanoemulsifying delivery system in high-fat diet induced hyperlipidemic mice: Formulation, in vitro and in vivo evaluation.

    PubMed

    Omari-Siaw, Emmanuel; Zhu, Yuan; Wang, Houyong; Peng, Wei; Firempong, Caleb Kesse; Wang, Yuan Wen; Cao, Xia; Deng, Wenwen; Yu, Jiangnan; Xu, Ximing

    2016-03-31

    This study reports the hypolipidemic effects of perillaldehyde-loaded self-nanoemulsifying delivery system (PAH-SNEDS) developed with D-optimal experimental design based on a three component system: 40% w/w drug-oil phase, X1 (a mixture of perillaldehyde-isopropyl myristate/medium chain triglyceride, 1:1, w/w); 48% surfactant, X2 (Kolliphor EL); and 12% co-surfactant, X3 (PEG 200). The design space was navigated using a linear model to produce spherical and homogenous droplets which were observed under TEM, with mean size, polydispersity index (PDI) and zeta potential of 32.8 ± 0.1 nm, 0.270 ± 0.029 and -10.14 ± 0.66 mV, respectively. PAH-SNEDS demonstrated significant increase in dissolution in vitro compared to the free PAH, and further yielded an oral relative bioavailability of about 206.18% in vivo which suggested a promising formulation design for potential liquid bioactive compounds. Oral administration of PAH-SNEDS (240 mg/kg per body weight) in high-fat induced hyperlipidemia in mice, also significantly decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) while increasing high-density lipoprotein cholesterol (HDL-C) level. The improved bioavailability and functional application of PAH via SNEDDS suggested a suitable approach to promote hypolipidemic effect of the drug. Perillaldehyde, therefore, promises to be a useful bioactive compound to prevent high-fat diet induced hyperlipidemia. PMID:26851382

  6. A novel benzenediamine derivative FC98 reduces insulin resistance in high fat diet-induced obese mice by suppression of metaflammation.

    PubMed

    Chen, Changmai; Zhang, Wei; Shi, Hengfei; Zhuo, Yujie; Yang, Guang; Zhang, Aihua; Hou, Yayi; Xiang Tan, Ren; Li, Erguang

    2015-08-15

    Chronic low-grade metabolic inflammation (metaflammation) is a hallmark of metabolic diseases. The aim of this study was to determine the effectiveness of a newly identified benzenediamine derivative (FC98, PubChem CID: 14989837) against metaflammation and insulin resistance using a high fat diet-induced obesity (DIO) murine model. LPS and free fatty acids (FFAs)-induced gene expression and signaling was determined in cell culture systems. Inflammasome activation was determined by measuring IL-1β release with ELISA. The in vivo activity was assayed in C57BL/6J mice fed with a high fat diet (HFD) by measuring body weight gains, glucose tolerance and insulin sensitivity. The effect was also evaluated by H&E and IHC staining, by measuring gene expression and cytokine production, and by analysis of F4/80(+)CD11b(+) macrophage infiltration. FC98 exhibited anti-inflammatory activity against LPS- and FFAs-induced IL-1β, IL-6, and TNF-α gene expression and JNK and p38 activation. The IC50 for FC98 to inhibit NO production was determined at 6.8μM. FC98 also dose-dependently inhibited IL-1β secretion. In DIO mice, FC98 at 10 and 20mg/kg significantly improved metabolic parameters, including body weight, fat mass, glucose disposal and insulin sensitivity. The reduction in adipocyte area, F4/80(+)CD11b(+) macrophage infiltration, proinflammatory gene expression, along with JNK activation, was also significant in those groups. Additionally, FC98-treated animals had increased AKT phosphorylation in response to insulin stimulation. FC98 inhibits metaflammation and ameliorates insulin resistance mainly by inhibiting signaling pathways of proinflammatory response in DIO animals. This study highlights the significance of targeting metaflammation for obesity-attributive metabolic syndrome. PMID:26086863

  7. Maternal high-fat diet-induced programing of gut taste receptor and inflammatory gene expression in rat offspring is ameliorated by CLA supplementation

    PubMed Central

    Reynolds, Clare M; Segovia, Stephanie A; Zhang, Xiaoyuan D; Gray, Clint; Vickers, Mark H

    2015-01-01

    Consumption of a high-fat (HF) diet during pregnancy and lactation influences later life predisposition to obesity and cardiometabolic disease in offspring. The mechanisms underlying this phenomenon remain poorly defined, but one potential target that has received scant attention and is likely pivotal to disease progression is that of the gut. The present study examined the effects of maternal supplementation with the anti-inflammatory lipid, conjugated linoleic acid (CLA), on offspring metabolic profile and gut expression of taste receptors and inflammatory markers. We speculate that preventing high-fat diet-induced metainflammation improved maternal metabolic parameters conferring beneficial effects on adult offspring. Sprague Dawley rats were randomly assigned to a purified control diet (CD; 10% kcal from fat), CD with CLA (CLA; 10% kcal from fat, 1% CLA), HF (45% kcal from fat) or HF with CLA (HFCLA; 45% kcal from fat, 1% CLA) throughout gestation and lactation. Plasma/tissues were taken at day 24 and RT-PCR was carried out on gut sections. Offspring from HF mothers were significantly heavier at weaning with impaired insulin sensitivity compared to controls. This was associated with increased plasma IL-1β and TNFα concentrations. Gut Tas1R1, IL-1β, TNFα, and NLRP3 expression was increased and Tas1R3 expression was decreased in male offspring from HF mothers and was normalized by maternal CLA supplementation. Tas1R1 expression was increased while PYY and IL-10 decreased in female offspring of HF mothers. These results suggest that maternal consumption of a HF diet during critical developmental windows influences offspring predisposition to obesity and metabolic dysregulation. This may be associated with dysregulation of taste receptor, incretin, and inflammatory gene expression in the gut. PMID:26493953

  8. Deficiency of Oncostatin M Receptor β (OSMRβ) Exacerbates High-fat Diet-induced Obesity and Related Metabolic Disorders in Mice*

    PubMed Central

    Komori, Tadasuke; Tanaka, Minoru; Senba, Emiko; Miyajima, Atsushi; Morikawa, Yoshihiro

    2014-01-01

    Oncostatin M (OSM) belongs to the IL-6 family of cytokines and has diverse biological effects, including the modulation of inflammatory responses. In the present study we analyzed the roles of OSM signaling in obesity and related metabolic disorders. Under a high-fat diet condition, OSM receptor β subunit-deficient (OSMRβ−/−) mice exhibited increases in body weight and food intake compared with those observed in WT mice. In addition, adipose tissue inflammation, insulin resistance, and hepatic steatosis were more severe in OSMRβ−/− mice than in wild-type (WT) mice. These metabolic phenotypes did not improve when OSMRβ−/− mice were pair-fed with WT mice, suggesting that the effects of OSM signaling on these phenotypes are independent of the increases in the body weight and food intake. In the liver of OSMRβ−/− mice, the insulin-induced phosphorylation of p70 S6 kinase remained intact, whereas insulin-induced FOXO1 phosphorylation was impaired. In addition, OSMRβ−/− mice displayed a higher expression of genes related to de novo lipogenesis in the liver than WT mice. Furthermore, treatment of genetically obese ob/ob mice with OSM improved insulin resistance, adipose tissue inflammation, and hepatic steatosis. Intraportal administration of OSM into ob/ob mice activated STAT3 and increased the expression of long-chain acyl-CoA synthetase (ACSL) 3 and ACSL5 with decreased expression of fatty acid synthase in the liver, suggesting that OSM directly induces lipolysis and suppresses lipogenesis in the liver of obese mice. These findings suggest that defects in OSM signaling promote the deterioration of high-fat diet-induced obesity and related metabolic disorders. PMID:24695736

  9. Anti-Obesity Effects of the Mixture of Eriobotrya japonica and Nelumbo nucifera in Adipocytes and High-Fat Diet-Induced Obese Mice.

    PubMed

    Sharma, Bhesh Raj; Oh, Jin; Kim, Hyeon-A; Kim, Yong Jae; Jeong, Kyu-Shik; Rhyu, Dong Young

    2015-01-01

    The present study is to evaluate the anti-obesity effects of Eriobotrya japonica (EJ), Nelumbo nucifera (NN), and their mixture (MIX, 1:1 ratio) in 3T3-L1 adipocytes and high-fat diet-induced obese mice. The treatment of EJ, NN, and MIX in 3T3-L1 adipocytes effectively inhibited lipid accumulation, significantly decreased expression of peroxisome proliferator-activated receptor gamma (PPARγ), sterol regulatory element binding protein (SREBP1c), and adipocyte lipid-binding protein (aP2), and significantly increased phosphorylation of AMP-activated protein kinase (AMPK). Moreover, oral treatment of MIX showed stronger effects than individual treatment. C57BL/6J mice (6 week old) were divided into two groups; low fat diet (LFD) containing 10% calories from fat and high fat diet (HFD) containing 60% calories from fat. The HFD groups were further divided into five subgroups; treated with distilled water (HFD), treated with 400 mg/kg EJ (EJ400), treated with 400 mg/kg NN (NN400), treated with 200 mg/kg MIX (MIX200), and treated with 400 mg/kg MIX (MIX400) during 13 weeks. In our results, the administration of EJ, NN, and MIX significantly decreased body weight (BW), fat weight, liver weight, hepatic triglyceride (TG) and total cholesterol (TC), lipid droplets in the liver, food efficacy ratio, and the plasma TG, TC, glucose, insulin, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels in a dose-dependent manner, and MIX treatment showed stronger effect than their individual treatments. Similarly, MIX treatment decreased the expression of PPARγ, SREBP-1c, FAS, and ACC more strongly in the adipose tissue than single treatments. In conclusion, the MIX of EJ and NN extract may strongly regulate BW gain than EJ or NN alone, and its anti-obesity effect is associated with the control of lipid metabolism, including adipogenesis and lipogenesis. PMID:26133751

  10. Sodium butyrate epigenetically modulates high-fat diet-induced skeletal muscle mitochondrial adaptation, obesity and insulin resistance through nucleosome positioning

    PubMed Central

    Henagan, Tara M; Stefanska, Barbara; Fang, Zhide; Navard, Alexandra M; Ye, Jianping; Lenard, Natalie R; Devarshi, Prasad P

    2015-01-01

    Background and Purpose Sodium butyrate (NaB), an epigenetic modifier, is effective in promoting insulin sensitivity. The specific genomic loci and mechanisms underlying epigenetically induced obesity and insulin resistance and the targets of NaB are not fully understood. Experimental Approach The anti-diabetic and anti-obesity effects of NaB treatment were measured by comparing phenotypes and physiologies of C57BL/6J mice fed a low-fat diet (LF), high-fat diet (HF) or high-fat diet plus NaB (HF + NaB) for 10 weeks. We determined a possible mechanism of NaB action through induction of beneficial skeletal muscle mitochondrial adaptations and applied microccocal nuclease digestion with sequencing (MNase-seq) to assess whole genome differences in nucleosome occupancy or positioning and to identify associated epigenetic targets of NaB. Key Results NaB prevented HF diet-induced increases in body weight and adiposity without altering food intake or energy expenditure, improved insulin sensitivity as measured by glucose and insulin tolerance tests, and decreased respiratory exchange ratio. In skeletal muscle, NaB increased the percentage of type 1 fibres, improved acylcarnitine profiles as measured by metabolomics and produced a chromatin structure, determined by MNase-seq, similar to that seen in LF. Targeted analysis of representative nuclear-encoded mitochondrial genes showed specific repositioning of the −1 nucleosome in association with altered gene expression. Conclusions and Implications NaB treatment may be an effective pharmacological approach for type 2 diabetes and obesity by inducing −1 nucleosome repositioning within nuclear-encoded mitochondrial genes, causing skeletal muscle mitochondrial adaptations that result in more complete β-oxidation and a lean, insulin sensitive phenotype. PMID:25559882

  11. Deficiency of oncostatin M receptor β (OSMRβ) exacerbates high-fat diet-induced obesity and related metabolic disorders in mice.

    PubMed

    Komori, Tadasuke; Tanaka, Minoru; Senba, Emiko; Miyajima, Atsushi; Morikawa, Yoshihiro

    2014-05-16

    Oncostatin M (OSM) belongs to the IL-6 family of cytokines and has diverse biological effects, including the modulation of inflammatory responses. In the present study we analyzed the roles of OSM signaling in obesity and related metabolic disorders. Under a high-fat diet condition, OSM receptor β subunit-deficient (OSMRβ(-/-)) mice exhibited increases in body weight and food intake compared with those observed in WT mice. In addition, adipose tissue inflammation, insulin resistance, and hepatic steatosis were more severe in OSMRβ(-/-) mice than in wild-type (WT) mice. These metabolic phenotypes did not improve when OSMRβ(-/-) mice were pair-fed with WT mice, suggesting that the effects of OSM signaling on these phenotypes are independent of the increases in the body weight and food intake. In the liver of OSMRβ(-/-) mice, the insulin-induced phosphorylation of p70 S6 kinase remained intact, whereas insulin-induced FOXO1 phosphorylation was impaired. In addition, OSMRβ(-/-) mice displayed a higher expression of genes related to de novo lipogenesis in the liver than WT mice. Furthermore, treatment of genetically obese ob/ob mice with OSM improved insulin resistance, adipose tissue inflammation, and hepatic steatosis. Intraportal administration of OSM into ob/ob mice activated STAT3 and increased the expression of long-chain acyl-CoA synthetase (ACSL) 3 and ACSL5 with decreased expression of fatty acid synthase in the liver, suggesting that OSM directly induces lipolysis and suppresses lipogenesis in the liver of obese mice. These findings suggest that defects in OSM signaling promote the deterioration of high-fat diet-induced obesity and related metabolic disorders. PMID:24695736

  12. The Roles of ATF3, an Adaptive-Response Gene, in High-Fat-Diet-Induced Diabetes and Pancreatic β-Cell Dysfunction

    PubMed Central

    Zmuda, Erik J.; Qi, Ling; Zhu, Michael X.; Mirmira, Raghavendra G.; Montminy, Marc R.; Hai, Tsonwin

    2010-01-01

    Most people with type 2 diabetes (T2D) have reduced β-cell mass, and apoptosis is a key factor for this reduction. Previously, we showed that ATF3, an adaptive-response gene, is induced by various stress signals relevant to T2D, such as high glucose and high fatty acid. Because ATF3 is proapoptotic in β-cells, we tested the hypothesis that ATF3 plays a detrimental role and contributes to the development of T2D. We compared wild-type (WT) and ATF3 knockout (KO) mice in an animal model for T2D, high-fat diet-induced diabetes. We also used INS-1 β-cells and primary islets to analyze the roles of ATF3 in β-cell function, including insulin gene expression and glucose-induced insulin secretion. Surprisingly, WT mice performed better in glucose tolerance test than KO mice, suggesting a protective, rather than detrimental, role of ATF3. At 12 wk on high-fat diet, no β-cell apoptosis was observed, and the WT and KO mice had comparable β-cell areas. However, ATF3 deficiency significantly reduced serum insulin levels in the KO mice without affecting insulin sensitivity, suggesting reduced β-cell function in the KO mice. Analyses using INS-1 cells and primary islets support the notion that this defect is due, at least partly, to reduced insulin gene transcription in the KO islets without detectable reduction in glucose-induced calcium influx, a critical step for insulin secretion. In conclusion, our results support a model in which, before apoptosis becomes obvious, expression of ATF3 can be beneficial by helping β-cells to cope with higher metabolic demand. PMID:20519332

  13. Improvement of thoracic aortic vasoreactivity by continuous and intermittent exercise in high-fat diet-induced obese rats

    PubMed Central

    LIU, HONGPENG; YANG, ZHEN; HU, JIAN; LUO, YAN; ZHU, LINGQIN; YANG, HUIFANG; LI, GUANGHUA

    2015-01-01

    The aim of the present study was to explore the effects of continuous and intermittent exercise on the thoracic aortic vasoreactivity and free radical metabolism in rats fed with a high-fat diet (HD). Sprague-Dawley (SD) rats were randomly divided into four groups (n=8, each group): Conventional diet (CD), HD, HD with continuous exercise (HCE) and HD with intermittent exercise (HIE). HCE rats swam once/day for 90 min; HIE rats performed swimming exercises 3 times/day, 30 min each time with an interval of 4 h. In these two groups, the exercise was conducted 5 days a week for 8 weeks. Rats in the CD and HD groups were fed without swimming training. At the end of the exercise, all the rats were sacrificed and the blood, thoracic aorta and myocardium were collected immediately. The thoracic aortic vasoreactivity, the plasma total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), superoxide dismutase (SOD), malondialdehyde (MDA) and vascular endothelial nitric oxide synthase (eNOS) gene expression were measured. Compared to the control group, in the HD group the enhanced contractile response of the thoracic aortic rings to noradrenaline (NA) was observed (P<0.01). The levels of TC and LDL (P<0.01) were also increased in serum while the HDL level was reduced without statistical significance. In addition, the MDA content was upregulated in the myocardium, but the SOD level decreased (P<0.01). Furthermore, the expression of vascular eNOS mRNA was reduced (P<0.01). However, following the exercise the contraction of the thoracic aorta vascular rings to NA was reduced in the HCE and HIE groups (P<0.01), and the decreased contractile response was more evident in the HIE group compared to the HCE group (P<0.01). Additionally, in the HCE group the level of TG (P<0.01) was decreased, while the HDL (P<0.01) level was increased. Although the reduction of the TC and LDL level was also observed there was no significant difference

  14. Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice.

    PubMed

    Horakova, Olga; Hansikova, Jana; Bardova, Kristina; Gardlo, Alzbeta; Rombaldova, Martina; Kuda, Ondrej; Rossmeisl, Martin; Kopecky, Jan

    2016-01-01

    Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. PMID:27183228

  15. Plasma Acylcarnitines and Amino Acid Levels As an Early Complex Biomarker of Propensity to High-Fat Diet-Induced Obesity in Mice

    PubMed Central

    Bardova, Kristina; Gardlo, Alzbeta; Rombaldova, Martina; Kuda, Ondrej; Rossmeisl, Martin; Kopecky, Jan

    2016-01-01

    Obesity is associated with insulin resistance and impaired glucose tolerance, which represent characteristic features of the metabolic syndrome. Development of obesity is also linked to changes in fatty acid and amino acid metabolism observed in animal models of obesity as well as in humans. The aim of this study was to explore whether plasma metabolome, namely the levels of various acylcarnitines and amino acids, could serve as a biomarker of propensity to obesity and impaired glucose metabolism. Taking advantage of a high phenotypic variation in diet-induced obesity in C57BL/6J mice, 12-week-old male and female mice (n = 155) were fed a high-fat diet (lipids ~32 wt%) for a period of 10 weeks, while body weight gain (BWG) and changes in insulin sensitivity (ΔHOMA-IR) were assessed. Plasma samples were collected before (week 4) and after (week 22) high-fat feeding. Both univariate and multivariate statistical analyses were then used to examine the relationships between plasma metabolome and selected phenotypes including BWG and ΔHOMA-IR. Partial least squares-discrimination analysis was able to distinguish between animals selected either for their low or high BWG (or ΔHOMA-IR) in male but not female mice. Among the metabolites that differentiated male mice with low and high BWG, and which also belonged to the major discriminating metabolites when analyzed in plasma collected before and after high-fat feeding, were amino acids Tyr and Orn, as well as acylcarnitines C16-DC and C18:1-OH. In general, the separation of groups selected for their low or high ΔHOMA-IR was less evident and the outcomes of a corresponding multivariate analysis were much weaker than in case of BWG. Thus, our results document that plasma acylcarnitines and amino acids could serve as a gender-specific complex biomarker of propensity to obesity, however with a limited predictive value in case of the associated impairment of insulin sensitivity. PMID:27183228

  16. 8-Hydroxyeicosapentaenoic Acid Decreases Plasma and Hepatic Triglycerides via Activation of Peroxisome Proliferator-Activated Receptor Alpha in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Yamada, Hidetoshi; Kikuchi, Sayaka; Hakozaki, Mayuka; Motodate, Kaori; Nagahora, Nozomi; Hirose, Masamichi

    2016-01-01

    PPARs regulate the expression of genes involved in lipid homeostasis. PPARs serve as molecular sensors of fatty acids, and their activation can act against obesity and metabolic syndromes. 8-Hydroxyeicosapentaenoic acid (8-HEPE) acts as a PPAR ligand and has higher activity than EPA. However, to date, the PPAR ligand activity of 8-HEPE has only been demonstrated in vitro. Here, we investigated its ligand activity in vivo by examining the effect of 8-HEPE treatment on high fat diet-induced obesity in mice. After the 4-week treatment period, the levels of plasma and hepatic triglycerides in the 8-HEPE-fed mice were significantly lower than those in the HFD-fed mice. The expression of genes regulated by PPARα was significantly increased in 8-HEPE-fed mice compared to those that received only HFD. Additionally, the level of hepatic palmitic acid in 8-HEPE-fed mice was significantly lower than in HFD-fed mice. These results suggested that intake of 8-HEPE induced PPARα activation and increased catabolism of lipids in the liver. We found no significant differences between EPA-fed mice and HFD-fed mice. We demonstrated that 8-HEPE has a larger positive effect on metabolic syndrome than EPA and that 8-HEPE acts by inducing PPARα activation in the liver. PMID:27239345

  17. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats.

    PubMed

    Zhang, Xu; Zhao, Yufeng; Xu, Jia; Xue, Zhengsheng; Zhang, Menghui; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping

    2015-01-01

    Accumulating evidence suggests that the gut microbiota is an important factor in mediating the development of obesity-related metabolic disorders, including type 2 diabetes. Metformin and berberine, two clinically effective drugs for treating diabetes, have recently been shown to exert their actions through modulating the gut microbiota. In this study, we demonstrated that metformin and berberine similarly shifted the overall structure of the gut microbiota in rats. Both drugs showed reverting effects on the high-fat diet-induced structural changes of gut microbiota. The diversity of gut microbiota was significantly reduced by both berberine- and metformin-treatments. Nearest shrunken centroids analysis identified 134 operational taxonomic units (OTUs) responding to the treatments, which showed close associations with the changes of obese phenotypes. Sixty out of the 134 OTUs were decreased by both drugs, while those belonging to putative short-chain fatty acids (SCFA)-producing bacteria, including Allobaculum, Bacteriodes, Blautia, Butyricoccus, and Phascolarctobacterium, were markedly increased by both berberine and, to a lesser extent, metformin. Taken together, our findings suggest that berberine and metformin showed similarity in modulating the gut microbiota, including the enrichment of SCFA-producing bacteria and reduction of microbial diversity, which may contribute to their beneficial effects to the host. PMID:26396057

  18. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats

    PubMed Central

    Zhang, Xu; Zhao, Yufeng; Xu, Jia; Xue, Zhengsheng; Zhang, Menghui; Pang, Xiaoyan; Zhang, Xiaojun; Zhao, Liping

    2015-01-01

    Accumulating evidence suggests that the gut microbiota is an important factor in mediating the development of obesity-related metabolic disorders, including type 2 diabetes. Metformin and berberine, two clinically effective drugs for treating diabetes, have recently been shown to exert their actions through modulating the gut microbiota. In this study, we demonstrated that metformin and berberine similarly shifted the overall structure of the gut microbiota in rats. Both drugs showed reverting effects on the high-fat diet-induced structural changes of gut microbiota. The diversity of gut microbiota was significantly reduced by both berberine- and metformin-treatments. Nearest shrunken centroids analysis identified 134 operational taxonomic units (OTUs) responding to the treatments, which showed close associations with the changes of obese phenotypes. Sixty out of the 134 OTUs were decreased by both drugs, while those belonging to putative short-chain fatty acids (SCFA)-producing bacteria, including Allobaculum, Bacteriodes, Blautia, Butyricoccus, and Phascolarctobacterium, were markedly increased by both berberine and, to a lesser extent, metformin. Taken together, our findings suggest that berberine and metformin showed similarity in modulating the gut microbiota, including the enrichment of SCFA-producing bacteria and reduction of microbial diversity, which may contribute to their beneficial effects to the host. PMID:26396057

  19. Coral calcium hydride prevents hepatic steatosis in high fat diet-induced obese rats: A potent mitochondrial nutrient and phase II enzyme inducer.

    PubMed

    Hou, Chen; Wang, Yongyao; Zhu, Erkang; Yan, Chunhong; Zhao, Lin; Wang, Xiaojie; Qiu, Yingfeng; Shen, Hui; Sun, Xuejun; Feng, Zhihui; Liu, Jiankang; Long, Jiangang

    2016-03-01

    Diet-induced nonalcoholic fatty liver disease (NAFLD) is characterized by profound lipid accumulation and associated with an inflammatory response, oxidative stress and hepatic mitochondrial dysfunction. We previously demonstrated that some mitochondrial nutrients effectively ameliorated high fat diet (HFD)-induced hepatic steatosis and metabolic disorders. Molecular hydrogen in hydrogen-rich liquid or inhaling gas, which has been confirmed in scavenging reactive oxygen species and preventing mitochondrial decay, improved metabolic syndrome in patients and animal models. Coral calcium hydride (CCH) is a new solid molecular hydrogen carrier made of coral calcium. However, whether and how CCH impacts HFD-induced hepatic steatosis remains uninvestigated. In the present study, we applied CCH to a HFD-induced NAFLD rat model for 13 weeks. We found that CCH durably generated hydrogen in vivo and in vitro. CCH treatment significantly reduced body weight gain, improved glucose and lipid metabolism and attenuated hepatic steatosis in HFD-induced obese rats with no influence on food and water intake. Moreover, CCH effectively improved HFD-induced hepatic mitochondrial dysfunction, reduced oxidative stress, and activated phase II enzymes. Our results suggest that CCH is an efficient hydrogen-rich agent, which could prevent HFD-induced NAFLD via activating phase II enzymes and improving mitochondrial function. PMID:26774456

  20. Polyphenol-rich extract of pomegranate peel alleviates tissue inflammation and hypercholesterolaemia in high-fat diet-induced obese mice: potential implication of the gut microbiota.

    PubMed

    Neyrinck, Audrey M; Van Hée, Vincent F; Bindels, Laure B; De Backer, Fabienne; Cani, Patrice D; Delzenne, Nathalie M

    2013-03-14

    Pomegranate extracts have been used for centuries in traditional medicine to confer health benefits in a number of inflammatory diseases, microbial infections and cancer. Peel fruit are rich in polyphenols that exhibit antioxidant and anti-inflammatory capacities in vitro. Recent studies strongly suggest that the gut microbiota is an environmental factor to be taken into account when assessing the risk factors related to obesity. The aim of the present study was to test the prebiotic potency of a pomegranate peel extract (PPE) rich in polyphenols in a nutritional model of obesity associated with hypercholesterolaemia and inflammatory disorders. Balb/c mice were fed either a control diet or a high-fat (HF) diet with or without PPE (6 mg/d per mouse) over a period of 4 weeks. Interestingly, PPE supplementation increased caecal content weight and caecal pool of bifidobacteria. It did not significantly modify body weight gain, glycaemia, glucose tolerance and inflammatory markers measured in the serum. However, it reduced the serum level of cholesterol (total and LDL) induced by HF feeding. Furthermore, it counteracted the HF-induced expression of inflammatory markers both in the colon and the visceral adipose tissue. Together, these findings support that pomegranate constitutes a promising food in the control of atherogenic and inflammatory disorders associated with diet-induced obesity. Knowing the poor bioavailability of pomegranate polyphenols, its bifidogenic effect observed after PPE consumption suggests the involvement of the gut microbiota in the management of host metabolism by polyphenolic compounds present in pomegranate. PMID:22676910

  1. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood

    PubMed Central

    de Fante, Thaís; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; de Souza, Monique; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  2. Extract of okra lowers blood glucose and serum lipids in high-fat diet-induced obese C57BL/6 mice.

    PubMed

    Fan, Shengjie; Zhang, Yu; Sun, Qinhu; Yu, Lijing; Li, Mingxia; Zheng, Bin; Wu, Ximin; Yang, Baican; Li, Yiming; Huang, Cheng

    2014-07-01

    Okra is an important tropical vegetable and source of dietary medicine. Here, we assayed the effects of an ethanol extract of okra (EO) and its major flavonoids isoquercitrin and quercetin 3-O-gentiobioside on metabolic disorders in high-fat diet-induced obese mouse. We found that treatment with EO, isoquercitrin and quercetin 3-O-gentiobioside reduced blood glucose and serum insulin levels and improved glucose tolerance in obese mice. Meanwhile, serum triglyceride levels and liver morphology in the mice were significantly ameliorated by EO and isoquercitrin treatment. Total cholesterol levels in isoquercitrin and quercetin 3-O-gentiobioside treated mice were also reduced. We also found that EO inhibited the expression of nuclear receptor transcription factor PPARγ, which is an important regulator of lipid and glucose homeostasis. Furthermore, we determined that EO and quercetin 3-O-gentiobioside have antioxidant activity in vitro. Our results indicate that okra may serve as a dietary therapy for hyperglycemia and hypertriglyceridemia. PMID:24746837

  3. Diet-Induced Maternal Obesity Alters Insulin Signalling in Male Mice Offspring Rechallenged with a High-Fat Diet in Adulthood.

    PubMed

    Fante, Thaís de; Simino, Laís Angélica; Reginato, Andressa; Payolla, Tanyara Baliani; Vitoréli, Débora Cristina Gustavo; Souza, Monique de; Torsoni, Márcio Alberto; Milanski, Marciane; Torsoni, Adriana Souza

    2016-01-01

    Modern lifestyle has resulted in an increase in the prevalence of obesity and its comorbidities in pregnant women and the young population. It has been well established that the consumption of a high-fat diet (HFD) has many direct effects on glucose metabolism. However, it is important to assess whether maternal consumption of a HFD during critical periods of development can lead to metabolic changes in the offspring metabolism. This study evaluated the potential effects of metabolic programming on the impairment of insulin signalling in recently weaned offspring from obese dams. Additionally, we investigated if early exposure to an obesogenic environment could exacerbate the impairment of glucose metabolism in adult life in response to a HFD. Swiss female mice were fed with Standard Chow (SC) or a HFD during gestation and lactation and tissues from male offspring were analysed at d28 and d82. Offspring from obese dams had greater weight gain and higher adiposity and food intake than offspring from control dams. Furthermore, they showed impairment in insulin signalling in central and peripheral tissues, which was associated with the activation of inflammatory pathways. Adipose tissue was ultimately the most affected in adult offspring after HFD rechallenge; this may have contributed to the metabolic deregulation observed. Overall, our results suggest that diet-induced maternal obesity leads to increased susceptibility to obesity and impairment of insulin signalling in offspring in early and late life that cannot be reversed by SC consumption, but can be aggravated by HFD re-exposure. PMID:27479001

  4. Antibody-assisted enhancement of biological activities of CXCL14 in human monocytic leukemia-derived THP-1 cells and high fat diet-induced obese mice.

    PubMed

    Tanegashima, Kosuke; Suzuki, Kenji; Nakayama, Yuki; Hara, Takahiko

    2010-04-15

    CXCL14 is a CXC-type chemokine acting on tissue macrophages, immature dendritic cells, natural killer cells, and epithelial tumor cells. It also serves as a metabolic regulator in obese mice by blunting insulin activity. In contrast to other CXC chemokines, it remains to be clarified how CXCL14 activates its putative receptors on the cell surface and whether it induces chemokinesis. This is mainly due to the insufficient sensitivity of currently available bioassays for CXCL14. In this study, we found that the anti-CXCL14 monoclonal antibody, MAB730, remarkably enhances the activities of CXCL14 in human monocytic leukemia-derived THP-1 cells and immature dendritic cells. MAB730 augmented CXCL14-mediated chemotaxis and chemokinesis with distinct dose requirement. Chemotaxis inducing activity was retained in the MAB730 F(ab')(2) fraction, but not in the Fab fraction, implying that ligand dimerization is involved in the MAB730-assisted enhancement of CXCL14 activity. In addition, MAB730 was more efficient than heparin at inhibiting CXCL14 binding to low affinity receptors on THP-1 cells. Finally, in vivo administration of MAB730 antibody into high fat diet-induced obese mice increased whole body insulin resistance and glucose intolerance. These unique properties of MAB730 will be useful for elucidating the molecular mechanism of cellular responses elicited by CXCL14. PMID:20083103

  5. Hyperinsulinemia shifted energy supply from glucose to ketone bodies in early nonalcoholic steatohepatitis from high-fat high-sucrose diet induced Bama minipigs.

    PubMed

    Yang, Shu-lin; Xia, Ji-han; Zhang, Yuan-yuan; Fan, Jian-gao; Wang, Hua; Yuan, Jing; Zhao, Zhan-zhao; Pan, Qin; Mu, Yu-lian; Xin, Lei-lei; Chen, Yao-xing; Li, Kui

    2015-01-01

    The minipig can serve as a good pharmacological model for human subjects. However, the long-term pathogenesis of high-calorie diet-induced metabolic syndromes, including NASH, has not been well described in minipigs. We examined the development of metabolic syndromes in Bama minipigs that were fed a high-fat, high-sucrose diet (HFHSD) for 23 months, by using histology and serum biochemistry and by profiling the gene expression patterns in the livers of HFHSD pigs compared to controls. The pathology findings revealed microvesicular steatosis, iron overload, arachidonic acid synthesis, lipid peroxidation, reduced antioxidant capacity, increased cellular damage, and inflammation in the liver. RNA-seq analysis revealed that 164 genes were differentially expressed between the livers of the HFHSD and control groups. The pathogenesis of early-stage NASH was characterized by hyperinsulinemia and by de novo synthesis of fatty acids and nascent triglycerides, which were deposited as lipid droplets in hepatocytes. Hyperinsulinemia shifted the energy supply from glucose to ketone bodies, and the high ketone body concentration induced the overexpression of cytochrome P450 2E1 (CYP2E1). The iron overload, CYP2E1 and alcohol dehydrogenase 4 overexpression promoted reactive oxygen species (ROS) production, which resulted in arachidonic and linoleic acid peroxidation and, in turn, led to malondialdehyde production and a cellular response to ROS-mediated DNA damage. PMID:26358367

  6. Hyperinsulinemia shifted energy supply from glucose to ketone bodies in early nonalcoholic steatohepatitis from high-fat high-sucrose diet induced Bama minipigs

    PubMed Central

    Yang, Shu-lin; Xia, Ji-han; Zhang, Yuan-yuan; Fan, Jian-gao; Wang, Hua; Yuan, Jing; Zhao, Zhan-zhao; Pan, Qin; Mu, Yu-lian; Xin, Lei-lei; Chen, Yao-xing; Li, Kui

    2015-01-01

    The minipig can serve as a good pharmacological model for human subjects. However, the long-term pathogenesis of high-calorie diet-induced metabolic syndromes, including NASH, has not been well described in minipigs. We examined the development of metabolic syndromes in Bama minipigs that were fed a high-fat, high-sucrose diet (HFHSD) for 23 months, by using histology and serum biochemistry and by profiling the gene expression patterns in the livers of HFHSD pigs compared to controls. The pathology findings revealed microvesicular steatosis, iron overload, arachidonic acid synthesis, lipid peroxidation, reduced antioxidant capacity, increased cellular damage, and inflammation in the liver. RNA-seq analysis revealed that 164 genes were differentially expressed between the livers of the HFHSD and control groups. The pathogenesis of early-stage NASH was characterized by hyperinsulinemia and by de novo synthesis of fatty acids and nascent triglycerides, which were deposited as lipid droplets in hepatocytes. Hyperinsulinemia shifted the energy supply from glucose to ketone bodies, and the high ketone body concentration induced the overexpression of cytochrome P450 2E1 (CYP2E1). The iron overload, CYP2E1 and alcohol dehydrogenase 4 overexpression promoted reactive oxygen species (ROS) production, which resulted in arachidonic and linoleic acid peroxidation and, in turn, led to malondialdehyde production and a cellular response to ROS-mediated DNA damage. PMID:26358367

  7. Low carbohydrate/high-fat diet attenuates cardiac hypertrophy, remodeling, and altered gene expression in hypertension

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of dietary fat intake on the development of left ventricular hypertrophy and accompanying structural and molecular remodeling in response to hypertension are not understood. The present study compared the effects of a high-fat versus a low-fat diet on development of left ventricular hype...

  8. Piperidine alkaloids from Piperretrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase

    SciTech Connect

    Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae; Hwang, Jae-Kwan

    2011-07-22

    Highlights: {yields} Piperidine alkaloids from Piperretrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, are isolated as the anti-obesity constituents. {yields} PRPA administration significantly reduces body weight gain without altering food intake and fat pad mass. {yields} PRPA reduces high-fat diet-induced triglyceride accumulation in liver. {yields} PRPAs attenuate HFD-induced obesity by activating AMPK and PPAR{delta}, and regulate lipid metabolism, suggesting their potential anti-obesity effects. -- Abstract: The fruits of Piperretrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor {delta} (PPAR{delta}) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPAR{delta} protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300 mg/kg/day for 8 weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also

  9. Corn Gluten Hydrolysate Affects the Time-Course of Metabolic Changes Through Appetite Control in High-Fat Diet-Induced Obese Rats

    PubMed Central

    Lee, Hyojung; Lee, Hyo Jin; Kim, Ji Yeon; Kwon, Oran

    2015-01-01

    This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague-Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats. PMID:26549503

  10. Corn Gluten Hydrolysate Affects the Time-Course of Metabolic Changes Through Appetite Control in High-Fat Diet-Induced Obese Rats.

    PubMed

    Lee, Hyojung; Lee, Hyo Jin; Kim, Ji Yeon; Kwon, Oran

    2015-12-31

    This study first investigated the effects of corn gluten hydrolysate (CGH) (1.5 g/day) administration for 7 days on appetite-responsive genes in lean Sprague-Dawley (SD) rats. In a second set of experiments, the metabolic changes occurring at multiple time points over 8 weeks in response to CGH (35.33% wt/wt) were observed in high-fat (HF, 60% of energy as fat) diet-fed SD rats. In lean rats, the hypothalamus neuropeptide-Y and proopiomelanocortin mRNA levels of the CGH group were significantly changed in response to CGH administration. In the second part of the study, CGH treatment was found to reduce body weight and perirenal and epididymal fat weight. CGH also prevented an increase in food intake at 2 weeks and lowered plasma leptin and insulin levels in comparison with the HF group. This reduction in the plasma and hepatic lipid levels was followed by improved insulin resistance, and the beneficial metabolic effects of CGH were also partly related to increases in plasma adiponectin levels. The Homeostasis Model of Assessment - Insulin Resistance (HOMA-IR), an index of insulin resistance, was markedly improved in the HF-CGH group compared with the HF group at 6 weeks. According to the microarray results, adipose tissue mRNA expression related to G-protein coupled receptor protein signaling pathway and sensory perception was significantly improved after 8 weeks of CGH administration. In conclusion, the present findings suggest that dietary CGH may be effective for improving hyperglycemia, dyslipidemia and insulin resistance in diet-induced obese rats as well as appetite control in lean rats. PMID:26549503

  11. Indomethacin Treatment Prevents High Fat Diet-induced Obesity and Insulin Resistance but Not Glucose Intolerance in C57BL/6J Mice*

    PubMed Central

    Fjære, Even; Aune, Ulrike L.; Røen, Kristin; Keenan, Alison H.; Ma, Tao; Borkowski, Kamil; Kristensen, David M.; Novotny, Guy W.; Mandrup-Poulsen, Thomas; Hudson, Brian D.; Milligan, Graeme; Xi, Yannan; Newman, John W.; Haj, Fawaz G.; Liaset, Bjørn; Kristiansen, Karsten; Madsen, Lise

    2014-01-01

    Chronic low grade inflammation is closely linked to obesity-associated insulin resistance. To examine how administration of the anti-inflammatory compound indomethacin, a general cyclooxygenase inhibitor, affected obesity development and insulin sensitivity, we fed obesity-prone male C57BL/6J mice a high fat/high sucrose (HF/HS) diet or a regular diet supplemented or not with indomethacin (±INDO) for 7 weeks. Development of obesity, insulin resistance, and glucose intolerance was monitored, and the effect of indomethacin on glucose-stimulated insulin secretion (GSIS) was measured in vivo and in vitro using MIN6 β-cells. We found that supplementation with indomethacin prevented HF/HS-induced obesity and diet-induced changes in systemic insulin sensitivity. Thus, HF/HS+INDO-fed mice remained insulin-sensitive. However, mice fed HF/HS+INDO exhibited pronounced glucose intolerance. Hepatic glucose output was significantly increased. Indomethacin had no effect on adipose tissue mass, glucose tolerance, or GSIS when included in a regular diet. Indomethacin administration to obese mice did not reduce adipose tissue mass, and the compensatory increase in GSIS observed in obese mice was not affected by treatment with indomethacin. We demonstrate that indomethacin did not inhibit GSIS per se, but activation of GPR40 in the presence of indomethacin inhibited glucose-dependent insulin secretion in MIN6 cells. We conclude that constitutive high hepatic glucose output combined with impaired GSIS in response to activation of GPR40-dependent signaling in the HF/HS+INDO-fed mice contributed to the impaired glucose clearance during a glucose challenge and that the resulting lower levels of plasma insulin prevented the obesogenic action of the HF/HS diet. PMID:24742673

  12. Effect of feeding a high-fat diet independently of caloric intake on reproductive function in diet-induced obese female rats

    PubMed Central

    Hussain, Mona A.; Abogresha, Noha M.; Tamany, Dalia A.; Lotfy, Mariam

    2016-01-01

    Introduction Globally, the prevalence of overweight and obesity is increasing, predisposing females to health hazards including compromised reproductive capacity. Our objective was to investigate the effect of ad libitum, isocalorically and hypocalorically restricted high-fat diet (HFD) feeding on reproductive function in diet-induced obese female rats. Material and methods Twenty female albino Sprague Dawley rats were used; 5 rats were kept on a standard pellet animal diet to serve as a control group (A) and 15 rats were fed a HFD for 9 weeks to induce obesity. The HFD fed animals were equally divided into three groups: an ad libitum HFD group (B), an isocalorically restricted HFD group (C), and a hypocalorically restricted HFD group (D). Estrous cyclicity, hormonal levels, ovarian histopathology and caspase-3 immunoreactivity were evaluated. Results The HFD-fed rats in groups B, C and D had significant irregularity in estrous cyclicity Vs group A (p = 0.001, 0.003 and 0.034 respectively). Groups C and D had significant reduction in serum progesterone level (p = 0.006 and 0.018 Vs A). Isocaloric restriction of HFD feeding significantly increased serum LH. Groups B and C had a significant increase in caspase-3 expression in the ovary (p < 0.001). Conclusions Ad libitum HFD interfered with the normal estrous cycle and enhanced apoptosis of luteal cells in obese female rats. The HFD restriction interfered with the normal estrous cycle and caused functional insufficiency of the corpus luteum in obese female rats. These results suggest that HFD feeding determinately affects female reproductive function independently of caloric intake. PMID:27478474

  13. Short and Long-Term Impact of Lipectomy on Expression Profile of Hepatic Anabolic Genes in Rats: A High Fat and High Cholesterol Diet-Induced Obese Model

    PubMed Central

    Ling, Bey-Leei; Chiu, Chun-Tang; Lu, Hsiu-Chin; Lin, Jin-Jin; Kuo, Chiung-Yin; Chou, Fen-Pi

    2014-01-01

    Objective To understand the molecular basis of the short and long-term effects of an immediate shortage of energy storage caused by lipectomy on expression profile of genes involved in lipid and carbohydrate metabolism in high fat and high cholesterol diet-induced obese rats. Methods The hepatic mRNA levels of enzymes, regulator and transcription factors involved in glucose and lipid metabolism were analyzed by quantitative real time polymerase chain reaction (RT-qPCR) ten days and eight weeks after lipectomy in obese rats. Body and liver weights and serum biochemical parameters, adiponectin, leptin and insulin were determined. Results No significant difference was observed on the food intake between the lipectomized and sham-operated groups during the experimental period. Ten days after the operation, the lipectomized animals showed significant higher triacylglycerol, glucose and insulin levels, a lower adiponectin concentration than the sham-operated rats, along with significant higher hepatic mRNA levels of hepatocyte nuclear factor 4α (HNF4α) and the enzymes involved in lipogenesis, sterol biosynthesis and gluconeogenesis. The results of immunohistochemical (IHC) analysis also confirmed increased levels of lipogenic enzymes in the liver of lipectomized versus sham-operated animals. The lipectomized group had a significantly lower adiponectin/leptin ratio that was positively correlated to the level of LDL (r = 0.823, P<0.05) and negatively to glucose and insulin (r = −0.821 and −0.892 respectively, P<0.05). Eight weeks after the operation, the lipectomized animals revealed significant higher body and liver weights, weight gain, liver to body weight ratio, hepatic triacylglycerol and serum insulin level. Conclusions In response to lipectomy a short term enhancement of the expression of hepatic anabolic genes involved in lipid and carbohydrate metabolism was triggered that might eventually lead to the final extra weight gain. These metabolic changes

  14. High-fat diet-induced met-hemoglobin formation in rats prone (WOKW) or resistant (DA) to the metabolic syndrome: effect of CoQ10 supplementation.

    PubMed

    Orlando, Patrick; Silvestri, Sonia; Brugè, Francesca; Tiano, Luca; Kloting, Ingrid; Falcioni, Giancarlo; Polidori, Carlo

    2014-01-01

    The aim of this study was to evaluate the effects of a high-fat diet (HFD) on oxidative indexes in WistarOttawaKarlsburg W (WOKW) rats used as a model of metabolic syndrome in comparison with Dark Agouti (DA) rats used as a control strain. This syndrome is defined by the occurrence of two or more risk factors including obesity, hypertension, dyslipidemia, and insulin resistance. Forty rats were used in the study and the effect of HFD was evaluated in terms of body weight and both hemoglobin and CoQ oxidative status. Moreover, 16 rats (8 of each strain) were supplemented with 3 mg/100 g b.w. of CoQ10 for 1 month in view of its beneficial properties in cardiovascular disease due to its antioxidant activity in the lipid environment. HFD promoted an increase in body weight, in particular in WOKW males, and in the methemoglobin (met-Hb) index in both strains. Moreover, HFD promoted endogenous CoQ10 oxidation. CoQ10 supplementation was able to efficiently counteract the HFD pro-oxidant effects, preventing met-Hb formation and CoQ oxidation. PMID:25428841

  15. Antiobesity Effects of an Edible Halophyte Nitraria retusa Forssk in 3T3-L1 Preadipocyte Differentiation and in C57B6J/L Mice Fed a High Fat Diet-Induced Obesity

    PubMed Central

    Zar Kalai, Feten; Han, Junkyu; Ksouri, Riadh; El Omri, Abdelfatteh; Abdelly, Chedly; Isoda, Hiroko

    2013-01-01

    Nitraria retusa is an edible halophyte, used in Tunisia for several traditional medicine purposes. The present study investigated the antiobesity effects of Nitraria retusa ethanol extract (NRE) in 3T3-L1 cells using different doses and in high-fat diet-induced obesity in mice. Male C57B6J/L mice were separately fed a normal diet (ND) or a high-fat diet (HFD) and daily administrated with NRE (50, 100 mg/kg) or one for 2 days with Naringenin (10 mg/kg). NRE administration significantly decreased body weight gain, fat pad weight, serum glucose, and lipid levels in HFD-induced obese mice. To elucidate the mechanism of action of NRE, the expression of genes involved in lipid and carbohydrate metabolism were measured in liver. Results showed that mice treated with NRE demonstrated a significant decrease in cumulative body weight and fat pad weight, a significant lowering in glucose and triglycerides serum levels, and an increase in the HDL-cholesterol serum level. Moreover mRNA expression results showed an enhancement of the expression of genes related to liver metabolism. Our findings suggest that NRE treatment had a protective or controlling effect against a high fat diet-induced obesity in C57B6J/L mice through the regulation of expression of genes involved in lipolysis and lipogenesis and thus the enhancement of the lipid metabolism in liver. PMID:24367387

  16. Antiaging Gene Klotho Deficiency Promoted High-Fat Diet-Induced Arterial Stiffening via Inactivation of AMP-Activated Protein Kinase.

    PubMed

    Lin, Yi; Chen, Jianglei; Sun, Zhongjie

    2016-03-01

    Klotho was originally discovered as an aging-suppressor gene. The objective of this study is to investigate whether klotho gene deficiency affects high-fat diet (HFD)-induced arterial stiffening. Heterozygous Klotho-deficient (KL(+/-)) mice and WT littermates were fed on HFD or normal diet. HFD increased pulse wave velocity within 5 weeks in KL(+/-) mice but not in wild-type mice, indicating that klotho deficiency accelerates and exacerbates HFD-induced arterial stiffening. A greater increase in blood pressure was found in KL(+/-) mice fed on HFD. Protein expressions of phosphorylated AMP-activated protein kinase-α (AMPKα), phosphorylated endothelial nitric oxide synthase (eNOS), and manganese-dependent superoxide dismutase (Mn-SOD) were decreased, whereas protein expressions of collagen I, transforming growth factor-β1, and Runx2 were increased in aortas of KL(+/-) mice fed on HFD. Interestingly, daily injections of an AMPKα activator, 5-aminoimidazole-4-carboxamide-3-ribonucleoside, abolished the increases in pulse wave velocity, blood pressure, and blood glucose in KL(+/-) mice fed on HFD. Treatment with 5-aminoimidazole-4-carboxamide-3-ribonucleoside for 2 weeks not only abolished the downregulation of phosphorylated AMPKα, phosphorylated eNOS, and Mn-SOD levels but also attenuated the increased levels of collagen I, transforming growth factor-β1, Runx2, superoxide, elastic lamellae breaks, and calcification in aortas of KL(+/-) mice fed on HFD. In cultured mouse aortic smooth muscle cells, cholesterol plus KL-deficient serum decreased phosphorylation levels of AMPKα and LKB1 (an important upstream regulator of AMPKα activity) but increased collagen I synthesis, which can be eliminated by activation of AMPKα by 5-aminoimidazole-4-carboxamide-3-ribonucleoside. In conclusions, Klotho deficiency promoted HFD-induced arterial stiffening and hypertension via downregulation of AMPKα activity. PMID:26781278

  17. Brown Alga Ecklonia cava polyphenol extract ameliorates hepatic lipogenesis, oxidative stress, and inflammation by activation of AMPK and SIRT1 in high-fat diet-induced obese mice.

    PubMed

    Eo, Hyeyoon; Jeon, You-jin; Lee, Myoungsook; Lim, Yunsook

    2015-01-14

    Obesity is considered to be a metaflammatory condition. Ecklonia cava, brown algae rich in polyphenols, has shown strong antioxidant activity in vitro. This study investigated the effect of E. cava polyphenol extract (ECPE) on the regulation of fat metabolism, inflammation, and the antioxidant defense system in high fat diet-induced obese mice. After obesity was induced by a high-fat diet (HFD), the mice were administered ECPE by gavage for 5 days/12 weeks. ECPE supplementation reduced body weight gain, adipose tissue mass, plasma lipid profiles, hepatic fat deposition, insulin resistance, and the plasma leptin/adiponectin ratio derived from HFD-induced obesity. Moreover, ECPE supplementation selectively ameliorated hepatic protein levels associated with lipogenesis, inflammation, and the antioxidant defense system as well as activation of AMPK and SIRT1. Collectively, ECPE supplement might have potential antiobesity effects via regulation of AMPK and SIRT1 in HFD-induced obesity. PMID:25479240

  18. Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats

    PubMed Central

    Adam, Clare L.; Gratz, Silvia W.; Peinado, Diana I.; Thomson, Lynn M.; Garden, Karen E.; Williams, Patricia A.; Richardson, Anthony J.; Ross, Alexander W.

    2016-01-01

    Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity. PMID:27224646

  19. Heat-killed and live Lactobacillus reuteri GMNL-263 exhibit similar effects on improving metabolic functions in high-fat diet-induced obese rats.

    PubMed

    Hsieh, Feng-Ching; Lan, Cheng-Che E; Huang, Tsui-Yin; Chen, Kuan-Wei; Chai, Chee-Yin; Chen, Wan-Tzu; Fang, Ai-Hui; Chen, Yi-Hsing; Wu, Ching-Shuang

    2016-05-18

    Our objective was to investigate and compare the effects of heat-killed (HK) and live Lactobacillus reuteri GMNL-263 (Lr263) on insulin resistance and its related complications in high-fat diet (HFD)-induced rats. Male Sprague-Dawley rats were fed with a HFD with either HK or live Lr263 for 12 weeks. The increases in the weight gain, serum glucose, insulin, and lipid profiles in the serum and liver observed in the HFD group were significantly reduced after HK or live Lr263 administration. Feeding HK or live Lr263 reversed the decreased number of probiotic bacteria and increased the number of pathogenic bacteria induced by high-fat treatment. The decreased intestinal barrier in the HFD group was markedly reversed by HK or live Lr263 treatments. The elevations of pro-inflammatory associated gene expressions in both adipose and hepatic tissues by high-fat administration were markedly decreased by HK or live Lr263 treatments. The increased macrophage infiltration noticed in adipose tissue after high-fat treatment was effectively suppressed by HK or live Lr263 consumption. The insulin resistance associated gene expressions in both adipose and hepatic tissues, which were downregulated in the HFD group, were markedly enhanced after HK or live Lr263 administration. HK or live Lr263 consumption significantly decreased hepatic lipogenic gene expressions stimulated by high-fat treatment. Administration of HK or live Lr263 significantly reduced hepatic oil red O staining and ameliorated the hepatic steatosis observed in high-fat treated rats. Our data suggested that similar to live Lr263, HK Lr263 exerted significant effects on attenuating obesity-induced metabolic abnormalities by reducing insulin resistance and hepatic steatosis formation. PMID:27163114

  20. Effect of high-fat diet on stress responsiveness in borderline hypertensive rats.

    PubMed

    Mitra, A; Crump, E M; Alvers, K M; Robertson, K L; Rowland, N E

    2011-01-01

    Stress in combination with genetic susceptibility is a factor in the development of hypertension. We used borderline hypertensive rats to investigate whether exposure to high-fat and/or junk-food diet at different stages of ontogeny has programing consequences on stress responses. Wistar dams were fed a high- or low-fat diet for 6 weeks prior to mating with spontaneously hypertensive males, and during gestation. At birth, litters were fostered either to a dam in the same or an alternative diet condition as during gestation. After weaning, male offspring were fed either a control-chow diet or an intermittent junk food fatty diet. Between postnatal days 57-61, half of the rats in each dietary group received daily social defeat sessions using a resident-intruder protocol, and the other half were unstressed controls. Blood pressure was measured indirectly both before and after each defeat session. On the final day, rats were killed for physiological measures. Socially defeated rats showed large increases in serum corticosterone concentration and adrenal hypertrophy, indicating the effectiveness of this non-adapting stressor. Serum corticosterone level was also higher in rats fed with the junk-food diet post-weaning compared with those fed with chow only, but there were no significant effects of gestational or lactational dietary history. PMID:20666663

  1. Effect of Corncob bedding on feed conversion efficiency in a high-fat diet-induced prediabetic model in C57Bl/6J mice.

    PubMed

    Ambery, Ashley G; Tackett, Lixuan; Penque, Brent A; Hickman, Debra L; Elmendorf, Jeffrey S

    2014-09-01

    Laboratory facilities use many varieties of contact bedding, including wood chips, paper products, and corncob, each with its own advantages and disadvantages. Corncob bedding, for example, is often used because of its high absorbency, ability to minimize detectable ammonia, and low cost. However, observations that mice eat the corncob lead to concerns that its use can interfere with dietary studies. We evaluated the effect of corncob bedding on feed conversion (change in body weight relative to the apparent number of kcal consumed over 7 d) in mice. Four groups of mice (6 to 12 per group) were housed in an individually ventilated caging system: (1) low-fat diet housed on recycled paper bedding, (2) low-fat diet housed on corncob bedding, (3) high-fat diet housed on recycled paper bedding, and (4) high-fat diet housed on corncob bedding. After 4 wk of the high-fat diet, feed conversion and percentage body weight change both were lower in corncob-bedded mice compared with paper-bedded mice. Low-fat-fed mice on corncob bedding versus paper bedding did not show statistically significant differences in feed conversion or change in percentage body weight. Average apparent daily feed consumption did not differ among the 4 groups. In conclusion, these data suggest that corncob bedding reduces the efficiency of feed conversion in mice fed a high-fat diet and that other bedding choices should be favored in these models. PMID:25255066

  2. The Korean Mistletoe (Viscum album coloratum) Extract Has an Antiobesity Effect and Protects against Hepatic Steatosis in Mice with High-Fat Diet-Induced Obesity

    PubMed Central

    Jung, Hoe-Yune; Kim, Yu-Hee; Kim, In-Bo; Jeong, Ju Seong; Lee, Jung-Han; Do, Myoung-Sool; Jung, Seung-Pil; Kim, Kwang-Soo; Kim, Kyong-Tai; Kim, Jong-Bae

    2013-01-01

    This study investigates the inhibitory effects of Korean mistletoe extract (KME) on adipogenic factors in 3T3-L1 cells and obesity and nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet. Male C57Bl/6 mice fed a high-fat diet were treated with KME (3 g/kg/day) for 15 weeks for the antiobesity and NAFLD experiments. Body weight and daily food intake were measured regularly during the experimental period. The epididymal pad was measured and liver histology was observed. The effects of KME on thermogenesis and endurance capacity were measured. The effects of KME on adipogenic factors were examined in 3T3-L1 cells. Body and epididymal fat pad weights were reduced in KME-treated mice, and histological examination showed an amelioration of fatty liver in KME-treated mice, without an effect on food consumption. KME potently induces mitochondrial activity by activating thermogenesis and improving endurance capacity. KME also inhibited adipogenic factors in vitro. These results demonstrate the inhibitory effects of KME on obesity and NAFLD in mice fed a high-fat diet. The effects appear to be mediated through an enhanced mitochondrial activity. Therefore, KME may be an effective therapeutic candidate for treating obesity and fatty liver caused by a high-fat diet. PMID:23935653

  3. Dietary supplementation of Chardonnay grape seed flour reduces plasma cholesterol concentration, hepatic steatosis, and abdominal fat content in high-fat diet-induced obese hamsters

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mechanisms for the hypocholesterolemic and anti-obesity effects of grape seed flours derived from white and red winemaking processing were investigated. Male Golden Syrian hamsters were fed high-fat (HF) diets supplemented with 10% partially defatted grape seed flours from Chardonnay (ChrSd), Ca...

  4. High fat diet-induced obesity reduces bone formation through activation of ppar gamma to suppress wnt/beta-catenin signaling in prepubertal rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effects of a high fat diet (HFD) and of obesity on skeletal development, maturation and remodeling remain largely unclear particularly in children. In this report, we utilized a total enteral nutrition (TEN) model to examine the direct effect of HFD feeding on bone prior to puberty. We chronical...

  5. Emodin protects against high-fat diet-induced obesity via regulation of AMP-activated protein kinase pathways in white adipose tissue.

    PubMed

    Tzeng, Thing-Fong; Lu, Hung-Jen; Liou, Shorong-Shii; Chang, Chia Ju; Liu, I-Min

    2012-06-01

    Emodin is an active herbal component traditionally used in China for treating a variety of diseases. The aim of this study was to examine the effect of emodin on the reducing lipid accumulation in white adipose tissue of high-fat diet-fed rats, and on the regulation of the expression of the genes involved in lipid metabolism to elucidate the mechanisms. After being fed a high-fat diet for two weeks, rats were dosed orally with emodin (20, 40, 80 mg/kg/day) or pioglitazone (20 mg/kg/day), once daily for eight weeks. Changes in body weight, feeding pattern, serum lipids, coronary artery risk index, and atherogenic index were investigated. Subcutaneous white adipose tissues were isolated for pathology histology and Western blot analyses. Changes of triglyceride accumulation in differentiated 3 T3-L1 adipocytes were also investigated. Emodin exhibited a significant concentration-dependent decrease in the intracellular accumulation of triglyceride in 3 T3-L1 adipocytes. Emodin (80 mg/kg/day) displayed similar characteristics to pioglitazone (20 mg/kg/day) in reducing body weight gain and plasma lipid levels as well as the coronary artery risk and atherogenic indices of high-fat diet-fed rats. Emodin also caused dose related reductions in epididymal white adipose tissue sizes in high-fat diet-fed rats. Emodin and pioglitazone enhanced the phosphorylation of AMP-activated protein kinase and its primary downstream targeting enzyme, acetyl-CoA carboxylase, upregulated gene expression of carnitine palmitoyl transferase 1, and downregulated sterol regulatory element binding protein 1 and fatty acid synthase protein levels in the epididymal white adipose tissue of high-fat diet-fed rats. Our findings suggest that emodin could attenuate lipid accumulation in white adipose tissue through AMP-activated protein kinase activation. PMID:22673833

  6. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE−/− mice

    PubMed Central

    Kumar, Saran; Chen, Mo; Li, Yan; Wong, Fiona H. S.; Thiam, Chung Wee; Hossain, Md Zakir; Poh, Kian Keong; Hirohata, Satoshi; Ogawa, Hiroko; Angeli, Véronique; Ge, Ruowen

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE−/−) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE−/− mice. ApoE−/−Adamts4−/− double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE−/− mice. PMID:27491335

  7. Ginger extract prevents high-fat diet-induced obesity in mice via activation of the peroxisome proliferator-activated receptor δ pathway.

    PubMed

    Misawa, Koichi; Hashizume, Kojiro; Yamamoto, Masaki; Minegishi, Yoshihiko; Hase, Tadashi; Shimotoyodome, Akira

    2015-10-01

    The initiation of obesity entails an imbalance wherein energy intake exceeds expenditure. Obesity is increasing in prevalence and is now a worldwide health problem. Food-derived peroxisome proliferator-activated receptor δ (PPARδ) stimulators represent potential treatment options for obesity. Ginger (Zingiber officinale Roscoe) was previously shown to regulate the PPARγ signaling pathway in adipocytes. In this study, we investigated the antiobesity effects of ginger in vivo and the mechanism of action in vitro. Energy expenditure was increased, and diet-induced obesity was attenuated in C57BL/6J mice treated with dietary ginger extract (GE). GE also increased the number of Type I muscle fibers, improved running endurance capacity and upregulated PPARδ-targeted gene expression in skeletal muscle and the liver. 6-Shogaol and 6-gingerol acted as specific PPARδ ligands and stimulated PPARδ-dependent gene expression in cultured human skeletal muscle myotubes. An analysis of cellular respiration revealed that pretreating cultured skeletal muscle myotubes with GE increased palmitate-induced oxygen consumption rate, which suggested an increase in cellular fatty acid catabolism. These results demonstrated that sustained activation of the PPARδ pathway with GE attenuated diet-induced obesity and improved exercise endurance capacity by increasing skeletal muscle fat catabolism. 6-Shogaol and 6-gingerol may be responsible for the regulatory effects of dietary ginger on PPARδ signaling. PMID:26101135

  8. Theaflavin Synthesized in a Selective, Domino-Type, One-Pot Enzymatic Biotransformation Method with Camellia sinensis Cell Culture Inhibits Weight Gain and Fat Accumulation to High-Fat Diet-Induced Obese Mice.

    PubMed

    Takemoto, Masumi; Takemoto, Hiroaki; Saijo, Ryoyasu

    2016-08-01

    The polyphenolic compound theaflavin, which is the main red pigment present in black tea, is reported to elicit various physiological effects. Because of the extremely low concentration of theaflavin present in black tea, its extraction from black tea leaves in quantities sufficient for use in medical studies has been difficult. We have developed a simple, inexpensive, selective, domino-type, one-pot enzymatic biotransformation method for the synthesis of theaflavin that is suitable for use in medical studies. Subsequent administration of this synthetic theaflavin to high-fat diet-induced obese mice inhibited both body weight gain and visceral fat accumulation, with no significant difference in the amount of faeces between the experimental and control mice. PMID:27237789

  9. Platycodon grandiflorum root attenuates vascular endothelial cell injury by oxidized low-density lipoprotein and prevents high-fat diet-induced dyslipidemia in mice by up-regulating antioxidant proteins.

    PubMed

    Chung, Mi Ja; Kim, Soo-Hyun; Park, Jeong-Won; Lee, Young Jin; Ham, Seung-Shi

    2012-05-01

    We hypothesized that a Platycodon grandiflorum root (PG) ethyl acetate extract (PGEA) would help reduce the vascular cell injury caused by oxidized low-density lipoprotein (oxLDL) and prevent high-fat (HF) diet-induced dyslipidemia and oxidative stress by up-regulating antioxidant proteins. We investigated the protective effects of PGEA against vascular endothelial cell injury induced by oxLDL and dyslipidemia induced by an HF diet, and the mechanisms underlying these effects were studied. The protective effects of PGEA were investigated with respect to calf pulmonary arterial endothelial (CPAE) cell viability and the lactate dehydrogenase release during oxLDL treatment. The in vivo effects of PGEA were examined using C57BL/6 mice, which were fed an HF diet for 9 weeks. The HF diet was supplemented with 0, 25, or 75 mg/kg PGEA during the last 4 weeks of the experimental period. Histologic analyses of hepatic lipid accumulation were performed. The changes in antioxidant protein levels induced by PGEA, which protects against HF diet-induced oxidative stress, were measured using a proteomics approach. We found that PGEA exhibited antioxidant activity. In CPAE cells, PGEA inhibited both oxLDL-induced cell death and lactate dehydrogenase release. In the HF diet-induced obese mice that received PGEA, we observed significantly reduced plasma and hepatic lipid levels, demonstrating that PGEA has beneficial effects on hyperlipidemia. In addition, we found that PGEA caused the up-regulation of antioxidant proteins. These findings suggest that the antioxidant effects of PGEA may protect against oxidative stress-related diseases. PMID:22652376

  10. Saturated fatty acid palmitate induces extracellular release of histone H3: A possible mechanistic basis for high-fat diet-induced inflammation and thrombosis

    SciTech Connect

    Shrestha, Chandan; Ito, Takashi; Kawahara, Ko-ichi; Shrestha, Binita; Yamakuchi, Munekazu; Hashiguchi, Teruto; Maruyama, Ikuro

    2013-08-09

    Highlights: •High-fat diet feeding and palmitate induces the release of nuclear protein histone H3. •ROS production and JNK signaling mediates the release of histone H3. •Extracellular histones induces proinflammatory and procoagulant response. -- Abstract: Chronic low-grade inflammation is a key contributor to high-fat diet (HFD)-related diseases, such as type 2 diabetes, non-alcoholic steatohepatitis, and atherosclerosis. The inflammation is characterized by infiltration of inflammatory cells, particularly macrophages, into obese adipose tissue. However, the molecular mechanisms by which a HFD induces low-grade inflammation are poorly understood. Here, we show that histone H3, a major protein component of chromatin, is released into the extracellular space when mice are fed a HFD or macrophages are stimulated with the saturated fatty acid palmitate. In a murine macrophage cell line, RAW 264.7, palmitate activated reactive oxygen species (ROS) production and JNK signaling. Inhibitors of these pathways dampened palmitate-induced histone H3 release, suggesting that the extracellular release of histone H3 was mediated, in part, through ROS and JNK signaling. Extracellular histone activated endothelial cells toexpress the adhesion molecules ICAM-1 and VCAM-1 and the procoagulant molecule tissue factor, which are known to contribute to inflammatory cell recruitment and thrombosis. These results suggest the possible contribution of extracellular histone to the pathogenesis of HFD-induced inflammation and thrombosis.

  11. Anti-Obesity Effect of 6,8-Diprenylgenistein, an Isoflavonoid of Cudrania tricuspidata Fruits in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Jo, Yang Hee; Choi, Kyeong-Mi; Liu, Qing; Kim, Seon Beom; Ji, Hyeong-Jin; Kim, Myounghwan; Shin, Sang-Kyung; Do, Seon-Gil; Shin, Eunju; Jung, Gayoung; Yoo, Hwan-Soo; Hwang, Bang Yeon; Lee, Mi Kyeong

    2015-01-01

    Obesity, which is characterized by excessive fat accumulation, is associated with several pathological disorders, including metabolic diseases. In this study, the anti-obesity effect of 6,8-diprenylgenistein (DPG), a major isoflavonoid of Cudrania tricuspidata fruits was investigated using high fat-diet (HFD)-induced obese mice at the doses of 10 and 30 mg/kg for six week. The body weight of the DPG-treated groups was significantly lower compared to the HFD-treated group. In addition, fat accumulation in epididymal adipose tissue and liver was dramatically decreased in the HFD + DPG groups. The food efficiency ratios of the HFD + DPG groups were also lower compared to the HFD group with the same food intake. Metabolic parameters that had increased in the HFD group were decreased in the HFD + DPG groups. Further studies demonstrate that DPG efficiently reduces lipogenic genes by regulation of transcription factors, such as peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and hormones, such as leptin and adiponection. DPG also regulates acetyl-CoA carboxylase (ACC) and hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) by AMP-activated protein kinase (AMPK) activation. Taken together, DPG is beneficial for the regulation of obesity, especially resulting from high fat intake. PMID:26694457

  12. Long-term high-fat diet induces pancreatic injuries via pancreatic microcirculatory disturbances and oxidative stress in rats with hyperlipidemia

    SciTech Connect

    Yan Mingxian; Li Yanqing . E-mail: mx8902@163.com; Meng Min; Ren Hongbo; Kou Yi

    2006-08-18

    Relations between hyperlipidemia and chronic pancreatitis remain unclear. Microcirculatory disturbances and oxidative stress are involved in pathogeneses of a high numbers of diseases. The objective of this study was to induce hyperlipidemia in rats by long-term high-fat diet intake, then investigate the biochemical, microcirculatory, and histological alterations in blood and pancreatic tissues of these animals, and discuss their potential significances. Pancreatic blood flow was detected by intravital microscope; malondialdehyde (MDA) content and superoxide dismutase (SOD) activity were measured in pancreatic tissues for assessment of oxidative stress and {alpha}-smooth muscle actin ({alpha}-SMA) expression was determined by immunohistochemical staining and RT-PCR. The results showed that the velocity of pancreatic microvascular blood flow of rats with hyperlipidemia decreased significantly as compared to control value (p = 0.008). Pancreatic MDA content increased whereas SOD activity decreased in these rats (p = 0.022; p = 0.039, respectively). Histologically, microvesicles in acinar and islet cells, dilated rough endoplasmic reticulum, swollen mitochondrion and modified vascular endothelial cells were observed under light microscope and transmission electron microscope. In addition, {alpha}-SMA expression was up-regulated significantly (p < 0.05). These results suggest that long-term high-fat diet can induce chronic pancreatic injuries which could be considered as 'nonalcoholic fatty pancreatic disease', and pancreatic microcirculatory disturbances and oxidative stress may play an important part in the underlying pathogenesis.

  13. Cucumis melo ssp. Agrestis var. Agrestis Ameliorates High Fat Diet Induced Dyslipidemia in Syrian Golden Hamsters and Inhibits Adipogenesis in 3T3-L1 Adipocytes

    PubMed Central

    Shankar, Kripa; Singh, Sumit K.; Kumar, Durgesh; Varshney, Salil; Gupta, Abhishek; Rajan, Sujith; Srivastava, Ankita; Beg, Muheeb; Srivastava, Anurag Kumar; Kanojiya, Sanjeev; Mishra, Dipak K.; Gaikwad, Anil N.

    2015-01-01

    Background: Cucumis melo ssp. agrestis var. agrestis (CMA) is a wild variety of C. melo. This study aimed to explore anti-dyslipidemic and anti-adipogenic potential of CMA. Materials and Methods: For initial anti-dyslipidemic and antihyperglycemic potential of CMA fruit extract (CMFE), male Syrian golden hamsters were fed a chow or high-fat diet with or without CMFE (100 mg/kg). Further, we did fractionation of this CMFE into two fractions namely; CMA water fraction (CMWF) and CMA hexane fraction (CMHF). Phytochemical screening was done with liquid chromatography-mass spectrometry LC- (MS)/MS and direct analysis in real time-MS to detect active compounds in the fractions. Further, high-fat diet fed dyslipidemic hamsters were treated with CMWF and CMHF at 50 mg/kg for 7 days. Results: Oral administration of CMFE and both fractions (CMWF and CMHF) reduced the total cholesterol, triglycerides, low‐density lipoprotein cholesterol, and very low‐density lipoprotein-cholesterol levels in high fat diet-fed dyslipidemic hamsters. CMHF also modulated expression of genes involved in lipogenesis, lipid metabolism, and reverse cholesterol transport. Standard biochemical diagnostic tests suggested that neither of fractions causes any toxicity to hamster liver or kidneys. CMFE and CMHF also decreased oil-red-O accumulation in 3T3-L1 adipocytes. Conclusion: Based on these results, it is concluded that CMA possesses anti-dyslipidemic and anti-hyperglycemic activity along with the anti-adipogenic activity. SUMMARY The oral administration of Cucumis melo agrestis fruit extract (CMFE) and its fractions (CMWF and CMHF) improved serum lipid profile in HFD fed dyslipidemic hamsters.CMFE, CMWF and CMHF significantly attenuated body weight gain and eWAT hypertrophy.The CMHF decreased lipogenesis in both liver and adipose tissue.CMFE and CMHF also inhibited adipogenesis in 3T3-L1 adipocytes. Abbreviation used: CMA: Cucumis melo ssp. agrestis var. agrestis, CMFE: CMA fruit extract, CMWF

  14. Triglyceride-Lowering Effects of Two Probiotics, Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601, in a Rat Model of High-Fat Diet-Induced Hypertriglyceridemia.

    PubMed

    Choi, Il-Dong; Kim, Sung-Hwan; Jeong, Ji-Woong; Lee, Dong Eun; Huh, Chul-Sung; Hong, Seong Soo; Sim, Jae-Hun; Ahn, Young-Tae

    2016-03-28

    The triglyceride-lowering effect of probiotics Lactobacillus plantarum KY1032 and Lactobacillus curvatus HY7601 were investigated. Male SD Wistar rats were randomly divided into three groups and fed high-fat diet (HFD), HFD and probiotics (5 X 10(9) CFU/day of L. plantarum KY1032 and 5 X 10(9) CFU/day of L. curvatus HY7601), or normal diet for 6 weeks. Probiotic treatment significantly lowered the elevated plasma triglyceride and increased plasma free fatty acid, glycerol, and plasma apolipoprotein A-V (ApoA-V) levels. The probiotic-treated group showed elevated hepatic mRNA expression of PPARα, bile acid receptor (FXR), and ApoA-V. These results demonstrate that L. plantarum KY1032 and L. curvatus HY7601 lower triglycerides in hypertriglyceridemic rats by upregulating ApoA-V, PPARα, and FXR. PMID:26699746

  15. Soy Protein Isolate Inhibits High-Fat Diet-Induced Senescence Pathways in Osteoblasts to Maintain Bone Acquisition in Male Rats

    PubMed Central

    Lazarenko, Oxana P.; Blackburn, Michael L.; Badger, Thomas M.; Ronis, Martin J. J.

    2015-01-01

    Chronic consumption by experimental animals of a typical Western diet high in saturated fats and cholesterol during postnatal life has been demonstrated to impair skeletal development. However, the underlying mechanism by which high-fat, energy-dense diets affect bone-forming cell phenotypes is poorly understood. Here, we show that male weanling rats fed a diet containing 45% fat and 0.5% cholesterol made with casein (HF-Cas) for 6 weeks displayed lower bone mineral density and strength compared with those of AIN-93G–fed dietary controls. Substitution of casein with soy protein isolate (SPI) in the high-fat diet (HF-SPI) prevented these effects. The bone-sparing effects of SPI were associated with prevention of HF-Cas–induced osteoblast senescence pathways through suppression of the p53/p21 signaling pathways. HF-Cas–fed rats had increased caveolin-1 and down-regulated Sirt1, leading to activations of peroxisome proliferator–activated receptor γ (PPARγ) and p53/p21, whereas rats fed HF-SPI suppressed caveolin-1 and activated Sirt1 to deacetylate PPARγ and p53 in bone. Treatment of osteoblastic cells with nonesterified free fatty acid (NEFA) increased cell senescence signaling pathways. Isoflavones significantly blocked activations of senescence-associated β-galactosidase and PPARγ/p53/p21 by NEFA. Finally, replicative senescent osteoblastic cells and bone marrow mesenchymal ST2 cells exhibited behavior similar to that of cells treated with NEFA and in vivo bone cells in rats fed the HF-Cas diet. These results suggest that (1) high concentrations of NEFA occurring with HF intake are mediators of osteoblast cell senescence leading to impairment of bone development and acquisition and (2) the molecular mechanisms underlying the SPI-protective effects involve isoflavone-induced inhibition of osteoblastic cell senescence to prevent HF-induced bone impairments. PMID:25490147

  16. Coffee intake mitigated inflammation and obesity-induced insulin resistance in skeletal muscle of high-fat diet-induced obese mice.

    PubMed

    Jia, Huijuan; Aw, Wanping; Egashira, Kenji; Takahashi, Shoko; Aoyama, Shinya; Saito, Kenji; Kishimoto, Yoshimi; Kato, Hisanori

    2014-05-01

    Epidemiologic findings offer the promise that coffee or its many constituents may be useful as a dietary intervention in type 2 diabetes (T2D) prevention. We aimed to elucidate the molecular mechanisms involved in the ameliorative effects of caffeinated coffee (CC), decaffeinated coffee (DC) and unroasted caffeinated green coffee (GC) on skeletal muscle gene expression profiles and their relationships in an obesity animal model. Eight-week-old male C57BL6 mice were raised for 9 weeks ad libitum on a normal diet, a high-fat diet, or high-fat diet containing 2 % freeze-dried CC, or DC, or GC. Total RNA and protein were extracted from skeletal muscle and subjected to microarray (Mouse Genome 430 2.0, Affymetrix) and western blotting analyses, respectively. Coffee intake mitigated the insulin resistance by decreasing plasma glucose levels during an insulin tolerance test and by increasing tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1), p85/IRS-1 complex and pAkt/PKB (protein kinase B). In addition, coffee intake down-regulated the anti-inflammatory genes activating transcription factor 3, FBJ osteosarcoma oncogene, heat shock protein 1A, heat shock protein 1B and synuclein, gamma and the inflammation-associated insulin signaling genes stearoyl-coenzyme A desaturase 1 and secreted phosphoprotein 1. These results provide scientific insight on the probable positive effects of coffee intake on impaired insulin signaling, inflammation and obesity, thereby providing a new perspective on the prevention of obesity and T2D. PMID:24599575

  17. The effect of exercise on expression of myokine and angiogenesis mRNA in skeletal muscle of high fat diet induced obese rat

    PubMed Central

    Shin, Ki Ok; Bae, Ju Yong; Woo, Jinhee; Jang, Ki Soeng; Kim, Keun Su; Park, Jung Sub; Kim, In Ki; Kang, Sunghwun

    2015-01-01

    [Purpose] The purpose of this study was to investigate the effect of regular treadmill exercise on the mRNA expressions of myokines and angiogenesis factors in the skeletal muscle of obese rats. [Methods] Thirty two male Sprague-Dawley rats (4weeks old) were divided into the CO (control) and HF (high fat diet) groups. Obesity was induced in the HF group by consumption of 45% high-fat diet for 15 weeks. These groups were further subdivided into training groups (COT and HFT); the training groups conducted moderate intensity treadmill training for 8 weeks. Soleus muscles were excised and analyzed by real-time quantitative PCR. [Results] mRNA expression of myokines, such as PGC-1α, IL-6, and IL-15, in the COT and HFT groups (which conducted regular exercise), were higher as compared with the CO and HF groups (p < 0.05). Also, the levels in the HF group were significantly lower when compared with CO group (p < 0.05). Expression of angiogenesis mRNA, namely mTOR, VEGF, and FLT1, were significantly lower in the HF group, as compared to the CO group (p < 0.05). In addition, COT group had a higher expression of mTORC1, mTORC2, VEGF and FLT mRNA, than the CO group (p < 0.05); the HFT group also had higher expressions of mTOR, VEGF and FLT1 mRNA than the HF group (p < 0.05). [Conclusion] These results indicate that mRNA expression of myokines was increased through the activity of muscle contraction, and it also promoted the mRNA expression of angiogenesis due to activation of mTOR. Thus, we conclude that not only under normal health conditions, but in obesity and excess nutritional circumstances also, regular exercise seems to act positively on the glycemic control and insulin sensitivity through the angiogenesis signaling pathway. PMID:26244127

  18. Metabolic phenotype and adipose and liver features in a high-fat Western diet-induced mouse model of obesity-linked NAFLD.

    PubMed

    Luo, Yuwen; Burrington, Christine M; Graff, Emily C; Zhang, Jian; Judd, Robert L; Suksaranjit, Promporn; Kaewpoowat, Quanhathai; Davenport, Samantha K; O'Neill, Ann Marie; Greene, Michael W

    2016-03-15

    nonalcoholic fatty liver disease (NAFLD), an obesity and insulin resistance associated clinical condition - ranges from simple steatosis to nonalcoholic steatohepatitis. To model the human condition, a high-fat Western diet that includes liquid sugar consumption has been used in mice. Even though liver pathophysiology has been well characterized in the model, little is known about the metabolic phenotype (e.g., energy expenditure, activity, or food intake). Furthermore, whether the consumption of liquid sugar exacerbates the development of glucose intolerance, insulin resistance, and adipose tissue dysfunction in the model is currently in question. In our study, a high-fat Western diet (HFWD) with liquid sugar [fructose and sucrose (F/S)] induced acute hyperphagia above that observed in HFWD-fed mice, yet without changes in energy expenditure. Liquid sugar (F/S) exacerbated HFWD-induced glucose intolerance and insulin resistance and impaired the storage capacity of epididymal white adipose tissue (eWAT). Hepatic TG, plasma alanine aminotransferase, and normalized liver weight were significantly increased only in HFWD+F/S-fed mice. HFWD+F/S also resulted in increased hepatic fibrosis and elevated collagen 1a2, collagen 3a1, and TGFβ gene expression. Furthermore, HWFD+F/S-fed mice developed more profound eWAT inflammation characterized by adipocyte hypertrophy, macrophage infiltration, a dramatic increase in crown-like structures, and upregulated proinflammatory gene expression. An early hypoxia response in the eWAT led to reduced vascularization and increased fibrosis gene expression in the HFWD+F/S-fed mice. Our results demonstrate that sugary water consumption induces acute hyperphagia, limits adipose tissue expansion, and exacerbates glucose intolerance and insulin resistance, which are associated with NAFLD progression. PMID:26670487

  19. Ameliorative Effect of Hexane Extract of Phalaris canariensis on High Fat Diet-Induced Obese and Streptozotocin-Induced Diabetic Mice

    PubMed Central

    Perez Gutierrez, Rosa Martha; Madrigales Ahuatzi, Diana; Horcacitas, Maria del Carmen; Garcia Baez, Efren; Cruz Victoria, Teresa; Mota-Flores, Jose Maria

    2014-01-01

    Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect of Phalaris canariensis seeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis. PMID:24523819

  20. Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

    PubMed Central

    Kim, Jongwan; Yun, Eun-Young; Park, Seong-Won; Goo, Tae-Won; Seo, Minchul

    2016-01-01

    Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress. PMID:26901224

  1. Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways.

    PubMed

    Kim, Jongwan; Yun, Eun-Young; Park, Seong-Won; Goo, Tae-Won; Seo, Minchul

    2016-02-01

    Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress. PMID:26901224

  2. Effect of Hypericum perforatum L. extract on insulin resistance and lipid metabolic disorder in high-fat-diet induced obese mice.

    PubMed

    Tian, Jin-ying; Tao, Rong-ya; Zhang, Xiao-lin; Liu, Qian; He, Yi-Bo; Su, Ya-lun; Ji, Teng-fei; Ye, Fei

    2015-01-01

    Natural product Hypericum perforatum L. has been used in folk medicine to improve mental performance. However, the effect of H. perforatum L. on metabolism is still unknown. In order to test whether H. perforatum L. extract (EHP) has an effect on metabolic syndrome, we treated diet induced obese (DIO) C57BL/6J mice with the extract. The chemical characters of EHP were investigated with thin-layer chromatography, ultraviolet, high-performance liquid chromatography (HPLC), and HPLC-mass spectrometry fingerprint analysis. Oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and the glucose infusion rate (GIR) in hyperinsulinemic-euglycemic clamp test were performed to evaluate the glucose metabolism and insulin sensitivity. Skeletal muscle was examined for lipid metabolism. The results suggest that EHP can significantly improve the glucose and lipid metabolism in DIO mice. In vitro, EHP inhibited the catalytic activity of recombinant human protein tyrosine phosphatase 1B (PTP1B) and reduced the protein and mRNA levels of PTP1B in the skeletal muscle. Moreover, expressions of genes related to fatty acid uptake and oxidation were changed by EHP in the skeletal muscle. These results suggest that EHP may improve insulin resistance and lipid metabolism in DIO mice. PMID:25266458

  3. Effect of high-fat diet during gestation, lactation, or postweaning on physiological and behavioral indexes in borderline hypertensive rats

    PubMed Central

    Mitra, Anaya; Alvers, Kristin M.; Crump, Erica M.; Rowland, Neil E.

    2009-01-01

    Maternal obesity is becoming more prevalent. We used borderline hypertensive rats (BHR) to investigate whether a high-fat diet at different stages of development has adverse programming consequences on metabolic parameters and blood pressure. Wistar dams were fed a high- or low-fat diet for 6 wk before mating with spontaneously hypertensive males and during the ensuing pregnancy. At birth, litters were fostered to a dam from the same diet group as during gestation or to the alternate diet condition. Female offspring were weaned on either control or “junk food” diets until about 6 mo of age. Rats fed the high-fat junk food diet were hyperphagic relative to their chow-fed controls. The junk food-fed rats were significantly heavier and had greater fat pad mass than those rats maintained on chow alone. Importantly, those rats suckled by high-fat dams had heavier fat pads than those suckled by control diet dams. Fasting serum leptin and insulin levels differed as a function of the gestational, lactational, and postweaning diet histories. Rats gestated in, or suckled by high-fat dams, or maintained on the junk food diet were hyperleptinemic compared with their respective controls. Indirect blood pressure did not differ as a function of postweaning diet, but rats gestated in the high-fat dams had lower mean arterial blood pressures than those gestated in the control diet dams. The postweaning dietary history affected food-motivated behavior; junk food-fed rats earned less food pellets on fixed (FR) and progressive (PR) ratio cost schedules than chow-fed controls. In conclusion, the effects of maternal high-fat diet during gestation or lactation were mostly small and transient. The postweaning effects of junk food diet were evident on the majority of the parameters measured, including body weight, fat pad mass, serum leptin and insulin levels, and operant performance. PMID:18971351

  4. Voluntary exercise prevents colonic inflammation in high-fat diet-induced obese mice by up-regulating PPAR-γ activity

    SciTech Connect

    Liu, Wei-Xin; Wang, Ting; Zhou, Feng; Wang, Ying; Xing, Jun-Wei; Zhang, Shen; Gu, Shou-Zhi; Sang, Li-Xuan; Dai, Cong; Wang, Hai-Lan

    2015-04-10

    Obesity is associated with increased colonic inflammation, which elevates the risk of colon cancer. Although exercise exerts anti-inflammatory actions in multiple chronic diseases associated with inflammation, it is unknown whether this strategy prevents colonic inflammation in obesity. We hypothesized that voluntary exercise would suppress colonic inflammation in high-fat diet (HFD)-induced obesity by modulation of peroxisome proliferator-activated receptor (PPAR)-γ. Male C57Bl/6J mice fed either a control diet (6.5% fat, CON) or a high-fat diet (24% fat, HFD) were divided into sedentary, voluntary exercise or voluntary exercise with PPAR-γ antagonist GW9662 (10 mg/kg/day). All interventions took place for 12 weeks. Compared with CON-sedentary group, HFD-sedentary mice gained significantly more body weight and exhibited metabolic disorders. Molecular studies revealed that HFD-sedentary mice had increased expression of inflammatory mediators and activation of nuclear factor (NF)-κB in the colons, which were associated with decreased expression and activity of PPAR-γ. Voluntary exercise markedly attenuated body weight gain, improved metabolic disorders, and normalized the expression of inflammatory mediators and activation of NF-κB in the colons in HFD-mice while having no effects in CON-animals. Moreover, voluntary exercise significantly increased expression and activity of PPAR-γ in the colons in both HFD- and CON-animals. However, all of these beneficial effects induced by voluntary exercise were abolished by GW9662, which inhibited expression and activity of PPAR-γ. The results suggest that decreased PPAR-γ activity in the colon of HFD-induced obesity may facilitate the inflammatory response and colon carcinogenesis. Voluntary exercise prevents colonic inflammation in HFD-induced obesity by up-regulating PPAR-γ activity. - Highlights: • Obesity down-regulates PPAR-γ in the colon. • Down-regulated colonic PPAR-γ may facilitate inflammatory

  5. The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

    PubMed Central

    Williams, Lynda M.; Campbell, Fiona M.; Drew, Janice E.; Koch, Christiane; Hoggard, Nigel; Rees, William D.; Kamolrat, Torkamol; Thi Ngo, Ha; Steffensen, Inger-Lise; Gray, Stuart R.; Tups, Alexander

    2014-01-01

    High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable. PMID:25170916

  6. Cellular cholesterol accumulation modulates high fat high sucrose (HFHS) diet-induced ER stress and hepatic inflammasome activation in the development of non-alcoholic steatohepatitis.

    PubMed

    Bashiri, Amir; Nesan, Dinushan; Tavallaee, Ghazaleh; Sue-Chue-Lam, Ian; Chien, Kevin; Maguire, Graham F; Naples, Mark; Zhang, Jing; Magomedova, Lilia; Adeli, Khosrow; Cummins, Carolyn L; Ng, Dominic S

    2016-07-01

    Non-alcoholic steatohepatitis (NASH), is the form of non-alcoholic fatty liver disease posing risk to progress into serious long term complications. Human and pre-clinical models implicate cellular cholesterol dysregulation playing important role in its development. Mouse model studies suggest synergism between dietary cholesterol and fat in contributing to NASH but the mechanisms remain poorly understood. Our laboratory previously reported the primary importance of hepatic endoplasmic reticulum cholesterol (ER-Chol) in regulating hepatic ER stress by comparing the responses of wild type, Ldlr-/-xLcat+/+ and Ldlr-/-xLcat-/- mice, to a 2% high cholesterol diet (HCD). Here we further investigated the roles of ER-Chol and ER stress in HFHS diet-induced NASH using the same strains. With HFHS diet feeding, both WT and Ldlr-/-xLcat+/+ accumulate ER-Chol in association with ER stress and inflammasome activation but the Ldlr-/-xLcat-/- mice are protected. By contrast, all three strains accumulate cholesterol crystal, in correlation with ER-Chol, albeit less so in Ldlr-/-xLcat-/- mice. By comparison, HCD feeding per se (i) is sufficient to promote steatosis and activate inflammasomes, and (ii) results in dramatic accumulation of cholesterol crystal which is linked to inflammasome activation in Ldlr-/-xLcat-/- mice, independent of ER-Chol. Our data suggest that both dietary fat and cholesterol each independently promote steatosis, cholesterol crystal accumulation and inflammasome activation through distinct but complementary pathways. In vitro studies using palmitate-induced hepatic steatosis in HepG2 cells confirm the key roles by cellular cholesterol in the induction of steatosis and inflammasome activations. These novel findings provide opportunities for exploring a cellular cholesterol-focused strategy for treatment of NASH. PMID:27090939

  7. Anti-Diabetic Effect of Balanced Deep-Sea Water and Its Mode of Action in High-Fat Diet Induced Diabetic Mice

    PubMed Central

    Ha, Byung Geun; Shin, Eun Ji; Park, Jung-Eun; Shon, Yun Hee

    2013-01-01

    In this study, we investigated the effects of balanced deep-sea water (BDSW) on hyperglycemia and glucose intolerance in high-fat diet (HFD)-induced diabetic C57BL/6J mice. BDSW was prepared by mixing deep-sea water (DSW) mineral extracts and desalinated water to give a final hardness of 500–2000. Mice given an HFD with BDSW showed lowered fasting plasma glucose levels compared to HFD-fed mice. Oral and intraperitoneal glucose tolerance tests showed that BDSW improves impaired glucose tolerance in HFD-fed mice. Histopathological evaluation of the pancreas showed that BDSW recovers the size of the pancreatic islets of Langerhans, and increases the secretion of insulin and glucagon in HFD-fed mice. Quantitative reverse transcription polymerase chain reaction results revealed that the expression of hepatic genes involved in glucogenesis, glycogenolysis and glucose oxidation were suppressed, while those in glucose uptake, β-oxidation, and glucose oxidation in muscle were increased in mice fed HFD with BDSW. BDSW increased AMP-dependent kinase (AMPK) phosphorylation in 3T3-L1 pre- and mature adipocytes and improved impaired AMPK phosphorylation in the muscles and livers of HFD-induced diabetic mice. BDSW stimulated phosphoinositol-3-kinase and AMPK pathway-mediated glucose uptake in 3T3-L1 adipocytes. Taken together, these results suggest that BDSW has potential as an anti-diabetic agent, given its ability to suppress hyperglycemia and improve glucose intolerance by increasing glucose uptake. PMID:24172214

  8. Hypermethylation of Cox5a Promoter Is Associated with Mitochondrial Dysfunction in Skeletal Muscle of High Fat Diet-Induced Insulin Resistant Rats

    PubMed Central

    Li, Jin; Su, Lei; Yu, Shuang; Zhu, Xiao-nan; Cao, Xiao-pei; Xiao, Hai-peng

    2014-01-01

    High-fat diet (HFD) is an environmental factor that contributes to the pathogenesis of obesity and type 2 diabetes. A number of genes influencing oxidative phosphorylation (OXPHOS) were found to be downregulated in skeletal muscle of humans and rats treated with HFD and have been implicated in mitochondrial dysfunction, insulin resistance, and consequent type 2 diabetes. In this study, we hypothesized that DNA methylation plays a crucial role in the regulation of OXPHOS genes in skeletal muscle of rats exposed to HFD. Using whole genome promoter methylation analysis of skeletal muscle followed by qPCR and bisulfite sequencing analysis, we identified hypermethylation of Cox5a in HFD rats. Furthermore, we found that Cox5a hypermethylation was associated with downregulation of Cox5a expression at the mRNA and protein level, and a reduction in mitochondrial complex IV activity and ATP content in HFD-induced insulin resistant rats compared to controls. Moreover, we found that while exposure to palmitate resulted in hypermethylation of the Cox5a promoter in rat myotubes, demethylation with 5-aza-2′-deoxycytidine was associated with preserved Cox5a expression, as well as restoration of complex IV activity and cellular ATP content. These novel observations indicate that Cox5a hypermethylation is associated with mitochondrial dysfunction in skeletal muscle of HFD-induced insulin resistant rats. PMID:25436770

  9. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a 1H NMR Metabolomics Approach

    PubMed Central

    Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

    2016-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a 1H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

  10. Perilla Oil Has Similar Protective Effects of Fish Oil on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Gut Dysbiosis

    PubMed Central

    Tian, Yu; Wang, Hualin; Yuan, Fahu; Li, Na; Huang, Qiang; He, Lei; Wang, Limei

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries. Recent studies indicated that the modification of gut microbiota plays an important role in the progression from simple steatosis to steatohepatitis. Epidemiological studies have demonstrated consumption of fish oil or perilla oil rich in n-3 polyunsaturated fatty acids (PUFAs) protects against NAFLD. However, the underlying mechanisms remain unclear. In the present study, we adopted 16s rRNA amplicon sequencing technique to investigate the impacts of fish oil and perilla oil on gut microbiomes modification in rats with high-fat diet- (HFD-) induced NAFLD. Both fish oil and perilla oil ameliorated HFD-induced hepatic steatosis and inflammation. In comparison with the low-fat control diet, HFD feeding significantly reduced the relative abundance of Gram-positive bacteria in the gut, which was slightly reversed by either fish oil or perilla oil. Additionally, fish oil and perilla oil consumption abrogated the elevated abundance of Prevotella and Escherichia in the gut from HFD fed animals. Interestingly, the relative abundance of antiobese Akkermansia was remarkably increased only in animals fed fish oil compared with HFD group. In conclusion, compared with fish oil, perilla oil has similar but slightly weaker potency against HFD-induced NAFLD and gut dysbiosis. PMID:27051672

  11. An Investigation into the Antiobesity Effects of Morinda citrifolia L. Leaf Extract in High Fat Diet Induced Obese Rats Using a (1)H NMR Metabolomics Approach.

    PubMed

    Gooda Sahib Jambocus, Najla; Saari, Nazamid; Ismail, Amin; Khatib, Alfi; Mahomoodally, Mohamad Fawzi; Abdul Hamid, Azizah

    2016-01-01

    The prevalence of obesity is increasing worldwide, with high fat diet (HFD) as one of the main contributing factors. Obesity increases the predisposition to other diseases such as diabetes through various metabolic pathways. Limited availability of antiobesity drugs and the popularity of complementary medicine have encouraged research in finding phytochemical strategies to this multifaceted disease. HFD induced obese Sprague-Dawley rats were treated with an extract of Morinda citrifolia L. leaves (MLE 60). After 9 weeks of treatment, positive effects were observed on adiposity, fecal fat content, plasma lipids, and insulin and leptin levels. The inducement of obesity and treatment with MLE 60 on metabolic alterations were then further elucidated using a (1)H NMR based metabolomics approach. Discriminating metabolites involved were products of various metabolic pathways, including glucose metabolism and TCA cycle (lactate, 2-oxoglutarate, citrate, succinate, pyruvate, and acetate), amino acid metabolism (alanine, 2-hydroxybutyrate), choline metabolism (betaine), creatinine metabolism (creatinine), and gut microbiome metabolism (hippurate, phenylacetylglycine, dimethylamine, and trigonelline). Treatment with MLE 60 resulted in significant improvement in the metabolic perturbations caused obesity as demonstrated by the proximity of the treated group to the normal group in the OPLS-DA score plot and the change in trajectory movement of the diseased group towards the healthy group upon treatment. PMID:26798649

  12. A High-Fat, High-Fructose Diet Induces Antioxidant Imbalance and Increases the Risk and Progression of Nonalcoholic Fatty Liver Disease in Mice

    PubMed Central

    Jearapong, Nattharat; Pimson, Charinya; Chatuphonprasert, Waranya

    2016-01-01

    Excessive fat liver is an important manifestation of nonalcoholic fatty liver disease (NAFLD), associated with obesity, insulin resistance, and oxidative stress. In the present study, the effects of a high-fat, high-fructose diet (HFFD) on mRNA levels and activities of the antioxidant enzymes, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), were determined in mouse livers and brains. The histomorphology of the livers was examined and the state of nonenzymatic reducing system was evaluated by measuring the glutathione system and the lipid peroxidation. Histopathology of the liver showed that fat accumulation and inflammation depended on the period of the HFFD-consumption. The levels of mRNA and enzymatic activities of SOD, CAT, and GPx were raised, followed by the increases in malondialdehyde levels in livers and brains of the HFFD mice. The oxidized GSSG content was increased while the total GSH and the reduced GSH were decreased, resulting in the increase in the GSH/GSSG ratio in both livers and brains of the HFFD mice. These observations suggested that liver damage and oxidative stress in the significant organs were generated by continuous HFFD-consumption. Imbalance of antioxidant condition induced by long-term HFFD-consumption might increase the risk and progression of NAFLD. PMID:27019761

  13. Inhibition of Src homology 2 domain-containing phosphatase 1 increases insulin sensitivity in high-fat diet-induced insulin-resistant mice.

    PubMed

    Krüger, Janine; Wellnhofer, Ernst; Meyborg, Heike; Stawowy, Philipp; Östman, Arne; Kintscher, Ulrich; Kappert, Kai

    2016-03-01

    Insulin resistance plays a crucial role in the development of type 2 diabetes. Insulin receptor signalling is antagonized and tightly controlled by protein tyrosine phosphatases (PTPs). However, the precise role of the PTP src homology 2 domain-containing phosphatase 1 (SHP-1) in insulin resistance has not been explored. Male C57BL/6J mice were fed a high-fat diet (HFD, 60% kcal from fat), to induce insulin resistance, or a low-fat diet (LFD, 10% kcal from fat) for 10 weeks. Afterwards, HFD-fed mice were pharmacologically treated with the SHP-1 (Ptpn6) inhibitor sodium stibogluconate and the broad spectrum pan-PTP inhibitor bis(maltolato)oxovanadium(IV) (BMOV). Both inhibitors ameliorated the metabolic phenotype, as evidenced by reduced body weight, improved insulin sensitivity and glucose tolerance, which was not due to altered PTP gene expression. In parallel, phosphorylation of the insulin receptor and of the insulin signalling key intermediate Akt was enhanced, and both PTP inhibitors and siRNA-mediated SHP-1 downregulation resulted in an increased glucose uptake in vitro. Finally, recombinant SHP-1 was capable of dephosphorylating the ligand-induced tyrosine-phosphorylated insulin receptor. These results indicate a central role of SHP-1 in insulin signalling during obesity, and SHP-1 inhibition as a potential therapeutic approach in metabolic diseases. PMID:27047746

  14. Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice

    PubMed Central

    Yu, Sung-Hsun; Chen, Szu-Yu Tina; Li, Wei-Shan; Dubey, Navneet Kumar; Chen, Wei-Hong; Chuu, Jiunn-Jye; Leu, Sy-Jye; Deng, Win-Ping

    2015-01-01

    Diabetes mellitus (DM) is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1) was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD-) induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS-1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-γ expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment. PMID:26258146

  15. Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

    PubMed

    Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

    2016-01-15

    Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease. PMID:26564715

  16. Perilla Oil Has Similar Protective Effects of Fish Oil on High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease and Gut Dysbiosis.

    PubMed

    Tian, Yu; Wang, Hualin; Yuan, Fahu; Li, Na; Huang, Qiang; He, Lei; Wang, Limei; Liu, Zhiguo

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease in developed countries. Recent studies indicated that the modification of gut microbiota plays an important role in the progression from simple steatosis to steatohepatitis. Epidemiological studies have demonstrated consumption of fish oil or perilla oil rich in n-3 polyunsaturated fatty acids (PUFAs) protects against NAFLD. However, the underlying mechanisms remain unclear. In the present study, we adopted 16s rRNA amplicon sequencing technique to investigate the impacts of fish oil and perilla oil on gut microbiomes modification in rats with high-fat diet- (HFD-) induced NAFLD. Both fish oil and perilla oil ameliorated HFD-induced hepatic steatosis and inflammation. In comparison with the low-fat control diet, HFD feeding significantly reduced the relative abundance of Gram-positive bacteria in the gut, which was slightly reversed by either fish oil or perilla oil. Additionally, fish oil and perilla oil consumption abrogated the elevated abundance of Prevotella and Escherichia in the gut from HFD fed animals. Interestingly, the relative abundance of antiobese Akkermansia was remarkably increased only in animals fed fish oil compared with HFD group. In conclusion, compared with fish oil, perilla oil has similar but slightly weaker potency against HFD-induced NAFLD and gut dysbiosis. PMID:27051672

  17. Resveratrol Ameliorates High Glucose and High-Fat/Sucrose Diet-Induced Vascular Hyperpermeability Involving Cav-1/eNOS Regulation

    PubMed Central

    Peng, Xiao lin; Qu, Wei; Wang, Lin zhi; Huang, Bin qing; Ying, Chen jiang; Sun, Xiu fa; Hao, Li ping

    2014-01-01

    Vascular endothelial hyperpermeability is one of the manifestations of endothelial dysfunction. Resveratrol (Res) is considered to be beneficial in protecting endothelial function. However, currently, the exact protective effect and involved mechanisms of Res on endothelial dysfunction-hyperpermeability have not been completely clarified. The aim of present study is to investigate the effects of Res on amelioration of endothelial hyperpermeability and the role of caveolin-1 (Cav-1)/endothelial nitric oxide synthase (eNOS) pathway. Adult male Wistar rats were treated with a normal or high-fat/sucrose diet (HFS) with or without Res for 13 weeks. HFS and in vitro treatment with high glucose increased hyperpermeability in rat aorta, heart, liver and kidney and cultured bovine aortic endothelial cells (BAECs), respectively, which was attenuated by Res treatment. Application of Res reversed the changes in eNOS and Cav-1 expressions in aorta and heart of rats fed HFS and in BAECs incubated with high glucose. Res stimulated the formation of NO inhibited by high glucose in BAECs. Beta-Cyclodextrin (β-CD), caveolae inhibitor, showed the better beneficial effect than Res alone to up-regulate eNOS phosphorylative levels, while NG-Nitro-77 L-arginine methyl ester (L-NAME), eNOS inhibitor, had no effect on Cav-1 expression. Our studies suggested that HFS and in vitro treatment with high glucose caused endothelial hyperpermeability, which were ameliorated by Res at least involving Cav-1/eNOS regulation. PMID:25419974

  18. The Effect of High-Fat Diet-Induced Pathophysiological Changes in the Gut on Obesity: What Should be the Ideal Treatment?

    PubMed Central

    Y Lee, Chooi

    2013-01-01

    Obesity is a metabolic disorder and fundamental cause of other fatal diseases including atherosclerosis and cancer. One of the main factor that contributes to the development of obesity is high-fat (HF) consumption. Lipid ingestion will initiate from the gut feedback mechanisms to regulate glucose and lipid metabolisms. But these lipid-sensing pathways are impaired in HF-induced insulin resistance, resulting in hyperglycemia. Besides that, duodenal lipid activates mucosal mast cells, leading to the disruption of the intestinal tight junction. Lipopolysaccharide that is co-transited with dietary fat postprandially, promotes the release of cytokines and the development of metabolic syndrome. HF-diet also alters microbiota composition and enhances fat storage. Although gut is protected by immune system and contains high level of antioxidants, obesity developed presumably when this protective mechanism is compromised by the presence of excessive fat. Several therapeutic approaches targeting different pathways have been proposed. There may be no one single most effective treatment, but all aimed to prevent obesity. This review will elaborate on the physiological and molecular changes in the gut that lead to obesity, and will provide a summary of potential treatments to manage these pathophysiological changes. PMID:23842483

  19. Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice

    PubMed Central

    Yoshizaki, Yumiko; Kawasaki, Chihiro; Cheng, Kai-Chun; Ushikai, Miharu; Amitani, Haruka; Asakawa, Akihiro; Okutsu, Kayu; Sameshima, Yoshihiro; Takamine, Kazunori

    2014-01-01

    Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD), which is a model for obesity. Mice were fed HFD containing 10% (w/w) of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed. PMID:25237599

  20. Metabolomics Profiling to Investigate the Pharmacologic Mechanisms of Berberine for the Treatment of High-Fat Diet-Induced Nonalcoholic Steatohepatitis

    PubMed Central

    Li, Jian; Liu, Zezhou; Xu, Kejia; Jiang, Miao; Lu, Aiping; Gao, Xiaoyan

    2015-01-01

    Objective. Berberine has been used to treat nonalcoholic steatohepatitis (NASH), which has been addressed in many studies. In this study, we investigated the molecular pharmacology mechanisms of berberine using metabolomic techniques. Methods. Sprague-Dawley rats were randomly divided into three groups (10 rats in each group): (i) normal control group; (ii) high-fat diet- (HFD-) induced NASH model group; and (iii) HFD berberine-treated group (i.d. 200 mg/kg). The handling procedure lasted eight weeks. Then, UPLC-Q-TOF/MS techniques coupled with histopathology and biochemical analyses were adopted to explore the mechanisms of berberine on the protective effects against NASH. Key Findings. (i) According to conventional test results, berberine treatment plays a fighting role in HFD-induced NASH due to its beneficial effects against insulin resistance, inflammation, and lipid metabolism. (ii) Based on UPLC-Q-TOF/MS techniques, metabolic profiles that involved sphingomyelin (SM), phosphatidylcholine (PC), lysophosphatidylcholine (LysoPC), 13-hydroperoxy-9, 11-octadecadienoic acid (13-HpODE), eicosatrienoic acid, docosatrienoic acid, and eicosenoic acid could provide potential metabolic biomarkers to address the pharmacological mechanisms of berberine. Conclusions. The parts of molecular pharmacological mechanisms of berberine for NASH treatment are related to the regulation of metabolic disruption involving phospholipid and unsaturated fatty acids in rats with NASH. PMID:25977701

  1. High fat diet induced insulin resistance and elevated retinol binding protein 4 in female rats; treatment and protection with Berberis vulgaris extract and vitamin A.

    PubMed

    El-Sayed, Mohamed Mohammed; Ghareeb, Doaa Ahmad; Talat, Heba Allah; Sarhan, Eman Mohammed

    2013-11-01

    This research was conducted to investigate two main aims; the first aim was to find if there is a relationship between insulin resistance (IR) and retinol binding protein 4 (RBP4). The second aim was to use berberis vulgaris extract and vitamin A as protective and/or curative agents against insulin resistance. IR was developed by feeding the female rats a high fat diet (HFD) for six weeks then treating or protecting them with b. vulgaris extract (0.2 g/Kg body weight) or vitamin A (12.8μg/Kg/day) for two weeks. HFD intake elevated insulin level and RBP4 expression that associated with hyperglycemia and hyperlipidemia. Co-administration of vitamin A and B. vulgaris extracts reduced blood glucose level, insulin, body weight and RBP4 expression before, during and after HFD. Furthermore, vitamin A reduced the blood glucose, triglycerides (TG) and cholesterol levels. IR syndrome associated with the RBP 4 alteration that gives high indication about the role of RBP4 expression in the IR progression and development. Furthermore, the treatment with vitamin A and/or b. vulgaris alleviated the IR syndrome through the action on RBP4 and Insulin secretion. On the other hand, vitamin A must be avoided for the predisposed IR and prediabetic patients. PMID:24191325

  2. Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice.

    PubMed

    Escande, Carlos; Chini, Claudia C S; Nin, Veronica; Dykhouse, Katherine Minter; Novak, Colleen M; Levine, James; van Deursen, Jan; Gores, Gregory J; Chen, Junjie; Lou, Zhenkun; Chini, Eduardo Nunes

    2010-02-01

    The enzyme sirtuin 1 (SIRT1) is a critical regulator of many cellular functions, including energy metabolism. However, the precise mechanisms that modulate SIRT1 activity remain unknown. As SIRT1 activity in vitro was recently found to be negatively regulated by interaction with the deleted in breast cancer-1 (DBC1) protein, we set out to investigate whether DBC1 regulates SIRT1 activity in vivo. We found that DBC1 and SIRT1 colocalized and interacted, and that DBC1 modulated SIRT1 activity, in multiple cell lines and tissues. In mouse liver, increased SIRT1 activity, concomitant with decreased DBC1-SIRT1 interaction, was detected after 24 hours of starvation, whereas decreased SIRT1 activity and increased interaction with DBC1 was observed with high-fat diet (HFD) feeding. Consistent with the hypothesis that DBC1 is crucial for HFD-induced inhibition of SIRT1 and for the development of experimental liver steatosis, genetic deletion of Dbc1 in mice led to increased SIRT1 activity in several tissues, including liver. Furthermore, DBC1-deficient mice were protected from HFD-induced liver steatosis and inflammation, despite the development of obesity. These observations define what we believe to be a new role for DBC1 as an in vivo regulator of SIRT1 activity and liver steatosis. We therefore propose that the DBC1-SIRT1 interaction may serve as a new target for therapies aimed at nonalcoholic liver steatosis. PMID:20071779

  3. Aging Increases Susceptibility to High Fat Diet-Induced Metabolic Syndrome in C57BL/6 Mice: Improvement in Glycemic and Lipid Profile after Antioxidant Therapy

    PubMed Central

    Nunes-Souza, Valéria; César-Gomes, Cheila Juliana; Da Fonseca, Lucas José Sá; Guedes, Glaucevane Da Silva; Smaniotto, Salete; Rabelo, Luíza Antas

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD) has been considered a novel component of the metabolic syndrome (MetS), with the oxidative stress participating in its progression. This study aimed to evaluate the metabolic profile in young and old mice with MetS, and the effects of apocynin and tempol on glycemic and lipid parameters. Young and old C57BL/6 mice with high fat diet- (HFD-) induced MetS received apocynin and tempol 50 mg·kg−1/day in their drinking water for 10 weeks. After HFD, the young group showed elevated fasting glucose, worsened lipid profile in plasma, steatosis, and hepatic lipid peroxidation. Nevertheless, the old group presented significant increase in fasting insulin levels, insulin resistance, plasma and hepatic lipid peroxidation, and pronounced steatosis. The hepatic superoxide dismutase and catalase activity did not differ between the groups. Tempol and apocynin seemed to prevent hepatic lipid deposition in both groups. Furthermore, apocynin improved glucose tolerance and insulin sensitivity in old mice. In summary, old mice are more susceptible to HFD-induced metabolic changes than their young counterparts. Also, the antioxidant therapy improved insulin sensitivity and glucose tolerance, and in addition, apocynin seemed to prevent the HFD-induced hepatic fat deposition, suggesting an important role of oxidative stress in the induction of NAFLD. PMID:27057272

  4. Effect of hydroalcoholic fruit extract of Persea americana Mill. on high fat diet induced obesity: A dose response study in rats.

    PubMed

    Monika, Padmanabhan; Geetha, Arumugam

    2016-06-01

    The fruits of Persea Americana Mill., commonly known as Avocado, are traditionally consumed for various health benefits including weight reduction. Here, we studied the effect of hydroalcoholic fruit extract of Persea americana (HAEPA) on high fat diet (HFD) induced obesity in rats. Obesity was induced in male Sprague Dawley rats by feeding HFD for 14 wk. The hypolipidemic effect was evaluated by co-administering 25, 50, 100 and 200 mg/kg body wt. of HAEPA. There was a significant increase in weight gain, body mass index (BMI), blood lipids, low density lipoproteins (LDL), lipid peroxides (LPO) and serum transaminases in HFD fed rats. HFD+HAEPA fed rats showed a significant decrease in blood lipids, LPO, liver lipids and increase in antioxidant status when compared to HFD control rats. The activity of lipid metabolic key enzymes such as fatty acid synthase and HMG CoA reductase in liver were also found to be decreased significantly in HAEPA co-administered rats. Lipoprotein lipase activity was found increased in HFD+HAEPA rats. Among the 4 doses studied, 100 mg of HAEPA/kg body wt. exhibited optimum hypolipidemic activity. Histopathological observations in liver and visceral adipose tissue added more evidence for the lipid lowering effect of HAEPA. It can be concluded that avocado fruit extract can act as hypolipidemic agent probably by modulating the activities of HMG CoA reductase and fatty acid synthase in liver. PMID:27468463

  5. Longxuetongluo Capsule Improves Erythrocyte Function against Lipid Peroxidation and Abnormal Hemorheological Parameters in High Fat Diet-Induced ApoE−/− Mice

    PubMed Central

    Zheng, Jiao; Liu, Binglin; Lun, Qixing; Yao, Weijuan; Zhao, Yunfang; Xiao, Wei; Huang, Wenzhe; Wang, Yonghua; Li, Jun; Tu, Pengfei

    2016-01-01

    Chinese dragon's blood, the red resin of Dracaena cochinchinensis, one of the renowned traditional medicines, has been used to facilitate blood circulation and disperse blood stasis for thousands of years. Phenolic compounds are considered to be responsible for its main biological activities. In this study, total phenolic compounds of Chinese dragon's blood were made into capsule (Longxuetongluo Capsule, LTC) and their effects on the abnormal hemorheological properties were examined by high fat diet (HFD) induced ApoE−/− mice. Compared to the model group, LTC recovered the abnormal hemorheological parameters in HFD-induced ApoE−/− mice by reducing whole blood viscosity (WBV) at high rate and improving erythrocyte function. In conclusion, LTC could ameliorate erythrocyte deformability and osmotic fragility through the reduction of lipid peroxidation on plasma and erythrocyte membranes in HFD-induced ApoE−/− mice, which supported the traditional uses of Chinese dragon's blood as an effective agent for improving blood microcirculation in hypercholesterolemia. PMID:26649134

  6. Enteric lactoferrin attenuates the development of high-fat and high-cholesterol diet-induced hypercholesterolemia and atherosclerosis in Microminipigs.

    PubMed

    Morishita, Satoru; Kawaguchi, Hiroaki; Ono, Tomoji; Miura, Naoki; Murakoshi, Michiaki; Sugiyama, Keikichi; Kato, Hisanori; Tanimoto, Akihide; Nishino, Hoyoku

    2016-01-01

    Previously, we found that enteric lactoferrin (eLF) could reduce the visceral fat accumulation known to associate strongly with metabolic syndrome symptoms and consequently with an increased risk of atherosclerosis. In this study, the atherosclerosis-preventive potential of LF was assessed in a high-fat and high-cholesterol diet (HFCD)-induced hypercholesterolemia and atherosclerosis model using Microminipig™. Eight-week orally administered eLF remarkably reduced the HFCD-induced serum total and low-density lipoprotein cholesterol levels but not high-density lipoprotein cholesterol levels. A histological analysis of 15 arteries revealed that eLF systemically inhibited the development of atherosclerotic lesions. Pathway analysis using identified genes that characterized eLF administration in liver revealed significant changes in the steroid biosynthesis pathway (ssc00100) and all affected genes in this pathway were upregulated, suggesting that cholesterol synthesis inhibited by HFCD was recovered by eLF. In summary, eLF could potentially prevent the hypercholesterolemia and atherosclerosis through protecting homeostasis from HFCD-induced dysfunction of cholesterol metabolism. PMID:26549014

  7. Andrographolide prevents high-fat diet-induced obesity in C57BL/6 mice by suppressing the sterol regulatory element-binding protein pathway.

    PubMed

    Ding, Lili; Li, Jinmei; Song, Baoliang; Xiao, Xu; Huang, Wendong; Zhang, Binfeng; Tang, Xiaowen; Qi, Meng; Yang, Qiming; Yang, Qiaoling; Yang, Li; Wang, Zhengtao

    2014-11-01

    Sterol regulatory element-binding proteins (SREBPs) are major transcription factors regulating the expression of genes involved in biosynthesis of cholesterol, fatty acids, and triglycerides. We investigated the effect of the specific SREBP suppressor andrographolide, a natural compound isolated from Andrographis paniculata, on the regulation of SREBP signaling by use of Western blot, reporter gene assay, and quantitative real-time polymerase chain reaction analysis. In addition, the antiobesity effects of andrographolide were evaluated in C57BL/6 mice with high-fat diet (HFD)-induced obesity. Our results showed that andrographolide downregulated the expressions of SREBPs target genes and decreased cellular lipid accumulation in vitro. Further, andrographolide (100 mg/kg per day) attenuated HFD-induced body weight gain and fat accumulation in liver or adipose tissues, and improved serum lipid levels and insulin or glucose sensitivity in HFD-induced obese mice. Andrographolide effectively suppressed the respiratory quotient, energy expenditure, and oxygen consumption, which may have contributed to the decreased body-weight gain of the obese mice fed with a HFD. Consistently, andrographolide regulated SREBP target genes and metabolism-associated genes in liver or brown adipose tissue, which may have directly contributed to the lower lipid levels and enhanced insulin sensitivity. Taken together, our results indicated that andrographolide ameliorated lipid metabolism and improved glucose use in mice with HFD-induced obesity. Andrographolide has potential as a leading compound in the prevention or treatment of obesity and insulin resistance. PMID:25204338

  8. Ameliorative effect of vanadyl(IV)-ascorbate complex on high-fat high-sucrose diet-induced hyperglycemia, insulin resistance, and oxidative stress in mice.

    PubMed

    Liu, Yanjun; Xu, Jie; Guo, Yongli; Xue, Yong; Wang, Jingfeng; Xue, Changhu

    2015-10-01

    There is mounting evidence demonstrating causative links between hyperglycemia, oxidative stress, and insulin resistance, the core pathophysiological features of type 2 diabetes mellitus. Using a combinational approach, we synthesized a vanadium-antioxidant (i.e., l-ascorbic acid) complex and examined its effect on insulin resistance and oxidative stress. This study was designed to examine whether vanadyl(IV)-ascorbate complex (VOAsc) would reduce oxidative stress, hyperglycemia, and insulin resistance in high-fat high-sucrose diet (HFSD)-induced type 2 diabetes in mice. Male C57BL/6J mice were fed a HFSD for 12 weeks to induce insulin resistance, rendering them diabetic. Diabetic mice were treated with rosiglitazone, sodium l-ascorbate, or VOAsc. At the end of treatment, fasting blood glucose, fasting serum insulin, homeostasis model assessment-insulin resistance index, and serum adipocytokine levels were measured. Serum levels of nitric oxide (NO) parameters were also determined. The liver was isolated and used for determination of malondialdehyde, reduced glutathione, and catalase levels, and superoxide dismutase and glutathione peroxidase activities. VOAsc groups exhibited significant reductions in serum adipocytokine and NO levels, and oxidative stress parameters compared to the corresponding values in the untreated diabetic mice. The results indicated that VOAsc is non-toxic. In conclusion, we identified VOAsc as a potentially effective adjunct therapy for the management of type 2 diabetes. PMID:26302923

  9. Pre-germinated brown rice prevented high fat diet induced hyperlipidemia through ameliorating lipid synthesis and metabolism in C57BL/6J mice.

    PubMed

    Shen, Kuo-Ping; Hao, Chi-Long; Yen, Hsueh-Wei; Chen, Chun-Yen; Chen, Jia-Hao; Chen, Fu-Chih; Lin, Hui-Li

    2016-07-01

    Pre-germinated brown rice (PGBR) can ameliorate hyperlipidemia, but the action mechanism is not clear. We focus the mechanisms of PGBR prevented hyperlipidemia. Six-week-old mice were divided into: standard-regular diet (SRD), high-fat diet (HFD) and HFD with PGBR (HFD + PGBR) groups for 16 weeks. The HFD group has higher concentrations of TG, TC, HDL and Non-HDL in the blood, and a higher atherosclerosis index (AI). The TG levels in the liver, and TG, bile acid levels in the feces were enhanced; and the total adipocytokines level in adipose tissue was reduced. The HFD group had higher protein expressions of SREBP-1, SCD-1, FAS, LDLR, and CYP7α1 in the liver. Moreover, the greater expressions of SREBP-1, SCD-1, FAS and the less expressions of PPAR-α and adiponectin were in adipose tissue. In the HFD + PGBR group, the PGBR regulated the levels of TG, TC, HDL, Non-HDL, AI and adipocytokines. PGBR increased more cholesterol and bile acid exhaust in feces. The SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α proteins in the liver; and the SREBP-1, SCD-1, FAS, PPAR-α and adiponectin proteins in adipose tissue were reversed by PGBR. Taken together, PGBR can improve lipid synthesis and metabolism, and we suggest PGBR is a recommendable food for controlling hyperlipidemia. PMID:27499577

  10. Oral administration of the Aureobasidium pullulans-derived β-glucan effectively prevents the development of high fat diet-induced fatty liver in mice

    PubMed Central

    Aoki, Shiho; Iwai, Atsushi; Kawata, Koji; Muramatsu, Daisuke; Uchiyama, Hirofumi; Okabe, Mitsuyasu; Ikesue, Masahiro; Maeda, Naoyoshi; Uede, Toshimitsu

    2015-01-01

    Aureobasidium pullulans-derived β-glucan (AP-PG) consisting of a β-(1,3)-linked glucose main chain and β-(1,6)-linked glucose branches is taken as a supplement to improve health. This study demonstrates that oral administration of AP-PG is effective to prevent the development of high-fat diet (HFD)-induced fatty liver in mice. Here, C57BL/6N mice were fed with a normal diet or HFD, and AP-PG diluted in drinking water was administered orally. After 16 weeks, the serological analysis showed that HFD-induced high blood cholesterol and triglyceride levels were reduced by the oral administration of AP-PG. Further, HFD induced-fatty liver was significantly reduced by the oral administration of AP-PG. The triglyceride accumulation in the liver was also significantly reduced in mice administered AP-PG. Liver injury as indicated by an increase in serum alanine aminotransferase (ALT) in the HFD-fed mice was significantly reduced in the mice administered AP-PG orally, and the gene expression of cholesterol 7 alpha-hydroxylase (CYP7A1) which is known to be involved in cholesterol degradation in the liver was significantly increased in the AP-PG administered mice. These results suggest the possibility that the oral administration of AP-PG is effective to prevent the development of non-alcoholic fatty liver disease (NAFLD). PMID:26179949

  11. Secretin receptor-knockout mice are resistant to high-fat diet-induced obesity and exhibit impaired intestinal lipid absorption.

    PubMed

    Sekar, Revathi; Chow, Billy K C

    2014-08-01

    Secretin, a classical gastrointestinal hormone released from S cells in response to acid and dietary lipid, regulates pleiotropic physiological functions, such as exocrine pancreatic secretion and gastric motility. Subsequent to recently proposed revisit on secretin's metabolic effects, we have confirmed lipolytic actions of secretin during starvation and discovered a hormone-sensitive lipase-mediated mechanistic pathway behind. In this study, a 12 wk high-fat diet (HFD) feeding to secretin receptor-knockout (SCTR(-/-)) mice and their wild-type (SCTR(+/+)) littermates revealed that, despite similar food intake, SCTR(-/-) mice gained significantly less weight (SCTR(+/+): 49.6±0.9 g; SCTR(-/-): 44.7±1.4 g; P<0.05) and exhibited lower body fat content. These SCTR(-/-) mice have corresponding alleviated HFD-associated hyperleptinemia and improved glucose/insulin tolerance. Further analyses indicate that SCTR(-/-) have impaired intestinal fatty acid absorption while having similar energy expenditure and locomotor activity. Reduced fat absorption in the intestine is further supported by lowered postprandial triglyceride concentrations in circulation in SCTR(-/-) mice. In jejunal cells, transcript and protein levels of a key fat absorption regulator, cluster of differentiation 36 (CD36), was reduced in knockout mice, while transcript of Cd36 and fatty-acid uptake in isolated enterocytes was stimulated by secretin. Based on our findings, a novel positive feedback pathway involving secretin and CD36 to enhance intestinal lipid absorption is being proposed. PMID:24769669

  12. Pre-germinated brown rice prevented high fat diet induced hyperlipidemia through ameliorating lipid synthesis and metabolism in C57BL/6J mice

    PubMed Central

    Shen, Kuo-Ping; Hao, Chi-Long; Yen, Hsueh-Wei; Chen, Chun-Yen; Chen, Jia-Hao; Chen, Fu-Chih; Lin, Hui-Li

    2016-01-01

    Pre-germinated brown rice (PGBR) can ameliorate hyperlipidemia, but the action mechanism is not clear. We focus the mechanisms of PGBR prevented hyperlipidemia. Six-week-old mice were divided into: standard-regular diet (SRD), high-fat diet (HFD) and HFD with PGBR (HFD + PGBR) groups for 16 weeks. The HFD group has higher concentrations of TG, TC, HDL and Non-HDL in the blood, and a higher atherosclerosis index (AI). The TG levels in the liver, and TG, bile acid levels in the feces were enhanced; and the total adipocytokines level in adipose tissue was reduced. The HFD group had higher protein expressions of SREBP-1, SCD-1, FAS, LDLR, and CYP7α1 in the liver. Moreover, the greater expressions of SREBP-1, SCD-1, FAS and the less expressions of PPAR-α and adiponectin were in adipose tissue. In the HFD + PGBR group, the PGBR regulated the levels of TG, TC, HDL, Non-HDL, AI and adipocytokines. PGBR increased more cholesterol and bile acid exhaust in feces. The SREBP-1, SCD-1, FAS, HMGCR, LDLR, CYP7α1 and PPAR-α proteins in the liver; and the SREBP-1, SCD-1, FAS, PPAR-α and adiponectin proteins in adipose tissue were reversed by PGBR. Taken together, PGBR can improve lipid synthesis and metabolism, and we suggest PGBR is a recommendable food for controlling hyperlipidemia. PMID:27499577

  13. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice.

    PubMed

    Jung, Un Ju; Cho, Yun-Young; Choi, Myung-Sook

    2016-01-01

    Several in vitro and in vivo studies have reported the anti-inflammatory, anti-diabetic and anti-obesity effects of the flavonoid apigenin. However, the long-term supplementary effects of low-dose apigenin on obesity are unclear. Therefore, we investigated the protective effects of apigenin against obesity and related metabolic disturbances by exploring the metabolic and transcriptional responses in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed an HFD or apigenin (0.005%, w/w)-supplemented HFD for 16 weeks. In HFD-fed mice, apigenin lowered plasma levels of free fatty acid, total cholesterol, apolipoprotein B and hepatic dysfunction markers and ameliorated hepatic steatosis and hepatomegaly, without altering food intake and adiposity. These effects were partly attributed to upregulated expression of genes regulating fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain and cholesterol homeostasis, downregulated expression of lipolytic and lipogenic genes and decreased activities of enzymes responsible for triglyceride and cholesterol ester synthesis in the liver. Moreover, apigenin lowered plasma levels of pro-inflammatory mediators and fasting blood glucose. The anti-hyperglycemic effect of apigenin appeared to be related to decreased insulin resistance, hyperinsulinemia and hepatic gluconeogenic enzymes activities. Thus, apigenin can ameliorate HFD-induced comorbidities via metabolic and transcriptional modulations in the liver. PMID:27213439

  14. The Rationality of the Hypolipidemic Effect of Alismatis Rhizoma Decoction, a Classical Chinese Medicine Formula in High-Fat Diet-Induced Hyperlipidemic Mice

    PubMed Central

    Song, Chengwu; Huang, Xiaofei; Lu, Kungang; Peng, Min; Yu, Shanggong; Fang, Nianbai

    2014-01-01

    Alismatis Rhizoma Decoction (ARD) is a classical Traditional Chinese Medicine (TCM) formula for treatment of vertigo with its long history of successful clinical effect. Since vertigo is a symptom of hyperlipidemia, this study aimed at evaluating the hypolipidemic effect of ARD in hyperlipidemic mice induced by high fat diet (HFD) and investigated the rationality of formula combination of Alismatis Rhizoma (AR) and Atractylodis Macrocephalae Rhizoma (AMR). Compared with control group, hyperlipidemic mice in AR and ARD groups displayed a reduction of the following parameters: body weight, liver and serum total cholesterol, triglyceride concentration, liver and spleen coefficients, activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT); whereas the serum HDL-cholesterol levels were significantly elevated in both AR and ARD groups. AR and ARD treatments significantly down regulated the expressions of 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoA reductase) and sterol regulatory element binding factor-2 (SREBF-2). These findings clearly provided evidences that the suppression on biosynthesis of cholesterol in liver may in part contribute to the hypolipidemic effects of ARD and AR. Since no significantly hypolipidemic effect of AMR was observed, the more prominent effect of ARD than that of AR indicated synergistic effects of AR and AMR, and confirmed the rationality of ARD formula. PMID:25237360

  15. Delayed Intervention With Pyridoxamine Improves Metabolic Function and Prevents Adipose Tissue Inflammation and Insulin Resistance in High-Fat Diet-Induced Obese Mice.

    PubMed

    Maessen, Dionne E; Brouwers, Olaf; Gaens, Katrien H; Wouters, Kristiaan; Cleutjens, Jack P; Janssen, Ben J; Miyata, Toshio; Stehouwer, Coen D; Schalkwijk, Casper G

    2016-04-01

    Obesity is associated with an increased risk for the development of type 2 diabetes and vascular complications. Advanced glycation end products are increased in adipose tissue and have been associated with insulin resistance, vascular dysfunction, and inflammation of adipose tissue. Here, we report that delayed intervention with pyridoxamine (PM), a vitamin B6 analog that has been identified as an antiglycating agent, protected against high-fat diet (HFD)-induced body weight gain, hyperglycemia, and hypercholesterolemia, compared with mice that were not treated. In both HFD-induced and db/db obese mice, impaired glucose metabolism and insulin resistance were prevented by PM supplementation. PM inhibited the expansion of adipose tissue and adipocyte hypertrophy in mice. In addition, adipogenesis of murine 3T3-L1 and human Simpson-Golabi-Behmel Syndrome preadipocytes was dose- and time-dependently reduced by PM, as demonstrated by Oil Red O staining and reduced expression of adipogenic differentiation genes. No ectopic fat deposition was found in the liver of HFD mice. The high expression of proinflammatory genes in visceral adipose tissue of the HFD group was significantly attenuated by PM. Treatment with PM partially prevented HFD-induced mild vascular dysfunction. Altogether, these findings highlight the potential of PM to serve as an intervention strategy in obesity. PMID:26718500

  16. Hypoglycemic Activity through a Novel Combination of Fruiting Body and Mycelia of Cordyceps militaris in High-Fat Diet-Induced Type 2 Diabetes Mellitus Mice.

    PubMed

    Yu, Sung-Hsun; Chen, Szu-Yu Tina; Li, Wei-Shan; Dubey, Navneet Kumar; Chen, Wei-Hong; Chuu, Jiunn-Jye; Leu, Sy-Jye; Deng, Win-Ping

    2015-01-01

    Diabetes mellitus (DM) is currently ranked among leading causes of death worldwide in which type 2 DM is reaching an epidemic proportion. Hypoglycemic medications for type 2 DM have either proven inadequate or posed adverse effects; therefore, the Chinese herbal products are under investigation as an alternative treatment. In this study, a novel combination of fruiting body and mycelia powder of herbal Cordyceps militaris number 1 (CmNo1) was administered to evaluate their potential hypoglycemic effects in high-fat diet- (HFD-) induced type 2 DM in C57BL/6J mice. Body weight, fasting blood glucose (FBG), oral glucose tolerance test (OGTT), and blood biochemistry indexes were measured. Results indicated that CmNo1 lowered the blood glucose level by increasing insulin sensitivity, while no change in body weight was observed. Increased protein expression of IRS-1, pIRS-1, AKT, pAKT, and GLUT-4 in skeletal muscle and adipose tissue was found indicating restoration of insulin signaling. Additionally, PPAR-γ expression in adipose tissue restored the triglyceride and cholesterol levels. Finally, our results suggest that CmNo1 possesses strong hypoglycemic, anticholesterolemic, and antihypertriglyceridemic actions and is more economical alternate for DM treatment. PMID:26258146

  17. Gpr97 is dispensable for metabolic syndrome but is involved in macrophage inflammation in high-fat diet-induced obesity in mice

    PubMed Central

    Shi, Jueping; Zhang, Xiaoyu; Wang, Shaoying; Wang, Jinjin; Du, Bing; Wang, Zhugang; Liu, Mingyao; Jiang, Wenzheng; Qian, Min; Ren, Hua

    2016-01-01

    Local inflammation in tissues is one of primary causes in development of metabolic disorder in obesity. The accumulation of macrophages in some tissues can induce inflammatory reactions in obesity. Gpr97 is highly expressed in some immunocytes, but its potential role in inflammatory regulation has not been revealed clearly. In our research, we investigated Gpr97 in regulating macrophage inflammation and metabolic dysfunction in the high-fat diet (HFD)-induced obese mice. The major metabolic phenotyping were not different after Gpr97 knockout in HFD-fed mice. Similar pathological alterations in adipose tissue, liver, and kidney were observed in Gpr97−/− HFD mice compared with WT-HFD mice. In white adipose tissue, loss of Gpr97 reduced the ratio of M1-macrophages and increased the M2-macrophage ratio, which was opposite to that seen in the wild-type HFD mice. More macrophages invaded in the liver and kidney after Gpr97 knockout in HFD mice. Furthermore, the levels of TNF-α were higher in the liver and kidney of Gpr97−/− HFD mice compared to those in wild-type HFD mice. The data indicate that Gpr97 might be required for local inflammation development in obesity-relative tissues, but does not play a role in metabolic disorder in HFD-induced obesity. PMID:27089991

  18. Apigenin Ameliorates Dyslipidemia, Hepatic Steatosis and Insulin Resistance by Modulating Metabolic and Transcriptional Profiles in the Liver of High-Fat Diet-Induced Obese Mice

    PubMed Central

    Jung, Un Ju; Cho, Yun-Young; Choi, Myung-Sook

    2016-01-01

    Several in vitro and in vivo studies have reported the anti-inflammatory, anti-diabetic and anti-obesity effects of the flavonoid apigenin. However, the long-term supplementary effects of low-dose apigenin on obesity are unclear. Therefore, we investigated the protective effects of apigenin against obesity and related metabolic disturbances by exploring the metabolic and transcriptional responses in high-fat diet (HFD)-induced obese mice. C57BL/6J mice were fed an HFD or apigenin (0.005%, w/w)-supplemented HFD for 16 weeks. In HFD-fed mice, apigenin lowered plasma levels of free fatty acid, total cholesterol, apolipoprotein B and hepatic dysfunction markers and ameliorated hepatic steatosis and hepatomegaly, without altering food intake and adiposity. These effects were partly attributed to upregulated expression of genes regulating fatty acid oxidation, tricarboxylic acid cycle, oxidative phosphorylation, electron transport chain and cholesterol homeostasis, downregulated expression of lipolytic and lipogenic genes and decreased activities of enzymes responsible for triglyceride and cholesterol ester synthesis in the liver. Moreover, apigenin lowered plasma levels of pro-inflammatory mediators and fasting blood glucose. The anti-hyperglycemic effect of apigenin appeared to be related to decreased insulin resistance, hyperinsulinemia and hepatic gluconeogenic enzymes activities. Thus, apigenin can ameliorate HFD-induced comorbidities via metabolic and transcriptional modulations in the liver. PMID:27213439

  19. Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice.

    PubMed

    Kim, Jong Min; Park, Seon Kyeong; Guo, Tian Jiao; Kang, Jin Yong; Ha, Jeong Su; Lee, Du Sang; Lee, Uk; Heo, Ho Jin

    2016-10-01

    The ameliorating effects of the ethyl acetate fraction from Dendropanax morbifera (EFDM) on cognitive impairment in high-fat diet (HFD)-induced diabetic mice were examined by measuring its possible pharmacological activities. Administration of EFDM (20 and 50mg/kg body weight) in HFD-induced diabetic mice significantly improved glucose tolerance status in the intraperitoneal glucose tolerance test (IPGTT). In animal experiments using Y-maze, passive avoidance and Morris water maze tests, the cognitive and behavioral disorders in HFD-induced diabetic mice were considerably recovered by regulating cholinergic systems, including acetylcholine (ACh) levels and acetylcholinesterase (AChE) inhibition, and antioxidant systems, including superoxide dismutase (SOD), glutathione (GSH), oxidized GSH, and malondialdehyde (MDA) levels. Furthermore, HFD-induced abnormal activity of mitochondria were also significantly protected by the improvement of the c-Jun N-terminal protein kinase (JNK) signaling pathway with phosphorylated JNK (p-JNK), phosphorylated insulin receptor substrate (p-IRS), serine/threonine protein kinase (Akt), phosphorylated Akt (p-Akt), and phosphorylated tau (p-tau). Finally, rutin, orientin, isoorientin, and luteolin-7-O-rutinoside as the main phenolics of EFDM were identified using ultra-performance liquid chromatography/quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS(2)). These findings suggest that EFDM may have an effect as a multiple preventive substances to reduce diabetes-associated cognitive dysfunction. PMID:27288590

  20. From the Cover: Zinc Deficiency Worsens and Supplementation Prevents High-Fat Diet Induced Vascular Inflammation, Oxidative Stress, and Pathological Remodeling.

    PubMed

    Chen, Jun; Wang, Shudong; Luo, Manyu; Zhang, Zhiguo; Dai, Xiaozhen; Kong, Maiying; Cai, Lu; Wang, Yuehui; Shi, Bingyin; Tan, Yi

    2016-09-01

    Obesity has become a common public health problem in the world and raises the risk of various cardiovascular diseases. Zinc is essential for multiple organs in terms of normal structure and function. The present study investigated the effects of high fat diet (HFD) induced obesity on the aorta in mice, and evaluated whether it can be affected by zinc deficiency or supplementation. Four-week-old male C57BL/6J mice were fed HFD with varied amounts of zinc (deficiency, adequate and supplementation) for 3 and 6 months. Results showed that HFD feeding induced a time-dependent aortic remodeling, demonstrated by increased vessel wall thickness, tunica cell proliferation and fibrotic responses, and inflammatory response, reflected by increased expression of inflammatory cytokines (tumor necrosis factor-α and vascular cell adhesion molecule 1). HFD feeding also caused aortic oxidative damage, reflected by 3-nitrotyrosine and 4-hydroxy-2-nonenal accumulation, and down-regulated nuclear factor (erythroid-derived 2)-like 2 (Nrf2) expression and function, shown by down-regulation of its downstream antioxidants, catalase, NAD(P)H dehydrogenase (quinone 1), and metallothionein expression. The vascular effects of obesity-induced by HFD was exacerbated by zinc deficiency but significantly improved by zinc supplementation. In addition, down-regulation of Nrf2 function and associated antioxidants expression were also worsened by zinc deficiency but improved by zinc supplementation. These results suggest that HFD induces aortic remodeling, which can be exacerbated by zinc deficiency and improved by zinc supplementation. PMID:27370414

  1. High-fat diet-induced β-cell proliferation occurs prior to insulin resistance in C57Bl/6J male mice

    PubMed Central

    Mosser, Rockann E.; Maulis, Matthew F.; Moullé, Valentine S.; Dunn, Jennifer C.; Carboneau, Bethany A.; Arasi, Kavin; Pappan, Kirk; Poitout, Vincent

    2015-01-01

    Both short- (1 wk) and long-term (2–12 mo) high-fat diet (HFD) studies reveal enhanced β-cell mass due to increased β-cell proliferation. β-Cell proliferation following HFD has been postulated to occur in response to insulin resistance; however, whether HFD can induce β-cell proliferation independent of insulin resistance has been controversial. To examine the kinetics of HFD-induced β-cell proliferation and its correlation with insulin resistance, we placed 8-wk-old male C57Bl/6J mice on HFD for different lengths of time and assayed the following: glucose tolerance, insulin secretion in response to glucose, insulin tolerance, β-cell mass, and β-cell proliferation. We found that β-cell proliferation was significantly increased after only 3 days of HFD feeding, weeks before an increase in β-cell mass or peripheral insulin resistance was detected. These results were confirmed by hyperinsulinemic euglycemic clamps and measurements of α-hydroxybutyrate, a plasma biomarker of insulin resistance in humans. An increase in expression of key islet-proliferative genes was found in isolated islets from 1-wk HFD-fed mice compared with chow diet (CD)-fed mice. These data indicate that short-term HFD feeding enhances β-cell proliferation before insulin resistance becomes apparent. PMID:25628421

  2. Alleviation of high-fat diet-induced atherosclerosis and glucose intolerance by a novel GLP-1 fusion protein in ApoE(-/-) mice.

    PubMed

    Kong, Yuelin; Tong, Yue; Chen, Chen; Gao, Mingming; Gao, Xiangdong; Yao, Wenbing

    2016-07-01

    We have previously constructed an engineered anti-diabetic fusion protein using glucagon-like peptide-1 and the globular domain of adiponectin. Herein, we evaluated the therapeutic effects of this fusion protein (GAD) on high-fat diet (HFD)-fed ApoE(-/-) mice. The lipid-lowering effect of GAD was determined in C57BL/6 mice using a lipid tolerance test. The effects of GAD on HFD-induced glucose intolerance, atherosclerosis, and hepatic steatosis were evaluated in HFD-fed ApoE(-/-) mice using glucose tolerance test, histological examinations and real-time quantitative PCR. The anti-inflammation activity of GAD was assessed in vitro on macrophages. GAD improved lipid metabolism in C57BL/6 mice. GAD treatment alleviated glucose intolerance, reduced blood lipid level, and attenuated atherosclerotic lesion in HFD-fed ApoE(-/-) mice, which was associated with a repressed macrophage infiltration in the vessel wall. GAD treatment also blocked hepatic macrophage infiltration and prevented hepatic inflammation. GAD suppressed lipopolysaccharide-triggered inflammation responses on macrophages, which can be abolished by H89, an inhibitor of protein kinase A. These findings demonstrate that GAD is able to generate a variety of metabolic benefits in HFD-fed ApoE(-/-) mice and indicate that this engineered fusion protein is a promising lead structure for anti-atherosclerosis drug discovery. PMID:26832342

  3. The combination of high-fat diet-induced obesity and chronic ulcerative colitis reciprocally exacerbates adipose tissue and colon inflammation

    PubMed Central

    2011-01-01

    Background This study evaluated the relationship between ulcerative colitis and obesity, which are both chronic diseases characterized by inflammation and increases in immune cells and pro-inflammatory cytokines. Methods Mice with chronic ulcerative colitis induced by 2 cycles of dextran sodium sulfate (DSS) in the first and fourth week of the experiment were fed a high-fat diet (HFD) to induce obesity by 8 weeks. The animals were divided into 4 \\ groups (control, colitis, HFD and colitis + HFD). Results Obesity alone did not raise histopathology scores, but the combination of obesity and colitis worsened the scores in the colon compared to colitis group. Despite the reduction in weight gain, there was increased inflammatory infiltrate in both the colon and visceral adipose tissue of colitis + HFD mice due to increased infiltration of macrophages, neutrophils and lymphocytes. Intravital microscopy of VAT microvasculature showed an increase in leukocyte adhesion and rolling and overexpression of adhesion molecules compared to other groups. Moreover, circulating lymphocytes, monocytes and neutrophils in the spleen and cecal lymph nodes were increased in the colitis + HFD group. Conclusion Our results demonstrated the relationship between ulcerative colitis and obesity as aggravating factors for each disease, with increased inflammation in the colon and adipose tissue and systemic alterations observed in the spleen, lymph nodes and bloodstream. PMID:22073943

  4. Catalpol ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by suppressing the JNK and NF-κB pathways.

    PubMed

    Zhou, Jun; Xu, Gang; Ma, Shuai; Li, Fen; Yuan, Miao; Xu, Huibi; Huang, Kaixun

    2015-11-27

    Catalpol, a bioactive component from the root of Rehmannia glutinosa, has been shown to possess hypoglycemic effects in type 2 diabetic animal models, however, the underlying mechanisms remain poorly understood. Here we investigated the effect of catalpol on high-fat diet (HFD)-induced insulin resistance and adipose tissue inflammation in mice. Oral administration of catalpol at 100 mg/kg for 4 weeks had no effect on body weight of HFD-induced obese mice, but it significantly improved fasting glucose and insulin levels, glucose tolerance and insulin tolerance. Moreover, macrophage infiltration into adipose tissue was markedly reduced by catalpol. Intriguingly, catalpol also significantly reduced mRNA expressions of M1 pro-inflammatory cytokines, but increased M2 anti-inflammatory gene expressions in adipose tissue. Concurrently, catalpol significantly suppressed the c-Jun NH2-terminal kinase (JNK) and nuclear factor-kappa B (NF-κB) signaling pathways in adipose tissue. Collectively, these results suggest that catalpol may ameliorate HFD-induced insulin resistance in mice by attenuating adipose tissue inflammation and suppressing the JNK and NF-κB pathways, and thus provide important new insights into the underlying mechanisms of the antidiabetic effect of catalpol. PMID:26474703

  5. Anti-vascular endothelial growth factor treatment induces blood flow recovery through vascular remodeling in high-fat diet induced diabetic mice.

    PubMed

    Xiao, Lamei; Yan, Kai; Yang, Yan; Chen, Ni; Li, Yongjie; Deng, Xin; Wang, Liqun; Liu, Yan; Mu, Lin; Li, Rong; Luo, Mao; Ren, Meiping; Wu, Jianbo

    2016-05-01

    Diabetes mellitus (DM) leads to the development of microvascular diseases and is associated with impaired angiogenesis. The presence of vascular endothelial growth factor (VEGF) can block PDGF-BB dependent regulation of neovascularization and vessel normalization. We tested the hypothesis that the inhibition of VEGF improves blood flow in a mouse hindlimb ischemia model produced by femoral artery ligation. In this study, we examined the effect of bevacizumab, a humanized monoclonal antibody against VEGF-A, on blood perfusion and angiogenesis after hindlimb ischemia. We showed that bevacizumab induces functional blood flow in high fat chow (HFC)-fed diabetic mice. Treatment with bevacizumab increased the expression of platelet derived growth factor-BB (PDGF-BB) in ischemic muscle, and led to vascular normalization. It also blocked vascular leakage by improving the recruitment of pericytes associated with nascent blood vessels, but it did not affect capillary formation. Furthermore, treatment with an anti-PDGF drug significantly inhibited blood flow perfusion in diabetic mice treated with bevacizumab. These results indicate that bevacizumab improves blood flow recovery through the induction of PDGF-BB in a diabetic mouse hindlimb ischemia model, and that vessel normalization may represent a useful strategy for the prevention and treatment of diabetic peripheral arterial disease. PMID:26808210

  6. Fucoidan alleviates high-fat diet-induced dyslipidemia and atherosclerosis in ApoE(shl) mice deficient in apolipoprotein E expression.

    PubMed

    Yokota, Takashi; Nomura, Koichi; Nagashima, Mikio; Kamimura, Naomi

    2016-06-01

    Fucoidan, a sulfated polysaccharide extracted from brown seaweeds, possesses many biological activities including anti-inflammatory and antioxidant activities. We aimed to investigate the protective effects of fucoidan on dyslipidemia and atherosclerosis in apolipoprotein E-deficient mice (ApoE(shl) mice) and to elucidate its molecular targets in the liver by using a transcriptomic approach. For 12weeks, ApoE(shl) mice were fed a high-fat diet (HFD) supplemented with either 1% or 5% fucoidan. Fucoidan supplementation significantly reduced tissue weight (liver and white adipose tissue), blood lipid, total cholesterol (TC), triglyceride (TG), non-high-density lipoprotein cholesterol (non-HDL-C) and glucose levels in HFD-fed ApoE(shl) mice but increased plasma lipoprotein lipase (LPL) activity and HDL-C levels. Fucoidan also reduced hepatic steatosis levels (liver size, TC and TG levels, and lipid peroxidation) and increased white adipose tissue LPL activity. DNA microarray analysis and quantitative reverse transcription-polymerase chain reaction demonstrated differential expression of genes encoding proteins involved in lipid metabolism, energy homeostasis and insulin sensitivity, by activating Ppara and inactivating Srebf1. Fucoidan supplementation markedly reduced the thickness of the lipid-rich plaque, lipid peroxidation and foaming macrophage accumulation in the aorta in HFD-fed ApoE(shl) mice. Thus, fucoidan supplementation appears to have anti-dyslipidemic and anti-atherosclerotic effects by inducing LPL activity and inhibiting the effects of inflammation and oxidative stress in HFD-fed ApoE(shl) mice. PMID:27142736

  7. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    PubMed

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats. PMID:26064395

  8. Excess iron modulates endoplasmic reticulum stress-associated pathways in a mouse model of alcohol and high-fat diet-induced liver injury.

    PubMed

    Tan, Terrence C H; Crawford, Darrell H G; Jaskowski, Lesley A; Subramaniam, V Nathan; Clouston, Andrew D; Crane, Denis I; Bridle, Kim R; Anderson, Gregory J; Fletcher, Linda M

    2013-12-01

    Endoplasmic reticulum (ER) stress is an important pathogenic mechanism for alcoholic (ALD) and nonalcoholic fatty liver disease (NAFLD). Iron overload is an important cofactor for liver injury in ALD and NAFLD, but its role in ER stress and associated stress signaling pathways is unclear. To investigate this, we developed a murine model of combined liver injury by co-feeding the mildly iron overloaded, the hemochromatosis gene-null (Hfe(-/)) mouse ad libitum with ethanol and a high-fat diet (HFD) for 8 weeks. This co-feeding led to profound steatohepatitis, significant fibrosis, and increased apoptosis in the Hfe(-/-) mice as compared with wild-type (WT) controls. Iron overload also led to induction of unfolded protein response (XBP1 splicing, activation of IRE-1α and PERK, as well as sequestration of GRP78) and ER stress (increased CHOP protein expression) following HFD and ethanol. This is associated with a muted autophagic response including reduced LC3-I expression and impaired conjugation to LC3-II, reduced beclin-1 protein, and failure of induction of autophagy-related proteins (Atg) 3, 5, 7, and 12. As a result of the impaired autophagy, levels of the sequestosome protein p62 were most elevated in the Hfe(-/-) group co-fed ethanol and HFD. Iron overload reduces the activation of adenosine monophosphate protein kinase associated with ethanol and HFD feeding. We conclude that iron toxicity may modulate hepatic stress signaling pathways by impairing adaptive cellular compensatory mechanisms in alcohol- and obesity-induced liver injury. PMID:24126888

  9. Pre-germinated brown rice prevents high-fat diet induced hyperglycemia through elevated insulin secretion and glucose metabolism pathway in C57BL/6J strain mice

    PubMed Central

    Shen, Kuo-Ping; Hao, Chi-Long; Yen, Hsueh-Wei; Chen, Chun-Yen; Wu, Bin-Nan; Lin, Hui-Li

    2015-01-01

    This study investigated the effect and mechanism of pre-germinated brown rice (PGBR) prevented hyperglycemia in C57BL/6J mice fed high-fat-diet (HFD). Normal six-week-old mice were randomly divided into three groups. Group 1 was fed standard-regular-diet (SRD) and group 2 was fed HFD for 16 weeks. In group 3, the mice were fed a HFD with its carbohydrate replaced with PGBR for 16 weeks. Comparing the SRD and HFD groups, we found the HFD group had higher blood pressure, higher concentrations of blood glucose and HbA1c. The HFD group had less protein expression of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), phosphatidylinositol-3-kinase (PI3K), glucose transporter-4 (GLUT-4) and glucokinase (GCK) and greater expression of glucogen synthase kinase (GSK) in skeletal muscle. The HFD group also had less expression of IR, serine/threonine kinase PI3K-linked protein kinase B (Akt/PKB), AMP-activated protein kinase (AMPK), GCK and peroxisome proliferator-activated receptor γ (PPARγ) in liver. In the HFD + PGBR group, the PGBR could reverse the disorders of blood pressure, blood glucose, HbA1c and increase insulin concentration. PGBR increased the IR, IRS-1, PI3K, Akt, GLUT-1 and GLUT-4 proteins, and ameliorated AMPK, GCK, GSK and PPARγ proteins. Together, PGBR prevented HFD-induced hyperglycemia through improving insulin levels, insulin receptor, glucose transporters and enhancing glucose metabolism. PMID:25834303

  10. High-fat diet-induced obesity alters nitric oxide-mediated neuromuscular transmission and smooth muscle excitability in the mouse distal colon.

    PubMed

    Bhattarai, Yogesh; Fried, David; Gulbransen, Brian; Kadrofske, Mark; Fernandes, Roxanne; Xu, Hui; Galligan, James

    2016-08-01

    We tested the hypothesis that colonic enteric neurotransmission and smooth muscle cell (SMC) function are altered in mice fed a high-fat diet (HFD). We used wild-type (WT) mice and mice lacking the β1-subunit of the BK channel (BKβ1 (-/-)). WT mice fed a HFD had increased myenteric plexus oxidative stress, a 28% decrease in nitrergic neurons, and a 20% decrease in basal nitric oxide (NO) levels. Circular muscle inhibitory junction potentials (IJPs) were reduced in HFD WT mice. The NO synthase inhibitor nitro-l-arginine (NLA) was less effective at inhibiting relaxations in HFD compared with control diet (CD) WT mice (11 vs. 37%, P < 0.05). SMCs from HFD WT mice had depolarized membrane potentials (-47 ± 2 mV) and continuous action potential firing compared with CD WT mice (-53 ± 2 mV, P < 0.05), which showed rhythmic firing. SMCs from HFD or CD fed BKβ1 (-/-) mice fired action potentials continuously. NLA depolarized membrane potential and caused continuous firing only in SMCs from CD WT mice. Sodium nitroprusside (NO donor) hyperpolarized membrane potential and changed continuous to rhythmic action potential firing in SMCs from HFD WT and BKβ1 (-/-) mice. Migrating motor complexes were disrupted in colons from BKβ1 (-/-) mice and HFD WT mice. BK channel α-subunit protein and β1-subunit mRNA expression were similar in CD and HFD WT mice. We conclude that HFD-induced obesity disrupts inhibitory neuromuscular transmission, SMC excitability, and colonic motility by promoting oxidative stress, loss of nitrergic neurons, and SMC BK channel dysfunction. PMID:27288421

  11. Deletion of intestinal epithelial insulin receptor attenuates high-fat diet-induced elevations in cholesterol and stem, enteroendocrine, and Paneth cell mRNAs

    PubMed Central

    Andres, Sarah F.; Santoro, M. Agostina; Mah, Amanda T.; Keku, J. Adeola; Bortvedt, Amy E.; Blue, R. Eric

    2014-01-01

    The insulin receptor (IR) regulates nutrient uptake and utilization in multiple organs, but its role in the intestinal epithelium is not defined. This study developed a mouse model with villin-Cre (VC) recombinase-mediated intestinal epithelial cell (IEC)-specific IR deletion (VC-IRΔ/Δ) and littermate controls with floxed, but intact, IR (IRfl/fl) to define in vivo roles of IEC-IR in mice fed chow or high-fat diet (HFD). We hypothesized that loss of IEC-IR would alter intestinal growth, biomarkers of intestinal epithelial stem cells (IESC) or other lineages, body weight, adiposity, and glucose or lipid handling. In lean, chow-fed mice, IEC-IR deletion did not affect body or fat mass, plasma glucose, or IEC proliferation. In chow-fed VC-IRΔ/Δ mice, mRNA levels of the Paneth cell marker lysozyme (Lyz) were decreased, but markers of other differentiated lineages were unchanged. During HFD-induced obesity, IRfl/fl and VC-IRΔ/Δ mice exhibited similar increases in body and fat mass, plasma insulin, mRNAs encoding several lipid-handling proteins, a decrease in Paneth cell number, and impaired glucose tolerance. In IRfl/fl mice, HFD-induced obesity increased circulating cholesterol; numbers of chromogranin A (CHGA)-positive enteroendocrine cells (EEC); and mRNAs encoding Chga, glucose-dependent insulinotrophic peptide (Gip), glucagon (Gcg), Lyz, IESC biomarkers, and the enterocyte cholesterol transporter Scarb1. All these effects were attenuated or lost in VC-IRΔ/Δ mice. These results demonstrate that IEC-IR is not required for normal growth of the intestinal epithelium in lean adult mice. However, our findings provide novel evidence that, during HFD-induced obesity, IEC-IR contributes to increases in EEC, plasma cholesterol, and increased expression of Scarb1 or IESC-, EEC-, and Paneth cell-derived mRNAs. PMID:25394660

  12. Impact of Korean pine nut oil on weight gain and immune responses in high-fat diet-induced obese mice

    PubMed Central

    Park, Soyoung; Lim, Yeseo; Shin, Sunhye

    2013-01-01

    Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-γ, and LPS-stimulated production of IL-6, IL-1β, and prostaglandin E2 (PGE2) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-1β (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-γ, IL-6, or PGE2 in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses. PMID:24133613

  13. Combined Mulberry Leaf and Fruit Extract Improved Early Stage of Cutaneous Wound Healing in High-Fat Diet-Induced Obese Mice.

    PubMed

    Eo, Hyeyoon; Lim, Yunsook

    2016-02-01

    Obesity is a pandemic that causes many health challenges, including difficulties in achieving proper wound healing without complications. The current study investigated the role of NLRP3 inflammasome in the early stages of cutaneous wound healing and the effect of combined mulberry leaf and fruit extract (MLFE) on cutaneous NLRP inflammasome involvement in delayed wound healing mice with high-fat diet (HFD)-induced obesity. After obesity was induced by HFD for 10 weeks, the mice were supplemented with MLFE (at a dose of 500 mg/kg containing 333.3 mg/kg of mulberry leaf extract and 166.7 mg/kg of mulberry fruit extract) by gavage, 5 days/week for 12 weeks. MLFE supplementation ameliorated delayed wound closure in obese mice. While wound size was positively correlated with fasting blood glucose level during the early stage of wound healing, it was strongly correlated with body weight gain and body fat mass during the later stage of wound healing. Under obese conditions, the levels of NLRP3 inflammasome and its related markers (pro-caspase-1 and precursor/mature interleukin 1 beta) were increased at a basal level, but the NLRP3 inflammasome was suppressed during the inflammatory stage of cutaneous wound healing. However, MLFE supplementation stimulated cutaneous NLRP3 inflammasome in HFD-induced obese mice (day 3). Taken together, stimulating the NLRP3 inflammasome might be beneficial in the early inflammatory stage of cutaneous wound healing and MLFE could be a potential therapeutic intervention in delayed wound healing through activation of the NLRP3 inflammasome in obesity. PMID:26491791

  14. Angiotensin II type 2 receptor promotes adipocyte differentiation and restores adipocyte size in high-fat/high-fructose diet-induced insulin resistance in rats.

    PubMed

    Shum, Michaël; Pinard, Sandra; Guimond, Marie-Odile; Labbé, Sébastien M; Roberge, Claude; Baillargeon, Jean-Patrice; Langlois, Marie-France; Alterman, Mathias; Wallinder, Charlotta; Hallberg, Anders; Carpentier, André C; Gallo-Payet, Nicole

    2013-01-15

    This study was aimed at establishing whether specific activation of angiotensin II (ANG II) type 2 receptor (AT2R) modulates adipocyte differentiation and function. In primary cultures of subcutaneous (SC) and retroperitoneal (RET) preadipocytes, both AT2R and AT1R were expressed at the mRNA and protein level. Cells were stimulated with ANG II or the AT2R agonist C21/M24, alone or in the presence of the AT1R antagonist losartan or the AT2R antagonist PD123,319. During differentiation, C21/M24 increased PPARγ expression in both RET and SC preadipocytes while the number of small lipid droplets and lipid accumulation solely increased in SC preadipocytes. In mature adipocytes, C21/M24 decreased the mean size of large lipid droplets. Upon abolishment of AT2R expression using AT2R-targeted shRNAs, expressions of AT2R, aP2, and PPARγ remained very low, and cells were unable to differentiate. In Wistar rats fed a 6-wk high-fat/high-fructose (HFHF) diet, a significant shift toward larger adipocytes was observed in RET and SC adipose tissue depots. C21/M24 treatments for 6 wk restored normal adipocyte size distribution in both these tissue depots. Moreover, C21/M24 and losartan decreased hyperinsulinemia and improved insulin sensitivity impaired by HFHF diet. A strong correlation between adipocyte size area and glucose infusion rate during euglycemic-hyperinsulinemic clamp was observed. These results indicate that AT2R is involved in early adipocyte differentiation, while in mature adipocytes and in a model of insulin resistance AT2R activation restores normal adipocyte morphology and improves insulin sensitivity. PMID:23149621

  15. Effect of dietary supplementation of Bacillus subtilis B10 on biochemical and molecular parameters in the serum and liver of high-fat diet-induced obese mice* #

    PubMed Central

    Lei, Kai; Li, Ya-li; Wang, Yang; Wen, Jing; Wu, Hong-zhao; Yu, Dong-you; Li, Wei-fen

    2015-01-01

    While a high-fat diet (HFD) is assumed to be related to fat-mediated oxidative stress decreasing antioxidant enzyme activity, probiotics are believed to have positive effects on the regulation of HFD-induced obesity as well as lipid metabolism, energy homeostasis, and anti-oxidation. Because Bacillus subtilis B10 has beneficial effects on the abnormal lipid metabolism and the oxidative stress in HFD-induced obese mice, ICR mice were randomly assigned into an HFD group and the HFD was supplemented with 0.1% (w/w) Bacillus subtilis B10 (HFD+B10 group). Thereafter, 30-d treatments were run, and then hepatic lipid level and antioxidant status were measured. The expression of genes related to lipid metabolism and oxidative stress in the liver was determined by reverse-transcription quantitative polymerase chain reaction (RT-qPCR). We found that HFD-induced obese mice treated with B10 showed a decrease in weight gain, serum glucose activity as well as hepatic triglyceride (TG), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT) activities. In addition, the gene expressions of antioxidant genes, glutathione reductase (GR), xanthine oxidase (XO), heat-shock protein 90 (Hsp90), and lipid synthesis gene 3β-hydroxysteroid-∆24 reductase (DHCR24) in the HFD+B10 group were down-regulated, suggesting alleviation of oxidative stress, while the lipolysis gene 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2), energy metabolism gene peroxisome proliferator-activated receptor α (PPARα) and the gene encoding tumor-suppressor protein p53 were up-regulated. The regulatory and positive effect of dietary supplementation of probiotic B10 suggests that it has a beneficial effect on the homeostasis of the lipid metabolism and on alleviating oxidative stress in HFD-induced obese mice. PMID:26055910

  16. Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.

    PubMed

    Tsoulis, Michael W; Chang, Pauline E; Moore, Caroline J; Chan, Kaitlyn A; Gohir, Wajiha; Petrik, James J; Vickers, Mark H; Connor, Kristin L; Sloboda, Deborah M

    2016-04-01

    Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood. PMID:26962114

  17. Possible modulation of FAS and PTP-1B signaling in ameliorative potential of Bombax ceiba against high fat diet induced obesity

    PubMed Central

    2013-01-01

    Background Bombax ceiba Linn., commonly called as Semal, is used in various gastro-intestinal disturbances. It contains Lupeol which inhibits PTP-1B, adipogenesis, TG synthesis and accumulation of lipids in adipocytes and adipokines whereas the flavonoids isolated from B. ceiba has FAS inhibitory activity. The present study was aimed to investigate ameliorative potential of Bombax ceiba to experimental obesity in Wistar rats, and its possible mechanism of action. Methods Male Wistar albino rats weighing 180-220 g were employed in present study. Experimental obesity was induced by feeding high fat diet for 10 weeks. Methanolic extract of B. ceiba extract 100, 200 and 400 mg/kg and Gemfibrozil 50 mg/kg as standard drug were given orally from 7th to 10th week. Results Induction with HFD for 10 weeks caused significant (p < 0.05) increase in % body wt, BMI, LEE indices; serum glucose, triglyceride, LDL, VLDL, cholesterol, free fatty acid, ALT, AST; tissue TBARS, nitrate/nitrite levels; different fat pads and relative liver weight; and significant decrease in food intake (g and kcal), serum HDL and tissue glutathione levels in HFD control rats. Treatment with B. ceiba extract and Gemfibrozil significantly attenuated these HFD induced changes, as compared to HFD control. The effect of B. ceiba 200 and 400 mg/kg was more pronounced in comparison to Gemfibrozil. Conclusion On the basis of results obtained, it may be concluded that the methanolic extract of stem bark of Bombax ceiba has significant ameliorative potential against HFD induced obesity in rats, possibly through modulation of FAS and PTP-1B signaling due to the presence of flavonoids and lupeol. PMID:24160453

  18. Anthocyanin-rich Phytochemicals from Aronia Fruits Inhibit Visceral Fat Accumulation and Hyperglycemia in High-fat Diet-induced Dietary Obese Rats.

    PubMed

    Takahashi, Azusa; Shimizu, Hisae; Okazaki, Yukako; Sakaguchi, Hirohide; Taira, Toshio; Suzuki, Takashi; Chiji, Hideyuki

    2015-01-01

    Aronia fruits (chokeberry: Aronia melanocarpa E.) containing phenolic phytochemicals, such as cyanidin 3-glycosides and chlorogenic acid, have attracted considerable attention because of their potential human health benefits in humans including antioxidant activities and ability to improved vision. In the present study, the effects of anthocyanin-rich phytochemicals from aronia fruits (aronia phytochemicals) on visceral fat accumulation and fasting hyperglycemia were examined in rats fed a high-fat diet (Experiment 1). Total visceral fat mass was significantly lower in rats fed aronia phytochemicals than that in both the control group and bilberry phytochemicals-supplemented rats (p < 0.05). Moreover, perirenal and epididymal adipose tissue mass in rats fed aronia phytochemicals was significantly lower than that in both the control and bilberry phytochemicals group. Additionally, the mesenteric adipose tissue mass in aronia phytochemicals-fed rats was significantly low (p < 0.05). Furthermore, the fasting blood glucose levels significantly decreased in rats fed aronia phytochemicals for 4 weeks compared to that in the control rats (p < 0.05). Therefore, we investigated the effects of phytochemicals on postprandial hyperlipidemia after corn oil loading in rats, pancreatic lipase activity in vitro, and the plasma glycemic response after sucrose loading in order to elucidate the preventive factor of aronia phytochemical on visceral fat accumulation. In the oral corn oil tolerance tests (Experiment 2), aronia phytochemicals significantly inhibited the increases in plasma triglyceride levels, with a half-maximal inhibitory concentration (IC(50)) of 1.50 mg/mL. However, the inhibitory activity was similar to that of bilberry and tea catechins. In the sucrose tolerance tests (Experiment 3), aronia phytochemicals also significantly inhibited the increases in blood glucose levels that were observed in the control animals (p < 0.05). These results suggest that anthocyanin

  19. Magnolia Bioactive Constituent 4-O-Methylhonokiol Prevents the Impairment of Cardiac Insulin Signaling and the Cardiac Pathogenesis in High-Fat Diet-Induced Obese Mice

    PubMed Central

    Zhang, Zhiguo; Chen, Jing; Zhou, Shanshan; Wang, Shudong; Cai, Xiaohong; Conklin, Daniel J.; Kim, Ki-Soo; Kim, Ki Ho; Tan, Yi; Zheng, Yang; Kim, Young Heui; Cai, Lu

    2015-01-01

    In obesity, cardiac insulin resistance is a putative cause of cardiac hypertrophy and dysfunction. In our previous study, we observed that Magnolia extract BL153 attenuated high-fat-diet (HFD)-induced cardiac pathogenic changes. In this study, we further investigated the protective effects of the BL153 bioactive constituent, 4-O-methylhonokiol (MH), against HFD-induced cardiac pathogenesis and its possible mechanisms. C57BL/6J mice were fed a normal diet or a HFD with gavage administration of vehicle, BL153, or MH (low or high dose) daily for 24 weeks. Treatment with MH attenuated HFD-induced obesity, as evidenced by body weight gain, and cardiac pathogenesis, as assessed by the heart weight and echocardiography. Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling. MH also inhibited cardiac expression of the inflammatory factors tumor necrosis factor-α and plasminogen activator inhibitor-1 and increased the phosphorylation of nuclear factor erythroid-derived 2-like 2 (Nrf2) as well as the expression of a Nrf2 downstream target gene heme oxygenase-1. The increased Nrf2 signaling was associated with decreased oxidative stress and damage, as reflected by lowered malondialdehyde and 3-nitrotyrosine levels. Furthermore, MH reduced HFD-induced cardiac lipid accumulation along with lowering expression of cardiac fatty acid translocase/CD36 protein. These results suggest that MH, a bioactive constituent of Magnolia, prevents HFD-induced cardiac pathogenesis by attenuating the impairment of cardiac insulin signaling, perhaps via activation of Nrf2 and Akt2 signaling to attenuate CD36-mediated lipid accumulation and lipotoxicity. PMID:26157343

  20. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice.

    PubMed

    Vida, Margarita; Gavito, Ana Luisa; Pavón, Francisco Javier; Bautista, Dolores; Serrano, Antonia; Suarez, Juan; Arrabal, Sergio; Decara, Juan; Romero-Cuevas, Miguel; Rodríguez de Fonseca, Fernando; Baixeras, Elena

    2015-07-01

    Interleukin-6 (IL-6) has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD) in wild-type (WT) and IL-6-deficient (IL-6(-/-)) mice. Additionally, HFD-fed IL-6(-/-) mice were also chronically treated with recombinant IL-6 (rIL-6). Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1) and signal transducer and activator of transcription-3 (STAT3), increased AMP kinase phosphorylation (p-AMPK), and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). The HFD-fed IL-6(-/-) mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β), FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6 -/-: mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis. PMID:26035386

  1. High-fat diet-induced deregulation of hippocampal insulin signaling and mitochondrial homeostasis deficiences contribute to Alzheimer disease pathology in rodents.

    PubMed

    Petrov, Dmitry; Pedrós, Ignacio; Artiach, Gonzalo; Sureda, Francesc X; Barroso, Emma; Pallàs, Mercè; Casadesús, Gemma; Beas-Zarate, Carlos; Carro, Eva; Ferrer, Isidro; Vazquez-Carrera, Manuel; Folch, Jaume; Camins, Antoni

    2015-09-01

    Global obesity is a pandemic status, estimated to affect over 2 billion people, that has resulted in an enormous strain on healthcare systems worldwide. The situation is compounded by the fact that apart from the direct costs associated with overweight pathology, obesity presents itself with a number of comorbidities, including an increased risk for the development of neurodegenerative disorders. Alzheimer disease (AD), the main cause of senile dementia, is no exception. Spectacular failure of the pharmaceutical industry to come up with effective AD treatment strategies is forcing the broader scientific community to rethink the underlying molecular mechanisms leading to cognitive decline. To this end, the emphasis is once again placed on the experimental animal models of the disease. In the current study, we have focused on the effects of a high-fat diet (HFD) on hippocampal-dependent memory in C57/Bl6 Wild-type (WT) and APPswe/PS1dE9 (APP/PS1) mice, a well-established mouse model of familial AD. Our results indicate that the continuous HFD administration starting at the time of weaning is sufficient to produce β-amyloid-independent, hippocampal-dependent memory deficits measured by a 2-object novel-object recognition test (NOR) in mice as early as 6months of age. Furthermore, the resulting metabolic syndrome appears to have direct effects on brain insulin regulation and mitochondrial function. We have observed pathological changes related to both the proximal and distal insulin signaling pathway in the brains of HFD-fed WT and APP/PS1 mice. These changes are accompanied by a significantly reduced OXPHOS metabolism, suggesting that mitochondria play an important role in hippocampus-dependent memory formation and retention in both the HFD-treated and AD-like rodents at a relatively young age. PMID:26003667

  2. The intake of high-fat diets induces an obesogenic-like gene expression profile in peripheral blood mononuclear cells, which is reverted by dieting.

    PubMed

    Reynés, Bàrbara; García-Ruiz, Estefanía; Palou, Andreu; Oliver, Paula

    2016-06-01

    Peripheral blood mononuclear cells (PBMC) are increasingly used for nutrigenomic studies. In this study, we aimed to identify whether these cells could reflect the development of an obesogenic profile associated with the intake of high-fat (HF) diets. We analysed, by real-time RT-PCR, the dietary response of key genes related to lipid metabolism, obesity and inflammation in PBMC of control rats, rats fed a cafeteria or a commercial HF diet and rats fed a control diet after the intake of a cafeteria diet (post-cafeteria model). Cafeteria diet intake, which resulted in important overweight and related complications, altered the expressions of most of the studied genes in PBMC, evidencing the development of an obesogenic profile. Commercial HF diet, which produced metabolic alterations but in the absence of noticeably increased body weight, also altered PBMC gene expression, inducing a similar regulatory pattern as that observed for the cafeteria diet. Regulation of carnitine palmitoyltransferase I (Cpt1a) mRNA expression was of special interest; its expression reflected metabolic alterations related to the intake of both obesogenic diets (independently of increased body weight) even at an early stage as well as metabolic recovery in post-cafeteria animals. Thus, PBMC constitute an important source of biomarkers that reflect the increased adiposity and metabolic deregulation associated with the intake of HF diets. In particular, we propose an analysis of Cpt1a expression as a good biomarker to detect the early metabolic alterations caused by the consumption of hyperlipidic diets, and also as a marker of metabolic recovery associated to weight loss. PMID:27080153

  3. Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats.

    PubMed

    Kim, Yonwook J; Bi, Sheng

    2016-01-15

    Neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) plays an important role in the regulation of energy balance. While DMH NPY overexpression causes hyperphagia and obesity in rats, knockdown of NPY in the DMH via adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) ameliorates these alterations. Whether this knockdown has a therapeutic effect on obesity and glycemic disorder has yet to be determined. The present study sought to test this potential using a rat model of high-fat diet (HFD)-induced obesity and insulin resistance, mimicking human obesity with impaired glucose homeostasis. Rats had ad libitum access to rodent regular chow (RC) or HFD. Six weeks later, an oral glucose tolerance test (OGTT) was performed for verifying HFD-induced glucose intolerance. After verification, obese rats received bilateral DMH injections of AAVshNPY or the control vector AAVshCTL, and OGTT and insulin tolerance test (ITT) were performed at 16 and 18 wk after viral injection (23 and 25 wk on HFD), respectively. Rats were killed at 26 wk on HFD. We found that AAVshCTL rats on HFD remained hyperphagic, obese, glucose intolerant, and insulin resistant relative to lean control RC-fed rats receiving DMH injection of AAVshCTL, whereas these alterations were reversed in NPY knockdown rats fed a HFD. NPY knockdown rats exhibited normal food intake, body weight, glucose tolerance, and insulin sensitivity, as seen in lean control rats. Together, these results demonstrate a therapeutic action of DMH NPY knockdown against obesity and impaired glucose homeostasis in rats, providing a potential target for the treatment of obesity and diabetes. PMID:26561644

  4. Lipolysis stimulating peptides of potato protein hydrolysate effectively suppresses high-fat-diet-induced hepatocyte apoptosis and fibrosis in aging rats

    PubMed Central

    Chiang, Wen-Dee; Huang, Chih Yang; Paul, Catherine Reena; Lee, Zong-Yan; Lin, Wan-Teng

    2016-01-01

    Background Non-alcoholic fatty liver disease (NAFLD) is one of the most common outcomes of obesity and is characterized by the accumulation of triglycerides, increased tissue apoptosis, and fibrosis. NAFLD is more common among elderly than in younger age groups, and it causes serious hepatic complications. Objective In this study, alcalase treatment derived potato protein hydrolysate (APPH) with lipolysis-stimulating property has been evaluated for its efficiency to provide hepato-protection in a high-fat-diet (HFD)-fed aging rats. Design Twenty-four-month-old SD rats were randomly divided into six groups (n=8): aged rats fed with standard chow, HFD-induced aged obese rats, HFD with low-dose (15 mg/kg/day) APPH treatment, HFD with moderate (45 mg/kg/day) APPH treatment, HFD with high (75 mg/kg/day) APPH treatment, and HFD with probucol. Results APPH was found to reduce the NAFLD-related effects in rat livers induced by HFD and all of the HFD-fed rats exhibited heavier body weight than those with control chow diet. However, the HFD-induced hepatic fat accumulation was effectively attenuated in rats administered with low (15 mg/kg/day), moderate (45 mg/kg/day), and high (75 mg/kg/day) doses of APPH. APPH oral administration also suppressed the hepatic apoptosis- and fibrosis-related proteins induced by HFD. Conclusions Our results thus indicate that APPH potentially attenuates hepatic lipid accumulation and anti-apoptosis and fibrosis effects in HFD-induced rats. APPH may have therapeutic potential in the amelioration of NAFLD liver damage. PMID:27415158

  5. Brain-specific natriuretic peptide receptor-B deletion attenuates high-fat diet-induced visceral and hepatic lipid deposition in mice.

    PubMed

    Yamashita, Yui; Yamada-Goto, Nobuko; Katsuura, Goro; Ochi, Yukari; Kanai, Yugo; Miyazaki, Yuri; Kuwahara, Koichiro; Kanamoto, Naotetsu; Miura, Masako; Yasoda, Akihiro; Ohinata, Kousaku; Inagaki, Nobuya; Nakao, Kazuwa

    2016-07-01

    C-type natriuretic peptide (CNP) and its receptor, natriuretic peptide receptor-B (NPR-B), are abundantly distributed in the hypothalamus. To explore the role of central CNP/NPR-B signaling in energy regulation, we generated mice with brain-specific NPR-B deletion (BND mice) by crossing Nestin-Cre transgenic mice and mice with a loxP-flanked NPR-B locus. Brain-specific NPR-B deletion prevented body weight gain induced by a high-fat diet (HFD), and the mesenteric fat and liver weights were significantly decreased in BND mice fed an HFD. The decreased liver weight in BND mice was attributed to decreased lipid accumulation in the liver, which was confirmed by histologic findings and lipid content. Gene expression analysis revealed a significant decrease in the mRNA expression levels of CD36, Fsp27, and Mogat1 in the liver of BND mice, and uncoupling protein 2 mRNA expression was significantly lower in the mesenteric fat of BND mice fed an HFD than in that of control mice. This difference was not observed in the epididymal or subcutaneous fat. Although previous studies reported that CNP/NPR-B signaling inhibits SNS activity in rodents, SNS is unlikely to be the underlying mechanism of the metabolic phenotype observed in BND mice. Taken together, CNP/NPR-B signaling in the brain could be a central factor that regulates visceral lipid accumulation and hepatic steatosis under HFD conditions. Further analyses of the precise mechanisms will enhance our understanding of the contribution of the CNP/NPR-B system to energy regulation. PMID:27020246

  6. Maternal conjugated linoleic acid supplementation reverses high-fat diet-induced skeletal muscle atrophy and inflammation in adult male rat offspring.

    PubMed

    Pileggi, C A; Segovia, S A; Markworth, J F; Gray, C; Zhang, X D; Milan, A M; Mitchell, C J; Barnett, M P G; Roy, N C; Vickers, M H; Reynolds, C M; Cameron-Smith, D

    2016-03-01

    A high-saturated-fat diet (HFD) during pregnancy and lactation leads to metabolic disorders in offspring concomitant with increased adiposity and a proinflammatory phenotype in later life. During the fetal period, the impact of maternal diet on skeletal muscle development is poorly described, despite this tissue exerting a major influence on life-long metabolic health. This study investigated the effect of a maternal HFD on skeletal muscle anabolic, catabolic, and inflammatory signaling in adult rat offspring. Furthermore, the actions of maternal-supplemented conjugated linoleic acid (CLA) on these measures of muscle phenotype were investigated. A purified control diet (CD; 10% kcal fat), a CD supplemented with CLA (CLA; 10% kcal fat, 1% total fat as CLA), a high-fat (HFD; 45% kcal fat from lard), or a HFD supplemented with CLA (HFCLA; 45% kcal fat from lard, 1% total fat as CLA) was fed ad libitum to female Sprague-Dawley rats for 10 days before mating and throughout gestation and lactation. Male offspring received a standard chow diet from weaning, and the gastrocnemius was collected for analysis at day 150. Offspring from HF and HFCLA mothers displayed lower muscular protein content accompanied by elevated monocyte chemotactic protein-1, IL-6, and IL-1β concentrations. Phosphorylation of NF-κBp65 (Ser(536)) and expression of the catabolic E3 ligase muscle ring finger 1 (MuRF1) were increased in HF offspring, an effect reversed by maternal CLA supplementation. The present study demonstrates the importance of early life interventions to ameliorate the negative effects of poor maternal diet on offspring skeletal muscle development. PMID:26632603

  7. Time-course metabolic changes in high-fat diet-induced obesity rats: A pilot study using hyperpolarized (13)C dynamic MRS.

    PubMed

    Kim, Gwang-Won; Ahn, Kyu-Youn; Kim, Yun-Hyeon; Jeong, Gwang-Woo

    2016-10-01

    The purpose of this study was to investigate the time-course metabolic changes based on hyperpolarized (13)C magnetic resonance spectroscopy (MRS) in high-fat diet (HFD)-induced obesity rats and the correlation between metabolic and serum enzyme levels. Sprague-Dawley rats were fed either HFD (60% fat) or normal diet (10% fat) for 6weeks. A HyperSense DNP was used to hyperpolarize [1-(13)C] pyruvic acid and the hyperpolarized (13)C MRS was examined every 2weeks in the course of 6weeks using a 3T GE MR750 scanner. The body weight of HFD-induced obese rats was significantly increased compared to normal rats at the 6th week after the onset of feeding (p=0.05). Simultaneously, the HFD-induced obese rats showed significantly increased levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and low-density lipoprotein (LDL)-cholesterol compared to normal rats (p≤0.05). In the dynamic (13)C MR spectra acquired at the 6th week, the obese rats showed significantly increased ratios of [1-(13)C] lactate/[1-(13)C] pyruvate and [1-(13)C] alanine/[1-(13)C] pyruvate (p=0.05). The (13)C spectral outcomes are positively correlated with the enzyme levels of ALT and LDH in the HFD-induced obesity. The [1-(13)C] lactate and [1-(13)C] alanine are potentially considered as noninvasive biomarkers for the HFD-induced obesity. PMID:27374624

  8. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle

    PubMed Central

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats. PMID:26064395

  9. Maté tea inhibits in vitro pancreatic lipase activity and has hypolipidemic effect on high-fat diet-induced obese mice.

    PubMed

    Martins, Fernanda; Noso, Tatiana M; Porto, Viviane B; Curiel, Alline; Gambero, Alessandra; Bastos, Deborah H M; Ribeiro, Marcelo L; Carvalho, Patrícia de O

    2010-01-01

    The inhibitory effects of maté tea (MT), a beverage produced with leaves from Ilex paraguariensis, in vitro lipase activity and on obesity in obese mice models were examined. For the in vitro experiment, porcine and human pancreatic lipase (PL) activities were determined by measuring the rate of release of oleic acid from hydrolysis of olive oil emulsified with taurocholate, phospholipids, gum arabic, or polyvinyl alcohol. For the in vivo experiments, animals were fed with a standard diet (SD, n = 10) or high-fat diet (HFD, n = 30) for 16 weeks. After the first 8 weeks on the HFD, the animals were treated with 1 and 2 g/kg of body weight of MT. The time course of the body weight and obesity-related biochemical parameters were evaluated. The results showed that MT inhibited both porcine and human PL (half-maximal inhibitory concentration = 1.5 mg MT/ml) and induced a strong inhibition of the porcine lipase activity in the hydrolysis of substrate emulsified with taurocholate + phosphatidylcholine (PC) (83 +/- 3.8%) or PC alone (62 +/- 4.3%). MT suppressed the increases in body weight (P < 0.05) and decreased the serum triglycerides and low-density lipoprotein (LDL)-cholesterol concentrations at both doses (from 190.3 +/- 5.7 to 135.0 +/- 8.9 mg/dl, from 189.1 +/- 7.3 to 129.3 +/- 17.6 mg/dl; P < 0.05, respectively) after they had been increased by the HFD. The liver lipid content was also decreased by the diet containing MT (from 132.6 +/- 3.9 to 95.6 +/- 6.1 mg/g of tissue; P < 0.05). These results suggest that MT could be a potentially therapeutic alternative in the treatment of obesity caused by a HFD. PMID:19543216

  10. Effect of sardine proteins on hyperglycaemia, hyperlipidaemia and lecithin:cholesterol acyltransferase activity, in high-fat diet-induced type 2 diabetic rats.

    PubMed

    Benaicheta, Nora; Labbaci, Fatima Z; Bouchenak, Malika; Boukortt, Farida O

    2016-01-14

    Type 2 diabetes (T2D) is a major risk factor of CVD. The effects of purified sardine proteins (SP) were examined on glycaemia, insulin sensitivity and reverse cholesterol transport in T2D rats. Rats fed a high-fat diet (HFD) for 5 weeks, and injected with a low dose of streptozotocin, were used. The diabetic rats were divided into four groups, and they were fed casein (CAS) or SP combined with 30 or 5% lipids, for 4 weeks. HFD-induced hyperglycaemia, insulin resistance and hyperlipidaemia in rats fed HFD, regardless of the consumed protein. In contrast, these parameters lowered in rats fed SP combined with 5 or 30% lipids, and serum insulin values reduced in SP v. CAS. HFD significantly increased total cholesterol and TAG concentrations in the liver and serum, whereas these parameters decreased with SP, regardless of lipid intake. Faecal cholesterol excretion was higher with SP v. CAS, combined with 30 or 5% lipids. Lecithin:cholesterol acyltransferase (LCAT) activity and HDL3-phospholipids (PL) were higher in CAS-HF than in CAS, whereas HDL2-cholesteryl esters (CE) were lower. Otherwise, LCAT activity and HDL2-CE were higher in the SP group than in the CAS group, whereas HDL3-PL and HDL3-unesterified cholesterol were lower. Moreover, LCAT activity lowered in the SP-HF group than in the CAS-HF group, when HDL2-CE was higher. In conclusion, these results indicate the potential effects of SP to improve glycaemia, insulin sensitivity and reverse cholesterol transport, in T2D rats. PMID:26507559

  11. PPARγ Ligands Switched High Fat Diet-Induced Macrophage M2b Polarization toward M2a Thereby Improving Intestinal Candida Elimination

    PubMed Central

    Olagnier, David; Bernad, José; Perez, Laurence; Burcelin, Rémy; Valentin, Alexis; Auwerx, Johan; Pipy, Bernard; Coste, Agnès

    2010-01-01

    Obesity is associated with a chronic low-grade inflammation that predisposes to insulin resistance and the development of type 2 diabetes. In this metabolic context, gastrointestinal (GI) candidiasis is common. We recently demonstrated that the PPARγ ligand rosiglitazone promotes the clearance of Candida albicans through the activation of alternative M2 macrophage polarization. Here, we evaluated the impact of high fat diet (HFD)-induced obesity and the effect of rosiglitazone (PPARγ ligand) or WY14643 (PPARα ligand) both on the phenotypic M1/M2 polarization of peritoneal and cecal tissue macrophages and on the outcome of GI candidiasis. We demonstrated that the peritoneal macrophages and the cell types present in the cecal tissue from HF fed mice present a M2b polarization (TNF-αhigh, IL-10high, MR, Dectin-1). Interestingly, rosiglitazone induces a phenotypic M2b-to-M2a (TNF-αlow, IL-10low, MRhigh, Dectin-1high) switch of peritoneal macrophages and of the cells present in the cecal tissue. The incapacity of WY14643 to switch this polarization toward M2a state, strongly suggests the specific involvement of PPARγ in this mechanism. We showed that in insulin resistant mice, M2b polarization of macrophages present on the site of infection is associated with an increased susceptibility to GI candidiasis, whereas M2a polarization after rosiglitazone treatment favours the GI fungal elimination independently of reduced blood glucose. In conclusion, our data demonstrate a dual benefit of PPARγ ligands because they promote mucosal defence mechanisms against GI candidiasis through M2a macrophage polarization while regulating blood glucose level. PMID:20877467

  12. Combination of deep sea water and Sesamum indicum leaf extract prevents high-fat diet-induced obesity through AMPK activation in visceral adipose tissue

    PubMed Central

    YUAN, HAIDAN; CHUNG, SUNGHYUN; MA, QIANQIAN; YE, LI; PIAO, GUANGCHUN

    2016-01-01

    The aim of the present study was to evaluate the protective effects of a combination of deep sea water (DSW) and Sesamum indicum leaf extract (SIE) against high-fat diet (HFD)-induced obesity and investigate its molecular mechanisms in adipose tissue. ICR mice were randomly divided into three groups: HFD control (HFC), DSW and DSW + 125 mg/kg SIE (DSS) groups. The mice in the HFC group had free access to drinking water while those in the DSW and DSS groups had free access to DSW. The mice in the DSS group were treated with SIE once per day for 8 weeks. The mice in all three groups were allowed to freely access a HFD. Compared with the HFC group, the DSS group showed lower body weight gain and serum levels of glucose, triglycerides and leptin. Histological analyses of the epididymal white, retroperitoneal white and scapular brown adipose tissue of mice in the DSS group revealed that the adipocytes were markedly decreased in size compared with those in the HFC group. Moreover, DSS significantly increased the levels of phosphorylated adenosine monophosphate-activated protein kinase (AMPK) and its substrate, acetyl-CoA carboxylase (ACC) in mice epididymal adipose tissues. Furthermore, DSS upregulated the expression levels of lipolysis-associated mRNA, specifically peroxisome proliferator-activated receptor-α (PPAR-α) and cluster of differentiation 36 (CD36), and energy expenditure-associated mRNA, namely uncoupling protein 2 (UCP2) and carnitine palmitoyltransferase-1 (CPT1) in the epididymal adipose tissues. By contrast, DSS suppressed the expression of the lipogenesis-related gene sterol regulatory element-binding protein-1 (SREBP1) at the mRNA level. These results suggest that DSS is effective for suppressing body weight gain and enhancing the lipid profile. PMID:26889265

  13. Magnolia bioactive constituent 4-O-methylhonokiol prevents the impairment of cardiac insulin signaling and the cardiac pathogenesis in high-fat diet-induced obese mice.

    PubMed

    Zhang, Zhiguo; Chen, Jing; Zhou, Shanshan; Wang, Shudong; Cai, Xiaohong; Conklin, Daniel J; Kim, Ki-Soo; Kim, Ki Ho; Tan, Yi; Zheng, Yang; Kim, Young Heui; Cai, Lu

    2015-01-01

    In obesity, cardiac insulin resistance is a putative cause of cardiac hypertrophy and dysfunction. In our previous study, we observed that Magnolia extract BL153 attenuated high-fat-diet (HFD)-induced cardiac pathogenic changes. In this study, we further investigated the protective effects of the BL153 bioactive constituent, 4-O-methylhonokiol (MH), against HFD-induced cardiac pathogenesis and its possible mechanisms. C57BL/6J mice were fed a normal diet or a HFD with gavage administration of vehicle, BL153, or MH (low or high dose) daily for 24 weeks. Treatment with MH attenuated HFD-induced obesity, as evidenced by body weight gain, and cardiac pathogenesis, as assessed by the heart weight and echocardiography. Mechanistically, MH treatment significantly reduced HFD-induced impairment of cardiac insulin signaling by preferentially augmenting Akt2 signaling. MH also inhibited cardiac expression of the inflammatory factors tumor necrosis factor-α and plasminogen activator inhibitor-1 and increased the phosphorylation of nuclear factor erythroid-derived 2-like 2 (Nrf2) as well as the expression of a Nrf2 downstream target gene heme oxygenase-1. The increased Nrf2 signaling was associated with decreased oxidative stress and damage, as reflected by lowered malondialdehyde and 3-nitrotyrosine levels. Furthermore, MH reduced HFD-induced cardiac lipid accumulation along with lowering expression of cardiac fatty acid translocase/CD36 protein. These results suggest that MH, a bioactive constituent of Magnolia, prevents HFD-induced cardiac pathogenesis by attenuating the impairment of cardiac insulin signaling, perhaps via activation of Nrf2 and Akt2 signaling to attenuate CD36-mediated lipid accumulation and lipotoxicity. PMID:26157343

  14. Piperidine alkaloids from Piper retrofractum Vahl. protect against high-fat diet-induced obesity by regulating lipid metabolism and activating AMP-activated protein kinase.

    PubMed

    Kim, Kyung Jin; Lee, Myoung-Su; Jo, Keunae; Hwang, Jae-Kwan

    2011-07-22

    The fruits of Piper retrofractum Vahl. have been used for their anti-flatulent, expectorant, antitussive, antifungal, and appetizing properties in traditional medicine, and they are reported to possess gastroprotective and cholesterol-lowering properties. However, their anti-obesity activity remains unexplored. The present study was conducted to isolate the anti-obesity constituents from P. retrofractum Vahl. and evaluate their effects in high-fat diet (HFD)-induced obese mice. Piperidine alkaloids from P. retrofractum Vahl. (PRPAs), including piperine, pipernonaline, and dehydropipernonaline, were isolated as the anti-obesity constituents through a peroxisome proliferator-activated receptor δ (PPARδ) transactivation assay. The molecular mechanism was investigated in 3T3-L1 adipocytes and L6 myocytes. PRPA treatment activated AMP-activated protein kinase (AMPK) signaling and PPARδ protein and also regulated the expression of lipid metabolism-related proteins. In the animal model, oral PRPA administration (50, 100, or 300mg/kg/day for 8weeks) significantly reduced HFD-induced body weight gain without altering the amount of food intake. Fat pad mass was reduced in the PRPA treatment groups, as evidenced by reduced adipocyte size. In addition, elevated serum levels of total cholesterol, low-density lipoprotein cholesterol, total lipid, leptin, and lipase were suppressed by PRPA treatment. PRPA also protected against the development of nonalcoholic fatty liver by decreasing hepatic triglyceride accumulation. Consistent with the in vitro results, PRPA activated AMPK signaling and altered the expression of lipid metabolism-related proteins in liver and skeletal muscle. Taken together, these findings demonstrate that PRPAs attenuate HFD-induced obesity by activating AMPK and PPARδ, and regulate lipid metabolism, suggesting their potential anti-obesity effects. PMID:21741367

  15. Chronic administration of recombinant IL-6 upregulates lipogenic enzyme expression and aggravates high-fat-diet-induced steatosis in IL-6-deficient mice

    PubMed Central

    Vida, Margarita; Gavito, Ana Luisa; Pavón, Francisco Javier; Bautista, Dolores; Serrano, Antonia; Suarez, Juan; Arrabal, Sergio; Decara, Juan; Romero-Cuevas, Miguel; Rodríguez de Fonseca, Fernando; Baixeras, Elena

    2015-01-01

    ABSTRACT Interleukin-6 (IL-6) has emerged as an important mediator of fatty acid metabolism with paradoxical effects in the liver. Administration of IL-6 has been reported to confer protection against steatosis, but plasma and tissue IL-6 concentrations are elevated in chronic liver diseases, including fatty liver diseases associated with obesity and alcoholic ingestion. In this study, we further investigated the role of IL-6 on steatosis induced through a high-fat diet (HFD) in wild-type (WT) and IL-6-deficient (IL-6−/−) mice. Additionally, HFD-fed IL-6−/− mice were also chronically treated with recombinant IL-6 (rIL-6). Obesity in WT mice fed a HFD associated with elevated serum IL-6 levels, fatty liver, upregulation of carnitine palmitoyltransferase 1 (CPT1) and signal transducer and activator of transcription-3 (STAT3), increased AMP kinase phosphorylation (p-AMPK), and downregulation of the hepatic lipogenic enzymes fatty acid synthase (FAS) and stearoyl-CoA desaturase 1 (SCD1). The HFD-fed IL-6−/− mice showed severe steatosis, no changes in CPT1 levels or AMPK activity, no increase in STAT3 amounts, inactivated STAT3, and marked downregulation of the expression of acetyl-CoA carboxylase (ACCα/β), FAS and SCD1. The IL-6 chronic replacement in HFD-fed IL-6−/− mice restored hepatic STAT3 and AMPK activation but also increased the expression of the lipogenic enzymes ACCα/β, FAS and SCD1. Furthermore, rIL-6 administration was associated with aggravated steatosis and elevated fat content in the liver. We conclude that, in the context of HFD-induced obesity, the administration of rIL-6 might contribute to the aggravation of fatty liver disease through increasing lipogenesis. PMID:26035386

  16. Zinc deficiency exacerbates while zinc supplement attenuates cardiac hypertrophy in high-fat diet-induced obese mice through modulating p38 MAPK-dependent signaling.

    PubMed

    Wang, Shudong; Luo, Manyu; Zhang, Zhiguo; Gu, Junlian; Chen, Jing; Payne, Kristen McClung; Tan, Yi; Wang, Yuehui; Yin, Xia; Zhang, Xiang; Liu, Gilbert C; Wintergerst, Kupper; Liu, Quan; Zheng, Yang; Cai, Lu

    2016-09-01

    Childhood obesity often leads to cardiovascular diseases, such as obesity-related cardiac hypertrophy (ORCH), in adulthood, due to chronic cardiac inflammation. Zinc is structurally and functionally essential for many transcription factors; however, its role in ORCH and underlying mechanism(s) remain unclear and were explored here in mice with obesity induced with high-fat diet (HFD). Four week old mice were fed on either HFD (60%kcal fat) or normal diet (ND, 10% kcal fat) for 3 or 6 months, respectively. Either diet contained one of three different zinc quantities: deficiency (ZD, 10mg zinc per 4057kcal), normal (ZN, 30mg zinc per 4057kcal) or supplement (ZS, 90mg zinc per 4057kcal). HFD induced a time-dependent obesity and ORCH, which was accompanied by increased cardiac inflammation and p38 MAPK activation. These effects were worsened by ZD in HFD/ZD mice and attenuated by ZS in HFD/ZS group, respectively. Also, administration of a p38 MAPK specific inhibitor in HFD mice for 3 months did not affect HFD-induced obesity, but completely abolished HFD-induced, and zinc deficiency-worsened, ORCH and cardiac inflammation. In vitro exposure of adult cardiomyocytes to palmitate induced cell hypertrophy accompanied by increased p38 MAPK activation, which was heightened by zinc depletion with its chelator TPEN. Inhibition of p38 MAPK with its specific siRNA also prevented the effects of palmitate on cardiomyocytes. These findings demonstrate that ZS alleviates but ZD heightens cardiac hypertrophy in HFD-induced obese mice through suppressing p38 MAPK-dependent cardiac inflammatory and hypertrophic pathways. PMID:27346292

  17. Effect of Stay-Green Wheat, a Novel Variety of Wheat in China, on Glucose and Lipid Metabolism in High-Fat Diet Induced Type 2 Diabetic Rats

    PubMed Central

    Ji, Jinshan; Zhang, Chao; Luo, Xiaoqin; Wang, Li; Zhang, Ruijuan; Wang, Zhenlin; Fan, Daidi; Yang, Haixia; Deng, Jianjun

    2015-01-01

    The use of natural hypoglycemic compounds is important in preventing and managing Type 2 diabetes mellitus (T2DM). Forty male Sprague-Dawley rats weighing 150–180 g were divided into four groups to investigate the effects of the compounds in stay-green wheat (SGW), a novel variety of wheat in China, on T2DM rats. The control group (NDC) was fed with a standard diet, while T2DM was induced in the rats belonging to the other three groups by a high-fat diet followed by a streptozotocin (STZ) injection. The T2DM rats were further divided into a T2DM control group (DC), which was fed with the normal diet containing 50% common wheat flour, a high dose SGW group (HGW) fed with a diet containing 50% SGW flour, and a low dose SGW group (LGW) fed with a diet containing 25% SGW flour and 25% common wheat flour. Our results showed that SGW contained cereal antioxidants, particularly high in flavonoids and anthocyanins (46.14 ± 1.80 mg GAE/100 g DW and 1.73 ± 0.14 mg CGE/100 g DW, respectively). Furthermore, SGW exhibited a strong antioxidant activity in vitro (30.33 ± 2.66 μg TE/g DW, p < 0.01). Administration of the SGW at a high and low dose showed significant down-regulatory effects on fasting blood glucose (decreasing by 11.3% and 7.0%, respectively), insulin levels (decreasing by 12.3% and 9.7%, respectively), and lipid status (decreasing by 9.1% and 7.5%, respectively) in T2DM rats (p < 0.01). In addition, the T2DM groups treated with SGW at a high and low dose showed a significant increase in the blood superoxide dismutase (1.17 fold and 1.15 fold, respectively) and glutathione peroxidase activities (1.37 fold and 1.30 fold, respectively) compared with the DC group (p < 0.01). The normalized impaired antioxidant status of the pancreatic islet and of the liver compared with the DC group was also significantly increased. Our results indicated that SGW components exerting a glycemic control and a serum lipid regulation effect may be due to their free radical

  18. Blueberry Peel Extracts Inhibit Adipogenesis in 3T3-L1 Cells and Reduce High-Fat Diet-Induced Obesity

    PubMed Central

    Jang, Sun-Hee; Lee, Soo-Jung; Ko, Yeoung-Gyu; Kim, Gon-Sup; Cho, Jae-Hyeon

    2013-01-01

    This study examined the anti-obesity effect and mechanism of action of blueberry peel extracts (BPE) in 3T3-L1 cells and high-fat diet (HFD)-induced obese rats. The levels of lipid accumulation were measured, along with the changes in the expression of genes and proteins associated with adipocyte differentiation in 3T3-L1 cells. Evidenced by Oil-red O staining and triglyceride assay, BPE dose-dependently inhibited lipid accumulation at concentrations of 0, 50, and 200 µg/ml. BPE decreased the expression of the key adipocyte differentiation regulator C/EBPβ, as well as the C/EBPα and PPARγ genes, during the differentiation of preadipocytes into adipocytes. Moreover, BPE down-regulated adipocyte-specific genes such as aP2 and FAS compared with control adipocytes. The specific mechanism mediating the effects of BP revealed that insulin-stimulated phosphorylation of Akt was strongly decreased, and its downstream substrate, phospho-GSK3β, was downregulated by BPE treatment in 3T3-L1 cells. Together, these data indicated that BP exerted anti-adipogenic activity by inhibiting the expression of PPARγ and C/EBPβ and the Akt signaling pathway in 3T3-L1 adipocytes. Next, we investigated whether BP extracts attenuated HFD-induced obesity in rats. Oral administration of BPE reduced HFD-induced body weight gain significantly without affecting food intake. The epididymal or perirenal adipose tissue weights were lower in rats on an HFD plus BPE compared with the tissue weights of HFD-induced obese rats. Total cholesterol and triglyceride levels in the rats fed BPE were modestly reduced, and the HDL-cholesterol level was significantly increased in HFD plus BP-fed rats compared with those of HFD-fed rats. Taken together, these results demonstrated an inhibitory effect of BP on adipogenesis through the down-regulation of C/EBPβ, C/EBPα, and PPARγ and the reduction of the phospho-Akt adipogenic factor in 3T3-L1 cells. Moreover, BPE reduced body weight gain and inhibited fat

  19. Testosterone and farnesoid X receptor agonist INT-747 counteract high fat diet-induced bladder alterations in a rabbit model of metabolic syndrome.

    PubMed

    Morelli, Annamaria; Comeglio, Paolo; Filippi, Sandra; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Yehiely-Cohen, Ravit; Maneschi, Elena; Gacci, Mauro; Carini, Marco; Adorini, Luciano; Vannelli, Gabriella B; Maggi, Mario

    2012-10-01

    In the male, metabolic syndrome (MetS) is associated to an increased risk of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). A recently established rabbit model of high fat diet (HFD)-induced MetS showed hypogonadism and the presence of prostate gland alterations, including inflammation, hypoxia and fibrosis. The present study investigated whether HFD-induced MetS might also alter bladder structure and function. Testosterone and the farnesoid X receptor (FXR) agonist INT-747, were evaluated for possible effects on HFD bladder. MetS rabbits develop bladder alterations, including fibrosis (reduced muscle/fiber ratio), hypoxia [2-fold increase as compared to regular diet (RD) group], low-grade inflammation (increased leukocyte infiltration and inflammatory markers) and RhoA/ROCK hyperactivity. Bladder strips from HFD rabbits, pre-contracted with carbachol, showed an overactive response to the selective ROCK inhibitor Y-27632. All these HFD-induced bladder alterations were partially blunted by testosterone and almost completely reverted by INT-747. Both treatments prevented some MetS features (glucose intolerance and visceral fat increase), thus suggesting that their effects on bladder could be ascribed to an improvement of the metabolic and/or hypogonadal state. However, a pathogenetic role for hypogonadism has been ruled out as GnRH analog-induced hypogonadal rabbits, fed a regular diet, did not show any detectable bladder alterations. In addition, INT-747 did not revert the MetS-induced hypogonadal state. FXR mRNA was highly expressed in rabbit bladder and positively associated with visceral fat increase. A direct effect of INT-747 on bladder smooth muscle was further suggested by inhibition of RhoA/ROCK-mediated activity by in vitro experiments on isolated cells. In conclusion, HFD-related MetS features are associated to bladder derangements, which are ameliorated by testosterone or INT-747 administration. INT-747 showed the most marked

  20. Differential effects of cobalt and mercury on lipid metabolism in the white adipose tissue of high-fat diet-induced obesity mice

    SciTech Connect

    Kawakami, Takashige Hanao, Norihide; Nishiyama, Kaori; Kadota, Yoshito; Inoue, Masahisa; Sato, Masao; Suzuki, Shinya

    2012-01-01

    Metals and metalloid species are involved in homeostasis in energy systems such as glucose metabolism. Enlarged adipocytes are one of the most important causes of obesity-associated diseases. In this study, we studied the possibility that various metals, namely, CoCl{sub 2}, HgCl{sub 2}, NaAsO{sub 2} and MnCl{sub 2} pose risk to or have beneficial effects on white adipose tissue (WAT). Exposure to the four metals resulted in decreases in WAT weight and the size of enlarged adipocytes in mice fed a high-fat diet (HFD) without changes in liver weight, suggesting that the size and function of adipocytes are sensitive to metals. Repeated administration of CoCl{sub 2} significantly increased serum leptin, adiponectin and high-density lipoprotein (HDL) cholesterol levels and normalized glucose level and adipose cell size in mice fed HFD. In contrast, HgCl{sub 2} treatment significantly decreased serum leptin level with the down-regulation of leptin mRNA expression in WAT and a reduction in adipocyte size. Next, we tried to investigate possible factors that affect adipocyte size. Repeated exposure to HgCl{sub 2} significantly decreased the expression levels of factors upon the regulation of energy such as the PPARα and PPARγ mRNA expression levels in adipocytes, whereas CoCl{sub 2} had little effect on those genes expressions compared with that in the case of the mice fed HFD with a vehicle. In addition, repeated administration of CoCl{sub 2} enhanced AMPK activation in a dose-dependent manner in the liver, skeletal muscle and WAT; HgCl{sub 2} treatment also enhanced AMPK activation in the liver. Thus, both Co and Hg reduced WAT weight and the size of enlarged adipocytes, possibly mediated by AMKP activation in the mice fed HFD. However, inorganic cobalt may have a preventive role in obesity-related diseases through increased leptin, adiponectin and HDL-cholesterol levels, whereas inorganic mercury may accelerate the development of such diseases. These results may lead

  1. Adipogenic changes of hepatocytes in a high-fat diet-induced fatty liver mice model and non-alcoholic fatty liver disease patients.

    PubMed

    Pan, Xiaoli; Wang, Pei; Luo, Jinzhuo; Wang, Zhijun; Song, Yuhu; Ye, Jin; Hou, Xiaohua

    2015-04-01

    Non-alcoholic fatty liver disease (NAFLD) is characterized by steatosis associated with liver inflammation. As NAFLD progresses, triglycerides increase within hepatocytes, causing typical vacuoles that resemble adipocytes. However, whether these morphological changes in hepatocytes indicate potential functional changes is unclear. C57BL/6J mice were fed a high-fat diet (HFD) containing 42% fat. Markers for adipocytes in the liver were measured using real-time PCR, Western blot, and double immunofluorescent labeling. Cytokines in cell culture supernatants were quantified with ELISA. To determine the macrophage phenotype, hepatic classical M1 markers and alternative M2 markers were analyzed. After a 24-week feeding period, adipocyte markers aP2 and PPARγ increased at both the mRNA and protein level in the liver of HFD-fed mice. FITC-labeled aP2 and rhodamine-labeled albumin were both stained in the cytoplasm of steatotic hepatocytes as observed under confocal laser scanning microscopy. Cell membrane-bound E-cadherin and albumin expression were reduced in steatotic hepatocytes compared to controls. However, hepatic adiponectin and adiponectin receptor-2 expression decreased with upregulation of hepatic CD36, suggesting impaired adiponectin activity in livers of HFD-fed mice. Moreover, steatotic primary hepatocytes not only released pro-inflammatory cytokines such as TNFα, MCP-1, IL-6, and IL-18, but also could activate macrophages when co-cultured in vitro. In vivo, hepatic expression of M1 genes such as iNOS and TNFα was markedly increased in HFD-fed mice. In contrast, hepatic expression of M2 genes such as Arg1 and CD206 was significantly reduced. Specifically, the ratio of TNFα to CD206 in HFD-fed mice was notably upregulated. Overexpression of adipocyte-specific genes in hepatocytes and their secretory function and epithelial phenotype impairment in NAFLD cause functional changes in steatotic hepatocytes aside from morphological changes. This suggests that

  2. High fat diet-induced modifications in membrane lipid and mitochondrial-membrane protein signatures precede the development of hepatic insulin resistance in mice

    PubMed Central

    Kahle, M.; Schäfer, A.; Seelig, A.; Schultheiß, J.; Wu, M.; Aichler, M.; Leonhardt, J.; Rathkolb, B.; Rozman, J.; Sarioglu, H.; Hauck, S.M.; Ueffing, M.; Wolf, E.; Kastenmueller, G.; Adamski, J.; Walch, A.; Hrabé de Angelis, M.; Neschen, S.

    2014-01-01

    Objective Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein signatures during high-fat diet (HF)-mediated development of hepatic insulin resistance. Methods We induced hepatosteatosis by feeding C3HeB/FeJ male mice an HF enriched with long-chain polyunsaturated C18:2n6 fatty acids for 7, 14, or 21 days. Longitudinal changes in hepatic insulin sensitivity were assessed via the euglycemic-hyperinsulinemic clamp, in membrane lipids via t-metabolomics- and membrane proteins via quantitative proteomics-analyses, and in hepatocyte morphology via electron microscopy. Data were compared to those of age- and litter-matched controls maintained on a low-fat diet. Results Excess long-chain polyunsaturated C18:2n6 intake for 7 days did not compromise hepatic insulin sensitivity, however, induced hepatosteatosis and modified major membrane lipid constituent signatures in liver, e.g. increased total unsaturated, long-chain fatty acid-containing acyl-carnitine or membrane-associated diacylglycerol moieties and decreased total short-chain acyl-carnitines, glycerophosphocholines, lysophosphatidylcholines, or sphingolipids. Hepatic insulin sensitivity tended to decrease within 14 days HF-exposure. Overt hepatic insulin resistance developed until day 21 of HF-intervention and was accompanied by morphological mitochondrial abnormalities and indications for oxidative stress in liver. HF-feeding progressively decreased the abundance of protein-components of all mitochondrial respiratory chain complexes, inner and outer mitochondrial membrane substrate transporters independent from the hepatocellular mitochondrial volume in liver. Conclusions We assume HF-induced modifications in membrane lipid

  3. Effect of polycan, a β-glucan originating from Aureobasidium, on a high-fat diet-induced hyperlipemic hamster model

    PubMed Central

    LIM, MEE-KYOUNG; KU, SAE-KWANG; CHOI, JAE-SUK; KIM, JOO-WAN

    2015-01-01

    The aim of the present study was to analyze the effect of polycan, a β-glucan originating from Aureobasidium, on high-fat diet (HFD)-induced hyperlipemia and hepatic damage. A total of 30 hamsters were divided into 6 groups based on their body weight following acclimatization: control, sham, simvastatin (SIMVA) and 3 Polycan groups. In the polycan groups, Polycan, at three concentrations (31.25, 62.5 and 125 mg/kg), was administered orally once a day for 56 days, in addition to the HFD. On the day of sacrifice, changes in the body weight, food consumption, liver weight and serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride and total cholesterol (T-CHOL) were observed, as well as changes to the liver and aorta (thoracic and abdominal) histopathology and histomorphometry. The results from the polycan groups were compared with a SIMVA 10 mg/kg oral treatment group, in addition to the sham and vehicle control groups. After the HFD-induced hyperlipidemic hamsters were administered Polycan, there was no significant change in their body weight and food consumption when compared with the hamsters in the vehicle control group. However, the serum levels of AST, ALT, triglyceride, T-CHOL and LDL were significantly reduced in a dose-dependent manner when compared with the vehicle control group (P<0.05). Furthermore, the levels of liver steatosis and arteriosclerosis in the abdominal and thoracic aorta were significantly decreased in a dose-dependent manner (P<0.01). In the SIMVA-treated group, body weight (P<0.05), the serum level of lipids (triglyceride, T-CHOL and LDL; P<0.01) and the level of arteriosclerosis (P<0.01) were significantly reduced when compared with the vehicle control group. However, liver weight and the serum levels of AST, ALT, and liver steatosis increased when compared with the vehicle control group. Based on these results, it was concluded that

  4. Exercise prevents high-fat diet-induced impairment of flexible memory expression in the water maze and modulates adult hippocampal neurogenesis in mice.

    PubMed

    Klein, C; Jonas, W; Iggena, D; Empl, L; Rivalan, M; Wiedmer, P; Spranger, J; Hellweg, R; Winter, Y; Steiner, B

    2016-05-01

    Obesity is currently one of the most serious threats to human health in the western civilization. A growing body of evidence suggests that obesity is associated with cognitive dysfunction. Physical exercise not only improves fitness but it has also been shown in human and animal studies to increase hippocampus-dependent learning and memory. High-fat diet (HFD)-induced obesity and physical exercise both modulate adult hippocampal neurogenesis. Adult neurogenesis has been demonstrated to play a role in hippocampus-dependent learning and memory, particularly flexible memory expression. Here, we investigated the effects of twelve weeks of HFD vs. control diet (CD) and voluntary physical activity (wheel running; -R) vs. inactivity (sedentary; -S) on hippocampal neurogenesis and spatial learning and flexible memory function in female C57Bl/6 mice assessed in the Morris water maze. HFD was initiated either in adolescent mice combined with long-term concurrent exercise (preventive approach) or in young adult mice with 14days of subsequent exercise (therapeutic approach). HFD resulted in impaired flexible memory expression only when initiated in adolescent (HFD-S) but not in young adult mice, which was successfully prevented by concurrent exercise (HFD-R). Histological analysis revealed a reduction of immature neurons in the hippocampus of the memory-impaired HFD-S mice of the preventive approach. Long-term physical exercise also led to accelerated spatial learning during the acquisition period, which was accompanied by increased numbers of newborn mature neurons (HFD-R and CD-R). Short-term exercise of 14days in the therapeutic group was not effective in improving spatial learning or memory. We show that (1) alterations in learning and flexible memory expression are accompanied by changes in the number of neuronal cells at different maturation stages; (2) these neuronal cells are in turn differently affected by HFD; (3) adolescent mice are specifically susceptible to the

  5. Syzygium aromaticum ethanol extract reduces high-fat diet-induced obesity in mice through downregulation of adipogenic and lipogenic gene expression

    PubMed Central

    JUNG, CHANG HWA; AHN, JIYUN; JEON, TAE-IL; KIM, TAE WAN; HA, TAE YOUL

    2012-01-01

    Numerous medicinal plants and their derivatives have been reported to prevent obesity and related diseases. Although Syzygium aromaticum has traditionally been used as an anodyne, carminative and anthelmintic in Asian countries, its potential in the prevention and treatment of obesity has not yet been explored. Therefore, the present study investigated the anti-obesity effect of S. aromaticum ethanol extract (SAE) both in vitro and in vivo. To evaluate the anti-obesity potential of SAE in vitro, the effect of SAE treatment on adipocyte differentiation in 3T3-L1 cells was investigated. To evaluate its potential in vivo, mice were assigned to three groups: a group fed the American Institute of Nutrition AIN-76A diet (normal group), an experimental group fed a high-fat diet (HFD group) and an experimental group fed an HFD supplemented with 0.5% (w/w) SAE (HFD + SAE group). After 9 weeks of feeding, the body weight; white adipose tissue (WAT) mass; serum triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, glucose, insulin and leptin; hepatic lipid accumulation; and levels of lipid metabolism-related genes in the liver and WAT were measured. In vitro investigation of the effect of SAE treatment on 3T3-L1 cells revealed that it had efficiently inhibited the conversion of cells into adipocytes in a dose-dependent manner. In vivo investigation revealed that SAE supplementation had significantly decreased HFD-induced increases in the body weight, liver weight, WAT mass, and serum TG, TC, lipid, glucose, insulin and leptin levels. Consistent with its effects on liver weight and WAT mass, SAE supplementation was found to have suppressed the expression of lipid metabolism-related proteins, including SREBP-1, FAS, CD36 and PPARγ in the liver and WAT, in addition to downregulating mRNA levels of transcription factors including Srebp and Pparg. SAE inhibits fat accumulation in HFD-fed mice via the suppression of transcription factors integral

  6. New Insights on the Maternal Diet Induced-Hypertension: Potential Role of the Phenotypic Plasticity and Sympathetic-Respiratory Overactivity

    PubMed Central

    Costa-Silva, João H.; de Brito-Alves, José L.; Barros, Monique Assis de V.; Nogueira, Viviane Oliveira; Paulino-Silva, Kássya M.; de Oliveira-Lira, Allan; Nobre, Isabele G.; Fragoso, Jéssica; Leandro, Carol G.

    2015-01-01

    Systemic arterial hypertension (SAH) is an important risk factor for cardiovascular disease and affects worldwide population. Current environment including life style coupled with genetic programming have been attributed to the rising incidence of hypertension. Besides, environmental conditions during perinatal development such as maternal malnutrition can program changes in the integration among renal, neural, and endocrine system leading to hypertension. This phenomenon is termed phenotypic plasticity and refers to the adjustment of a phenotype in response to environmental stimuli without genetic change, following a novel or unusual input during development. Human and animal studies indicate that fetal exposure to an adverse maternal environment may alter the renal morphology and physiology that contribute to the development of hypertension. Recently, it has been shown that the maternal protein restriction alter the central control of SAH by a mechanism that include respiratory dysfunction and enhanced sympathetic-respiratory coupling at early life, which may contribute to adult hypertension. This review will address the new insights on the maternal diet induced-hypertension that include the potential role of the phenotypic plasticity, specifically the perinatal protein malnutrition, and sympathetic-respiratory overactivity. PMID:26635631

  7. A Combination of Human Embryonic Stem Cell-Derived Pancreatic Endoderm Transplant with LDHA-Repressing miRNA Can Attenuate High-Fat Diet Induced Type II Diabetes in Mice

    PubMed Central

    Chen, Yunya; Wang, Xiujie; Shao, Xinyu

    2015-01-01

    Type II diabetes mellitus (T2D) is a chronic metabolic disorder that results from defects in both insulin secretion and insulin action. The deficit and dysfunction of insulin secreting β-cell are signature symptom for T2D. Additionally, in pancreatic β-cell, a small group of genes which are abundantly expressed in most other tissues are highly selectively repressed. Lactate dehydrogenase A (LDHA) is one of such genes. Upregulation of LDHA is found in both human T2D and rodent T2D models. In this study, we identified a LDHA-suppressing microRNA (hsa-miR-590-3p) and used it together with human embryonic stem cell (hESC) derived pancreatic endoderm (PE) transplantation into a high-fat diet induced T2D mouse model. The procedure significantly improved glucose metabolism and other symptoms of T2D. Our findings support the potential T2D treatment using the combination of microRNA and hESC-differentiated PE cells. PMID:26770982

  8. 5-HT2A/2C receptor and 5-HT transporter densities in mice prone or resistant to chronic high-fat diet-induced obesity: a quantitative autoradiography study.

    PubMed

    Huang, Xu-Feng; Huang, Xin; Han, Mei; Chen, Feng; Storlien, Len; Lawrence, Andrew J

    2004-08-27

    The present study examined the density of 5-HT2A/2C receptors and 5-HT transporters in the brains of chronic high-fat diet-induced obese (cDIO) and obese-resistant (cDR) mice. Thirty-five male mice were used in this study. Twenty-eight mice were fed with a high-fat diet (40% of calories from fat) for 6 weeks and then classified as the cDIO (n=8) or cDR (n=8) mice according to the highest and lowest body weight gainers. Seven mice were placed on a low-fat diet (LF: 10% of calories from fat) and were used as controls. After 20 weeks of feeding, the sum of epididymal, perirenal, omental and inguinal fat masses was 9.3+/-0.3 g in the cDIO group versus 3.1+/-0.5 g in the cDR (p<0.005) and 1.5+/-0.1 g in the LF (p<0.001) groups. Using quantitative autoradiography techniques, the binding site densities of 5-HT2A/2C receptors and 5-HT transporters were measured in multiple brain sections of mice from the three groups. Most regions did not differ between groups but, importantly, the cDIO mice had a significantly higher 5-HT2A/2C binding density in the anterior olfactory nucleus and ventromedial hypothalamic nucleus (VMH) compared to the cDR and LF mice (+39% and +47%, p=0.003 and 0.045, respectively), whereas the latter two groups did not differ. The density of 5-HT2A/2C receptors in the VMH was associated with total amount of fat mass (r=0.617, p=0.032). On the other hand, the cDR mice had significantly lower 5-HT transporter binding than the cDIO and LF mice, respectively, in the nucleus accumbens (-44%, -38%, both p<0.02), central nucleus of the amygdaloid nucleus (-40%, -44%, p=0.003 and 0.009), and olfactory tubercle nucleus (-42%, -42%, both p=0.03). In conclusion, this study has demonstrated differentially regulated levels of the 5-HT2A/2C receptor and 5-HT transporter in specific brain regions of the cDIO and cDR mice. It provides neural anatomical bases by which genetic variability in 5-HT2A/2C receptors and 5-HT transporter may influence satiety and sensory

  9. Differential expression of dopamine D2 and D4 receptor and tyrosine hydroxylase mRNA in mice prone, or resistant, to chronic high-fat diet-induced obesity.

    PubMed

    Huang, Xu-Feng; Yu, Yinghua; Zavitsanou, Katerina; Han, Mei; Storlien, Len

    2005-04-27

    The present study examined brain dopamine D2 and D4 receptor and tyrosine hydroxylase (TH) mRNA expression in chronic high-fat diet-induced obese (cDIO) and obese-resistant (cDR) mice. Twenty-eight mice were fed a high-fat diet (HF: 40% of calories from fat) for 6 weeks and then classified as cDIO (n = 8) or cDR (n = 8) mice according to the highest and lowest body weight gainers, respectively. Seven mice were fed a low-fat diet (LF: 10% of calories from fat) and used as controls. After 20 weeks of feeding, visceral fat per gram of initial body weight was significantly higher in the cDIO group (ratio: 0.25, 0.09, and 0.04; P < 0.01 cDIO vs. cDR and LF, respectively). Using quantitative in situ hybridization techniques, the levels of D2 and D4 receptor and tyrosine hydroxylase (TH) mRNAs were measured in multiple brain sections. The cDIO mice had a significantly higher level of D2 receptor mRNA expression in the core of the nucleus accumbens (AcbC, +16%) and ventral parts of caudate putamen (CPu, 21% and 24%) compared to the cDR and LF mice. The levels of D2 receptor mRNA expression in the AcbC and ventromedial part of the CPu were positively related to the final body weight. This study is the first to systematically examine the D4 mRNA expression in the mouse brain using in situ hybridization method. D4 receptor mRNA expression in the ventromedial hypothalamic nucleus (VMH) and the ventral part of the lateral septal nucleus were also significantly higher in the cDIO mice compared to the cDR and LF mice (+31% and +60%; P < 0.05). TH mRNA expression was significantly higher in the ventral tegmental area (+17%, P

  10. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

    SciTech Connect

    Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.; Flaws, Jodi A.; Helferich, William G.; Pan, Yuan-Xiang; Lezmi, Stéphane

    2015-04-15

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague–Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. - Highlights: • Developmental BPA exposure exacerbates HF-diet induced steatosis in adult males. • Gestational BPA exposure increases hepatic lipid accumulation in neonatal males. • BPA decreases Cpt1a and other hepatic β-oxidation genes in neonatal males. • BPA alters neonatal male Cpt1a

  11. Effects of high-fat diet-induced obesity and diabetes on Kiss1 and GPR54 expression in the hypothalamic-pituitary-gonadal (HPG) axis and peripheral organs (fat, pancreas and liver) in male rats.

    PubMed

    Dudek, M; Kołodziejski, P A; Pruszyńska-Oszmałek, E; Sassek, M; Ziarniak, K; Nowak, K W; Sliwowska, J H

    2016-04-01

    Recent data indicates that kisspeptin, encoded by the KISS1 gene, could play a role in transducing metabolic information into the hypothalamic-pituitary-gonadal (HPG) axis, the mechanism that controls reproductive functions. Numerous studies have shown that in a state of negative energy balance, the hypothalamic kisspeptin system is impaired. However, data concerning positive energy balance (e.g. diabetes and obesity) and the role of kisspeptin in the peripheral tissues is scant. We hypothesized that: 1) in diet-induced obese (DIO) male rats and/or rats with diabetes type 1 (DM1) and type 2 (DM2), altered reproductive functions are related to an imbalance in Kiss1 and GPR54 mRNA in the HPG axis; and 2) in DIO and/or DM1 and/or DM2 rats, Kiss1 and GPR 54 expression are altered in the peripheral tissues involved in metabolic functions (fat, pancreas and liver). Animals were fed a high-fat or control diets and STZ (streptozotocin - toxin, which destroys the pancreas) was injected in high or low doses to induce diabetes type 1 (DM1) or diabetes type 2 (DM2), respectively. RT-PCR and Western blot techniques were used to assess the expression of Kiss1 and GRP54 in tissues. At the level of mRNA, we found that diabetic but not obese rats have alterations in Kiss1 and/or GPR54 mRNA levels in the HPG axis as well as in peripheral tissues involved in metabolic functions (fat, pancreas and liver). The most severe changes were seen in DM1 rats. However, in the case of protein levels in the peripheral tissues (fat, pancreas and liver), changes in Kiss1/GPR54 expression were noticed in DIO, DM1 and DM2 animals and were tissue-specific. Our data support the hypothesis that alterations in Kiss1/GPR54 balance may account for both reproductive and metabolic abnormalities reported in obese and diabetic rats. PMID:26853724

  12. Changes in baroreflex control of renal sympathetic nerve activity in high-fat-fed rats as a predictor of hypertension.

    PubMed

    Fardin, Núbia M; Oyama, Lila M; Campos, Ruy R

    2012-08-01

    There is evidence that obesity is associated with increased sympathetic activity and hypertension. However, the mechanisms responsible for these changes are not fully understood. Therefore, the aim of the present study was to evaluate the cardiovascular function and the baroreceptor reflex control of renal sympathetic nerve activity (rSNA) in rats exposed to a high-fat diet over different periods (10 and 20 weeks) compared to control rats. Serum leptin levels were assessed for all time points. Male Wistar rats weighing 150-180 g were used. Four groups of rats were studied: control 10 weeks (Ct10), obese 10 weeks (Ob10), control 20 weeks (Ct20), and obese 20 weeks (Ob20). Blood pressure (BP) and rSNA were recorded in urethane-anesthetized rats (1.4 g/kg, intravenous).The sensitivity of rSNA responses to baroreceptor reflex was assessed by changes in BP induced by increasing doses of phenylephrine or sodium nitroprusside. Significant and progressive increases in serum leptin levels were found in the obese rats, but not in the control rats. No changes in basal BP or rSNA were found in the Ob10 and Ob20 groups; however, a significant impairment in the baroreceptor sensitivity was observed in the Ob20 group for phenylephrine (slope Ob20: -0.78 ± 0.12 vs. Ct20: -1.00 ± 0.08 potential per second (pps)/mm Hg, P < 0.05) and sodium nitroprusside (slope Ob20: -0.82 ± 0.09 vs. 1.13 ± 0.13 pps/mm Hg, P < 0.05). The results suggest that the baroreceptor dysfunction that controls the rSNA is an initial change in the obesity induced in high-fat-fed rats, which might be a predictor of sympathoexcitation and hypertension associated to obesity. PMID:22257982

  13. Effects of telmisartan and olmesartan on insulin sensitivity and renal function in spontaneously hypertensive rats fed a high fat diet.

    PubMed

    Yanagihara, Hayato; Ushijima, Kentaro; Arakawa, Yusuke; Aizawa, Ken-Ichi; Fujimura, Akio

    2016-07-01

    Although telmisartan, an angiotensin II receptor blocker (ARB), has an agonistic action for proliferator-activated receptor (PPAR)-γ in vitro, it remains to be determined whether telmisartan exerts such an action in vivo using a non-toxic dose (<5 mg/kg in rats). To address the issue, telmisartan (2 mg/kg) and olmesartan (2 mg/kg), another ARB without PPAR-γ agonistic action, were given to spontaneously hypertensive rats (SHR) fed a high fat diet (HFD). HFD decreased plasma adiponectin, and caused insulin resistance, hypertriglyceridemia and renal damage, which were improved by ARBs. Protective effects of telmisartan and olmesartan did not significantly differ. In addition, in vitro study showed that 1 μM of telmisartan did not elevate the mRNA expression of adipose protein 2, which is a PPAR-γ-stimulated adipogenic marker gene, in preadipocytes with 3% albumin. To obtain 1 μM of plasma concentration, oral dose of telmisartan was calculated to be 6 mg/kg, which indicates that PPAR-γ agonistic action is negligible with a non-toxic dose of telmisartan (<5 mg/kg) in rats. This study showed that 2 mg/kg of telmisartan and olmesartan ameliorated insulin resistance, hypertriglyceridemia and renal damage in SHR fed a HFD. As beneficial effects of telmisartan and olmesartan did not significantly differ, these were mediated through the PPAR-γ-independent actions. PMID:27430988

  14. Isocaloric pair-fed high-carbohydrate diet induced more hepatic steatosis and inflammation than high-fat diet mediated by miR- 34a/SIRT1 axis in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA- 34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Li...

  15. Perinatal exposure to germinated brown rice and its gamma amino-butyric acid-rich extract prevents high fat diet-induced insulin resistance in first generation rat offspring

    PubMed Central

    Adamu, Hadiza Altine; Imam, Mustapha Umar; Ooi, Der-Jiun; Esa, Norhaizan Mohd; Rosli, Rozita; Ismail, Maznah

    2016-01-01

    Background Evidence suggests perinatal environments influence the risk of developing insulin resistance. Objective The present study was aimed at determining the effects of intrauterine exposure to germinated brown rice (GBR) and GBR-derived gamma (γ) aminobutyric acid (GABA) extract on epigenetically mediated high fat diet–induced insulin resistance. Design Pregnant Sprague Dawley rats were fed high-fat diet (HFD), HFD+GBR, or HFD+GABA throughout pregnancy until 4 weeks postdelivery. The pups were weighed weekly and maintained on normal pellet until 8 weeks postdelivery. After sacrifice, biochemical markers of obesity and insulin resistance including oral glucose tolerance test, adiponectin, leptin, and retinol binding protein-4 (RBP4) were measured. Hepatic gene expression changes and the global methylation and histone acetylation levels were also evaluated. Results Detailed analyses revealed that mothers given GBR and GABA extract, and their offspring had increased adiponectin levels and reduced insulin, homeostasis model assessment of insulin resistance, leptin, oxidative stress, and RBP4 levels, while their hepatic mRNA levels of GLUT2 and IPF1 were increased. Furthermore, GBR and GABA extract lowered global DNA methylation levels and modulated H3 and H4 acetylation levels. Conclusions These results showed that intrauterine exposure to GBR-influenced metabolic outcomes in offspring of rats with underlying epigenetic changes and transcriptional implications that led to improved glucose homeostasis. PMID:26842399

  16. Glucocorticoid receptor haploinsufficiency causes hypertension and attenuates hypothalamic-pituitary-adrenal axis and blood pressure adaptions to high-fat diet.

    PubMed

    Michailidou, Z; Carter, R N; Marshall, E; Sutherland, H G; Brownstein, D G; Owen, E; Cockett, K; Kelly, V; Ramage, L; Al-Dujaili, E A S; Ross, M; Maraki, I; Newton, K; Holmes, M C; Seckl, J R; Morton, N M; Kenyon, C J; Chapman, K E

    2008-11-01

    Glucocorticoid hormones are critical to respond and adapt to stress. Genetic variations in the glucocorticoid receptor (GR) gene alter hypothalamic-pituitary-adrenal (HPA) axis activity and associate with hypertension and susceptibility to metabolic disease. Here we test the hypothesis that reduced GR density alters blood pressure and glucose and lipid homeostasis and limits adaption to obesogenic diet. Heterozygous GR(betageo/+) mice were generated from embryonic stem (ES) cells with a gene trap integration of a beta-galactosidase-neomycin phosphotransferase (betageo) cassette into the GR gene creating a transcriptionally inactive GR fusion protein. Although GR(betageo/+) mice have 50% less functional GR, they have normal lipid and glucose homeostasis due to compensatory HPA axis activation but are hypertensive due to activation of the renin-angiotensin-aldosterone system (RAAS). When challenged with a high-fat diet, weight gain, adiposity, and glucose intolerance were similarly increased in control and GR(betageo/+) mice, suggesting preserved control of intermediary metabolism and energy balance. However, whereas a high-fat diet caused HPA activation and increased blood pressure in control mice, these adaptions were attenuated or abolished in GR(betageo/+) mice. Thus, reduced GR density balanced by HPA activation leaves glucocorticoid functions unaffected but mineralocorticoid functions increased, causing hypertension. Importantly, reduced GR limits HPA and blood pressure adaptions to obesogenic diet. PMID:18697839

  17. Isocaloric Pair-Fed High-Carbohydrate Diet Induced More Hepatic Steatosis and Inflammation than High-Fat Diet Mediated by miR-34a/SIRT1 Axis in Mice

    PubMed Central

    Li, Xinli; Lian, Fuzhi; Liu, Chun; Hu, Kang-Quan; Wang, Xiang-Dong

    2015-01-01

    To investigate the different effects of isocaloric high-fat diet (HFD) and high-carbohydrate diet (HCD) on hepatic steatosis and the underlying mechanisms, especially the role of microRNA-34a/silent information regulator T1 (SIRT1) axis, C57BL/6J mice (n = 12/group) were isocaloric pair-fed with Lieber-DeCarli liquid diet containing either high fat (HFLD) or high carbohydrate (HCLD) for 16 weeks. As compared to the HFLD fed mice, despite the similar final body weights, HCLD feeding: (1) induced more severe hepatic steatosis; (2) up-regulated hepatic expression of miR-34a accompanied with significant decrease of SIRT1 and nicotinamide phosphoribosyltransferase (NAMPT), SIRT1 activity and phosphorylation of AMPK; (3) up-regulated de novo lipogenesis (DNL) related proteins expression (ACC, SCD1), and down-regulated expressions of miR-122, miR-370 and miR-33; (4) decreased mRNA expressions of genes Cpt1, Pparα and Pgc1α related to fatty acid oxidation; (5) increased hepatic total cholesterol concentration and decreased expression of cholesterol metabolism related genes Abcg5, Abcg8, Abcg11, Cyp7a1 and Cyp8b1; and (6) induced higher hepatic inflammatory response accompanied with significant increased mRNA expressions of Il1β, Tnfα and Mcp1. Thus, isocaloric HCLD feeding induced greater severity in hepatic steatosis and inflammatory response than HFLD feeding, potentially through miR-34a/SIRT1 axis mediated promotion of DNL, inhibition of fatty acid oxidation and cholesterol metabolism. PMID:26608583

  18. Olive leaf extract suppresses messenger RNA expression of proinflammatory cytokines and enhances insulin receptor substrate 1 expression in the rats with streptozotocin and high-fat diet-induced diabetes.

    PubMed

    Liu, Ya-Nan; Jung, Ji-Hye; Park, Hyunjin; Kim, HyunSook

    2014-05-01

    Type 2 diabetes, characterized by hyperglycemia and hyperlipidemia, is a metabolic disease resulting from defects in both insulin secretion and insulin resistance. Recently, olive leaf has been reported as an anti-inflammatory, antioxidant, and antidiabetic agent. This study sought to investigate whether olive leaf extract can improve the insulin resistance and inflammation response in rats with type 2 diabetes induced by high-fat diet and streptozotocin. After administering olive leaf extract for 8 weeks (200 and 400 mg/kg body weight), rats given the higher dose showed significantly lower blood glucose, serum total cholesterol, and triglyceride levels compared with those of diabetic control rats (P < .05). Results of oral glucose tolerance tests, homeostasis model assessment of insulin resistance, and messenger RNA (mRNA) expression of tumor necrosis factor α and interleukin (IL) 6 in the liver show significantly decreased glucose level in rats given either dose of olive leaf extract (P < .05). Both olive leaf extract-treated groups showed significantly increased insulin receptor substrate 1 expression (P < .05). Tumor necrosis factor α, IL-6 and IL-1β mRNA expressions in epididymis adipose tissue were significantly lower in rats that received higher dose of olive leaf extract (P < .05). Lymphocyte infiltration was not observed in these rats. The results suggest that olive leaf extract may attenuate insulin resistance by suppressing mRNA expression of proinflammatory cytokines and elevating of insulin receptor substrate 1 expression. PMID:24916559

  19. Indirubin-3'-oxime, an activator of Wnt/β-catenin signaling, enhances osteogenic commitment of ST2 cells and restores bone loss in high-fat diet-induced obese male mice.

    PubMed

    Zahoor, Muhammad; Cha, Pu-Hyeon; Choi, Kang-Yell

    2014-08-01

    Obesity is a growing issue of the modern world, and its negative impact on bones in obese male patients has been recently reported. The Wnt/β-catenin pathway has an established role in the regulation of body fat content and bone density. We investigated the effects of indirubin-3'-oxime (I3O), the GSK3β inhibitor that activates Wnt/β-catenin signaling, on trabecular bone in high-fat diet (HFD)-induced obese male mice. I3O reverses the downregulating effect of fatty acid (FA) on Wnt/β-catenin signaling and enhances the osteogenic commitment of the bone marrow-derived stromal cell line ST2. FA induces the adipogenic differentiation of bone marrow stromal cells in vitro. In a male mouse model of HFD-induced obesity, trabecular bone loss was observed in the femora, with a gross increase in abdominal fat; however, the HFD effects were rescued with the activation of Wnt/β-catenin signaling by I3O treatment. I3O administration also reversed the increase in the number of HFD-induced adipocytes in the femur bone marrow in trabecular bone. Overall, our results indicate that I3O could be a potential therapeutic agent for obese male patients through downregulation of abdominal fat and net increment in trabecular bone density. PMID:24815917

  20. Inhibition of mitogen-activated protein kinases/nuclear factor κB-dependent inflammation by a novel chalcone protects the kidney from high fat diet-induced injuries in mice.

    PubMed

    Fang, Qilu; Deng, Liancheng; Wang, Lintao; Zhang, Yali; Weng, Qiaoyou; Yin, Haimin; Pan, Yong; Tong, Chao; Wang, Jingying; Liang, Guang

    2015-11-01

    The prevalence of obesity has increased dramatically worldwide leading to increases in obesity-related complications, such as obesity-related glomerulopathy (ORG). Obesity is a state of chronic, low-grade inflammation, and increased inflammation in the adipose and kidney tissues has been shown to promote the progression of renal damage in obesity. Current therapeutic options for ORG are fairly limited and, as a result, we are seeing increased rates of progression to end-stage renal disease. Chalcones are a class of naturally occurring compounds with various pharmacological properties. 1-(3,4-Dihydroxyphenyl)-3-(2-methoxyphenyl)prop-2-en-1-one (L2H17) is a chalcone that we have previously synthesized and found capable of inhibiting the lipopolysaccharide-induced inflammatory response in macrophages. In this study, we investigated L2H17's effect on obesity-induced renal injury using palmitic acid-induced mouse peritoneal macrophages and high fat diet-fed mice. Our results indicate that L2H17 protects against renal injury through the inhibition of the mitogen-activated protein kinase/nuclear factor κB pathways significantly by decreasing the expression of proinflammatory cytokines and cell adhesion molecules and improving kidney histology and pathology. These findings lead us to believe that L2H17, as an anti-inflammatory agent, can be a potential therapeutic option in treating ORG. PMID:26354992

  1. Transcriptional regulatory factor X6 (Rfx6) increases gastric inhibitory polypeptide (GIP) expression in enteroendocrine K-cells and is involved in GIP hypersecretion in high fat diet-induced obesity.

    PubMed

    Suzuki, Kazuyo; Harada, Norio; Yamane, Shunsuke; Nakamura, Yasuhiko; Sasaki, Kazuki; Nasteska, Daniela; Joo, Erina; Shibue, Kimitaka; Harada, Takanari; Hamasaki, Akihiro; Toyoda, Kentaro; Nagashima, Kazuaki; Inagaki, Nobuya

    2013-01-18

    Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K-cells in response to nutrient ingestion. GIP potentiates glucose-stimulated insulin secretion and induces energy accumulation into adipose tissue, resulting in obesity. Plasma GIP levels are reported to be increased in the obese state. However, the molecular mechanisms of GIP secretion and high fat diet (HFD)-induced GIP hypersecretion remain unclear, primarily due to difficulties in separating K-cells from other intestinal epithelial cells in vivo. In this study, GIP-GFP knock-in mice that enable us to visualize K-cells by enhanced GFP were established. Microarray analysis of isolated K-cells from these mice revealed that transcriptional regulatory factor X6 (Rfx6) is expressed exclusively in K-cells. In vitro experiments using the mouse intestinal cell line STC-1 showed that knockdown of Rfx6 decreased mRNA expression, cellular content, and secretion of GIP. Rfx6 bound to the region in the gip promoter that regulates gip promoter activity, and overexpression of Rfx6 increased GIP mRNA expression. HFD induced obesity and GIP hypersecretion in GIP-GFP heterozygous mice in vivo. Immunohistochemical and flow cytometry analysis showed no significant difference in K-cell number between control fat diet-fed (CFD) and HFD-fed mice. However, GIP content in the upper small intestine and GIP mRNA expression in K-cells were significantly increased in HFD-fed mice compared with those in CFD-fed mice. Furthermore, expression levels of Rfx6 mRNA were increased in K-cells of HFD-fed mice. These results suggest that Rfx6 increases GIP expression and content in K-cells and is involved in GIP hypersecretion in HFD-induced obesity. PMID:23192339

  2. Lactobacillus sakei OK67 ameliorates high-fat diet-induced blood glucose intolerance and obesity in mice by inhibiting gut microbiota lipopolysaccharide production and inducing colon tight junction protein expression.

    PubMed

    Lim, Su-Min; Jeong, Jin-Ju; Woo, Kyung Hee; Han, Myung Joo; Kim, Dong-Hyun

    2016-04-01

    A high-fat diet (HFD) induces obesity and the associated increases in blood glucose and inflammation through changes in gut microbiota, endotoxemia, and increased gut permeability. To counteract this, researchers have suggested that the use of probiotics that suppress production of proinflammatory lipopolysaccharide (LPS). Here, we tested whether Lactobacillus sakei OK67, which inhibits gut microbiota LPS production selected from among the lactic acid bacteria isolated from kimchi, exerted antihypoglycemic or anti-inflammatory effects in HFD-fed mice. Mice were randomly divided into 2 groups and fed an HFD or a low-fat diet for 4 weeks. These groups were further subdivided; 1 subgroup was treated with L sakei OK67 and fed the experimental diet for 4.5 weeks, whereas the other subgroup was fed the experimental diet alone. L sakei OK67 treatment lowered HFD-elevated LPS levels in blood and colonic fluid and significantly decreased HFD-elevated fasting blood glucose levels and the area under the curve in an oral glucose tolerance test. L sakei OK67 treatment inhibited HFD-induced body and epididymal fat weight gains, suppressed HFD-induced tumor necrosis factor-α and interleukin-1β expression and nuclear factor-κB activation in the colon, and significantly increased HFD-suppressed interleukin-10 and tight junction protein expression in the colon. Oral administration of L sakei OK67 significantly downregulated HFD-induced expression of peroxisome proliferator-activated receptor γ, fatty acid synthase, and tumor necrosis factor-α in adipose tissue. In addition, L sakei OK67 treatment strongly inhibited nuclear factor-κB activation in LPS-stimulated peritoneal macrophages. We report that L sakei OK67 ameliorates HFD-induced hyperglycemia and obesity by reducing inflammation and increasing the expression of colon tight junction proteins in mice. PMID:27001279

  3. Developmental Bisphenol A (BPA) Exposure Leads to Sex-specific Modification of Hepatic Gene Expression and Epigenome at Birth that May Exacerbate High-fat Diet-induced Hepatic Steatosis

    PubMed Central

    Strakovsky, Rita S.; Wang, Huan; Engeseth, Nicki J.; Flaws, Jodi A.; Helferich, William G.; Pan, Yuan-Xiang; Lezmi, Stéphane

    2015-01-01

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague-Dawley rats were dosed with vehicle (oil) or BPA (100 μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglycerides (TG) and free fatty acid (FFA) composition in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation, histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially thorough the epigenetic regulation of genes, and further alters the response to a HF diet. PMID:25748669

  4. Alternate-day fasting protects the livers of mice against high-fat diet-induced inflammation associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling.

    PubMed

    Yang, Wanwei; Cao, Meng; Mao, Xiaodong; Wei, Xiao; Li, Xingjia; Chen, Guofang; Zhang, Jiaming; Wang, Zhiguo; Shi, Jianfeng; Huang, HouCai; Yao, Xiaoming; Liu, Chao

    2016-06-01

    Because of unhealthy lifestyles, a large number of people are suffering from hepatic lipid accumulation and nonalcoholic steatohepatitis. Energy restriction (ER) is an effective nutritional intervention for preventing chronic disease. However, poor compliance with continuous ER limits its effectiveness. As an alternative to daily ER, alternate-day fasting (ADF) may be more effective. We hypothesized that ADF would improve obesity, hyperglycemia, and insulin resistance and protect the liver against high-fat diet (HFD)-induced steatosis and inflammation. In this study, we used C57BL/6 mice to test the beneficial effects of ADF. Thirty male 6-week-old C57BL/6 mice were divided into 3 groups (10 per group, total N = 30): 1 group was fed chow diet, the second was fed HFD ad libitum, and the third group was submitted to ADF. The mice in the third group were fed the HFD ad libitum every other day and fasted the following day. After 12 months, the mice submitted to ADF exhibited reduced body weights and fasting glucose levels and improved insulin resistance and hepatic steatosis compared with continuous HFD-fed mice. In addition, the serum transaminase levels in the mice of the ADF group were lower than those of the HFD group. Moreover, the ADF regimen suppressed the expression levels of Toll-like receptor 4 and nuclear factor κB protein in the liver and suppressed the inflammatory pathway genes interleukin 1β, tumor necrosis factor α, and serum amyloid A. These finding indicate that long-term ADF protects mouse livers against HFD-induced hepatic steatosis and hepatocellular damage associated with the suppression of Toll-like receptor 4/nuclear factor κB signaling. PMID:27188904

  5. Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis.

    PubMed

    Strakovsky, Rita S; Wang, Huan; Engeseth, Nicki J; Flaws, Jodi A; Helferich, William G; Pan, Yuan-Xiang; Lezmi, Stéphane

    2015-04-15

    Developmental bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague-Dawley rats were dosed with vehicle (oil) or BPA (100μg/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45% fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and β-oxidation-related genes (Dgat, Agpat6, Cebpα, Cebpβ, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPβ, SREBP1) within the male Cpt1a gene, the key β-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic β-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet. PMID:25748669

  6. Reducing the Dietary Omega-6:Omega-3 Utilizing α-Linolenic Acid; Not a Sufficient Therapy for Attenuating High-Fat-Diet-Induced Obesity Development Nor Related Detrimental Metabolic and Adipose Tissue Inflammatory Outcomes

    PubMed Central

    Enos, Reilly T.; Velázquez, Kandy T.; McClellan, Jamie L.; Cranford, Taryn L.; Walla, Michael D.; Murphy, E. Angela

    2014-01-01

    Aims To examine the effect of manipulating the omega-6:omega-3 (1∶1, 5∶1, 10∶1, and 20∶1) utilizing only α-linolenic and linoleic acid within a clinically-relevant high-fat diet (HFD) composed of up to seven sources of fat and designed to be similar to the standard American diet (MUFA∶PUFA of 2∶1, 12% and 40% of calories from saturated and total fat, respectively) on body composition, macrophage polarization, inflammation, and metabolic dysfunction in mice. Methods Diets were administered for 20 weeks. Body composition and metabolism (HOMA index and lipid profile) were examined monthly. GC-MS was utilized to determine the eicosapentaenoic acid (EPA):arachidonic acid (AA) and the docosahexaenoic acid (DHA):AA in AT phospholipids. Adipose tissue (AT) mRNA expression of chemokines (MCP-1, Fetuin-A, CXCL14), marker genes for M1 and M2 macrophages (CD11c and CD206, respectively) and inflammatory markers (TNF-α, IL-6, IL-1β, TLR-2, TLR-4, IL-10, GPR120) were measured along with activation of NFκB, JNK, and STAT-3. Macrophage infiltration into AT was examined using F4/80 immunohistochemistry. Results Any therapeutic benefit produced by reducing the omega-6:omega-3 was evident only when comparing the 1∶1 to 20∶1 HFD; the 1∶1 HFD resulted in a lower TC:HDL-C and decreased AT CXCL14 gene expression and AT macrophage infiltration, which was linked to a higher EPA:AA and DHA:AA in AT phospholipids. However, despite these effects, and independent of the omega-6:omega-3, all HFDs, in general, led to similar levels of adiposity, insulin resistance, and AT inflammation. Conclusion Reducing the omega-6:omega-3 using α-linolenic acid is not an effective therapy for attenuating obesity and type II diabetes mellitus development. PMID:24733548

  7. The Herbal Medicine KBH-1 Inhibits Fat Accumulation in 3T3-L1 Adipocytes and Reduces High Fat Diet-Induced Obesity through Regulation of the AMPK Pathway.

    PubMed

    Lee, Ji-Hye; Kim, Taesoo; Lee, Jung-Jin; Lee, Kwang Jin; Kim, Hyun-Kyu; Yun, Bora; Jeon, Jongwook; Kim, Sang Kyum; Ma, Jin Yeul

    2015-01-01

    The aim of this study was to investigate whether a novel formulation of an herbal extract, KBH-1, has an inhibitory effect on obesity. To determine its anti-obesity effects and its underlying mechanism, we performed anti-obesity-related experiments in vitro and in vivo. 3T3-L1 preadipocytes were analyzed for lipid accumulation as well as the protein and gene expression of molecular targets involved in fatty acid synthesis. To determine whether KBH-1 oral administration results in a reduction in high-fat diet (HFD)-induced obesity, we examined five groups (n = 9) of C57BL/6 mice as follows: 10% kcal fat diet-fed mice (ND), 60% kcal fat diet-fed mice (HFD), HFD-fed mice treated with orlistat (tetrahydrolipstatin, marketed under the trade name Xenical), HFD-fed mice treated with 150 mg/kg KBH-1 (KBH-1 150) and HFD-fed mice treated with 300 mg/kg KBH-1 (KBH-1 300). During adipogenesis of 3T3-L1 cells in vitro, KBH-1 significantly reduced lipid accumulation and down-regulated the expression of master adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP) β, C/EBP α and peroxisome proliferation-activity receptor (PPAR) γ, which led to the suppression of the expression of several adipocyte-specific genes and proteins. KBH-1 also markedly phosphorylated the adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, KBH-1-induced the inhibition effect on lipid accumulation and AMPK-mediated signal activation were decreased by blocking AMPK phosphorylation using AMPK siRNA. Furthermore, daily oral administration of KBH-1 resulted in dose-dependent decreases in body weight, fat pad mass and fat tissue size without systemic toxicity. These results suggest that KBH-1 inhibits lipid accumulation by down-regulating the major transcription factors of the adipogenesis pathway by regulating the AMPK pathway in 3T3-L1 adipocytes and in mice with HFD-induced obesity. These results implicate KBH-1, a safe herbal

  8. The Herbal Medicine KBH-1 Inhibits Fat Accumulation in 3T3-L1 Adipocytes and Reduces High Fat Diet-Induced Obesity through Regulation of the AMPK Pathway

    PubMed Central

    Lee, Ji-Hye; Kim, Taesoo; Lee, Jung-Jin; Lee, Kwang Jin; Kim, Hyun-Kyu; Yun, Bora; Jeon, Jongwook; Kim, Sang Kyum; Ma, Jin Yeul

    2015-01-01

    The aim of this study was to investigate whether a novel formulation of an herbal extract, KBH-1, has an inhibitory effect on obesity. To determine its anti-obesity effects and its underlying mechanism, we performed anti-obesity-related experiments in vitro and in vivo. 3T3-L1 preadipocytes were analyzed for lipid accumulation as well as the protein and gene expression of molecular targets involved in fatty acid synthesis. To determine whether KBH-1 oral administration results in a reduction in high-fat diet (HFD)-induced obesity, we examined five groups (n = 9) of C57BL/6 mice as follows: 10% kcal fat diet-fed mice (ND), 60% kcal fat diet-fed mice (HFD), HFD-fed mice treated with orlistat (tetrahydrolipstatin, marketed under the trade name Xenical), HFD-fed mice treated with 150 mg/kg KBH-1 (KBH-1 150) and HFD-fed mice treated with 300 mg/kg KBH-1 (KBH-1 300). During adipogenesis of 3T3-L1 cells in vitro, KBH-1 significantly reduced lipid accumulation and down-regulated the expression of master adipogenic transcription factors, including CCAAT/enhancer binding protein (C/EBP) β, C/EBP α and peroxisome proliferation-activity receptor (PPAR) γ, which led to the suppression of the expression of several adipocyte-specific genes and proteins. KBH-1 also markedly phosphorylated the adenosine monophosphate-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC). In addition, KBH-1-induced the inhibition effect on lipid accumulation and AMPK-mediated signal activation were decreased by blocking AMPK phosphorylation using AMPK siRNA. Furthermore, daily oral administration of KBH-1 resulted in dose-dependent decreases in body weight, fat pad mass and fat tissue size without systemic toxicity. These results suggest that KBH-1 inhibits lipid accumulation by down-regulating the major transcription factors of the adipogenesis pathway by regulating the AMPK pathway in 3T3-L1 adipocytes and in mice with HFD-induced obesity. These results implicate KBH-1, a safe herbal

  9. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome.

    PubMed

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L; Ward, Leigh C; Mouatt, Peter; Brown, Lindsay

    2015-09-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  10. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

    PubMed Central

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L.; Ward, Leigh C.; Mouatt, Peter; Brown, Lindsay

    2015-01-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  11. High-fat diet exacerbates renal dysfunction in SHR: reversal by induction of HO-1-adiponectin axis.

    PubMed

    Cao, Jian; Inoue, Kazuyoshi; Sodhi, Komal; Puri, Nitin; Peterson, Stephen J; Rezzani, Rita; Abraham, Nader G

    2012-05-01

    High-dietary fat intake is a major risk factor for development of metabolic and cardiovascular-renal dysfunction including obesity, coronary artery disease, hypertension, and chronic renal failure. We examined the effect of a high-fat diet on renal function and morphology in spontaneously hypertensive rats (SHR), a phenotype designed to mimic metabolic syndrome. High-fat diet induced increase (P < 0.05) in blood pressure, body weight, and renal lipid deposition in these rats. This increase in body weight was accompanied by elevations (P < 0.05) of blood glucose and low-density lipoprotein (LDL) levels, a decrease (P < 0.05) in adiponectin and increases (P < 0.05) in plasma monocyte chemotactic protein-1 (MCP-1) along with renal macrophage infiltration. These pathophysiological perturbations were attenuated (P < 0.05) by heme oxygenase-1 (HO-1) induction by treatment with cobalt protoporphyrin (CoPP). Further effects of CoPP included increased (P < 0.05) renal expression of adiponectin along with enhancement (P < 0.05) of pAKT, pAMPK, and p-eNOS in SHRs fed a high-fat diet. Prevention of such beneficial effects of CoPP by the concurrent administration of the heme-HO inhibitor stannous mesoporphyrin (SnMP) corroborates the role of HO system in mediating such effects. Taken together, our results demonstrate that high-fat diet induces a metabolic syndrome-like phenotype in hypertensive rats, which is amenable to rescue by increases in HO-1- and adiponectin-dependent pathways. PMID:22193921

  12. Effects of (-)-epicatechin on a diet-induced rat model of cardiometabolic risk factors.

    PubMed

    Gutiérrez-Salmeán, Gabriel; Ortiz-Vilchis, Pilar; Vacaseydel, Claudia Maria; Garduño-Siciliano, Leticia; Chamorro-Cevallos, German; Meaney, Eduardo; Villafaña, Santiago; Villarreal, Francisco; Ceballos, Guillermo; Ramírez-Sánchez, Israel

    2014-04-01

    Overweight and obesity have been associated with increase in cardiometabolic risk. Therapeutics include lifestyle changes and/or pharmacologic agents. However, such interventions are often limited by poor compliance and/or significant side effects. The consumption of certain dietary products, such as cocoa, exerts positive effects on cardiometabolic risk factors. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao has been reported to replicate such effects. However its mechanisms of action have not been fully elucidated.In a rat model of high-fat diet-induced obesity and its associated cardiometabolic risk factors, we administered 1mg/kg of EPI, by gavage, for 2 weeks. Endpoints included weight-gain, glycemia, triglyceridemia, and systolic blood pressure. We also assessed food intake and fecal excretion. Mitochondrial function and structure related proteins were measured by Westerns.Obesity, hyperglycemia, hypertriglyceridemia, and systolic hypertension were developed after the administration of the high-fat diet for five weeks. EPI significantly decreased the rate of weight gain, glycemia and hypertriglyceridemia. The ratio between energy intake and excretion was not significantly modified by treatment. EPI restored the obesity-induced decreases in the levels of skeletal muscle and abdominal tissue sirtuins (SIRTs), peroxisome proliferator-activated receptor coactivator (PGC-1α), mitofilin, transcription factor A mitochondrial (TFAM), uncoupling protein 1 (UCP1), and deiodinase.EPI treatment yielded beneficial effects on high fat diet-induced endpoints thus may be considered as a potential agent for the treatment of obesity and its cardiometabolic associated abnormalities. Mechanism of action may be attributed to the modulation of cellular/mitochondrial function, thus improving overall metabolism. PMID:24491839

  13. Tocotrienols Reverse Cardiovascular, Metabolic and Liver Changes in High Carbohydrate, High Fat Diet-Fed Rats

    PubMed Central

    Wong, Weng-Yew; Poudyal, Hemant; Ward, Leigh C.; Brown, Lindsay

    2012-01-01

    Tocotrienols have been reported to improve lipid profiles, reduce atherosclerotic lesions, decrease blood glucose and glycated haemoglobin concentrations, normalise blood pressure in vivo and inhibit adipogenesis in vitro, yet their role in the metabolic syndrome has not been investigated. In this study, we investigated the effects of palm tocotrienol-rich fraction (TRF) on high carbohydrate, high fat diet-induced metabolic, cardiovascular and liver dysfunction in rats. Rats fed a high carbohydrate, high fat diet for 16 weeks developed abdominal obesity, hypertension, impaired glucose and insulin tolerance with increased ventricular stiffness, lower systolic function and reduced liver function. TRF treatment improved ventricular function, attenuated cardiac stiffness and hypertension, and improved glucose and insulin tolerance, with reduced left ventricular collagen deposition and inflammatory cell infiltration. TRF improved liver structure and function with reduced plasma liver enzymes, inflammatory cell infiltration, fat vacuoles and balloon hepatocytes. TRF reduced plasma free fatty acid and triglyceride concentrations but only omental fat deposition was decreased in the abdomen. These results suggest that tocotrienols protect the heart and liver, and improve plasma glucose and lipid profiles with minimal changes in abdominal obesity in this model of human metabolic syndrome. PMID:23201770

  14. Early postnatal treatment with soluble epoxide hydrolase inhibitor or 15-deoxy-Δ(12,14)-prostagandin J2 prevents prenatal dexamethasone and postnatal high saturated fat diet induced programmed hypertension in adult rat offspring.

    PubMed

    Lu, Pei-Chen; Sheen, Jiunn-Ming; Yu, Hong-Ren; Lin, Yu-Ju; Chen, Chih-Cheng; Tiao, Mao-Meng; Tsai, Ching-Chou; Huang, Li-Tung; Tain, You-Lin

    2016-07-01

    Prenatal dexamethasone (DEX) exposure, postnatal high-fat (HF) intake, and arachidonic acid pathway are closely related to hypertension. We tested whether a soluble epoxide hydrolase (SEH) inhibitor, 12-(3-adamantan-1-yl-ureido)-dodecanoic acid (AUDA) or 15-deoxy-Δ(12,14)-prostagandin J2 (15dPGJ2) therapy can rescue programmed hypertension in the DEX+HF two-hit model. Four groups of Sprague Dawley rats were studied: control, DEX+HF, AUDA, and 15dPGJ2. Dexamethasone (0.1mg/kg body weight) was intraperitoneally administered to pregnant rats from gestational day 16-22. Male offspring received high-fat diet (D12331, Research Diets) from weaning to 4 months of age. In AUDA group, mother rats received 25mg/L in drinking water during lactation. In the 15dPGJ2 group, male offspring received 15dPGJ2 1.5mg/kg BW by subcutaneous injection once daily for 1 week after birth. We found postnatal HF diet aggravated prenatal DEX-induced programmed hypertension, which was similarly prevented by early treatment with AUDA or 15dPGJ2. The beneficial effects of AUDA and 15d-PGJ2 therapy include inhibition of SEH, increases of renal angiotensin converting enzyme-2 (ACE2) and angiotensin II type 2 receptor (AT2R) protein levels, and restoration of nitric oxide bioavailability. Better understanding of the impact of arachidonic acid pathway in the two-hit model will help prevent programmed hypertension in children exposed to corticosteroids and postnatal HF intake. PMID:27210044

  15. CD11c expression in adipose tissue and blood and its role in diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine CD11c, a beta(2)-integrin, on adipose tissue (AT) leukocytes, and blood monocytes and its role in diet-induced obesity. High-fat diet-induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blo...

  16. Proinsulin-producing, hyperglycemia-induced adipose tissue macrophages underlie insulin resistance in high fat-fed diabetic mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue macrophages play an important role in the pathogenesis of obese type 2 diabetes. High-fat diet-induced obesity has been shown to lead to adipose tissue macrophages accumulation in rodents;however, the impact of hyperglycemia on adipose tissue macrophages dynamics in high-fat diet-fed ...

  17. Adipocyte deficiency of angiotensinogen prevents obesity-induced hypertension in male mice.

    PubMed

    Yiannikouris, Frederique; Gupte, Manisha; Putnam, Kelly; Thatcher, Sean; Charnigo, Richard; Rateri, Debra L; Daugherty, Alan; Cassis, Lisa A

    2012-12-01

    Previous studies demonstrated that diet-induced obesity increased plasma angiotensin II concentrations and elevated systolic blood pressures in male mice. Adipocytes express angiotensinogen and secrete angiotensin peptides. We hypothesize that adipocyte-derived angiotensin II mediates obesity-induced increases in systolic blood pressure in male high fat-fed C57BL/6 mice. Systolic blood pressure was measured by radiotelemetry during week 16 of low-fat or high-fat feeding in Agt(fl/fl) and adipocyte angiotensinogen-deficient mice (Agt(aP2)). Adipocyte angiotensinogen deficiency had no effect on diet-induced obesity. Basal 24-hour systolic blood pressure was not different in low fat-fed Agt(fl/fl) compared with Agt(aP2) mice (124 ± 3 versus 128 ± 3 mm Hg, respectively). In Agt(fl/fl) mice, high-fat feeding significantly increased systolic blood pressure (24 hours; 134 ± 2 mm Hg; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit an increase in systolic blood pressure (126 ± 2 mm Hg). Plasma angiotensin II concentrations were increased by high-fat feeding in Agt(fl/fl) mice (low fat, 32 ± 14; high fat, 219 ± 58 pg/mL; P<0.05). In contrast, high fat-fed Agt(aP2) mice did not exhibit elevated plasma angiotensin II concentrations (high fat, 18 ± 7 pg/mL). Similarly, adipose tissue concentrations of angiotensin II were significantly decreased in low fat- and high fat-fed Agt(aP2) mice compared with controls. In conclusion, adipocyte angiotensinogen deficiency prevented high fat-induced elevations in plasma angiotensin II concentrations and systolic blood pressure. These results suggest that adipose tissue serves as a major source of angiotensin II in the development of obesity hypertension. PMID:23108647

  18. Chronic vagal nerve stimulation prevents high-salt diet-induced endothelial dysfunction and aortic stiffening in stroke-prone spontaneously hypertensive rats.

    PubMed

    Chapleau, Mark W; Rotella, Diane L; Reho, John J; Rahmouni, Kamal; Stauss, Harald M

    2016-07-01

    Parasympathetic activity is often reduced in hypertension and can elicit anti-inflammatory mechanisms. Thus we hypothesized that chronic vagal nerve stimulation (VNS) may alleviate cardiovascular end-organ damage in stroke-prone spontaneously hypertensive rats. Vagal nerve stimulators were implanted, a high-salt diet initiated, and the stimulators turned on (VNS, n = 10) or left off (sham, n = 14) for 4 wk. Arterial pressure increased equally in both groups. After 4 wk, endothelial function, assessed by in vivo imaging of the long posterior ciliary artery (LPCA) after stimulation (pilocarpine) and inhibition (N(ω)-nitro-l-arginine methyl ester) of endothelial nitric oxide synthase (eNOS), had significantly declined (-2.3 ± 1.2 μm, P < 0.05) in sham, but was maintained (-0.7 ± 0.8 μm, nonsignificant) in VNS. Furthermore, aortic eNOS activation (phosphorylated to total eNOS protein content ratio) was greater in VNS (0.83 ± 0.07) than in sham (0.47 ± 0.08, P < 0.05). After only 3 wk, ultrasound imaging of the aorta demonstrated decreased aortic strain (-9.7 ± 2.2%, P < 0.05) and distensibility (-2.39 ± 0.49 1,000/mmHg, P < 0.05) and increased pulse-wave velocity (+2.4 ± 0.7 m/s, P < 0.05) in sham but not in VNS (-3.8 ± 3.8%, -0.70 ± 1.4 1,000/mmHg, and +0.1 ± 0.7 m/s, all nonsignificant). Interleukin (IL)-6 serum concentrations tended to be higher in VNS than in sham (34.3 ± 8.3 vs. 16.1 ± 4.6 pg/ml, P = 0.06), and positive correlations were found between NO-dependent relaxation of the LPCA and serum levels of IL-6 (r = +0.70, P < 0.05) and IL-10 (r = +0.56, P < 0.05) and between aortic eNOS activation and IL-10 (r = +0.48, P < 0.05). In conclusion, chronic VNS prevents hypertension-induced endothelial dysfunction and aortic stiffening in an animal model of severe hypertension. We speculate that anti-inflammatory mechanisms may contribute to these effects. PMID:27208157

  19. Long-term voluntary running improves diet-induced adiposity in young adult mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of long-term voluntary running on diet-induced adiposity in male C57BL/6 mice. Four-week old mice (n = 15 per group) were fed the AIN93G diet or a 45% high-fat diet (% kcal.) with or without access to in-cage activity wheels for 14 weeks. The high-fat die...

  20. Time-restricted feeding reduces adiposity in mice fed a high-fat diet.

    PubMed

    Sundaram, Sneha; Yan, Lin

    2016-06-01

    Disruption of the circadian rhythm contributes to obesity. This study tested the hypothesis that time-restricted feeding (TRF) reduces high-fat diet-induced increase in adiposity. Male C57BL/6 mice were fed the AIN93G or the high-fat diet ad libitum (ad lib); TRF of the high-fat diet for 12 or 8hours during the dark cycle was initiated when high-fat diet-fed mice exhibited significant increases in body weight. Energy intake of the TRF 12-hour group was not different from that of the high-fat ad lib group, although that of the TRF 8-hour group was slightly but significantly lower. Restricted feeding of the high-fat diet reduced body fat mass and body weight compared with mice fed the high-fat diet ad lib. There were no differences in respiratory exchange ratio (RER) among TRF and high-fat ad lib groups, but the RER of these groups was lower than that of the AIN93G group. Energy expenditure of the TRF groups was slightly but significantly lower than that of the high-fat ad lib group. Plasma concentrations of ghrelin were increased in TRF groups compared with both AIN93G and high-fat ad lib groups. Elevations of plasma concentrations of insulin, leptin, monocyte chemoattractant protein-1, and tissue inhibitor metalloproteinase-1 by high-fat ad lib feeding were reduced by TRF to the levels of mice fed the AIN93G diet. In conclusion, TRF during the dark cycle reduces high-fat diet-induced increases in adiposity and proinflammatory cytokines. These results indicate that circadian timing of food intake may prevent obesity and abate obesity-related metabolic disturbance. PMID:27188906

  1. Persistent Chromatin Modifications Induced by High Fat Diet.

    PubMed

    Leung, Amy; Trac, Candi; Du, Juan; Natarajan, Rama; Schones, Dustin E

    2016-05-13

    Obesity is a highly heritable complex disease that results from the interaction of multiple genetic and environmental factors. Formerly obese individuals are susceptible to metabolic disorders later in life, even after lifestyle changes are made to mitigate the obese state. This is reminiscent of the metabolic memory phenomenon originally observed for persistent complications in diabetic patients, despite subsequent glycemic control. Epigenetic modifications represent a potential mediator of this observed memory. We previously demonstrated that a high fat diet leads to changes in chromatin accessibility in the mouse liver. The regions of greatest chromatin changes in accessibility are largely strain-dependent, indicating a genetic component in diet-induced chromatin alterations. We have now examined the persistence of diet-induced chromatin accessibility changes upon diet reversal in two strains of mice. We find that a substantial fraction of loci that undergo chromatin accessibility changes with a high fat diet remains in the remodeled state after diet reversal in C57BL/6J mice. In contrast, the vast majority of diet-induced chromatin accessibility changes in A/J mice are transient. Our data also indicate that the persistent chromatin accessibility changes observed in C57BL/6J mice are associated with specific transcription factors and histone post-translational modifications. The persistent loci identified here are likely to be contributing to the overall phenotype and are attractive targets for therapeutic intervention. PMID:27006400

  2. Diet-Induced Metabolic Disturbances As Modulators of Brain Homeostasis

    PubMed Central

    Zhang, Le; Bruce-Keller, Annadora J.; Dasuri, Kalavathi; Nguyen, AnhThao; Liu, Dr Ying; Keller, Jeffrey N.

    2009-01-01

    A number of metabolic disturbances occur in response to the consumption of a high fat Western diet. Such metabolic disturbances can include the progressive development of hyperglycemia, hyperinsulemia, obesity, metabolic syndrome, and diabetes. Cumulatively, diet-induced disturbance in metabolism are known to promote increased morbidity and negatively impact life expectancy through a variety of mechanisms. While the impact of metabolic disturbances on the hepatic, endocrine, and cardiovascular systems are well established there remains a noticeable void in understanding the basis by which the central nervous system (CNS) becomes altered in response to diet-induced metabolic dysfunction. In particular, it remains to be fully elucidated which established features of diet-induced pathogenesis (observed in non-CNS tissues) are recapitulated in the brain, and identification as to whether the observed changes in the brain are a direct or indirect effect of peripheral metabolic disturbances. This review will focus on each of these key issues and identify some critical experimental questions which remain to be elucidated experimentally, as well as provide an outline of our current understanding for how diet-induced alterations in metabolism may impact the brain during aging and age-related diseases of the nervous system. PMID:18926905

  3. Nonalcoholic steatohepatitis induced by a high-fat diet promotes diethylnitrosamine initiated early hepatocarcinogenesis in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) are at a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low dose of hepatic carcinogen die...

  4. Nonalcoholic Steatohepatitis Induced by a High-Fat Diet Promotes Diethylnitrosamine Initiated Early Hepatocarcinogenesis in Rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been suggested that patients with nonalcoholic steatohepatitis (NASH) have a high risk for liver cancer. However, it is unknown whether high-fat diet induced NASH promotes chemical carcinogen-initiated hepatocarcinogenesis. In the present study, Sprague-Dawley rats were injected with a low d...

  5. Eicosapentaenoic acid regulates brown adipose tissue gene expression and metabolism in high fat fed mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) is a thermogenic tissue, a key regulator of energy balance and a potential therapeutic target for obesity. We previously reported that eicosapentaenoic acid (EPA) reduced high fat (HF) diet-induced obesity and insulin resistance in mice, independent of energy intake. We hy...

  6. Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet.

    PubMed

    Senaphan, Ketmanee; Kukongviriyapan, Upa; Sangartit, Weerapon; Pakdeechote, Poungrat; Pannangpetch, Patchareewan; Prachaney, Parichat; Greenwald, Stephen E; Kukongviriyapan, Veerapol

    2015-08-01

    Metabolic syndrome is a cluster of metabolic abnormalities characterized by obesity, insulin resistance, hypertension and dyslipidemia. Ferulic acid (FA) is the major phenolic compound found in rice oil and various fruits and vegetables. In this study, we examined the beneficial effects of FA in minimizing insulin resistance, vascular dysfunction and remodeling in a rat model of high-carbohydrate, high-fat diet-induced metabolic changes, which is regarded as an analogue of metabolic syndrome (MS) in man. Male Sprague-Dawley rats were fed a high carbohydrate, high fat (HCHF) diet and 15% fructose in drinking water for 16 weeks, where control rats were fed with standard chow diet and tap water. FA (30 or 60 mg/kg) was orally administered to the HCHF and control rats during the last six weeks of the study. We observed that FA significantly improved insulin sensitivity and lipid profiles, and reduced elevated blood pressure, compared to untreated controls (p < 0.05). Moreover, FA also improved vascular function and prevented vascular remodeling of mesenteric arteries. The effects of FA in HCHF-induced MS may be realized through suppression of oxidative stress by down-regulation of p47phox, increased nitric oxide (NO) bioavailability with up-regulation of endothelial nitric oxide synthase (eNOS) and suppression of tumor necrosis factor-α (TNF-α). Our results suggest that supplementation of FA may have health benefits by minimizing the cardiovascular complications of MS and alleviating its symptoms. PMID:26247970

  7. Ferulic Acid Alleviates Changes in a Rat Model of Metabolic Syndrome Induced by High-Carbohydrate, High-Fat Diet

    PubMed Central

    Senaphan, Ketmanee; Kukongviriyapan, Upa; Sangartit, Weerapon; Pakdeechote, Poungrat; Pannangpetch, Patchareewan; Prachaney, Parichat; Greenwald, Stephen E.; Kukongviriyapan, Veerapol

    2015-01-01

    Metabolic syndrome is a cluster of metabolic abnormalities characterized by obesity, insulin resistance, hypertension and dyslipidemia. Ferulic acid (FA) is the major phenolic compound found in rice oil and various fruits and vegetables. In this study, we examined the beneficial effects of FA in minimizing insulin resistance, vascular dysfunction and remodeling in a rat model of high-carbohydrate, high-fat diet-induced metabolic changes, which is regarded as an analogue of metabolic syndrome (MS) in man. Male Sprague-Dawley rats were fed a high carbohydrate, high fat (HCHF) diet and 15% fructose in drinking water for 16 weeks, where control rats were fed with standard chow diet and tap water. FA (30 or 60 mg/kg) was orally administered to the HCHF and control rats during the last six weeks of the study. We observed that FA significantly improved insulin sensitivity and lipid profiles, and reduced elevated blood pressure, compared to untreated controls (p < 0.05). Moreover, FA also improved vascular function and prevented vascular remodeling of mesenteric arteries. The effects of FA in HCHF-induced MS may be realized through suppression of oxidative stress by down-regulation of p47phox, increased nitric oxide (NO) bioavailability with up-regulation of endothelial nitric oxide synthase (eNOS) and suppression of tumor necrosis factor-α (TNF-α). Our results suggest that supplementation of FA may have health benefits by minimizing the cardiovascular complications of MS and alleviating its symptoms. PMID:26247970

  8. High Fat Feeding Induces Hepatic Fatty Acid Elongation in Mice

    PubMed Central

    Oosterveer, Maaike H.; van Dijk, Theo H.; Tietge, Uwe J. F.; Boer, Theo; Havinga, Rick; Stellaard, Frans; Groen, Albert K.; Kuipers, Folkert; Reijngoud, Dirk-Jan

    2009-01-01

    by fish oil prevents from high fat diet-induced hepatic steatosis in mice. PMID:19557132

  9. Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity.

    PubMed

    Lim, Kyungjoon; Barzel, Benjamin; Burke, Sandra L; Armitage, James A; Head, Geoffrey A

    2016-08-01

    High fat diet (HFD)-induced hypertension in rabbits is neurogenic and caused by the central action of leptin, which is thought to be dependent on activation of α-melanocortin-stimulating hormone (α-MSH) and neuropeptide Y-positive neurons projecting to the dorsomedial hypothalamus (DMH) and ventromedial hypothalamus (VMH). However, leptin may act directly in these nuclei. Here, we assessed the contribution of leptin, α-MSH, and neuropeptide Y signaling in the DMH and VMH to diet-induced hypertension. Male New Zealand white rabbits were instrumented with a cannula for drug injections into the DMH or VMH and a renal sympathetic nerve activity (RSNA) electrode. After 3 weeks of an HFD (13.3% fat; n=19), rabbits exhibited higher RSNA, mean arterial pressure (MAP), and heart rate compared with control diet-fed animals (4.2% fat; n=15). Intra-VMH injections of a leptin receptor antagonist or SHU9119, a melanocortin 3/4 receptor antagonist, decreased MAP, heart rate, and RSNA compared with vehicle in HFD rabbits (P<0.05) but not in control diet-fed animals. By contrast, α-MSH or neuropeptide Y injected into the VMH had no effect on MAP but produced sympathoexcitation in HFD rabbits (P<0.05) but not in control diet-fed rabbits. The effects of the leptin antagonist, α-MSH, or neuropeptide Y injections into the DMH on MAP or RSNA of HFD rabbits were not different from those after vehicle injection. α-MSH into the DMH of control diet-fed animals did increase MAP, heart rate, and RSNA. We conclude that the VMH is the likely origin of leptin-mediated sympathoexcitation and α-MSH hypersensitivity that contribute to obesity-related hypertension. PMID:27296999

  10. High-carbohydrate high-fat diet–induced metabolic syndrome and cardiovascular remodeling in rats.

    PubMed

    Panchal, Sunil K; Poudyal, Hemant; Iyer, Abishek; Nazer, Reeza; Alam, Ashraful; Diwan, Vishal; Kauter, Kathleen; Sernia, Conrad; Campbell, Fiona; Ward, Leigh; Gobe, Glenda; Fenning, Andrew; Brown, Lindsay

    2011-01-01

    The prevalence of metabolic syndrome including central obesity, insulin resistance, impaired glucose tolerance, hypertension, and dyslipidemia is increasing. Development of adequate therapy for metabolic syndrome requires an animal model that mimics the human disease state. Therefore, we have characterized the metabolic, cardiovascular, hepatic, renal, and pancreatic changes in male Wistar rats (8-9 weeks old) fed on a high-carbohydrate, high-fat diet including condensed milk (39.5%), beef tallow (20%), and fructose (17.5%) together with 25% fructose in drinking water; control rats were fed a cornstarch diet. During 16 weeks on this diet, rats showed progressive increases in body weight, energy intake, abdominal fat deposition, and abdominal circumference along with impaired glucose tolerance, dyslipidemia, hyperinsulinemia, and increased plasma leptin and malondialdehyde concentrations. Cardiovascular signs included increased systolic blood pressure and endothelial dysfunction together with inflammation, fibrosis, hypertrophy, increased stiffness, and delayed repolarization in the left ventricle of the heart. The liver showed increased wet weight, fat deposition, inflammation, and fibrosis with increased plasma activity of liver enzymes. The kidneys showed inflammation and fibrosis, whereas the pancreas showed increased islet size. In comparison with other models of diabetes and obesity, this diet-induced model more closely mimics the changes observed in human metabolic syndrome. PMID:20966763

  11. Diet-Induced Obesity in the Selenocysteine Lyase Knockout Mouse

    PubMed Central

    Gilman, Christy L.; Hashimoto, Ann C.; Ogawa-Wong, Ashley N.; Berry, Marla J.

    2015-01-01

    Abstract Aims: Selenocysteine lyase (Scly) mediates selenocysteine decomposition. It was previously demonstrated that, upon adequate caloric intake (12% kcal fat) and selenium deficiency, disruption of Scly in mice leads to development of metabolic syndrome. In this study, we investigate the effect of a high-fat (45% kcal) selenium-adequate diet in Scly knockout (KO) mice on development of metabolic syndrome. Involvement of selenoproteins in energy metabolism after Scly disruption was also examined in vitro in the murine hepatoma cell line, Hepa1-6, following palmitate treatment. Results: Scly KO mice were more susceptible to diet-induced obesity than their wild-type counterparts after feeding a high-fat selenium-adequate diet. Scly KO mice had aggravated hyperinsulinemia, hypercholesterolemia, glucose, and insulin intolerance, but unchanged inflammatory cytokines and expression of most selenoproteins, except increased serum selenoprotein P (Sepp1). Scly KO mice also exhibited enhanced hepatic levels of pyruvate and enzymes involved in the regulation of pyruvate cycling, such as pyruvate carboxylase (Pcx) and pyruvate dehydrogenase (Pdh). However, in vitro silencing of Scly in Hepa1-6 cells led to diminished Sepp1 expression, and concomitant palmitate treatment decreased Pdh expression. Innovation: The role of selenium in lipid metabolism is recognized, but specific selenium-dependent mechanisms leading to obesity are unclear. This study uncovers that Scly has a remarkable effect on obesity and metabolic syndrome development triggered by high-fat exposure, independent of the expression of most selenoproteins. Conclusion: Diet-induced obesity in Scly KO mice is aggravated, with effects on pyruvate levels and consequent activation of energy metabolism independent of selenoprotein levels. Antioxid. Redox Signal. 23, 761–774. PMID:26192035

  12. Mulberry ethanol extract attenuates hepatic steatosis and insulin resistance in high-fat diet-fed mice.

    PubMed

    Song, Haizhao; Lai, Jia; Tang, Qiong; Zheng, Xiaodong

    2016-07-01

    Nonalcoholic fatty liver disease is one of the most common complications of obesity. Mulberry is an important source of phytochemicals, such as anthocyanins, polyphenols and flavonoids, which are related to its antioxidant activity. In this study, we developed a hypothesis that mulberry exerted beneficial effects on metabolic disorders and evaluated the influence of the mulberry ethanol extract (MEE) on high-fat diet-induced hepatic steatosis and insulin resistance in mice. Thirty-six male C57BL/6J mice were assigned into 3 groups and fed either a low-fat diet or a high-fat diet with or without supplementation with MEE. Our results showed that administration of MEE reduced diet-induced body weight gain, improved high-fat diet-induced hepatic steatosis and adipose hypertrophy, alleviated insulin resistance, and improved glucose homeostasis. Analysis of hepatic gene expression indicated that MEE treatment changed the expression profile of genes involved in lipid and cholesterol metabolism. In conclusion, the present study demonstrated that MEE supplementation protected mice from high-fat diet-induced obesity, hepatic steatosis, and insulin resistance. Moreover, the protective effects of MEE were associated with the induction of fatty acid oxidation and decreased fatty acid and cholesterol biosynthesis. PMID:27262537

  13. Time-restricted feeding of a high-fat diet reduces diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Reducing obesity may alleviate many medical complications including diabetes, cardiovascular disease and cancer. It has been suggested that obesity is contributed by the disruption of the circadian rhythms in addition to increased caloric intake. Restricting feeding to particular times of the day ma...

  14. Effect of tomato extract supplementation against high-fat diet-induced hepatic lesions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Higher intake of tomatoes or tomato-based products has been associated with lower risk for liver cancer. In this study, we investigated the effects of supplementing tomato extract (TE), which contains mainly lycopene (LY) and less amounts of its precursors, phytoene (PT) and phytofluene (PTF) agains...

  15. Curcumin modulation of high fat diet-induced atherosclerosis and steatohepatosis in LDL receptor deficient mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consuming curcumin may benefit health by modulating lipid metabolism and suppressing atherogenesis. Fatty acid binding proteins (FABP-4/aP2) and CD36 expression are key factors in lipid accumulation in macrophages and foam cell formation in atherogenesis. Our earlier observations suggest that curcum...

  16. Moderate alcohol consumption aggravates high fat-diet induced steatohepatitis in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Nonalcoholic steatohepatitis (NASH) develops in the absence of chronic and excessive alcohol consumption. However, it remains unknown whether moderate alcohol consumption aggravates liver inflammation in pre-existing NASH condition. Methods: Sprague-Dawley rats were first fed ad libitum...