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Sample records for high-fat fed rats

  1. Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet

    PubMed Central

    Mangge, Harald; Prüller, Florian; Zelzer, Sieglinde; Ainödhofer, Herwig; Pailer, Sabine; Kieslinger, Petra; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Cvirn, Gerhard; Gruber, Hans-Jürgen

    2015-01-01

    Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased—and hyperthyroid animals significantly decreased—ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition. PMID:26184174

  2. Hypothyroidism Exacerbates Thrombophilia in Female Rats Fed with a High Fat Diet.

    PubMed

    Mangge, Harald; Prüller, Florian; Zelzer, Sieglinde; Ainödhofer, Herwig; Pailer, Sabine; Kieslinger, Petra; Haybaeck, Johannes; Obermayer-Pietsch, Barbara; Cvirn, Gerhard; Gruber, Hans-Jürgen

    2015-01-01

    Clotting abnormalities are discussed both in the context with thyroid dysfunctions and obesity caused by a high fat diet. This study aimed to investigate the impact of hypo-, or hyperthyroidism on the endogenous thrombin potential (ETP), a master indicator of clotting activation, on Sprague Dawley rats fed a normal or high fat diet. Female Sprague Dawley rats (n = 66) were grouped into normal diet (ND; n = 30) and high-fat diet (HFD; n = 36) groups and subdivided into controls, hypothyroid and hyperthyroid groups, induced through propylthiouracil or triiodothyronine (T3) treatment, respectively. After 12 weeks of treatment ETP, body weight and food intake were analyzed. Successfully induced thyroid dysfunction was shown by T3 levels, both under normal and high fat diet. Thyroid dysfunction was accompanied by changes in calorie intake and body weight. In detail, compared to euthyroid controls, hypothyroid rats showed significantly increased-and hyperthyroid animals significantly decreased-ETP levels. High fat diet potentiated these effects in both directions. In summary, we are the first to show that hypothyroidism and high fat diet potentiate the thrombotic capacity of the clotting system in Sprague Dawley rats. This effect may be relevant for cardiovascular disease where thyroid function is poorly understood as a pathological contributor in the context of clotting activity and obesogenic nutrition. PMID:26184174

  3. Adipose tissue chromium and vanadium disbalance in high-fat fed Wistar rats.

    PubMed

    Tinkov, Alexey A; Popova, Elizaveta V; Polyakova, Valentina S; Kwan, Olga V; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-01-01

    The primary objective of the current study is to investigate the relationship between adipose tissue chromium and vanadium content and adipose tissue dysfunction in a model of diet-induced obesity. A total of 26 female Wistar rats were fed either standard or high-fat diet (31.6% of fat from total caloric content) for 3 months. High-fat-feeding resulted in 21 and 33% decrease in adipose tissue chromium and vanadium content, respectively. No change was seen in hair chromium or vanadium levels. Statistical analysis revealed a significant inverse correlation of adipose tissue Cr and V with animal morphometric parameters and adipocyte size. Significant inverse dependence was observed between adipose tissue Cr and V and serum leptin and proinflammatory cytokines' levels. At the same time, adipose tissue Cr and V levels were characterized by positive correlation between serum adiponectin and adiponectin/leptin ratio. Adipose tissue Cr and V were inversely correlated (p<0.05) with insulin and homeostatic model assessment insulin resistance index (HOMA-IR) levels. Cr and V concentrations were not correlated with serum glucose in either high-fat fed or control rats; however, both serum glucose and HOMA-IR levels were significantly higher in high-fat fed, compared to control, rats. The results allow to hypothesize that impairment of adipose tissue Cr and V content plays a certain role in the development of adipose tissue endocrine dysfunction in obesity. PMID:25194956

  4. A krill oil supplemented diet suppresses hepatic steatosis in high-fat fed rats.

    PubMed

    Ferramosca, Alessandra; Conte, Annalea; Burri, Lena; Berge, Kjetil; De Nuccio, Francesco; Giudetti, Anna Maria; Zara, Vincenzo

    2012-01-01

    Krill oil (KO) is a dietary source of n-3 polyunsaturated fatty acids, mainly represented by eicosapentaenoic acid and docosahexaenoic acid bound to phospholipids. The supplementation of a high-fat diet with 2.5% KO efficiently prevented triglyceride and cholesterol accumulation in liver of treated rats. This effect was accompanied by a parallel reduction of the plasma levels of triglycerides and glucose and by the prevention of a plasma insulin increase. The investigation of the molecular mechanisms of KO action in high-fat fed animals revealed a strong decrease in the activities of the mitochondrial citrate carrier and of the cytosolic acetyl-CoA carboxylase and fatty acid synthetase, which are both involved in hepatic de novo lipogenesis. In these animals a significant increase in the activity of carnitine palmitoyl-transferase I and in the levels of carnitine was also observed, suggesting a concomitant stimulation of hepatic fatty acid oxidation. The KO supplemented animals also retained an efficient mitochondrial oxidative phosphorylation, most probably as a consequence of a KO-induced arrest of the uncoupling effects of a high-fat diet. Lastly, the KO supplementation prevented an increase in body weight, as well as oxidative damage of lipids and proteins, which is often found in high-fat fed animals. PMID:22685607

  5. Endurance in high-fat-fed rats: effects of carbohydrate content and fatty acid profile.

    PubMed

    Helge, J W; Ayre, K; Chaunchaiyakul, S; Hulbert, A J; Kiens, B; Storlien, L H

    1998-10-01

    The purpose of this experiment was to study endurance performance and substrate storage and utilization in fat- or carbohydrate-fed rats. Ninety-nine rats were randomly divided into three groups and over 4 wk were fed either a carbohydrate-rich [CHO; 10% total energy content in the diet (E%) fat, 20 E% protein, 70 E% carbohydrate] diet or one of two fat-rich diets (65 E% fat, 20 E% protein, 15 E% carbohydrate) containing either saturated (Sat) or monounsaturated fatty acids (Mono). Each dietary group was randomly assigned to a trained (6 days/wk, progressive to 60 min, 28 m/min at a 10% incline) or a sedentary group. Rats were killed either before or after a treadmill endurance run to exhaustion. Training increased endurance (206%), but diet composition did not affect endurance in either trained or sedentary rats. beta-Hydroxyacyl-CoA dehydrogenase activity was increased in fat-fed but not carbohydrate-fed rats (P < 0.05). Respiratory exchange ratio during the initial phase of exercise was lower after the Mono compared with the Sat diet (P < 0. 05) and higher after the CHO than the Sat diet (P < 0.05). Thus adaptation to a high-fat diet containing a moderate amount of carbohydrates did not induce enhanced endurance in either trained or untrained rats; however, substrate utilization was modulated by both amount and type of dietary fat during the initial stage of exercise in trained and sedentary rats. PMID:9760326

  6. 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

  7. Supplementary chromium(III) propionate complex does not protect against insulin resistance in high-fat-fed rats.

    PubMed

    Król, Ewelina; Krejpcio, Zbigniew; Iwanik, Katarzyna

    2014-02-01

    Improper eating habits such as high-fat or high-carbohydrate diets are responsible for metabolic changes resulting in impaired glucose tolerance, hyperinsulinemia, insulin resistance, and ultimately diabetes. Although the essentiality of trivalent chromium for humans has been recently questioned by researchers, pharmacological dosages of this element can improve insulin sensitivity in experimental animals and diabetic subjects. The aim of the study was to assess the preventive potential of the supplementary chromium(III) propionate complex (CrProp) in rats fed a high-fat diet. The experiment was conducted on 32 male Wistar rats divided into four groups and fed the following diets: the control (C, AIN-93G), high-fat diets (HF, 40% energy from fat), and a high-fat diet supplemented with CrProp at dosages of 10 and 50 mg Cr/kg diet (HF + Cr10 and HF + Cr50, respectively). After 8 weeks, high-fat feeding led to an increased body mass, hyperinsulinemia, insulin resistance, a decreased serum urea concentration, accumulation of lipid droplets in hepatocytes, and increased renal Fe and splenic Cu contents. Supplementary CrProp in both dosages did not alleviate these changes but increased renal Cr content and normalized splenic Cu content in high-fat-fed rats. Supplementary CrProp does not prevent the development of insulin resistance in rats fed a high-fat diet. PMID:24415067

  8. Arctium lappa ameliorates endothelial dysfunction in rats fed with high fat/cholesterol diets

    PubMed Central

    2012-01-01

    Background Arctium lappa L. (Asteraceae), burdock, is a medicinal plant that is popularly used for treating hypertension, gout, hepatitis, and other inflammatory disorders. This study was performed to test the effect of ethanol extract of Arctium lappa L. (EAL) seeds on vascular reactivity and inflammatory factors in rats fed a high fat/cholesterol diet (HFCD). Method EAL-I (100 mg·kg−1/day), EAL-II (200 mg·kg−1/day), and fluvastatin (3 mg·kg−1/day) groups initially received HFCD alone for 8 weeks, with EAL supplementation provided during the final 6 weeks. Results Treatment with low or high doses of EAL markedly attenuated plasma levels of triglycerides and augmented plasma levels of high-density lipoprotein (HDL) in HFCD-fed rats. Chronic treatment with EAL markedly reduced impairments of acetylcholine (ACh)-induced relaxation of aortic rings. Furthermore, chronic treatment with EAL significantly lowered systolic blood pressure (SBP) and maintained smooth and flexible intimal endothelial layers in HFCD-fed rats. Chronic treatment with EAL suppressed upregulation of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in the aorta. Chronic treatment with EAL also suppressed increases in matrix metalloproteinase (MMP)-2 expression. These results suggested that EAL can inhibit HFCD-induced vascular inflammation in the rat model. Conclusion The present study provides evidence that EAL ameliorates HFCD-induced vascular dysfunction through protection of vascular relaxation and suppression of vascular inflammation. PMID:22866890

  9. Lipoprotein lipase activity and chylomicron clearance in rats fed a high fat diet

    SciTech Connect

    Brown, C.M.; Layman, D.K.

    1988-11-01

    The relationships of tissue and plasma lipoprotein lipase (LPL) activities to tissue uptake and plasma clearance of UC-labeled chylomicron-triglyceride ( UC-CM-TG) were studied in female rats fed isoenergetic and isonitrogenous control (12% kJ from fat) or high fat diets (72% kJ from fat) for 8 wk. Animals fed the high-fat diet had higher levels of fasting plasma triglycerides and lower LPL activities in heart, renal adipose tissue and post-heparin plasma. Changes in LPL activities of skeletal muscles varied among muscles with higher values in the soleus and plantaris (32-61%) and no differences in the gastrocnemius. The lower LPL activity in renal adipose tissue was associated with lower uptake of fatty acids from UC-CM-TG by adipose. Fatty-acid uptake from labeled TG was not associated with tissue LPL activity in other tissues. Clearance of UC-CM-TG from plasma and the half-lives of UC-CM-TG were similar in both dietary groups. These data indicate that tissue and plasma LPL activities are not a direct index of uptake of fatty acids by tissues or clearance of chylomicron triglycerides.

  10. 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

  11. Spent turmeric reduces fat mass in rats fed a high-fat diet.

    PubMed

    Han, Kyu-Ho; Lee, Chang-Hyun; Kinoshita, Mikio; Oh, Chan-Ho; Shimada, Ken-Ichiro; Fukushima, Michihiro

    2016-04-20

    Indigestible carbohydrates may improve obesity. Spent turmeric contains high levels of dietary fibre and resistant starch (RS), which have fermentation potential in vitro. We hypothesised that indigestible carbohydrates in spent turmeric might prevent obesity development. In the first study, rats were administered 10% turmeric powder (TP) or spent turmeric powder (STP) in a high-fat (HF) diet for 28 d. In the second study, rats were fed 10% STP in a HF diet with or without antibiotics for 15 d. In the third study, rats were treated with a STP-containing suspension. In study 1, the TP and STP diet increased the caecal short-chain fatty acid (SCFA) content compared to that of a control diet. The lower energy intake in the TP and STP group was strongly related to the decrease in visceral fat weight. In study 2, after caecal fermentation suppression with antibiotics, STP treatment decreased the visceral fat mass. In study 3, the plasma glucose levels and incremental area under the curve (AUC) after ingestion of a STP-containing suspension were lower than those after ingestion of suspension alone. These findings suggest the reduction of carbohydrate absorption during the gastrointestinal passage after TP and STP treatment. Our data indicate that the reduced obesity development in rats fed a HF diet may be attributed to the low metabolisable energy density of carbohydrates in the spent turmeric, independent of SCFA-mediated factors. PMID:26583652

  12. Dietary chitosan improves hypercholesterolemia in rats fed high-fat diets.

    PubMed

    Zhang, Jiali; Liu, Jingna; Li, Ling; Xia, Wenshui

    2008-06-01

    The hypolipidemic mechanism of chitosan was investigated in male Sprague-Dawley rats. Animals were divided into 5 groups (n = 8): a normal fat control group, a high-fat control group (HF), a positive control group (CR), and 2 chitosan groups (CIS1 and CIS2). Chitosan was fed at the beginning (CIS1) and after 2 weeks (CIS2). A commercial diet with 5% (wt/wt) cellulose (HF), cholestyramine (CR), or chitosan (CIS1, CIS2) was fed for 6 weeks. Chitosan did not affect food intake but decreased body weight gain and significantly increased fecal fat and cholesterol excretion, reduced the lipid level in plasma and liver, increased liver hepatic and lipoprotein lipase activities compared with HF (P < .05), and tended to relieve the degenerated fatty liver tissue. No significant differences in all measurements were found between the CIS1 and CIS2 groups although the CIS1 rats exhibited lower lipid levels compared to those in the CIS2 group. The results suggest that chitosan reduced the absorption of dietary fat and cholesterol in vivo and could effectively improve hypercholesterolemia in rats. PMID:19083436

  13. Myocardial stereological adaptations in wistar rats fed with different high-fat diets during 18 months.

    PubMed

    Aguila, M B; Mandarim-de-Lacerda, C A

    2001-12-01

    This study has the purpose of investigating the influence of different high-fat experimental diets on myocardial structure in rats. Twenty-seven male rats were fed from 21 d old (postnatal age) until 18 mo old with one of the following supplemented diets: soybean oil (S) (n= 6), canola oil (CA) (n= 8), or lard and egg yolk (LE) (n= 6) or canola oil+ lard and egg yolk (CA+LE) (n=7). The blood pressure (BP) was measured, and after the sacrifice the cardiac biometry and the myocardial stereology were determined: cross-sectional area of cardiomyocyte (A), volume density (Vv), surface density (Sv), and length density (Lv) in relation to the cardiomyocytes (cm), connective tissue (ct), and blood vessels (v). The CA group rats had lower BP, A[cm], and Vv[ct]; they had greater Vv[cm], Sv[cm], Vv[v], Lv[v], and Sv[v] than the other groups. The S rats had intermediary values for the myocardium and blood vessel parameters between the CA and LE group rats. These results support the notion that the long-term use of canola oil in the diet is better to preserve the myocardium structure, including microvascularization, than soybean oil or lard and egg yolk. PMID:11922113

  14. Hypolipidemic effect of dihydroisoquinoline oxaziridine in high-fat diet-fed rats.

    PubMed

    Aydi, Rihab; Gara, Amel Ben; Chaaben, Rim; Saad, Hajer Ben; Fki, Lotfi; ElFeki, Abdelfattah; Belghith, Hafedh; Belghith, Karima; Kammoun, Majed

    2016-08-01

    Obesity is a serious health problem that increases the risk of many complications, including diabetes and cardiovascular disease. This study aims to evaluate, for the first time, the effects of oxaziridine 3 on lipoprotein lipase activity in the serum of rats fed with a high-fat diet (HFD) on body weight, lipid profile and liver-kidney functions. The administration of oxaziridine 3 to HFD-rats lowered body weight and inhibited the lipase activity of obese rats leading to notable decrease of T-Ch, TGs and LDL-Ch levels accompanied with an increase in HDL-Ch concentration in serum. Moreover, the findings of this study revealed that oxaziridine 3 helped to protect liver tissue from the appearance of fatty cysts. Additionally, oxaziridine 3 administration to HFD-rats induces antioxidant activity proven by the increase of superoxide dismutase (SOD) and catalase (CAT) activities and the decrease in Thiobarbituric acid reactive substances (TBARS) levels. It also induces the protection of liver-kidney functions confirmed by a decrease in the levels of toxicity parameters in blood. PMID:27470409

  15. Alaska pollack protein prevents the accumulation of visceral fat in rats fed a high fat diet.

    PubMed

    Oishi, Yoshie; Dohmoto, Nobuhiko

    2009-04-01

    In the first study (Study 1), 4-wk-old Sprague-Dawley (SD) rats were fed high fat diets containing casein, Alaska pollack, yellowfin tuna, or chicken as the protein source for 28 d. The purpose of this study was to compare the effect of Alaska pollack protein with other animal proteins (casein, yellowfin tuna, and chicken) on the prevention of visceral fat accumulation. We found that Alaska pollack protein was a more potent inhibitor of visceral fat accumulation than the other proteins (p<0.05). In the second study (Study 2), we determined the quantity of Alaska pollack protein needed to have an effect. To test this, 4-wk-old SD rats were fed diets containing different percentages of Alaska pollack proteins (0, 3, 10, 30 or 100%) to replace casein as the protein source for 28 d. The diets with 30 or 100% Alaska pollack protein as the protein source prevented visceral fat accumulation and elevated plasma adiponectin levels. Based on these findings, an inhibitory effect on the accumulation of visceral fats can be achieved by consuming a diet in which 30% or more of the total protein content comes from Alaska pollack. PMID:19436142

  16. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    PubMed

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects. PMID:23982154

  17. Beneficial influence of dietary curcumin, capsaicin and garlic on erythrocyte integrity in high-fat fed rats.

    PubMed

    Kempaiah, Rayavara K; Srinivasan, Krishnapura

    2006-07-01

    In rats rendered hyperlipidemic by maintaining them on a high-fat diet (30%) for 8 weeks, inclusion of spice principles [curcumin (0.2%) or capsaicin (0.015%)] or garlic (2.0%) in the diet produced significant hypotriglyceridemic effect. Plasma cholesterol remained unaffected in high-fat treatment. Hepatic triglyceride content was significantly higher in high-fat fed rats, and this increase was effectively countered by inclusion of the hypolipidemic spice agents -- curcumin, capsaicin or garlic in the diet. The lipid profile of erythrocyte membranes of hyperlipidemic rats was similar to basal controls. An examination of the osmotic fragility of erythrocytes in various groups indicated that the red blood cells of hyperlipidemic rats display a slight resistance to osmotic lysis. Inclusion of spice principles [curcumin (0.2%) or capsaicin (0.015%)] or garlic (2.0%) in the diet, which produced the hypotriglyceridemic effect, appeared to beneficially correct this altered osmotic fragility of erythrocytes. Activities of ouabain-sensitive Na(+),K(+)-ATPase as well as acetylcholinesterase of erythrocyte membranes in high-fat fed rats remained unaltered. Activity of Ca(2+),Mg(2+)-ATPase in erythrocyte membrane was significantly decreased in high-fat fed animals, whereas dietary spice principles and garlic countered this reduction in enzyme activity. In the absence of any change in the cholesterol/phospholipid molar ratio in the erythrocyte membrane, a decreased activity of membrane-bound Ca(2+),Mg(2+)-ATPase could have probably contributed to the accumulation of intracellular calcium leading to the diminished deformability of the erythrocytes in high-fat fed rats. PMID:16263255

  18. Effects of α-lipoic acid on endothelial function in aged diabetic and high-fat fed rats

    PubMed Central

    Sena, C M; Nunes, E; Louro, T; Proença, T; Fernandes, R; Boarder, M R; Seiça, R M

    2007-01-01

    Background and purpose: This study was conducted to investigate the effects of α-lipoic acid (α-LA) on endothelial function in diabetic and high-fat fed animal models and elucidate the potential mechanism underlying the benefits of α-LA. Experimental approach: Plasma metabolites reflecting glucose and lipid metabolism, endothelial function, urinary albumin excretion (UAE), plasma and aortic malondialdehyde (MDA) and urinary 8-hydroxydeoxyguanosine (8-OHdG) were assessed in non-diabetic controls (Wistar rats), untreated Goto-Kakizaki (GK) diabetic and high-fat fed GK rats (fed with atherogenic diet only, treated with α-LA and treated with vehicle, for 3 months). Vascular eNOS, nitrotyrosine, carbonyl groups and superoxide anion were also assessed in the different groups. Key results: α-LA and soybean oil significantly reduced both total and non-HDL serum cholesterol and triglycerides induced by atherogenic diet. MDA, carbonyl groups, vascular superoxide and 8-OHdG levels were higher in GK and high-fat fed GK groups and fully reversed with α-LA treatment. High-fat fed GK diabetic rats showed significantly reduced endothelial function and increased UAE, effects ameliorated with α-LA. This endothelial dysfunction was associated with decreased NO production, decreased expression of eNOS and increased vascular superoxide production and nitrotyrosine expression. Conclusions and implications: α-LA restores endothelial function and significantly improves systemic and local oxidative stress in high-fat fed GK diabetic rats. Improved endothelial function due to α-LA was at least partially attributed to recoupling of eNOS and increased NO bioavailability and represents a pharmacological approach to prevent major complications associated with type 2 diabetes. PMID:17906683

  19. High fat diet-fed obese rats are highly sensitive to doxorubicin-induced cardiotoxicity

    SciTech Connect

    Mitra, Mayurranjan S.; Donthamsetty, Shashikiran; White, Brent; Mehendale, Harihara M.

    2008-09-15

    Often, chemotherapy by doxorubicin (Adriamycin) is limited due to life threatening cardiotoxicity in patients during and posttherapy. Recently, we have shown that moderate diet restriction remarkably protects against doxorubicin-induced cardiotoxicity. This cardioprotection is accompanied by decreased cardiac oxidative stress and triglycerides and increased cardiac fatty-acid oxidation, ATP synthesis, and upregulated JAK/STAT3 pathway. In the current study, we investigated whether a physiological intervention by feeding 40% high fat diet (HFD), which induces obesity in male Sprague-Dawley rats (250-275 g), sensitizes to doxorubicin-induced cardiotoxicity. A LD{sub 10} dose (8 mg doxorubicin/kg, ip) administered on day 43 of the HFD feeding regimen led to higher cardiotoxicity, cardiac dysfunction, lipid peroxidation, and 80% mortality in the obese (OB) rats in the absence of any significant renal or hepatic toxicity. Doxorubicin toxicokinetics studies revealed no change in accumulation of doxorubicin and doxorubicinol (toxic metabolite) in the normal diet-fed (ND) and OB hearts. Mechanistic studies revealed that OB rats are sensitized due to: (1) higher oxyradical stress leading to upregulation of uncoupling proteins 2 and 3, (2) downregulation of cardiac peroxisome proliferators activated receptor-{alpha}, (3) decreased plasma adiponectin levels, (4) decreased cardiac fatty-acid oxidation (666.9 {+-} 14.0 nmol/min/g heart in ND versus 400.2 {+-} 11.8 nmol/min/g heart in OB), (5) decreased mitochondrial AMP-{alpha}2 protein kinase, and (6) 86% drop in cardiac ATP levels accompanied by decreased ATP/ADP ratio after doxorubicin administration. Decreased cardiac erythropoietin and increased SOCS3 further downregulated the cardioprotective JAK/STAT3 pathway. In conclusion, HFD-induced obese rats are highly sensitized to doxorubicin-induced cardiotoxicity by substantially downregulating cardiac mitochondrial ATP generation, increasing oxidative stress and downregulating

  20. Piperine potentiates the hypocholesterolemic effect of curcumin in rats fed on a high fat diet.

    PubMed

    Tu, Yaosheng; Sun, Dongmei; Zeng, Xiaohui; Yao, Nan; Huang, Xuejun; Huang, Dane; Chen, Yuxing

    2014-07-01

    It has previously been demonstrated that curcumin possesses a hypocholesterolemic effect and potentiates numerous pharmacological effects of curcumin, however, the mechanisms underlying this hypocholesterolemic effect and the interaction between curcumin and piperine remain to be elucidated. In the present study, male Sprague-Dawley rats were fed on a high-fat diet (HFD) to establish a hyperlipidemia (HLP) model. Co-administration of curcumin plus piperine was found to decrease the levels of total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol in the serum and liver, as well as increase the levels of fecal TC, TG and total bile acid, compared with administration of curcumin alone. Curcumin plus piperine also markedly increased the levels of high-density lipoprotein cholesterol. Furthermore, compared with administration of curcumin alone, administration of curcumin plus piperine resulted in a significant upregulation of the activity and gene expression of apolipoprotein AI (ApoAI), lecithin cholesterol acyltransferase (LCAT), cholesterol 7α-hydroxylase (CYP7A1) and low-density lipoprotein receptor (LDLR). In conclusion, these results indicated that co-administration of curcumin plus piperine potentiates the hypocholesterolemic effects of curcumin by increasing the activity and gene expression of ApoAI, CYP7A1, LCAT and LDLR, providing a promising combination for the treatment of HLP. PMID:24944632

  1. Antihyperglycemic effects of fruits of privet (Ligustrum obtusifolium) in streptozotocin-induced diabetic rats fed a high fat diet.

    PubMed

    Lee, Sang-Il; Oh, Sung-Hee; Park, Kun-Young; Park, Bum-Ho; Kim, Jeong-Sook; Kim, Soon-Dong

    2009-02-01

    The protective effects of freeze-dried privet (Ligustrum obtusifolium) fruits (PFs) were observed in streptozotocin (STZ)-induced diabetic rats on a high fat diet by measuring levels of blood glucose, serum insulin, fructosamine, and hepatic reactive oxygen species generating and scavenging enzyme activities. A PF-supplemented diet was prepared by mixing an AIN-76 diet with powdered PF (final concentration, 1% or 2%). It was fed to STZ-induced diabetic rats on a high fat diet for 6 weeks. Diabetic animals receiving the PF-supplemented diet showed a significant increase in body weight, feed efficiency ratio, liver, kidney, and heart weight, and serum glucose, insulin, and fructosamine levels compared with high fat diet-fed diabetic animals. The treatment with PF showed improved hepatic glutathione S-transferase, superoxide dismutase, and xanthine oxidase activities as well as glutathione and lipid peroxide levels in the diabetic animals. Intracellular swelling and vacuole formation in diabetic pancreatic beta- and delta-cells were ameliorated by the PF-supplemented diet. Furthermore, necrosis of tubular epithelial cells and dilatation of luminal space in diabetic kidneys exhibited near-noninjured condition. This is the first time an antihyperglycemic effect of L. obtusifolium fruit in STZ-induced diabetic rats has been identified. PMID:19298203

  2. Effect of exercise and caloric restriction on DMBA induced mammary tumorigenesis and plasma lipids in rats fed high fat diets

    SciTech Connect

    Magrane, D. )

    1991-03-15

    Female Sprague-Dawley rats were given a single 10 mg dose of 7, 12-Dimethylbenz(a)anthracene (DMBA) and grouped as follows: (1) low fat-sedentary (LF-SED), (2) low fat-exercised (LF-EX), (3) high fat-sedentary (HF-SED), (4) high fat-exercised (HF-EX), (5) high fat-caloric restricted (HF-RES). Diets were isocaloric and contained 3.9% (LF) and 19.4% (HF) of corn oil. Group 5 was fed a 25% caloric restricted diet but with 24.6% fat content to equalize fat intake to HF-SED. After 12 weeks of diet or treadmill exercise, tumor data and plasma lipid profiles were determined. Results show that rats on HF-EX had more total tumors, % of tumors and tumors per tumor bearing rat than rats on HF-SED. The effect of exercise was also evident in LF-EX rats, when compared to LF-SED. Average tumor size and tumor volumes were not affected. The HF-RES group showed reduced tumor profiles compared to HF-SED. HDL, LDL, triglycerides and total cholesterol were unaffected by HF or LF diets or exercise. These data suggest that tumorigenesis is increased by moderate and constant exercise.

  3. Anti-Obesity Effects of Melastoma malabathricum var Alba Linn in Rats Fed with a High-Fat Diet.

    PubMed

    Karupiah, Sundram; Ismail, Zhari

    2015-06-01

    Obesity is one of the major public health problems worldwide and it is generally associated with many diseases. Although synthetic drugs are available for the treatment of obesity, herbal remedies may provide safe, natural, and cost-effective alternative to synthetic drugs. One example of such drugs is Melastoma malabathricum var Alba Linn (MM). Although several studies have been reported for the pharmacological activities of MM, there is no report on the anti-obesity effect of MM. The aim of the present study is to evaluate the anti-obesity potential of methanolic extract of MM. The anti-obesity effect of MM on rats fed with a high-fat diet was investigated through determination of the changes in body weight, fat weight, organ weights, and blood biochemicals. The animals in this study were divided into three groups: a normal group with a standard diet (N), a control group fed with high-fat diet (C), and a MM treatment group fed with high-fat (HFD + MM) diet for 8 weeks. There was no significant difference in the amount of food intake between control and HFD + MM treatments. These results also suggest that MM does not induce a dislike for the diet due to its smell or taste. The study shows that MM significantly prevented increases in body weight, cholesterol, LDL, HDL, and total lipids that resulted from the high-fat diet. MM also decreased the epididymal fat (E-fat) and retroperitoneal fat (R-fat) weights and phospholipid concentrations induced by the high-fat diet. On the basis of these findings, it was concluded that MM had anti-obesity effects by suppressing body weight gain and abdominal fat formation. PMID:25374344

  4. Increased contractile responses to 5-hydroxytryptamine and Angiotensin II in high fat diet fed rat thoracic aorta

    PubMed Central

    Ghatta, Srinivas; Ramarao, Poduri

    2004-01-01

    Background Feeding normal rats with high dietary levels of saturated fat leads to pathological conditions, which are quite similar to syndrome X in humans. These conditions such as hypertriglyceridemia, hypercholesterolemia, obesity, and hyperglycemia might induce hypertension through various mechanisms. Metabolic syndrome and the resulting NIDDM represent a major clinical challenge because implementation of treatment strategies is difficult. Vascular abnormalities probably contribute to the etiology of many diabetic complications including nephropathy, neuropathy, retinopathy, and cardiomyopathy. It has been shown that in Streptozotocin induced diabetic animals there is an increase in maximal responses to 5-Hydroxytryptamine and Angiotensin II. The purpose of this study was to evaluate High fat diet fed rats for the development of hypertriglyceridemia, hypercholesterolemia, hyperinsulinemia and hyperglycemia and to assess their vascular responses to 5-Hydroxytryptamine and Angiotensin II. Methods Male Sprague Dawley rats were used for this study and were divided into two equal groups. One of the groups was fed with normal pellet diet and they served as the control group, whereas the other group was on a high fat diet for 4 weeks. Body weight, plasma triglycerides, plasma cholesterol, and plasma glucose were measured every week. Intraperitoneal glucose tolerance test was performed after 4 weeks of feeding. At the end of fourth week of high fat diet feeding, thoracic aortae were removed, and cut into helical strips for vascular reactivity studies. Dose-response curves of 5-Hydroxytryptamine and Angiotensin II were obtained. Results There was no significant difference in pD2, with 5-Hydroxytryptamine and Angiotensin II in both groups but Emax was increased. Conclusions These results suggest that hypertension in high fat diet rats is associated with increased in vitro vascular reactivity to 5-HT and Ang II. PMID:15287987

  5. Effects of chitosan and water-soluble chitosan micro- and nanoparticles in obese rats fed a high-fat diet

    PubMed Central

    Zhang, Hong-liang; Zhong, Xiao-bin; Tao, Yi; Wu, Si-hui; Su, Zheng-quan

    2012-01-01

    Purpose: This study determined the effects of chitosan (CTS) and water-soluble chitosan (WSC) microparticles (MPs) and nanoparticles (NPs) in rats with high-fat diet-induced obesity. Methods: The rats were randomly separated into eight groups: a normal diet group (the blank control), a high-fat emulsion group (the negative control), CTS and WSC control groups, CTS-MP and WSC-MP groups, and CTS-NP and WSC-NP groups. All groups (except the blank control group) were fed the high-fat diet for 4 weeks to establish the obesity model. Different samples were administered orally once daily to the treatment groups for 4 weeks. Results: A significantly lower weight gain was observed in the WSC-MP and WSC-NP groups, as well as in the CTS-MP and CTS-NP groups, compared with rats given a normal diet and a high-fat diet (P < 0.05). The WSC-MP rats had the least weight gain among all the groups. The food intake in the eight groups had the same trend as weight gain. CTS and WSC MPs and NPs significantly reduced the final amounts of epididymal and perirenal white adipose tissue. Liver weight was reduced in the CTS-MP group compared to rats fed a high-fat diet. Serum total cholesterol and low-density lipoprotein cholesterol were significantly reduced in all treatment groups, with the WSC-MP and CTS-MP groups showing a more significant reduction than the other groups. Triacylglycerol levels were significantly reduced in the WSC-NP group compared to the high-fat group. The mortality rates of CTS-MP, CTS-NP, WSC-MP, and WSC-NP groups were 30%, 30%, 55%, and 65%, respectively. The median lethal dose for the WSC-MP and WSC-NP groups were 4080 mg/kg and 2370 mg/kg, respectively. Conclusion: These results indicate that CTS and WSC MPs and NPs have greater effects than commercially available CTS and WSC, and can be used as potential antiobesity agents. PMID:22888243

  6. Effects of Lipid Regulation Using Raw and Processed Radix Polygoni Multiflori in Rats Fed a High-Fat Diet

    PubMed Central

    Li, Na; Chen, Zhen; Mao, Xiaojian; Yu, Jie; Zhao, Ronghua

    2012-01-01

    Raw and processed Radix Polygoni Multiflori have been used in the prevention and treatment of nonalcoholic fatty liver disease (NAFLD), hyperlipidemia, and related diseases in Asian counties for centuries. The lipid regulation ability of raw and processed Poligoni Multiflori Radix were compared in high-fat diet fed rats in this research. Total cholesterol (TC) and low density lipoprotein-cholesterol (LDL-C) in blood and liver tissue were all significantly higher in model rats. However, triglyceride (TG) contents increased only in liver tissue, not in the blood samples. The rats fed the high-fat diets were considered the model of type IIa hyperlipidemia and early-stage nonalcoholic fatty liver disease. Both Radix Polygoni Multiflori (RPM) and Radix Polygoni Multiflori Praeparata (RPMP) revealed TC-lowing effects, and middling doses of RPMP displayed the most significant TC-lowing effects, as indicated by blood samples. Neither RPM nor RPMP was found to reduce LDL-C in rats' blood. Nevertheless, RPM showed dose-dependent TC- and TG-lowing effects in the liver tissue samples. In conclusion, RPM showed more pronounced effects on lipid regulation in liver samples in the treatment of early-stage NAFLD. RPMP, however, displayed better effects in regulating lipids in circulating blood for the treatment of hyperlipidemia. PMID:23304197

  7. Seaweed supplements normalise metabolic, cardiovascular and liver responses in high-carbohydrate, high-fat fed rats.

    PubMed

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C; Paul, Nicholas A; Brown, Lindsay

    2015-02-01

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330-340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium. PMID:25648511

  8. Seaweed Supplements Normalise Metabolic, Cardiovascular and Liver Responses in High-Carbohydrate, High-Fat Fed Rats

    PubMed Central

    Kumar, Senthil Arun; Magnusson, Marie; Ward, Leigh C.; Paul, Nicholas A.; Brown, Lindsay

    2015-01-01

    Increased seaweed consumption may be linked to the lower incidence of metabolic syndrome in eastern Asia. This study investigated the responses to two tropical green seaweeds, Ulva ohnoi (UO) and Derbesia tenuissima (DT), in a rat model of human metabolic syndrome. Male Wistar rats (330–340 g) were fed either a corn starch-rich diet or a high-carbohydrate, high-fat diet with 25% fructose in drinking water, for 16 weeks. High-carbohydrate, high-fat diet-fed rats showed the signs of metabolic syndrome leading to abdominal obesity, cardiovascular remodelling and non-alcoholic fatty liver disease. Food was supplemented with 5% dried UO or DT for the final 8 weeks only. UO lowered total final body fat mass by 24%, systolic blood pressure by 29 mmHg, and improved glucose utilisation and insulin sensitivity. In contrast, DT did not change total body fat mass but decreased plasma triglycerides by 38% and total cholesterol by 17%. UO contained 18.1% soluble fibre as part of 40.9% total fibre, and increased magnesium, while DT contained 23.4% total fibre, essentially as insoluble fibre. UO was more effective in reducing metabolic syndrome than DT, possibly due to the increased intake of soluble fibre and magnesium. PMID:25648511

  9. Effects of xanthohumol-rich extract from the hop on fatty acid metabolism in rats fed a high-fat diet.

    PubMed

    Yui, Kazuki; Kiyofuji, Ayane; Osada, Kyoichi

    2014-01-01

    Xanthohumol is the major prenylated flavonoid of female inflorescences of the hop plant (Humulus lupulus L.) and is a hydrophobic flavonoid. We examined the effects of dietary xanthohumol-rich hop extract in obese rats that was induced by feeding a high-fat diet. Dietary xanthohumol-rich hop extract significantly lowered the body weight gain of these rats compared to rats fed a high-fat diet without the extract. The increase of body weight, liver weight, and triacylglycerol levels in the plasma and liver of the rats fed a high-fat diet was ameliorated by dietary xanthohumol-rich hop extract. Dietary xanthohumol-rich hop extract tended to reduce hepatic fatty acid synthesis through the reduction of hepatic SREBP1c mRNA expression in the rats fed a high-fat diet. The excreted of triacylglycerol into feces also was promoted by dietary xanthohumol-rich hop extract. Plasma adiponectin levels in the rats fed a high-fat diet also tended to be elevated by dietary xanthohumol-rich hop extract. Thus, xanthohumol-rich hop extract may inhibit the increase of body weight, liver weight, and triacylglycerol in the plasma and liver induced by feeding high-fat diet through the regulation of hepatic fatty acid metabolism and inhibition of intestinal fat absorption. Therefore, xanthohumol-rich hop extract may exert preventive function on the increase of body weight and tissue triacylglycerol levels by overnutrition. PMID:24420065

  10. Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats

    PubMed Central

    Lee, Hyun-Ho; Paudel, Keshav Raj; Jeong, Jieun; Wi, An-Jin; Park, Whoa-Shig; Kim, Dong-Wook

    2016-01-01

    Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: 100, 400, and 800 mg·kg−1·day−1 (CJF 100, 400, and 800, resp.). Our results showed that CJF possessed strong cholesterol-lowering potency as indicated by the decrease in serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), accompanied by an increase in serum high-density lipoprotein (HDL). Furthermore, CJF reduced serum lipid peroxidation by suppressing the formation of thiobarbituric acid reactive substance. In addition, oil red O (ORO) staining of rat arteries showed decreased lipid-positive staining in the CJF-treated groups compared to the control HFD group. Taken together, these results suggest that CJF could be a potent herbal therapeutic option and source of a functional food for the prevention and treatment of atherosclerosis and other diseases associated with hypercholesterolemia. PMID:27340422

  11. Antiatherogenic Effect of Camellia japonica Fruit Extract in High Fat Diet-Fed Rats.

    PubMed

    Lee, Hyun-Ho; Paudel, Keshav Raj; Jeong, Jieun; Wi, An-Jin; Park, Whoa-Shig; Kim, Dong-Wook; Oak, Min-Ho

    2016-01-01

    Hypercholesterolemia is a well-known etiological factor for cardiovascular disease and a common symptom of most types of metabolic disorders. Camellia japonica is a traditional garden plant, and its flower and seed have been used as a base oil of traditional cosmetics in East Asia. The present study was carried out to evaluate the effect of C. japonica fruit extracts (CJF) in a high fat diet- (HFD-) induced hypercholesterolemic rat model. CJF was administered orally at three different doses: 100, 400, and 800 mg·kg(-1)·day(-1) (CJF 100, 400, and 800, resp.). Our results showed that CJF possessed strong cholesterol-lowering potency as indicated by the decrease in serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL), accompanied by an increase in serum high-density lipoprotein (HDL). Furthermore, CJF reduced serum lipid peroxidation by suppressing the formation of thiobarbituric acid reactive substance. In addition, oil red O (ORO) staining of rat arteries showed decreased lipid-positive staining in the CJF-treated groups compared to the control HFD group. Taken together, these results suggest that CJF could be a potent herbal therapeutic option and source of a functional food for the prevention and treatment of atherosclerosis and other diseases associated with hypercholesterolemia. PMID:27340422

  12. The effects of black garlic (Allium satvium) extracts on lipid metabolism in rats fed a high fat diet

    PubMed Central

    Ha, Ae Wha; Ying, Tian

    2015-01-01

    BACKGROUD/OBEJECTIVES The mechanism of how black garlic effects lipid metabolism remains unsolved. Therefore, the objectives of this study were to determine the effects of black garlic on lipid profiles and the expression of related genes in rats fed a high fat diet. MATERIALS/METHODS Thirty-two male Sqrague-Dawley rats aged 4 weeks were randomly divided into four groups (n=8) and fed the following diets for 5 weeks: normal food diet, (NF); a high-fat diet (HF); and a high-fat diet + 0.5% or 1.5% black garlic extract (HFBG0.5 or HFBG1.5). Body weights and blood biochemical parameters, including lipid profiles, and expressions of genes related to lipid metabolism were determined. RESULTS Significant differences were observed in the final weights between the HFBG1.5 and HF groups. All blood biochemical parameters measured in the HFBG1.5 group showed significantly lower values than those in the HF group. Significant improvements of the plasama lipid profiles as well as fecal excretions of total lipids and triglyceride (TG) were also observed in the HFBG1.5 group, when compared to the HF diet group. There were significant differences in the levels of mRNA of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and glucose-6-phosphate dehydrogenase (G6PDH) in the HFBG1.5 group compared to the HF group. In addition, the hepatic expression of (HMG-CoA) reductase and Acyl-CoA cholesterol acyltransferase (ACAT) mRNA was also significantly lower than the HF group. CONCLUSIONS Consumption of black garlic extract lowers SREBP-1C mRNA expression, which causes downregulation of lipid and cholestrol metahbolism. As a result, the blood levels of total lipids, TG, and cholesterol were decreased. PMID:25671065

  13. Voluntary exercise improves metabolic profile in high-fat fed glucocorticoid-treated rats.

    PubMed

    Beaudry, Jacqueline L; Dunford, Emily C; Leclair, Erwan; Mandel, Erin R; Peckett, Ashley J; Haas, Tara L; Riddell, Michael C

    2015-06-01

    Diabetes is rapidly induced in young male Sprague-Dawley rats following treatment with exogenous corticosterone (CORT) and a high-fat diet (HFD). Regular exercise alleviates insulin insensitivity and improves pancreatic β-cell function in insulin-resistant/diabetic rodents, but its effect in an animal model of elevated glucocorticoids is unknown. We examined the effect of voluntary exercise (EX) on diabetes development in CORT-HFD-treated male Sprague-Dawley rats (∼6 wk old). Animals were acclimatized to running wheels for 2 wk, then given a HFD, either wax (placebo) or CORT pellets, and split into 4 groups: placebo-sedentary (SED) or -EX and CORT-SED or -EX. After 2 wk of running combined with treatment, CORT-EX animals had reduced visceral adiposity, and increased skeletal muscle type IIb/x fiber area, oxidative capacity, capillary-to-fiber ratio and insulin sensitivity compared with CORT-SED animals (all P < 0.05). Although CORT-EX animals still had fasting hyperglycemia, these values were significantly improved compared with CORT-SED animals (14.3 ± 1.6 vs. 18.8 ± 0.9 mM). In addition, acute in vivo insulin response to an oral glucose challenge was enhanced ∼2-fold in CORT-EX vs. CORT-SED (P < 0.05) which was further demonstrated ex vivo in isolated islets. We conclude that voluntary wheel running in rats improves, but does not fully normalize, the metabolic profile and skeletal muscle composition of animals administered CORT and HFD. PMID:25792713

  14. Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression

    PubMed Central

    Yu, J.; Zheng, J.; Liu, X.F.; Feng, Z.L.; Zhang, X.P.; Cao, L.L.; Zhou, Z.P.

    2016-01-01

    This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin. PMID:27143172

  15. Exercise improved lipid metabolism and insulin sensitivity in rats fed a high-fat diet by regulating glucose transporter 4 (GLUT4) and musclin expression.

    PubMed

    Yu, J; Zheng, J; Liu, X F; Feng, Z L; Zhang, X P; Cao, L L; Zhou, Z P

    2016-01-01

    This study aimed to evaluate the effects of exercise training on triglyceride deposition and the expression of musclin and glucose transporter 4 (GLUT4) in a rat model of insulin resistance. Thirty male Sprague-Dawley rats (8 weeks old, weight 160±10 g) were fed a high-fat diet (40% calories from fat) and randomly divided into high-fat control group and swimming intervention group. Rats fed with standard food served as normal control. We found that 8-week swimming intervention significantly decreased body weight (from 516.23±46.27 to 455.43±32.55 g) and visceral fat content (from 39.36±2.50 to 33.02±2.24 g) but increased insulin sensitivity index of the rats fed with a high-fat diet. Moreover, swimming intervention improved serum levels of TG (from 1.40±0.83 to 0.58±0.26 mmol/L) and free fatty acids (from 837.80±164.25 to 556.38±144.77 μEq/L) as well as muscle triglycerides deposition (from 0.55±0.06 to 0.45±0.02 mmol/g) in rats fed a high-fat diet. Compared with rats fed a standard food, musclin expression was significantly elevated, while GLUT4 expression was decreased in the muscles of rats fed a high-fat diet. In sharp contrast, swimming intervention significantly reduced the expression of musclin and increased the expression of GLUT4 in the muscles of rats fed a high-fat diet. In conclusion, increased musclin expression may be associated with insulin resistance in skeletal muscle, and exercise training improves lipid metabolism and insulin sensitivity probably by upregulating GLUT4 and downregulating musclin. PMID:27143172

  16. 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

  17. Anti-obesity efficacy of nanoemulsion oleoresin capsicum in obese rats fed a high-fat diet

    PubMed Central

    Kim, Joo-Yeon; Lee, Mak-Soon; Jung, Sunyoon; Joo, Hyunjin; Kim, Chong-Tai; Kim, In-Hwan; Seo, Sangjin; Oh, Soojung; Kim, Yangha

    2014-01-01

    Purpose This study determined the effects of oleoresin capsicum (OC) and nanoemulsion OC (NOC) on obesity in obese rats fed a high-fat diet. Methods The rats were randomly separated into three groups: a high-fat (HF) diet group, HF + OC diet group, and HF + NOC diet group. All groups were fed the diet and water ad libitum for 14 weeks. Results NOC reduced the body weight and adipose tissue mass, whereas OC did not. OC and NOC reduced mRNA levels of adipogenic genes, including peroxisome proliferator-activated receptor (PPAR)-γ, sterol regulatory element-binding protein-1c, and fatty acid-binding protein in white adipose tissue. The mRNA levels of genes related to β-oxidation or thermogenesis including PPAR-α, palmitoyltransferase-1α, and uncoupling protein-2 were increased by the OC and NOC relative to the HF group. Both OC and NOC clearly stimulated AMP-activated protein kinase (AMPK) activity. In particular, PPAR-α, palmitoyltransferase-1α, uncoupling protein-2 expression, and AMPK activity were significantly increased in the NOC group compared to in the OC group. NOC decreased glycerol-3-phosphate dehydrogenase activity whereas OC did not. Conclusion From these results, NOC could be suggested as a potential anti-obesity agent in obese rats fed a HF diet. The effects of the NOC on obesity were associated with changes of multiple gene expression, activation of AMPK, and inhibition of glycerol-3-phosphate dehydrogenase in white adipose tissue. PMID:24403834

  18. The impact of chronic blackberry intake on the neuroinflammatory status of rats fed a standard or high-fat diet.

    PubMed

    Meireles, Manuela; Marques, Cláudia; Norberto, Sónia; Fernandes, Iva; Mateus, Nuno; Rendeiro, Catarina; Spencer, Jeremy P E; Faria, Ana; Calhau, Conceição

    2015-11-01

    Neuroinflammation has been suggested as a central mediator of central nervous system dysfunction, including in dementia and neurodegenerative disease. Flavonoids have emerged as promising candidates for the prevention of neurodegenerative diseases and are thought to be capable of antiinflammatory effects in the brain. In the present study, the impact of a chronic intake of an anthocyanin extract from blackberry (BE) on brain inflammatory status in the presence or absence of a high-fat diet was investigated. Following intake of the dietary regimes for 17 weeks neuroinflammatory status in Wistar rat cortex, hippocampus and plasma were assessed using cytokine antibody arrays. In the cortex, intake of the high-fat diet resulted in an increase of at least 4-fold, in expression of the cytokine-induced neutrophil chemoattractant CINC-3, the ciliary neurotrophic factor CNTF, the platelet-derived growth factor PDGF-AA, IL-10, the tissue inhibitor of metalloproteinase TIMP-1 and the receptor for advanced glycation end products RAGE. BE intake partially decreased the expression of these mediators in the high-fat challenged brain. In standard-fed animals, BE intake significantly increased cortical levels of fractalkine, PDGF-AA, activin, the vascular endothelial growth factor VEGF and agrin expression, suggesting effects as neuronal growth and synaptic connection modulators. In hippocampus, BE modulates fractalkine and the thymus chemokine TCK-1 expression independently of diet intake and, only in standard diet, increased PDGF-AA. Exploring effects of anthocyanins on fractalkine transcription using the neuronal cell line SH-SY5Y suggested that other cell types may be involved in this effect. This is the first evidence, in in vivo model, that blackberry extract intake may be capable of preventing the detrimental effects of neuroinflammation in a high-fat challenged brain. Also, fractalkine and TCK-1 expression may be specific targets of anthocyanins and their metabolites on

  19. Bitter gourd (Momordica charantia) improves insulin sensitivity by increasing skeletal muscle insulin-stimulated IRS-1 tyrosine phosphorylation in high-fat-fed rats.

    PubMed

    Sridhar, M G; Vinayagamoorthi, R; Arul Suyambunathan, V; Bobby, Z; Selvaraj, N

    2008-04-01

    The aim of this present study was to investigate the effect of bitter gourd extract on insulin sensitivity and proximal insulin signalling pathways in high-fat-fed rats. High-fat feeding of male Wistar rats for 10 weeks decreased the glucose tolerance and insulin sensitivity compared to chow-fed control rats. Bitter gourd extract supplementation for 2 weeks (9th and 10th) of high-fat feeding improved the glucose tolerance and insulin sensitivity. In addition bitter gourd extract reduced the fasting insulin (43 (se 4.4) v. 23 (se 5.2) microU/ml, P < 0.05), TAG (134 (se 12) v. 96 (se 5.5) mg/dl, P < 0.05), cholesterol (97 (se 6.3) v. 72 (se 5.2) mg/dl, P < 0.05) and epidydimal fat (4.8 (se 0.29) v. 3.6 (se 0.24) g, P < 0.05), which were increased by high-fat diet (HFD). High-fat feeding and bitter gourd supplementation did not have any effect on skeletal muscle insulin receptor, insulin receptor subtrate-1 (IRS-1) and insulin- stimulated insulin receptor tyrosine phosphorylation compared to chow-fed control rats. However high-fat feeding for 10 weeks reduced the insulin-stimulated IRS-1 tyrosine phosphorylation compared to control rats. Bitter gourd supplementation together with HFD for 2 weeks improved the insulin-stimulated IRS-1 tyrosine phosphorylation compared to rats fed with HFD alone. Our results show that bitter gourd extract improves insulin sensitivity, glucose tolerance and insulin signalling in HFD-induced insulin resistance. Identification of potential mechanism(s) by which bitter gourd improves insulin sensitivity and insulin signalling in high-fat-fed rats may open new therapeutic targets for the treatment of obesity/dyslipidemia-induced insulin resistance. PMID:17942003

  20. Fish Oil and Microalga Omega-3 as Dietary Supplements: A Comparative Study on Cardiovascular Risk Factors in High-Fat Fed Rats.

    PubMed

    Haimeur, Adil; Mimouni, Virginie; Ulmann, Lionel; Martineau, Anne-Sophie; Messaouri, Hafida; Pineau-Vincent, Fabienne; Tremblin, Gérard; Meskini, Nadia

    2016-09-01

    Dietary supplementation with marine omega-3 polyunsaturated fatty acids (n-3 PUFA) can have beneficial effects on a number of risk factors for cardiovascular disease (CVD). We compared the effects of two n-3 PUFA rich food supplements (freeze-dried Odontella aurita and fish oil) on risk factors for CVD. Male rats were randomly divided into four groups of six animals each and fed with the following diets: control group (C) received a standard diet containing 7 % lipids; second group (HF high fat) was fed with a high-fat diet containing 40 % lipids; third group (HFFO high fat+fish oil) was fed with the high-fat diet supplemented with 0.5 % fish oil; and fourth group (HFOA high fat+O. aurita) received the high-fat diet supplemented with 12 % of freeze-dried O. aurita. After 8 weeks rats fed with the high-fat diet supplemented with O. aurita displayed a significantly lower bodyweight than those in the other groups. Both the microalga and the fish oil significantly reduced insulinemia and serum lipid levels. O. aurita was more effective than the fish oil in reducing hepatic triacyglycerol levels and in preventing high-fat diet-induced steatosis. O. aurita and fish oil also reduced platelet aggregation and oxidative status induced by high fat intake. After an OA supplementation, the adipocytes in the HFOA group were smaller than those in the HF group. Freeze-dried O. aurita showed similar or even greater biological effects than the fish oil. This could be explained by a potential effect of the n-3 PUFA but also other bioactive compounds of the microalgae. PMID:27503614

  1. 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

  2. Effects of 17β-estradiol on cardiac Na(+)/K(+)-ATPase in high fat diet fed rats.

    PubMed

    Obradovic, Milan; Zafirovic, Sonja; Jovanovic, Aleksandra; Milovanovic, Emina Sudar; Mousa, Shaker A; Labudovic-Borovic, Milica; Isenovic, Esma R

    2015-11-15

    The aim of this study was to investigate in vivo effects of estradiol on Na(+)/K(+)-ATPase activity/expression in high fat (HF) diet fed rats. Adult male Wistar rats were fed normally (Control, n = 7) or with a HF diet (Obese, n = 14) for 10 weeks. After 10 weeks, half of the obese rats were treated with estradiol (Obese + Estradiol, n = 7, 40 μg/kg, i.p.) as a bolus injection and 24 h after treatment all the rats were sacrificed. Estradiol in vivo in obese rats in comparison with obese non-treated rats led to a statistically significant increase in concentration of serum Na(+) (p < 0.05), Na(+)/K(+)-ATPase activity (p < 0.01), expression of α1 (p < 0.01) and α2 (p < 0.05) subunit of Na(+)/K(+)-ATPase, both PI3K subunits p85 (p < 0.01), p110 (p < 0.05), and association of IRS-1 with p85 (p < 0.05), while significantly decrease expression of AT1 (p < 0.05) and Rho A (p < 0.01) proteins. Our results suggest that estradiol in vivo in pathophysiological conditions, such as obesity accompanied with insulin resistance stimulates activity and expression of Na(+)/K(+)-ATPase by a mechanism that involves the participation of IRS-1/PI3K/Akt signaling. In addition, the decreasing level of AT1 and Rho A proteins estradiol probably attenuates the detrimental effect of obesity to decreased IRS-1/PI3K association and consequently reduce Na(+)/K(+)-ATPase activity/expression. PMID:26284496

  3. Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats

    PubMed Central

    da Rocha, Guilherme L.; Crisp, Alex H.; de Oliveira, Maria R. M.; da Silva, Carlos A.; Silva, Jadson O.; Duarte, Ana C. G. O.; Sene-Fiorese, Marcela; Verlengia, Rozangela

    2016-01-01

    This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

  4. Effect of High Intensity Interval and Continuous Swimming Training on Body Mass Adiposity Level and Serum Parameters in High-Fat Diet Fed Rats.

    PubMed

    da Rocha, Guilherme L; Crisp, Alex H; de Oliveira, Maria R M; da Silva, Carlos A; Silva, Jadson O; Duarte, Ana C G O; Sene-Fiorese, Marcela; Verlengia, Rozangela

    2016-01-01

    This study aimed to investigate the effects of interval and continuous training on the body mass gain and adiposity levels of rats fed a high-fat diet. Forty-eight male Sprague-Dawley rats were randomly divided into two groups, standard diet and high-fat diet, and received their respective diets for a period of four weeks without exercise stimuli. After this period, the animals were randomly divided into six groups (n = 8): control standard diet (CS), control high-fat diet (CH), continuous training standard diet (CTS), continuous training high-fat diet (CTH), interval training standard diet (ITS), and interval training high-fat diet (ITH). The interval and continuous training consisted of a swimming exercise performed over eight weeks. CH rats had greater body mass gain, sum of adipose tissues mass, and lower serum high density lipoprotein values than CS. The trained groups showed lower values of feed intake, caloric intake, body mass gain, and adiposity levels compared with the CH group. No significant differences were observed between the trained groups (CTS versus ITS and CTH versus ITH) on body mass gains and adiposity levels. In conclusion, both training methodologies were shown to be effective in controlling body mass gain and adiposity levels in high-fat diet fed rats. PMID:26904718

  5. Fructus xanthii improves lipid homeostasis in the epididymal adipose tissue of rats fed a high-fat diet

    PubMed Central

    LI, XIUMIN; YANG, MINGXING; LI, ZHIPENG; XUE, MEI; SHANGGUAN, ZHAOSHUI; OU, ZHIMIN; LIU, MING; LIU, SUHUAN; YANG, SHUYU; LI, XUEJUN

    2016-01-01

    High fat diet (HFD)-induced obesity triggers common features of human metabolic syndrome in rats. Our previous study showed that Fructus xanthii (FX) attenuates HFD-induced hepatic steatosis. The present study was designed to investigate the effects of FX on lipid metabolism in epididymal fat (EF), and examine its underlying mechanisms. Aqueous extraction fractions of FX or vehicle were orally administered by gavage for 6 weeks to rats fed either a HFD or a normal chow diet (NCD). The levels of circulating free fatty acid (FFA) were determined in plasma, and the expression levels of lipid metabolism- and inflammation-associated genes in the EF were measured using reverse transcription-quantitative polymerase chain reaction analysis. The general morphology, size and number of adipocytes in the EF, and the levels of macrophage infiltration were evaluated using hematoxylin and eosin staining or immunohistochemical staining. FX decreased circulating levels of FFA, increased the expression levels of sterol-regulatory-element-binding protein-1c, FAS, acetyl coenzyme A carboxylase, diacylglycerol acyltransferase and lipoprotein lipase lipogenic genes in the EF. FX increased the numbers of adipocytes in the EF, and featured a shift towards smaller adipocyte size. Compared with the vehicle-treated rats, positive staining of F4/80 was more dispersed in the FX-treated rats, and the percentage of F4/80 positive cells was significantly decreased. FX attenuated HFD-induced lipid dyshomeostasis in the epididymal adipose tissue. PMID:26648271

  6. Fructus xanthii improves lipid homeostasis in the epididymal adipose tissue of rats fed a high-fat diet.

    PubMed

    Li, Xiumin; Yang, Mingxing; Li, Zhipeng; Xue, Mei; Shangguan, Zhaoshui; Ou, Zhimin; Liu, Ming; Liu, Suhuan; Yang, Shuyu; Li, Xuejun

    2016-01-01

    High fat diet (HFD)-induced obesity triggers common features of human metabolic syndrome in rats. Our previous study showed that Fructus xanthii (FX) attenuates HFD-induced hepatic steatosis. The present study was designed to investigate the effects of FX on lipid metabolism in epididymal fat (EF), and examine its underlying mechanisms. Aqueous extraction fractions of FX or vehicle were orally administered by gavage for 6 weeks to rats fed either a HFD or a normal chow diet (NCD). The levels of circulating free fatty acid (FFA) were determined in plasma, and the expression levels of lipid metabolism‑ and inflammation‑associated genes in the EF were measured using reverse transcription‑quantitative polymerase chain reaction analysis. The general morphology, size and number of adipocytes in the EF, and the levels of macrophage infiltration were evaluated using hematoxylin and eosin staining or immunohistochemical staining. FX decreased circulating levels of FFA, increased the expression levels of sterol‑regulatory‑element‑binding protein‑1c, FAS, acetyl coenzyme A carboxylase, diacylglycerol acyltransferase and lipoprotein lipase lipogenic genes in the EF. FX increased the numbers of adipocytes in the EF, and featured a shift towards smaller adipocyte size. Compared with the vehicle‑treated rats, positive staining of F4/80 was more dispersed in the FX‑treated rats, and the percentage of F4/80 positive cells was significantly decreased. FX attenuated HFD‑induced lipid dyshomeostasis in the epididymal adipose tissue. PMID:26648271

  7. The anti-inflammatory action of fermented soybean products in kidney of high-fat-fed rats.

    PubMed

    Choi, Jehun; Kwon, Sun-Hwa; Park, Kun-Young; Yu, Byung Pal; Kim, Nam Deuk; Jung, Jee H; Chung, Hae Young

    2011-03-01

    Soybean has many compounds with a variety of biological properties that potentially benefit human health; among them, isoflavones have inhibitory effects on lipid oxidation in adipose tissue. In this study, we examined two Korean traditional fermented soybean products--doenjang (DNJ) and cheonggukjang (CGJ)--for their ability to suppress redox-sensitive nuclear factor κB (NF-κB) activation in the kidney of rats fed a high-fat diet. Sprague-Dawley rats, 4 weeks old, were fed soybean, DNJ, or CGJ (1 g/kg/day) with a 20% fat diet for 6 weeks. Body weight and food intake were carefully monitored. NF-κB-related activities of genes for inflammatory proteins, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and vascular cell adhesion molecule-1 (VCAM-1), were determined. The soybean products exhibited antioxidative action by maintaining redox regulation, suppressing NF-κB activation, and modulating the expression of genes for NF-κB-induced inflammatory proteins such as COX-2, iNOS, and VCAM-1. Based on these results, we conclude that Korean traditional soybean fermented products, especially CGJ, suppress the generation of reactive species, NF-κB activity, and NF-κB-related inflammatory genes. PMID:21332402

  8. Brown (BAT) and white (WAT) adipose tissue in high-fat junk food (HFJF) and chow-fed rats with dorsomedial hypothalamic lesions (DMNL rats).

    PubMed

    Bernardis, L L; Bellinger, L L

    1991-05-15

    Male weanling rats received dorsomedial hypothalamic nucleus lesions (DMNL) or sham operations and were fed for 173 postoperative days a high-fat diet and given a 32% sucrose solution as drinking fluid. This was supplemented with chocolate chip cookies, potato chips and marshmallows. Other DMNL and sham-operated controls were fed lab chow instead of the above high-fat junk food diet (HFJF) and given tap water instead of 32% sucrose solution. All animals were killed on postoperative day 174. Caloric intake per 100 g body weight was similar in all groups; however, the HFJF fed control and DMNL rats had significantly elevated carcass fat. Since HFJF-DMNL rats were not nearly as obese as the HFJF control animals, it appears that the DMNL offered some protection against the HFJF-diet-produced obesity. When their smaller body size is considered. DMN lesions had no effect on brown adipose tissue (BAT) mass in chow-fed or HFJF fed rats, whereas BAT size was significantly enlarged in HFJF-fed control animals. This suggests but does not prove that HFJF-fed controls, but not DMNL rats, may be using dietary-induced thermogenesis (DIT) to attenuate their obesity. We hypothesize that the HFJF-fed DMNL may not be enhancing DIT as reflected in normal BAT size, because they had not attained a degree of fatness to activate this system, or the DMN lesions impaired its activation. Both HFJF-fed groups showed reduced linear growth compared to their counterparts. The reason for stunting is uncertain, but may be related to their low plasma insulin concentrations. PMID:1867761

  9. Effects of Dietary Carbohydrate Replaced with Wild Rice (Zizania latifolia (Griseb) Turcz) on Insulin Resistance in Rats Fed with a High-Fat/Cholesterol Diet

    PubMed Central

    Han, Shufen; Zhang, Hong; Qin, Liqiang; Zhai, Chengkai

    2013-01-01

    Wild rice (WR) is a very nutritious grain that has been used to treat diabetes in Chinese medicinal practice. City diet (CD) is based on the diet consumed by Asian area residents in modern society, which is rich in saturated fats, cholesterol and carbohydrates. The present study was aimed at evaluating the effects of replacing white rice and processed wheat starch of CD with WR as the chief source of dietary carbohydrates on insulin resistance in rats fed with a high-fat/cholesterol diet. Except the rats of the low-fat (LF) diet group, the rats of the other three groups, including to high-fat/cholesterol (HFC) diet, CD and WR diet, were fed with high-fat/cholesterol diets for eight weeks. The rats fed with CD exhibited higher weight gain and lower insulin sensitivity compared to the rats consuming a HFC diet. However, WR suppressed high-fat/cholesterol diet-induced insulin resistance. WR decreased liver homogenate triglyceride and free fatty acids levels, raised serum adiponectin concentration and reduced serum lipocalin-2 and visfatin concentrations. In addition, the WR diet potently augmented the relative expressions of adiponectin receptor 2, peroxisome proliferator-activated receptors, alpha and gamma, and abated relative expressions of leptin and lipocalin-2 in the tissues of interest. These findings indicate that WR is effective in ameliorating abnormal glucose metabolism and insulin resistance in rats, even when the diet consumed is high in fat and cholesterol. PMID:23434909

  10. Effects of dietary carbohydrate replaced with wild rice (Zizania latifolia (Griseb) Turcz) on insulin resistance in rats fed with a high-fat/cholesterol diet.

    PubMed

    Han, Shufen; Zhang, Hong; Qin, Liqiang; Zhai, Chengkai

    2013-02-01

    Wild rice (WR) is a very nutritious grain that has been used to treat diabetes in Chinese medicinal practice. City diet (CD) is based on the diet consumed by Asian area residents in modern society, which is rich in saturated fats, cholesterol and carbohydrates. The present study was aimed at evaluating the effects of replacing white rice and processed wheat starch of CD with WR as the chief source of dietary carbohydrates on insulin resistance in rats fed with a high-fat/cholesterol diet. Except the rats of the low-fat (LF) diet group, the rats of the other three groups, including to high-fat/cholesterol (HFC) diet, CD and WR diet, were fed with high-fat/cholesterol diets for eight weeks. The rats fed with CD exhibited higher weight gain and lower insulin sensitivity compared to the rats consuming a HFC diet. However, WR suppressed high-fat/cholesterol diet-induced insulin resistance. WR decreased liver homogenate triglyceride and free fatty acids levels, raised serum adiponectin concentration and reduced serum lipocalin-2 and visfatin concentrations. In addition, the WR diet potently augmented the relative expressions of adiponectin receptor 2, peroxisome proliferator-activated receptors, alpha and gamma, and abated relative expressions of leptin and lipocalin-2 in the tissues of interest. These findings indicate that WR is effective in ameliorating abnormal glucose metabolism and insulin resistance in rats, even when the diet consumed is high in fat and cholesterol. PMID:23434909

  11. The effects of Angelica keiskei Koidz on the expression of antioxidant enzymes related to lipid profiles in rats fed a high fat diet

    PubMed Central

    Choi, Jinho; Yeo, Ikhyun

    2012-01-01

    This study was performed to examine the feeding effects of Angelica keiskei Koidz (AK) and its processed products on serum, liver, and body fat content and the expression of antioxidant genes in rats fed a high fat diet. AK and its processed products were added at 3-5% to a high fat diet and fed to adult rats for 6 weeks. In experiment 1 (EXP 1), the rats were fed with one of six diets including a control diet (normal fat), high fat diet (HF), and HF + AK additives groups (four groups). In experiment 2 (EXP 2), the rats were separated into three groups of HF, HF + AK whole leaves, and HF + fermented juice (FS) + squeeze (SA). Body weight was not different among the groups in either experiment. The liver weight was lower in the FS and SA groups compared to that in the other groups (P < 0.05). Serum luteolin was higher in the AK and processed products groups compared to that in the HF group (P < 0.05). Gene expression of the antioxidative enzymes catalase and glutathione-s-reductase in the liver was higher in the AK processed products group than that in the other groups (P < 0.05). The results suggest that the intake of AK and its processed products increased the expression of antioxidant enzymes in animals fed a high fat diet, reduced hepatic cholesterol content, and increased the effective absorption of luteolin. PMID:22413035

  12. Gut microbiota are linked to increased susceptibility to hepatic steatosis in low aerobic capacity rats fed an acute high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that low capacity running (LCR) rats fed acute high fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with...

  13. Changes in Gut Microbiota in Rats Fed a High Fat Diet Correlate with Obesity-Associated Metabolic Parameters

    PubMed Central

    Maloney, Christopher A.; Raipuria, Mukesh; Huinao, Karina D.; Mitchell, Hazel M.; Morris, Margaret J.

    2015-01-01

    The gut microbiota is emerging as a new factor in the development of obesity. Many studies have described changes in microbiota composition in response to obesity and high fat diet (HFD) at the phylum level. In this study we used 16s RNA high throughput sequencing on faecal samples from rats chronically fed HFD or control chow (n = 10 per group, 16 weeks) to investigate changes in gut microbiota composition at the species level. 53.17% dissimilarity between groups was observed at the species level. Lactobacillus intestinalis dominated the microbiota in rats under the chow diet. However this species was considerably less abundant in rats fed HFD (P<0.0001), this being compensated by an increase in abundance of propionate/acetate producing species. To further understand the influence of these species on the development of the obese phenotype, we correlated their abundance with metabolic parameters associated with obesity. Of the taxa contributing the most to dissimilarity between groups, 10 presented significant correlations with at least one of the tested parameters, three of them correlated positively with all metabolic parameters: Phascolarctobacterium, Proteus mirabilis and Veillonellaceae, all propionate/acetate producers. Lactobacillus intestinalis was the only species whose abundance was negatively correlated with change in body weight and fat mass. This species decreased drastically in response to HFD, favouring propionate/acetate producing bacterial species whose abundance was strongly correlated with adiposity and deterioration of metabolic factors. Our observations suggest that these species may play a key role in the development of obesity in response to a HFD. PMID:25992554

  14. Antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in rats fed a high fat diet

    PubMed Central

    2010-01-01

    Background Lotus (Nelumbo nucifera) leaf has been used to treat obesity. The purpose of this study was to investigate the antiobesity and hypolipidemic effects of lotus leaf hot water extract with taurine supplementation in high fat diet-induced obese rats. Methods Four week-old male Sprague-Dawley rats were randomly divided into four groups with 8 rats in each group for a period of 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus leaf hot water extract, HFL group; high fat diet + lotus leaf hot water extract + taurine, HFLT group). Lotus leaf hot water extract was orally administrated to HFL and HFLT groups and the same amount of distilled water was orally administered (400 mg/kg/day) to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). Results The body weight gain and relative weights of epididymal and retroperitoneal adipose tissues were significantly lower in N, HFL and HFLT groups compared to HF group. HFL and HFLT groups showed lower concentrations of total cholesterol, triglyceride and low density lipoprotein cholesterol in serum. HFLT group showed higher the ratio of high density lipoprotein cholesterol/total cholesterol compared to HFL group. HFLT group showed better blood lipid profiles compared to HFL group. Conclusions Lotus leaf hot water extract with taurine supplementation showed antiobesity and hypolipidemic effects in high fat diet-induced obese rats, which was more effective than lotus leaf hot water extract alone. PMID:20804619

  15. Antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in rats fed a high fat diet

    PubMed Central

    2010-01-01

    Background Nelumbo nucifera, known as sacred lotus, is a well-known medicinal plant and this lotus root is commonly used as food compared to different parts of this plant. This study was conducted to investigate the antioxidant and hepatic protective effects of lotus root hot water extract with taurine supplementation in high fat diet-induced obese rats. Methods Thirty-two male Sprague-Dawley rats (4-week-old) were randomly divided into four groups (n=8) for 6 weeks (normal diet, N group; high fat diet, HF group; high fat diet + lotus root hot water extract, HFR group; high fat diet + lotus root hot water extract + taurine, HFRT group). Lotus root hot water extract was orally administrated (400mg/kg/day) to HFR and HFRT groups and the same amount of distilled water was orally administered to N and HF groups. Taurine was supplemented by dissolving in feed water (3% w/v). Results The activities of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase in serum were lower in HFR and HFRT groups compared to HF group. Thiobarbituric acid reactive substance contents in all groups fed a high fat diet were higher compared to N group. The activities of hepatic antioxidant enzymes were higher in HFR and HFRT groups compared to HF group. Conclusions These results suggest that lotus root hot water extract with taurine supplementation shows antioxidant and hepatic protective effects in high fat diet-induced obese rats. PMID:20804615

  16. High-viscosity dietary fibers reduce adiposity and decrease hepatic steatosis in rats fed a high-fat diet.

    PubMed

    Brockman, David A; Chen, Xiaoli; Gallaher, Daniel D

    2014-09-01

    Viscous dietary fiber consumption lowers the postprandial glucose curve and may decrease obesity and associated comorbidities such as insulin resistance and fatty liver. We determined the effect of 2 viscous fibers, one fermentable and one not, on the development of adiposity, fatty liver, and metabolic flexibility in a model of diet-induced obesity. Rats were fed a normal-fat (NF) diet (26% energy from fat), a high-fat diet (60% energy from fat), each containing 5% fiber as cellulose (CL; nonviscous and nonfermentable), or 5% of 1 of 2 highly viscous fibers-hydroxypropyl methylcellulose (HPMC; nonfermentable) or guar gum (GG; fermentable). After 10 wk, fat mass percentage in the NF (18.0%; P = 0.03) and GG groups (17.0%; P < 0.01) was lower than the CL group (20.7%). The epididymal fat pad weight of the NF (3.9 g; P = 0.04), HPMC (3.9 g; P = 0.03), and GG groups (3.6 g; P < 0.01) was also lower than the CL group (5.0 g). The HPMC (0.11 g/g liver) and GG (0.092 g/g liver) groups had lower liver lipid concentrations compared with the CL group (0.14 g/g liver). Fat mass percentage, epididymal fat pad weight, and liver lipid concentration were not different among the NF, HPMC, and GG groups. The respiratory quotient was higher during the transition from the diet-deprived to fed state in the GG group (P = 0.002) and tended to be higher in the HPMC group (P = 0.06) compared with the CL group, suggesting a quicker shift from fatty acid (FA) to carbohydrate oxidation. The HPMC group [15.1 nmol/(mg ⋅ h)] had higher ex vivo palmitate oxidation in muscle compared with the GG [11.7 nmol/(mg ⋅ h); P = 0.04] and CL groups [10.8 nmol/(mg ⋅ h); P < 0.01], implying a higher capacity to oxidize FAs. Viscous fibers can reduce the adiposity and hepatic steatosis that accompany a high-fat diet, and increase metabolic flexibility, regardless of fermentability. PMID:24991042

  17. Nerium oleander Distillate Improves Fat and Glucose Metabolism in High-Fat Diet-Fed Streptozotocin-Induced Diabetic Rats.

    PubMed

    Bas, Ahmet Levent; Demirci, Sule; Yazihan, Nuray; Uney, Kamil; Ermis Kaya, Ezgi

    2012-01-01

    Diabetes was induced by intraperitoneal injection of streptozotocin (35 mg/kg bw) in all rats of five groups after being fed for 2 weeks high-fat diet. Type 2 diabetic Nerium-oleander- (NO-) administered groups received the NO distillate at a dose of 3.75, 37.5, and 375 μg/0.5 mL of distilled water (NO-0.1, NO-1, NO-10, resp.); positive control group had 0.6 mg glibenclamide/kg bw/d by gavage daily for 12 weeks. Type 2 diabetic negative control group had no treatment. NO distillate administration reduced fasting blood glucose, HbA1c, insulin resistance, total cholesterol, low density lipoprotein, atherogenic index, triglyceride-HDL ratio, insulin, and leptin levels. Improved beta cell function and HDL concentration were observed by NO usage. HDL percentage in total cholesterol of all NO groups was similar to healthy control. NO-10 distillate enhanced mRNA expressions of peroxisome proliferator-activated-receptor- (PPAR-) α, β, and γ in adipose tissue and PPAR-α-γ in liver. The findings from both in vivo and in vitro studies suggest that the considerable beneficial effect of NO distillate administration at a dose of 375 μg/0.5 mL of distilled water may offer new approaches to treatment strategies that target both fat and glucose metabolism in type 2 diabetes. PMID:23251156

  18. Wholegrain barley β-glucan fermentation does not improve glucose tolerance in rats fed a high-fat diet.

    PubMed

    Belobrajdic, Damien P; Jobling, Stephen A; Morell, Matthew K; Taketa, Shin; Bird, Anthony R

    2015-02-01

    Fermentation of oat and barley β-glucans is believed to mediate in part their metabolic health benefits, but the exact mechanisms remain unclear. In this study, we sought to test the hypothesis that barley β-glucan fermentation raises circulating incretin hormone levels and improves glucose control, independent of other grain components. Male Sprague-Dawley rats (n = 30) were fed a high-fat diet for 6 weeks and then randomly allocated to 1 of 3 dietary treatments for 2 weeks. The low- (LBG, 0% β-glucan) and high- (HBG, 3% β-glucan) β-glucan diets contained 25% wholegrain barley and similar levels of insoluble dietary fiber, available carbohydrate, and energy. A low-fiber diet (basal) was included for comparison. Immediately prior to the dietary intervention, gastric emptying rate (using the (13)C-octanoic breath test) and postprandial glycemic response of each diet were determined. At the end of the study, circulating gut hormone levels were determined; and a glucose tolerance test was performed. The rats were then killed, and indices of cecal fermentation were assessed. Diet did not affect live weight; however, the HBG diet, compared to basal and LBG, reduced food intake, tended to slow gastric emptying, increased cecal digesta mass and individual and total short-chain fatty acid pools, and lowered digesta pH. In contrast, circulating levels of glucose, insulin, gastric-inhibitory peptide, and glucagon-like peptide-1, and glucose tolerance were unaffected by diet. In conclusion, wholegrain barley β-glucan suppressed feed intake and increased cecal fermentation but did not improve postprandial glucose control or insulin sensitivity. PMID:25622537

  19. The Flower Tea Coreopsis tinctoria Increases Insulin Sensitivity and Regulates Hepatic Metabolism in Rats Fed a High-Fat Diet.

    PubMed

    Jiang, Baoping; Le, Liang; Wan, Wenting; Zhai, Wei; Hu, Keping; Xu, Lijia; Xiao, Peigen

    2015-06-01

    An infusion of Coreopsis tinctoria (CT) flowering tops is traditionally used in Portugal to control hyperglycemia; however, the effects of CT protection against high-fat diet (HFD)-induced hepatic insulin resistance have not been systematically studied and the precise mechanism of action is not clear. The metabolomic profiles of insulin-resistant rats fed a HFD and a CT-supplemented diet (HFD supplemented with CT drinking) for 8 weeks were investigated. Serum samples for clinical biochemistry and liver samples for histopathology and liquid chromatography-mass spectrometry-based metabolomic research were collected. Western blot and quantitative real-time PCR analyses were further used to measure the expression of several relevant enzymes together with perturbed metabolic pathways. Using analysis software, the CT treatment was found to significantly ameliorate the disturbance in 10 metabolic pathways. Combined metabolomic, Western blot, and quantitative real-time PCR analyses revealed that CT treatment significantly improved the glucose homeostasis by, on the one hand, through inhibiting the expression of gluconeogenic pathway key proteins glucose-6-phosphatase and phosphoenolpyruvate carboxykinase and, on the other hand, via regulating the mRNA or protein levels of the Krebs cycle critical enzymes (citrate synthase, succinate dehydrogenase complex, subunit A, flavoprotein, and dihydrolipoamide S-succinyltransferase). These results provide metabolic evidence of the complex pathogenic mechanism involved in hepatic insulin resistance and that the supplementation with CT improves insulin resistance at a global scale. Liquid chromatography-mass spectrometry-based metabolomics approaches are helpful to further understand diabetes-related mechanisms. PMID:25774555

  20. Ethanol Extract of Persimmon Tree Leaves Improves Blood Circulation and Lipid Metabolism in Rats Fed a High-Fat Diet.

    PubMed

    Ryu, Ri; Kim, Hye-Jin; Moon, Byeongseok; Jung, Un Ju; Lee, Mi-Kyung; Lee, Dong Gun; Ryoo, ZaeYoung; Park, Yong Bok; Choi, Myung-Sook

    2015-07-01

    The leaves of the persimmon tree (PL) are known to have beneficial effects on hyperglycemia, dyslipidemia, and nonalcoholic fatty liver disease. We recently demonstrated that PL had antithrombotic properties in vitro. However, little is known about the antiplatelet and anticoagulant properties of PL in vivo. Omega-3 fatty acid (n-3 FA)-containing fish oil has been widely prescribed to improve blood circulation. This study compared the effects of dietary supplementation with an ethanol extract of PL or n-3 FA on blood coagulation, platelet activation, and lipid levels in vivo. Sprague-Dawley rats were fed a high-fat diet with either PL ethanol extract (0.5% w/w) or n-3 FA (2.5% w/w) for 9 weeks. Coagulation was examined by monitoring the activated partial thromboplastin time (aPTT) and prothrombin time. We examined plasma thromboxane B2 (TXB2), serotonin, and soluble P-selectin (sP-selectin) levels. The aPTT was significantly prolonged in the PL and n-3 FA supplement groups. PL also attenuated the TXB2 level and lowered arterial serotonin transporter mRNA expression, although it did not alter plasma serotonin or sP-selectin levels. C-reactive protein and leptin levels were significantly reduced by PL and n-3 FA supplementation. In addition, PL decreased plasma total- and low-density lipoprotein-cholesterol levels, as did n-3 FA treatment. These results indicated that the PL ethanol extract may have the potential to improve circulation by inhibiting blood coagulation and platelet activation and by reducing plasma cholesterol levels. PMID:26061228

  1. The role of Odontella aurita, a marine diatom rich in EPA, as a dietary supplement in dyslipidemia, platelet function and oxidative stress in high-fat fed rats

    PubMed Central

    2012-01-01

    Background Dietary changes are a major factor in determining cardiovascular risk. n-3 polyunsaturated fatty acids modulate the risk factors for metabolic syndrome via multiple mechanisms, including the regulation of the lipid metabolism. We therefore investigated the effect of Odontella aurita, a microalga rich in EPA, which is already used as a food supplement, on the risk factors for high-fat diet induced metabolic syndrome in rats. Methods Male Wistar rats were divided into 4 groups and were fed with a standard diet (control); with the standard diet supplemented with 3% freeze-dried O. aurita (COA); with a high-fat diet (HF); or with the high-fat diet supplemented with 3% of freeze-dried O. aurita (HFOA) for 7 weeks. In this study we evaluated the impact of these different diets on the risk factors for metabolic syndrome, such as hyperlipidemia, platelet aggregation, thromboxane B2 production, and oxidative stress. Results After 7 weeks of treatment, high fat feeding had increased final body weight, glycemia, triacylglycerol, and total cholesterol levels in plasma and liver compared to the control diet. Collagen-induced platelet aggregation and basal platelet thromboxane B2 were also higher in the high-fat fed rats than in those in the control group. In the liver, oxidative stress was greater in the HF group than in the control group. O. aurita intake in HFOA-fed rats resulted in lower glycemia and lipid levels in the plasma and liver relative than in the HF group. Thus, in the HFOA group, n-3 polyunsaturated fatty acid levels in the tissues studied (plasma, liver, and platelets) were higher than in the HF group. Platelet hyper-aggregability tended to decrease in HFOA-fed rats as basal platelet thromboxane B2 production decreased. Finally, O. aurita reduced oxidative stress in the liver, with lower malondialdehyde levels and increased glutathione peroxidase activity. Conclusions O. aurita is a marine diatom rich in EPA as well as in other bioactive molecules

  2. Salvianolic acid A protects against vascular endothelial dysfunction in high-fat diet fed and streptozotocin-induced diabetic rats.

    PubMed

    Yang, Xiu-Ying; Qiang, Gui-Fen; Zhang, Li; Zhu, Xiao-Ming; Wang, Shou-Bao; Sun, Lan; Yang, Hai-Guang; Du, Guan-Hua

    2011-10-01

    Salvianolic acid A (SalA) is one of the main active ingredients of Salvia miltiorrhizae. The objective of this study was to evaluate the effect of SalA on the diabetic vascular endothelial dysfunction (VED). The rats were given a high-fat and high-sucrose diet for 1 month followed by intraperitoneal injection of streptozotocin (30 mg/kg). The diabetic rats were treated with SalA (1 mg/kg, 90% purity) orally for 10 weeks after modeling, and were given a high-fat diet. Contractile and relaxant responses of aorta rings as well as the serum indications were measured. Our results indicated that SalA treatment decreased the level of serum Von Willebrand factor and ameliorated acetylcholine-induced relaxation and KCl-induced contraction in aorta rings of the diabetic rats. SalA treatment also reduced the serum malondialdehyde, the content of aortic advanced glycation end products (AGEs), and the nitric oxide synthase (NOS) activity as well as the expression of endothelial NOS protein in the rat aorta. Exposure of EA.hy926 cells to AGEs decreased the cell viability and changed the cell morphology, whereas SalA had protective effect on AGEs-induced cellular vitality. Our data suggested that SalA could protect against vascular VED in diabetes, which might attribute to its suppressive effect on oxidative stress and AGEs-induced endothelial dysfunction. PMID:21972802

  3. Rice Protein isolate improves lipid and glucose homeostasis in rats fed high fat/high cholesterol diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Hundreds of phytochemicals are bound to rice protein isolate (RPI) and many are bioactive. To determine the metabolic effects of feeding RPI in early development, weanling rats were fed AIN-93G diets made with casein or RPI for 14 d. Reduced growth rate and adiposity prior to puberty in RPI-fed ra...

  4. Intake of Tibetan Hull-Less Barley is Associated with a Reduced Risk of Metabolic Related Syndrome in Rats Fed High-Fat-Sucrose Diets

    PubMed Central

    Gong, Lingxiao; Gong, Lingyun; Zhang, Ying

    2014-01-01

    The objective of this study was to assess the effects of whole grain Tibetan hull-less barley on metabolic related syndrome induced by high-fat-sucrose diets in rats. The diets were designed to reflect the dietary patterns of Chinese individuals (>30% energy fat) with refined wheat flour (HFS-W) or Tibetan hull-less barley (HFS-THB) as the main carbohydrate sources. Rats fed HFS-W had increased body weight, abdominal fat deposition, liver weight, liver fat deposition, triglyceride (TG), fasting blood glucose (FBG), serum fasting insulin (FINS), and homeostasis model assessment of insulin resistance (HOMA-IR) scores, and decreased low-density lipoprotein cholesterol (LDL-C) levels compared to rats fed a basal diet (BD). However, rats fed HFS-THB had reduced body weight gain, dyslipidemia, and insulin resistance. These findings indicate that whole Tibetan hull-less barley is a functional food that can reduce the prevalence of metabolic related syndrome induced by high-fat-sucrose diets. PMID:24763110

  5. Chronic effects of aerobic exercise on gene expression of LOX-1 receptor in the heart of rats fed with high fat diet

    PubMed Central

    Riahi, Simin; Mohammadi, Mohammad Taghi; Sobhani, Vahid; Soleimany, Mansureh

    2015-01-01

    Objective(s): Lectin-like low density lipoprotein receptor (LOX-1) has pivot role in vascular complications, which is upregulated in numerous pathological conditions. Since exercise has beneficial effects in prevention of hyperlipidemic complications, present study examined protective effects of aerobic exercise through reduction of LOX-1 expression in heart during dyslipidemia. Materials and Methods: Four groups of rats were used (N=25): Normal, Normal and exercise, High fat and High fat and exercise. High fat diet (HFD) was made by adding 10% animal oil, 2% cholesterol and 0.5% colic acid to standard rodent chow. Exercise protocol consisted of swimming 1 hr/day, and 5 days/week for 8 weeks. Plasma lipids were evaluated at the end of experiment, 48 hr after final session of exercise. At the end, rats were sacrificed and heart was removed for determination of malondialdehyde (MDA) content, and LOX-1 expression. Results: HFD meaningfully changed lipid profile (>50%), but chronic exercise had no significant effects on lipid profile. LOX-1 expression was significantly increased in heart of rats fed with HFD, while swimming exercise considerably reduced gene expression of LOX-1. MDA content was significantly enhanced in rats fed with HFD (4.37±0.6 nmol/mg, P<0.01) compared to normal group (1.56±0.48 nmol/mg), whereas swimming exercise decreased MDA level of heart in rats fed with HFD (2.28±0.32, P<0.01). Conclusion: Findings indicated that swimming exercise is able to diminish heart expression of LOX-1 receptor concomitant reduction of oxidative stress. Since these parameters are involved in generation of dyslipidemic complications, swimming exercise is a good candidate to reduce these complications. PMID:26557970

  6. Acute induction of uncoupling protein 1 by citrulline in cultured explants of white adipose tissue from lean and high-fat-diet-fed rats

    PubMed Central

    Joffin, Nolwenn; Jaubert, Anne-Marie; Bamba, Jessica; Barouki, Robert; Noirez, Philippe; Forest, Claude

    2015-01-01

    A diet enriched with citrulline (CIT) reduces white adipose tissue (WAT) mass. We recently showed that CIT stimulated β-oxidation in rat WAT explants from young (2–4 months) but not old (25 months) rats. Here we show that both in old rats and high-fat-diet-fed young rats, uncoupling protein one (UCP1) mRNA and protein expressions were weaker than those in young control rats. Selectively in WAT from young rats, a 24h CIT treatment up-regulated expressions of UCP1, peroxisome proliferator-activated receptor-α (PPARα), PPARγ-coactivator-1-α and mitochondrial-transcription-factor-A whereas it down-regulated PPARγ2 gene expression, whatever the diet. These results suggest that CIT induces a new metabolic status in WAT, with increased β-oxidation and uncoupling of respiratory chain, resulting in energy expenditure that favors fat mass reduction. PMID:26167416

  7. Alpha-lipoic acid supplementation reduces mTORC1 signaling in skeletal muscle from high fat fed, obese Zucker rats.

    PubMed

    Li, Zhuyun; Dungan, Cory M; Carrier, Bradley; Rideout, Todd C; Williamson, David L

    2014-12-01

    The mammalian target of rapamycin (mTOR) signaling pathway is hyperactive in liver, adipose and skeletal muscle tissues of obese rodents. Alpha-lipoic acid (αLA) has been well accepted as a weight-loss treatment, though there are limited studies on its effect on mTOR signaling in high-fat fed, obese rodents. Therefore, the goal of this study was to determine mTOR signaling and oxidative protein alterations in skeletal muscle of high-fat fed, obese rats after αLA supplementation. Phosphorylation of the mTOR substrate, eukaryotic initiation factor (eIF) 4E-binding protein 1 (4E-BP1) and eIF4B were significantly reduced (p < 0.05) in muscle from αLA supplemented rats. Activation of AMP-activated protein kinase (AMPK), an mTOR inhibitory kinase, was higher (p < 0.05) in the αLA group. Protein expression of markers of oxidative metabolism, acetyl CoA carboxylase (ACC), cytochrome c oxidase IV (COX IV), peroxisome proliferator-activated receptor (PPAR), and PPAR gamma coactivator 1-alpha (PGC-1α) were significantly higher (p < 0.05) after αLA supplementation compared to non-supplemented group. Our findings show that αLA supplementation limits the negative ramifications of consuming a high fat diet on skeletal muscle markers of oxidative metabolism and mTORC1 signaling. PMID:25366515

  8. Decreased vascular H2S production is associated with vascular oxidative stress in rats fed a high-fat western diet.

    PubMed

    Jenkins, Trisha A; Nguyen, Jason C D; Hart, Joanne L

    2016-07-01

    A Western-style high-fat diet is known to cause vascular dysfunction and oxidative stress. H2S contributes to the regulation of vascular function and acts as a vasoprotective molecule; however, the effects of high-fat diet on vascular H2S production and function are not known. The aim of this study was to investigate the effects of high-fat diet on vascular function and H2S production. Wistar hooded rats were fed a western diet (WD, 21 % fat) or control rat chow (6 % fat) for 12 weeks. At the end of the experiment, the aorta was collected for assessing vascular function and NO and H2S bioavailability. Superoxide anion production was quantitated by lucigenin-enhanced chemiluminescence. The expression of NADPH oxidase subunit Nox2 and the H2S-producing protein cystathionine-γ-lyase (CSE) were examined by Western blotting. WD rats had significantly higher body weight and body fat than control (p < 0.001). Endothelial function and NO bioavailability were significantly reduced in the WD group (p < 0.05), but vascular smooth muscle cell function was unaffected. Vascular superoxide production and Nox2 expression were significantly increased in the aorta from WD rats. L-Cysteine-induced vasorelaxation was reduced in the WD group (p < 0.05) and insensitive to the inhibition of the CSE. In addition, vascular H2S bioavailability and CSE expression were significantly reduced in the aorta from WD rats (p < 0.01). These data show that fat feeding induces vascular oxidative stress and a reduction in endothelial function. Furthermore, there is a reduced capacity for both basal and stimulated vascular H2S production via CSE in fat fed rats. PMID:27087304

  9. Multi-Strain Probiotics Inhibit Cardiac Myopathies and Autophagy to Prevent Heart Injury in High-Fat Diet-Fed Rats

    PubMed Central

    Lai, Chao-Hung; Tsai, Cheng-Chih; Kuo, Wei-Wen; Ho, Tsung-Jung; Day, Cecilia-Hsuan; Pai, Pei-ying; Chung, Li-Chin; Huang, Chun-Chih; Wang, Hsueh-Fang; Liao, Po-Hsiang; Huang, Chih-Yang

    2016-01-01

    High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats. PMID:27076784

  10. Multi-Strain Probiotics Inhibit Cardiac Myopathies and Autophagy to Prevent Heart Injury in High-Fat Diet-Fed Rats.

    PubMed

    Lai, Chao-Hung; Tsai, Cheng-Chih; Kuo, Wei-Wen; Ho, Tsung-Jung; Day, Cecilia-Hsuan; Pai, Pei-Ying; Chung, Li-Chin; Huang, Chun-Chih; Wang, Hsueh-Fang; Liao, Po-Hsiang; Huang, Chih-Yang

    2016-01-01

    High-fat diets induce obesity, leading to cardiomyocyte fibrosis and autophagy imbalance. In addition, no previous studies have indicated that probiotics have potential health effects associated with cardiac fibrosis and autophagy in obese rats. This study investigates the effects of probiotics on high-fat (HF) diet-induced obesity and cardiac fibrosis and autophagy in rat hearts. Eight-week-old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (control) and high-fat (HF) diet groups and groups fed a high-fat diet supplemented with low (HL), medium (HM) or high (HH) doses of multi-strain probiotic powders. These experiments were designed for an 8-week trial period. The myocardial architecture of the left ventricle was evaluated using Masson's trichrome staining and immunohistochemistry staining. Key probiotics-related pathway molecules were analyzed using western blotting. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HF hearts. These interstitial spaces were significantly decreased in groups provided with multi-strain probiotics compared with HF hearts. Western blot analysis demonstrated that key components of the TGF/MMP2/MMP9 fibrosis pathways and ERK5/uPA/ANP cardiac hypertrophy pathways were significantly suppressed in probiotic groups compared to the HF group. Autophagy balance is very important in cardiomyocytes. In this study, we observed that the beclin-1/LC3B/Atg7 autophagy pathway in HF was increased after probiotic supplementation was significantly decreased. Together, these results suggest that oral administration of probiotics may attenuate cardiomyocyte fibrosis and cardiac hypertrophy and the autophagy-signaling pathway in obese rats. PMID:27076784

  11. Optimized Rapeseed Oils Rich in Endogenous Micronutrients Protect High Fat Diet Fed Rats from Hepatic Lipid Accumulation and Oxidative Stress

    PubMed Central

    Xu, Jiqu; Liu, Xiaoli; Gao, Hui; Chen, Chang; Deng, Qianchun; Huang, Qingde; Ma, Zhonghua; Huang, Fenghong

    2015-01-01

    Micronutrients in rapeseed exert a potential benefit to hepatoprotection, but most of them are lost during the conventional refining processing. Thus some processing technologies have been optimized to improve micronutrient retention in oil. The aim of this study is to assess whether optimized rapeseed oils (OROs) have positive effects on hepatic lipid accumulation and oxidative stress induced by a high-fat diet. Methods: Rats received experiment diets containing 20% fat and refined rapeseed oil or OROs obtained with various processing technologies as lipid source. After 10 weeks of treatment, liver was assayed for lipid accumulation and oxidative stress. Results: All OROs reduced hepatic triglyceride contents. Microwave pretreatment-cold pressing oil (MPCPO) which had the highest micronutrients contents also reduced hepatic cholesterol level. MPCPO significantly decreased hepatic sterol regulatory element-binding transcription factor 1 (SREBP1) but increased peroxisome proliferator activated receptor α (PPARα) expressions, and as a result, MPCPO significantly suppressed acetyl CoA carboxylase and induced carnitine palmitoyl transferase-1 and acyl CoA oxidase expression. Hepatic catalase (CAT) and glutathione peroxidase (GPx) activities as well as reduced glutathione (GSH) contents remarkably increased and lipid peroxidation levels decreased in parallel with the increase of micronutrients. Conclusion: OROs had the ability to reduce excessive hepatic fat accumulation and oxidative stress, which indicated that OROs might contribute to ameliorating nonalcoholic fatty liver induced by high-fat diet. PMID:26473919

  12. Burdock fermented by Aspergillus awamori elevates cecal Bifidobacterium, and reduces fecal deoxycholic acid and adipose tissue weight in rats fed a high-fat diet.

    PubMed

    Okazaki, Yukako; Sitanggang, Novita Vivi; Sato, Satoko; Ohnishi, Nanae; Inoue, Junji; Iguchi, Takafumi; Watanabe, Toshiro; Tomotake, Hiroyuki; Harada, Kazuki; Kato, Norihisa

    2013-01-01

    This study investigated the effects of dietary supplementation with burdock powder and Aspergillus awamori-fermented burdock powder at 5% on the intestinal luminal environment and body fat in rats fed a high-fat (HF) diet. Food intake and growth were unaffected by dietary manipulation. Consumption of the burdock and fermented burdock diets significantly elevated fecal IgA and mucins (indices of intestinal immune and barrier functions) and reduced fecal lithocholic acid (a risk factor for colon cancer) (p<0.05). The fermented burdock diet markedly elevated cecal Bifidobacterium and organic acids, including lactate, acetate, propionate, and butyrate, and reduced fecal deoxycholic acid (a risk factor for colon cancer) and perirenal adipose tissue weight (p<0.05), but the burdock diet did not. These results suggest that consumption of fermented burdock improves the intestinal luminal environment and suppresses obesity in rats fed a HF diet. PMID:23291748

  13. Hepatoprotective and Antioxidant Potential of Organic and Conventional Grape Juices in Rats Fed a High-Fat Diet

    PubMed Central

    Buchner, Iselde; Medeiros, Niara; dos Santos Lacerda, Denise; Normann, Carlos Augusto B. M.; Gemelli, Tanise; Rigon, Paula; Wannmacher, Clovis Milton Duval; Henriques, João Antônio Pegas; Dani, Caroline; Funchal, Cláudia

    2014-01-01

    The objective of this study was to investigate the antioxidant and hepatoprotective effect of the chronic use of conventional (CGJ) or organic (OGJ) grape juice from the Bordeaux variety grape on oxidative stress and cytoarchitecture in the liver of rats supplemented with a high-fat diet (HFD) for three months. The results demonstrated that HFD induced an increase in thiobarbituric acid-reactive substances (TBARS), catalase (CAT) activity and 2′,7′-dihydrodichlorofluorescein (DCFH) oxidation and a decrease in sulfhydryl content and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. HFD also induced hepatocellular degeneration and steatosis. These alterations were prevented by CGJ and OGJ, where OGJ was more effective. Therefore, it was concluded that HFD induced oxidative stress and liver damage and that the chronic use of grape juice was able to prevent these alterations. PMID:26784874

  14. Hepatoprotective and Antioxidant Potential of Organic and Conventional Grape Juices in Rats Fed a High-Fat Diet.

    PubMed

    Buchner, Iselde; Medeiros, Niara; Lacerda, Denise Dos Santos; Normann, Carlos Augusto B M; Gemelli, Tanise; Rigon, Paula; Wannmacher, Clovis Milton Duval; Henriques, João Antônio Pegas; Dani, Caroline; Funchal, Cláudia

    2014-01-01

    The objective of this study was to investigate the antioxidant and hepatoprotective effect of the chronic use of conventional (CGJ) or organic (OGJ) grape juice from the Bordeaux variety grape on oxidative stress and cytoarchitecture in the liver of rats supplemented with a high-fat diet (HFD) for three months. The results demonstrated that HFD induced an increase in thiobarbituric acid-reactive substances (TBARS), catalase (CAT) activity and 2',7'-dihydrodichlorofluorescein (DCFH) oxidation and a decrease in sulfhydryl content and superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. HFD also induced hepatocellular degeneration and steatosis. These alterations were prevented by CGJ and OGJ, where OGJ was more effective. Therefore, it was concluded that HFD induced oxidative stress and liver damage and that the chronic use of grape juice was able to prevent these alterations. PMID:26784874

  15. Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets

    PubMed Central

    Tao, Yi; Zhang, Hong-Liang; Hu, Yin-Ming; Wan, Shuo; Su, Zheng-Quan

    2013-01-01

    This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC. PMID:23429200

  16. Preparation of Chitosan and Water-Soluble Chitosan Microspheres via Spray-Drying Method to Lower Blood Lipids in Rats Fed with High-Fat Diets.

    PubMed

    Tao, Yi; Zhang, Hong-Liang; Hu, Yin-Ming; Wan, Shuo; Su, Zheng-Quan

    2013-01-01

    This experiment aimed to investigate the effects of the chitosan (CTS) and water-soluble chitosan (WSC) microspheres on plasma lipids in male Sprague-Dawley rats fed with high-fat diets. CTS microspheres and WSC microspheres were prepared by the spray-drying technique. Scanning electron microscopy (SEM) micrographs showed that the microspheres were nearly spherical in shape. The mean size of CTS microspheres was 4.07 μm (varying from 1.50 to 7.21 μm) and of WSC microspheres was 2.00 μm (varying from 0.85 to 3.58 μm). The rats were classified into eight groups (n = 8) and were fed with high-fat diets for two weeks to establish the hyperlipidemic condition and were then treated with CTS microspheres and WSC microspheres, CTS and WSC for four weeks. The results showed that CTS and WSC microspheres reduced blood lipids and plasma viscosity and increased the serum superoxide dismutase (SOD) levels significantly. This study is the first report of the lipid-lowering effects of CTS and WSC microspheres. CTS and WSC microspheres were found to be more effective in improving hyperlipidemia in rats than common CTS and WSC. PMID:23429200

  17. Effects of black adzuki bean (Vigna angularis, Geomguseul) extract on body composition and hypothalamic neuropeptide expression in rats fed a high-fat diet

    PubMed Central

    Kim, Mina; Song, Seok-Bo; Cha, Youn-Soo

    2015-01-01

    Background Obesity is often considered to result from either excessive food intake or insufficient physical activity. Adzuki beans have been evaluated as potential remedies for various health conditions, and recent studies have reported their effects on the regulation of lipid metabolism, but it remains to be determined whether they may be effective in overcoming obesity by regulating appetite and satiety. Objective This study investigated the effect of black adzuki bean (BAB) extract on body composition and hypothalamic neuropeptide expression in Sprague Dawley rats (Rattus norvegicus) fed a high-fat diet. Design The rats were fed for 8 weeks with a control diet containing 10 kcal% from fat (CD), a high-fat diet containing 60 kcal% from fat (HD), or a high-fat diet with 1% or 2% freeze-dried ethanolic extract powder of BAB (BAB-1 and BAB-2). Results The body weights and epididymal fat weights were significantly reduced and the serum lipid profiles were improved in the group fed the diet containing BAB compared to the HD group. The expression of AGRP mRNA significantly decreased in the BAB groups, and treatment with BAB-2 resulted in a marked induction of the mRNA expression of POMC and CART, which are anorexigenic neuropeptides that suppress food intake. Furthermore, mRNA expression levels of ObRb, a gene related to leptin sensitivity in the hypothalamus, were significantly higher in the BAB groups than in the HD group. Conclusions These results suggest that supplementation with BAB has a significant effect on body weight via regulation of hypothalamic neuropeptides. PMID:26493717

  18. Urine and serum metabolite profiling of rats fed a high-fat diet and the anti-obesity effects of caffeine consumption.

    PubMed

    Kim, Hyang Yeon; Lee, Mee Youn; Park, Hye Min; Park, Yoo Kyoung; Shon, Jong Cheol; Liu, Kwang-Hyeon; Lee, Choong Hwan

    2015-01-01

    In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling. PMID:25689639

  19. Abdominal adiposity, insulin and bone quality in young male rats fed a high-fat diet containing soybean or canola oil

    PubMed Central

    da Costa, Carlos Alberto Soares; Carlos, Aluana Santana; de Sousa dos Santos, Aline; Monteiro, Alexandra Maria Vieira; de Moura, Egberto Gaspar; Nascimento-Saba, Celly Cristina Alves

    2011-01-01

    OBJECTIVES: A low ratio of omega-6/omega-3 polyunsaturated fatty acids is associated with healthy bone properties. However, fatty diets can induce obesity. Our objective was to evaluate intra-abdominal adiposity, insulin, and bone growth in rats fed a high-fat diet containing low ratios of omega-6/omega-3 provided in canola oil. METHODS: After weaning, rats were grouped and fed either a control diet (7S), a high-fat diet containing soybean oil (19S) or a high-fat diet of canola oil (19C) until they were 60 days old. Differences were considered to be significant if p<0.05. RESULTS: After 60 days, the 19S and 19C groups showed more energy intake, body density growth and intra-abdominal fat mass. However, the 19S group had a higher area (200%) and a lower number (44%) of adipocytes, while the 7S and 19C groups did not differ. The serum concentrations of glucose and insulin and the insulin resistance index were significantly increased in the 19C group (15%, 56%, and 78%, respectively) compared to the 7S group. Bone measurements of the 19S and 19C groups showed a higher femur mass (25%) and a higher lumbar vertebrae mass (11%) and length (5%). Computed tomography analysis revealed more radiodensity in the proximal femoral epiphysis and lumbar vertebrae of 19C group compared to the 7S and 19S groups. CONCLUSIONS: Our results suggest that the amount and source of fat used in the diet after weaning increase body growth and fat depots and affect insulin resistance and, consequently, bone health. PMID:22012056

  20. Effects of Long-Term Exposure to Free Nε-(Carboxymethyl)lysine on Rats Fed a High-Fat Diet.

    PubMed

    Li, Mei; Zeng, Maomao; He, Zhiyong; Zheng, Zongping; Qin, Fang; Tao, Guanjun; Zhang, Shuang; Chen, Jie

    2015-12-30

    Recently correlation studies between dietary advanced glycation end products (AGEs) and the progression of chronic diseases have attracted much attention. To explore the impact of dietary AGEs on the health risk of people consuming a high-fat diet (HFD), male Sprague-Dawley rats were used as the research subject. Under HFD, free N(ε)-(carboxymethyl)lysine (CML, a major AGE, 60 mg/kg body weight/day) was administered by gavage for 12 consecutive weeks. The results indicated that protein-bound CML accumulation in the kidney, heart, lung, pancreas, and muscle significantly increased to 178 ± 36, 161 ± 2, 106 ± 11, 39 ± 8, and 141 ± 20 μg/g dry matter, respectively, compared to HFD control levels of 86 ± 9, 127 ± 10, 89 ± 6, 23 ± 2, and 95 ± 3 μg/g dry matter, whereas no statistical increase was found in the liver and spleen. An increase of the protein-bound CML might be due to free CML binding to proteins in tissues by covalent bonds. Moreover, the rats' serum low-density lipoprotein cholesterol concentration, fasting blood glucose levels, and energy expenditure also increased obviously. These findings indicated that long-term intake of high-dose free CML might be a health risk factor for rats with HFD. This could provide valuable information for further study on the possible effects of long-term consumption of CML-rich fatty foods on human health, involving the progression of chronic disease. PMID:26652688

  1. Gut microbiota are linked to increased susceptibility to hepatic steatosis in low-aerobic-capacity rats fed an acute high-fat diet.

    PubMed

    Panasevich, Matthew R; Morris, E M; Chintapalli, S V; Wankhade, U D; Shankar, K; Britton, S L; Koch, L G; Thyfault, J P; Rector, R S

    2016-07-01

    Poor aerobic fitness is linked to nonalcoholic fatty liver disease and increased all-cause mortality. We previously found that rats with a low capacity for running (LCR) that were fed an acute high-fat diet (HFD; 45% kcal from fat) for 3 days resulted in positive energy balance and increased hepatic steatosis compared with rats that were highly aerobically fit with a high capacity for running (HCR). Here, we tested the hypothesis that poor physiological outcomes in LCR rats following acute HFD feeding are associated with alterations in cecal microbiota. LCR rats exhibited greater body weight, feeding efficiency, 3 days of body weight change, and liver triglycerides after acute HFD feeding compared with HCR rats. Furthermore, compared with HCR rats, LCR rats exhibited reduced expression of intestinal tight junction proteins. Cecal bacterial 16S rDNA revealed that LCR rats had reduced cecal Proteobacteria compared with HCR rats. Microbiota of HCR rats consisted of greater relative abundance of Desulfovibrionaceae and unassigned genera within this family, suggesting increased reduction of endogenous mucins and proteins. Although feeding rats an acute HFD led to reduced Firmicutes in both strains, short-chain fatty acid-producing Phascolarctobacterium was reduced in LCR rats. In addition, Ruminococcae and Ruminococcus were negatively correlated with energy intake in the LCR/HFD rats. Predicted metagenomic function suggested that LCR rats had a greater capacity to metabolize carbohydrate and energy compared with HCR rats. Overall, these data suggest that the populations and metabolic capacity of the microbiota in low-aerobically fit LCR rats may contribute to their susceptibility to acute HFD-induced hepatic steatosis and poor physiologic outcomes. PMID:27288420

  2. Kaempferol regulates the lipid-profile in high-fat diet-fed rats through an increase in hepatic PPARα levels.

    PubMed

    Chang, Chia Ju; Tzeng, Thing-Fong; Liou, Shorong-Shii; Chang, Yuan-Shiun; Liu, I-Min

    2011-11-01

    The aim of this study was to investigate the antiobesity and antihyperlipidemic effects of the flavonoid kaempferol (3,5,7,4'-tetrahydroxyflavone). After being fed a high-fat diet (HFD) for two weeks, rats were dosed orally with kaempferol (75, 150, or 300 mg/kg) or fenofibrate (100 mg/kg) once daily for eight weeks. Fenofibrate is an antilipemic agent that exerts its therapeutic effects through activation of peroxisome proliferator-activated receptor α (PPAR α). Kaempferol (300 mg/kg/day) produced effects similar to fenofibrate in reducing body weight gain, visceral fat-pad weights, plasma lipid levels, as well as the coronary artery risk and atherogenic indices of HFD-fed rats. Kaempferol also caused dose-related reductions in hepatic triglyceride and cholesterol content and lowered hepatic lipid droplet accumulation and the size of epididymal adipocytes in HFD-fed rats. Kaempferol and fenofibrate reversed the HFD-induced downregulation of hepatic PPAR α. HFD-induced reductions in the hepatic levels of acyl-CoA oxidase (ACO), and cytochrome P450 isoform 4A1 (CYP4A1) proteins were reversed by kaempferol and fenofibrate. The elevated expression of hepatic sterol regulatory element binding proteins (SREBPs) in HFD-fed rats were lowered by kaempferol and fenofibrate. These results suggest that kaempferol reduced the accumulation of visceral fat and improved hyperlipidemia in HFD-fed obese rats by increasing lipid metabolism through the downregulation of SREBPs and promoting the hepatic expression of ACO and CYP4A1, secondary to a direct upregulation hepatic PPAR α expression. PMID:21728151

  3. Wild rice ( Zizania latifolia (Griseb) Turcz) improves the serum lipid profile and antioxidant status of rats fed with a high fat/cholesterol diet.

    PubMed

    Zhang, Hong; Cao, Pei; Agellon, Luis B; Zhai, Cheng-Kai

    2009-12-01

    The diet consumed by urban residents in modern China has become rich in saturated fats and cholesterol. In addition, the diet is high in carbohydrates from white rice and processed wheat starch. The aim of the present study was to determine the effects of replacing white rice and processed wheat starch with wild rice (WR) as the chief source of dietary carbohydrates. Rats fed with the diet patterned after the diet consumed by city residents of modern China showed elevated serum lipid levels comparable with rats consuming a high fat/cholesterol diet known to induce hyperlipidaemia in this species. Meanwhile, rats consuming the city diet with WR as the carbohydrate source suppressed the increase in serum TAG and total cholesterol, and the decrease in HDL cholesterol level. In addition, the rats fed the WR diet suppressed the build-up of oxidative stress by improving antioxidant capacity, increasing superoxide dismutase activity and reducing malondialdehyde concentration, both in the serum and liver. These findings illustrate that WR is effective in suppressing hyperlipidaemia and oxidative stress in rats even when the diet consumed is high in fat and cholesterol. PMID:19631021

  4. Grape pomace and grape pomace extract improve insulin signaling in high-fat-fructose fed rat-induced metabolic syndrome.

    PubMed

    Rodriguez Lanzi, Cecilia; Perdicaro, Diahann Jeanette; Antoniolli, Andrea; Fontana, Ariel Ramón; Miatello, Roberto Miguel; Bottini, Rubén; Vazquez Prieto, Marcela Alejandra

    2016-03-01

    In this study the effect of diet supplementation with grape pomace (GP) and grape pomace extract (GPE) on insulin sensitive tissues (adipose, liver and muscle) was evaluated in an experimental model of metabolic syndrome (MetS). MetS was developed by giving a high-fat-fructose (HFF) diet to Wistar rats. Six weeks of HFF diet induced weight gain, which was partially attenuated by GP (1 g per kg per day) and GPE (300 mg per kg per day) supplementation. HFF diet increased systolic blood pressure, triglycerides, insulin resistance (HOMA:IR) and inflammation (c-reactive protein (CRP)). Supplementation with GP prevented SBP, triglycerides and CRP increased and partially attenuated insulin resistance. On the other hand, GPE partially reduced SBP and triglycerides and significantly prevented insulin resistance and inflammation. Also, HFF diet induced higher triglycerides content and enhanced NADPH oxidase activity in the liver. Also, HFF diet increased the epididymal adipose tissue weight, enlarged adipocyte size, and c-jun N-terminal kinase (JNK) activation, probably contributing to a pro-inflammatory cytokine pattern (higher resistin) and lower adiponectin protein expression. These alterations may result in an impairment of insulin signaling cascade observed in adipose, liver and muscle tissue (IRS1, Akt, and extracellular signal-regulated kinases (ERK1/2)) from HFF rats. Supplementation with GP and to a greater extent GPE attenuated liver triglyceride content and adiposity and restored adipose, liver and muscle response to insulin. These findings show that supplementation with GP and GPE to a greater extent can counteract adiposity, inflammation, liver damage and impaired insulin signaling associated to MetS, supporting the utilization of winemaking residues in food industry/human health due to their high amount of bioactive compounds. PMID:26901521

  5. Protective Effect of Dietary Lily Bulb on Dextran Sulfate Sodium-Induced Colitis in Rats Fed a High-Fat Diet.

    PubMed

    Okazaki, Yukako; Chiji, Hideyuki; Kato, Norihisa

    2016-01-01

    Lily bulb is traditionally consumed in East Asia and contains high amounts of glucomannan. This study investigated the effect of dietary lily bulb on dextran sulfate sodium (DSS)-induced colitis in rats fed a high-fat (HF) diet. Male Sprague-Dawley rats were fed a diet containing 30% beef tallow with or without 7% steamed lily bulb powder for 17 d. Experimental colitis was induced by replacing drinking water with DSS during the last 7 d. The disease activity index (DAI) was significantly lower in the lily bulb+DSS group than in the DSS group on day 17. The fecal abundance of Bifidobacterium was significantly reduced in the DSS group compared with that in the control group, but it was recovered by lily bulb intake. Cecal butyrate, fecal mucins, and alkaline phosphatase (ALP) activity were significantly higher in the DSS group than in the control group. Dietary lily bulb potentiated the increase in cecal butyrate, fecal mucins, and the ALP activity caused by DSS treatment. These results indicate that lily bulb attenuates DSS-induced colitis by modulating colonic microflora, organic acids, mucins, and ALP activity in HF diet-fed rats. PMID:27465728

  6. Effects of Yogurt Containing Fermented Pepper Juice on the Body Fat and Cholesterol Level in High Fat and High Cholesterol Diet Fed Rat

    PubMed Central

    Yeon, Su-Jung; Hong, Go-Eun; Kim, Chang-Kyu; Park, Woo Joon; Kim, Soo-Ki; Lee, Chi-Ho

    2015-01-01

    This experiment investigated whether yogurt containing fermented pepper juice (FPJY) affects cholesterol level in high fat and high cholesterol diet (HFCD) fed rat. Twenty five Sprague-Dawley male rats of 7 wk were divided into 5 groups, and fed following diets for 9 wk; CON (control diet), HFCD (HFCD), PY (HFCD supplemented with 2% of plain yogurt), LFY (HFCD supplemented with 2% of FPJY), and HFY (HFCD supplemented with 5% of FPJY). In the LFY group, hepatic total lipid level decreased significantly compared to the HFCD group (p<0.05). Serum HDL cholesterol level tended to increase and hepatic total cholesterol level decreased and were comparable to the CON group (p>0.05). In HFY group, body weight and hepatic total lipid level significantly decreased over the HFCD group (p<0.05). Serum and hepatic total cholesterol level, kidney, and body fat weights decreased, and were compared to the CON group (p>0.05). Liver weight decreased as FPJY content was increased. Results suggested FPJY would inhibit organ hypertrophy and accumulation of body fat, hepatic lipid, and cholesterol in HFCD fed rat. PMID:26761869

  7. Terminalia paniculata bark extract attenuates non-alcoholic fatty liver via down regulation of fatty acid synthase in high fat diet-fed obese rats

    PubMed Central

    2014-01-01

    Background This study was performed to understand the possible therapeutic activity of Terminalia paniculata ethanolic extract (TPEE) on non alcoholic fatty liver in rats fed with high fat diet. Methods Thirty six SD rats were divided into 6 groups (n = 6): Normal control (NC), high fat diet (HFD), remaining four groups were fed on HFD along with different doses of TPEE (100,150 and 200 mg/kg b.wt) or orlistat, for ten weeks. Liver tissue was homogenized and analyzed for lipid profiles, activities of superoxide dismutase (SOD), catalase (CAT) and malondialdehyde (MDA) content. Further, the expression levels of FAS and AMPK-1α were also studied in addition to histopathology examination of liver tissue in all the groups. Results HFD significantly increased hepatic liver total cholesterol (TC), triglycerides (TG), free fatty acids (FFA) and MDA but decreased the activities of SOD and CAT which were subsequently reversed by supplementation with TPEE in a dose-dependent manner. In addition, TPEE administration significantly down regulated hepatic mRNA expression of FAS but up regulated AMPK-1α compared to HFD alone fed group. Furthermore, western blot analysis of FAS has clearly demonstrated decreased expression of FAS in HFD + TPEE (200 mg/kg b.wt) treated group when compared to HFD group at protein level. Conclusions Our biochemical studies on hepatic lipid profiles and antioxidant enzyme activities supported by histological and expression studies suggest a potential therapeutic role for TPEE in regulating obesity through FAS. PMID:24678767

  8. Alpha-Lipoic Acid Reduces LDL-Particle Number and PCSK9 Concentrations in High-Fat Fed Obese Zucker Rats

    PubMed Central

    Carrier, Bradley; Wen, Shin; Zigouras, Sophia; Browne, Richard W.; Li, Zhuyun; Patel, Mulchand S.; Williamson, David L.; Rideout, Todd C.

    2014-01-01

    We characterized the hypolipidemic effects of alpha-lipoic acid (LA, R-form) and examined the associated molecular mechanisms in a high fat fed Zucker rat model. Rats (n = 8) were assigned to a high fat (HF) diet or the HF diet with 0.25% LA (HF-LA) for 30 days and pair fed to remove confounding effects associated with the anorectic properties of LA. Compared with the HF controls, the HF-LA group was protected against diet-induced obesity (102.5±3.1 vs. 121.5±3.6,% change BW) and hypercholesterolemia with a reduction in total-C (−21%), non-HDL-C (−25%), LDL-C (−16%), and total LDL particle number (−46%) and an increase in total HDL particles (∼22%). This cholesterol-lowering response was associated with a reduction in plasma PCSK9 concentration (−70%) and an increase in hepatic LDLr receptor protein abundance (2 fold of HF). Compared with the HF-fed animals, livers of LA-supplemented animals were protected against TG accumulation (−46%), likely through multiple mechanisms including: a suppressed lipogenic response (down-regulation of hepatic acetyl-CoA carboxylase and fatty acid synthase expression); enhanced hepatic fat oxidation (increased carnitine palmitoyltransferase Iα expression); and enhanced VLDL export (increased hepatic diacylglycerol acyltransferase and microsomal triglyceride transfer protein expression and elevated plasma VLDL particle number). Study results also support an enhanced fatty acid uptake (2.8 fold increase in total lipase activity) and oxidation (increased CPT1β protein abundance) in muscle tissue in LA-supplemented animals compared with the HF group. In summary, in the absence of a change in caloric intake, LA was effective in protecting against hypercholesterolemia and hepatic fat accumulation under conditions of strong genetic and dietary predisposition toward obesity and dyslipidemia. PMID:24595397

  9. Effects of the Polysaccharide from the Sporophyll of Brown Alga Undaria Pinnatifida on Serum Lipid Profile and Fat Tissue Accumulation in Rats Fed a High-Fat Diet.

    PubMed

    Kim, Byoung-Mok; Park, Jae-Ho; Kim, Dong-Soo; Kim, Young-Myung; Jun, Joon-Young; Jeong, In-Hak; Chi, Young-Min

    2016-07-01

    We investigated the effects of the polysaccharide from the sporophyll of a selected brown alga Undaria pinnatifida on serum lipid profile, fat tissue accumulation, and gastrointestinal transit time in rats fed a high-fat diet. The algal polysaccharide (AP) was prepared by the treatment of multiple cellulase-producing fungi Trichoderma reesei and obtained from the sporophyll with a yield of 38.7% (dry basis). The AP was mostly composed of alginate and fucoidan (up to 89%) in a ratio of 3.75:1. The AP was added to the high-fat diet in concentrations of 0.6% and 1.7% and was given to male Sprague-Dawley rats (5-wk-old) for 5 wk. The 1.7% AP addition notably reduced body weight gain and fat tissue accumulation, and it improved the serum lipid profile, including triglycerides, total cholesterol, and very low-density lipoprotein-cholesterol. The effects were associated with increased feces weight and shortened gastrointestinal transit time. In addition, the lipid peroxidation of the liver was decreased in both groups. PMID:27384013

  10. PPARγ activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats.

    PubMed

    Sato, Daisuke; Oda, Kanako; Kusunoki, Masataka; Nishina, Atsuyoshi; Takahashi, Kazuaki; Feng, Zhonggang; Tsutsumi, Kazuhiko; Nakamura, Takao

    2016-02-15

    It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARγ agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARγ activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes. PMID:26825545

  11. Protective Effect of Vanillic Acid against Hyperinsulinemia, Hyperglycemia and Hyperlipidemia via Alleviating Hepatic Insulin Resistance and Inflammation in High-Fat Diet (HFD)-Fed Rats.

    PubMed

    Chang, Wen-Chang; Wu, James Swi-Bea; Chen, Chen-Wen; Kuo, Po-Ling; Chien, Hsu-Min; Wang, Yuh-Tai; Shen, Szu-Chuan

    2015-12-01

    Excess free fatty acid accumulation from abnormal lipid metabolism results in the insulin resistance in peripheral cells, subsequently causing hyperinsulinemia, hyperglycemia and/or hyperlipidemia in diabetes mellitus (DM) patients. Herein, we investigated the effect of phenolic acids on glucose uptake in an insulin-resistant cell-culture model and on hepatic insulin resistance and inflammation in rats fed a high-fat diet (HFD). The results show that vanillic acid (VA) demonstrated the highest glucose uptake ability among all tested phenolic acids in insulin-resistant FL83B mouse hepatocytes. Furthermore, rats fed HFD for 16 weeks were orally administered with VA daily (30 mg/kg body weight) at weeks 13-16. The results show that levels of serum insulin, glucose, triglyceride, and free fatty acid were significantly decreased in VA-treated HFD rats (p < 0.05), indicating the protective effects of VA against hyperinsulinemia, hyperglycemia and hyperlipidemia in HFD rats. Moreover, VA significantly reduced values of area under the curve for glucose (AUCglucose) in oral glucose tolerance test and homeostasis model assessment-insulin resistance (HOMA-IR) index, suggesting the improving effect on glucose tolerance and insulin resistance in HFD rats. The Western blot analysis revealed that VA significantly up-regulated expression of hepatic insulin-signaling and lipid metabolism-related protein, including insulin receptor, phosphatidylinositol-3 kinase, glucose transporter 2, and phosphorylated acetyl CoA carboxylase in HFD rats. VA also significantly down-regulated hepatic inflammation-related proteins, including cyclooxygenase-2 and monocyte chemoattractant protein-1 expressions in HFD rats. These results indicate that VA might ameliorate insulin resistance via improving hepatic insulin signaling and alleviating inflammation pathways in HFD rats. These findings also suggest the potential of VA in preventing the progression of DM. PMID:26633482

  12. Green tea supplementation benefits body composition and improves bone properties in obese female rats fed with high-fat diet and caloric restricted diet.

    PubMed

    Shen, Chwan-Li; Han, Jia; Wang, Shu; Chung, Eunhee; Chyu, Ming-Chien; Cao, Jay J

    2015-12-01

    This study investigated the effects of green tea polyphenols (GTP) supplementation on body composition, bone properties, and serum markers in obese rats fed a high-fat diet (HFD) or a caloric restricted diet (CRD). Forty-eight female rats were fed an HFD ad libitum for 4 months, and then either continued on the HFD or the CRD with or without 0.5% GTP in water. Body composition, bone efficacy, and serum markers were measured. We hypothesized that GTP supplementation would improve body composition, mitigate bone loss, and restore bone microstructure in obese animals fed either HFD or CRD. CRD lowered percent fat mass; bone mass and trabecular number of tibia, femur and lumbar vertebrae; femoral strength; trabecular and cortical thickness of tibia; insulin-like growth factor-I and leptin. CRD also increased percent fat-free mass; trabecular separation of tibia and femur; eroded surface of tibia; bone formation rate and erosion rate at tibia shaft; and adiponectin. GTP supplementation increased femoral mass and strength (P = .026), trabecular thickness (P = .012) and number (P = .019), and cortical thickness of tibia (P < .001), and decreased trabecular separation (P = .021), formation rate (P < .001), and eroded surface (P < .001) at proximal tibia, and insulin-like growth factor-I and leptin. There were significant interactions (diet type × GTP) on osteoblast surface/bone surface, mineral apposition rate at periosteal and endocortical bones, periosteal bone formation rate, and trabecular thickness at femur and lumbar vertebrate (P < .05). This study demonstrates that GTP supplementation for 4 months benefited body composition and improved bone microstructure and strength in obese rats fed with HFD or HFD followed by CRD diet. PMID:26525915

  13. Salvianolic Acid a prevents the pathological progression of hepatic fibrosis in high-fat diet-fed and streptozotocin-induced diabetic rats.

    PubMed

    Qiang, Guifen; Yang, Xiuying; Xuan, Qi; Shi, Lili; Zhang, Hengai; Chen, Bainian; Li, Xiaoxiu; Zu, Mian; Zhou, Dan; Guo, Jing; Yang, Haiguang; Zhang, Li; Du, Guanhua

    2014-01-01

    Type 2 diabetes patients have an increased risk of developing hepatic fibrosis. Salvianolic acid A (SalA) has been reported to be a strong polyphenolic anti-oxidant and free radical scavenger. The aim of the present study was to evaluate the effect of SalA on the pathological progression of hepatic fibrosis in high-fat diet (HFD)-fed and streptozotocin (STZ)-induced diabetic rats and to clarify the underlying mechanisms. Type 2 diabetic animal model with hepatic fibrosis was developed by a high-sucrose, HFD and low-dose STZ injection (i.p.). Diabetic rats were randomly divided into SalA group (0.3 mg/kg/day) and diabetic control groups fed with a HFD. After administration for four months, SalA reversed the hyperlipidemia and reduced hepatic triglyceride (TG). Hematoxylin-Eosin (HE) and Picro acid-Sirius red staining results indicated that SalA significantly alleviated the lesions of hepatic steatosis and fibrosis, with the reduction of type I and III collagens. The expression of α-smooth-muscle-actin (α-SMA) and transforming growth factor β1 (TGF-β1) in the liver were markedly down-regulated by SalA treatment. TUNEL staining showed that SalA reduced apoptosis in hepatocytes. In addition, SalA improved hepatic mitochondrial respiratory function in diabetic rats. Taken together, these findings demonstrated that SalA could prevent the pathological progression of hepatic fibrosis in HFD-fed and STZ-induced diabetic rats. The underlying mechanisms may be involved in reducing oxidative stress, suppressing α-SMA and TGF-β1 expression, as well as exerting anti-apoptotic and mitochondria-protective effects. PMID:25183303

  14. Anti-diabetic activity of the semi-purified fractions of Averrhoa bilimbi in high fat diet fed-streptozotocin-induced diabetic rats.

    PubMed

    Tan, Benny Kwong Huat; Tan, Chee Hong; Pushparaj, Peter Natesan

    2005-04-29

    The present study was designed to investigate the hypoglycemic and hypolipidemic activities of the semi-purified fractions of an ethanolic leaf extract of Averrhoa bilimbi (ABe) in high fat diet (HFD)-streptozotocin (STZ)-induced diabetic rats. Male Sprague-Dawley rats aged 10 weeks (200-250 g) were fed with a high fat diet obtained from Glen Forrest stock feeders (Western Australia) for 2 weeks prior to intraperitoneal injection with streptozotocin (STZ, 50 mg/kg). The leaves of A.bilimbi were exhaustively extracted with 80% ethanol, concentrated at 40 degrees C using a rotavapor and partitioned successively with butanol, ethylacetate and hexane to get aqueous (AF), butanol (BuF), ethylacetate (EF), and hexane fractions (HF). The fractions were freeze-dried to obtain powders of each. To investigate the effect of long term administration of the hypoglycemic fractions, diabetic animals were treated with vehicle (distilled water), AF (125 mg/kg), or BuF (125 mg/kg), twice a day for 14 days. The long term administration of AF and BuF at a dose of 125 mg/kg significantly (P < 0.05) lowered blood glucose and triglyceride concentrations when compared to the vehicle. The hepatic glycogen content was significantly higher (P < 0.05) in AF-treated rats when compared to diabetic control, however no change was found in the BuF-treated rats. Moreover, AF as well as BuF did not cause any significant change in the total cholesterol and HDL-cholesterol. There was also no difference in liver thiobarbituric acid reactive substances (TBARS) and cytochrome P450 values between AF, BuF and vehicle-treated control rats. In conclusion, the results indicate that AF is more potent than BuF in the amelioration of hyperglycemia and hyperlipidemia in HFD fed-STZ diabetic rats. Hence, AF is a potential source for the isolation of active principle(s) for oral anti-diabetic therapy. PMID:15808883

  15. Delayed physical and neurobehavioral development and increased aggressive and depression-like behaviors in the rat offspring of dams fed a high-fat diet.

    PubMed

    Giriko, Catherine Ássuka; Andreoli, Carla Albuquerque; Mennitti, Laís Vales; Hosoume, Lilian Fazion; Souto, Tayane Dos Santos; Silva, Alexandre Valotta da; Mendes-da-Silva, Cristiano

    2013-12-01

    Early maternal exposure to a high-fat diet (HFD) may influence the brain development of rat offspring and consequently affect physiology and behavior. Thus, in the present study, we investigated the somatic, physical, sensory-motor and neurobehavioral development of the offspring of dams fed an HFD (52% calories from fat, mainly saturated) and the offspring of dams fed a control diet (CD - 14.7% fat) during lactation from the 1st to the 21st postnatal day (P). Maternal body weights were evaluated during lactation. In the progeny, somatic (body weight, head and lengths axes) and physical (ear unfolding, auditory conduit opening, eruption of the incisors and eye opening) development and the consolidation of reflex responses (palm grasp, righting, vibrissa placing, cliff avoidance, negative geotaxis, auditory startle response and free-fall righting) were determined during suckling. Depressive and aggressive behaviors were tested with the forced swimming test (FST) and the "foot-shock" test on days 60 and 110, respectively. The open field test was used to assess motor function. Compared to controls, the HFD-pups exhibited decreases in body weight (P7-P21) and body length (P4-P18), but by days P71 and P95, these pups were overweight. All indicators of physical maturation and the consolidation of the following reflexes, vibrissa placing, auditory startle responses, free-fall righting and negative geotaxis, were delayed in HFD-progeny. In addition, the pups from HFD dam rats also exhibited reduced swimming and climbing times in the FST and increased aggressive behavior. No changes in locomotion were observed. These findings show developmental and neurobehavioral changes in the rat offspring of dams fed the HFD during lactation and suggest possible disruption of physical and sensory-motor maturation and increased susceptibility to depressive and aggressive-like behavior. PMID:24071008

  16. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

    PubMed Central

    El-Zeftawy, Marwa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling. PMID:27579151

  17. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet.

    PubMed

    Balbaa, Mahmoud; El-Zeftawy, Marwa; Ghareeb, Doaa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) "NS" or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling. PMID:27579151

  18. Energy restriction and exercise modulate angiopoietins and vascular endothelial growth factor expression in the cavernous tissue of high-fat diet-fed rats

    PubMed Central

    Tomada, Inês; Tomada, Nuno; Almeida, Henrique; Neves, Delminda

    2012-01-01

    The purpose of the current study was to evaluate the effect of a high-fat (HF) diet, energy restriction and exercise on the expression of vascular endothelial growth factor (VEGF), angiopoietin (Ang) 1 and 2, and their receptors in rat corpus cavernosum (CC). Male Wistar rats were fed ad libitum with an HF diet for 8 or 16 weeks. After 8 weeks of the HF diet, a group of rats was subjected to energy restriction with or without exercise for 8 weeks. Control animals had free access to standard diet for the same period. After euthanasia, blood was collected and the penises removed for immunofluorescence assays (VEGF, VEGF receptor (VEGFR) 1 and 2, Ang1, Ang2 and Tie2) and semiquantification of VEGF, VEGFR1, VEGFR2, Ang1, Ang2, Tie2, endothelial nitric oxide synthase (eNOS) and Akt/phospho-Akt by Western blotting. HF diet-fed rats exhibited lower high-density lipoprotein cholesterol (HDL-c) levels, higher systolic blood pressure and an increased atherogenic index. A significant increase in Ang2 expression in the CC was verified and coupled to a decrease in VEGF and VEGFRs. The Akt pathway was activated by the HF diet. Energy restriction and exercise increased eNOS expression and restored most HF diet-induced modifications except for VEGFR2 expression. These results emphasize the role of diet on vascular function regulation, demonstrating that cavernous imbalance of VEGF/VEGFRs and Angs/Tie2 systems occurs before serum lipid changes and obesity onset, antedating structural atherosclerotic features. PMID:22138901

  19. EET agonist prevents adiposity and vascular dysfunction in rats fed a high fat diet via a decrease in Bach 1 and an increase in HO-1 levels.

    PubMed

    Sodhi, Komal; Puri, Nitin; Inoue, Kazuyoshi; Falck, John R; Schwartzman, Michal L; Abraham, Nader G

    2012-08-01

    Recent reports have shown interplay between EETs (epoxides) and the heme oxygenase (HO) system in attenuating adipogenesis in cell culture models; prompting an examination of the effectiveness of EET agonist on obesity and associated cardio-metabolic dysfunction. Patho-physiological effects of an EET agonist (NUDSA) were contrasted in the absence and in the presence of stannous mesoporphyrin (an HO inhibitor) in SD rats fed a high fat (58%, HF) for 16 weeks. Animals on HF diet exhibited enhanced oxidative stress, increased levels of inflammatory cytokines and decreased levels of adiponectin along with reduced vascular and adipose tissue levels of EETs, HO-1; as compared to control rats (11% dietary fat). Treatment with NUDSA not only reversed serum adiponectin and vascular and adipose tissue levels of EETs and HO-1, but also, decreased blood pressure, subcutaneous and visceral fat content and serum TNFα and IL-6 levels in rats on HF diet. Aortic endothelial function, peNOS expression and adipose tissue markers of energy homeostasis i.e. pAMPK, Sirt1 and FAS, impaired in rats fed a HF diet, were restored in animals treated with this EET agonist. That NUDSA enhanced HO-1 expression, was accompanied by increase in p-GSK-3β and pAKT levels along with attenuation of adipose tissue levels of Bach 1--the transcriptional suppresser of HO-1 expression. Prevention of these beneficial effects of NUDSA, in animals on HF diet and concurrently exposed to NUDSA and SnMP, supports the role of EET-HO interaction in mediating such effects. Taken together, our findings suggest that the EETs stimulate HO-1 expression via suppression of Bach 1 and interplay of these two systems affords vascular and metabolic protection in diet induced obesity. PMID:22209722

  20. Ethanol extract of lotus (Nelumbo nucifera) root exhibits an anti-adipogenic effect in human pre-adipocytes and anti-obesity and anti-oxidant effects in rats fed a high-fat diet.

    PubMed

    You, Jeong Soon; Lee, Yun Ju; Kim, Kyoung Soo; Kim, Sung Hoon; Chang, Kyung Ja

    2014-03-01

    Lotus (Nelumbo Nucifera) root, a well-known medicinal plant in Asia, is reported to have various therapeutic benefits, including anti-diabetes, anti-hypertension, and anti-hyperlipidaemia. We hypothesized that the ethanol extract of lotus root (ELR) would exhibit an anti-adipogenic effect in human pre-adipocytes as well as anti-obesity and anti-oxidant effects in rats fed a high-fat diet. Treatment with ELR in human pre-adipocytes resulted in inhibition of lipid accumulation and attenuated expression of adipogenic transcription factors such as peroxisome proliferator-activated receptor gamma and adipocyte marker genes, such as glucose transporter 4 and leptin. Administration of ELR resulted in a significant decrease in relative weights of adipose tissues in rats fed a high-fat diet. Consumption of a high-fat diet resulted in an increase in serum total cholesterol (TC) and triglyceride (TG) levels; however, administration of ELR resulted in a decrease in the levels of TC and TG. Administration of ELR resulted in a decrease in the level of serum leptin and insulin. Administration of ELR in rats fed a high-fat diet resulted in a decrease in hepatic thiobarbituric acid reactive substance content, elevated by a high-fat diet and an increase in superoxide dismutase activity and hepatic glutathione content. These results suggest that lotus root exerts anti-oxidant and anti-obesity effects and could be used as a functional and nutraceutical ingredient in combatting obesity-related diseases. PMID:24655493

  1. Intermittent hypoxia upregulates hepatic heme oxygenase-1 and ferritin-1, thereby limiting hepatic pathogenesis in rats fed a high-fat diet.

    PubMed

    Maeda, Hideyuki; Yoshida, Ken-Ichi

    2016-07-01

    Non-alcoholic fatty liver disease (NAFLD) is prevalent in patients with sleep apnea syndrome (SAS). Intermittent hypoxia (IH) and a high-fat diet (HFD) reproduce SAS and NAFLD, respectively, in rodents. In this study, rats were fed either an HFD or a standard diet (SD) for 2 weeks, and breathed either IH air or normoxic air for 4 days (early phase) or 6 weeks (late phase), with the same diets maintained during the exposure. HFD increased hepatic lipid accumulation, as detected by oil-red staining and triglyceride content. However, IH exposure reversed the hepatic steatosis at the late phase in these HFD-rats. IH exposure also increased hepatic expression of HO-1 and iron-binding protein ferritin-1 at the late phase, in association with increase in serum iron, bilirubin, and hepatic levels of lipid peroxides, such as 4-hydroxy-2-nonenal (HNE). IH exposure increased serum levels of hemoglobin (Hb) at the early phase and immunofluorescence of Hb and HO-1 in CD68-positive Kupffer cells (KCs) at the late phase. These findings support that IH induces erythrocytosis, erythro-phagocytosis, and generation of Hb in the KCs. The Hb promotes HO-1 expression in KCs, thereby produces iron, bilirubin, and carbon monoxide (CO). The iron would be either sequestrated by ferritin-1, transferred to the bone marrow for erythropoiesis, or would produce hydroxyradicals and HNE in the liver of rats fed an HFD. HNE might also contribute to the upregulation of HO-1, transferrin-1, and IκB, thereby limiting hepatic steatosis and inflammation via inhibition of nuclear factor κB (NFκB) activation. PMID:27021659

  2. Induction of ketosis in rats fed low-carbohydrate, high-fat diets depends on the relative abundance of dietary fat and protein.

    PubMed

    Bielohuby, Maximilian; Menhofer, Dominik; Kirchner, Henriette; Stoehr, Barbara J M; Müller, Timo D; Stock, Peggy; Hempel, Madlen; Stemmer, Kerstin; Pfluger, Paul T; Kienzle, Ellen; Christ, Bruno; Tschöp, Matthias H; Bidlingmaier, Martin

    2011-01-01

    Low-carbohydrate/high-fat diets (LC-HFDs) in rodent models have been implicated with both weight loss and as a therapeutic approach to treat neurological diseases. LC-HFDs are known to induce ketosis; however, systematic studies analyzing the impact of the macronutrient composition on ketosis induction and weight loss success are lacking. Male Wistar rats were pair-fed for 4 wk either a standard chow diet or one of three different LC-HFDs, which only differed in the relative abundance of fat and protein (percentages of fat/protein in dry matter: LC-75/10; LC-65/20; LC-55/30). We subsequently measured body composition by nuclear magnetic resonance (NMR), analyzed blood chemistry and urine acetone content, evaluated gene expression changes of key ketogenic and gluconeogenic genes, and measured energy expenditure (EE) and locomotor activity (LA) during the first 4 days and after 3 wk on the respective diets. Compared with chow, rats fed with LC-75/10, LC-65/20, and LC-55/30 gained significantly less body weight. Reductions in body weight were mainly due to lower lean body mass and paralleled by significantly increased fat mass. Levels of β-hydroxybutyate were significantly elevated feeding LC-75/10 and LC-65/20 but decreased in parallel to reductions in dietary fat. Acetone was about 16-fold higher with LC-75/10 only (P < 0.001). In contrast, rats fed with LC-55/30 were not ketotic. Serum fibroblast growth factor-21, hepatic mRNA expression of hydroxymethylglutaryl-CoA-lyase, peroxisome proliferator-activated receptor-γ coactivator-1α, and peroxisome proliferator-activated receptor-γ coactivator-1β were increased with LC-75/10 only. Expression of phosphoenolpyruvate carboxykinase and glucose-6-phosphatase was downregulated by 50-70% in LC-HF groups. Furthermore, EE and LA were significantly decreased in all groups fed with LC-HFDs after 3 wk on the diets. In rats, the absence of dietary carbohydrates per se does not induce ketosis. LC-HFDs must be high in fat

  3. The effect of dietary curcumin and capsaicin on hepatic fetuin-A expression and fat accumulation in rats fed on a high-fat diet.

    PubMed

    Seyithanoğlu, Muhammed; Öner-İyidoğan, Yıldız; Doğru-Abbasoğlu, Semra; Tanrıkulu-Küçük, Sevda; Koçak, Hikmet; Beyhan-Özdaş, Şule; Koçak-Toker, Necla

    2016-05-01

    Effects of curcumin (turmeric) and capsaicin (red pepper) on hepatic fat accumulation and fetuin-A expression in rats fed high-fat diet (HFD) is aimed to be investigated. Male Sprague-Dawley rats received HFD (60% of total calories from fat) and 0.15 g capsaicin/kg HFD and/or 1.5 g curcumin/kg HFD for 16 weeks. Hepatic AMPK, p-AMPK and fetuin-A expressions were determined by western blotting, liver lipid levels were measured with colorimetric methods and serum fetuin-A, insulin, leptin and adiponectin levels were detected using commercial ELISA kits. HFD increased hepatic lipid levels, fetuin-A expression and serum leptin, insülin and fetuin-A levels. Curcumin and capsaicin treatments significantly reduced hepatic fat accumulation and leptin levels; liver fetuin-A expression was decreased significantly by the curcumin treatment. Curcumin and capsaicin treatments attenuated hepatic fat accumulation and increased leptin levels related to inflammation. The suppression of hepatic fetuin-A expression is observed to be especially sensitive to curcumin. PMID:26706937

  4. Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet

    PubMed Central

    Boonloh, Kampeebhorn; Kukongviriyapan, Veerapol; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Thawornchinsombut, Supawan; Pannangpetch, Patchareewan

    2015-01-01

    A high carbohydrate-high fat (HCHF) diet causes insulin resistance (IR) and metabolic syndrome (MS). Rice bran has been demonstrated to have anti-dyslipidemic and anti-atherogenic properties in an obese mouse model. In the present study, we investigated the beneficial effects of rice bran protein hydrolysates (RBP) in HCHF-induced MS rats. After 12 weeks on this diet, the HCHF-fed group was divided into four subgroups, which were orally administered RBP 100 or 500 mg/kg, pioglitazone 10 mg/kg, or tap water for a further 6 weeks. Compared with normal diet control group, the MS rats had elevated levels of blood glucose, lipid, insulin, and HOMA-IR. Treatment with RBP significantly alleviated all those changes and restored insulin sensitivity. Additionally, RBP treatment increased adiponectin and suppressed leptin levels. Expression of Ppar-γ mRNA in adipose tissues was significantly increased whereas expression of lipogenic genes Srebf1 and Fasn was significantly decreased. Levels of mRNA of proinflammatory cytokines, Il-6, Tnf-α, Nos-2 and Mcp-1 were significantly decreased. In conclusion, the present findings support the consumption of RBP as a functional food to improve insulin resistance and to prevent the development of metabolic syndrome. PMID:26247962

  5. Black soybean extract reduces fatty acid contents in subcutaneous, but not in visceral adipose triglyceride in high-fat fed rats.

    PubMed

    Sato, Daisuke; Kusunoki, Masataka; Seino, Narumi; Nishina, Atsuyoshi; Feng, Zhonggang; Tsutsumi, Kazuhiko; Nakamura, Takao

    2015-01-01

    It is known that black soybean (BS) extract, rich in polyphenols, has beneficial effects against obesity, inflammation and insulin resistance. However, detailed effects of BS on lipid metabolism have not been documented well. In the present study, we compared fatty acid composition in visceral and subcutaneous adipose tissues of high-fat fed (HFF) rats and BS administered HFF rats. Black soybean administration for 6 weeks influenced neither body nor adipose tissue weights, blood glucose, plasma insulin levels, or insulin sensitivity. However, BS reduced several saturated (C14:0 and C16:0), monounsaturated (C14:1n-5 and C18:1n-9) and n-6 polyunsaturated (C18:2n-6, C20:3n-6, C20:4n-6 and C22:4n-6) fatty acid contents in subcutaneous fat without any change in n-3 polyunsaturated fatty acid contents. No such effect was observed in fatty acid composition in visceral fat. Long-chain fatty acids are involved in regulation of inflammation. Therefore, those reduced fatty acids may be linked to the effects on suppressing inflammation. PMID:25830948

  6. Rice Bran Protein Hydrolysates Improve Insulin Resistance and Decrease Pro-inflammatory Cytokine Gene Expression in Rats Fed a High Carbohydrate-High Fat Diet.

    PubMed

    Boonloh, Kampeebhorn; Kukongviriyapan, Veerapol; Kongyingyoes, Bunkerd; Kukongviriyapan, Upa; Thawornchinsombut, Supawan; Pannangpetch, Patchareewan

    2015-08-01

    A high carbohydrate-high fat (HCHF) diet causes insulin resistance (IR) and metabolic syndrome (MS). Rice bran has been demonstrated to have anti-dyslipidemic and anti-atherogenic properties in an obese mouse model. In the present study, we investigated the beneficial effects of rice bran protein hydrolysates (RBP) in HCHF-induced MS rats. After 12 weeks on this diet, the HCHF-fed group was divided into four subgroups, which were orally administered RBP 100 or 500 mg/kg, pioglitazone 10 mg/kg, or tap water for a further 6 weeks. Compared with normal diet control group, the MS rats had elevated levels of blood glucose, lipid, insulin, and HOMA-IR. Treatment with RBP significantly alleviated all those changes and restored insulin sensitivity. Additionally, RBP treatment increased adiponectin and suppressed leptin levels. Expression of Ppar-γ mRNA in adipose tissues was significantly increased whereas expression of lipogenic genes Srebf1 and Fasn was significantly decreased. Levels of mRNA of proinflammatory cytokines, Il-6, Tnf-α, Nos-2 and Mcp-1 were significantly decreased. In conclusion, the present findings support the consumption of RBP as a functional food to improve insulin resistance and to prevent the development of metabolic syndrome. PMID:26247962

  7. Ethanol Extract of Peanut Sprout Lowers Blood Triglyceride Levels, Possibly Through a Pathway Involving SREBP-1c in Rats Fed a High-Fat Diet.

    PubMed

    Ha, Ae Wha; Kang, Nam E; Kim, Woo Kyoung

    2015-08-01

    The hypothesis of this study was that peanut sprout extracts (PSE) could reduce fat accumulation through activating the transcription of SREBP-1c genes. Sprague-Dawley (SD) were randomly assigned into two groups and fed the following diet for 4 weeks; 10 normal fat (NF, 7 g of fat/100 g diet) and 30 high fat (HF, 20 g of fat/100 g diet). After 4 weeks, the HF group was divided into three groups; HF, HF with 15 mg of PSE/kg diet (HF+low PSE, 0.025% resveratrol), and HF with 30 mg of PSE/kg diet (HF+high PSE, 0.05% resveratrol) and fed for an additional 5 weeks. The HF+high PSE group had significantly lower weight gain than the HF group. Plasma triglyceride (TG) level and the hepatic total lipid level were significantly lower in the HF+high PSE group compared to the HF group. Fecal excretions of total lipids, cholesterol, and TG in the HF+high PSE group tended to be higher than in the HF group, but these differences were not significant. The mRNA expressions of fatty acid synthase, glucose-6-phosphate dehydrogenase, and sterol regulatory element binding protein-c (SREBP-1c) were significantly lower in the HF+high PSE group than in the HF group. The mRNA expressions of hydroxy-3-methylglutaryl coenzyme A reductase and acyl-CoA cholesterol acyltransferase were significantly lower in the HF+high PSE groups compared to the HF group. The mRNA expression of cholesterol 7α-hydroxylase1 was significantly higher than the HF group in both the HF+low PSE and HF+high PSE groups, with much greater increase observed in the HF+high PSE group. In conclusion, consumption of PSE was effective for improving blood lipid levels, possibly by suppressing the expression of SREBP-1c, in rats fed a high-fat diet. PMID:25946626

  8. Variations in the efficacy of resistant maltodextrin on body fat reduction in rats fed different high-fat models.

    PubMed

    Chu, Hui-Fang; Pan, Min-Hsiung; Ho, Chi-Tang; Tseng, Yu-Han; Wang, William Wei-Li; Chau, Chi-Fai

    2014-01-01

    Many studies have utilized a variety of methods to induce obesity in rodents, but they often received inconsistent results. The present study intended to use resistant maltodextrin (RMD) as a means to investigate the variations in its efficacy on body fat accumulation under the influence of four high-fat (HF) models of 23% or 40% total fat, comprising soybean oil, lard, and/or condensed milk. Results indicated that integrating condensed milk into the diets could help increase diet intake, boost energy intake, increase weight gain, and enhance fat formation. Supplementation of RMD (2.07 g/kg) notably reduced total body fat levels in three HF models, with the exception of a condensed-milk-added 40%-fat diet that may have misrepresented the functions of RMD. The uses of the 23% HF diets, with and without milk, and the milk-free 40% HF diet were therefore recommended as suitable models for antiobesity evaluations of RMD, or other fiber-rich products. PMID:24313233

  9. Perinatal exposure to bisphenol A exacerbates nonalcoholic steatohepatitis-like phenotype in male rat offspring fed on a high-fat diet.

    PubMed

    Wei, Jie; Sun, Xia; Chen, Yajie; Li, Yuanyuan; Song, Liqiong; Zhou, Zhao; Xu, Bing; Lin, Yi; Xu, Shunqing

    2014-09-01

    Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 μg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population. PMID:25112833

  10. Effects of swim training on liver carcinogenesis in male Wistar rats fed a low-fat or high-fat diet.

    PubMed

    Aguiar e Silva, Marco Aurélio; Vechetti-Junior, Ivan José; Nascimento, André Ferreira do; Furtado, Kelly Silva; Azevedo, Luciana; Ribeiro, Daniel Araki; Barbisan, Luis Fernando

    2012-12-01

    The present study aimed to investigate the beneficial effects of swim training on the promotion-progression stages of rat liver carcinogenesis. Male Wistar rats were submitted to chemically induced liver carcinogenesis and allocated into 4 major groups, according their dietary regimen (16 weeks) and swim training of 5 days per week (8 weeks): 2 groups were fed low-fat diet (LFD, 6% fat) and trained or not trained and 2 groups were fed high-fat diet (HFD, 21% fat) and trained or not trained. At week 20, the animals were killed and liver samples were processed for histological analyses; immunohistochemical detection of persistent or remodeling preneoplastic lesions (pPNL and rPNL) expressing placental glutathione S-transferase (GST-P) enzyme; or proliferating cell nuclear antigen (PCNA), cleaved caspase-3, and bcl-2 protein levels by Western blotting or malonaldehyde (MDA) and total glutathione detection by HPLC. Overall analysis indicated that swim training reduced the body weight and body fat in both LFD and HFD groups, normalized total cholesterol levels in the HFD group while decreased the MDA levels, increased glutathione levels and both number of GST-P-positive pPNL and hepatocellular adenomas in LFD group. Also, a favorable balance in PCNA, cleaved caspase-3, and bcl-2 levels was detected in the liver from the LFD-trained group in relation to LFD-untrained group. The findings of this study indicate that the swim training protocol as a result of exercise postconditioning may attenuate liver carcinogenesis under an adequate dietary regimen with lowered fat intake. PMID:22957766

  11. Independent and Combined Effects of Lactitol, Polydextrose, and Bacteroides thetaiotaomicron on Postprandial Metabolism and Body Weight in Rats Fed a High-Fat Diet

    PubMed Central

    Olli, Kaisa; Saarinen, Markku T.; Forssten, Sofia D.; Madetoja, Mari; Herzig, Karl-Heinz; Tiihonen, Kirsti

    2016-01-01

    Obesity is related to the consumption of energy-dense foods in addition to changes in the microbiome where a higher abundance of gut Bacteroidetes can be found in lean subjects or after weight loss. Lactitol, a sweet-tasting sugar alcohol, is a common sugar-replacement in foods. Polydextrose (PDX), a highly branched glucose polymer, is known to reduce energy intake. Here, we test if the combined effects of lactitol or PDX in combination with Bacteroides species will have a beneficial metabolic response in rats fed a high-fat (HF) diet. A total of 175 male Wistar rats were fed either a LF or HF diet. Bacteroides thetaiotaomicron (1010 bacteria/animal/day) was orally administered with or without lactitol (1.6−2 g/animal/day) or PDX (2 g/animal/day) for 8 days. Postprandial blood samples, cecal digesta, and feces were collected on the last day. Measurements included: body weight, feed consumption, cecal short-chain fatty acids, fecal dry matter and heat value, blood glucose, insulin, triglyceride, and satiety hormone concentrations. Lactitol and PDX decreased the mean body weight when administered with B. thetaiotaomicron or when lactitol was administered alone. Levels of postprandial plasma triglycerides declined with lactitol and PDX when administered with B. thetaiotaomicron. For intestinal hormone release, lactitol – alone or with B. thetaiotaomicron – increased the release of gastrointestinal peptide tyrosine tyrosine (PYY) as well as the area under the curve (AUC) measured for PYY (0–8 h). In addition, levels of insulin AUC (0–8 h) decreased in the lactitol and PDX-supplemented groups. Lactitol and PDX may both provide additional means to regulate postprandial metabolism and weight management, whereas the addition of B. thetaiotaomicron in the tested doses had only minor effects on the measured parameters. PMID:27376068

  12. Independent and Combined Effects of Lactitol, Polydextrose, and Bacteroides thetaiotaomicron on Postprandial Metabolism and Body Weight in Rats Fed a High-Fat Diet.

    PubMed

    Olli, Kaisa; Saarinen, Markku T; Forssten, Sofia D; Madetoja, Mari; Herzig, Karl-Heinz; Tiihonen, Kirsti

    2016-01-01

    Obesity is related to the consumption of energy-dense foods in addition to changes in the microbiome where a higher abundance of gut Bacteroidetes can be found in lean subjects or after weight loss. Lactitol, a sweet-tasting sugar alcohol, is a common sugar-replacement in foods. Polydextrose (PDX), a highly branched glucose polymer, is known to reduce energy intake. Here, we test if the combined effects of lactitol or PDX in combination with Bacteroides species will have a beneficial metabolic response in rats fed a high-fat (HF) diet. A total of 175 male Wistar rats were fed either a LF or HF diet. Bacteroides thetaiotaomicron (10(10) bacteria/animal/day) was orally administered with or without lactitol (1.6-2 g/animal/day) or PDX (2 g/animal/day) for 8 days. Postprandial blood samples, cecal digesta, and feces were collected on the last day. Measurements included: body weight, feed consumption, cecal short-chain fatty acids, fecal dry matter and heat value, blood glucose, insulin, triglyceride, and satiety hormone concentrations. Lactitol and PDX decreased the mean body weight when administered with B. thetaiotaomicron or when lactitol was administered alone. Levels of postprandial plasma triglycerides declined with lactitol and PDX when administered with B. thetaiotaomicron. For intestinal hormone release, lactitol - alone or with B. thetaiotaomicron - increased the release of gastrointestinal peptide tyrosine tyrosine (PYY) as well as the area under the curve (AUC) measured for PYY (0-8 h). In addition, levels of insulin AUC (0-8 h) decreased in the lactitol and PDX-supplemented groups. Lactitol and PDX may both provide additional means to regulate postprandial metabolism and weight management, whereas the addition of B. thetaiotaomicron in the tested doses had only minor effects on the measured parameters. PMID:27376068

  13. Inhibition of fetal bone development through epigenetic down- regulation of HoxA10 in obese rats fed high fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological studies show that maternal obesity during intrauterine and early postnatal life increases the risk of low bone mass and fracture later in life. Here, we show that bone development is inhibited in GED 18.5 embryos from rat dams made obese by feeding a high fat diet (HFD). Moreover, fe...

  14. Postprandial glucagon-like peptide-1 secretion is increased during the progression of glucose intolerance and obesity in high-fat/high-sucrose diet-fed rats.

    PubMed

    Nakajima, Shingo; Hira, Tohru; Hara, Hiroshi

    2015-05-14

    Glucagon-like peptide-1 (GLP-1) is secreted by distal enteroendocrine cells in response to luminal nutrients, and exerts insulinotropic and anorexigenic effects. Although GLP-1 secretory responses under established obese or diabetic conditions have been studied, it has not been investigated whether or how postprandial GLP-1 responses were affected during the progression of diet-induced obesity. In the present study, a meal tolerance test was performed every week in rats fed a high-fat and high-sucrose (HF/HS) diet to evaluate postprandial glycaemic, insulin and GLP-1 responses. In addition, gastric emptying was assessed by the acetaminophen method. After 8 weeks of HF/HS treatment, portal vein and intestinal mucosa were collected to examine GLP-1 production. Postprandial glucose in response to normal meal ingestion was increased in the HF/HS group within 2 weeks, and its elevation gradually returned close to that of the control group until day 50. Slower postprandial gastric emptying was observed in the HF/HS group on days 6, 13 and 34. Postprandial GLP-1 and insulin responses were increased in the HF/HS group at 7 weeks. Higher portal GLP-1 and insulin levels were observed in the HF/HS group, but mucosal gut hormone mRNA levels were unchanged. These results revealed that the postprandial GLP-1 response to meal ingestion is enhanced during the progression of diet-induced glucose intolerance and obesity in rats. The boosted postprandial GLP-1 secretion by chronic HF/HS diet treatment suggests increased sensitivity to luminal nutrients in the gut, and this may slow the establishment of glucose intolerance and obesity. PMID:25827219

  15. Reshaping faecal gut microbiota composition by the intake of trans-resveratrol and quercetin in high-fat sucrose diet-fed rats.

    PubMed

    Etxeberria, U; Arias, N; Boqué, N; Macarulla, M T; Portillo, M P; Martínez, J A; Milagro, F I

    2015-06-01

    Diet-induced obesity is associated to an imbalance in the normal gut microbiota composition. Resveratrol and quercetin, widely known for their health beneficial properties, have low bioavailability, and when they reach the colon, they are targets of the gut microbial ecosystem. Hence, the use of these molecules in obesity might be considered as a potential strategy to modulate intestinal bacterial composition. The purpose of this study was to determine whether trans-resveratrol and quercetin administration could counteract gut microbiota dysbiosis produced by high-fat sucrose diet (HFS) and, in turn, improve gut health. Wistar rats were randomised into four groups fed an HFS diet supplemented or not with trans-resveratrol [15 mg/kg body weight (BW)/day], quercetin (30 mg/kg BW/day) or a combination of both polyphenols at those doses. Administration of both polyphenols together prevented body weight gain and reduced serum insulin levels. Moreover, individual supplementation of trans-resveratrol and quercetin effectively reduced serum insulin levels and insulin resistance. Quercetin supplementation generated a great impact on gut microbiota composition at different taxonomic levels, attenuating Firmicutes/Bacteroidetes ratio and inhibiting the growth of bacterial species previously associated to diet-induced obesity (Erysipelotrichaceae, Bacillus, Eubacterium cylindroides). Overall, the administration of quercetin was found to be effective in lessening HFS-diet-induced gut microbiota dysbiosis. In contrast, trans-resveratrol supplementation alone or in combination with quercetin scarcely modified the profile of gut bacteria but acted at the intestinal level, altering the mRNA expression of tight-junction proteins and inflammation-associated genes. PMID:25762527

  16. Changes in intestinal barrier function and gut microbiota in high-fat diet-fed rats are dynamic and region dependent.

    PubMed

    Hamilton, M Kristina; Boudry, Gaëlle; Lemay, Danielle G; Raybould, Helen E

    2015-05-15

    A causal relationship between the pathophysiological changes in the gut epithelium and altered gut microbiota with the onset of obesity have been suggested but not defined. The aim of this study was to determine the temporal relationship between impaired intestinal barrier function and microbial dysbiosis in the small and large intestine in rodent high-fat (HF) diet-induced obesity. Rats were fed HF diet (45% fat) or normal chow (C, 10% fat) for 1, 3, or 6 wk; food intake, body weight, and adiposity were measured. Barrier function ex vivo using FITC-labeled dextran (4,000 Da, FD-4) and horseradish peroxidase (HRP) probes in Ussing chambers, gene expression, and gut microbial communities was assessed. After 1 wk, there was an immediate but reversible increase in paracellular permeability, decrease in IL-10 expression, and decrease in abundance of genera within the class Clostridia in the ileum. In the large intestine, HRP flux and abundance of genera within the order Bacteroidales increased with time on the HF diet and correlated with the onset of increased body weight and adiposity. The data show immediate insults in the ileum in response to ingestion of a HF diet, which were rapidly restored and preceded increased passage of large molecules across the large intestinal epithelium. This study provides an understanding of microbiota dysbiosis and gut pathophysiology in diet-induced obesity and has identified IL-10 and Oscillospira in the ileum and transcellular flux in the large intestine as potential early impairments in the gut that might lead to obesity and metabolic disorders. PMID:25747351

  17. Possible Role of Intestinal Fatty Acid Oxidation in the Eating-Inhibitory Effect of the PPAR-α Agonist Wy-14643 in High-Fat Diet Fed Rats

    PubMed Central

    Karimian Azari, Elnaz; Leitner, Claudia; Jaggi, Thomas; Langhans, Wolfgang; Mansouri, Abdelhak

    2013-01-01

    PPAR-α plays a key role in lipid metabolism; it enhances fatty acid oxidation (FAO) and ketogenesis. Pharmacological PPAR-α activation improves insulin sensitivity and reduces food intake, but its mechanisms of action remain unknown. We here report that intraperitoneal (IP) administration of the PPAR-α agonist Wy-14643 (40 mg/kg BW) reduced food intake in adult male rats fed a high-fat diet (HFD, 49% of the energy) mainly through an increase in the latency to eat after injection, and without inducing a conditioned taste avoidance. Also, IP administered Wy-14643 caused an acute (the first 60 min) decrease in the respiratory quotient (RQ) and an increase in hepatic portal vein β-hydroxybutyrate level (at 35 min) without affecting plasma non-esterified fatty acids. Given the known stimulatory effect of PPAR-α on FAO and ketogenesis, we measured the protein expression level of carnitine palmitoyltransferase-1 (CPT 1A) and mitochondrial 3-hydroxy-3-methylglutaryl-coenzyme A synthase (HMG-CoAS2), two key enzymes for FAO and ketogenesis, respectively, in liver, duodenum and jejunum. Wy-14643 induced a significant increase in the expression of CPT 1A in the jejunum and duodenum and of HMG-CoAS2 in the jejunum, but neither CPT 1A nor HMG-CoAS2 expression was increased in the liver. The induction of CPT 1A and HMG-CoAS2 expression was associated with a decrease in the lipid droplet content selectively in the jejunum. Our findings indicate that Wy-14643 stimulates FAO and ketogenesis in the intestine, in particular in the jejunum, rather than in the liver, thus supporting the hypothesis that PPAR-α activation inhibits eating by stimulating intestinal FAO. PMID:24069361

  18. Hypolipidemic and Antioxidative Effects of Aqueous Enzymatic Extract from Rice Bran in Rats Fed a High-Fat and -Cholesterol Diet

    PubMed Central

    Wang, Yu-Xin; Li, Yang; Sun, An-Min; Wang, Feng-Jiao; Yu, Guo-Ping

    2014-01-01

    Purpose: The aqueous enzymatic extract from rice bran (AEERB) was rich in protein, γ-oryzanol and tocols. The aim of this study was to investigate the effects of AEERB on the regulation of lipid metabolism and the inhibition of oxidative damage. Methods: The antioxidant activity of AEERB in vitro was measured in terms of radical scavenging capacity, ferric reducing ability power (FRAP) and linoleic acid emulsion system-ferric thiocyanate method (FTC). Male Wistar rats were fed with a normal diet and a high-fat and high-cholesterol diet with or without AEERB. After treatment, biochemical assays of serum, liver and feces lipid levels, the antioxidant enzyme activity, malondialdehyde (MDA) and protein carbonyl were determined. Result: AEERB is completely soluble in water and rich in hydrophilic and lipophilic functional ingredients. AEERB scavenged DPPH• and ABTS•+ and exhibited antioxidant activity slightly lower than that of ascorbic acid in the linoleic acid system. The administration of AEERB reduced serum lipid levels and the atherogenic index compared with those of the hyperlipidemic diet group (HD). The administration of AEERB significantly lowered liver lipid levels, inhibited hepatic 3-hydroxyl-3-methylglutaryl CoA reductase activity, and efficiently promoted the fecal excretion of total lipids and total cholesterol (TC) (p < 0.05). Dietary AEERB enhanced antioxidant status in the serum, liver and brain by increasing the antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and decreasing the content of MDA and protein carbonyl. Conclusions: The results indicated that AEERB might act as a potent hypolipidemic and antioxidant functional food. PMID:25230211

  19. Regulation of low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase expression by Zingiber officinale in the liver of high-fat diet-fed rats.

    PubMed

    Nammi, Srinivas; Kim, Moon S; Gavande, Navnath S; Li, George Q; Roufogalis, Basil D

    2010-05-01

    Zingiber officinale has been used to control lipid disorders and reported to possess remarkable cholesterol-lowering activity in experimental hyperlipidaemia. In the present study, the effect of a characterized and standardized extract of Zingiber officinale on the hepatic lipid levels as well as on the hepatic mRNA and protein expression of low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was investigated in a high-fat diet-fed rat model. Rats were treated with an ethanol extract of Zingiber officinale (400 mg/kg) extract along with a high-fat diet for 6 weeks. The extract of Zingiber officinale significantly decreased hepatic triglyceride and tended to decrease hepatic cholesterol levels when administered over 6 weeks to the rats fed a high-fat diet. We found that in parallel, the extract up-regulated both LDL receptor mRNA and protein level and down-regulated HMG-CoA reductase protein expression in the liver of these rats. The metabolic control of body lipid homeostasis is in part due to enhanced cholesterol biosynthesis and reduced expression of LDL receptor sites following long-term consumption of high-fat diets. The present results show restoration of transcriptional and post-transcriptional changes in low-density lipoprotein and HMG CoA reductase by Zingiber officinale administration with a high-fat diet and provide a rational explanation for the effect of ginger in the treatment of hyperlipidaemia. PMID:20002065

  20. A Root-Based Combination Supplement Containing Pueraria lobata and Rehmannia glutinosa and Exercise Preserve Bone Mass in Ovariectomized Rats Fed a High-Fat Diet.

    PubMed

    Ok, Hyang Mok; Gebreamanuel, Meron Regu; Oh, Sang A; Jeon, Hyejin; Lee, Won Jun; Kwon, Oran

    2015-12-01

    The aim of this study was to evaluate the effects of a supplement containing Pueraria lobata/Rehmannia glutinosa (PR) root extracts on bone turnover in ovariectomized (OVX) rats (a model for postmenopausal osteoporosis). Female Sprague-Dawley rats (8 weeks old) were randomized into eight groups: sham-operated rats with low-fat control diet + vehicle, OVX rats with low-fat control diet + vehicle, OVX rats with high-fat diet (HFD) + vehicle, OVX rats with HFD + vehicle + exercise, OVX rats with HFD + PR (400 mg/kg body weight/day p.o.), OVX rats with HFD + PR + exercise, OVX rats with HFD + 17β-estradiol (0.5 mg/kg body weight/day p.o.), OVX rats with HFD + 17β-estradiol + exercise. Bone microarchitecture, bone turnover markers (e.g., plasma alkaline phosphatase and osteocalcin), expressions of osteogenic and resorptive gene markers in the bone were measured. Eight weeks of PR and/or aerobic exercise improved cortical microarchitecture of the femur and decreased markers of bone turnover and expression of skeletal osteoclastogenic genes in the femur. PR supplementation combined with exercise preserved bone loss induced by estrogen deficiency and should be investigated further as an alternative to hormone replacement therapy for preventing osteoporosis in postmenopausal women. PMID:26319677

  1. Effects of lactic acid bacteria on cardiac apoptosis are mediated by activation of the phosphatidylinositol-3 kinase/AKT survival-signalling pathway in rats fed a high-fat diet.

    PubMed

    Wang, Hsueh-Fang; Lin, Pei-Pei; Chen, Chun-Hua; Yeh, Yu-Lan; Huang, Chun-Chih; Huang, Chih-Yang; Tsai, Cheng-Chih

    2015-02-01

    Through a high-fat diet, obesity leads to cardiomyocyte dysfunction and apoptosis. In addition, there is no evidence that probiotics have potential health effects associated with cardiac apoptosis in obese rats. The present study aimed to explore the effects of probiotics on obesity and cardiac apoptosis in rats fed a high-fat diet (HF). Eight‑week‑old male Wistar rats were separated randomly into five equally sized experimental groups: Normal diet (NC) and high-fat diet (HFC) groups, and high-fat diet supplemented with low (HFL), medium (HFM) or high (HFH) doses of multi‑strain probiotics groups. The rats were subsequently studied for 8 weeks. Food intake and body weights were recorded following sacrifice, and food utilization rates, body fat and serum cholesterol levels were analysed. The myocardial architecture of the left ventricle was evaluated by hematoxylin‑eosin staining, and key apoptotic‑related pathway molecules were analysed by western blotting. Rat weights and triglyceride levels were decreased with oral administration of high doses of probiotics (HFH) compared to the HFC group. Abnormal myocardial architecture and enlarged interstitial spaces were observed in HFC hearts, but were significantly decreased in groups that were provided multi‑strain probiotics compared with NC hearts. Western blot analysis demonstrated that key components of the Fas receptor‑ and mitochondrial‑dependent apoptotic pathways were significantly suppressed in multi‑strain probiotic treated groups compared to the HF group. Additionally, cardiac insulin, such as the insulin‑like growth factor I receptor (IGFIR)‑dependent survival signalling components, were highly induced in left ventricles from rats administered probiotics. Together, these findings strongly suggest that oral administration of probiotics may attenuate cardiomyocyte apoptosis by activation of the phosphatidylinositol‑3 kinase/AKT survival‑signalling pathway in obese rats. PMID:25484003

  2. Effects of a Lactobacillus paracasei B21060 based synbiotic on steatosis, insulin signaling and toll-like receptor expression in rats fed a high-fat diet.

    PubMed

    Raso, Giuseppina Mattace; Simeoli, Raffaele; Iacono, Anna; Santoro, Anna; Amero, Paola; Paciello, Orlando; Russo, Roberto; D'Agostino, Giuseppe; Di Costanzo, Margherita; Canani, Roberto Berni; Calignano, Antonio; Meli, Rosaria

    2014-01-01

    Insulin resistance (IR) has been identified as crucial pathophysiological factor in the development and progression of non-alcoholic fatty liver disease (NAFLD). Although mounting evidence suggests that perturbation of gut microflora exacerbates the severity of chronic liver diseases, therapeutic approaches using synbiotic has remained overlooked. Here, we show that a synbiotic composed by Lactobacillus paracasei B21060 plus arabinogalactan and fructo-oligosaccharides lessens NAFLD progression in a rat model of high fat feeding. IR and steatosis were induced by administration of high fat diet (HFD) for 6 weeks. Steatosis and hepatic inflammation, Toll-like receptor (TLR) pattern, glucose tolerance, insulin signaling and gut permeability were studied. Liver inflammatory markers were down-regulated in rats receiving the synbiotic, along with an increased expression of nuclear peroxisome proliferator-activated receptors and expression of downstream target genes. The synbiotic improved many aspects of IR, such as fasting response, hormonal homeostasis and glycemic control. Indeed it prevented the impairment of hepatic insulin signaling, reducing the phosphorylation of insulin receptor substrate-1 in Ser 307 and down-regulating suppressor of cytokine signaling 3. Gene expression analysis revealed that in the liver the synbiotic reduced cytokines synthesis and restored the HFD-dysregulated TLR 2, 4 and 9 mRNAs toward a physiological level of expression. The synbiotic preserved gut barrier integrity and reduced the relative amount of Gram-negative Enterobacteriales and Escherichia coli in colonic mucosa. Overall, our data indicate that the L. paracasei B21060 based synbiotic is effective in reducing the severity of liver injury and IR associated with high fat intake, suggesting its possible therapeutic/preventive clinical utilization. PMID:24314869

  3. Supplemental fermented plant product (‘Manda Koso’) reduces succinate and deoxycholate, as well as elevates IgA and mucin levels, in rats fed a high-fat diet

    PubMed Central

    YANG, YONGSHOU; SITANGGANG, NOVITA VIVI; OKAZAKI, YUKAKO; TOMOTAKE, HIROYUKI; ARITA, KENTARO; ASHIDA, TAKAYUKI; KATO, NORIHISA

    2015-01-01

    ‘Manda Koso’ is a commercial fermented plant product (FPP) made from 53 types of fruits and vegetables that have been fermented for >3 years and 3 months. We hypothesized that FPP intake improves the luminal environment of rats fed a high-fat diet. Thus, the present study examined the effects of consumption of 5% FPP diet for 3 weeks on colonic luminal parameters in rats fed a 30% beef tallow diet. Food intake and body weight gain were unaffected. Consumption of the FPP diet did not influence the proportions of Bifidobacterium, Lactobacillus, Bacteroides, Prevotella or Clostridium in cecal contents. However, the FPP diet caused a significant reduction (−88%) in the level of cecal succinate, a putative inflammatory signal (P<0.01), but did not affect the levels of n-butyrate, propionate, acetate and lactate. The fecal levels of deoxycholate and hyodeoxycholate, which are toxic bile acids, were also significantly reduced by the FPP diet (P<0.05). The FPP diet significantly increased fecal immunoglobulin A and mucins responsible for intestinal immune and barrier functions (P<0.05). The results suggest that the consumption of FPP is beneficial for the colonic luminal environment in rats fed a high-fat diet. PMID:26623016

  4. Dietary high-fat lard intake induces thyroid dysfunction and abnormal morphology in rats

    PubMed Central

    Shao, Shan-shan; Zhao, Yuan-fei; Song, Yong-feng; Xu, Chao; Yang, Jian-mei; Xuan, Shi-meng; Yan, Hui-li; Yu, Chun-xiao; Zhao, Meng; Xu, Jin; Zhao, Jia-jun

    2014-01-01

    Aim: Excess dietary fat intake can induce lipotoxicity in non-adipose tissues. The aim of this study was to observe the effects of dietary high-fat lard intake on thyroid in rats. Methods: Male Sprague-Dawley rats were fed a high-fat lard diet for 24 weeks, and then the rats were fed a normal control diet (acute dietary modification) or the high-fat lard diet for another 6 weeks. The serum lipid profile, total thyroxine (TT4), free thyroxine (FT4) and thyrotropin (TSH) levels were determined at the 12, 18, 24 and 30 weeks. High-frequency ultrasound scanning of the thyroid glands was performed at the 24 or 30 weeks. After the rats were sacrificed, the thyroid glands were collected for histological and immunohistochemical analyses. Results: The high-fat lard diet significantly increased triglyceride levels in both the serum and thyroid, and decreased serum TT4 and FT4 levels in parallel with elevated serum TSH levels. Ultrasonic imaging revealed enlarged thyroid glands with lowered echotexture and relatively heterogeneous features in the high-fat lard fed rats. The thyroid glands from the high-fat lard fed rats exhibited enlarged follicle cavities and flattened follicular epithelial cells under light microscopy, and dilated endoplasmic reticulum cisternae, twisted nuclei, fewer microvilli and secretory vesicles under transmission electron microscopy. Furthermore, the thyroid glands from the high-fat lard fed rats showed markedly low levels of thyroid hormone synthesis-related proteins TTF-1 and NIS. Acute dietary modification by withdrawal of the high-fat lard diet for 6 weeks failed to ameliorate the high-fat lard diet-induced thyroid changes. Conclusion: Dietary high-fat lard intake induces significant thyroid dysfunction and abnormal morphology in rats, which can not be corrected by short-term dietary modification. PMID:25263336

  5. Effects of Nonalcoholic Fatty Liver Disease on Hepatic CYP2B1 and in Vivo Bupropion Disposition in Rats Fed a High-Fat or Methionine/Choline-Deficient Diet.

    PubMed

    Cho, Sung-Joon; Kim, Sang-Bum; Cho, Hyun-Jong; Chong, Saeho; Chung, Suk-Jae; Kang, Il-Mo; Lee, Jangik Ike; Yoon, In-Soo; Kim, Dae-Duk

    2016-07-13

    Nonalcoholic fatty liver disease (NAFLD) refers to hepatic pathologies, including simple fatty liver (SFL), nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis, that may progress to hepatocellular carcinoma. These liver disease states may affect the activity and expression levels of drug-metabolizing enzymes, potentially resulting in an alteration in the pharmacokinetics, therapeutic efficacy, and safety of drugs. This study investigated the hepatic cytochrome P450 (CYP) 2B1-modulating effect of a specific NAFLD state in dietary rat models. Sprague-Dawley rats were given a methionine/choline-deficient (MCD) or high-fat (HF) diet to induce NASH and SFL, respectively. The induction of these disease states was confirmed by plasma chemistry and liver histological analysis. Both the protein and mRNA levels of hepatic CYP2B1 were considerably reduced in MCD diet-fed rats; however, they were similar between the HF diet-fed and control rats. Consistently, the enzyme-kinetic and pharmacokinetic parameters for CYP2B1-mediated bupropion metabolism were considerably reduced in MCD diet-fed rats; however, they were also similar between the HF diet-fed and control rats. These results may promote a better understanding of the influence of NAFLD on CYP2B1-mediated metabolism, which could have important implications for the safety and pharmacokinetics of drug substrates for the CYP2B subfamily in patients with NAFLD. PMID:27321734

  6. Antidiabetic and Hypolipidemic Activities of Curculigo latifolia Fruit:Root Extract in High Fat Fed Diet and Low Dose STZ Induced Diabetic Rats

    PubMed Central

    Ishak, Nur Akmal; Ismail, Maznah; Hamid, Muhajir; Ahmad, Zalinah; Abd Ghafar, Siti Aisyah

    2013-01-01

    Curculigo latifolia fruit is used as alternative sweetener while root is used as alternative treatment for diuretic and urinary problems. The antidiabetic and hypolipidemic activities of C. latifolia fruit:root aqueous extract in high fat diet (HFD) and 40 mg streptozotocin (STZ) induced diabetic rats through expression of genes involved in glucose and lipid metabolisms were investigated. Diabetic rats were treated with C. latifolia fruit:root extract for 4 weeks. Plasma glucose, insulin, adiponectin, lipid profiles, alanine aminotransferase (ALT), gamma glutamyltransferase (GGT), urea, and creatinine levels were measured before and after treatments. Regulations of selected genes involved in glucose and lipid metabolisms were determined. Results showed the significant (P < 0.05) increase in body weight, high density lipoprotein (HDL), insulin, and adiponectin levels and decreased glucose, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), urea, creatinine, ALT, and GGT levels in diabetic rats after 4 weeks treatment. Furthermore, C. latifolia fruit:root extract significantly increased the expression of IRS-1, IGF-1, GLUT4, PPARα, PPARγ, AdipoR1, AdipoR2, leptin, LPL, and lipase genes in adipose and muscle tissues in diabetic rats. These results suggest that C. latifolia fruit:root extract exerts antidiabetic and hypolipidemic effects through altering regulation genes in glucose and lipid metabolisms in diabetic rats. PMID:23762147

  7. Managing the Combination of Nonalcoholic Fatty Liver Disease and Metabolic Syndrome with Chinese Herbal Extracts in High-Fat-Diet Fed Rats

    PubMed Central

    Tan, Yi; Lao, Weiguo; Xiao, Linda; Wang, Zhenzhong; Xiao, Wei; Kamal, Mohamed A.; Seale, J. Paul; Qu, Xianqin

    2013-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome (MetS). The aim of the study was to evaluate the effects of Chinese herbal extracts from Salvia miltiorrhiza and Gardenia jasminoides (SGE) on the combination of NAFLD and MetS induced by a high-fat diet (HFD) in rats. After 6 weeks of HFD feeding, rats (n = 10 each group) were treated with saline, rosiglitazone (RSG), and SGE for 4 weeks. HFD rats were obese, hyperinsulinemic, hyperlipidemic and increased hepatic enzymes with the histological images of NAFLD. Treatment with SGE significantly reduced serum triglycerides (TG), nonesterified fatty acids and enhanced insulin sensitivity, and ameliorated the elevated serum hepatic enzymes compared with HFD-saline group. SGE treatment also attenuated hepatic TG by 18.5% (P < 0.05). Histological stains showed SGE decreased lipids droplets in hepatocytes (P < 0.05) and normalized macrovesicular steatosis in HFD rats. Significant reduction of TNF-α and IL6 in adipose tissue was detected in SGE treated rats. The anti-inflammatory action may be, at least in part, the mechanism of SGE on MetS associated with NAFLD. This study discovered that SGE is capable of managing metabolic and histological abnormalities of NAFLD and MetS. SGE may be an optimal treatment for the combination of NAFLD and MetS. PMID:23476686

  8. Influences of dietary vitamin D restriction on bone strength, body composition and muscle in rats fed a high-fat diet: involvement of mRNA expression of MyoD in skeletal muscle.

    PubMed

    Oku, Yuno; Tanabe, Rieko; Nakaoka, Kanae; Yamada, Asako; Noda, Seiko; Hoshino, Ayumi; Haraikawa, Mayu; Goseki-Sone, Masae

    2016-06-01

    Vitamin D insufficiency is associated with a greater risk of osteoporosis and also influences skeletal muscle functions, differentiation and development. The present study investigated the influences of vitamin D restriction on the body composition, bone and skeletal muscle in rats fed a high-fat diet. Sprague-Dawley strain male rats (11weeks old) were divided into four groups and fed experimental diets: a basic control diet (Cont.), a basic control diet with vitamin D restriction (DR), a high-fat diet (F) and a high-fat diet with vitamin D restriction (FDR). At 28days after starting the experimental diets, the visceral fat mass was significantly increased in the F group compared with Cont. group, and the muscle mass tended to decrease in the DR group compared with Cont. group. The total volume of the femur was significantly lower in the DR group compared with Cont. group, and the bone mineral density (BMD) of the femur was significantly lower in the FDR group compared with F group. MyoD is one of the muscle-specific transcription factors. The levels of mRNA expression of MyoD of the gastrocnemius and soleus muscles from the DR group were reduced markedly compared with those from the Cont. group. In conclusion, our findings revealed the influences of a vitamin D-restricted high-fat diet on the bone strength, body composition and muscle. Further studies on vitamin D insufficiency in the regulation of muscle as well as fat and bone metabolism would provide valuable data for the prevention of lifestyle-related disorders, including osteoporosis and sarcopenia. PMID:27142740

  9. Impact of eight weeks endurance training on biochemical parameters and obesity-induced oxidative stress in high fat diet-fed rats

    PubMed Central

    Emami, Seyed Reza; Jafari, Mahvash; Haghshenas, Rouhollah; Ravasi, Aliasghar

    2016-01-01

    [Purpose] High-fat diets (HFD) feeding is an important risk factor for obesity that is accompanied with metabolic syndrome. Appropriate exercise is recommended for obesity prevention. The molecular mechanisms and cellular pathways activated in response to HFD and exercise are not well understood. The purpose of this study was to investigate the effect of 8 weeks endurance training on some plasma biochemical parameters and oxidative stress in HFD induced obese rats. [Methods] Twenty-eight male Wistar rats were randomly divided into 4 groups: the standard diet (SD) group, endurance training group with a standard diet (ESD), HFD group, and endurance training group with high-fat diet (EHFD). After 8 weeks, blood samples were taken by cardiac puncture and plasma were used for determination of biochemical parameters and oxidative stress biomarkers. [Results] HFD significantly increased malondialdehyde level and decreased the activities of superoxide dismutase, catalase, and glutathione S-transferase and the content of glutathione in the plasma. HFD also increased activities of aspartate transaminase, alanine transaminase, lactate dehydrogenase, as well as levels of total cholesterol, triglyceride and low-density-lipoprotein-cholesterol. However, endurance training showed protective effect on changes in these parameters. [Conclusion] These findings suggested that HFD alters the oxidant-antioxidant balance, as evidenced by reduction in the antioxidant enzymes activities and glutathione level and enhanced lipid peroxidation. Endurance training can be beneficial for the suppression of obesity-induced oxidative stress in HFD rats through modulating antioxidant defense system and reduces the risk of obesity-associated diseases. PMID:27298810

  10. Plasma lipids, lipoproteins, and fecal excretion of neutral sterols and bile acids in rats fed various high fat diets or a low fat/high sucrose diet.

    PubMed

    Høstmark, A T; Lystad, E; Haug, A; Eilertsen, E

    1989-03-01

    The effect of feeding various diets on plasma lipids and lipoproteins and on fecal excretion of neutral sterols and bile acids was studied in rats fed for 7 wk diets containing 42% of energy as either coconut oil (CO), sunflower seed oil (SO), fish body oil (FBO), cod liver oil (CLO), or a low fat/high sucrose diet (SU). Triacylglycerols (TG) in whole plasma and VLDL + LDL were lower in rats fed high amounts of polyunsaturated fatty acids (PUFA) than in those fed the CO diet. Plasma HDL2 components in FBO and CLO groups were generally lower than in the other groups. Percentages of liver and heart linoleic and arachidonic acid were higher in the SO group, but lower in groups fed marine oils, than in the CO group. There was a high relative amount of eicosapentaenoic and docosahexaenoic acid in liver and heart of rats fed marine oils. Fecal excretion of bile acids was lower in the PUFA groups than in the CO group, whereas the sum of neutral sterols was similar in all groups. Plasma HDL2 (and VLDL + LDL) correlated positively, but HDL3 negatively, with fecal bile acid excretion. Accordingly, increased bile acid excretion does not seem to account for hypolipemia following intake of PUFA diets. PMID:2921639

  11. Barley malt increases hindgut and portal butyric acid, modulates gene expression of gut tight junction proteins and Toll-like receptors in rats fed high-fat diets, but high advanced glycation end-products partially attenuate the effects.

    PubMed

    Zhong, Yadong; Teixeira, Cristina; Marungruang, Nittaya; Sae-Lim, Watina; Tareke, Eden; Andersson, Roger; Fåk, Frida; Nyman, Margareta

    2015-09-01

    Barley malt, a product of controlled germination, has been shown to produce high levels of butyric acid in the cecum and portal serum of rats and may therefore have anti-inflammatory effects. The aim of the study was to investigate how four barley malts, caramelized and colored malts, 50-malt and 350-malt, differing in functional characteristics concerning beta-glucan content and color, affect short-chain fatty acids (SCFA), barrier function and inflammation in the hindgut of rats fed high-fat diets. Male Wistar rats were given malt-supplemented high-fat diets for four weeks. Low and high-fat diets containing microcrystalline cellulose were incorporated as controls. All diets contained 70 g kg(-1) dietary fiber. The malt-fed groups were found to have had induced higher amounts of butyric and propionic acids in the hindgut and portal serum compared with controls, while cecal succinic acid only increased to a small extent. Fat increased the mRNA expression of tight junction proteins and Toll-like receptors (TLR) in the small intestine and distal colon of the rats, as well as the concentration of some amino acids in the portal plasma, but malt seemed to counteract these adverse effects to some extent. However, the high content of advanced glycation end-products (AGE) in caramelized malt tended to prohibit the positive effects on occludin in the small intestine and plasma amino acids seen with the other malt products. In conclusion, malting seems to be an interesting process for producing foods with positive health effects, but part of these effects may be destroyed if the malt contains a high content of AGE. PMID:26227569

  12. A prescribed Chinese herbal medicine improves glucose profile and ameliorates oxidative stress in Goto-Kakisaki rats fed with high fat diet.

    PubMed

    Wu, Lin; Li, Xiang; Zhu, Hongguang; Xu, Ping; Gao, Xin

    2013-01-01

    Oxidative stress (OS) plays a role in hyperglycemia induced islet β cell dysfunction, however, studies on classic anti-oxidants didn't show positive results in treating diabetes. We previously demonstrated that the prescribed Chinese herbal medicine preparation "Qing Huo Yi Hao" (QHYH) improved endothelial function in type 2 diabetic patients. QHYH protected endothelial cells from high glucose-induced damages by scavenging superoxide anion and reducing production of reactive oxygen species. Its active component protected C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction. In the present study, we investigated whether QHYH protected islet β cell function exacerbated by high fat diet (HFD) in hyperglycemic GK rats. 4-week-old male rats were randomly divided into high HFD feeding group (n = 20) and chow diet feeding group (n = 10). Each gram of HFD contained 4.8 kcal of energy, 52% of which from fat. Rats on HFD were further divided into 2 groups given either QHYH (3 ml/Kg/d) or saline through gastric tube. After intervention, serum glucose concentrations were monitored; IPGTTs were performed without anesthesia on 5 fasting rats randomly chosen from each group on week 4 and 16. Serum malondialdehyde (MDA) concentrations and activities of serum antioxidant enzymes were measured on week 4 and 16. Islet β cell mass and OS marker staining was done by immunohistochemistry on week 16. QHYH prevented the exacerbation of hyperglycemia in HFD feeding GK rats for 12 weeks. On week 16, it improved the exacerbated glucose tolerance and prevented the further loss of islet β cell mass induced by HFD. QHYH markedly decreased serum MDA concentration, increased serum catalase (CAT) and SOD activities on week 4. However, no differences of serum glucose concentration or OS were observed on week 16. We concluded that QHYH decreased hyperglycemia exacerbated by HFD in GK rats by improving β cell function partly via its antioxidant effect

  13. Differential effects of low-fat and high-fat diets on fed-state hepatic triacylglycerol secretion, hepatic fatty acid profiles, and DGAT-1 protein expression in obese-prone Sprague–Dawley rats

    PubMed Central

    Heden, Timothy D.; Morris, E. Matthew; Kearney, Monica L.; Liu, Tzu-Wen; Park, Young-min; Kanaley, Jill A.; Thyfault, John P.

    2015-01-01

    The purpose of this study was to compare the effects of short-term low-fat (LF) and high-fat (HF) diets on fed-state hepatic triacylglycerol (TAG) secretion, the content of proteins involved in TAG assembly and secretion, fatty acid oxidation (FAO), and the fatty acid profile of stored TAG. Using selectively bred obese-prone Sprague–Dawley rats, we directly measured fed-state hepatic TAG secretion, using Tyloxapol (a lipoprotein lipase inhibitor) and a standardized oral mixed meal (45% carbohydrate, 40% fat, 15% protein) bolus in animals fed a HF or LF diet for 2 weeks, after which the rats were maintained on their respective diet for 1 week (washout) prior to the liver being excised to measure protein content, FAO, and TAG fatty acid profiles. Hepatic DGAT-1 protein expression was ~27% lower in HF- than in LF-fed animals (p < 0.05); the protein expression of all other molecules was similar in the 2 diets. The fed-state hepatic TAG secretion rate was ~39% lower (p < 0.05) in HF- (4.62 ± 0.18 mmol·h−1) than in LF- (7.60 ± 0.57 mmol·h−1) fed animals. Hepatic TAG content was ~2-fold higher (p < 0.05) in HF- (1.07 ± 0.15 nmol·g−1 tissue) than in LF- (0.50 ± 0.16 nmol·g−1 tissue) fed animals. In addition, the fatty acid profile of liver TAG in HF-fed animals closely resembled the diet, whereas in LF-fed animals, the fatty acid profile consisted of mostly de novo synthesized fatty acids. FAO was not altered by diet. LF and HF diets differentially alter fed-state hepatic TAG secretion, hepatic fatty acid profiles, and DGAT-1 protein expression. PMID:24669989

  14. High-fat diet lowers the nutritional status indicators of pantothenic acid in weaning rats.

    PubMed

    Yoshida, Erina; Fukuwatari, Tsutomu; Ohtsubo, Masako; Shibata, Katsumi

    2010-01-01

    Weaning rats were fed a 5% or 30% fat diet containing limited calcium pantothenate for 28 d. The plasma, liver and adrenal pantothenic acid levels in the rats fed on the 30% fat diet were significantly lower than with the 5% fat diet. The results suggest that the high-fat diet affected pantothenic acid metabolism. PMID:20699566

  15. The physico-chemical properties of dietary fibre determine metabolic responses, short-chain Fatty Acid profiles and gut microbiota composition in rats fed low- and high-fat diets.

    PubMed

    Fåk, Frida; Jakobsdottir, Greta; Kulcinskaja, Evelina; Marungruang, Nittaya; Matziouridou, Chrysoula; Nilsson, Ulf; Stålbrand, Henrik; Nyman, Margareta

    2015-01-01

    The aim of this study was to investigate how physico-chemical properties of two dietary fibres, guar gum and pectin, affected weight gain, adiposity, lipid metabolism, short-chain fatty acid (SCFA) profiles and the gut microbiota in male Wistar rats fed either low- or high-fat diets for three weeks. Both pectin and guar gum reduced weight gain, adiposity, liver fat and blood glucose levels in rats fed a high-fat diet. Methoxylation degree of pectin (low, LM and high (HM)) and viscosity of guar gum (low, medium or high) resulted in different effects in the rats, where total blood and caecal amounts of SCFA were increased with guar gum (all viscosities) and with high methoxylated (HM) pectin. However, only guar gum with medium and high viscosity increased the levels of butyric acid in caecum and blood. Both pectin and guar gum reduced cholesterol, liver steatosis and blood glucose levels, but to varying extent depending on the degree of methoxylation and viscosity of the fibres. The medium viscosity guar gum was the most effective preparation for prevention of diet-induced hyperlipidaemia and liver steatosis. Caecal abundance of Akkermansia was increased with high-fat feeding and with HM pectin and guar gum of all viscosities tested. Moreover, guar gum had distinct bifidogenic effects independent of viscosity, increasing the caecal abundance of Bifidobacterium ten-fold. In conclusion, by tailoring the viscosity and possibly also the degree of methoxylation of dietary fibre, metabolic effects may be optimized, through a targeted modulation of the gut microbiota and its metabolites. PMID:25973610

  16. The Physico-Chemical Properties of Dietary Fibre Determine Metabolic Responses, Short-Chain Fatty Acid Profiles and Gut Microbiota Composition in Rats Fed Low- and High-Fat Diets

    PubMed Central

    Kulcinskaja, Evelina; Marungruang, Nittaya; Matziouridou, Chrysoula; Nilsson, Ulf; Stålbrand, Henrik; Nyman, Margareta

    2015-01-01

    The aim of this study was to investigate how physico-chemical properties of two dietary fibres, guar gum and pectin, affected weight gain, adiposity, lipid metabolism, short-chain fatty acid (SCFA) profiles and the gut microbiota in male Wistar rats fed either low- or high-fat diets for three weeks. Both pectin and guar gum reduced weight gain, adiposity, liver fat and blood glucose levels in rats fed a high-fat diet. Methoxylation degree of pectin (low, LM and high (HM)) and viscosity of guar gum (low, medium or high) resulted in different effects in the rats, where total blood and caecal amounts of SCFA were increased with guar gum (all viscosities) and with high methoxylated (HM) pectin. However, only guar gum with medium and high viscosity increased the levels of butyric acid in caecum and blood. Both pectin and guar gum reduced cholesterol, liver steatosis and blood glucose levels, but to varying extent depending on the degree of methoxylation and viscosity of the fibres. The medium viscosity guar gum was the most effective preparation for prevention of diet-induced hyperlipidaemia and liver steatosis. Caecal abundance of Akkermansia was increased with high-fat feeding and with HM pectin and guar gum of all viscosities tested. Moreover, guar gum had distinct bifidogenic effects independent of viscosity, increasing the caecal abundance of Bifidobacterium ten-fold. In conclusion, by tailoring the viscosity and possibly also the degree of methoxylation of dietary fibre, metabolic effects may be optimized, through a targeted modulation of the gut microbiota and its metabolites. PMID:25973610

  17. Amelioration of oxidative stress and insulin resistance by soy isoflavones (from Glycine max) in ovariectomized Wistar rats fed with high fat diet: the molecular mechanisms.

    PubMed

    Sankar, P; Zachariah, Bobby; Vickneshwaran, V; Jacob, Sajini Elizabeth; Sridhar, M G

    2015-03-01

    Estrogen deficiency after menopause accelerates the redox imbalance and insulin signaling, leading to oxidative stress (OS) and insulin resistance (IR). The molecular mechanisms by which the loss of ovarian hormone leads to OS and IR remain unclear. In the present study we found that rats when subjected to ovariectomy (OVX) resulted in reduction of whole blood antioxidants and elevation of oxidant markers. The expression of anti-oxidant enzymes, superoxide dismutase (SOD1) and glutathione peroxidase (GPX1) was suppressed whereas the pro-oxidative enzyme NADPH oxidase (NOX4) and mitogen activated protein (MAP) kinases ERK 1/2 and p38 were increased at different tissues. Treatment with soy (SIF, 150 mg/kg BW for 12 weeks) extract markedly reversed these metabolic changes and improved OS. Ovariectomized rats also displayed glucose intolerance (GI) and IR as evident from the impaired glucose tolerance test, and reduced expression of adipose and hepatic insulin receptor beta (IRβ) and adipose tissue GLUT4. Treatment with SIF reversed the ovariectomy induced GI and IR. On the other hand, all these metabolic changes were further augmented when ovariectomy was followed by a high fat diet, and these changes were also reversed by SIF. Taken together, these findings emphasized the antioxidant property and anti-diabetic effects of soy isoflavones suggesting the use of this natural phytoestrogen as a strategy for relieving oxidative stress and insulin resistance in postmenopausal women. PMID:25660477

  18. Safety and Health Benefits of Novel Dietary Supplements Consisting Multiple Phytochemicals, Vitamins, Minerals and Essential Fatty Acids in High Fat Diet Fed Rats.

    PubMed

    Ramprasath, Vanu Ramkumar; Jones, Peter J H

    2016-01-01

    The objective was to determine safety and efficacy of health supplements "Beyond Tangy Tangerine," a multivitamin/mineral complex and combination of multivitamin/mineral complex, "Osteofx," a bone healthy supplement and "Ultimate Essential Fatty Acids" in Sprague Dawley rats consuming high-fat diets. Initially a pilot study was conducted which confirmed palatability and acceptability of supplements. In a second study, rats (n = 15/group) were randomized to Control; Multivitamin/mineral complex (2 g/kg BW) or Combination (2 g Multivitamin/mineral complex, 1.5 g Bone healthy supplement and 0.34 g Essential fatty acids/kg BW). No differences were observed in BW change, feed intake, organ weights or bone mineral composition with supplementations compared to control. Multivitamin/mineral complex supplementation decreased abdominal white adipose tissue weights (WAT) (p = .005), total (p = .033) and fat mass (p = .040), plasma IL-6 (p = .016) and ALKP (p = .038) and elevated plasma calcium (p < .001), phosphorus (p = .038), total protein (p = .002), albumin (p = .014) and globulin (p = .018), compared to control. Similarly, combination supplementation reduced WAT (p < .001), total (p = .023) and fat mass (p = .045), plasma triglycerides (p = .018), IL-6 (p = .002) and ALKP (p < .001) with increases in plasma calcium (p = .031), phosphorus (p < .001) compared to control. Results indicate that consuming either supplement can be considered safe and improves overall health by reducing inflammation, abdominal fat mass and plasma triglycerides, as well as promote bone health. PMID:26317447

  19. Tripterygium Glycosides Tablet Ameliorates Renal Tubulointerstitial Fibrosis via the Toll-Like Receptor 4/Nuclear Factor Kappa B Signaling Pathway in High-Fat Diet Fed and Streptozotocin-Induced Diabetic Rats.

    PubMed

    Ma, Ze-Jun; Zhang, Xiao-Na; Li, Li; Yang, Wei; Wang, Shan-Shan; Guo, Xin; Sun, Pei; Chen, Li-Ming

    2015-01-01

    Tripterygium glycosides tablet (TGT) is a Chinese traditional medicine that has been shown to protect podocytes from injury and reduce the proteinuria. The aim of this study was to assess the effect of TGT on renal tubulointerstitial fibrosis and its potential mechanism in high-fat diet fed and STZ-induced diabetic rats. Rats were randomly divided into normal control rats (NC group), diabetic rats without drug treatment (DM group), and diabetic rats treated with TGT (1, 3, or 6 mg/kg/day, respectively) for 8 weeks. The results showed that 24 h proteinuria and urinary N-acetyl-glucosaminidase (NAG) in diabetic rats were decreased by TGT treatment without affecting blood glucose. Masson's trichrome stains showed that apparent renal tubulointerstitial fibrosis was found in DM group, which was ameliorated by TGT treatment. The expression of α-SMA was significantly decreased, accompanied by increased expression of E-cadherin in TGT-treated rats, but not in untreated DM rats. Further studies showed that TGT administration markedly reduced expression of TLR4, NF-κB, IL-1β, and MCP-1 in TGT-treated diabetic rats. These results showed that TGT could ameliorate renal tubulointerstitial fibrosis, the mechanism which may be at least partly associated with the amelioration of EMT through suppression of the TLR4/NF-κB pathway. PMID:26347890

  20. Effect of chronic treatment with conventional and organic purple grape juices (Vitis labrusca) on rats fed with high-fat diet.

    PubMed

    Cardozo, Marcia Gilceane; Medeiros, Niara; Lacerda, Denise dos Santos; de Almeida, Daniela Campos; Henriques, João Antônio Pegas; Dani, Caroline; Funchal, Cláudia

    2013-11-01

    Serra Gaucha is described as the most important wine region of Brazil. Regarding cultivars widespread in the Serra Gaucha, about 90 % of the area is occupied by vines of Vitis labrusca that is the most important specie used in grape juice production. The objective of this study was to investigate the antioxidant and neuroprotective effect of chronic intake of purple grape juice (organic and conventional) from Bordo variety (V. labrusca) on oxidative stress in different brain regions of rats supplemented with high-fat diet (HFD) for 3 months. A total of 40 male rats were randomly divided into 4 groups. Group 1 received a standard diet and water, group 2 HFD and water, group 3 HFD and conventional grape juice (CGJ), and group 4 HFD and organic grape juice (OGJ). All groups had free access to food and drink and after 3 months of treatment the rats were euthanized by decapitation and the cerebral cortex, hippocampus and cerebellum isolated and homogenized on ice for oxidative stress analysis. We observed that the consumption of calories in HFD and control groups, were higher than the groups supplemented with HFD and grape juices and that HFD diet group gain more weight than the other animals. Our results also demonstrated that HDF enhanced lipid peroxidation (TBARS) and protein damage (carbonyl) in cerebral cortex and hippocampus, reduced the non-enzymatic antioxidants defenses (sulfhydryl) in cerebral cortex and cerebellum, reduced catalase and superoxide dismutase activities in all brain tissues and enhanced nitric oxide production in all cerebral tissues. CGJ and OGJ were able to ameliorate these oxidative alterations, being OGJ more effective in this protection. Therefore, grape juices could be useful in the treatment of some neurodegenerative diseases associated with oxidative damage. PMID:23989908

  1. Obesity-prone high-fat-fed rats reduce caloric intake and adiposity and gain more fat-free mass when allowed to self-select protein from carbohydrate:fat intake.

    PubMed

    Azzout-Marniche, Dalila; Chalvon-Demersay, Tristan; Pimentel, Grégory; Chaumontet, Catherine; Nadkarni, Nachiket A; Piedcoq, Julien; Fromentin, Gilles; Tomé, Daniel; Gaudichon, Claire; Even, Patrick C

    2016-06-01

    We tested the hypothesis that, for rats fed a high-fat diet (HFD), a prioritization of maintaining protein intake may increase energy consumption and hence result in obesity, particularly for individuals prone to obesity ("fat sensitive," FS, vs. "fat resistant," FR). Male Wistar rats (n = 80) first received 3 wk of HFD (protein 15%, fat 42%, carbohydrate 42%), under which they were characterized as being FS (n = 18) or FR (n = 20) based on body weight gain. They then continued on the same HFD but in which protein (100%) was available separately from the carbohydrate:fat (50:50%) mixture. Under this second regimen, all rats maintained their previous protein intake, whereas intake of fat and carbohydrate was reduced by 50%. This increased protein intake to 26% and decreased fat intake to 37%. Adiposity gain was prevented in both FR and FS rats, and gain in fat-free mass was increased only in FS rats. At the end of the study, the rats were killed 2 h after ingestion of a protein meal, and their tissues and organs were collected for analysis of body composition and measurement of mRNA levels in the liver, adipose tissue, arcuate nucleus, and nucleus accumbens. FS rats had a higher expression of genes encoding enzymes involved in lipogenesis in the liver and white adipose tissue. These results show that FS rats strongly reduced food intake and adiposity gain through macronutrient selection, despite maintenance of a relatively high-fat intake and overexpression of genes favoring lipogenesis. PMID:27030668

  2. The pecan nut (Carya illinoinensis) and its oil and polyphenolic fractions differentially modulate lipid metabolism and the antioxidant enzyme activities in rats fed high-fat diets.

    PubMed

    Domínguez-Avila, Jesús A; Alvarez-Parrilla, Emilio; López-Díaz, José A; Maldonado-Mendoza, Ignacio E; Gómez-García, María Del Consuelo; de la Rosa, Laura A

    2015-02-01

    Tree nuts such as pecans (Carya illinoinensis) contain mostly oil but are also a source of polyphenols. Nut consumption has been linked to a reduction in serum lipid levels and oxidative stress. These effects have been attributed to the oil while overlooking the potential contribution of the polyphenols. Because the evidence regarding each fraction's bioactivity is scarce, we administered high-fat (HF) diets to male Wistar rats, supplementing them with pecan oil (HF+PO), pecan polyphenols (HF+PP) or whole pecans (HF+WP), and analysed the effects of each fraction. The HF diet increased the serum leptin and total cholesterol (TC) with respect to the control levels. The HF+WP diet prevented hyperleptinemia and decreased the TC compared with the control. The HF+WP diet upregulated the hepatic expression of apolipoprotein B and LDL receptor mRNAs with respect to the HF levels. The HF+PO diet reduced the level of triacylglycerols compared with the control. The HF+PP diet stimulated the hepatic expression of liver X receptor alpha mRNA. The HF+WP diet increased the activities of hepatic catalase, glutathione peroxidase and glutathione S transferase compared with the control, and decreased the degree of lipid peroxidation compared with the HF diet. The most bioactive diet was the WP diet. PMID:25172744

  3. Lipoic acid improves neuronal insulin signalling and rescues cognitive function regulating VGlut1 expression in high-fat-fed rats: Implications for Alzheimer's disease.

    PubMed

    Rodriguez-Perdigon, Manuel; Solas, Maite; Moreno-Aliaga, Maria Jesús; Ramirez, Maria Javier

    2016-04-01

    The concept of central insulin resistance and dysfunctional insulin signalling in sporadic Alzheimer's disease (AD) is now widely accepted and diabetes is recognized as one of the main risk factors for developing AD. Moreover, some lines of evidence indicated that VGlut1 is impaired in frontal regions of AD patients and this impairment is correlated with the progression of cognitive decline in AD. The present work hypothesizes that ketosis associated to insulin resistance could interfere with the normal activity of VGlut1 and its role in the release of glutamate in the hippocampus, which might ultimately lead to cognitive deficits. High fat diet (HFD) rats showed memory impairments and both peripheral (as shown by increased fasting plasma insulin levels and HOMA index) and hippocampal (as shown by decreased activation of insulin receptor, IRS-1 and pAkt) insulin pathway alterations, accompanied by increased ketone bodies production. All these effects were counteracted by α-lipoic acid (LA) administration. VGlut1 levels were significantly decreased in the hippocampus of HFD rats, and this decrease was reversed by LA. Altogether, the present results suggest that HFD induced alterations in central insulin signalling could switch metabolism to produce ketone bodies, which in turn, in the hippocampus, might lead to a decreased expression of VGlut1, and therefore to a decreased release of glutamate and hence, to the glutamatergic deficit described in AD. The ability of LA treatment to prevent the alterations in insulin signalling in this model of HFD might represent a possible new therapeutic target for the treatment of AD. PMID:26769360

  4. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells

    SciTech Connect

    Hwang, Yong Pil; Choi, Jae Ho; Kim, Hyung Gyun; Khanal, Tilak; Song, Gye Young; Nam, Myoung Soo; Lee, Hyun-Sun; Chung, Young Chul; Lee, Young Chun; Jeong, Hye Gwang

    2013-03-01

    AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and sterol regulatory element-binding protein-1c (SREBP-1c) pathway. Saponins, particularly platycodin D, from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have a variety of pharmacological properties, including antioxidant and hepatoprotective properties. The aim of this study was to investigate the effects of CKS on hepatic lipogenesis and on the expression of genes involved in lipogenesis, and the mechanisms involved. CKS attenuated fat accumulation and the induction of the lipogenic genes encoding SREBP-1c and fatty acid synthase in the livers of HFD-fed rats and in steatotic HepG2 cells. Blood biochemical analyses and histopathological examinations showed that CKS prevented liver injury. CKS and platycodin D each increased the phosphorylation of AMPK and acetyl-CoA carboxylase in HFD-fed rats and HepG2 cells. The use of specific inhibitors showed that platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells. This study demonstrates that CKS or platycodin D alone can regulate hepatic lipogenesis via an AMPK-dependent signalling pathway. - Highlights: ► CKS attenuated fat accumulation in HFD-fed rats and in steatotic HepG2 cells. ► CKS and its major component, platycodin D, inhibited the levels of SREBP-1 and FAS. ► CKS and platycodin D increased the phosphorylation of AMPK and ACC. ► Platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells.

  5. The effects of leptin in combination with a cannabinoid receptor 1 antagonist, AM 251, or cannabidiol on food intake and body weight in rats fed a high-fat or a free-choice high sugar diet.

    PubMed

    Wierucka-Rybak, M; Wolak, M; Bojanowska, E

    2014-08-01

    High intake of fats and sugars has prompted a rapid growth in the number of obese individuals worldwide. To further investigate whether simultaneous pharmacological intervention in the leptin and cannabinoid system might change food and water intake, preferences for palatable foods, and body weight, we have examined the effects of concomitant intraperitoneal administration of leptin and AM 251, a cannabinoid 1 (CB1) receptor antagonist, or cannabidiol (CBD), a plant cannabinoid, in rats maintained on either a high-fat (HF) diet (45% energy from fat) or free-choice (FC) diet consisting of high-sucrose and normal rat chow (83% and 61% energy from carbohydrates, respectively). Leptin at a dose of 100 μg/kg injected individually for 3 subsequent days to rats fed a HF diet reduced significantly the daily caloric intake and inhibited body weight gain. The hormone had no significant effects, however, on either caloric intake, body weight or food preferences in rats fed an FC diet. Co-injection of leptin and 1 mg/kg AM 251 resulted in a further significant decrease in HF diet intake and a profound reduction in body weight gain both in HF diet- and FC diet-fed rats. This drug combination, however, had no effect on the consumption of high-sucrose chow. In contrast, 3mg/kg of CBD co-injected with leptin did not modify leptin effects on food intake in rats maintained on an FC or HF diet. None of the drug combinations affected water consumption. It is concluded that the concomitant treatment with leptin and AM 251 attenuated markedly body weight gain in rats maintained on high-calorie diets rich in fat and carbohydrates but did not affect preferences for sweet food. PMID:25179081

  6. Saponins, especially platycodin D, from Platycodon grandiflorum modulate hepatic lipogenesis in high-fat diet-fed rats and high glucose-exposed HepG2 cells.

    PubMed

    Hwang, Yong Pil; Choi, Jae Ho; Kim, Hyung Gyun; Khanal, Tilak; Song, Gye Young; Nam, Myoung Soo; Lee, Hyun-Sun; Chung, Young Chul; Lee, Young Chun; Jeong, Hye Gwang

    2013-03-01

    AMP-activated protein kinase (AMPK) plays a central role in controlling hepatic lipid metabolism through modulating the downstream acetyl CoA carboxylase (ACC) and sterol regulatory element-binding protein-1c (SREBP-1c) pathway. Saponins, particularly platycodin D, from the roots of Platycodon grandiflorum (Changkil saponins, CKS) have a variety of pharmacological properties, including antioxidant and hepatoprotective properties. The aim of this study was to investigate the effects of CKS on hepatic lipogenesis and on the expression of genes involved in lipogenesis, and the mechanisms involved. CKS attenuated fat accumulation and the induction of the lipogenic genes encoding SREBP-1c and fatty acid synthase in the livers of HFD-fed rats and in steatotic HepG2 cells. Blood biochemical analyses and histopathological examinations showed that CKS prevented liver injury. CKS and platycodin D each increased the phosphorylation of AMPK and acetyl-CoA carboxylase in HFD-fed rats and HepG2 cells. The use of specific inhibitors showed that platycodin D activated AMPK via SIRT1/CaMKKβ in HepG2 cells. This study demonstrates that CKS or platycodin D alone can regulate hepatic lipogenesis via an AMPK-dependent signalling pathway. PMID:23319015

  7. Exercise improves skeletal muscle insulin resistance without reduced basal mTOR/S6K1 signaling in rats fed a high-fat diet.

    PubMed

    Liao, Bagen; Xu, Yong

    2011-11-01

    Exercise improves high-fat diet (HFD)-induced skeletal muscle insulin resistance, but the mechanism is unresolved. This study aims to explore whether the improvement in response to exercise is associated with mTOR/S6K1 signaling and whether the signaling changes are muscle-specific. Male SD rats (150-180 g) were used for this study. After the experimental period, 6 weeks of exercise improved HFD-impaired intraperitoneal glucose tolerance and insulin-stimulated 2-deoxyglucose uptake in soleus (SOL) and extensor digitorum longus (EDL) muscles. Furthermore, 6 weeks of the HFD resulted in a reduced type I fiber ratio of SOL, an increased type I ratio of EDL, and a reduced fiber size of EDL, whereas exercise increased type I fiber ratio of SOL as well as type I fiber cross-sectional areas of EDL. However, the HFD had a main effect on basal cytosolic phosphorylation of S6K1 on Thr(389) content in SOL, which was also influenced by a significant interaction between the diet and exercise in EDL. Exercise had no direct effect on the basal phosphorylation of Akt on Ser(473), mTOR on Ser(2448), S6K1 on Thr(389) content in SOL. On the contrary, exercise prevented HFD-induced decrease in basal phosphorylation of S6K1 on Thr(389) content in EDL. These results indicate that 6 weeks of HFD and exercise lead to alterations in fiber type shift, fiber size, and basal phosphorylation of S6K1 on Thr(389) content in a muscle-specific pattern. Exercise prevents HFD-induced skeletal muscle insulin resistance, which is not associated with a reduced basal phosphorylation of mTOR/S6K1 alteration in the muscles. PMID:21404070

  8. Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats.

    PubMed

    Gopalakrishnan, Veerasamy; Iyyam Pillai, Subramanian; Subramanian, Sorimuthu Pillai

    2015-01-01

    In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus. PMID:26783461

  9. Synthesis, Spectral Characterization, and Biochemical Evaluation of Antidiabetic Properties of a New Zinc-Diosmin Complex Studied in High Fat Diet Fed-Low Dose Streptozotocin Induced Experimental Type 2 Diabetes in Rats

    PubMed Central

    Gopalakrishnan, Veerasamy; Iyyam Pillai, Subramanian; Subramanian, Sorimuthu Pillai

    2015-01-01

    In view of the established antidiabetic properties of zinc, the present study was aimed at evaluating the hypoglycemic properties of a new zinc-diosmin complex in high fat diet fed-low dose streptozotocin induced experimental type 2 diabetes in rats. Zinc-diosmin complex was synthesized and characterized by various spectral studies. The complexation between zinc ions and diosmin was further evidenced by pH-potentiometric titrations and Job's plot. Diabetic rats were orally treated with zinc-diosmin complex at a concentration of 20 mg/kg b.w./rat/day for 30 days. At the end of the experimental period, the rats were subjected to oral glucose tolerance test. In addition, HOMA-IR and various biochemical parameters related to glucose homeostasis were analyzed. Treatment with zinc-diosmin complex significantly improved the glucose homeostasis in diabetic rats. Treatment with zinc-diosmin complex significantly improved insulin sensitivity, at least in part, through enhancing protein metabolism and alteration in the levels of muscle and liver glycogen. The assay of clinical marker enzymes revealed the nontoxic nature of the complex. Determination of renal tissue markers such as blood urea and serum creatinine indicates the renoprotective nature of the complex. These findings suggest that zinc-diosmin complex is nontoxic and has complimentary potential to develop as an antihyperglycemic agent for the treatment of diabetes mellitus. PMID:26783461

  10. Decreased beige adipocyte number and mitochondrial respiration coincide with reduced FGF21 gene expression in Sprague Dawley rats fed prenatal low protein and postnatal high fat diets

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have shown that protein malnutrition during fetal growth followed by postnatal high-fat diets results in a rapid increase in subcutaneous adipose tissue mass in the offspring contributing to development of obesity and insulin resistance. Recent studies have shown that the absence of a key transcr...

  11. A high-fat diet negatively affects rat sperm mitochondrial respiration.

    PubMed

    Ferramosca, A; Conte, A; Moscatelli, N; Zara, V

    2016-05-01

    Recent evidences have linked abdominal obesity, insulin resistance, and dyslipidemia to male infertility. Since a defective energy metabolism may play an important role in the impairment of sperm quality, the aim of this study is to investigate the sperm energetic metabolism in rats fed with a high-fat diet, an animal model associated with metabolic syndrome development. Sexually mature male Sprague-Dawley rats were divided into two groups and fed for 4 weeks a standard diet (control group) or a diet enriched in 35% of fat (high fat group). Liver and adipose tissue weight, plasma glucose, insulin, and lipid concentrations were determined. Activities of enzymes involved in sperm energetic metabolism were evaluated by spectrophotometric assays. Sperm mitochondrial respiratory activity was evaluated with a polarographic assay of oxygen consumption. The administration of a high-fat diet caused a significant increase in body weight of rats and provoked hyperglycemia, hyperinsulinemia, and dyslipidemia. In these animals, we also observed a reduction in sperm concentration and motility. The investigation of sperm energetic metabolism in animals fed a high-fat diet revealed an impairment in the activity of pyruvate and lactate dehydrogenase, citrate synthase, and respiratory chain complexes. A parallel reduction in the cellular levels of adenosine triphosphate (ATP) and an increase in oxidative damage were also observed. A defective energy metabolism may play an important role in the impairment of sperm quality in the high-fat diet fed rats. PMID:27062222

  12. Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet.

    PubMed

    Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

    2016-01-01

    Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID:27410429

  13. Long-Term Administration of Dehydroepiandrosterone Accelerates Glucose Catabolism via Activation of PI3K/Akt-PFK-2 Signaling Pathway in Rats Fed a High-Fat Diet

    PubMed Central

    Kang, Jian; Ge, Chongyang; Yu, Lei; Li, Longlong; Ma, Haitian

    2016-01-01

    Dehydroepiandrosterone (DHEA) has a fat-reducing effect, while little information is available on whether DHEA regulates glucose metabolism, which would in turn affect fat deposition. To investigate the effects of DHEA on glucose metabolism, rats were administered a high-fat diet containing either 0 (HCG), 25 (HLG), 50 (HMG), or 100 (HHG) mg·kg-1 DHEA per day via gavage for 8 weeks. Results showed that long-term administration of DHEA inhibited body weight gain in rats on a high-fat diet. No statistical differences in serum glucose levels were observed, whereas hepatic glycogen content in HMG and HHG groups and muscle glycogen content in HLG and HMG groups were higher than those in HCG group. Glucokinase, malate dehydrogenase and phosphofructokinase-2 activities in HMG and HHG groups, pyruvate kinase and succinate dehydrogenase activities in HMG group, and pyruvate dehydrogenase activity in all DHEA treatment groups were increased compared with those in HCG group. Phosphoenolpyruvate carboxykinase and glycogen phosphorylase mRNA levels were decreased in HMG and HHG groups, whereas glycogen synthase-2 mRNA level was increased in HMG group compared with those in HCG. The abundance of Glut2 mRNA in HMG and HHG groups and Glut4 mRNA in HMG group was higher than that in HCG group. DHEA treatment increased serum leptin content in HMG and HHG groups compared with that in HCG group. Serum insulin content and insulin receptor mRNA level in HMG group and insulin receptor substrate-2 mRNA level in HMG and HHG group were increased compared with those in HCG group. Furthermore, Pi3k mRNA level in HMG and Akt mRNA level in HMG and HHG groups were significantly increased than those in HCG group. These data showed that DHEA treatment could enhance glycogen storage and accelerate glucose catabolism in rats fed a high-fat diet, and this effect may be associated with the activation of PI3K/Akt-PFK-2 signaling pathway. PMID:27410429

  14. Green tea, black tea, and epigallocatechin modify body composition, improve glucose tolerance, and differentially alter metabolic gene expression in rats fed a high-fat diet.

    PubMed

    Chen, Nora; Bezzina, Rebecca; Hinch, Edward; Lewandowski, Paul A; Cameron-Smith, David; Mathai, Michael L; Jois, Markandeya; Sinclair, Andrew J; Begg, Denovan P; Wark, John D; Weisinger, Harrison S; Weisinger, Richard S

    2009-11-01

    The mechanisms of how tea and epigallocatechin-3-gallate (EGCG) lower body fat are not completely understood. This study investigated long-term administration of green tea (GT), black tea (BT), or isolated EGCG (1 mg/kg per day) on body composition, glucose tolerance, and gene expression related to energy metabolism and lipid homeostasis; it was hypothesized that all treatments would improve the indicators of metabolic syndrome. Rats were fed a 15% fat diet for 6 months from 4 weeks of age and were supplied GT, BT, EGCG, or water. GT and BT reduced body fat, whereas GT and EGCG increased lean mass. At 16 weeks GT, BT, and EGCG improved glucose tolerance. In the liver, GT and BT increased the expression of genes involved in fatty acid synthesis (SREBP-1c, FAS, MCD, ACC) and oxidation (PPAR-alpha, CPT-1, ACO); however, EGCG had no effect. In perirenal fat, genes that mediate adipocyte differentiation were suppressed by GT (Pref-1, C/EBP-beta, and PPAR-gamma) and BT (C/EBP-beta), while decreasing LPL, HSL, and UCP-2 expression; EGCG increased expression of UCP-2 and PPAR-gamma genes. Liver triacylglycerol content was unchanged. The results suggest that GT and BT suppressed adipocyte differentiation and fatty acid uptake into adipose tissue, while increasing fat synthesis and oxidation by the liver, without inducing hepatic fat accumulation. In contrast, EGCG increased markers of thermogenesis and differentiation in adipose tissue, while having no effect on liver or muscle tissues at this dose. These results show novel and separate mechanisms by which tea and EGCG may improve glucose tolerance and support a role for these compounds in obesity prevention. PMID:19932867

  15. Preventing dyslipidemia by Chlorella pyrenoidosa in rats and hamsters after chronic high fat diet treatment.

    PubMed

    Cherng, Jong-Yuh; Shih, Mei-Fen

    2005-05-13

    The effects of Chlorella pyrenoidosa on serum lipid profiles, after concomitant long-term treatment of high-fat diet (HFD) in rats and hamsters was studied. Wistar rats and Syrian hamsters were fed with or without various concentrations of Chlorella pyrenoidosa contained high-fat diet (CHFD) for 2, 4 and 8 weeks prior to assay of serum lipids. Fasting triglycerides, total cholesterol, and LDL cholesterol as well as HDL cholesterol levels in high-fat diet treated rats and hamster were determined. Results showed that triglycerides, total cholesterol and LDL cholesterol levels in HFD treated rats and hamsters were increased from the normal rodent diet (NRD) treated controls after 2, 4, and 8-week treatments. However, the presence of Chlorella pyrenoidosa in high-fat diets significantly decreased the levels of triglycerides, total cholesterol and LDL cholesterol with comparison to HFD group in rats and hamsters. The total cholesterol/HDL ratios, an indication of occurrence of coronary heart disease, were decreased in all CHFD treated grouped rats and hamsters which suggests administration of Chlorella pyrenoidosa could lower the occurring risk of heart diseases. In conclusion, Chlorella pyrenoidosa has the ability to prevent dyslipidemia in chronic high-fat fed animals and could be potential in use to prevent intestinal absorption of redundant lipid from our daily intake and subsequently to prevent hyperlipidemia as well as atherosclerosis. PMID:15850594

  16. Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet

    PubMed Central

    Carter, Lindsay G; Ngo Tenlep, Sara Y; Woollett, Laura A; Pearson, Kevin J

    2016-01-01

    Objective Physical activity has been suggested as a non-pharmacological intervention that can be used to improve glucose homeostasis in women with gestational diabetes mellitus. The purpose of this study was to determine the effects of voluntary exercise on glucose tolerance and body composition in pregnant high fat diet fed mice. Methods Female mice were put on a standard diet or high fat diet for two weeks. The mice were then split into 4 groups; control standard diet fed, exercise standard diet fed, control high fat diet fed, and exercise high fat diet fed. Exercise mice had voluntary access to a running wheel in their home cage one week prior to mating, during mating, and throughout pregnancy. Glucose tolerance and body composition were measured during pregnancy. Akt levels were quantified in skeletal muscle and adipose tissue isolated from saline or insulin injected pregnant dams as a marker for insulin signaling. Results Consumption of the high fat diet led to significantly increased body weight, fat mass, and impaired glucose tolerance in control mice. However, voluntary running in the high fat diet fed dams significantly reduced weight gain and fat mass and ultimately improved glucose tolerance compared to control high fat diet fed dams. Further, body weight, fat mass, and glucose disposal in exercise high fat diet dams were indistinguishable from control dams fed the standard diet. High fat diet fed exercise dams also had significantly increased insulin stimulated phosphorylated Akt expression in adipose tissue, but not skeletal muscle, compared to control dams on high fat diet. Conclusion The use of voluntary exercise improves glucose homeostasis and body composition in pregnant female mice. Thus, future studies could investigate potential long-term health benefits in offspring born to obese exercising dams. PMID:26966635

  17. Decreased beige adipocyte number and mitochondrial respiration coincide with increased histone methyl transferase (G9a) and reduced FGF21 gene expression in Sprague-Dawley rats fed prenatal low protein and postnatal high-fat diets.

    PubMed

    Claycombe, Kate J; Vomhof-DeKrey, Emilie E; Garcia, Rolando; Johnson, William Thomas; Uthus, Eric; Roemmich, James N

    2016-05-01

    We have shown that prenatal low-protein (LP) followed by postnatal high-fat (HF) diets result in a rapid increase in subcutaneous adipose tissue (subc-AT) mass in the offspring, contributing to development of obesity and insulin resistance. Studies have shown that a key transcription factor, PR domain containing 16 (PRDM16), and fibroblast growth factor 21 (FGF21) are involved in conversion of precursor cells into mitochondria (mt)-enriched beige adipocytes (BA). Our hypothesis is that a maternal LP and postnatal HF diets increase the risk of obesity and insulin resistance in offspring, in part, by reducing the conversion of precursor cell into BA in the subc-AT of offspring. Using obese-prone Sprague-Dawley rats fed 8% LP or 20% normal-protein (NP) diets for 3 weeks prior to conception and throughout pregnancy and lactation followed by 12 weeks of 10% normal-fat (NF) or 45% HF diet feeding, we investigated whether prenatal LP and postnatal HF diets affect BA number and oxidative respiratory function in subc-AT. Results showed that subc-AT and liver FGF21, PRDM16 and BA marker CD137 mRNA increase with postnatal HF diet in maternal NP group rats. In contrast, rats fed maternal LP and postnatal HF diets showed no increase in subc-AT mt copy number, oxygen consumption rate, FGF21, PRDM16 and CD137 mRNA, whereas protein expression of an inhibitor for FGF21 transcription (histone methyltransferase, G9a) increased. These findings suggest that LPHF diets cause offspring metabolic alterations by reduced BA and FGF21 mRNA and increased G9a protein expression in subc-AT. PMID:27133430

  18. Diets containing soy or rice protein isolate increase insulin sensitivity and improve lipid homeostasis in weanling rats fed high fat, high cholesterol Western diets as a result of activation of PPAR and LXR-mediated pathways

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The current study examined the effects of feeding soy protein isolate (SPI) and rice protein isolate (RPI) on insulin sensitivity and fat breakdown in weanling rats consuming high fat/high cholesterol diets. Male Sprague-Dawley rats were placed on semi-purified diets containing the milk protein case...

  19. Maternal obesity and post-natal high fat diet disrupt hepatic circadian rhythm in rat offspring

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Offspring of obese (Ob) rat dams gain greater body wt and fat mass when fed high-fat diet (HFD) as compared to controls. Alterations of diurnal circadian rhythm are known to detrimentally impact metabolically active tissues such as liver. We sought to determine if maternal obesity (MOb) leads to p...

  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. Sechium edule Shoot Extracts and Active Components Improve Obesity and a Fatty Liver That Involved Reducing Hepatic Lipogenesis and Adipogenesis in High-Fat-Diet-Fed Rats.

    PubMed

    Yang, Mon-Yuan; Chan, Kuei-Chuan; Lee, Yi-Ju; Chang, Xiao-Zong; Wu, Cheng-Hsun; Wang, Chau-Jong

    2015-05-13

    Excess fat accumulation in the liver increases the risk of developing progressive liver injuries ranging from a fatty liver to hepatocarcinoma. In a previous study, we demonstrated that the polyphenol components of Sechium edule shoots attenuated hepatic lipid accumulation in vitro. Therefore, we investigated the effects and mechanisms of the extract of S. edule shoots (SWE) to modulate fat accumulation in a high-fat-diet (HFD)-induced animal model. In this study, we found that the SWE can reduce the body weight, adipose tissue fat, and regulate hepatic lipid contents (e.g., triglyceride and cholesterol). Additionally, treatment of caffeic acid (CA) and hesperetin (HPT), the main ingredients of SWE, also inhibited oleic acid (OA)-induced lipid accumulation in HepG2 cells. SWE enhanced the activation of AMP-activating protein kinase (AMPK) and decreased numerous lipogenic-related enzymes, such as sterol regulator element-binding proteins (SREBPs), e.g., SREBP-1 and SREBP-2, and HMG-CoA reductase (HMGCoR) proteins, which are critical regulators of hepatic lipid metabolism. Taken together, the results demonstrated that SWE can prevent a fatty liver and attenuate adipose tissue fat by inhibiting lipogenic enzymes and stimulating lipolysis via upregulating AMPK. It was also demonstrated that the main activation components of SWE are both CA and HPT. PMID:25912298

  2. Time-restricted feeding reduces adiposity in mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Disruption of the circadian rhythm contributes to obesity. The present study investigated the effects of time-restricted feeding (TRF) of a high-fat diet on adiposity in male C57BL/6 mice. Three-week-old mice were fed a low-fat or high-fat diet (16% or 45% of energy from corn oil) ad libitum (ad l...

  3. Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet

    PubMed Central

    Cho, Kangok; Kwon, Daekeun; Park, Jaeyong; Song, Youngju

    2015-01-01

    [Purpose] This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats. [Methods] Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks. [Results] Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1β (p<0.001) and IL-6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1β: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1β: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels. [Conclusion] Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet. PMID:27274463

  4. Experimental Nonalcoholic Steatohepatitis Induced by Neonatal Streptozotocin Injection and a High-Fat Diet in Rats.

    PubMed

    Hsu, Huai-Che; Dozen, Masaharu; Matsuno, Naoto; Obara, Hiromichi; Tanaka, Ryou; Enosawa, Shin

    2013-12-30

    Nonalcoholic steatohepatitis (NASH) has become a major concern in clinical hepatology. To elucidate the disease mechanisms and to develop a treatment, the advent of an appropriate experimental model is crucial. Pregnant Sprague-Dawley rats were fed a high-fat diet from gestational day 16. Two days after birth, the neonates were injected subcutaneously with streptozotocin (STZ) (180, 200, or 256 mg/kg). The mothers were fed a high-fat diet during the nursing period. After being weaned (4 weeks of age), the juvenile rats were fed the same high-fat diet. The survival rates at the time of weaning were 25.6% (180 mg/kg STZ), 22.8% (200 mg/kg STZ), and 19.4% (256 mg/kg STZ). The mean body weight of NASH rats was approximately 20% less than that of normal rats. Serum levels of glucose, alanine aminotransferase, and hyaluronic acid increased in NASH rats. Histologically, typical features of steatohepatitis such as ballooning, inflammatory cell infiltration, and perivenular and pericellular fibrosis were observed. In an indocyanine green loading test, the blood half-life was significantly longer in NASH rats (5.04 ± 2.14 vs. 2.72 ± 0.72 min; p < 0.05), which was suggestive of an impaired hepatobiliary transportation function. Concomitantly, biliary ICG concentrations in NASH rats stabilized in a delayed fashion compared with normal rats. In addition, the amount of bile excreted in NASH rats was significantly lower than that in normal rats (4.32 ± 0.83 vs. 7.66 ± 1.05 mg/min; p < 0.01). The rat NASH model presented here mimics the clinical features of the disease and will be a helpful tool for medical and bioscience research. PMID:26858881

  5. Krill Oil Ameliorates Mitochondrial Dysfunctions in Rats Treated with High-Fat Diet.

    PubMed

    Ferramosca, Alessandra; Conte, Annalea; Zara, Vincenzo

    2015-01-01

    In recent years, several studies focused their attention on the role of dietary fats in the pathogenesis of hepatic steatosis. It has been demonstrated that a high-fat diet is able to induce hyperglycemia, hyperinsulinemia, obesity, and nonalcoholic fatty liver disease. On the other hand, krill oil, a novel dietary supplement of n-3 PUFAs, has the ability to improve lipid and glucose metabolism, exerting possible protective effects against hepatic steatosis. In this study we have investigated the effects of krill oil on mitochondrial energetic metabolism in animals fed a high-fat diet. To this end, male Sprague-Dawley rats were divided into three groups and fed for 4 weeks with a standard diet (control group), a diet with 35% fat (HF group), or a high-fat diet supplemented with 2.5% krill oil (HF+KO group). The obtained results suggest that krill oil promotes the burning of fat excess introduced by the high-fat diet. This effect is obtained by stimulating mitochondrial metabolic pathways such as fatty acid oxidation, Krebs cycle, and respiratory chain complexes activity. Modulation of the expression of carrier proteins involved in mitochondrial uncoupling was also observed. Overall, krill oil counteracts the negative effects of a high-fat diet on mitochondrial energetic metabolism. PMID:26301251

  6. 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

  7. Exercise and a High Fat Diet Synergistically Increase the Pantothenic Acid Requirement in Rats.

    PubMed

    Takahashi, Kei; Fukuwatari, Tsutomu; Shibata, Katsumi

    2015-01-01

    It is thought that both exercise and dietary composition increase the utilization of, and thus the requirement for, certain water-soluble vitamins. However, there have been no studies evaluating the combined impacts of exercise and dietary composition on vitamin utilization. In this experiment, rats were fed a pantothenic acid (PaA)-restricted (0.004 g PaA-Ca/kg diet) diet containing 5% (ordinary amount of dietary fat) or 20% fat (high fat), and were forced to swim until exhaustion every other day for 22 d. PaA status was assessed by urinary excretion, which reflects body stores of water-soluble vitamins. The urinary excretion of PaA in rats fed a 5% fat diet was not affected by swimming (5% fat + non-swimming vs. 5% fat + swim; p>0.05). Excretion of PaA was decreased by the high-fat diet (5% fat + non-swim vs. 20% fat + non-swim; p<0.05) and synergistically decreased by exercise (20% fat + non-swim vs. 20% fat + swim; p<0.05). There was a significant interaction between exercise and a high-fat diet. Plasma PaA concentrations showed changes similar to those seen for urinary excretion. The experiment was then repeated using rats fed a PaA-sufficient (0.016 g PaA-Ca/kg diet) diet, and PaA excretion was again synergistically decreased by the combination of exercise and a high-fat diet (p<0.05). These results suggest that the combination of exercise and a high-fat diet synergistically increases the requirement for PaA. PMID:26226957

  8. High fat diet exacerbates vascular endothelial dysfunction in rats exposed to continuous hypobaric hypoxia.

    PubMed

    Zhao, Yan-Xia; Tang, Feng; Ga, Qin; Wuren, Tana; Wang, Ya-Ping; Rondina, Matthew T; Ge, Ri-Li

    2015-02-13

    Independently, a high fat diet and hypoxia are associated with vascular endothelial dysfunction (VED) and often occur concurrently in patients. Nevertheless, the effects of a high fat diet on vascular endothelial function combined with hypoxia, a situation occurring with increasing frequency in many parts of the world, remain largely unknown. We investigated the effects of a high fat diet on vascular endothelial function in rats exposed to continuous hypoxia for 4 weeks. Seventy two male Sprague-Dawley rats were randomly divided into 3 groups: a hypoxia group fed regular chow, a combined hypoxia and high fat diet (HFD) group, and for comparison, rats maintained in normoxia, regular chow conditions were set as baseline (BL) group. The experimental data of BL group were obtained at beginning of hypoxia given in the other groups. Continuous hypoxia was induced in a hypobaric chamber maintained at an altitude of 5000 m. Compared to hypoxic conditions alone, hypoxia plus a HFD prevented adaptive changes in plasma nitric oxide (NOx) levels and caused earlier and more severe changes in aortic endothelial structures. Functionally, hypoxia plus a HFD resulted in impaired endothelium-dependent vasorelaxation responses to acetylcholine and altered the bioavailability of the nitric oxide synthase (NOS) substrate L-Arginine. At the molecular level, hypoxia plus a HFD blunted increases in endothelial NOS (eNOS) mRNA and protein in aortic endothelial tissue. Taken together, our findings demonstrate that in the setting of hypoxia, a high fat diet leads to earlier and more severe VED than hypoxia alone. These data have important implications for populations residing at high-altitude, as dietary patterns shift towards increased fat intake. PMID:25603049

  9. Effects of secoisolariciresinol diglucoside lignan-enriched flaxseed powder on body weight, visceral fat, lipid profile, adipokines, and blood pressure in rats fed a high-fructose and high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The potential effects of secoisolariciresinol diglucoside (SDG) lignan-enriched flaxseed powder LEFP) on body weight, visceral fat, lipid profile, adipokines, and blood pressure were investigated using Sprague-Dawley rats. The animals were divided into three groups (n=8) that were fed either a norm...

  10. Adipokine production in mice fed high-fat diets containing different types of dietary fats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study compared high-fat diets containing different types of dietary fats with various levels of linoleic acid (18:2n6, LA) and a-linolenic acid (18:3n3, ALA) on adipokine production in male C57BL/6 mice. Three-week old mice were fed AIN93G diet (15% of energy from corn oil, control) or ...

  11. Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats.

    PubMed

    Abu, Mohd Nazri; Samat, Suhana; Kamarapani, Norathirah; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani; Hassan, Hamzah Fansuri

    2015-01-01

    The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet. PMID:25821506

  12. Tinospora crispa Ameliorates Insulin Resistance Induced by High Fat Diet in Wistar Rats

    PubMed Central

    Kamarapani, Norathirah; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani; Hassan, Hamzah Fansuri

    2015-01-01

    The antidiabetic properties of Tinospora crispa, a local herb that has been used in traditional Malay medicine and rich in antioxidant, were explored based on obesity-linked insulin resistance condition. Male Wistar rats were randomly divided into four groups, namely, the normal control (NC) which received standard rodent diet, the high fat diet (HFD) which received high fat diet only, the high fat diet treated with T. crispa (HFDTC), and the high fat diet treated with orlistat (HFDO). After sixteen weeks of treatment, blood and organs were harvested for analyses. Results showed that T. crispa significantly (p < 0.05) reduced the body weight (41.14 ± 1.40%), adiposity index serum levels (4.910 ± 0.80%), aspartate aminotransferase (AST: 161 ± 4.71 U/L), alanine aminotransferase (ALT: 100.95 ± 3.10 U/L), total cholesterol (TC: 18.55 ± 0.26 mmol/L), triglycerides (TG: 3.70 ± 0.11 mmol/L), blood glucose (8.50 ± 0.30 mmo/L), resistin (0.74 ± 0.20 ng/mL), and leptin (17.428 ± 1.50 ng/mL) hormones in HFDTC group. The insulin (1.65 ± 0.07 pg/mL) and C-peptide (136.48 pmol/L) hormones were slightly decreased but within normal range. The histological results showed unharmed and intact liver tissues in HFDTC group. As a conclusion, T. crispa ameliorates insulin resistance-associated with obesity in Wistar rats fed with high fat diet. PMID:25821506

  13. Effects of High Fat Feeding on Adipose Tissue Gene Expression in Diabetic Goto-Kakizaki Rats

    PubMed Central

    Xue, Bai; Nie, Jing; Wang, Xi; DuBois, Debra C; Jusko, William J; Almon, Richard R

    2015-01-01

    Development and progression of type 2 diabetes is a complex interaction between genetics and environmental influences. High dietary fat is one environmental factor that is conducive to the development of insulin-resistant diabetes. In the present report, we compare the responses of lean poly-genic, diabetic Goto-Kakizaki (GK) rats to those of control Wistar-Kyoto (WKY) rats fed a high fat diet from weaning to 20 weeks of age. This comparison included a wide array of physiological measurements along with gene expression profiling of abdominal adipose tissue using Affymetrix gene array chips. Animals of both strains fed a high fat diet or a normal diet were sacrificed at 4, 8, 12, 16, and 20 weeks for this comparison. The microarray analysis revealed that the two strains developed different adaptations to increased dietary fat. WKY rats decrease fatty acid synthesis and lipogenic processes whereas GK rats increase lipid elimination. However, on both diets the major differences between the two strains remained essentially the same. Specifically relative to the WKY strain, the GK strain showed lipoatrophy, chronic inflammation, and insulin resistance. PMID:26309393

  14. 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

  15. Gallic acid attenuates high-fat diet fed-streptozotocin-induced insulin resistance via partial agonism of PPARγ in experimental type 2 diabetic rats and enhances glucose uptake through translocation and activation of GLUT4 in PI3K/p-Akt signaling pathway.

    PubMed

    Gandhi, Gopalsamy Rajiv; Jothi, Gnanasekaran; Antony, Poovathumkal James; Balakrishna, Kedike; Paulraj, Michael Gabriel; Ignacimuthu, Savarimuthu; Stalin, Antony; Al-Dhabi, Naif Abdullah

    2014-12-15

    In this study, the therapeutic efficacy of gallic acid from Cyamopsis tetragonoloba (L.) Taub. (Fabaceae) beans was examined against high-fat diet fed-streptozotocin-induced experimental type 2 diabetic rats. Molecular-dockings were done to determine the putative binding modes of gallic acid into the active sites of key insulin-signaling markers. Gallic acid (20 mg/kg) given to high-fat diet fed-streptozotocin-induced rats lowered body weight gain, fasting blood glucose and plasma insulin in diabetic rats. It further restored the alterations of biochemical parameters to near normal levels in diabetic treated rats along with cytoprotective action on pancreatic β-cell. Histology of liver and adipose tissues supported the biochemical findings. Gallic acid significantly enhanced the level of peroxisome proliferator-activated receptor γ (PPARγ) expression in the adipose tissue of treated rat compared to untreated diabetic rat; it also slightly activated PPARγ expressions in the liver and skeletal muscle. Consequently, it improved insulin-dependent glucose transport in adipose tissue through translocation and activation of glucose transporter protein 4 (GLUT4) in phosphatidylinositol 3-kinase (PI3K)/phosphorylated protein kinase B (p-Akt) dependent pathway. Gallic acid docked with PPARγ; it exhibited promising interactions with the GLUT4, glucose transporter protein 1 (GLUT1), PI3K and p-Akt. These findings provided evidence to show that gallic acid could improve adipose tissue insulin sensitivity, modulate adipogenesis, increase adipose glucose uptake and protect β-cells from impairment. Hence it can be used in the management of obesity-associated type 2 diabetes mellitus. PMID:25445038

  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. Effects of a high fat diet on bone of growing rats. Correlations between visceral fat, adiponectin and bone mass density

    PubMed Central

    Lac, Gerard; Cavalie, Helian; Ebal, Edmond; Michaux, Odile

    2008-01-01

    In this study, we investigated some bone parameters (bone mineral content, bone mineral density, skeleton area) in growing rats fed with a high fat diet. Correlations between bone and body composition parameters are reported. Two groups of Wistar male rats (35 days old, body mass 80 ± 6 g) were used. Water and food were given "ad libitum" during 10 weeks. Sixteen rats (L) were given a lipid enriched diet and were compared to 16 rats (S) fed with a standard diet. Body composition and bone parameters were assessed using DXA. Results indicated that L rats had lower body mass, lean body mass; fat mass was not different between the two groups. Bone mineral content, bone mineral density, skeleton area of L rats were lower compared with S rats. Significant correlations were noted between body composition, adiponectin and bone parameters. High fat diet intake during the growing period has deleterious effects on bone parameters in rats. This study confirms in growing rats that a high fat diet is pathogenic, including bone metabolism. PMID:18442361

  18. Sex differences in high fat-induced obesity in rats: Effects of 18-methoxycoronaridine.

    PubMed

    Taraschenko, Olga D; Maisonneuve, Isabelle M; Glick, Stanley D

    2011-06-01

    Evidence suggests that the development of diet-induced obesity in males and females might be mediated by distinct mechanisms, warranting different treatment approaches. In previous studies from this laboratory, a high sucrose diet induced excessive weight gain in female but not in male Sprague-Dawley rats, while weight gain in both sexes was similarly attenuated by the administration of a selective antagonist of α3β4 nicotinic receptors, 18-methoxycoronaridine (18-MC). In the present study, assessment of high-fat induced weight gain, consummatory behavior and biochemical markers of obesity was conducted in male and female Sprague-Dawley rats and the effects of 18-MC treatment were compared in the two sexes. Male rats consuming a high-fat (HF) diet developed excessive weight gain and fat deposition compared to same same-sex controls fed with a low-fat (LF) diet. The development of obesity in these rats was attenuated by repeated administration of 18-MC (20mg/kg, i.p.), which significantly reduced their food intake without altering water intake. In contrast, female rats consuming a HF diet did not become obese and did not respond to 18-MC treatment. These results show that males and females are differentially responsive to HF-induced obesity; the 18-MC data suggest that α3β4 nicotinic receptors may participate in maintaining obesity, possibly becoming a new and important target for anti-obesity agents. PMID:21324333

  19. Dietary krill oil supplementation reduces hepatic steatosis, glycemia, and hypercholesterolemia in high-fat-fed mice.

    PubMed

    Tandy, Sally; Chung, Rosanna W S; Wat, Elaine; Kamili, Alvin; Berge, Kjetil; Griinari, Mikko; Cohn, Jeffrey S

    2009-10-14

    Krill oil (KO) is rich in n-3 fatty acids that are present in phospholipids rather than in triglycerides. In the present study, we investigated the effects of dietary KO on cardiometabolic risk factors in male C57BL/6 mice fed a high-fat diet. Mice (n = 6-10 per group) were fed for 8 weeks either: (1) a nonpurified chow diet (N); (2) a high-fat semipurified diet containing 21 wt % buttermilk + 0.15 wt % cholesterol (HF); (3) HF supplemented with 1.25 wt % KO (HFKO1.25); (4) HF with 2.5 wt % KO (HFKO2.5); or (5) HF with 5 wt % KO (HFKO5.0). Dietary KO supplementation caused a significant reduction in liver wt (i.e., hepatomegaly) and total liver fat (i.e., hepatic steatosis), due to a dose-dependent reduction in hepatic triglyceride (mean +/- SEM: 35 +/- 6, 47 +/- 4, and 51 +/- 5% for HFKO1.25, -2.5, and -5.0 vs HF, respectively, P < 0.001) and cholesterol (55 +/- 5, 66 +/- 3, and 71 +/- 3%, P < 0.001). Serum cholesterol levels were reduced by 20 +/- 3, 29 +/- 4, and 29 +/- 5%, and blood glucose was reduced by 36 +/- 5, 34 +/- 6, and 42 +/- 6%, respectively. Serum adiponectin was increased in KO-fed animals (HF vs HFKO5.0: 5.0 +/- 0.2 vs 7.5 +/- 0.6 microg/mL, P < 0.01). These results demonstrate that dietary KO is effective in improving metabolic parameters in mice fed a high-fat diet, suggesting that KO may be of therapeutic value in patients with the metabolic syndrome and/or nonalcoholic fatty liver disease. PMID:19761211

  20. Preventive effects of bitter melon (Momordica charantia) against insulin resistance and diabetes are associated with the inhibition of NF-κB and JNK pathways in high-fat-fed OLETF rats.

    PubMed

    Yang, Soo Jin; Choi, Jung Mook; Park, Se Eun; Rhee, Eun Jung; Lee, Won Young; Oh, Ki Won; Park, Sung Woo; Park, Cheol-Young

    2015-03-01

    Bitter melon (BM; Momordica charantia) has been used as a treatment method for various diseases including cancer and diabetes. The objective of this study was to investigate whether BM has preventive effects against insulin resistance and diabetes and to identify the underlying mechanism by which BM ameliorates insulin resistance in obese and diabetic rats. The rats were separated into three groups as follows: (a) high-fat (HF) diet control, (b) HF diet and 1% BM and (c) HF diet and 3% BM. After 6 weeks of assigned treatments, body weight and food intake were not altered by BM administration. Bitter melon treatment significantly improved glucose tolerance and insulin sensitivity. The levels of proinflammatory cytokines were significantly down-regulated in liver, muscle and epididymal fats from BM-treated rats. The activation of nuclear factor-κB (NF-κB) in the liver and muscle was decreased by BM compared with HF controls. The 3% BM supplementation significantly increased the levels of phospho-insulin receptor substrate-1 (Tyr612) and phospho-Akt (Ser473). It also significantly decreased the levels of phospho-NF-κB (p65) (Ser536) and phospho-c-Jun N-terminal kinase (JNK) (Thr183/Tyr185) in liver, muscle and epididymal fats. The findings of this study indicate that BM exerted preventive effects against insulin resistance and diabetes through the modulation of NF-κB and JNK pathways. Therefore, BM may be useful in the prevention of insulin resistance and diabetes. PMID:25488547

  1. Exercise Increases and Browns Muscle Lipid in High-Fat Diet-Fed Mice

    PubMed Central

    Morton, Tiffany L.; Galior, Kornelia; McGrath, Cody; Wu, Xin; Uzer, Gunes; Uzer, Guniz Bas; Sen, Buer; Xie, Zhihui; Tyson, David; Rubin, Janet; Styner, Maya

    2016-01-01

    Muscle lipid increases with high-fat feeding and diabetes. In trained athletes, increased muscle lipid is not associated with insulin resistance, a phenomenon known as the athlete’s paradox. To understand if exercise altered the phenotype of muscle lipid, female C57BL/6 mice fed CTL or high-fat diet (HFD for 6 or 18 weeks) were further divided into sedentary or exercising groups (CTL-E or HFD-E) with voluntary access to running wheels for the last 6 weeks of experiments, running 6 h/night. Diet did not affect running time or distance. HFD mice weighed more than CTL after 18 weeks (p < 0.01). Quadriceps muscle TG was increased in running animals and in sedentary mice fed HFD for 18 weeks (p < 0.05). In exercised animals, markers of fat, Plin1, aP2, FSP27, and Fasn, were increased significantly in HFD groups. Ucp1 and Pgc1a, markers for brown fat, increased with exercise in the setting of high fat feeding. Fndc5, which encodes irisin, and CytC were sensitive to exercise regardless of diet. Plin5 was increased with HFD and unaffected by exercise; the respiratory exchange ratio was 15% lower in the 18-week HFD group compared with CTL (p < 0.001) and 10% lower in 18 weeks HFD-E compared with CTL-E (p < 0.001). Increased Ucp1 and Pgc1a in exercised muscle of running mice suggests that a beige/brown fat phenotype develops, which differs from the fat phenotype that induces insulin resistance in high fat feeding. This suggests that increased muscle lipid may develop a “brown” phenotype in the setting of endurance exercise training, a shift that is further promoted by HFD. PMID:27445983

  2. Swimming improves high-fat induced insulin resistance by regulating lipid and energy metabolism and the insulin pathway in rats.

    PubMed

    Song, An; Wang, Chao; Ren, Luping; Zhao, Jiajun

    2014-06-01

    In this study, we aimed to determine the preventive and therapeutic effects of swimming on insulin resistance in high-fat-fed rats. Sprague-Dawley rats were divided into 4 groups and fed for 8 weeks as follows: i) the control (Con) group fed a control diet; ii) the high-fat (HF) group fed a high-fat diet; iii) the treatment (ST) group fed a high-fat diet and trained with swimming from the 4th week; and iv) the prevention (SP) group fed a high-fat diet and trained with swimming from the 1st week of the experiment. A hyperinsulinemic-euglycemic clamp was used to evaluate the insulin sensitivity of the rats. The ultrastructure of the liver cells was observed by electron microscopy. Hepatic lipid accumulation was observed by Oil Red O staining. Quantitative RT-PCR and western blot analysis were performed to detect the expression of proteins related to lipid metabolism, energy metabolism and insulin signaling transduction. After 8 weeks of feeding, compared with the Con group, the glucose infusion rate (GIR) was significantly decreased; a significant lipid accumulation was observed in the liver, while the ultrastructure of the liver cells was damaged in the HF group. Proteins related to lipid metabolism in the liver and skeletal muscle, including FAT and FABP were upregulated, while CPT1 and PPAR levels were downregulated in the HF group. The levels of the energy-metabolism-related molecules, AMPKα2, PGC1α, PGC1β and MFN2 were downregulated in skeletal muscle in the HF group. The expression levels of insulin signaling transduction molecules, INSR, IRS1, PI3K/p85, AKT2 and GLUT4, as well as the phosphorylation levels of INSR, IRS1, PI3K/p85 and AKT2 were lower in skeletal muscles in the HF rats. Compared with HF group, the GIR levels were significantly increased in the ST and SP groups. Lipid accumulation and damage to the ultrastructure of the liver cells were improved in both groups. The expression of molecules related to lipid metabolism in the liver and skeletal

  3. Detrimental effects of a high fat/high cholesterol diet on memory and hippocampal markers in aged rats.

    PubMed

    Ledreux, Aurélie; Wang, Xiuzhe; Schultzberg, Marianne; Granholm, Ann-Charlotte; Freeman, Linnea R

    2016-10-01

    High fat diets have detrimental effects on cognitive performance, and can increase oxidative stress and inflammation in the brain. The aging brain provides a vulnerable environment to which a high fat diet could cause more damage. We investigated the effects of a high fat/high cholesterol (HFHC) diet on cognitive performance, neuroinflammation markers, and phosphorylated Tau (p-Tau) pathological markers in the hippocampus of Young (4-month old) versus Aged (14-month old) male rats. Young and Aged male Fisher 344 rats were fed a HFHC diet or a normal control diet for 6 months. All animals underwent cognitive testing for 12days in a water radial arm maze to assess spatial and working reference memory. Hippocampal tissue was analyzed by immunohistochemistry for structural changes and inflammation, and Western blot analysis. Young and Aged rats fed the HFHC diet exhibited worse performance on a spatial working memory task. They also exhibited significant reduction of NeuN and calbindin-D28k immunoreactivity as well as an increased activation of microglial cells in the hippocampal formation. Western blot analysis of the hippocampus showed higher levels of p-Tau S202/T205 and T231 in Aged HFHC rats, suggesting abnormal phosphorylation of Tau protein following the HFHC diet exposure. This work demonstrates HFHC diet-induced cognitive impairment with aging and a link between high fat diet consumption and pathological markers of Alzheimer's disease. PMID:27343935

  4. Increased Aβ pathology in aged Tg2576 mice born to mothers fed a high fat diet

    PubMed Central

    Nizari, Shereen; Carare, Roxana O.; Hawkes, Cheryl A.

    2016-01-01

    Maternal obesity is associated with increased risk of developing diabetes, obesity and premature death in adult offspring. Mid-life diabetes, hypertension and hypercholesterolaemia are risk factors for the development of sporadic Alzheimer’s disease (AD). A key pathogenic feature of AD is the accumulation of β-amyloid (Aβ) in the brain. The purpose of this study was to investigate the effect of high fat diet feeding during early life on Aβ pathology in the Tg2576 mouse model of AD. Female mice were fed a standard (C) or high fat (HF) diet before mating and during gestation and lactation. At weaning, male offspring were fed a C diet. Significantly higher levels of guanidine-soluble Aβ and plaque loads were observed in the hippocampi of 11-month old Tg2576 mice born to mothers fed a HF diet. Changes in the extracellular matrix led to increased retention of Aβ within the parenchyma. These data support a role for maternal and gestational health on the health of the aged brain and pathologies associated with AD and may provide a novel target for both the prevention and treatment of AD. PMID:26911528

  5. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice

    PubMed Central

    Harada, Naoki; Hanaoka, Ryo; Horiuchi, Hiroko; Kitakaze, Tomoya; Mitani, Takakazu; Inui, Hiroshi; Yamaji, Ryoichi

    2016-01-01

    Late-onset hypogonadism (i.e. androgen deficiency) raises the risk for abdominal obesity in men. The mechanism for this obesity is unclear. Here, we demonstrated that hypogonadism after castration caused abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with antibiotics that disrupt the intestinal microflora. In HFD-fed mice, castration increased feed efficiency and decreased fecal weight per food intake. Castration also induced in an increase of visceral fat mass only in the absence of antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by castration irrespective of antibiotics. Castration reduced the expression in the mesenteric fat of both adipose triglyceride lipase and hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of antibiotics. Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting blood glucose levels, and increased liver triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that androgen (e.g. testosterone) deficiency can alter the intestinal microbiome and induce abdominal obesity in a diet-dependent manner. PMID:26961573

  6. Castration influences intestinal microflora and induces abdominal obesity in high-fat diet-fed mice.

    PubMed

    Harada, Naoki; Hanaoka, Ryo; Horiuchi, Hiroko; Kitakaze, Tomoya; Mitani, Takakazu; Inui, Hiroshi; Yamaji, Ryoichi

    2016-01-01

    Late-onset hypogonadism (i.e. androgen deficiency) raises the risk for abdominal obesity in men. The mechanism for this obesity is unclear. Here, we demonstrated that hypogonadism after castration caused abdominal obesity in high-fat diet (HFD)-fed, but not in standard diet (SD)-fed, C57BL/6J mice. Furthermore, the phenotype was not induced in mice treated with antibiotics that disrupt the intestinal microflora. In HFD-fed mice, castration increased feed efficiency and decreased fecal weight per food intake. Castration also induced in an increase of visceral fat mass only in the absence of antibiotics in HFD-fed mice, whereas subcutaneous fat mass was increased by castration irrespective of antibiotics. Castration reduced the expression in the mesenteric fat of both adipose triglyceride lipase and hormone-sensitive lipase in HFD-fed mice, which was not observed in the presence of antibiotics. Castration decreased thigh muscle (i.e. quadriceps and hamstrings) mass, elevated fasting blood glucose levels, and increased liver triglyceride levels in a HFD-dependent manner, whereas these changes were not observed in castrated mice treated with antibiotics. The Firmicutes/Bacteroidetes ratio and Lactobacillus species increased in the feces of HFD-fed castrated mice. These results show that androgen (e.g. testosterone) deficiency can alter the intestinal microbiome and induce abdominal obesity in a diet-dependent manner. PMID:26961573

  7. Effect of high fat, fiber and caloric restriction on rat mammary tumorigenesis

    SciTech Connect

    Magrane, D.; Van Sant, J.; Butler, B.

    1986-03-05

    Female rats given 7,12-Dimethylbenz(a)anthracene (DMBA) were placed on diets of control fat (CF-4.5%) or high fat (HF-20%) with either control fiber (6%) or high fiber (FB-12%). A 60% reduction in the CF diet was used to study the effects of caloric restriction on tumorigenesis. Results showed that HF diets had a shorter latency period than CF rats. The respective average number of tumors per rat and tumor volume were 7.3 +/- 1.3 and 23694 mm/sup 2/ for rats on a HF diet and 5.1+/-1.1 and 9144 mm/sup 3/ for CF rats. Addition of high fiber to the diets reduced the tumor incidence from 95% to 70% in the CF group but did not reduce the incidence in HF group. Although tumor number was reduced to 3.7+/-1.5 in CF+FB rats, the tumor volumes were not reduced (8950 mm/sup 3/). Rats fed HF+FB did not have fewer tumors (7.0+/-1.1), but did show a 53% reduction in tumor load. The estrogen dependent enzyme glucose-6-phosphate dehydrogenase was not affected by dietary levels of fat, which suggests that the promotional effects of fat may not be through estrogen stimulation. None of the caloric restricted rats had tumors 12 weeks post-DMBA. These restricted rats all had significantly elevated levels of serum corticosterone.

  8. 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

  9. Bromocriptine increased operant responding for high fat food but decreased chow intake in both obesity-prone and resistant rats

    SciTech Connect

    Thanos, P.K.; Wang, G.; Thanos, P.K.; Cho, J. Kim, R.; Michaelides, M.; Primeaux, S.; Bray, G.; Wang, G.-J.; Volkow, N.D.

    2010-10-27

    Dopamine (DA) and DAD{sub 2} receptors (D2R) have been implicated in obesity and are thought to be involved in the rewarding properties of food. Osborne-Mendel (OM) rats are susceptible to diet induced obesity (DIO) while S5B/P (S5B) rats are resistant when given a high-fat diet. Here we hypothesized that the two strains would differ in high-fat food self-administration (FSA) and that the D2R agonist bromocriptine (BC) would differently affect their behavior. Ad-libitum fed OM and S5B/P rats were tested in a FSA operant chamber and were trained to lever press for high-fat food pellets under a fixed-ratio (FR1) and a progressive ratio (PR) schedule. After sixteen days of PR sessions, rats were treated with three different doses of BC (1, 10 and 20 mg/kg). No significant differences were found between the two strains in the number of active lever presses. BC treatment (10 mg/kg and 20 mg/kg) increased the number of active lever presses (10 mg/kg having the strongest effect) whereas it decreased rat chow intake in the home cage with equivalent effects in both strains. These effects were not observed on the day of BC administration but on the day following its administration. Our results suggest that these two strains have similar motivation for procuring high fat food using this paradigm. BC increased operant responding for high-fat pellets but decreased chow intake in both strains, suggesting that D2R stimulation may have enhanced the motivational drive to procure the fatty food while correspondingly decreasing the intake of regular food. These findings suggest that susceptibility to dietary obesity (prior to the onset of obesity) may not affect operant motivation for a palatable high fat food and that differential susceptibility to obesity may be related to differential sensitivity to D2R stimulation.

  10. Three dissimilar high fat diets differentially regulate lipid and glucose metabolism in obesity-resistant Slc:Wistar/ST rats.

    PubMed

    Hashimoto, Yoko; Yamada, Kazuyo; Tsushima, Hiromi; Miyazawa, Daisuke; Mori, Mayumi; Nishio, Koji; Ohkubo, Takeshi; Hibino, Hidehiko; Ohara, Naoki; Okuyama, Harumi

    2013-08-01

    Epidemiologic and ecologic studies suggest that dietary fat plays an important role in the development of obesity. Certain Wistar rat strains do not become obese when fed high-fat diets unlike others. In a preliminary study, we confirmed that Slc:Wistar/ST rats did not become obese when fed high-fat diets. The mechanisms governing the response of hepatic lipid-metabolizing enzymes to large quantities of dietary lipids consumed by obesity-resistant animals are unknown. The aim of the present study is to examine how obesity-resistant animals metabolize various types of high-fat diets and why they do not become obese. For this purpose, male Slc:Wistar/ST rats were fed a control low-fat diet (LS) or a high-fat diet containing fish oil (HF), soybean oil (HS), or lard (HL) for 4 weeks. We observed their phenotypes and determined lipid profiles in plasma and liver as well as mRNA expression levels in liver of genes related to lipid and glucose metabolism using DNA microarray and quantitative reverse transcriptase polymerase chain analyses. The body weights of all dietary groups were similar due to isocaloric intakes, whereas the weight of white adipose tissues in the LS group was significantly lower. The HF diet lowered plasma lipid levels by accelerated lipolysis in the peroxisomes and suppressed levels of very-low-density lipoprotein (VLDL) secretion. The HS diet promoted hepatic lipid accumulation by suppressed lipolysis in the peroxisomes and normal levels of VLDL secretion. The lipid profiles of rats fed the LS or HL diet were similar. The HL diet accelerated lipid and glucose metabolism. PMID:23807365

  11. Dietary cocoa reduces metabolic endotoxemia and adipose tissue inflammation in high-fat fed mice.

    PubMed

    Gu, Yeyi; Yu, Shan; Park, Jong Yung; Harvatine, Kevin; Lambert, Joshua D

    2014-04-01

    In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6 J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 weeks. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40-60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cyclooxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia. PMID:24561154

  12. Dietary Cocoa Reduces Metabolic Endotoxemia and Adipose Tissue Inflammation in High-Fat Fed Mice

    PubMed Central

    Gu, Yeyi; Yu, Shan; Park, Jong Yung; Harvatine, Kevin; Lambert, Joshua D.

    2014-01-01

    In diet-induced obesity, adipose tissue (AT) is in a chronic state of inflammation predisposing the development of metabolic syndrome. Cocoa (Theobroma cacao) is a polyphenol-rich food with putative anti-inflammatory activities. Here, we examined the impact and underlying mechanisms of action of cocoa on AT inflammation in high fat-fed mice. In the present study, male C57BL/6J mice were fed a high fat diet (HF), a HF diet with 8% (w/w) unsweetened cocoa powder (HFC), or a low-fat diet (LF) for 18 wk. Cocoa supplementation decreased AT mRNA levels of tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and EGF-like module-containing mucin-like hormone receptor-like 1 by 40 – 60% compared to HF group, and this was accompanied by decreased nuclear protein levels of nuclear factor-κB. Cocoa treatment reduced the levels of arachidonic acid in the AT by 33% compared to HF controls. Moreover, cocoa treatment also reduced protein levels of the eicosanoid-generating enzymes, adipose-specific phospholipase A2 and cycloxygenase-2 by 53% and 55%, respectively, compared to HF-fed mice. Finally, cocoa treatment ameliorated metabolic endotoxemia (40% reduction in plasma endotoxin) and improved gut barrier function (as measured by increased plasma levels of glucagon-like peptide-2). In conclusion, the present study has shown for the first time that long-term cocoa supplementation can reduce AT inflammation in part by modulating eicosanoid metabolism and metabolic endotoxemia. PMID:24561154

  13. Impaired Lipid and Glucose Homeostasis in Hexabromocyclododecane-Exposed Mice Fed a High-Fat Diet

    PubMed Central

    Koike, Eiko; Win-Shwe, Tin-Tin; Yamamoto, Megumi; Takano, Hirohisa

    2014-01-01

    Background: Hexabromocyclododecane (HBCD) is an additive flame retardant used in the textile industry and in polystyrene foam manufacturing. Because of its lipophilicity and persistency, HBCD accumulates in adipose tissue and thus has the potential of causing metabolic disorders through disruption of lipid and glucose homeostasis. However, the association between HBCD and obesity remains unclear. Objectives: We investigated whether exposure to HBCD contributes to initiation and progression of obesity and related metabolic dysfunction in mice fed a normal diet (ND) or a high-fat diet (HFD). Methods: Male C57BL/6J mice were fed a HFD (62.2 kcal% fat) or a ND and treated orally with HBCD (0, 1.75, 35, or 700 μg/kg body weight) weekly from 6 to 20 weeks of age. We examined body weight, liver weight, blood biochemistry, histopathological changes, and gene expression profiles in the liver and adipose tissue. Results: In HFD-fed mice, body and liver weight were markedly increased in mice treated with the high (700 μg/kg) and medium (35 μg/kg) doses of HBCD compared with vehicle. This effect was more prominent in the high-dose group. These increases were paralleled by increases in random blood glucose and insulin levels and enhancement of microvesicular steatosis and macrophage accumulation in adipose tissue. HBCD-treated HFD-fed mice also had increased mRNA levels of Pparg (peroxisome proliferator-activated receptor-γ) in the liver and decreased mRNA levels of Glut4 (glucose transporter 4) in adipose tissue compared with vehicle-treated HFD-fed mice. Conclusions: Our findings suggest that HBCD may contribute to enhancement of diet-induced body weight gain and metabolic dysfunction through disruption of lipid and glucose homeostasis, resulting in accelerated progression of obesity. Citation: Yanagisawa R, Koike E, Win-Shwe TT, Yamamoto M, Takano H. 2014. Impaired lipid and glucose homeostasis in hexabromocyclododecane-exposed mice fed a high-fat diet. Environ Health

  14. Decreased beige adipocyte number and mitochondrial respiration coincide with increased histone methyl transferase (G9a) and reduced FGF21 gene expression in Sprague Dawley rats fed prenatal low protein and postnatal high fat

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have shown that protein malnutrition during fetal growth followed by postnatal high-fat diets results in a rapid increase in subcutaneous adipose tissue mass in the offspring contributing to development of obesity and insulin resistance. Recent studies have shown that the absence of a key transcr...

  15. Glycogen repletion and exercise endurance in rats adapted to a high fat diet.

    PubMed

    Conlee, R K; Hammer, R L; Winder, W W; Bracken, M L; Nelson, A G; Barnett, D W

    1990-03-01

    It is well accepted that exercise endurance is directly related to the amount of carbohydrate stored in muscle and that a low carbohydrate diet reduces glycogen storage and exercise performance. However, more recent evidence has shown that when the organism adapts to a high fat diet endurance is not hindered. The present study was designed to test that claim and to further determine if animals adapted to a high fat diet could recover from exhausting exercise and exercise again in spite of carbohydrate deprivation. Fat-adapted (3 to 4 weeks, 78% fat, 1% carbohydrates) rats (FAT) ran (28 m/min, 10% grade) as long as carbohydrate-fed (69% carbohydrates) animals (CHO) (115 v 109 minutes, respectively) in spite of lower pre-exercise glycogen levels in red vastus muscle (36 v 54 mumols/g) and liver (164 v 313 mumols/g) in the FAT group. Following 72 hours of recovery on the FAT diet, glycogen in muscle had replenished to 42 mumols/g (v 52 for CHO) and liver glycogen to 238 mumols/g (v 335 for CHO). The animals were run to exhaustion a second time and run times were again similar (122 v 132 minutes FAT v CHO). When diets were switched after run 1, FAT-adapted animals, which received carbohydrates for 72 hours, restored muscle and liver glycogen (48 and 343 mumols/g, respectively) and then ran longer (144 minutes) than CHO-adapted animals (104 minutes) that ate fat for 72 hours and that had reduced glycogen repletion. We conclude that, in contrast to the classic CHO loading studies in humans that involved acute (72 hours) fat feedings and subsequently reduced endurance, rats adapted to a high fat diet do not have a decrease in endurance capacity even after recovery from previous exhausting work bouts. Part of this adaptation may involve the increased storage and utilization of intramuscular triglycerides (TG) as observed in the present experiment. PMID:2308519

  16. 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

  17. Antihyperlipidemic effects of Sesamum indicum L. in rabbits fed a high-fat diet.

    PubMed

    Asgary, Sedigheh; Rafieian-Kopaei, Mahmoud; Najafi, Somayeh; Heidarian, Esfandiar; Sahebkar, Amirhossein

    2013-01-01

    The present study aimed to investigate the anti-hyperlipidemic effects of sesame in a high-fat fed rabbit model. Animals were randomly divided into four groups of eight animals each for 60 days as follows: normal diet, hypercholesterolemic diet (1% cholesterol), hypercholesterolemic diet (1% cholesterol) + sesame seed (10%), and hypercholesterolemic diet (1% cholesterol) + sesame oil (5%). Serum concentrations of total cholesterol, LDL-C, HDL-C, triglycerides, apoA and apoB, SGOT, SGPT, glucose and insulin were measured at the end of supplementation period in all studied groups. Hypercholesterolemic feeding resulted in a significant elevation of TC, TG, LDL-C, HDL-C, SGOT and SGPT as compared to the normocholesterolemic diet group (P < 0.05). Supplementation with sesame seed did not cause any significant alteration in lipid profile parameters, apolipoproteins, hepatic transaminases, glucose and insulin as compared to the hypercholesterolemic diet group (P > 0.05). In contrast, rabbits supplemented with sesame oil were found to have lower circulating concentrations of TC, LDL-C, HDL-C, SGOT and SGPT (P < 0.05), whilst concentrations of TG, apoA, apoB, insulin and glucose remained unaltered compared to the hypercholesterolemic diet group (P > 0.05). Supplementation with sesame oil, but not sesame seed, can ameliorate serum levels of lipids and hepatic enzymes in rabbits under a high-fat diet. PMID:24082850

  18. Novel mitochondrial complex I inhibitors restore glucose-handling abilities of high-fat fed mice.

    PubMed

    Martin, Darren S D; Leonard, Siobhán; Devine, Robert; Redondo, Clara; Kinsella, Gemma K; Breen, Conor J; McEneaney, Victoria; Rooney, Mary F; Munsey, Tim S; Porter, Richard K; Sivaprasadarao, Asipu; Stephens, John C; Findlay, John B C

    2016-04-01

    Metformin is the main drug of choice for treating type 2 diabetes, yet the therapeutic regimens and side effects of the compound are all undesirable and can lead to reduced compliance. The aim of this study was to elucidate the mechanism of action of two novel compounds which improved glucose handling and weight gain in mice on a high-fat diet. Wildtype C57Bl/6 male mice were fed on a high-fat diet and treated with novel, anti-diabetic compounds. Both compounds restored the glucose handling ability of these mice. At a cellular level, these compounds achieve this by inhibiting complex I activity in mitochondria, leading to AMP-activated protein kinase activation and subsequent increased glucose uptake by the cells, as measured in the mouse C2C12 muscle cell line. Based on the inhibition of NADH dehydrogenase (IC50 27µmolL(-1)), one of these compounds is close to a thousand fold more potent than metformin. There are no indications of off target effects. The compounds have the potential to have a greater anti-diabetic effect at a lower dose than metformin and may represent a new anti-diabetic compound class. The mechanism of action appears not to be as an insulin sensitizer but rather as an insulin substitute. PMID:26759391

  19. 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

  20. Prenatal nicotine exposure induces poor articular cartilage quality in female adult offspring fed a high-fat diet and the intrauterine programming mechanisms.

    PubMed

    Tie, Kai; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2016-04-01

    Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism. PMID:26769161

  1. Glucocorticoids inhibited hypothalamic target of rapamycin in high fat diet-fed chicks.

    PubMed

    Liu, L; Wang, X; Jiao, H; Zhao, J; Lin, H

    2015-09-01

    The present study was conducted with broiler chicks exposed to dexamethasone (DEX) to explore its effects on hypothalamic target of rapamycin (TOR) signaling and regulating appetite in diets containing different energy levels. At 5 d age, 48 chicks were divided into one of 4 groups: high-fat diet (HFD) or low-fat diet (LFD) and intracerebroventricular (ICV) injected with either dexamethasone (DEX; 4 μg/2 μL) or saline at 10 d age. The results showed that DEX significantly inhibited gene expression of cocaine- and amphetamine-regulated transcripts (CART), melanocortin receptor 4 (MC4R), and corticotropin-releasing hormone (CRH), and inhibited the protein level of the phospho-TOR compared with the control in HFD-fed chicks (P<0.05) but not in LFD-fed chicks (P>0.05). After DEX treatment, hypothalamic agouti-related peptide levels were decreased significantly in HFD-fed chicks (P<0.05) but not in LFD-fed chicks (P>0.05). Compared to the control, DEX-treated chicks did not present any significant changes in neuropeptide Y gene expression with either HFD or LFD (P>0.05), but pro-opiomelanocortin levels were depressed by ICV DEX treatment with both diets (P<0.05). In conclusion, glucocorticoids (GC) downregulated hypothalamic gene expression of CART, CRH, and MC4R in HFD-fed chicks, suggesting that the regulatory network formed by these genes is associated with the appetite control during stress. The TOR pathway may be involved in the regulation of GC on appetite-related genes. PMID:26188033

  2. Dietary cocoa ameliorates obesity-related inflammation in high fat-fed mice

    PubMed Central

    Gu, Yeyi; Yu, Shan

    2013-01-01

    Purpose To investigate the effect of cocoa powder supplementation on obesity-related inflammation in high fat (HF)-fed obese mice. Methods Male C57BL/6J (n = 126) were fed with either low-fat (LF, 10 % kcal from fat) or HF (60 % kcal from fat) diet for 18 weeks. After 8 weeks, mice from HF group were randomized to HF diet or HF diet supplemented with 8 % cocoa powder (HF–HFC group) for 10 weeks. Blood and tissue samples were collected for biochemical analyses. Results Cocoa powder supplementation significantly reduced the rate of body weight gain (15.8 %) and increased fecal lipid content (55.2 %) compared to HF-fed control mice. Further, cocoa supplementation attenuated insulin resistance, as indicated by improved HOMA-IR, and reduced the severity of obesity-related fatty liver disease (decreased plasma alanine aminotransferase and liver triglyceride) compared to HF group. Cocoa supplementation also significantly decreased plasma levels of the pro-inflammatory mediators interleukin-6 (IL-6, 30.4 %), monocyte chemoattractant protein-1 (MCP-1, 25.2 %), and increased adiponectin (33.7 %) compared to HF-fed mice. Expression of pro-inflammatory genes (Il6, Il12b, Nos2, and Emr1) in the stromal vascular fraction (SVF) of the epididymal white adipose tissue (WAT) was significantly reduced (37–56 %) in the cocoa-supplemented mice. Conclusions Dietary supplementation with cocoa ameliorates obesity-related inflammation, insulin resistance, and fatty liver disease in HF-fed obese mice, principally through the down-regulation of pro-inflammatory gene expression in WAT. These effects appear to be mediated in part by a modulation of dietary fat absorption and inhibition of macrophage infiltration in WAT. PMID:23494741

  3. 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

  4. 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

  5. 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

  6. Hypolipidemic effects of chitosan nanoparticles in hyperlipidemia rats induced by high fat diet.

    PubMed

    Zhang, Hong-liang; Tao, Yi; Guo, Jiao; Hu, Yin-ming; Su, Zheng-quan

    2011-04-01

    The aim of this study was to investigate the hypolipidemic effects of chitosan nanoparticles(CTS-NP) preparations with ionotropic gelation, rotary evaporation, and spray-drying technique. Male SD (Sprague-Dawley) rats were separated into five groups, a normal diet group, a high fat emulsions group, a CTS control group and CTS-NP groups treated with two different doses of CTS-NP. The nanoparticles were spherical in shape and had a smooth surface. The size range of the nanoparticles was between 500 and 1000 nm. The apparent serum lipid and plasma viscosity in CTS-NP group was significantly lower than that in the CTS group, as well as the serum superoxide dismutate (SOD) levels was increased. Although no significant difference in adipose tissue was found among the groups, the rats fed on CTS-NP had lower relative liver weight and body weight when compared with those fed on normal diet. This study was the first report of the effects of CTS-NP in the hyperlipidemia rats, and suggests that the CTS-NP could be used for the treatment of hyperlipidemia. PMID:21215349

  7. High-fat diet caused widespread epigenomic differences on hepatic methylome in rat.

    PubMed

    Zhang, Yukun; Wang, Huan; Zhou, Dan; Moody, Laura; Lezmi, Stéphane; Chen, Hong; Pan, Yuan-Xiang

    2015-10-01

    A high-fat (HF) diet is associated with progression of liver diseases. To illustrate genome-wide landscape of DNA methylation in liver of rats fed either a control or HF diet, two enrichment-based methods, namely methyl-DNA immunoprecipitation assay with high-throughput sequencing (MeDIP-seq) and methylation-sensitive restriction enzyme sequencing (MRE-seq), were performed in our study. Rats fed with the HF diet exhibited an increased body weight and liver fat accumulation compared with that of the control group when they were 12 wk of age. Genome-wide analysis of differentially methylated regions (DMRs) showed that 12,494 DMRs induced by HF diet were hypomethylated and 6,404 were hypermethylated. DMRs with gene annotations [differentially methylated genes (DMGs)] were further analyzed to show gene-specific methylation profile. There were 88, 2,680, and 95 hypomethylated DMGs identified with changes in DNA methylation in the promoter, intragenic and downstream regions, respectively, compared with fewer hypermethylated DMGs (45, 1,623, and 50 in the respective regions). Some of these genes also contained an ACGT cis-acting motif whose DNA methylation status may affect gene expression. Pathway analysis showed that these DMGs were involved in critical hepatic signaling networks related to hepatic development. Therefore, HF diet had global impacts on DNA methylation profile in the liver of rats, leading to differential expression of genes in hepatic pathways that may involve in functional changes in liver development. PMID:26199400

  8. High fat diet and body weight have different effects on cannabinoid CB1 receptor expression in rat nodose ganglia

    PubMed Central

    Cluny, N.L.; Baraboi, E.D.; Mackie, K; Burdyga, G.; Richard, D.; Dockray, G.J.; Sharkey, K.A.

    2013-01-01

    Energy balance is regulated, in part, by orexigenic signaling pathways of the vagus nerve. Fasting-induced modifications in the expression of orexigenic signaling systems have been observed in vagal afferents of lean animals. Altered basal cannabinoid (CB)1 receptor expression in the nodose ganglia in obesity has been reported. Whether altered body weight or a high fat diet modifies independent or additive changes in CB1 expression is unknown. We investigated the expression of CB1 and orexin 1 receptor (OX-1R) in nodose ganglia of rats fed ad libitum or food deprived (24h), maintained on low or high fat diets (HFD), with differing body weights. Male Wistar rats were fed chow or HFD (diet-induced obese: DIO or diet-resistant: DR) or were body weight matched to the DR group but fed chow (wmDR). CB1 and OX-1R immunoreactivity were investigated and CB1 mRNA density was determined using in situ hybridization. CB1 immunoreactivity was measured in fasted rats after sulfated cholecystokinin octapeptide (CCK8s) administration. In chow rats, fasting did not modify the level of CB1 mRNA. More CB1 immunoreactive cells were measured in fed DIO, DR and wmDR rats than chow rats; levels increased after fasting in chow and wmDR rats but not in DIO or DR rats. In HFD fasted rats CCK8s did not reduce CB1 immunoreactivity. OX-1R immunoreactivity was modified by fasting only in DR rats. These data suggest that body weight contributes to the proportion of neurons expressing CB1 immunoreactivity in the nodose ganglion, while HFD blunts fasting-induced increases, and CCK-induced suppression of, CB1-immunoreactivity. PMID:24145047

  9. 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

  10. Effects of puerarin on lipid accumulation and metabolism in high-fat diet-fed mice.

    PubMed

    Zheng, Guodong; Lin, Lezhen; Zhong, Shusheng; Zhang, Qingfeng; Li, Dongming

    2015-01-01

    In order to investigate the mechanisms by which puerarin from kudzu root extract regulates lipid metabolism, fifty mice were randomly assigned to five groups: normal diet, high-fat diet (HFD), and HFD containing 0.2%, 0.4% or 0.8% puerarin for 12 weeks. Body weight, intraperitioneal adipose tissue (IPAT) weight, serum biochemical parameters, and hepatic and feces lipids were measured. Activity and mRNA and protein expressions of hepatic lipid metabolism-related enzymes were analyzed. Compared with HFD, 0.4% and 0.8% puerarin significantly decreased body and IPAT weight. There was a significant decrease in the serum and hepatic concentrations of total cholesterol, triglycerides and leptin in mice fed the 0.4% and 0.8% puerarin diets compared with HFD. Fatty acid synthase activity was suppressed in mice fed the 0.4% and 0.8% puerarin diets, while the activities of AMP-activated protein kinase (AMPK), carnitine acyltransferase (CAT) and hormone-sensitive lipase (HSL) were increased. mRNA expression of peroxisome proliferator-activated receptor γ 2 (PPARγ 2) was down-regulated in liver of mice fed the 0.8% diet compared with HFD, while mRNA expression of CAT and HSL was considerably up-regulated by 0.4% and 0.8% puerarin diets. The protein expression of PPARγ2 in liver was decreased and those of p-AMPK, HSL and p-HSL were increased in mice fed 0.4% and 0.8% puerarin diets. These results suggest that > 0.4% puerarin influenced the activity, mRNA and protein levels of hepatic lipid metabolism-related enzymes, decreasing serum and liver lipids, body weight gain and fat accumulation. Puerarin might be beneficial to prevent lifestyle-related diseases. PMID:25822741

  11. Thermoneutrality decreases thermogenic program and promotes adiposity in high-fat diet-fed mice.

    PubMed

    Cui, Xin; Nguyen, Ngoc Ly T; Zarebidaki, Eleen; Cao, Qiang; Li, Fenfen; Zha, Lin; Bartness, Timothy; Shi, Hang; Xue, Bingzhong

    2016-05-01

    Brown/beige adipocytes are therapeutic targets to combat obesity due to their abilities to dissipate energy through adaptive thermogenesis. Most studies investigating induction of brown/beige adipocytes were conducted in cold condition (e.g., 4°C); much is unknown about how the thermogenic program of brown/beige adipocytes is regulated in thermoneutral condition (e.g., 30°C), which is within the thermal comfort zone of human dwellings in daily life. Therefore, this study aims to characterize the thermogenic program of brown/beige adipocytes in mice housed under ambient (22°C) versus thermoneutral condition (30°C). Male mice raised at 22°C or 30°C were fed either chow diet or high-fat (HF) diet for 20 weeks. Despite less food intake, chow-fed mice housed at 30°C remained the same body weight compared to mice at 22°C. However, these thermoneutrally housed mice displayed a decrease in the expression of thermogenic program in both brown and white fat depots with larger adipocytes. When pair-fed with chow diet, thermoneutrally housed mice showed an increase in body weight. Moreover, thermoneutrality increased body weight of mice fed with HF diet. This was associated with decreased expression of the thermogenic program in both brown and white fat depots of the thermoneutrally housed mice. The downregulation of the thermogenic program might have resulted from decreased sympathetic drive in the thermoneutrally housed mice evident by decreased expression of tyrosine hydroxylase expression and norepinephrine turnover in both brown and white fat depots. Our data demonstrate that thermoneutrality may negatively regulate the thermogenic program and sympathetic drive, leading to increased adiposity in mice. PMID:27230905

  12. 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

  13. Liver Fatty Acid Binding Protein Gene-ablation Exacerbates Weight Gain in High-Fat Fed Female Mice

    PubMed Central

    McIntosh, Avery L.; Atshaves, Barbara P.; Landrock, Danilo; Landrock, Kerstin K.; Martin, Gregory G.; Storey, Stephen M.; Kier, Ann B.; Schroeder, Friedhelm

    2013-01-01

    Loss of liver fatty acid binding protein (L-FABP) decreases long chain fatty acid uptake and oxidation in primary hepatocytes and in vivo. On this basis, L-FABP gene ablation would potentiate high-fat diet-induced weight gain and weight gain/energy intake. While this was indeed the case when L-FABP null (−/−) mice on the C57BL/6NCr background were pair-fed high fat diet, whether this would also be observed under high-fat diet fed ad libitum was not known. Therefore, this possibility was examined in female L-FABP (−/−) mice on the same background. L-FABP (−/−) mice consumed equal amounts of defined high-fat or isocaloric control diets fed ad libitum. However, on the ad libitum fed high-fat diet the L-FABP (−/−) mice exhibited: 1) Decreased hepatic long chain fatty acid (LCFA) β-oxidation as indicated by lower serum β–hydroxybutyrate level; 2) Decreased hepatic protein levels of key enzymes mitochondrial (rate limiting carnitine palmitoyl acyltransferase A1, CPT1A; HMG-CoA synthase) and peroxisomal (acyl CoA oxidase 1, ACOX1) LCFA β-oxidation; 3) Increased fat tissue mass (FTM) and FTM/energy intake to the greatest extent; and 4) Exacerbated body weight gain, weight gain/energy intake, liver weight, and liver weight/body weight to the greatest extent. Taken together, these findings showed that L-FABP gene-ablation exacerbated diet-induced weight gain and fat tissue mass gain in mice fed high-fat diet ad libitum—consistent with the known biochemistry and cell biology of L-FABP. PMID:23539345

  14. 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

  15. 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

  16. Relaxin Treatment Reverses Insulin Resistance in Mice Fed a High-Fat Diet

    PubMed Central

    Bonner, Jeffrey S.; Lantier, Louise; Hocking, Kyle M.; Kang, Li; Owolabi, Mark; James, Freyja D.; Bracy, Deanna P.; Brophy, Colleen M.; Wasserman, David H.

    2013-01-01

    The endogenous hormone relaxin increases vascular reactivity and angiogenesis. We demonstrate that acute relaxin infusion in lean C57BL/6J mice enhances skeletal muscle perfusion and augments muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. However, an acute effect was absent in mice fed a high-fat (HF) diet for 13 weeks. In contrast, mice fed an HF diet for 13 weeks and continuously treated with relaxin for the final 3 weeks of the diet exhibited decreased fasting blood glucose. Insulin-stimulated whole-body glucose disappearance and percent suppression of hepatic glucose production are corrected by chronic relaxin. The increase in peripheral glucose utilization is a result of augmented in vivo skeletal muscle glucose uptake. Relaxin intervention improves endothelial-dependent vascular reactivity and induces a two-fold proliferation in skeletal muscle capillarity. The metabolic effects of the treatment are not attributed to changes in myocellular insulin signaling. Relaxin intervention reverses the accumulation of collagen III in the liver and collagen III and collagen IV in the heart; this is induced by HF feeding. These studies show the potential of relaxin in the treatment of diet-induced insulin resistance and vascular dysfunction. Relaxin provides a novel therapeutic approach targeting the extramyocellular barriers to insulin action, which are critical to the pathogenesis of insulin resistance. PMID:23801576

  17. (-)-Epicatechin improves insulin sensitivity in high fat diet-fed mice.

    PubMed

    Cremonini, Eleonora; Bettaieb, Ahmed; Haj, Fawaz G; Fraga, Cesar G; Oteiza, Patricia I

    2016-06-01

    Obesity constitutes a major public health concern, being frequently associated with type 2 diabetes (T2D). Evidence from studies in humans and experimental animals suggest that consumption of the flavan-3-ol (-)-epicatechin (EC) and of EC-rich foods may improve insulin sensitivity. To further understand the potential benefits of dietary EC consumption on insulin resistance, this study investigated the capacity of EC supplementation to prevent high fat diet (HFD)-induced insulin resistance in mice. To assess the underlying mechanisms, the effects of HFD and EC consumption on the activation of the insulin cascade and of its negative modulators were evaluated. HFD consumption for 15 w caused obesity and insulin resistance in C57BL/6J mice as evidenced by high fasted and fed plasma glucose and insulin levels, and impaired ITT and GTT tests. This was associated with alterations in the activation of components of the insulin-triggered signaling cascade (insulin receptor, IRS1, ERK1/2, Akt) in adipose and liver tissues. EC supplementation prevented/ameliorated all these parameters. EC acted improving insulin sensitivity in the HFD-fed mice in part through a downregulation of the inhibitory molecules JNK, IKK, PKC and protein tyrosine phosphatase 1B (PTP1B). Thus, the above results suggest that consumption of EC-rich foods could constitute a dietary strategy to mitigate obesity-associated insulin resistance. PMID:26968772

  18. Protective potentials of wild rice (Zizania latifolia (Griseb) Turcz) against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats.

    PubMed

    Han, Shu-Fen; Zhang, Hong; Zhai, Cheng-Kai

    2012-07-01

    The study evaluates the protective potentials of wild rice against obesity and lipotoxicity induced by a high-fat/cholesterol diet in rats. In addition to the rats of low-fat diet group, others animals were exposed to a high-fat/cholesterol diet condition for 8 weeks. The city diet (CD) is based on the diet consumed by urban residents in modern China, which is rich in fat/cholesterol and high in carbohydrates from white rice and processed wheat starch. The chief source of dietary carbohydrates of wild rice diet (WRD) is from Chinese wild rice and other compositions are the same with CD. Rats fed CD showed elevated body and liver organ weights, lipid profiles, free fatty acids (FFA) and leptin comparable with rats fed high-fat/cholesterol diet (HFD) known to induce obesity and hyperlipidaemia in this species. However, rats consuming WRD suppressed the increase of lipid droplets accumulation, FFA, and leptin, and the decrease of lipoprotein lipase and adipose triglyceride lipase. Meanwhile, WRD prevented high-fat/cholesterol diet-induced elevation in protein expression of sterol-regulatory element binding protein-1c, and gene expression of fatty acid synthase and acetyl-CoA carboxylase. These findings indicate that wild rice as a natural food has the potentials of preventing obesity and liver lipotoxicity induced by a high-fat/cholesterol diet in rats. PMID:22579924

  19. Cardiac metabolism in a new rat model of type 2 diabetes using high-fat diet with low dose streptozotocin

    PubMed Central

    2013-01-01

    Background To study the pathogenesis of diabetic cardiomyopathy, reliable animal models of type 2 diabetes are required. Physiologically relevant rodent models are needed, which not only replicate the human pathology but also mimic the disease process. Here we characterised cardiac metabolic abnormalities, and investigated the optimal experimental approach for inducing disease, in a new model of type 2 diabetes. Methods and results Male Wistar rats were fed a high-fat diet for three weeks, with a single intraperitoneal injection of low dose streptozotocin (STZ) after fourteen days at 15, 20, 25 or 30 mg/kg body weight. Compared with chow-fed or high-fat diet fed control rats, a high-fat diet in combination with doses of 15–25 mg/kg STZ did not change insulin concentrations and rats maintained body weight. In contrast, 30 mg/kg STZ induced hypoinsulinaemia, hyperketonaemia and weight loss. There was a dose-dependent increase in blood glucose and plasma lipids with increasing concentrations of STZ. Cardiac and hepatic triglycerides were increased by all doses of STZ, in contrast, cardiac glycogen concentrations increased in a dose-dependent manner with increasing STZ concentrations. Cardiac glucose transporter 4 protein levels were decreased, whereas fatty acid metabolism-regulated proteins, including uncoupling protein 3 and pyruvate dehydrogenase (PDH) kinase 4, were increased with increasing doses of STZ. Cardiac PDH activity displayed a dose-dependent relationship between enzyme activity and STZ concentration. Cardiac insulin-stimulated glycolytic rates were decreased by 17% in 15 mg/kg STZ high-fat fed diabetic rats compared with control rats, with no effect on cardiac contractile function. Conclusions High-fat feeding in combination with a low dose of STZ induced cardiac metabolic changes that mirror the decrease in glucose metabolism and increase in fat metabolism in diabetic patients. While low doses of 15–25 mg/kg STZ induced a type 2 diabetic

  20. 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

  1. 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

  2. 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

  3. High fat diet promotes achievement of peak bone mass in young rats

    SciTech Connect

    Malvi, Parmanand; Piprode, Vikrant; Chaube, Balkrishna; Pote, Satish T.; Mittal, Monika; Chattopadhyay, Naibedya; Wani, Mohan R.; Bhat, Manoj Kumar

    2014-12-05

    Highlights: • High fat diet helps in achieving peak bone mass at younger age. • Shifting from high fat to normal diet normalizes obese parameters. • Bone parameters are sustained even after withdrawal of high fat diet. - Abstract: The relationship between obesity and bone is complex. Epidemiological studies demonstrate positive as well as negative correlation between obesity and bone health. In the present study, we investigated the impact of high fat diet-induced obesity on peak bone mass. After 9 months of feeding young rats with high fat diet, we observed obesity phenotype in rats with increased body weight, fat mass, serum triglycerides and cholesterol. There were significant increases in serum total alkaline phosphatase, bone mineral density and bone mineral content. By micro-computed tomography (μ-CT), we observed a trend of better trabecular bones with respect to their microarchitecture and geometry. This indicated that high fat diet helps in achieving peak bone mass and microstructure at younger age. We subsequently shifted rats from high fat diet to normal diet for 6 months and evaluated bone/obesity parameters. It was observed that after shifting rats from high fat diet to normal diet, fat mass, serum triglycerides and cholesterol were significantly decreased. Interestingly, the gain in bone mineral density, bone mineral content and trabecular bone parameters by HFD was retained even after body weight and obesity were normalized. These results suggest that fat rich diet during growth could accelerate achievement of peak bone mass that is sustainable even after withdrawal of high fat diet.

  4. Hepatic Gene Expression Related to Lower Plasma Cholesterol in Hamsters Fed High Fat Diets Supplemented with Blueberry Pomace and Extract

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We analyzed plasma lipid profiles, and genes related to cholesterol and bile acid metabolism, and inflammation in livers as well as adipose tissue from Syrian Golden hamsters fed high-fat diets supplemented with blueberry (BB) pomace byproducts including 8% dried whole blueberry peels (BBPWHL), 2% d...

  5. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    SciTech Connect

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  6. 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

  7. Effect of High Fructose and High Fat Diets on Pulmonary Sensitivity, Motor Activity, and Body Composition of Brown Norway Rats Exposed to Ozone

    EPA Science Inventory

    Diet-induced obesity has been suggested to lead to increased susceptibility to air pollutants such as ozone (03); however, there is little experimental evidence. Thirty day old male and female Brown Norway rats were fed a normal, high-fructose or high-fat diet for 12 weeks and th...

  8. Effect of High Fat Diets on Body Mass, Oleylethanolamide Plasma Levels and Oxytocin Expression in Growing Rats.

    PubMed

    Sospedra, Isabel; Moral, Raquel; Escrich, Raquel; Solanas, Montserrat; Vela, Elena; Escrich, Eduard

    2015-06-01

    Obesity prevalence in developed countries has promoted the need to identify the mechanisms involved in control of feeding and energy balance. We have tested the hypothesis that different fats present in diet composition may contribute in body weight gain and body indexes by regulation of oxytocin gene (oxt) expression in hypothalamus and Oleylethanolamide (OEA) levels in plasma. Sprague-Dawley rats were fed two high fat diets, based on corn (HCO) and extra virgin olive oil (HOO) and results were compared to a low fat diet (LF). LC-MS/MS analysis showed an increasing trend of OEA plasma levels in HOO group, although no significant differences were found. However, body weight gain of LF and HOO were similar and significantly lower than HCO. HCO rats also had higher Lee index than HOO. Rats fed HOO diet showed higher levels of hypothalamic oxt mRNA expression, which could indicate that oxytocin may be modulated by dietary lipids. PMID:25976631

  9. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High-Fat Diets.

    PubMed

    Lindenmaier, Laurence B; Philbrick, Kenneth A; Branscum, Adam J; Kalra, Satya P; Turner, Russell T; Iwaniec, Urszula T

    2016-01-01

    Low bone mass is often associated with elevated bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell (MSC) progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Leptin deficiency and high-fat diet-induced obesity are associated with increased marrow adipose tissue (MAT) and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice following recombinant adeno-associated virus (rAAV) gene therapy. Eight- to 10-week-old male ob/ob mice were randomized into four groups: (1) untreated, (2) rAAV-Lep, (3) rAAV-green fluorescent protein (rAAV-GFP), or (4) pair-fed to rAAV-Lep. For vector administration, mice were injected intracerebroventricularly with either rAAV-leptin gene therapy (rAAV-Lep) or rAAV-GFP (9 × 10(7) particles) and maintained for 30 weeks. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high-fat diets; ob/ob mice were randomized into two groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high-fat diet for 8 weeks. Wild-type (WT) controls included age-matched mice fed regular or high-fat diet. High-fat diet resulted in a threefold increase in MAT in WT mice, whereas MAT was increased by leptin deficiency up to 50-fold. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high-fat diet to values similar to WT mice fed regular diet. These findings suggest

  10. Hypothalamic Leptin Gene Therapy Reduces Bone Marrow Adiposity in ob/ob Mice Fed Regular and High-Fat Diets

    PubMed Central

    Lindenmaier, Laurence B.; Philbrick, Kenneth A.; Branscum, Adam J.; Kalra, Satya P.; Turner, Russell T.; Iwaniec, Urszula T.

    2016-01-01

    Low bone mass is often associated with elevated bone marrow adiposity. Since osteoblasts and adipocytes are derived from the same mesenchymal stem cell (MSC) progenitor, adipocyte formation may increase at the expense of osteoblast formation. Leptin is an adipocyte-derived hormone known to regulate energy and bone metabolism. Leptin deficiency and high-fat diet-induced obesity are associated with increased marrow adipose tissue (MAT) and reduced bone formation. Short-duration studies suggest that leptin treatment reduces MAT and increases bone formation in leptin-deficient ob/ob mice fed a regular diet. Here, we determined the long-duration impact of increased hypothalamic leptin on marrow adipocytes and osteoblasts in ob/ob mice following recombinant adeno-associated virus (rAAV) gene therapy. Eight- to 10-week-old male ob/ob mice were randomized into four groups: (1) untreated, (2) rAAV-Lep, (3) rAAV-green fluorescent protein (rAAV-GFP), or (4) pair-fed to rAAV-Lep. For vector administration, mice were injected intracerebroventricularly with either rAAV-leptin gene therapy (rAAV-Lep) or rAAV-GFP (9 × 107 particles) and maintained for 30 weeks. In a second study, the impact of increased hypothalamic leptin levels on MAT was determined in mice fed high-fat diets; ob/ob mice were randomized into two groups and treated with either rAAV-Lep or rAAV-GFP. At 7 weeks post-vector administration, half the mice in each group were switched to a high-fat diet for 8 weeks. Wild-type (WT) controls included age-matched mice fed regular or high-fat diet. High-fat diet resulted in a threefold increase in MAT in WT mice, whereas MAT was increased by leptin deficiency up to 50-fold. Hypothalamic leptin gene therapy increased osteoblast perimeter and osteoclast perimeter with minor change in cancellous bone architecture. The gene therapy decreased MAT levels in ob/ob mice fed regular or high-fat diet to values similar to WT mice fed regular diet. These findings suggest

  11. Hypolipidemic Effect and Mechanism of Palmatine from Coptis chinensis in Hamsters Fed High-Fat diet.

    PubMed

    Ning, Na; He, Kai; Wang, Yanzhi; Zou, Zongyao; Wu, Hao; Li, Xuegang; Ye, Xiaoli

    2015-05-01

    Palmatine (PAL) is one of the main alkaloids in Coptis chinensis. The present aim was to investigate the hypolipidemic effect and mechanism of palmatine in hamsters fed with high-fat diet (HFD). PAL treatment decreased serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels, as well as increased fecal excretion of TC and total bile acids (TBA) in hyperlipidemic hamsters. Furthermore, PAL treatment up-regulated low-density lipoprotein receptor (LDLR) and cholesterol 7α-hydroxylase (CYP7A1) mRNA and protein expression and down-regulated apical sodium-dependent bile salt transporter (ASBT) mRNA and protein expression. These results demonstrated that PAL as a potential natural cholesterol lowering agent works by up-regulating LDLR and CYP7A1 mRNA and protein expression, down-regulating ASBT mRNA and protein expression, as well as enhancing fecal excretion of TC and TBA. The findings in our study suggest that palmatine could be a potential natural agent for treating hyperlipidemia. PMID:25586479

  12. Quercetin alleviates inflammation after short-term treatment in high-fat-fed mice.

    PubMed

    Das, Nilanjan; Sikder, Kunal; Bhattacharjee, Surajit; Majumdar, Suchandra Bhattacharya; Ghosh, Santinath; Majumdar, Subrata; Dey, Sanjit

    2013-06-01

    Consumption of a high-fat diet (HFD) promotes reactive oxygen species (ROS) which ultimately trigger inflammation. The aim of this study was to investigate the role of Moringa oleifera leaf extract (MoLE) and its active component quercetin in preventing NF-κB-mediated inflammation raised by short-term HFD. Quercetin was found to be one of the major flavonoid components from HPLC of MoLE. Swiss mice were fed for 15 days on HFD, both with or without MoLE/quercetin. The antioxidant profile was estimated from liver homogenate. NF-κB and some relevant inflammatory markers were evaluated by immunoblotting, RT-PCR and ELISA. Significantly (P < 0.05) lower antioxidant profile and higher lipid peroxidation was found in HFD group compared to control (P < 0.05). Increased nuclear import of NF-κB and elevated expressions of pro-inflammatory markers were further manifestations in the HFD group. All these changes were reversed in the MoLE/quercetin-treated groups with significant improvement of antioxidant activity compared to the HFD group. MoLE was found to be rich in polyphenols and both MoLE and quercetin showed potent free radical and hydroxyl radical quenching activity. Thus, the present study concluded that short-term treatment with MoLE and its constituent quercetin prevent HFD-mediated inflammation in mice. PMID:23644882

  13. Mangosteen Extract Attenuates the Metabolic Disorders of High-Fat-Fed Mice by Activating AMPK.

    PubMed

    Chae, Hee-Sung; Kim, Young-Mi; Bae, Jin-Kyung; Sorchhann, Sochivak; Yim, Sreymom; Han, Ling; Paik, Jin Hyub; Choi, Young Hee; Chin, Young-Won

    2016-02-01

    This study investigated the effects of mangosteen on metabolic syndromes in high-fat (HF) diet-fed mice and the underlying mechanisms related to adipogenesis. Mangosteen-supplemented mice gained significantly less body weight, compared with the HF group. The levels were markedly elevated in HF mice for serum glutamate oxaloacetate transaminase, glutamate pyruvate transaminase, glucose, triglyceride, total cholesterol, low-density lipoprotein (LDL) cholesterol, and free fatty acid; whereas these levels were significantly lower in the 200 mg/kg of the mangosteen extract-treated group. The mangosteen extract did not modify high-density lipoprotein (HDL)-cholesterol, however, LDL-cholesterol was lower and HDL/LDL ratio was higher (9.4 vs. 3.7 in HF group). Furthermore, 200 mg/kg of mangosteen treatment activated the hepatic AMP-activated protein kinase and Sirtuin 1 in an in vivo system. Thus, the results of this study suggest that mangosteen extract exerts antiobesity effects by regulating energy metabolism and hepatic lipid homeostasis. PMID:26452017

  14. Serotonin Deficiency Rescues Lactation on Day 1 in Mice Fed a High Fat Diet.

    PubMed

    Weaver, Samantha R; Bohrer, Justin C; Prichard, Allan S; Perez, Paola K; Streckenbach, Liana J; Olson, Jake M; Cook, Mark E; Hernandez, Laura L

    2016-01-01

    Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation. Fourteen mice were genetically deficient for Tph1 (Tph1-/-), and twelve were wild type. Milk yield, pup mortality, and dam weights were recorded and milk samples were collected. On day 10 of lactation, dams were sacrificed and mammary glands were harvested for RT-PCR and histological evaluation. HFD dams weighed more than LFD dams at the onset of lactation. WT HFD dams were unable to lactate on day 1 of lactation and exhibited increased pup mortality relative to all other treatments, including Tph1-/- HFD dams. mRNA expression of immune markers C-X-C motif chemokine 5 and tumor necrosis factor alpha were elevated in WT HFD mammary glands. Mammary gland histology showed a reduced number of alveoli in WT compared to Tph1-/- dams, regardless of diet, and the alveoli of HFD dams were smaller than those of LFD dams. Finally, fatty acid profile in milk was dynamic in both early and peak lactation, with reduced de novo synthesis of fatty acids on day 10 of lactation in the HFD groups. Administration of a HFD to C57BL/6 dams produced an obese phenotype in the mammary gland, which was alleviated by a genetic deficiency of Tph1. Serotonin may modulate the effects of obesity on the mammary gland, potentially contributing to the delayed onset of lactogenesis seen in obese women. PMID:27603698

  15. 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

  16. Blueberry supplementation improves memory in middle-aged mice fed a high-fat diet

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Consuming a high-fat diet may result in behavioral deficits similar to those observed in aging animals; our lab has demonstrated that blueberry supplementation can allay age-related behavioral deficits. To determine if supplementation of a high-fat diet with blueberries offers protection against put...

  17. Effects of fenugreek seed extract in obese mice fed a high-fat diet.

    PubMed

    Handa, Toshiaki; Yamaguchi, Kohji; Sono, Yoshikatsu; Yazawa, Kazunaga

    2005-06-01

    It was found that fenugreek seed extract reduced the body weight gain induced by a high-fat diet in obese mice. The extract decreased plasma triglyceride gain induced by oil administration. The major component of the extract, 4-hydroxyisoleucine, also decreased plasma triglyceride gain. Consequently, fenugreek seed extract is expected to prevent the obesity induced by a high-fat diet. PMID:15973051

  18. Effect of proximal versus distal 50% enterectomy on nutritional parameters in rats preconditioned with a high-fat diet or regular chow

    PubMed Central

    Yanala, Ujwal R.; Reidelberger, Roger D.; Thompson, Jon S.; Shostrom, Valerie K.; Carlson, Mark A.

    2015-01-01

    Obesity may protect against the nutritional consequences of short bowel syndrome. We hypothesized that rats preconditioned with an obesogenic diet would have better outcomes after surgical induction of short bowel syndrome compared to rats on regular chow. Rats were fed a high-fat diet or regular rat chow for six months, and then underwent 50% proximal, 50% distal, or sham enterectomy. Food intake, weight, and body composition were monitored before and for 4 weeks after surgery. The high-fat diet consistently produced obesity (>25% body fat). All procedures induced weight loss, but there was no discernable difference between resection vs. sham resection. Rats on the high-fat diet had a greater post-resection loss of body fat compared to rats on chow (36 vs. 26 g, respectively). There was a nonsignificant trend of less lean mass loss in the former compared to the latter rats (16 vs. 33 g, respectively). Enterectomy moderated serum ghrelin, GIP, PPY, insulin, and leptin. Intestinal adaptation was not different between obese vs. non-obese rats. Rats preconditioned with the high-fat diet may have had better retention of lean body mass after a surgical procedure compared to rats on chow. The effect of 50% enterectomy was less than expected. PMID:26612764

  19. 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

  20. 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

  1. Effects of escin mixture from the seeds of Aesculus hippocastanum on obesity in mice fed a high fat diet.

    PubMed

    Avci, Gülcan; Küçükkurt, Ismail; Küpeli Akkol, Esra; Yeşilada, Erdem

    2010-03-01

    Escins, a triterpene glycoside mixture obtained from the ethanol extract of Aesculus hippocastanum L. (Hippocastanaceae) seed, was evaluated for its in vivo effects on the plasma levels of some hormones (leptin, insulin, FT(3), FT(4)) and biochemical parameters (glucose, triglyceride, total cholesterol, HDL-C, LDL-C concentrations) in mice fed with a high fat diet for 5 weeks. A high fat diet induced a remarkable increment in the plasma leptin (p <0.01), total cholesterol (p <0.01) and LDL-C (p <0.001) concentrations compared to control group animals. Combined administration of a high-fat diet with escins decreased leptin (31.6%) (p<0.05) and FT(4) (36.0%) (p<0.05) levels, increased HDL-C concentration (17.0%), while remained ineffective on LDL-C concentration in mice. Results have shown that escins may have beneficial effects in the understanding of obesity. PMID:20645808

  2. p13 overexpression in pancreatic β-cells ameliorates type 2 diabetes in high-fat-fed mice.

    PubMed

    Higashi, Shintaro; Katagi, Kazuhiko; Shintani, Norihito; Ikeda, Kazuya; Sugimoto, Yukihiko; Tsuchiya, Soken; Inoue, Naoki; Tanaka, Shota; Koumoto, Mai; Kasai, Atsushi; Nakazawa, Takanobu; Hayata-Takano, Atsuko; Hamagami, Ken-Ichi; Tomimoto, Shuhei; Yoshida, Takuya; Ohkubo, Tadayasu; Nagayasu, Kazuki; Ago, Yukio; Onaka, Yusuke; Hashimoto, Ryota; Ichikawa, Atsushi; Baba, Akemichi; Hashimoto, Hitoshi

    2015-06-12

    We examined the pancreatic function of p13 encoded by 1110001J03Rik, whose expression is decreased in pancreatic islets in high-fat-fed diabetic mice, by generating transgenic mice overexpressing p13 (p13-Tg) in pancreatic β-cells. p13-Tg mice showed normal basal glucose metabolism; however, under high-fat feeding, these animals showed augmented glucose-induced first-phase and total insulin secretion, improved glucose disposal, greater islet area and increased mitotic insulin-positive cells. In addition, high-fat diet-induced 4-hydroxynonenal immunoreactivity, a reliable marker and causative agent of lipid peroxidative stress, was significantly decreased in p13-Tg mouse islets. These results indicate that p13 is a novel pancreatic factor exerting multiple beneficial effects against type 2 diabetes. PMID:25912136

  3. 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

  4. Edible bird's nest attenuates procoagulation effects of high-fat diet in rats.

    PubMed

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Hou, Zhiping

    2015-01-01

    Edible bird's nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipoprotein (oxLDL), adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count) were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia. PMID:26251574

  5. Edible bird’s nest attenuates procoagulation effects of high-fat diet in rats

    PubMed Central

    Yida, Zhang; Imam, Mustapha Umar; Ismail, Maznah; Ismail, Norsharina; Hou, Zhiping

    2015-01-01

    Edible bird’s nest (EBN) is popular in Asia, and has long been used traditionally as a supplement. There are, however, limited evidence-based studies on its efficacy. EBN has been reported to improve dyslipidemia, which is closely linked to hypercoagulation states. In the present study, the effects of EBN on high-fat diet- (HFD-) induced coagulation in rats were evaluated. Rats were fed for 12 weeks with HFD alone or in combination with simvastatin or EBN. Food intake was estimated, and weight measurements were made during the experimental period. After sacrifice, serum oxidized low-density lipoprotein (oxLDL), adiponectin, leptin, von willibrand factor, prostacyclin, thromboxane and lipid profile, and whole blood coagulation indices (bleeding time, prothrombin time, activated partial thromboplastin time, red blood count count, and platelet count) were estimated. Furthermore, hepatic expression of coagulation-related genes was evaluated using multiplex polymerase chain reaction. The results indicated that EBN could attenuate HFD-induced hypercholesterolemia and coagulation similar to simvastatin, partly through transcriptional regulation of coagulation-related genes. The results suggested that EBN has the potential for lowering the risk of cardiovascular disease-related hypercoagulation due to hypercholesterolemia. PMID:26251574

  6. TNF-α upregulates sclerostin expression in obese mice fed a high-fat diet.

    PubMed

    Baek, Kyunghwa; Hwang, Hyo Rin; Park, Hyun-Jung; Kwon, Arang; Qadir, Abdul S; Ko, Seong-Hee; Woo, Kyung Mi; Ryoo, Hyun-Mo; Kim, Gwan-Shik; Baek, Jeong-Hwa

    2014-05-01

    Sclerostin decreases bone mass by antagonizing the Wnt signaling pathway. We examined whether obesity-induced bone loss is associated with the expression of sclerostin. Five-week-old male mice were assigned to one of two groups (n = 10 each) and fed either a control diet (10% kcal from fat; CON) or a high-fat diet (60% kcal from fat; HF) for 12 weeks. Thex final body weight and whole body fat mass of the HF mice were higher than those of the CON mice. The distal femur cancellous bone mineral density and bone formation rate was lower in HF mice than in CON mice. The percent erosion surface was higher in the HF mice than the CON mice. The serum levels and femoral osteocytic protein expression levels of tumor necrosis factor-α (TNF-α) were significantly higher in HF mice than in CON mice. Sclerostin mRNA levels and osteocytic sclerostin protein levels in femoral cortex were also higher in HF mice than in CON mice. Sclerostin expression in MLO-Y4 osteocytes increased with TNF-α treatment, and TNF-α-induced sclerostin expression was blocked by the inhibition of NF-κB activation. Chromatin immunoprecipitation and a luciferase reporter assay demonstrated that NF-κB directly binds to the NF-κB binding elements on the mouse sost promoter and stimulates sclerostin expression. These results support a model in which, in the context of obesity or other inflammatory diseases that increase the production of TNF-α, TNF-α upregulates the expression of sclerostin through NF-κB signaling pathway, thus contributing to bone loss. PMID:24446199

  7. PTEN Inhibition Improves Muscle Regeneration in Mice Fed a High-Fat Diet

    PubMed Central

    Hu, Zhaoyong; Wang, Huiling; Lee, In Hee; Modi, Swati; Wang, Xiaonan; Du, Jie; Mitch, William E.

    2010-01-01

    OBJECTIVE Mechanisms impairing wound healing in diabetes are poorly understood. To identify mechanisms, we induced insulin resistance by chronically feeding mice a high-fat diet (HFD). We also examined the regulation of phosphatidylinositol 3,4,5-trisphosphate (PIP3) during muscle regeneration because augmented IGF-1 signaling can improve muscle regeneration. RESEARCH DESIGN AND METHODS Muscle regeneration was induced by cardiotoxin injury, and we evaluated satellite cell activation and muscle maturation in HFD-fed mice. We also measured PIP3 and the enzymes regulating its level, IRS-1–associated phosphatidylinositol 3-kinase (PI3K) and PTEN. Using primary cultures of muscle, we examined how fatty acids affect PTEN expression and how PTEN knockout influences muscle growth. Mice with muscle-specific PTEN knockout were used to examine how the HFD changes muscle regeneration. RESULTS The HFD raised circulating fatty acids and impaired the growth of regenerating myofibers while delaying myofiber maturation and increasing collagen deposition. These changes were independent of impaired proliferation of muscle progenitor or satellite cells but were principally related to increased expression of PTEN, which reduced PIP3 in muscle. In cultured muscle cells, palmitate directly stimulated PTEN expression and reduced cell growth. Knocking out PTEN restored cell growth. In mice, muscle-specific PTEN knockout improved the defects in muscle repair induced by HFD. CONCLUSIONS Insulin resistance impairs muscle regeneration by preventing myofiber maturation. The mechanism involves fatty acid–stimulated PTEN expression, which lowers muscle PIP3. If similar pathways occur in diabetic patients, therapeutic strategies directed at improving the repair of damaged muscle could include suppression of PTEN activity. PMID:20200318

  8. Nrf2 Deficiency Improves Glucose Tolerance in Mice Fed a High-Fat Diet

    PubMed Central

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-01-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. PMID:23017736

  9. Chronic Angiotensin-(1-7) Improves Insulin Sensitivity in High-Fat Fed Mice Independent of Blood Pressure.

    PubMed

    Williams, Ian M; Otero, Yolanda F; Bracy, Deanna P; Wasserman, David H; Biaggioni, Italo; Arnold, Amy C

    2016-05-01

    Angiotensin-(1-7) improves glycemic control in animal models of cardiometabolic syndrome. The tissue-specific sites of action and blood pressure dependence of these metabolic effects, however, remain unclear. We hypothesized that Ang-(1-7) improves insulin sensitivity by enhancing peripheral glucose delivery. Adult male C57BL/6J mice were placed on standard chow or 60% high-fat diet for 11 weeks. Ang-(1-7) (400 ng/kg per minute) or saline was infused subcutaneously during the last 3 weeks of diet, and hyperinsulinemic-euglycemic clamps were performed at the end of treatment. High-fat fed mice exhibited modest hypertension (systolic blood pressure: 137 ± 3 high fat versus 123 ± 5 mm Hg chow;P=0.001), which was not altered by Ang-(1-7) (141 ± 4 mm Hg;P=0.574). Ang-(1-7) did not alter body weight or fasting glucose and insulin in chow or high-fat fed mice. Ang-(1-7) increased the steady-state glucose infusion rate needed to maintain euglycemia in high-fat fed mice (31 ± 5 Ang-(1-7) versus 16 ± 1 mg/kg per minute vehicle;P=0.017) reflecting increased whole-body insulin sensitivity, with no effect in chow-fed mice. The improved insulin sensitivity in high-fat fed mice was because of an enhanced rate of glucose disappearance (34 ± 5 Ang-(1-7) versus 20 ± 2 mg/kg per minute vehicle;P=0.049). Ang-(1-7) enhanced glucose uptake specifically into skeletal muscle by increasing translocation of glucose transporter 4 to the sarcolemma. Our data suggest that Ang-(1-7) has direct insulin-sensitizing effects on skeletal muscle, independent of changes in blood pressure. These findings provide new insight into mechanisms by which Ang-(1-7) improves insulin action, and provide further support for targeting this peptide in cardiometabolic disease. PMID:26975707

  10. Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling

    PubMed Central

    Zhou, Zi-yu; Ren, Li-wei; Zhan, Ping; Yang, Han-yan; Chai, Dan-dan; Yu, Zhi-wen

    2016-01-01

    Aim: Accumulating evidence shows that lipopolysaccharides (LPS) derived from gut gram-negative bacteria can be absorbed, leading to endotoxemia that triggers systemic inflammation and insulin resistance. In this study we examined whether metformin attenuated endotoxemia, thus improving insulin signaling in high-fat diet fed mice. Methods: Mice were fed a high-fat diet for 18 weeks to induce insulin resistance. One group of the mice was treated with oral metformin (100 mg·kg−1·d−1) for 4 weeks. Another group was treated with LPS (50 μg·kg−1·d−1, sc) for 5 days followed by the oral metformin for 10 d. Other two groups received a combination of antibiotics for 7 d or a combination of antibiotics for 7 d followed by the oral metformin for 4 weeks, respectively. Glucose metabolism and insulin signaling in liver and muscle were evaluated, the abundance of gut bacteria, gut permeability and serum LPS levels were measured. Results: In high-fat fed mice, metformin restored the tight junction protein occludin-1 levels in gut, reversed the elevated gut permeability and serum LPS levels, and increased the abundance of beneficial bacteria Lactobacillus and Akkermansia muciniphila. Metformin also increased PKB Ser473 and AMPK T172 phosphorylation, decreased MDA contents and redox-sensitive PTEN protein levels, activated the anti-oxidative Nrf2 system, and increased IκBα in liver and muscle of the mice. Treatment with exogenous LPS abolished the beneficial effects of metformin on glucose metabolism, insulin signaling and oxidative stress in liver and muscle of the mice. Treatment with antibiotics alone produced similar effects as metformin did. Furthermore, the beneficial effects of antibiotics were addictive to those of metformin. Conclusion: Metformin administration attenuates endotoxemia and enhances insulin signaling in high-fat fed mice, which contributes to its anti-diabetic effects. PMID:27180982