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Sample records for diet-induced weight reduction

  1. Improvement of impaired diastolic left ventricular function after diet-induced weight reduction in severe obesity

    PubMed Central

    Karimian, Sevda; Stein, Juergen; Bauer, Boris; Teupe, Claudius

    2017-01-01

    Background/objectives Obesity is independently associated with left ventricular (LV) diastolic dysfunction and altered cardiac morphology. Morbidity and mortality in patients with diastolic dysfunction are similar to values observed in patients with systolic heart failure. We hypothesized that dysfunctional cardiac responses in people with obesity are reversible after weight loss. Thus, we studied the effect of dietary weight reduction on LV diastolic function as well as on cardiac structure using transthoracic echocardiography and tissue Doppler imaging (TDI). Subjects/methods Thirty-two subjects with obesity underwent a 12-week low-calorie fasting phase of a formula diet. Echocardiographic tissue Doppler indices of diastolic function and measurements of cardiac size were obtained prior to and after the fasting phase. Results A 12-week diet significantly reduced body mass index from 40.3 ± 6.6 kg/m2 to 33.2 ± 6.1 kg/m2 (p < 0.01). Weight loss was associated with a significant reduction in blood pressure and heart rate. Echocardiography revealed diastolic dysfunction in subjects with obesity, which was improved by dieting. After weight loss, trans-mitral Doppler echocardiography showed a significant reduction in A-wave velocity, from 65.8 ± 19.2 cm/s to 57.0 ± 16.8 cm/s, and an increase in E/A ratio from 1.2 ± 0.4 to 1.4 ± 0.5 (p < 0.01). TDI displayed a significantly lower a′-wave velocity (10.3 ± 2.3 cm/s and 8.9 ± 1.7 cm/s; p < 0.01). Left atrial and LV dimensions were normal and remained unchanged after weight loss. Conclusion Obesity is associated with diastolic dysfunction. A 12-week low-calorie diet with successful weight loss can reduce blood pressure and heart rate and partially normalize diastolic dysfunction. PMID:28123309

  2. Reduction of body weight, liver steatosis and expression of stearoyl-CoA desaturase 1 by the isoflavone daidzein in diet-induced obesity

    PubMed Central

    Crespillo, A; Alonso, M; Vida, M; Pavón, FJ; Serrano, A; Rivera, P; Romero-Zerbo, Y; Fernández-Llebrez, P; Martínez, A; Pérez-Valero, V; Bermúdez-Silva, FJ; Suárez, J; de Fonseca, FR

    2011-01-01

    BACKGROUND AND PURPOSE The lack of safe and effective treatments for obesity has increased interest in natural products that may serve as alternative therapies. From this perspective, we have analysed the effects of daidzein, one of the main soy isoflavones, on diet-induced obesity in rats. EXPERIMENTAL APPROACH Rats made obese after exposure to a very (60%) high fat-content diet were treated with daidzein (50 mg·kg−1) for 14 days. The dose was selected on the basis of the acute effects of this isoflavone on a feeding test. After 14 days, animals were killed and plasma, white and brown adipose tissue, muscle and liver studied for the levels and expression of metabolites, proteins and genes relevant to lipid metabolism. KEY RESULTS A single treatment (acute) with daidzein dose-dependently reduced food intake. Chronic treatment (daily for 14 days) reduced weight gain and fat content in liver, accompanied by high leptin and low adiponectin levels in plasma. While skeletal muscle was weakly affected by treatment, both adipose tissue and liver displayed marked changes after treatment with daidzein, affecting transcription factors and lipogenic enzymes, particularly stearoyl coenzyme A desaturase 1, a pivotal enzyme in obesity. Expression of uncoupling protein 1, an important enzyme for thermogenesis, was increased in brown adipose tissue after daidzein treatment. CONCLUSIONS AND IMPLICATIONS These results support the use of isoflavones in diet-induced obesity, especially when hepatic steatosis is present and open a new field of use for these natural products. PMID:21557739

  3. Propolis prevents diet-induced hyperlipidemia and mitigates weight gain in diet-induced obesity in mice.

    PubMed

    Koya-Miyata, Satomi; Arai, Norie; Mizote, Akiko; Taniguchi, Yoshifumi; Ushio, Shimpei; Iwaki, Kanso; Fukuda, Shigeharu

    2009-12-01

    We examined the hypolipidemic effect of propolis in a mouse obesity model induced by a high fat-diet. C57BL/6N mice were fed a high-fat diet ad libitum and given propolis extract intragastrically at 0 mg/kg (control), 5 mg/kg or 50 mg/kg twice daily for 10 d. Compared with mice in the control group, mice in the propolis extract-administrated groups displayed a reduction in all of the following parameters: body weight gain, weight of visceral adipose tissue, liver and serum triglycerides, cholesterol, and non-esterified fatty acids. Real-time polymerase chain reaction analysis of the liver showed down-regulation of mRNA expression associated with fatty acid biosynthesis, including fatty acid synthase, acetyl-CoA carboxylase alpha, and sterol regulatory element binding protein in the propolis-administrated mice. Subsequently, obese C57BL/6N mice that had been administered a high-fat diet were given propolis extract at 0 mg/kg (control), 2.5 mg/kg or 25 mg/kg for 4 weeks. The propolis extract treated mice showed a decrease in weight gain, a reduction of serum non-esterified fatty acids, and lipid accumulation in the liver. These results suggest that propolis extract prevented and mitigated high-fat diet-induced hyperlipidemia by down-regulating the expression of genes associated with lipid metabolism.

  4. Voluntary exercise contributed to an amelioration of abnormal feeding behavior, locomotor activity and ghrelin production concomitantly with a weight reduction in high fat diet-induced obese rats.

    PubMed

    Mifune, Hiroharu; Tajiri, Yuji; Nishi, Yoshihiro; Hara, Kento; Iwata, Shimpei; Tokubuchi, Ichiro; Mitsuzono, Ryouichi; Yamada, Kentaro; Kojima, Masayasu

    2015-09-01

    In the present study, effects of voluntary exercise in an obese animal model were investigated in relation to the rhythm of daily activity and ghrelin production. Male Sprague-Dawley rats were fed either a high fat diet (HFD) or a chow diet (CD) from four to 16 weeks old. They were further subdivided into either an exercise group (HFD-Ex, CD-Ex) with a running wheel for three days of every other week or sedentary group (HFD-Se, CD-Se). At 16 weeks old, marked increases in body weight and visceral fat were observed in the HFD-Se group, together with disrupted rhythms of feeding and locomotor activity. The induction of voluntary exercise brought about an effective reduction of weight and fat, and ameliorated abnormal rhythms of activity and feeding in the HFD-Ex rats. Wheel counts as voluntary exercise was greater in HFD-Ex rats than those in CD-Ex rats. The HFD-obese had exhibited a deterioration of ghrelin production, which was restored by the induction of voluntary exercise. These findings demonstrated that abnormal rhythms of feeding and locomotor activity in HFD-obese rats were restored by infrequent voluntary exercise with a concomitant amelioration of the ghrelin production and weight reduction. Because ghrelin is related to food anticipatory activity, it is plausible that ghrelin participates in the circadian rhythm of daily activity including eating behavior. A beneficial effect of voluntary exercise has now been confirmed in terms of the amelioration of the daily rhythms in eating behavior and physical activity in an animal model of obesity.

  5. Corn gluten hydrolysate and capsaicin have complimentary actions on body weight reduction and lipid-related genes in diet-induced obese rats.

    PubMed

    Mun, Joo-Mi; Ok, Hyang Mok; Kwon, Oran

    2014-05-01

    The aim of this study was to test the hypothesis that a combination of corn gluten hydrolysate (CGH) and capsaicin may have an additive or synergistic effect on body weight reduction. For 13 weeks, male Sprague-Dawley rats were provided a diet to induce obesity. Afterward, the rats were randomly divided into 5 dietary groups: the normal control (n = 5), the high-fat control (n = 8), the high-fat diet (HFD) containing 35% CGH (n = 7), the HFD containing 0.02% capsaicin (HF-P) (n = 8), and the HFD containing both CGH and capsaicin (HF-CP) (n = 7) for an additional 4 weeks. Administration of CGH plus capsaicin, along with a HFD, led to significant decreases in body weight, fat mass, lipids in the liver, and plasma leptin as well as increases in plasma adiponectin. The pattern of gene expression was different in each target organ. In the liver, up-regulation of peroxisome proliferator-activated receptor α, carnitine palmitoyltransferase 1α, and acyl-coenzyme A oxidase was found in the HF-CP group. In contrast, down-regulation of peroxisome proliferator-activated receptor γ was found in both the HFD containing 35% CGH and HF-CP groups. In skeletal muscle, up-regulation of insulin receptor and uncoupling protein 3 was found in the HF-P group only, whereas up-regulation of the glucose transporter 4 gene was observed in both the HF-CP and HF-P groups. In adipose tissue, up-regulation of peroxisome proliferator-activated receptor γ and hormone-sensitive lipase was only found in the HF-CP group. In summary, this study suggests that CGH and capsaicin perform complementary actions on food intake, lipid metabolism, and insulin sensitivity by a coordinated control of energy metabolism in the liver, adipose tissue, and skeletal muscle, thus exerting an additive effect on body weight reduction.

  6. Purple Sweet Potato Attenuate Weight Gain in High Fat Diet Induced Obese Mice.

    PubMed

    Ju, Ronghui; Zheng, Shujuan; Luo, Hongxia; Wang, Changgang; Duan, Lili; Sheng, Yao; Zhao, Changhui; Xu, Wentao; Huang, Kunlun

    2017-03-01

    Purple sweet potato (PSP) is widely grown in Asia and considered as a healthy vegetable. The objective of the current study was to determine the anti-obesity effect of the PSP on high fat diet induced obese C57BL/6J mice. The mice were administrated with high fat diet supplemented with the sweet potato (SP) or PSP at the concentration of 15% and 30% for 12 wk, respectively. The results showed that the supplementation of SP or PSP at 30% significantly ameliorated high fat diet induced obesity and its associated risk factors, including reduction of body weight and fat accumulation, improvement of lipid profile and modulation of energy expenditure. Moreover, PSP also posed beneficial effect on the liver and kidney functions. These results indicate that PSP and SP have anti-obesity effect and are effective to reduce the metabolic risk.

  7. Effects of deoxynivalenol consumption on body weight and adiposity in the diet-induced obese mouse.

    PubMed

    Amuzie, C J; Flannery, B M; Ulrich, A M; Pestka, J J

    2011-01-01

    The potential for the obese state to alter sensitivity to toxic chemicals is poorly understood. In this study, dose-response effects of the trichothecene deoxynivalenol (DON), a common food-borne mycotoxin, were determined on body weight of diet-induced obese mice. In study 1, the effects of feeding adult female B6C3F1 mice a high-fat diet (HFD; 60% kcal from fat) containing 0, 2, 5, or 10 ppm DON for 10 wk on body weight and adiposity were compared. Mice consuming 5 or 10 ppm DON exhibited a 15 and 24% decrease in weight gain and a 50 and 83% reduction in periuterine fat, respectively. In study 2, mice were fed HFD for 8 wk to induce obesity and the effects of consuming HFD + 0, 2, 5, or 10 ppm DON for 8 wk were then determined. Mice fed 5 or 10 ppm DON exhibited a 16 and 23% weight reduction and a 0 and 40% periuterine fat reduction, respectively. In a follow-up experiment, food consumption was measured prior to and after the transition from HFD to HFD + 10 ppm DON. Exposure to DON was found to lower HFD consumption within 1 d, with significant weight loss in DON-fed mice evident after 6 d. In both studies 1 and 2, consumption of 5 or 10 ppm DON diminished circulating levels of insulin-like growth factor acid-labile subunit. Taken together, DON consumption lowered weight gain and produced weight loss in diet-induced obese mice at higher thresholds than that observed previously in normal B6C3F1 mice.

  8. Effects of sleep restriction on glucose control and insulin secretion during diet-induced weight loss

    PubMed Central

    Nedeltcheva, A. V.; Imperial, J. G.; Penev, P. D.

    2012-01-01

    Insufficient sleep is associated with changes in glucose tolerance, insulin secretion, and insulin action. Despite widespread use of weight-loss diets for metabolic risk reduction, the effects of insufficient sleep on glucose regulation in overweight dieters are not known. To examine the consequences of recurrent sleep restriction on 24-hour blood glucose control during diet-induced weight loss, 10 overweight and obese adults (3F/7M; mean [SD] age 41 [5] y; BMI 27.4 [2.0] kg/m2) completed two 14-day treatments with hypocaloric diet and 8.5 or 5.5-h nighttime sleep opportunity in random order 7 [3] months apart. Oral and intravenous glucose tolerance test (IVGTT) data, fasting lipids and free-fatty acids (FFA), and 24-hour blood glucose, insulin, C-peptide, and counter-regulatory hormone measurements were collected after each treatment. Participants had comparable weight loss (1.0 [0.3] BMI units) during each treatment. Bedtime restriction reduced sleep by 131 [30] min/day. Recurrent sleep curtailment decreased 24-hour serum insulin concentrations (i.e. enhanced 24-hour insulin economy) without changes in oral glucose tolerance and 24-hour glucose control. This was accompanied by a decline in fasting blood glucose, increased fasting FFA which suppressed normally following glucose ingestion, and lower total and LDL cholesterol concentrations. Sleep-loss-related changes in counter-regulatory hormone secretion during the IVGTT limited the utility of the test in this study. In conclusion, sleep restriction enhanced 24-hour insulin economy without compromising glucose homeostasis in overweight individuals placed on a balanced hypocaloric diet. The changes in fasting blood glucose, insulin, lipid and FFA concentrations in sleep-restricted dieters resembled the pattern of human metabolic adaptation to reduced carbohydrate availability. PMID:22513492

  9. Does diet-induced weight change effect anxiety in overweight and obese adults?

    PubMed

    Eyres, Stacey L; Turner, Anne I; Nowson, Caryl A; Torres, Susan J

    2014-01-01

    Anxiety is the most prevalent type of mental disorder and a significant health concern. Cross-sectional studies have detected a positive association between obesity and anxiety. What is less clear is whether weight loss can reduce anxiety. We sought to answer three questions: 1. Can weight loss improve symptoms of anxiety in the overweight and obese population? 2. Does the macronutrient content of energy-restricted diets that induce weight loss affect anxiety? 3. Is the change in anxiety related to the amount of weight lost? We investigated the findings from seven interventional studies, which induced weight loss by dietary intervention, in overweight and obese individuals, using established anxiety assessment tools. Mean weight loss ranged from 0.7 to 18.6 kg (SD 4.5) and in three of the studies, anxiety fell by 9.2% to 11.4% and did not change in four studies. When macronutrient content was considered, only one of four interventional studies and one pilot study reported a beneficial effect of a moderate-fat diet on anxiety. There appears to be no strong evidence to indicate that diet-induced weight loss has a beneficial effect on anxiety, however, none of the diet-induced weight loss studies assessed had a detrimental effect on anxiety.

  10. Diet-induced weight loss: the effect of dietary protein on bone.

    PubMed

    Tang, Minghua; O'Connor, Lauren E; Campbell, Wayne W

    2014-01-01

    High-protein (>30% of energy from protein or >1.2 g/kg/day) and moderately high-protein (22% to 29% of energy from protein or 1.0 to 1.2 g/kg/day) diets are popular for weight loss, but the effect of dietary protein on bone during weight loss is not well understood. Protein may help preserve bone mass during weight loss by stimulating insulin-like growth factor 1, a potent bone anabolism stimulator, and increasing intestinal calcium absorption. Protein-induced acidity is considered to have minimal effect on bone resorption in adults with normal kidney function. Both the quantity and predominant source of protein influence changes in bone with diet-induced weight loss. Higher-protein, high-dairy diets may help attenuate bone loss during weight loss.

  11. CNX-012-570, a direct AMPK activator provides strong glycemic and lipid control along with significant reduction in body weight; studies from both diet-induced obese mice and db/db mice models

    PubMed Central

    2014-01-01

    Objectives AMP activated protein kinase (AMPK) regulates the coordination of anabolic and catabolic processes and is an attractive therapeutic target for T2DM, obesity and metabolic syndrome. We report the anti-hyperglycemic and anti-hyperlipidemic effects of CNX-012-570 is an orally bioavailable small molecule (molecular weight of 530 Daltons) that directly activates AMPK in DIO and db/db animal models of diabetes. Methods Activity and efficacy of the compound was tested in cell based as well as cell free systems in vitro. Male C57BL/6 mice fed with high fat diet (HFD) were assigned to either vehicle or CNX-012-570 (3 mg/kg, orally once a day) for 8 weeks (n = 8). Genetically diabetic db/db mice on chow diet were dosed with vehicle control or CNX-012-570 (2.5 mg/kg, orally once a day) for 6 weeks (n = 8). Results CNX-012-570 is a highly potent and orally bioavailable compound activating AMPK in both cell and cell free systems. It inhibits lipolysis (33%) and gluconeogenesis (28%) in 3T3L1 cells and rat primary hepatocytes respectively. The efficacy of the molecule was translated to both DIO and db/db animal models of diabetes. CNX-012-570 has reduced fasting blood glucose levels by 14%, body weight by 24% and fasting serum triglycerides (TG) by 24%. CNX-012-570 showed a 22% reduction in fed serum cholesterol levels and 19% increase in HDL levels. In db/db mice model, CNX-012-570 has shown 18% decrease in fed glucose and 32% decrease in fasting glucose with a 2.57% reduction in absolute HbA1c. Decrease in serum insulin and glucose AUC indicates the increased insulin sensitivity. Body weight was reduced by 13% with increased browning of adipose tissue and decreased inguinal and mesenteric fat mass. There was significant reduction in liver TG and liver total cholesterol. Conclusions CNX-012-570 has the potential to control hyperglycemia and hyperlipidemia. It also reduces body weight gain with an additional benefit of minimizing cardiovascular risks in

  12. Ciliary neurotrophic factorAx15 alters energy homeostasis, decreases body weight, and improves metabolic control in diet-induced obese and UCP1-DTA mice.

    PubMed

    Blüher, Susann; Moschos, Stergios; Bullen, John; Kokkotou, Efi; Maratos-Flier, Eleftheria; Wiegand, Stanley J; Sleeman, Mark W; Sleemann, Mark W; Mantzoros, Christos S

    2004-11-01

    Ciliary neurotrophic factor (CNTF) potently reduces appetite and body weight in rodents and humans. We studied the short- and long-term effects of CNTF(Ax15), a second-generation CNTF analog, in diet-induced obese C57BL/6J mice and brown adipose tissue (BAT)-deficient obese UCP1-DTA (uncoupling protein 1-diphtheria toxin A) mice. CNTF(Ax15) administration (0.1, 0.3, or 1.0 microg . g(-1) . day(-1) s.c.) for 3 or 7 days reduced food intake and body weight (mainly body fat mass). The effect of CNTF(Ax15) on food intake and body weight was more pronounced in CNTF(Ax15)-treated diet-induced obese C57BL/6J mice compared with pair-fed controls and was associated with suppressed expression of hypothalamic neuropeptide Y and agouti gene-related protein. Moreover, CNTF(Ax15) increased uncoupling protein 1 mRNA expression in BAT and energy expenditure in diet-induced obese C57BL/6J mice. Longitudinal observations revealed a sustained reduction in body weight for several days post-CNTF(Ax15) treatment of CNTF(Ax15)-treated but not pair-fed mice, followed by a gradual regain in body weight over 28 days. Finally, CNTF(Ax15) administration improved the metabolic profile in both diet-induced obese C57BL/6J and UCP1-DTA mice and resulted in a significantly improved glycemic response to oral glucose tolerance tests in CNTF(Ax15)-treated UCP1-DTA compared with pair-fed mice of similar body weight. These data suggest that CNTF(Ax15) may act through a pathway downstream of the putative point responsible for leptin resistance in diet-induced obese C57BL/6J and UCP1-DTA mice to alter food intake, body weight, body composition, and metabolism. CNTF(Ax15) has delayed and persistent effects in diet-induced obese C57BL/6J mice, which account for a reduction in body weight over and above what would be expected based on decreased foot intake alone.

  13. Predictors of Diet-Induced Weight Loss in Overweight Adults with Type 2 Diabetes

    PubMed Central

    Mulder, Monique T.; Verhoeven, Adrie J. M.; van Wietmarschen, Herman; Boessen, Ruud; Pellis, Linette P.; van t Spijker, Adriaan; Timman, Reinier; Ozcan, Behiye; Sijbrands, Eric J. G.

    2016-01-01

    Aims A very low calorie diet improves the metabolic regulation of obesity related type 2 diabetes, but not for all patients, which leads to frustration in patients and professionals alike. The aim of this study was to develop a prediction model of diet-induced weight loss in type 2 diabetes. Methods 192 patients with type 2 diabetes and BMI>27 kg/m2 from the outpatient diabetes clinic of the Erasmus Medical Center underwent an 8-week very low calorie diet. Baseline demographic, psychological and physiological parameters were measured and the C-index was calculated of the model with the largest explained variance of relative weight loss using backward linear regression analysis. The model was internally validated using bootstrapping techniques. Results Weight loss after the diet was 7.8±4.6 kg (95%CI 7.2–8.5; p<0.001) and was independently associated with the baseline variables fasting glucose (B = -0.33 (95%CI -0.49, -0.18), p = 0.001), anxiety (HADS; B = -0.22 (95%CI -0.34, -0.11), p = 0.001), numb feeling in extremities (B = 1.86 (95%CI 0.85, 2.87), p = 0.002), insulin dose (B = 0.01 (95%CI 0.00, 0.02), p = 0.014) and waist-to-hip ratio (B = 6.79 (95%CI 2.10, 11.78), p = 0.003). This model explained 25% of the variance in weight loss. The C-index of this model to predict successful (≥5%) weight loss was 0.74 (95%CI 0.67–0.82), with a sensitivity of 0.93 (95% CI 0.89–0.97) and specificity of 0.29 (95% CI 0.16–0.42). When only the obese T2D patients (BMI≥30 kg/m2; n = 181) were considered, age also contributed to the model (B = 0.06 (95%CI 0.02, 0.11), p = 0.008), whereas waist-to-hip ratio did not. Conclusions Diet-induced weight loss in overweight adults with T2D was predicted by five baseline parameters, which were predominantly diabetes related. However, failure seems difficult to predict. We propose to test this prediction model in future prospective diet intervention studies in patients with type 2 diabetes. PMID:27494531

  14. Antagonism of T-type calcium channels inhibits high-fat diet-induced weight gain in mice.

    PubMed

    Uebele, Victor N; Gotter, Anthony L; Nuss, Cindy E; Kraus, Richard L; Doran, Scott M; Garson, Susan L; Reiss, Duane R; Li, Yuxing; Barrow, James C; Reger, Thomas S; Yang, Zhi-Qiang; Ballard, Jeanine E; Tang, Cuyue; Metzger, Joseph M; Wang, Sheng-Ping; Koblan, Kenneth S; Renger, John J

    2009-06-01

    The epidemics of obesity and metabolic disorders have well-recognized health and economic burdens. Pharmacologic treatments for these diseases remain unsatisfactory with respect to both efficacy and side-effect profiles. Here, we have identified a potential central role for T-type calcium channels in regulating body weight maintenance and sleep. Previously, it was shown that mice lacking CaV3.1 T-type calcium channels have altered sleep/wake activity. We found that these mice were also resistant to high-fat diet-induced weight gain, without changes in food intake or sensitivity to high-fat diet-induced disruptions of diurnal rhythm. Administration of a potent and selective antagonist of T-type calcium channels, TTA-A2, to normal-weight animals prior to the inactive phase acutely increased sleep, decreased body core temperature, and prevented high-fat diet-induced weight gain. Administration of TTA-A2 to obese rodents reduced body weight and fat mass while concurrently increasing lean muscle mass. These effects likely result from better alignment of diurnal feeding patterns with daily changes in circadian physiology and potentially an increased metabolic rate during the active phase. Together, these studies reveal what we believe to be a previously unknown role for T-type calcium channels in the regulation of sleep and weight maintenance and suggest the potential for a novel therapeutic approach to treating obesity.

  15. Intranasal leptin reduces appetite and induces weight loss in rats with diet-induced obesity (DIO).

    PubMed

    Schulz, Carla; Paulus, Kerstin; Jöhren, Olaf; Lehnert, Hendrik

    2012-01-01

    Resistance to brain-mediated effects of leptin is a characteristic feature of obesity, resulting from alterations in leptin receptor signaling in hypothalamic neurons and/or transport across the blood-brain-barrier. We have shown previously, that the latter can be circumvented by intranasal (i.n.) application of leptin in lean rats. This prompted us to test i.n. leptin in animals with diet-induced obesity (DIO) as a basis for future human administration. DIO was induced in male Wistar rats by feeding a cafeteria diet for 25 or 32 wk, respectively. Consecutively, these DIO animals (seven to eight per treatment) and standard diet rats (lean) (14-15 per treatment, matched for age and diet duration) were treated with 0.1, 0.2 mg/kg leptin, or control solution i.n. daily for 4 wk before onset of dark period. Energy intake and body weight were measured daily; blood glucose, serum insulin, and leptin were measured before and after treatment. Expression of hypothalamic neuropeptides was assessed by quantitative real-time PCR. We demonstrate, for the first time, that i.n. leptin reduces appetite and induces weight loss in DIO to the same extent as in lean rats. Our findings are supported accordingly by an altered expression pattern of anorexigenic and orexigenic neuropeptides in the hypothalamus, e.g. proopiomelanocortin, cocaine and amphetamine-related transcript, neuropeptide Y, agouti-related protein. It now appears clear that i.n. leptin is effectively acting in obese animals in the same fashion as in their lean counterparts. These findings now clearly warrant studies in humans and may open new perspectives in the treatment of obesity.

  16. Treatment with 17β-Estradiol Reduced Body Weight and the Risk of Cardiovascular Disease in a High-Fat Diet-Induced Animal Model of Obesity

    PubMed Central

    Ting, Wei-Jen; Huang, Chih-Yang; Jiang, Chong-He; Lin, Yueh-Min; Chung, Li-Chin; Shen, Chia-Yao; Pai, Peiying; Lin, Kuan-Ho; Viswanadha, Vijaya Padma; Liao, Shih-Chieh

    2017-01-01

    Estrogen receptor α (ERα) and estrogen receptor β (ERβ) play important roles in cardiovascular disease (CVD) prevention. Recently, these estrogen receptors were reconsidered as an important treatment target of obesity leading to CVD. In this study, 17β-estradiol (17β-E) replacement therapy applied to high-fat diet-induced obese C57B male mice and ovariectomized (OVX) rats were evaluated, and the protective effects against high-fat diet-induced obesity were assessed in C57B mouse hearts. The results showed that 17β-E treatment activated both ERα and ERβ, and ERβ levels increased in a dose-dependent manner in high-fat diet C57B mouse cardiomyocytes following 17β-E treatment. Notably, an almost 16% reduction in body weight was observed in the 17β-E-treated (12 μg/kg/day for 60 days) high-fat diet-induced obese C57B male mice. These results suggested that 17β-E supplements may reduce CVD risk due to obesity. PMID:28335423

  17. Caffeine Treatment Prevented from Weight Regain after Calorie Shifting Diet Induced Weight Loss

    PubMed Central

    Davoodi, Sayed Hossein; Hajimiresmaiel, Seyed Javad; Ajami, Marjan; Mohseni-Bandpei, Anoushiravan; Ayatollahi, Seyyed Abdulmajid; Dowlatshahi, Kamran; Javedan, Gholamali; Pazoki-Toroudi, Hamidreza

    2014-01-01

    Low calorie diets are always difficult for obese subjects to follow and lead to metabolic and behavioral adaptation. Therefore, we evaluated the effect of caffeine treatment with calorie shifting diet (CSD) on weight loss. Female subjects (n=60; BMI≥25) completed 4-weeks control diet, 6-weeks CSD (3 repeated phases; each 2-weeks) and 4-weeks follow-up diet, with or without caffeine treatment (5 mg/Kg/day). The first 11 days of each phase included calorie restriction with four meals every day and 4 hours intervals. Significant weight and fat loss were observed after 4-weeks of CSD (5.7 ± 1.24 Kg and 4.84 ± 1.53 Kg) or CSD+Caffeine (7.57 ± 2.33 Kg and 5.24 ± 2.07 Kg) which was consistent for one month of the follow-up (CSD: 5.24 ± 1.83 Kg and 4.3 ± 1.62 Kg, CSD+Caffeine: 12.11 ± 2.31 Kg and 9.85 ± 1.6 Kg, p < 0.05 vs CSD group) and correlated to the restricted energy intake (p < 0.05). During three CSD phases, RMR tended to remain unchanged in both groups.While, CSD or CSD + Caffeine treatments, significantly decreased plasma glucose, total-cholesterol, and triacylglycerol (p < 0.05), even during follow-up period (p < 0.05). HDL-cholesterol was not changed by CSD. Feeling of hunger decreased and subject’s satisfaction increased after 4-weeks of CSD (p < 0.05) and remained low to the end of study, while satiety was not affected. Coffeine increased the effect of CSD on feeling of hunger and subject’s satisfaction after week 7 (p < 0.05 vs. CSD). These findings indicated that combination of caffeine treatment with CSD could be an effective alternative approach to weight and fat loss with small changes in RMR and improved tolerance of subjects to the new diet. PMID:25237367

  18. Synergistic Effects of a GPR119 Agonist with Metformin on Weight Loss in Diet-Induced Obese Mice.

    PubMed

    Al-Barazanji, Kamal; McNulty, Judi; Binz, Jane; Generaux, Claudia; Benson, William; Young, Andrew; Chen, Lihong

    2015-06-01

    G protein-coupled receptor 119 (GPR119) is a G protein-coupled receptor expressed predominantly in pancreatic β-cells and gastrointestinal enteroendocrine cells. Metformin is a first-line treatment of type 2 diabetes, with minimal weight loss in humans. In this study, we investigated the effects of GSK2041706 [2-([(1S)-1-(1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl)ethyl]oxy)-5-[4-(methylsulfonyl)phenyl]pyrazine], a GPR119 agonist, and metformin as monotherapy or in combination on body weight in a diet-induced obese (DIO) mouse model. Relative to vehicle controls, 14-day treatment with GSK2041706 (30 mg/kg b.i.d.) or metformin at 30 and 100 mg/kg b.i.d. alone caused a 7.4%, 3.5%, and 4.4% (all P < 0.05) weight loss, respectively. The combination of GSK2041706 with metformin at 30 or 100 mg/kg resulted in a 9.5% and 16.7% weight loss, respectively. The combination of GSK2041706 and metformin at 100 mg/kg caused a significantly greater weight loss than the projected additive weight loss of 11.8%. This body weight effect was predominantly due to a loss of fat. Cumulative food intake was reduced by 17.1% with GSK2041706 alone and 6.6% and 8.7% with metformin at 30 and 100 mg/kg, respectively. The combination of GSK2041706 with metformin caused greater reductions in cumulative food intake (22.2% at 30 mg/kg and 37.5% at 100 mg/kg) and higher fed plasma glucagon-like peptide 1 and peptide tyrosine tyrosine levels and decreased plasma insulin and glucose-dependent insulinotropic polypeptide levels compared with their monotherapy groups. In addition, we characterized the effect of GSK2041706 and metformin as monotherapy or in combination on neuronal activation in the appetite regulating centers in fasted DIO mice. In conclusion, our data demonstrate the beneficial effects of combining a GPR119 agonist with metformin in the regulation of body weight in DIO mice.

  19. A rapidly occurring compensatory decrease in physical activity counteracts diet-induced weight loss in female monkeys.

    PubMed

    Sullivan, Elinor L; Cameron, Judy L

    2010-04-01

    To study changes in energy balance occurring during the initial phases of dieting, 18 adult ovariectomized female monkeys were placed on a low-fat diet, and available calories were reduced by 30% compared with baseline consumption for 1 mo. Surprisingly, there was not significant weight loss; however, daily activity level (measured by accelerometry) decreased soon after diet initiation and reached statistical significance by the 4th wk of dieting (18 +/- 5.6% decrease, P = 0.02). During a 2nd mo of dieting, available calories were reduced by 60% compared with baseline consumption, leading to 6.4 +/- 1.7% weight loss and further suppression of activity. Metabolic rate decreased by 68 +/- 12 kcal/day, with decreased activity accounting for 41 +/- 9 kcal/day, and the metabolic activity of the weight lost accounting for 21 +/- 5 kcal/day. A second group of three monkeys was trained to run on a treadmill for 1 h/day, 5 days/wk, at 80% maximal capacity, leading to increased calorie expenditure of 69.6 +/- 10.7 kcal/day (equivalent to 49 kcal/day for 7 days). We conclude that a diet-induced decrease in physical activity is the primary mechanism the body uses to defend against diet-induced weight loss, and undertaking a level of exercise that is recommended to counteract weight gain and promote weight loss is able to prevent the compensatory decrease in physical activity-associated energy expenditure that slows diet-induced weight loss.

  20. Peripheral reduction of FGFR4 with antisense oligonucleotides increases metabolic rate and lowers adiposity in diet-induced obese mice.

    PubMed

    Yu, Xing Xian; Watts, Lynnetta M; Manchem, Vara Prasad; Chakravarty, Kaushik; Monia, Brett P; McCaleb, Michael L; Bhanot, Sanjay

    2013-01-01

    Obesity is a primary risk factor for multiple metabolic disorders. Many drugs for the treatment of obesity, which mainly act through CNS as appetite suppressants, have failed during development or been removed from the market due to unacceptable adverse effects. Thus, there are very few efficacious drugs available and remains a great unmet medical need for anti-obesity drugs that increase energy expenditure by acting on peripheral tissues without severe side effects. Here, we report a novel approach involving antisense inhibition of fibroblast growth factor receptor 4 (FGFR4) in peripheral tissues. Treatment of diet-induce obese (DIO) mice with FGFR4 antisense oligonucleotides (ASO) specifically reduced liver FGFR4 expression that not only resulted in decrease in body weight (BW) and adiposity in free-feeding conditions, but also lowered BW and adiposity under caloric restriction. In addition, combination treatment with FGFR4 ASO and rimonabant showed additive reduction in BW and adiposity. FGFR4 ASO treatment increased basal metabolic rate during free-feeding conditions and, more importantly, prevented adaptive decreases of metabolic rate induced by caloric restriction. The treatment increased fatty acid oxidation while decreased lipogenesis in both liver and fat. Mechanistic studies indicated that anti-obesity effect of FGFR4 ASO was mediated at least in part through an induction of plasma FGF15 level resulted from reduction of hepatic FGFR4 expression. The anti-obesity effect was accompanied by improvement in plasma glycemia, whole body insulin sensitivity, plasma lipid levels and liver steatosis. Therefore, FGFR4 could be a potential novel target and antisense reduction of hepatic FGFR4 expression could be an efficacious therapy as an adjunct to diet restriction or to an appetite suppressant for the treatment of obesity and related metabolic disorders.

  1. Transgenic rescue of adipocyte glucose-dependent insulinotropic polypeptide receptor expression restores high fat diet-induced body weight gain.

    PubMed

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

    2011-12-30

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

  2. Performance on the Iowa Gambling Task is related to magnitude of weight loss and salivary cortisol in a diet-induced weight loss intervention in overweight women.

    PubMed

    Witbracht, Megan G; Laugero, Kevin D; Van Loan, Marta D; Adams, Sean H; Keim, Nancy L

    2012-05-15

    The overall objective of this study was to examine the relationship between executive function, specifically decision-making, and weight loss. We used the Iowa Gambling Task (IGT) to characterize decision-making and compared performance on this task to weight loss in obese women (n=29) participating in a 12-week controlled, calorie-reduced intervention. We hypothesized that a greater amount of weight loss over the course of the intervention would be associated with better performance on the IGT, assessed at the end of the intervention. The intervention led to significant weight loss of 5.8±3.1 kg (p<0.05) and fat loss of 5.1±3.0 kg (p<0.05). Body weight and fat mass losses over the 12-week intervention varied widely, ranging from -12.5 kg to 0.0 kg for body weight and -10.4 kg to +0.8 kg for fat mass. A greater amount of body weight loss was correlated (r=0.425; p<0.01) with a higher total score on the IGT. Similarly, the reduction in body fat mass was also correlated with the IGT score (r=0.408; p<0.05). We examined other physiological (salivary cortisol), metabolic (resting energy expenditure), and behavioral (food intake; dietary restraint) factors that might be related to differences in the magnitude of weight loss. Of these variables, ad libitum consumption of energy, fat and protein during a buffet meal was inversely related to weight loss (r=-0.428; p<0.05; r=-0.375; p<0.05 and r=-0.472; p=0.01, respectively). The present study is the first to report an association between diet-induced weight loss and performance on the IGT, and this association was specific to the loss of body fat. Our results suggest that differences in weight loss may be linked to executive function that involves decision-making about events that have emotionally or socially salient ramifications. These findings underscore the need to further investigate higher cognitive and neuroendocrine pathways that may influence or be altered by the process of dieting and weight loss.

  3. Effects of different intermittent peptide YY (3-36) dosing strategies on food intake, body weight, and adiposity in diet-induced obese rats.

    PubMed

    Reidelberger, Roger D; Haver, Alvin C; Chelikani, Prasanth K; Buescher, James L

    2008-08-01

    Chronic administration of anorexigenic substances to experimental animals by injections or continuous infusion typically produces either no effect or a transient reduction in food intake and body weight. Our aim here was to identify an intermittent dosing strategy for intraperitoneal infusion of peptide YY(3-36) [PYY(3-36)] that produces a sustained reduction in daily food intake and adiposity in diet-induced obese rats. Rats (665+/-10 g body wt, 166+/-7 g body fat) with intraperitoneal catheters tethered to infusion swivels had free access to a high-fat diet. Vehicle-treated rats (n=23) had relatively stable food intake, body weight, and adiposity during the 9-wk test period. None of 15 PYY(3-36) dosing regimens administered in succession to a second group of rats (n=22) produced a sustained 15-25% reduction in daily food intake for >5 days, although body weight and adiposity were reduced across the 9-wk period by 12% (594+/-15 vs. 672+/-15 g) and 43% (96+/-7 vs. 169+/-9 g), respectively. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was >or=3 h appeared to be due in part to an increase in food intake between infusions. The declining inhibitory effect of PYY(3-36) on daily food intake when the interinfusion interval was <3 h suggested possible receptor downregulation and tolerance to frequent PYY(3-36) administration; however, food intake significantly increased when PYY(3-36) treatments were discontinued for 1 day following apparent loss in treatment efficacies. Together, these results demonstrate the development of a potent homeostatic response to increase food intake when PYY(3-36) reduces food intake and energy reserves in diet-induced obese rats.

  4. Deoxynivalenol-induced weight loss in the diet-induced obese mouse is reversible and PKR-independent.

    PubMed

    Flannery, Brenna M; He, Kaiyu; Pestka, James J

    2013-07-31

    The trichothecene deoxynivalenol (DON), a potent ribotoxic mycotoxin produced by the cereal blight fungus Fusarium graminearum, commonly contaminates grain-based foods. Oral exposure to DON causes decreased food intake, reduced weight gain and body weight loss in experimental animals - effects that have been linked to dysregulation of hormones responsible for mediating satiety at the central nervous system level. When diet-induced obese (DIO) mice are fed DON, they consume less food, eventually achieving body weights of control diet-fed mice. Here, we extended these findings by characterizing: (1) reversibility of DON-induced body weight loss and anorexia in DIO mice and (2) the role of double-stranded RNA-activated protein kinase (PKR) which has been previously linked to initiation of the ribotoxic stress response. The results demonstrated that DON-induced weight loss was reversible in DIO mice and this effect corresponded to initiation of a robust hyperphagic response. When DIO mice deficient in PKR were exposed to DON, they exhibited weight suppression similar to DIO wild-type fed the toxin, suggesting the toxin's weight effects were not dependent on PKR. Taken together, DON's effects on food consumption and body weight are not permanent and, furthermore, PKR is not an essential signaling molecule for DON's anorectic and weight effects.

  5. Effect of Bergenia crassifolia L. extracts on weight gain and feeding behavior of rats with high-caloric diet-induced obesity.

    PubMed

    Shikov, Alexander N; Pozharitskaya, Olga N; Makarova, Marina N; Kovaleva, Maria A; Laakso, Into; Dorman, H J Damien; Hiltunen, Raimo; Makarov, Valery G; Galambosi, Bertalan

    2012-11-15

    The objective of this study was to evaluate the feeding behavior and weight gain in rats with high-calorie diet-induced obesity that are treated with Bergenia crassifolia black and fermented leaves extracts. The daily dietary intake of all treated animals was reduced to 40% compared with the control group on day 22 of the experiment. A significant improvement in glucose tolerance was noted after 7 days of treatment with the Bergenia extracts. In rats treated with an extract of black leaves for 7 days, a significant reduction in the serum triglyceride level, 45% (p<0.05), compared with the control group was observed. However, the treatment did not affect the cholesterol level. Our results provide evidence for the potential use of B. crassifolia as an appetite and energy intake suppressant.

  6. Loss of UCP1 exacerbates Western diet-induced glycemic dysregulation independent of changes in body weight in female mice.

    PubMed

    Winn, Nathan C; Vieira-Potter, Victoria J; Gastecki, Michelle L; Welly, Rebecca J; Scroggins, Rebecca J; Zidon, Terese M; Gaines, T'Keaya L; Woodford, Makenzie L; Karasseva, Natalia G; Kanaley, Jill A; Sacks, Harold S; Padilla, Jaume

    2017-01-01

    We tested the hypothesis that female mice null for uncoupling protein 1 (UCP1) would have increased susceptibility to Western diet-induced "whitening" of brown adipose tissue (AT) and glucose intolerance. Six-week-old C57BL/6J wild-type (WT) and UCP1 knockout (UCP1(-/-)) mice, housed at 25°C, were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 28 wk. Loss of UCP1 had no effect on energy intake, energy expenditure, spontaneous physical activity, weight gain, or visceral white AT mass. Despite similar susceptibility to weight gain compared with WT, UCP1(-/-) exhibited whitening of brown AT evidenced by a striking ~500% increase in mass and appearance of large unilocular adipocytes, increased expression of genes related to inflammation, immune cell infiltration, and endoplasmic reticulum/oxidative stress (P < 0.05), and decreased mitochondrial subunit protein (COX I, II, III, and IV, P < 0.05), all of which were exacerbated by Western diet (P < 0.05). UCP1(-/-) mice also developed liver steatosis and glucose intolerance, which was worsened by Western diet. Collectively, these findings demonstrate that loss of UCP1 exacerbates Western diet-induced whitening of brown AT, glucose intolerance, and induces liver steatosis. Notably, the adverse metabolic manifestations of UCP1(-/-) were independent of changes in body weight, visceral adiposity, and energy expenditure. These novel findings uncover a previously unrecognized metabolic protective role of UCP1 that is independent of its already established role in energy homeostasis.

  7. Effects of exendin-4 alone and with peptide YY(3-36) on food intake and body weight in diet-induced obese rats.

    PubMed

    Reidelberger, Roger D; Haver, Alvin C; Apenteng, Bettye A; Anders, Krista L; Steenson, Sharalyn M

    2011-01-01

    Significant weight loss following Roux-en-Y gastric bypass surgery (RYGB) in obese humans correlates with enhanced secretion of anorexigenic gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY(3-36) (PYY(3-36)). Our aim here was to identify a dosing strategy for intraperitoneal (IP) infusion of GLP-1 homologue exendin-4 alone and with PYY(3-36) that produces a sustained reduction in daily food intake and body weight in diet-induced obese (DIO) rats. We tested 12 exendin-4 strategies over 10 weeks. Exendin-4 infused during the first and last 3 h of the dark period at 15-20 pmol/h (0.15 nmol/kg/day) produced a sustained 24 ± 1% reduction in daily food intake for 17 days, and decreased body weight by 7%. In a separate group of DIO rats, none of seven dosing strategies combining exendin-4 and PYY(3-36) produced a similar reduction in daily food intake for >10 days. The subsequent decline in efficacies of exendin-4 alone and with PYY(3-36) on food intake and body weight in each experiment suggested possible receptor downregulation and tolerance to treatments. However, when treatments were discontinued for 1 day following losses in efficacies, daily food intake significantly increased. Together, these results demonstrate that (i) intermittent IP infusion of a low dose of exendin-4 can produce a relatively prolonged reduction in daily food intake and body weight in DIO rats, (ii) co-infusion of exendin-4 and PYY(3-36) does not further prolong this response, and (iii) activation of an orexigenic mechanism gradually occurs to counteract the inhibitory effects of exendin-4 alone and with PYY(3-36) on food intake and body weight.

  8. Cyp8b1 ablation prevents western diet-induced weight gain and hepatic steatosis due to impaired fat absorption.

    PubMed

    Bertaggia, Enrico; Jensen, Kristian K; Castro-Perez, Jose; Xu, Yimeng; Di Paolo, Gilbert; Chan, Robin B; Wang, Liangsu; Haeusler, Rebecca A

    2017-04-04

    Bile acids (BAs) are cholesterol derivatives that regulate lipid metabolism, through their dual abilities to promote lipid absorption and activate BA receptors. However, different BA species have varying abilities to perform these functions. Eliminating 12α-hydroxy BAs in mice via Cyp8b1 knockout causes low body weight and improved glucose tolerance. The goal of this study was to determine mechanisms of low body weight in Cyp8b1(-/-) mice. We challenged Cyp8b1(-/-) mice with western type diet and assessed body weight and composition. We measured energy expenditure, fecal calories, lipid absorption and performed lipidomic studies on feces and intestine. We investigated the requirement for dietary fat in the phenotype using a fat-free diet. Cyp8b1(-/-) mice were resistant to western diet-induced body weight gain, hepatic steatosis, and insulin resistance. These changes were associated with increased fecal calories, due to malabsorption of hydrolyzed dietary triglycerides. This was reversed by treating the mice with taurocholic acid, the major 12α-hydroxylated BA species. The improvements in body weight and steatosis were normalized by feeding mice a fat-free diet. The effects of BA composition on intestinal lipid handling are important for whole-body energy homeostasis. Thus, modulating BA composition is a potential tool for obesity or diabetes therapy.

  9. A dual epigenomic approach for the search of obesity biomarkers: DNA methylation in relation to diet-induced weight loss.

    PubMed

    Milagro, Fermin I; Campión, Javier; Cordero, Paúl; Goyenechea, Estíbaliz; Gómez-Uriz, Ana M; Abete, Itziar; Zulet, Maria A; Martínez, J Alfredo

    2011-04-01

    Epigenetics could help to explain individual differences in weight loss after an energy-restriction intervention. Here, we identify novel potential epigenetic biomarkers of weight loss, comparing DNA methylation patterns of high and low responders to a hypocaloric diet. Twenty-five overweight or obese men participated in an 8-wk caloric restriction intervention. DNA was isolated from peripheral blood mononuclear cells and treated with bisulfite. The basal and endpoint epigenetic differences between high and low responders were analyzed by methylation microarray, which was also useful in comparing epigenetic changes due to the nutrition intervention. Subsequently, MALDI-TOF mass spectrometry was used to validate several relevant CpGs and the surrounding regions. DNA methylation levels in several CpGs located in the ATP10A and CD44 genes showed statistical baseline differences depending on the weight-loss outcome. At the treatment endpoint, DNA methylation levels of several CpGs on the WT1 promoter were statistically more methylated in the high than in the low responders. Finally, different CpG sites from WT1 and ATP10A were significantly modified as a result of the intervention. In summary, hypocaloric-diet-induced weight loss in humans could alter DNA methylation status of specific genes. Moreover, baseline DNA methylation patterns may be used as epigenetic markers that could help to predict weight loss.

  10. Chronic 5-HT6 receptor modulation by E-6837 induces hypophagia and sustained weight loss in diet-induced obese rats

    PubMed Central

    Fisas, Angels; Codony, Xavier; Romero, Gonzalo; Dordal, Alberto; Giraldo, Jesus; Mercé, Ramon; Holenz, Jörg; Heal, David; Buschmann, Helmut; Pauwels, Petrus Johan

    2006-01-01

    E-6837 is a novel, selective and high-affinity 5-HT6 receptor ligand (pKi: 9.13) which in vitro demonstrates partial agonism at a presumably silent rat 5-HT6 receptor and full agonism at a constitutively active human 5-HT6 receptor by monitoring the cAMP signaling pathway. The effects of chronic treatment with E-6837 were determined in diet-induced obese (DIO)-rats on changes in body weight, food and water intake, plasma indices of comorbid risk factors, and weight regain on compound withdrawal. The centrally acting antiobesity drug, sibutramine, was used as the reference comparator. Sustained body weight loss and decreased cumulative food intake of DIO-rats was observed with E-6837 (30 mg kg−1, p.o., twice a day) during the 4-week treatment period. The onset of the E-6837 effect on body weight was slower than that of sibutramine (5 mg kg−1, p.o.), while its maximal effect was greater, that is −15.7 versus −11.0%. E-6837-induced weight loss was exclusively mediated by a decrease (31.7%) in fat mass, with a concomitant reduction (49.6%) in plasma leptin. Reduced obesity was also reflected in improved glycemic control. Although weight regain occurred after withdrawal from either compound, the body weights after E-6837 (−6.6%) remained lower than after sibutramine (−3.8%) indicating that the greater efficacy of the former did not result in profound rebound hyperphagia/weight gain. These results show that the 5-HT6 receptor partial agonist, E-6837, is a promising new approach to the management of obesity with the potential to produce greater sustained weight loss than sibutramine. PMID:16783408

  11. Intermittent Moderate Energy Restriction Improves Weight Loss Efficiency in Diet-Induced Obese Mice

    PubMed Central

    Seimon, Radhika V.; Shi, Yan-Chuan; Slack, Katy; Lee, Kailun; Fernando, Hamish A.; Nguyen, Amy D.; Zhang, Lei; Lin, Shu; Enriquez, Ronaldo F.; Lau, Jackie

    2016-01-01

    Background Intermittent severe energy restriction is popular for weight management. To investigate whether intermittent moderate energy restriction may improve this approach by enhancing weight loss efficiency, we conducted a study in mice, where energy intake can be controlled. Methods Male C57/Bl6 mice that had been rendered obese by an ad libitum diet high in fat and sugar for 22 weeks were then fed one of two energy-restricted normal chow diets for a 12-week weight loss phase. The continuous diet (CD) provided 82% of the energy intake of age-matched ad libitum chow-fed controls. The intermittent diet (ID) provided cycles of 82% of control intake for 5–6 consecutive days, and ad libitum intake for 1–3 days. Weight loss efficiency during this phase was calculated as (total weight change) ÷ [(total energy intake of mice on CD or ID)–(total average energy intake of controls)]. Subsets of mice then underwent a 3-week weight regain phase involving ad libitum re-feeding. Results Mice on the ID showed transient hyperphagia relative to controls during each 1–3-day ad libitum feeding period, and overall ate significantly more than CD mice (91.1±1.0 versus 82.2±0.5% of control intake respectively, n = 10, P<0.05). There were no significant differences between CD and ID groups at the end of the weight loss or weight regain phases with respect to body weight, fat mass, circulating glucose or insulin concentrations, or the insulin resistance index. Weight loss efficiency was significantly greater with ID than with CD (0.042±0.007 versus 0.018±0.001 g/kJ, n = 10, P<0.01). Mice on the CD exhibited significantly greater hypothalamic mRNA expression of proopiomelanocortin (POMC) relative to ID and control mice, with no differences in neuropeptide Y or agouti-related peptide mRNA expression between energy-restricted groups. Conclusion Intermittent moderate energy restriction may offer an advantage over continuous moderate energy restriction, because it induces

  12. Enhanced amylin-mediated body weight loss in estradiol-deficient diet-induced obese rats.

    PubMed

    Trevaskis, James L; Turek, Victoria F; Wittmer, Carrie; Griffin, Peter S; Wilson, Julie K; Reynolds, James M; Zhao, Yu; Mack, Christine M; Parkes, David G; Roth, Jonathan D

    2010-12-01

    In rodents, ovariectomy (OVX) elicits weight gain and diminished responsiveness to homeostatic signals. Here we characterized the response of obese OVX rats to peripheral amylin. Rats received sham surgery (SHAM), OVX, or OVX with hormonal replacement (17β-estradiol, 2 μg per 4 d; OVX+E) and were infused with vehicle or amylin (50 μg/kg · d) for 28 d. Amylin reduced body weight (5.1 ± 1.1%) and food intake (10.9 ± 3.4%) in SHAM rats but was twice as efficacious in OVX rats in reducing weight (11.2 ± 1.9%) and food intake (23.0 ± 2.0%). There were no differences between amylin-treated SHAM and OVX+E rats. OVX decreased metabolic rate (∼24%) and increased respiratory exchange ratio relative to SHAM. Amylin partially normalized metabolic rate (13% increase) in OVX rats and decreased respiratory exchange ratio in OVX and SHAM rats. Regarding central mechanisms, amylin infusion corrected the OVX-induced decrease in hippocampal neurogenesis and increased immobility in the forced swim test. Additionally, amylin increased neurogenesis (∼2-fold) within the area postrema of OVX rats. To assess the contribution of endogenous leptin to amylin-mediated weight loss in OVX rats, amylin was administered to SHAM or OVX Zucker diabetic fatty rats. In SHAM rats, amylin infusion reduced food intake but not body weight, whereas in OVX Zucker diabetic fatty rats, food intake, body weight, and insulin were reduced. Overall, amylin induced greater body weight loss in the absence of estradiol via central and peripheral actions that did not require leptin. These findings support the clinical investigation of amylin in low estradiol (e.g. postmenopausal) states.

  13. Diet induced weight loss accelerates onset of negative alliesthesia in obese women

    PubMed Central

    Frankham, Patrick; Gosselin, Caroline; Cabanac, Michel

    2005-01-01

    Background The physiological and behavioral responses to hypocaloric diet are to increase energy intake to defend a steady body weight. We utilized the method of "negative alliesthesia" for measuring the hedonic reponse to sweet stimulus before (Initial session) and 3 months after entering a weight loss program. The negative alliesthesia test is known by physiologists but few clinical data exist. It is based on the observation that repeated pleasant gustatory stimuli turn into unpleasantness in the process of alliesthesia. At first visit participants repeatedly ingested sweet stimuli until they found them unpleasant and rated quantitatively on a linear analogue scale their hedonic experience. This procedure was repeated every 3 min until participants felt displeasure to end the session. The same protocol was followed after three months of following a weight loss diet. Dieting energy intake was from 1400 – 2000 kcal/d for 8 wk. Energy composition was 50% carb:25% prot: 25% lipid. After 8 wk caloric intake increased by 50 kcal/wk, to reach daily intake of 1800 – 2400 kcal/d. Energy composition was 50% carb:22% prot: 27% lipid. We report results on the effect of slow weight loss on negative alliesthesia in ten obese female participants enrolled in a commercial diet program based on Canada's Food Guide (Mincavi®). Results Results showed that diet lowered the mean BMI (Initial session 36.8 +/- 1.8 vs. 3 mo 34.9 +/- 1.8 kg/m2). At 3 mo the onset of negative alliesthesia, time to abandon experimental session, was shortened (Initial session 33 vs. 3 mo 24 min). The same trend was observed in the time to reach indifference (Initial session 21.9 +/- 3.8 vs. 3 mo 16.2 +/-2.4 min). There was no observed difference in maximum (Initial session +79.5 +/- 11.7; 3 mo +94.5 +/- 9.9 mm) and minimum (Initial session -90.0 +/- 14.4; 3 mo -106 +/- 11.1 mm) hedonic rating. Conclusion Earlier onset of negative alliesthesia, as seen in our participants, is not consistent with previous

  14. Zingiber mioga reduces weight gain, insulin resistance and hepatic gluconeogenesis in diet-induced obese mice

    PubMed Central

    LEE, DA-HYE; AHN, JIYUN; JANG, YOUNG JIN; HA, TAE-YOUL; JUNG, CHANG HWA

    2016-01-01

    Zingiber mioga is a perennial herb belonging to the ginger family (Zingiberaceae) that is used medicinally to treat cough and rheumatism in China and consumed throughout Japan. The aim of the present study was to investigate the anti-obesity effects of Z. mioga following extraction with distilled water or 70% ethanol. In 3T3-L1 preadipocyte cells, Z. mioga water extract (ZMW) markedly inhibited adipogenesis, whereas the ethanol extract had no effect. In addition, we conducted ZMW feeding experiments (0.25 or 0.5% ZMW) in high-fat diet (HFD)-fed mice to examine the anti-obesity effects of Z. mioga in vivo. Body weight and serum triglyceride and cholesterol levels significantly decreased in the HFD + ZMW 0.5% group. Notably, ZMW decreased liver weight but not adipose tissue weight. Furthermore, insulin resistance and hepatic mRNA expression of gluconeogenic genes, such as phosphoenolpyruvate carboxykinase and G6Pase, were improved in the HFD + ZMW 0.5% group. Furthermore, ZMW treatment decreased hepatic lipogenic gene expression; however, it did not alter adipogenesis in fat tissue, suggesting that ZMW inhibits hepatosteatosis through the suppression of lipogenesis. ZMW improved HFD-induced hepatic inflammation. Collectively, the present findings suggest that ZMW may serve as a new and promising strategy for the treatment of hepatosteatosis. PMID:27347064

  15. Diet-induced changes in n-3 and n-6 derived endocannabinoids and reductions in headache pain and psychological distress

    PubMed Central

    Ramsden, Christopher E.; Zamora, Daisy; Makriyannis, Alexandros; Wood, JodiAnne T.; Mann, J. Douglas; Faurot, Keturah R.; MacIntosh, Beth A.; Majchrzak-Hong, Sharon F.; Gross, Jacklyn R.; Courville, Amber B.; Davis, John M.; Hibbeln, Joseph R.

    2015-01-01

    Omega-3 and omega-6 fatty acids are biosynthetic precursors to endocannabinoids with antinociceptive, anxiolytic, and neurogenic properties. We recently reported that targeted dietary manipulation—increasing omega-3 fatty acids while reducing omega-6 linoleic acid (the H3-L6 intervention)—reduced headache pain and psychological distress among chronic headache patients. It is not yet known whether these clinical improvements were due to changes in endocannabinoids and related mediators derived from omega-3 and omega-6 fatty acids. We therefore used data from this trial (n=55) to investigate (1) whether the H3-L6 intervention altered omega-3 and omega-6 derived endocannabinoids in plasma, and (2) whether diet-induced changes in these bioactive lipids were associated with clinical improvements. The H3-L6 intervention significantly increased the omega-3 docosahexaenoic acid derivatives 2-docosahexaenoylglycerol (+65%, p<0.001) and docosahexaenoylethanolamine (+99%, p<0.001), and reduced the omega-6 arachidonic acid derivative 2-arachidonoylglycerol (-25%, p=0.001). Diet-induced changes in these endocannabinoid derivatives of omega-3 docosahexaenoic acid, but not omega-6 arachidonic acid, correlated with reductions in physical pain and psychological distress. These findings demonstrate that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids in humans, and suggest that 2-docosahexaenoylglycerol and docosahexaenoylethanolamine could have physical and/or psychological pain modulating properties. Trial Registration: ClinicalTrials.gov (NCT01157208) Perspective This article demonstrates that targeted dietary manipulation can alter endocannabinoids derived from omega-3 and omega-6 fatty acids, and that these changes are related to reductions in headache pain and psychological distress. These findings suggest that dietary interventions could provide an effective, complementary approach for managing chronic pain and related

  16. High-Density Lipoprotein-Associated miR-223 Is Altered after Diet-Induced Weight Loss in Overweight and Obese Males

    PubMed Central

    Tabet, Fatiha; Cuesta Torres, Luisa F.; Ong, Kwok Leung; Shrestha, Sudichhya; Choteau, Sébastien A.; Barter, Philip J.; Clifton, Peter; Rye, Kerry-Anne

    2016-01-01

    Background and Aims microRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males. Methods HDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically. Results miR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size. Conclusion HDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss. PMID:26962854

  17. Does Diet-Induced Weight Loss Lead to Bone Loss in Overweight or Obese Adults? A Systematic Review and Meta-Analysis of Clinical Trials.

    PubMed

    Zibellini, Jessica; Seimon, Radhika V; Lee, Crystal M Y; Gibson, Alice A; Hsu, Michelle S H; Shapses, Sue A; Nguyen, Tuan V; Sainsbury, Amanda

    2015-12-01

    Diet-induced weight loss has been suggested to be harmful to bone health. We conducted a systematic review and meta-analysis (using a random-effects model) to quantify the effect of diet-induced weight loss on bone. We included 41 publications involving overweight or obese but otherwise healthy adults who followed a dietary weight-loss intervention. The primary outcomes examined were changes from baseline in total hip, lumbar spine, and total body bone mineral density (BMD), as assessed by dual-energy X-ray absorptiometry (DXA). Secondary outcomes were markers of bone turnover. Diet-induced weight loss was associated with significant decreases of 0.010 to 0.015 g/cm(2) in total hip BMD for interventions of 6, 12, or 24 (but not 3) months' duration (95% confidence intervals [CIs], -0.014 to -0.005, -0.021 to -0.008, and -0.024 to -0.000 g/cm(2), at 6, 12, and 24 months, respectively). There was, however, no statistically significant effect of diet-induced weight loss on lumbar spine or whole-body BMD for interventions of 3 to 24 months' duration, except for a significant decrease in total body BMD (-0.011 g/cm(2); 95% CI, -0.018 to -0.003 g/cm(2)) after 6 months. Although no statistically significant changes occurred in serum concentrations of N-terminal propeptide of type I procollagen (P1NP), interventions of 2 or 3 months in duration (but not of 6, 12, or 24 months' duration) induced significant increases in serum concentrations of osteocalcin (0.26 nmol/L; 95% CI, 0.13 to 0.39 nmol/L), C-terminal telopeptide of type I collagen (CTX) (4.72 nmol/L; 95% CI, 2.12 to 7.30 nmol/L) or N-terminal telopeptide of type I collagen (NTX) (3.70 nmol/L; 95% CI, 0.90 to 6.50 nmol/L bone collagen equivalents [BCEs]), indicating an early effect of diet-induced weight loss to promote bone breakdown. These data show that in overweight and obese individuals, a single diet-induced weight-loss intervention induces a small decrease in total hip BMD, but not lumbar spine

  18. Ventromedial hypothalamic NPY Y2 receptor in the maintenance of body weight in diet-induced obesity in mice.

    PubMed

    Huang, Xu-Feng; Yu, Yinghua; Li, Yulin; Tim, South; Deng, Chao; Wang, Qing

    2008-09-01

    This study examined changes in neuropeptide Y (NPY) Y2 receptor binding in the brains of C57BL/6 mice in response to different levels of high-fat diets via three dietary intervention methods: high-fat diet, switching from high- to low-fat diet and finally, energy restricted high-fat diet. Forty-five C57Bl/6 male mice were fed a high-fat diet for 8 weeks and then classified as diet-induced obese (DIO) or diet-resistant (DR) mice according to the highest and lowest body weight gainers, respectively. The DIO and DR mice were then randomly divided into three groups each and either continued on their high-fat diet ad libitum (DIO-H and DR-H), changed to a low-fat diet (DIO-L and DR-L) or pair-fed via energy restricted high-fat diet (DIO-P and DR-P) for a further 6 weeks. During the course of this study, body weight, energy intake and plasma peptide YY (PYY) were measured. The study revealed that the replacement of a high-fat diet with a low-fat diet was associated with a significant lowering of ventromedial hypothalamic (VMH) Y2 receptor binding in both the DIO-L and DR-L mice (-37%, -36%), and also a lowered plasma PYY level in the DIO-L mice (-25%). Despite a continued consumption of the high-fat diet, energy restricted pair feeding caused a lower VMH Y2 receptor binding in the obese mice (DIO-P) following weight loss compared to the DR-P mice (-14%). In conclusion, this study showed that changing diets from high- to low-fat can significantly lower the VMH Y2 receptor binding irrespective to the obesity phenotype. Energy restriction, even while on high-fat feeding, can cause a lower VMH Y2 receptor binding compared to DR mice even after body weight loss to similar levels. This suggests either a possible intrinsic nature of the DIO mice or a body weight set-point re-establishment to drive body weight regain.

  19. Maternal diet-induced obesity programs cardiovascular dysfunction in adult male mouse offspring independent of current body weight.

    PubMed

    Blackmore, Heather L; Niu, Youguo; Fernandez-Twinn, Denise S; Tarry-Adkins, Jane L; Giussani, Dino A; Ozanne, Susan E

    2014-10-01

    Obese pregnancies are not only associated with adverse consequences for the mother but also the long-term health of her child. Human studies have shown that individuals from obese mothers are at increased risk of premature death from cardiovascular disease (CVD), but are unable to define causality. This study aimed to determine causality using a mouse model of maternal diet-induced obesity. Obesity was induced in female C57BL/6 mice by feeding a diet rich in simple sugars and saturated fat 6 weeks prior to pregnancy and throughout pregnancy and lactation. Control females were fed laboratory chow. Male offspring from both groups were weaned onto chow and studied at 3, 5, 8, and 12 weeks of age for gross cardiac morphometry using stereology, cardiomyocyte cell area by histology, and cardiac fetal gene expression using qRT-PCR. Cardiac function was assessed by isolated Langendorff technology at 12 weeks of age and hearts were analyzed at the protein level for the expression of the β1 adrenergic receptor, muscarinic type-2 acetylcholine receptor, and proteins involved in cardiac contraction. Offspring from obese mothers develop pathologic cardiac hypertrophy associated with re-expression of cardiac fetal genes. By young adulthood these offspring developed severe systolic and diastolic dysfunction and cardiac sympathetic dominance. Importantly, cardiac dysfunction occurred in the absence of any change in corresponding body weight and despite the offspring eating a healthy low-fat diet. These findings provide a causal link to explain human observations relating maternal obesity with premature death from CVD in her offspring.

  20. Potential probiotic Bifidobacterium animalis ssp. lactis 420 prevents weight gain and glucose intolerance in diet-induced obese mice.

    PubMed

    Stenman, L K; Waget, A; Garret, C; Klopp, P; Burcelin, R; Lahtinen, S

    2014-12-01

    Alterations of the gut microbiota and mucosal barrier are linked with metabolic diseases. Our aim was to investigate the potential benefit of the potential probiotic Bifidobacterium animalis ssp. lactis 420 in reducing high-fat diet-induced body weight gain and diabetes in mice. In the obesity model, C57Bl/6J mice were fed a high-fat diet (60 energy %) for 12 weeks, and gavaged daily with B. lactis 420 (109 cfu) or vehicle. In the diabetes model, mice were fed a high-fat, ketogenic diet (72 energy % fat) for 4 weeks, with a 6-week subsequent treatment with B. lactis 420 (108-1010 cfu/day) or vehicle, after which they were analysed for body composition. We also analysed glucose tolerance, plasma lipopolysaccharide and target tissue inflammation using only one of the B. lactis 420 groups (109 cfu/day). Intestinal bacterial translocation and adhesion were analysed in a separate experiment using an Escherichia coli gavage. Body fat mass was increased in both obese (10.7 ± 0.8 g (mean ± standard error of mean) vs. 1.86 ± 0.21 g, P<0.001) and diabetic mice (3.01 ± 0.4 g vs. 1.14 ± 0.15 g, P<0.001) compared to healthy controls. Treatment with B. lactis 420 significantly decreased fat mass in obese (7.83 ± 0.67 g, P=0.007 compared to obese with vehicle) and diabetic mice (1.89 ± 0.16 g, P=0.02 for highest dose). This was reflected as reduced weight gain and improved glucose tolerance. Furthermore, B. lactis 420 decreased plasma lipopolysaccharide levels (P<0.001), liver inflammation (P=0.04), and E. coli adhesion in the distal gut (P<0.05). In conclusion, B. lactis 420 reduces fat mass and glucose intolerance in both obese and diabetic mice. Reduced intestinal mucosal adherence and plasma lipopolysaccharide suggest a mechanism related to reduced translocation of gut microbes.

  1. Endurance exercise training increases APPL1 expression and improves insulin signaling in the hepatic tissue of diet-induced obese mice, independently of weight loss.

    PubMed

    Marinho, R; Ropelle, E R; Cintra, D E; De Souza, C T; Da Silva, A S R; Bertoli, F C; Colantonio, E; D'Almeida, V; Pauli, J R

    2012-07-01

    Hepatic insulin resistance is the major contributor to fasting hyperglycemia in type 2 diabetes. The protein kinase Akt plays a central role in the suppression of gluconeogenesis involving forkhead box O1 (Foxo1) and peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α), and in the control of glycogen synthesis involving the glycogen synthase kinase beta (GSK3β) in the liver. It has been demonstrated that endosomal adaptor protein APPL1 interacts with Akt and blocks the association of Akt with its endogenous inhibitor, tribbles-related protein 3 (TRB3), improving the action of insulin in the liver. Here, we demonstrated that chronic exercise increased the basal levels and insulin-induced Akt serine phosphorylation in the liver of diet-induced obese mice. Endurance training was able to increase APPL1 expression and the interaction between APPL1 and Akt. Conversely, training reduced both TRB3 expression and TRB3 and Akt association. The positive effects of exercise on insulin action are reinforced by our findings that showed that trained mice presented an increase in Foxo1 phosphorylation and Foxo1/PGC-1α association, which was accompanied by a reduction in gluconeogenic gene expressions (PEPCK and G6Pase). Finally, exercised animals demonstrated increased at basal and insulin-induced GSK3β phosphorylation levels and glycogen content at 24 h after the last session of exercise. Our findings demonstrate that exercise increases insulin action, at least in part, through the enhancement of APPL1 and the reduction of TRB3 expression in the liver of obese mice, independently of weight loss.

  2. Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol

    PubMed Central

    Cluny, Nina L.; Keenan, Catherine M.; Reimer, Raylene A.; Le Foll, Bernard; Sharkey, Keith A.

    2015-01-01

    Objective Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users. Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice. Methods Adult male DIO and lean mice were treated daily with vehicle or THC (2mg/kg for 3 weeks and 4 mg/kg for 1 additional week). Body weight, fat mass, energy intake, locomotor activity, whole gut transit and gut microbiota were measured longitudinally. Results THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC. THC had no effect on locomotor activity or whole gut transit in either lean or DIO mice. Conclusions Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity. PMID:26633823

  3. Porcine adiponectin receptor 1 transgene resists high-fat/sucrose diet-induced weight gain, hepatosteatosis and insulin resistance in mice.

    PubMed

    Liu, Bing-Hsien; Lin, Yuan-Yu; Wang, Ya-Chin; Huang, Chao-Wei; Chen, Chih-Chien; Wu, Shinn-Chih; Mersmann, Harry J; Cheng, Winston T K; Ding, Shih-Torng

    2013-01-01

    Adiponectin and its receptors have been demonstrated to play important roles in regulating glucose and lipid metabolism in mice. Obesity, type II diabetes and cardiovascular disease are highly correlated with down-regulated adiponectin signaling. In this study, we generated mice overexpressing the porcine Adipor1 transgene (pAdipor1) to study its beneficial effects in metabolic syndromes as expressed in diet-induced obesity, hepatosteatosis and insulin resistance. Wild-type (WT) and pAdipor1 transgenic mice were fed ad libitum with a standard chow diet (Chow) or a high-fat/sucrose diet (HFSD) for 24 weeks, beginning at 6 to 7 weeks of age. There were 12 mice per genetic/diet/sex group. When challenged with HFSD to induce obesity, the pAdipor1 transgenic mice resisted development of weight gain, hepatosteatosis and insulin resistance. These mice had lowered plasma adiponectin, triglyceride and glycerol concentrations compared to WT mice. Moreover, we found that (indicated by mRNA levels) fatty acid oxidation was enhanced in skeletal muscle and adipose tissue, and liver lipogenesis was inhibited. The pAdipor1 transgene also restored HFSD-reduced phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose transporter 4 mRNA in the adipose tissues, implying that the increased Pck1 may promote glyceroneogenesis to reduce glucose intolerance and thus activate the flux of glyceride-glycerol to resist diet-induced weight gain in the adipose tissues. Taken together, we demonstrated that pAdipor1 can prevent diet-induced weight gain and insulin resistance. Our findings may provide potential therapeutic strategies for treating metabolic syndromes and obesity, such as treatment with an ADIPOR1 agonist or activation of Adipor1 downstream targets.

  4. Weight loss following diet-induced obesity does not alter colon tumorigenesis in the AOM mouse model.

    PubMed

    Velázquez, Kandy T; Enos, Reilly T; Carson, Meredith S; Cranford, Taryn L; Bader, Jackie E; Chatzistamou, Ioulia; Singh, Udai P; Nagarkatti, Prakash S; Nagarkatti, Mitzi; Davis, J Mark; Carson, James A; Murphy, E Angela

    2016-10-01

    Obesity presents a significant public health concern given its association with increased cancer incidence, unfavorable prognosis, and metastasis. However, there is very little literature on the effects of weight loss, following obesity, on risk for colon cancer or liver cancer. Therefore, we sought to study whether intentional weight loss through diet manipulation was capable of mitigating colon and liver cancer in mice. We fed mice with a high-fat diet (HFD) comprised of 47% carbohydrates, 40% fat, and 13% protein for 20 wk to mimic human obesity. Subsequently, azoxymethane (AOM) was used to promote colon and liver carcinogenesis. A subset of obese mice was then switched to a low-fat diet (LFD) containing 67.5% carbohydrate, 12.2% fat, and 20% protein to promote intentional weight loss. Body weight loss and excess fat reduction did not protect mice from colon cancer progression and liver dysplastic lesion in the AOM-chemical-cancer model even though these mice had improved blood glucose and leptin levels. Intentional weight loss in AOM-treated mice actually produced histological changes that resemble dysplastic alterations in the liver and presented a higher percentage of F4/80(+)CD206(+) macrophages and activated T cells (CD4(+)CD69(+)) in the spleen and lymph nodes, respectively. In addition, the liver of AOM-treated mice exposed to a HFD during the entire period of the experiment exhibited a marked increase in proliferation and pNF-κB activation. Altogether, these data suggest that intentional weight loss following chemical-induced carcinogenesis does not affect colon tumorigenesis but may in fact negatively impact liver repair mechanisms.

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

    PubMed

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

    2016-02-01

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

  6. Popular weight reduction diets.

    PubMed

    Volpe, Stella Lucia

    2006-01-01

    The percentage of people who are overweight and obese has increased tremendously over the last 30 years. It has become a worldwide epidemic. This is evident by the number of children are being diagnosed with a body mass index >85th percentile, and the number of children begin diagnosed with type 2 diabetes mellitus, a disease previously reserved for adults. The weight loss industry has also gained from this epidemic; it is a billion dollar industry. People pay large sums of money on diet pills, remedies, and books, with the hope of losing weight permanently. Despite these efforts, the number of individuals who are overweight or obese continues to increase. Obesity is a complex, multifactorial disorder. It would be impossible to address all aspects of diet, exercise, and weight loss in this review. Therefore, this article will review popular weight loss diets, with particular attention given to comparing low fat diets with low carbohydrate diets. In addition, the role that the environment plays on both diet and exercise and how they impact obesity will be addressed. Finally, the National Weight Control Registry will be discussed.

  7. Diet-induced weight loss is sufficient to reduce senescent cell number in white adipose tissue of weight-cycled mice

    PubMed Central

    List, Edward O.; Jensen, Elizabeth; Kowalski, Jesse; Buchman, Mathew; Berryman, Darlene E.; Kopchick, John J.

    2016-01-01

    Previously, our laboratory reported that weight-cycled mice outlive their obese counterparts. To gain a better mechanistic understanding of these results, we evaluated cellular senescence in white adipose tissue (WAT) of lean, obese, and weight cycled mice. Our results show that at the end of a 28 day weight loss cycle cellular senescence is significantly reduced in multiple WAT depots compared to obese mice, which also corresponds to a reduction in circulating activin A (a marker of senescence). These findings suggest that a previously undescribed benefit to weight loss may be a reduction of cellular senescence in WAT. PMID:28035346

  8. Nesfatin-130−59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions

    PubMed Central

    Prinz, Philip; Teuffel, Pauline; Lembke, Vanessa; Kobelt, Peter; Goebel-Stengel, Miriam; Hofmann, Tobias; Rose, Matthias; Klapp, Burghard F.; Stengel, Andreas

    2015-01-01

    Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130−59, was identified as active core of full length nesfatin-11−82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130−59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130−59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130−59 under conditions of diet-induced obesity (DIO). Male Sprague–Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130−59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130−59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130−59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4–8 h post injection (−29%) with the strongest reduction during the fifth hour (−75%), an effect detectable for 24 h (−12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130−59 was due to a reduction in meal size (−44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130−59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130−59 injected icv reduced food intake in the third hour post injection (−71%), an effect due to a reduced meal frequency (

  9. Nesfatin-130-59 Injected Intracerebroventricularly Differentially Affects Food Intake Microstructure in Rats Under Normal Weight and Diet-Induced Obese Conditions.

    PubMed

    Prinz, Philip; Teuffel, Pauline; Lembke, Vanessa; Kobelt, Peter; Goebel-Stengel, Miriam; Hofmann, Tobias; Rose, Matthias; Klapp, Burghard F; Stengel, Andreas

    2015-01-01

    Nesfatin-1 is well-established to induce an anorexigenic effect. Recently, nesfatin-130-59, was identified as active core of full length nesfatin-11-82 in mice, while its role in rats remains unclear. Therefore, we investigated the effects of nesfatin-130-59 injected intracerebroventricularly (icv) on the food intake microstructure in rats. To assess whether the effect was also mediated peripherally we injected nesfatin-130-59 intraperitoneally (ip). Since obesity affects the signaling of various food intake-regulatory peptides we investigated the effects of nesfatin-130-59 under conditions of diet-induced obesity (DIO). Male Sprague-Dawley rats fed ad libitum with standard diet were icv cannulated and injected with vehicle (5 μl ddH2O) or nesfatin-130-59 at 0.37, 1.1, and 3.3 μg (0.1, 0.3, 0.9 nmol/rat) and the food intake microstructure assessed using a food intake monitoring system. Next, naïve rats were injected ip with vehicle (300 μl saline) or nesfatin-130-59 (8.1, 24.3, 72.9 nmol/kg). Lastly, rats were fed a high fat diet for 10 weeks and those developing DIO were icv cannulated. Nesfatin-1 (0.9 nmol/rat) or vehicle (5 μl ddH2O) was injected icv and the food intake microstructure assessed. In rats fed standard diet, nesfatin-130-59 caused a dose-dependent reduction of dark phase food intake reaching significance at 0.9 nmol/rat in the period of 4-8 h post injection (-29%) with the strongest reduction during the fifth hour (-75%), an effect detectable for 24 h (-12%, p < 0.05 vs. vehicle). The anorexigenic effect of nesfatin-130-59 was due to a reduction in meal size (-44%, p < 0.05), while meal frequency was not altered compared to vehicle. In contrast to icv injection, nesfatin-130-59 injected ip in up to 30-fold higher doses did not alter food intake. In DIO rats fed high fat diet, nesfatin-130-59 injected icv reduced food intake in the third hour post injection (-71%), an effect due to a reduced meal frequency (-27%, p < 0.05), while meal size was

  10. Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We studied the effects of weight loss induced by either a low-fat normal diet or restriction of high-fat diet on hepatic steatosis, inflammation in the liver and adipose tissue, and blood monocytes of obese mice. In mice with high-fat diet-induced obesity, weight loss was achieved by switching from ...

  11. The DPP-IV inhibitor linagliptin and GLP-1 induce synergistic effects on body weight loss and appetite suppression in the diet-induced obese rat.

    PubMed

    Hansen, Henrik H; Hansen, Gitte; Paulsen, Sarah; Vrang, Niels; Mark, Michael; Jelsing, Jacob; Klein, Thomas

    2014-10-15

    Linagliptin is a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes. DPP-IV inhibitors are considered weight neutral, suggesting that elevation of endogenous incretin levels is not sufficient to promote weight loss per se. Here we evaluated the effect of linagliptin in combination with subcutaneous treatment of GLP-1(7-36) on body weight regulation in diet-induced obese (DIO) rats. Linagliptin administered perorally (1.5mg/kg, b.i.d.), but not subcutaneously (0.5mg/kg, b.i.d.), evoked a very modest body weight loss (2.2%) after 28 days of treatment. GLP-1 (0.5mg/kg, s.c.) treatment alone induced a body weight loss of 4.1%. In contrast, combined linagliptin (1.5mg/kg, p.o., or 0.5mg/kg, s.c.) and GLP-1 (0.5mg/kg) treatment evoked a marked anorectic response with both routes of linagliptin administration being equally effective on final body weight loss (7.5-8.0%). In comparison, liraglutide monotherapy (0.2mg/kg, s.c., b.i.d.) reduced body weight by 10.1%. Interestingly, the weight lowering effect of combined linagliptin and GLP-1 treatment was associated with a marked increase in chow preference, being more pronounced as compared to liraglutide treatment. In addition, linagliptin and GLP-1 co-treatment, but not liraglutide, specifically increased prepro-dynorphin mRNA levels in the caudate-putamen, an effect not obtained with administration of the compounds individually. In conclusion, co-treatment with linagliptin and GLP-1 synergistically reduces body weight in obese rats. The anti-obesity effect was caused by appetite suppression with a concomitant change in diet preference, which may potentially be associated with increased dynorphin activity in forebrain regions involved in reward anticipation and habit learning.

  12. Reprogramming of defended body weight after Roux-en-Y gastric bypass surgery in diet-induced obese mice

    PubMed Central

    Hao, Zheng; Mumphrey, Michael B.; Townsend, R. Leigh; Morrison, Christopher D.; Münzberg, Heike; Ye, Jianping; Berthoud, Hans-Rudolf

    2015-01-01

    Objective Roux-en-Y gastric bypass surgery (RYGB) results in sustained lowering of body weight in most patients, but the mechanisms involved are poorly understood. The aim of this study was to obtain support for the notion that reprogramming of defended body weight, rather than passive restriction of energy intake, is a fundamental mechanism of RYGB. Methods Male C57BL6J mice reaching different degrees of obesity on a high-fat diet either with ad libitum access or with caloric restriction (weight-reduced) were subjected to RYGB. Results RYGB-induced weight loss and fat mass loss was proportional to pre-surgical levels, with moderately obese mice losing less body weight and fat compared with very obese mice. Remarkably, mice that were weight-reduced to the level of chow controls before surgery, immediately gained weight after surgery, exclusively accounted for by lean mass gain. Conclusions The results provide additional evidence for re-programming of a new defended body weight as an important principle by which RYGB lastingly suppresses body weight. RYGB appears to selectively abolish defense of a higher fat mass level, while remaining sensitive to the defense of lean mass. The molecular and physiological mechanisms underlying this re-programming remain to be elucidated. PMID:26847390

  13. Factors influencing individual variability in high fat diet-induced weight gain in out-bred MF1 mice.

    PubMed

    Vaanholt, L M; Sinclair, R E; Mitchell, S E; Speakman, J R

    2015-05-15

    Easy access to high-energy palatable foods has been suggested to have contributed to the world-wide obesity epidemic. However, within these 'obesogenic' environments many people manage to remain lean. Mice also show variability in their weight gain responses to high-fat diet (HFD) feeding and their weight loss responses to calorically restricted (CR) feeding. In this study we investigated which factors contribute to determining susceptibility to HFD-induced obesity in mice, and whether the responses in weight gain on HFD are correlated with the responses to CR. One-hundred twenty four mice were exposed to 30% CR for 28days followed by a 14day recovery period, and subsequent exposure to 60% HFD for 28days. Responses in various metabolic factors were measured before and after each exposure (body mass; BM, body composition, food intake; FI, resting metabolic rate; RMR, physical activity, body temperature and glucose tolerance; GT). Weight changes on HFD ranged from -1 to 26%, equivalent to -0.2g to 10.5g in absolute mass. Multiple regression models showed that fat free mass (FFM) of the mice before exposure to HFD predicted 12% of the variability in weight gain on HFD (p<0.001). Also, FI during the first week of HFD feeding predicted 20% of the variability in BM and fat mass (FM) gain 4weeks later. These data may point to a role for the reward system in driving individual differences in FI and weight gain. Weight gain on the HFD was significantly negatively correlated to weight loss on CR, indicating that animals that are poor at defending against weight gain on HFD, were also poor at defending against CR-induced weight loss. Changes in FM and FFM in response to HFD or CR were not correlated however.

  14. Dietary licorice root supplementation improves diet-induced weight gain, lipid deposition and hepatic steatosis in ovariectomized mice without stimulating reproductive tissues and mammary gland

    PubMed Central

    Erdogan, Zeynep Madak; Gong, Ping; Zhao, Yiru Chen; Xu, Liwen; Wrobel, Kinga U.; Hartman, James A.; Wang, Michelle; Cam, Anthony; Iwaniec, Urszula T.; Turner, Russell T.; Twaddle, Nathan C.; Doerge, Daniel R.; Khan, Ikhlas A.; Katzenellenbogen, John A.; Katzenellenbogen, Benita S.; Helferich, William G.

    2015-01-01

    Scope We studied the impact of dietary supplementation with licorice root components on diet-induced obesity, fat accumulation and hepatic steatosis in ovariectomized C57BL/6 mice as a menopause model. Materials and Methods We evaluated the molecular and physiological effects of dietary licorice root administered to ovariectomized C57BL/6 mice as root powder (LRP), extracts (LRE) or isolated isoliquiritegenin (ILQ) on reproductive (uterus and mammary gland) and non-reproductive tissues important in regulating metabolism (liver, perigonadal, perirenal, mesenteric and subcutaneous fat). Quantitative outcome measures including body weight, fat distribution (MRI), food consumption, bone density and weight (DXA) and gene expression were assessed by the degree of restoration to the premenopausal health state. We characterized histological (H&E and oil red O staining) and molecular properties (expression of certain disease markers) of these tissues, and correlated these with metabolic phenotype as well as blood levels of bioactives. Conclusions Although LRE and ILQ provided some benefit, LRP was the most effective in reducing body weight gain, overall fat deposition, liver steatosis, and expression of hepatic lipid synthesis genes following ovariectomy. Our data demonstrate that licorice root provided improvement of multiple metabolic parameters under conditions of menopausal low estrogen and high-fat diets without stimulating reproductive tissues. PMID:26555669

  15. Glutamate dehydrogenase activator BCH stimulating reductive amination prevents high fat/high fructose diet-induced steatohepatitis and hyperglycemia in C57BL/6J mice

    PubMed Central

    Han, Seung Jin; Choi, Sung-E; Yi, Sang-A; Jung, Jong Gab; Jung, Ik-Rak; Shin, Maureen; Kang, Seok; Oh, Hyunhee; Kim, Hae Jin; Kim, Dae Jung; Kwon, Ji Eun; Choi, Cheol Soo; Lee, Kwan Woo; Kang, Yup

    2016-01-01

    Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes. Long-term BCH treatment improved most metabolic alterations induced by high fat/high fructose (HF/HFr) diet in C57BL/6J mice. BCH prevented HF/HFr-induced fat accumulation and activation of stress/inflammation signals such as phospho-JNK, phospho-PERK, phospho-p38, and phospho-NFκB in liver tissues. Furthermore, BCH treatment reduced the expression levels of inflammatory cytokines such as TNF-α and IL-1β in HF/HFr-fed mouse liver. BCH also reduced liver collagen and plasma levels of alanine transaminase and aspartate transaminase. On the other hand, BCH significantly improved fasting hyperglycemia and glucose tolerance in HF/HFr-fed mice. In conclusion, stimulation of reductive amination through GDH activation can be used as a strategy to prevent high calorie western diet-induced NAFLD and T2D. PMID:27874078

  16. Lack of weight gain after angiotensin AT1 receptor blockade in diet-induced obesity is partly mediated by an angiotensin-(1–7)/ Mas-dependent pathway

    PubMed Central

    Schuchard, Johanna; Winkler, Martina; Stölting, Ines; Schuster, Franziska; Vogt, Florian M; Barkhausen, Jörg; Thorns, Christoph; Santos, Robson A; Bader, Michael; Raasch, Walter

    2015-01-01

    Background and Purpose Angiotensin AT1 receptor antagonists induce weight loss; however, the mechanism underlying this phenomenon is unknown. The Mas receptor agonist angiotensin-(1-7) is a metabolite of angiotensin I and of angiotensin II. As an agonist of Mas receptors, angiotensin-(1-7) has beneficial cardiovascular and metabolic effects. Experimental Approach We investigated the anti-obesity effects of transgenically overexpressed angiotensin-(1-7) in rats. We secondly examined whether weight loss due to telmisartan (8 mg·kg−1·d−1) in diet-induced obese Sprague Dawley (SD) rats can be blocked when the animals were co-treated with the Mas receptor antagonist A779 (24 or 72 μg·kg−1·d−1). Key Results In contrast to wild-type controls, transgenic rats overexpressing angiotensin-(1-7) had 1.) diminished body weight when they were regularly fed with chow; 2.) were protected from developing obesity although they were fed with cafeteria diet (CD); 3.) showed a reduced energy intake that was mainly related to a lower CD intake; 5.) remained responsive to leptin despite chronic CD feeding; 6.) had a higher, strain-dependent energy expenditure, and 7.) were protected from developing insulin resistance despite CD feeding. Telmisartan-induced weight loss in SD rats was partially antagonized after a high, but not a low dose of A779. Conclusions and Implications Angiotensin-(1-7) regulated food intake and body weight and contributed to the weight loss after AT1 receptor blockade. Angiotensin-(1-7)-like agonists may be drug candidates for treating obesity. PMID:25906670

  17. Exercise and diet-induced weight loss attenuates oxidative stress related-coronary vasoconstriction in obese adolescents.

    PubMed

    Gao, Zhaohui; Novick, Marsha; Muller, Matthew D; Williams, Ronald J; Spilk, Samson; Leuenberger, Urs A; Sinoway, Lawrence I

    2013-02-01

    Obesity is a disease of oxidative stress (OS). Acute hyperoxia (breathing 100 % O(2)) can evoke coronary vasoconstriction by the oxidative quenching of nitric oxide (NO). To examine if weight loss would alter the hyperoxia-related coronary constriction seen in obese adolescents, we measured the coronary blood flow velocity (CBV) response to hyperoxia using transthoracic Doppler echocardiography before and after a 4-week diet and exercise regimen in 6 obese male adolescents (age 13-17 years, BMI 36.5 ± 2.3 kg/m(2)). Six controls of similar age and BMI were also studied. The intervention group lost 9 ± 1 % body weight, which was associated with a reduced resting heart rate (HR), reduced diastolic blood pressure (BP), and reduced RPP (all P < 0.05). Before weight loss, hyperoxia reduced CBV by 33 ± 3 %. After weight loss, CBV only fell by 15 ± 3 % (P < 0.05). In the control group, CBV responses to hyperoxia were unchanged during the two trials. Thus weight loss: (1) reduces HR, BP, and RPP; and (2) attenuates the OS-related coronary constrictor response seen in obese adolescents. We postulate that: (1) the high RPP before weight loss led to higher myocardial O(2) consumption, higher coronary flow and greater NO production, and in turn a large constrictor response to hyperoxia; and (2) weight loss decreased myocardial oxygen demand and NO levels. Under these circumstances, hyperoxia-induced vasoconstriction was attenuated.

  18. Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats.

    PubMed

    van de Giessen, Elsmarieke; de Bruin, Kora; la Fleur, Susanne E; van den Brink, Wim; Booij, Jan

    2012-04-01

    The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine re-uptake and is a promising candidate for the treatment of obesity. Obesity is associated with lower striatal dopamine D2 receptor availability, which may be related to disturbed regulation of food intake. This study assesses the effects of chronic tesofensine treatment on food intake and body weight in association with changes in striatal dopamine D2/D3 receptor (D2/3R) availability of diet-induced obese (DIO) rats. Four groups of 15 DIO rats were randomized to one of the following treatments for 28 days: 1. tesofensine (2.0 mg/kg), 2. vehicle, 3. vehicle+restricted diet isocaloric to caloric intake of group 1, and 4. tesofensine (2.0 mg/kg)+ a treatment-free period of 28 days. Caloric intake and weight gain decreased significantly more in the tesofensine-treated rats compared to vehicle-treated rats, which confirms previous findings. After treatment discontinuation, caloric intake and body weight gain gradually increased again. Tesofensine-treated rats showed significantly lower D2/3R availability in nucleus accumbens and dorsal striatum than both vehicle-treated rats and vehicle-treated rats on restricted isocaloric diet. No correlations were observed between food intake or body weight and D2/3R availability. Thus, chronic tesofensine treatment leads to decreased food intake and weight gain. However, this appears not to be directly related to the decreased striatal D2/3R availability, which is mainly a pharmacological effect.

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

    PubMed Central

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

    2016-01-01

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

  20. A Novel Selective Inhibitor of Delta-5 Desaturase Lowers Insulin Resistance and Reduces Body Weight in Diet-Induced Obese C57BL/6J Mice

    PubMed Central

    Yashiro, Hiroaki; Takagahara, Shuichi; Tamura, Yumiko Okano; Miyahisa, Ikuo; Matsui, Junji; Suzuki, Hideo; Ikeda, Shota; Watanabe, Masanori

    2016-01-01

    Obesity is now recognized as a state of chronic low-grade inflammation and is called as metabolic inflammation. Delta-5 desaturase (D5D) is an enzyme that metabolizes dihomo-γ-linolenic acid (DGLA) to arachidonic acid (AA). Thus, D5D inhibition increases DGLA (precursor to anti-inflammatory eicosanoids) while decreasing AA (precursor to pro-inflammatory eicosanoids), and could result in synergistic improvement in the low-grade inflammatory state. Here, we demonstrate reduced insulin resistance and the anti-obesity effect of a D5D selective inhibitor (compound-326), an orally active small-molecule, in a high-fat diet-induced obese (DIO) mouse model. In vivo D5D inhibition was confirmed by determining changes in blood AA/DGLA profiles. In DIO mice, chronic treatment with compound-326 lowered insulin resistance and caused body weight loss without significant impact on cumulative calorie intake. Decreased macrophage infiltration into adipose tissue was expected from mRNA analysis. Increased daily energy expenditure was also observed following administration of compound-326, in line with sustained body weight loss. These data indicate that the novel D5D selective inhibitor, compound-326, will be a new class of drug for the treatment of obese and diabetic patients. PMID:27832159

  1. Co-agonist of glucagon and GLP-1 reduces cholesterol and improves insulin sensitivity independent of its effect on appetite and body weight in diet-induced obese C57 mice.

    PubMed

    Patel, Vishal; Joharapurkar, Amit; Dhanesha, Nirav; Kshirsagar, Samadhan; Patel, Kartik; Bahekar, Rajesh; Shah, Gaurang; Jain, Mukul

    2013-12-01

    Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors reduce body weight without inducing hyperglycemia in rodents. However, the effect of a co-agonist on insulin sensitivity and lipid metabolism has not been thoroughly assessed. Diet-induced obese (DIO) mice received 0.5 mg·kg(-1) of co-agonist or 2.5 mg·kg(-1) of glucagon or 8 μg·kg(-1) of exendin-4 by subcutaneous route, twice daily, for 28 days. A separate group of mice was pair-fed to the co-agonist-treated group for 28 days. Co-agonist treatment reduced food intake and reduced body weight up to 28 days. In addition, it reduced leptin levels and increased fibroblast growth factor 21 (FGF21) levels in plasma, when compared with control and pair-fed groups. Co-agonist treatment decreased triglyceride levels in serum and liver and reduced serum cholesterol, mainly due to reduction in low-density lipoprotein (LDL) cholesterol. These changes were not seen with pair-fed controls. Co-agonist treatment improved glucose tolerance and increased insulin sensitivity, as observed during glucose and insulin-tolerance test, hyperinsulinemic clamp, and reduced gluconeogenesis, as observed in pyruvate-tolerance test. The effects on insulin sensitivity and lipid levels are mostly independent of the food intake or body weight lowering effect of the co-agonist.

  2. High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss.

    PubMed

    Siersbæk, Majken; Varticovski, Lyuba; Yang, Shutong; Baek, Songjoon; Nielsen, Ronni; Mandrup, Susanne; Hager, Gordon L; Chung, Jay H; Grøntved, Lars

    2017-01-10

    Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers. After return to the same body weight as chow fed control mice, the fasting insulin, glucose, and hepatic triglyceride levels were fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome.

  3. High fat diet-induced changes of mouse hepatic transcription and enhancer activity can be reversed by subsequent weight loss

    PubMed Central

    Siersbæk, Majken; Varticovski, Lyuba; Yang, Shutong; Baek, Songjoon; Nielsen, Ronni; Mandrup, Susanne; Hager, Gordon L.; Chung, Jay H.; Grøntved, Lars

    2017-01-01

    Epigenetic factors have been suggested to play an important role in metabolic memory by trapping and maintaining initial metabolic changes within the transcriptional regulatory machinery. In this study we fed mice a high fat diet (HFD) for seven weeks followed by additional five weeks of chow, to identify HFD-mediated changes to the hepatic transcriptional program that may persist after weight loss. Mice fed a HFD displayed increased fasting insulin levels, hepatosteatosis and major changes in hepatic gene transcription associated with modulation of H3K27Ac at enhancers, but no significant changes in chromatin accessibility, indicating that HFD-regulated gene transcription is primarily controlled by modulating the activity of pre-established enhancers. After return to the same body weight as chow fed control mice, the fasting insulin, glucose, and hepatic triglyceride levels were fully restored to normal levels. Moreover, HFD-regulated H3K27Ac and mRNA levels returned to similar levels as control mice. These data demonstrates that the transcription regulatory landscape in the liver induced by HFD is highly dynamic and can be reversed by weight loss. This provides hope for efficient treatment of early obesity-associated changes to hepatic complications by simple weight loss intervention without persistent reprograming of the liver transcriptome. PMID:28071704

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

    PubMed

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

    2016-09-01

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

  5. Dietary supplements in weight reduction.

    PubMed

    Dwyer, Johanna T; Allison, David B; Coates, Paul M

    2005-05-01

    We summarize evidence on the role of dietary supplements in weight reduction, with particular attention to their safety and benefits. Dietary supplements are used for two purposes in weight reduction: (a) providing nutrients that may be inadequate in calorie-restricted diets and (b) for their potential benefits in stimulating weight loss. The goal in planning weight-reduction diets is that total intake from food and supplements should meet recommended dietary allowance/adequate intake levels without greatly exceeding them for all nutrients, except energy. If nutrient amounts from food sources in the reducing diet fall short, dietary supplements containing a single nutrient/element or a multivitamin-mineral combination may be helpful. On hypocaloric diets, the addition of dietary supplements providing nutrients at a level equal to or below recommended dietary allowance/adequate intake levels or 100% daily value, as stated in a supplement's facts box on the label, may help dieters to achieve nutrient adequacy and maintain electrolyte balance while avoiding the risk of excessive nutrient intakes. Many botanical and other types of dietary supplements are purported to be useful for stimulating or enhancing weight loss. Evidence of their efficacy in stimulating weight loss is inconclusive at present. Although there are few examples of safety concerns related to products that are legal and on the market for this purpose, there is also a paucity of evidence on safety for this intended use. Ephedra and ephedrine-containing supplements, with or without caffeine, have been singled out in recent alerts from the Food and Drug Administration because of safety concerns, and use of products containing these substances cannot be recommended. Dietitians should periodically check the Food and Drug Administration Web site ( www.cfsan.fda.gov ) for updates and warnings and alert patients/clients to safety concerns. Dietetics professionals should also consult authoritative sources for

  6. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss12

    PubMed Central

    Josse, Andrea R; Gburcik, Valentina; Raymond, Frederic; Good, Liam; Atherton, Philip J

    2016-01-01

    Background: A hypothesis exists whereby an exercise- or dietary-induced negative energy balance reduces human subcutaneous white adipose tissue (scWAT) mass through the formation of brown-like adipocyte (brite) cells. However, the validity of biomarkers of brite formation has not been robustly evaluated in humans, and clinical data that link brite formation and weight loss are sparse. Objectives: We used rosiglitazone and primary adipocytes to stringently evaluate a set of biomarkers for brite formation and determined whether the expression of biomarker genes in scWAT could explain the change in body composition in response to exercise training combined with calorie restriction in obese and overweight women (n = 79). Design: Gene expression was derived from exon DNA microarrays and preadipocytes from obesity-resistant and -sensitive mice treated with rosiglitazone to generate candidate brite biomarkers from a microarray. These biomarkers were evaluated against data derived from scWAT RNA from obese and overweight women before and after supervised exercise 5 d/wk for 16 wk combined with modest calorie restriction (∼0.84 MJ/d). Results: Forty percent of commonly used brite gene biomarkers exhibited an exon or strain-specific regulation. No biomarkers were positively related to weight loss in human scWAT. Greater weight loss was significantly associated with less uncoupling protein 1 expression (P = 0.006, R2 = 0.09). In a follow-up global analysis, there were 161 genes that covaried with weight loss that were linked to greater CCAAT/enhancer binding protein α activity (z = 2.0, P = 6.6 × 10−7), liver X receptor α/β agonism (z = 2.1, P = 2.8 × 10−7), and inhibition of leptin-like signaling (z = −2.6, P = 3.9 × 10−5). Conclusion: We identify a subset of robust RNA biomarkers for brite formation and show that calorie-restriction–mediated weight loss in women dynamically remodels scWAT to take on a more-white rather than a more-brown adipocyte phenotype

  7. Defense of Elevated Body Weight Setpoint in Diet-Induced Obese Rats on Low Energy Diet Is Mediated by Loss of Melanocortin Sensitivity in the Paraventricular Hypothalamic Nucleus.

    PubMed

    Luchtman, Dirk W; Chee, Melissa J S; Doslikova, Barbora; Marks, Daniel L; Baracos, Vickie E; Colmers, William F

    2015-01-01

    Some animals and humans fed a high-energy diet (HED) are diet-resistant (DR), remaining as lean as individuals who were naïve to HED. Other individuals become obese during HED exposure and subsequently defend the obese weight (Diet-Induced Obesity- Defenders, DIO-D) even when subsequently maintained on a low-energy diet. We hypothesized that the body weight setpoint of the DIO-D phenotype resides in the hypothalamic paraventricular nucleus (PVN), where anorexigenic melanocortins, including melanotan II (MTII), increase presynaptic GABA release, and the orexigenic neuropeptide Y (NPY) inhibits it. After prolonged return to low-energy diet, GABA inputs to PVN neurons from DIO-D rats exhibited highly attenuated responses to MTII compared with those from DR and HED-naïve rats. In DIO-D rats, melanocortin-4 receptor expression was significantly reduced in dorsomedial hypothalamus, a major source of GABA input to PVN. Unlike melanocortin responses, NPY actions in PVN of DIO-D rats were unchanged, but were reduced in neurons of the ventromedial hypothalamic nucleus; in PVN of DR rats, NPY responses were paradoxically increased. MTII-sensitivity was restored in DIO-D rats by several weeks' refeeding with HED. The loss of melanocortin sensitivity restricted to PVN of DIO-D animals, and its restoration upon prolonged refeeding with HED suggest that their melanocortin systems retain the ability to up- and downregulate around their elevated body weight setpoint in response to longer-term changes in dietary energy density. These properties are consistent with a mechanism of body weight setpoint.

  8. Fructans from Agave tequilana with a Lower Degree of Polymerization Prevent Weight Gain, Hyperglycemia and Liver Steatosis in High-Fat Diet-Induced Obese Mice.

    PubMed

    Márquez-Aguirre, A L; Camacho-Ruíz, R M; Gutiérrez-Mercado, Y K; Padilla-Camberos, E; González-Ávila, M; Gálvez-Gastélum, F J; Díaz-Martínez, N E; Ortuño-Sahagún, D

    2016-12-01

    Fructans from agave have received specific attention because of their highly branched fructan content. We have previously reported that the degree of polymerization (dp) influences their biological activity. Therefore, the aim of this study was to investigate the effect of unfractionated and fractionated fructans (higher and lower dps) from Agave tequilana in high-fat diet-induced (HFD) obese mice. Fructans with a lower dp (HFD+ScF) decreased weight gain by 30 %, body fat mass by 51 %, hyperglycemia by 25 % and liver steatosis by 40 %. Interestingly, unfractionated fructans (HFD+F) decreased glucose and triglycerides (TG), whereas fractionated fructans with a higher dp (HFD+LcF) decreased TG but not glucose; in contrast, HFD+ScF decreased glucose but not TG. Our findings suggest that both higher and lower dp agave fructans have complementary effects in metabolic disorders related to obesity. These findings may contribute to the development of improved food supplements with a specific ratio combination of fructans with different dps.

  9. Deficiency of FcϵR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice.

    PubMed

    Lee, Yun-Jung; Liu, Conglin; Liao, Mengyang; Sukhova, Galina K; Shirakawa, Jun; Abdennour, Meriem; Iamarene, Karine; Andre, Sebastien; Inouye, Karen; Clement, Karine; Kulkarni, Rohit N; Banks, Alexander S; Libby, Peter; Shi, Guo-Ping

    2015-11-01

    Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcϵR1-deficient (Fcer1a(-/-)) mice and diet-induced obesity (DIO) mice demonstrated that FcϵR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain but improved glucose tolerance and glucose-induced insulin secretion. White adipose tissue from Fcer1a(-/-) mice showed an increased expression of phospho-AKT, CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, glucose transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake but induces energy expenditure, adipocyte apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited the expression of CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ, and preadipocyte adipogenesis and induced adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a(-/-) mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion.

  10. Allomyrina Dichotoma Larvae Regulate Food Intake and Body Weight in High Fat Diet-Induced Obese Mice Through mTOR and Mapk Signaling Pathways

    PubMed Central

    Kim, Jongwan; Yun, Eun-Young; Park, Seong-Won; Goo, Tae-Won; Seo, Minchul

    2016-01-01

    Recent evidence has suggested that the Korean horn beetle (Allomyrina dichotoma) has anti-hepatofibrotic, anti-neoplastic, and antibiotic effects and is recognized as a traditional medicine. In our previous works, Allomyrina dichotoma larvae (ADL) inhibited differentiation of adipocytes both in vitro and in vivo. However, the anorexigenic and endoplasmic reticulum(ER) stress-reducing effects of ADL in obesity has not been examined. In this study, we investigated the anorexigenic and ER stress-reducing effects of ADL in the hypothalamus of diet-induced obese (DIO) mice. Intracerebroventricular (ICV) administration of ethanol extract of ADL (ADE) suggested that an antagonizing effect on ghrelin-induced feeding behavior through the mTOR and MAPK signaling pathways. Especially, ADE resulted in strong reduction of ER stress both in vitro and in vivo. These findings strongly suggest that ADE and its constituent bioactive compounds are available and valuable to use for treatment of various diseases driven by prolonged ER stress. PMID:26901224

  11. Performance on the Iowa gambling task is related to magnitude of weight loss and salivary cortisol in a diet-induced weight loss intervention in overweight women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The overall objective of this study was to examine the relationship between executive function, specifically decision making, and weight loss. We used the Iowa Gambling Task (IGT) to characterize decision making and compared performance on this task to weight loss in obese women (n=29) participatin...

  12. Ameliorating effects of fennel and cumin extracts on sperm quality and spermatogenic cells apoptosis by inducing weight loss and reducing leptin concentration in diet-induced obese rats.

    PubMed

    Nejatbakhsh, R; Riyahi, S; Farrokhi, A; Rostamkhani, S; Mahmazi, S; Yazdinezhad, A; Kazemi, M; Shokri, S

    2016-11-30

    This study was established a model of obesity to estimate the impact of fennel and cumin as anti-obesity extracts on body weight, body mass index (BMI), food consumption, leptin concentration, sperm quality and testis architecture to determine the reversibility of reproductive function of obese animals. Male rats were randomly assigned to either a normal or high-fat diet for 8 weeks. Then, we divided 56 adult rats into seven groups: control (CO); obesity (OB); fennel 100 and 200 mg/kg; cumin 50 and 100 mg/kg; and fennel 100 mg/kg plus cumin 50 mg/kg. From weeks 9-16, the animals treated extracts by gavages daily. We analysed leptin concentration, sperm quality and apoptosis of testis along with evaluating changes in body weight. Body weight of animals increased 25% at week 8. However, body weight, BMI, leptin concentration and apoptosis indices of OB rats increased at the end of study. However, the relative sperm parameters decreased. Nevertheless, fennel and cumin treatment improved sperm quality, and spermatogenic cells apoptosis following weight loss. Concomitant with weight loss, leptin concentration and food consumption decreased. In conclusion, fennel and cumin as supplements may ameliorate sperm quality of obese animals following weight loss and reduction in leptin concentration.

  13. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    PubMed Central

    Litwak, Sara A.; Loh, Kim; Stanley, William J.; Pappas, Evan G.; Wali, Jibran A.; Selck, Claudia; Strasser, Andreas; Thomas, Helen E.; Gurzov, Esteban N.

    2016-01-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14–17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

  14. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    PubMed

    Litwak, Sara A; Loh, Kim; Stanley, William J; Pappas, Evan G; Wali, Jibran A; Selck, Claudia; Strasser, Andreas; Thomas, Helen E; Gurzov, Esteban N

    2016-04-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity.

  15. Extract of Irish potatoes (Solanum tuberosum L.) decreases body weight gain and adiposity and improves glucose control in the mouse model of diet-induced obesity.

    PubMed

    Kubow, Stan; Hobson, Luc; Iskandar, Michèle M; Sabally, Kebba; Donnelly, Danielle J; Agellon, Luis B

    2014-11-01

    Both sexes of mice were fed a high fat diet (HFD) for 10 weeks without and with polyphenolic-rich potato extracts (PRPE) of cultivars Onaway and Russet Burbank. PRPE attenuated weight gain in male and female mice by as much as 63.2%, which was associated mostly with a reduction in adiposity. Mice receiving PRPE showed enhanced capacity for blood glucose clearance. Sex differences regarding the impact of HFD and PRPE on plasma levels of insulin, ghrelin, leptin, gastric inhibitory peptide, and resistin were noted. PRPE may serve as part of a preventative dietary strategy against the development of obesity and type 2 diabetes.

  16. Impact of Korean pine nut oil on weight gain and immune responses in high-fat diet-induced obese mice.

    PubMed

    Park, Soyoung; Lim, Yeseo; Shin, Sunhye; Han, Sung Nim

    2013-10-01

    Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-γ, and LPS-stimulated production of IL-6, IL-1β, and prostaglandin E2 (PGE2) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-1β (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-γ, IL-6, or PGE2 in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses.

  17. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats

    PubMed Central

    Kanyan Enchang, Francis; Nor Hussein, Fuzina

    2017-01-01

    Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat. PMID:28246535

  18. Four-Week Consumption of Malaysian Honey Reduces Excess Weight Gain and Improves Obesity-Related Parameters in High Fat Diet Induced Obese Rats.

    PubMed

    Samat, Suhana; Kanyan Enchang, Francis; Nor Hussein, Fuzina; Wan Ismail, Wan Iryani

    2017-01-01

    Many studies revealed the potential of honey consumption in controlling obesity. However, no study has been conducted using Malaysian honey. In this study, we investigated the efficacy of two local Malaysian honey types: Gelam and Acacia honey in reducing excess weight gain and other parameters related to obesity. The quality of both honey types was determined through physicochemical analysis and contents of phenolic and flavonoid. Male Sprague-Dawley rats were induced to become obese using high fat diet (HFD) prior to introduction with/without honey or orlistat for four weeks. Significant reductions in excess weight gain and adiposity index were observed in rats fed with Gelam honey compared to HFD rats. Moreover, levels of plasma glucose, triglycerides, and cholesterol, plasma leptin and resistin, liver enzymes, renal function test, and relative organ weight in Gelam and Acacia honey treated groups were reduced significantly when compared to rats fed with HFD only. Similar results were also displayed in rats treated with orlistat, but with hepatotoxicity effects. In conclusion, consumption of honey can be used to control obesity by regulating lipid metabolism and appears to be more effective than orlistat.

  19. Effects of Dietary Fibre (Pectin) and/or Increased Protein (Casein or Pea) on Satiety, Body Weight, Adiposity and Caecal Fermentation in High Fat Diet-Induced Obese Rats

    PubMed Central

    Adam, Clare L.; Gratz, Silvia W.; Peinado, Diana I.; Thomson, Lynn M.; Garden, Karen E.; Williams, Patricia A.; Richardson, Anthony J.; Ross, Alexander W.

    2016-01-01

    Dietary constituents that suppress appetite, such as dietary fibre and protein, may aid weight loss in obesity. The soluble fermentable dietary fibre pectin promotes satiety and decreases adiposity in diet-induced obese rats but effects of increased protein are unknown. Adult diet-induced obese rats reared on high fat diet (45% energy from fat) were given experimental diets ad libitum for 4 weeks (n = 8/group): high fat control, high fat with high protein (40% energy) as casein or pea protein, or these diets with added 10% w/w pectin. Dietary pectin, but not high protein, decreased food intake by 23% and induced 23% body fat loss, leading to 12% lower final body weight and 44% lower total body fat mass than controls. Plasma concentrations of satiety hormones PYY and total GLP-1 were increased by dietary pectin (168% and 151%, respectively) but not by high protein. Plasma leptin was decreased by 62% on pectin diets and 38% on high pea (but not casein) protein, while plasma insulin was decreased by 44% on pectin, 38% on high pea and 18% on high casein protein diets. Caecal weight and short-chain fatty acid concentrations in the caecum were increased in pectin-fed and high pea protein groups: caecal succinate was increased by pectin (900%), acetate and propionate by pectin (123% and 118%, respectively) and pea protein (147% and 144%, respectively), and butyrate only by pea protein (309%). Caecal branched-chain fatty acid concentrations were decreased by pectin (down 78%) but increased by pea protein (164%). Therefore, the soluble fermentable fibre pectin appeared more effective than high protein for increasing satiety and decreasing caloric intake and adiposity while on high fat diet, and produced a fermentation environment more likely to promote hindgut health. Altogether these data indicate that high fibre may be better than high protein for weight (fat) loss in obesity. PMID:27224646

  20. Weight Reduction Techniques Adopted When Weight Standards are Enforced

    DTIC Science & Technology

    1993-01-01

    ORGANIZATION NAME(S) AND ADDRESS(ES) 8, PERFORMING ORGANIZATION Military Nutrition Division REPORT NUMBER U. S. Army Research Institute of Environmental...affecting more soldiers than those Identified by the AWCP and possibly developing during a career In the Army. Nutrition /education programs should...that appeas to be Inevitable with aging and a career in the’Army. 14. SUBJECT TERMS 15. NUMBIEN OF PAGES Nutrition , weight reduction, Army weight

  1. Maternal low protein diet-induced low birth weight in male, neonate Sprague-Dawley rats is mediated by altered brown adipose tissue thermogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Brown adipose tissue (BAT) plays an important role in regulating body weight (BW) by modifying thermogenesis. Maternal low protein (LP) diets reduce offspring birth weight. Increased BAT thermogenesis in utero may be one mechanism for the lower BW. However, whether maternal LP nutrition alters BAT...

  2. Weight Stigma Reduction and Genetic Determinism.

    PubMed

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of-and responsibility for-obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention's gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity.

  3. Weight Stigma Reduction and Genetic Determinism

    PubMed Central

    Hilbert, Anja

    2016-01-01

    One major approach to weight stigma reduction consists of decreasing beliefs about the personal controllability of—and responsibility for—obesity by educating about its biogenetic causes. Evidence on the efficacy of this approach is mixed, and it remains unclear whether this would create a deterministic view, potentially leading to detrimental side-effects. Two independent studies from Germany using randomized designs with delayed-intervention control groups served to (1) develop and pilot a brief, interactive stigma reduction intervention to educate N = 128 university students on gene × environment interactions in the etiology of obesity; and to (2) evaluate this intervention in the general population (N = 128) and determine mechanisms of change. The results showed (1) decreased weight stigma and controllability beliefs two weeks post-intervention in a student sample; and (2) decreased internal attributions and increased genetic attributions, knowledge, and deterministic beliefs four weeks post-intervention in a population sample. Lower weight stigma was longitudinally predicted by a decrease in controllability beliefs and an increase in the belief in genetic determinism, especially in women. The results underline the usefulness of a brief, interactive intervention promoting an interactionist view of obesity to reduce weight stigma, at least in the short term, lending support to the mechanisms of change derived from attribution theory. The increase in genetic determinism that occurred despite the intervention’s gene × environment focus had no detrimental side-effect on weight stigma, but instead contributed to its reduction. Further research is warranted on the effects of how biogenetic causal information influences weight management behavior of individuals with obesity. PMID:27631384

  4. Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

    PubMed

    Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

    2014-07-01

    In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of Sirt1 in the brain, particularly the hypothalamus, in body weight and energy balance regulation is debated. Among the first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague Dawley rats. In that study, central inhibition of Sirt1 decreased body weight and food intake as a result of a Forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which, in turn, increased phosphorylated FoxO1 via improved insulin/pAKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-MSH maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

  5. Central Sirt1 regulates body weight and energy expenditure along with the POMC-derived peptide α-MSH and the processing enzyme CPE production in diet-induced obese male rats.

    PubMed

    Cyr, Nicole E; Steger, Jennifer S; Toorie, Anika M; Yang, Jonathan Z; Stuart, Ronald; Nillni, Eduardo A

    2015-03-01

    In the periphery, the nutrient-sensing enzyme Sirtuin 1 (silent mating type information regulation 2 homolog 1 [Sirt1]) reduces body weight in diet-induced obese (DIO) rodents. However, the role of hypothalamic Sirt1 in body weight and energy balance regulation is debated. The first studies to reveal that central Sirt1 regulates body weight came from experiments in our laboratory using Sprague-Dawley rats. Central inhibition of Sirt1 decreased body weight and food intake as a result of a forkhead box protein O1 (FoxO1)-mediated increase in the anorexigenic proopiomelanocortin (POMC) and decrease in the orexigenic Agouti-related peptide in the hypothalamic arcuate nucleus. Here, we demonstrate that central inhibition of Sirt1 in DIO decreased body weight and increased energy expenditure at higher levels as compared with the lean counterpart. Brain Sirt1 inhibition in DIO increased acetylated FoxO1, which in turn increased phosphorylated FoxO1 via improved insulin/phosphorylated AKT signaling. Elevated acetylated FoxO1 and phosphorylated FoxO1 increased POMC along with the α-melanocyte-stimulating hormone (α-MSH) maturation enzyme carboxypeptidase E, which resulted in more of the bioactive POMC product α-MSH released into the paraventricular nucleus. Increased in α-MSH led to augmented TRH levels and circulating T3 levels (triiodothyronine, thyroid hormone). These results indicate that inhibiting hypothalamic Sirt1 in DIO enhances the activity of the hypothalamic-pituitary-thyroid axis, which stimulates energy expenditure. Because we show that blocking central Sirt1 causes physiological changes that promote a negative energy balance in an obese individual, our results support brain Sirt1 as a significant target for weight loss therapeutics.

  6. Spexin is a Novel Human Peptide that Reduces Adipocyte Uptake of Long Chain Fatty Acids and Causes Weight Loss in Rodents with Diet-induced Obesity*

    PubMed Central

    Walewski, José L.; Ge, Fengxia; Lobdell, Harrison; Levin, Nancy; Schwartz, Gary J.; Vasselli, Joseph; Pomp, Afons; Dakin, Gregory; Berk, Paul D.

    2014-01-01

    Objective Microarray studies identified Ch12:orf39 (Spexin) as the most dysregulated gene in obese human fat. Therefore we examined its role in obesity pathogenesis. Design and Methods Spexin effects on food intake, meal patterns, body weight, Respiratory Exchange Ratio (RER), and locomotor activity were monitored electronically in C57BL/6J mice or Wistar rats with dietary-induced obesity (DIO). Its effects on adipocyte [3H]-oleate uptake were determined. Results In humans, Spexin gene expression was down-regulated 14.9-fold in obese omental and subcutaneous fat. Circulating Spexin changed in parallel, correlating (r = −0.797) with Leptin. In rats, Spexin (35 μg/kg/day s.c) reduced caloric intake ~32% with corresponding weight loss. Meal patterns were unaffected. In mice, Spexin (25 μg/kg/day i.p.) significantly reduced the RER at night, and increased locomotion. Spexin incubation in vitro significantly inhibited facilitated fatty acid (FA) uptake into DIO mouse adipocytes. Conditioned taste aversion testing (70μg/kg/day i.p.) demonstrated no aversive Spexin effects. Conclusions Spexin gene expression is markedly down-regulated in obese human fat. The peptide produces weight loss in DIO rodents. Its effects on appetite and energy regulation are presumably central; those on adipocyte FA uptake appear direct and peripheral. Spexin is a novel hormone involved in weight regulation, with potential for obesity therapy. PMID:24550067

  7. COH-SR4 Reduces Body Weight, Improves Glycemic Control and Prevents Hepatic Steatosis in High Fat Diet-Induced Obese Mice

    PubMed Central

    Figarola, James Lester; Singhal, Preeti; Rahbar, Samuel; Gugiu, Bogdan Gabriel; Awasthi, Sanjay; Singhal, Sharad S.

    2013-01-01

    Obesity is a chronic metabolic disorder caused by imbalance between energy intake and expenditure, and is one of the principal causative factors in the development of metabolic syndrome, diabetes and cancer. COH-SR4 (“SR4”) is a novel investigational compound that has anti-cancer and anti-adipogenic properties. In this study, the effects of SR4 on metabolic alterations in high fat diet (HFD)-induced obese C57BL/J6 mice were investigated. Oral feeding of SR4 (5 mg/kg body weight.) in HFD mice for 6 weeks significantly reduced body weight, prevented hyperlipidemia and improved glycemic control without affecting food intake. These changes were associated with marked decreases in epididymal fat mass, adipocyte hypertrophy, increased plasma adiponectin and reduced leptin levels. SR4 treatment also decreased liver triglycerides, prevented hepatic steatosis, and normalized liver enzymes. Western blots demonstrated increased AMPK activation in liver and adipose tissues of SR4-treated HFD obese mice, while gene analyses by real time PCR showed COH-SR4 significantly suppressed the mRNA expression of lipogenic genes such as sterol regulatory element binding protein-1c (Srebf1), acetyl-Coenzyme A carboxylase (Acaca), peroxisome proliferator-activated receptor gamma (Pparg), fatty acid synthase (Fasn), stearoyl-Coenzyme A desaturase 1 (Scd1), carnitine palmitoyltransferase 1a (Cpt1a) and 3-hydroxy-3-methyl-glutaryl-CoA reductase (Hmgcr), as well as gluconeogenic genes phosphoenolpyruvate carboxykinase 1 (Pck1) and glucose-6-phosphatase (G6pc) in the liver of obese mice. In vitro, SR4 activates AMPK independent of upstream kinases liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ). Together, these data suggest that SR4, a novel AMPK activator, may be a promising therapeutic compound for treatment of obesity, fatty liver disease, and related metabolic disorders. PMID:24376752

  8. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats

    PubMed Central

    Miana, María; Galán, María; Martínez-Martínez, Ernesto; Varona, Saray; Jurado-López, Raquel; Bausa-Miranda, Belén; Antequera, Alfonso; Luaces, María; Martínez-González, José; Rodríguez, Cristina; Cachofeiro, Victoria

    2015-01-01

    ABSTRACT Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD). Interestingly, treatment with β-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters – it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA) index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4), as well as the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX

  9. The lysyl oxidase inhibitor β-aminopropionitrile reduces body weight gain and improves the metabolic profile in diet-induced obesity in rats.

    PubMed

    Miana, María; Galán, María; Martínez-Martínez, Ernesto; Varona, Saray; Jurado-López, Raquel; Bausa-Miranda, Belén; Antequera, Alfonso; Luaces, María; Martínez-González, José; Rodríguez, Cristina; Cachofeiro, Victoria

    2015-06-01

    Extracellular matrix (ECM) remodelling of the adipose tissue plays a pivotal role in the pathophysiology of obesity. The lysyl oxidase (LOX) family of amine oxidases, including LOX and LOX-like (LOXL) isoenzymes, controls ECM maturation, and upregulation of LOX activity is essential in fibrosis; however, its involvement in adipose tissue dysfunction in obesity is unclear. In this study, we observed that LOX is the main isoenzyme expressed in human adipose tissue and that its expression is strongly upregulated in samples from obese individuals that had been referred to bariatric surgery. LOX expression was also induced in the adipose tissue from male Wistar rats fed a high-fat diet (HFD). Interestingly, treatment with β-aminopropionitrile (BAPN), a specific and irreversible inhibitor of LOX activity, attenuated the increase in body weight and fat mass that was observed in obese animals and shifted adipocyte size toward smaller adipocytes. BAPN also ameliorated the increase in collagen content that was observed in adipose tissue from obese animals and improved several metabolic parameters - it ameliorated glucose and insulin levels, decreased homeostasis model assessment (HOMA) index and reduced plasma triglyceride levels. Furthermore, in white adipose tissue from obese animals, BAPN prevented the downregulation of adiponectin and glucose transporter 4 (GLUT4), as well as the increase in suppressor of cytokine signaling 3 (SOCS3) and dipeptidyl peptidase 4 (DPP4) levels, triggered by the HFD. Likewise, in the TNFα-induced insulin-resistant 3T3-L1 adipocyte model, BAPN prevented the downregulation of adiponectin and GLUT4 and the increase in SOCS3 levels, and consequently normalised insulin-stimulated glucose uptake. Therefore, our data provide evidence that LOX plays a pathologically relevant role in the metabolic dysfunction induced by obesity and emphasise the interest of novel pharmacological interventions that target adipose tissue fibrosis and LOX activity for

  10. Hypoenergetic diet-induced reductions in myofibrillar protein synthesis are restored with resistance training and balanced daily protein ingestion in older men

    PubMed Central

    Murphy, Caoileann H.; Churchward-Venne, Tyler A.; Mitchell, Cameron J.; Kolar, Nathan M.; Kassis, Amira; Karagounis, Leonidas G.; Burke, Louise M.; Hawley, John A.

    2015-01-01

    Strategies to enhance weight loss with a high fat-to-lean ratio in overweight/obese older adults are important since lean loss could exacerbate sarcopenia. We examined how dietary protein distribution affected muscle protein synthesis during energy balance (EB), energy restriction (ER), and energy restriction plus resistance training (ER + RT). A 4-wk ER diet was provided to overweight/obese older men (66 ± 4 yr, 31 ± 5 kg/m2) who were randomized to either a balanced (BAL: 25% daily protein/meal × 4) or skewed (SKEW: 7:17:72:4% daily protein/meal; n = 10/group) pattern. Myofibrillar and sarcoplasmic protein fractional synthetic rates (FSR) were measured during a 13-h primed continuous infusion of l-[ring-13C6]phenylalanine with BAL and SKEW pattern of protein intake in EB, after 2 wk ER, and after 2 wk ER + RT. Fed-state myofibrillar FSR was lower in ER than EB in both groups (P < 0.001), but was greater in BAL than SKEW (P = 0.014). In ER + RT, fed-state myofibrillar FSR increased above ER in both groups and in BAL was not different from EB (P = 0.903). In SKEW myofibrillar FSR remained lower than EB (P = 0.002) and lower than BAL (P = 0.006). Fed-state sarcoplasmic protein FSR was reduced similarly in ER and ER + RT compared with EB (P < 0.01) in both groups. During ER in overweight/obese older men a BAL consumption of protein stimulated the synthesis of muscle contractile proteins more effectively than traditional, SKEW distribution. Combining RT with a BAL protein distribution “rescued” the lower rates of myofibrillar protein synthesis during moderate ER. PMID:25738784

  11. Long-term results of aggressive weight reduction treatment.

    PubMed

    Svacina, S; Haas, T; Nedĕlníková, K; Sonka, J; Sucharda, P; Fried, M; Pesková, M

    1998-01-01

    We have checked weight changes in 11 patients eight years after 2-weeks in-patient weight reduction treatment and weight changes of another group of 11 patients three years after gastric banding. Using multiple linear regression we've looked for factors which could influence the aforementioned weight changes. For weight reduction regimens we confirmed only the following connection: BMI reduction in 8 years = 12.256 - 2.827 x BMI reduction in 2 weeks. For gastric banding it was: BMI reduction in 3 years = -7.880 + 2.383 x BMI reduction in 6 months. We therefore conclude that the long term effects of reduction regimens is not influenced by any hormonal or metabolic characteristics of the patient, but can be predicted by the early weight loss of the patient. Patients who lose too much during the reduction regimen will find it more difficult to keep the weight down, whereas patients who lose weight rapidly after gastric banding have the best long term prognosis.

  12. Ipragliflozin Improves Hepatic Steatosis in Obese Mice and Liver Dysfunction in Type 2 Diabetic Patients Irrespective of Body Weight Reduction.

    PubMed

    Komiya, Chikara; Tsuchiya, Kyoichiro; Shiba, Kumiko; Miyachi, Yasutaka; Furuke, Shunsaku; Shimazu, Noriko; Yamaguchi, Shinobu; Kanno, Kazuo; Ogawa, Yoshihiro

    2016-01-01

    Type 2 diabetes mellitus (T2DM) is associated with a high incidence of non-alcoholic fatty liver disease (NAFLD) related to obesity and insulin resistance. Currently, medical interventions for NAFLD have focused on diet control and exercise to reduce body weight, and there is a requirement for effective pharmacological therapies. Sodium-glucose cotransporter 2 (SGLT2) inhibitors are oral antidiabetic drugs that promote the urinary excretion of glucose by blocking its reabsorption in renal proximal tubules. SGLT2 inhibitors lower blood glucose independent of insulin action and are expected to reduce body weight because of urinary calorie loss. Here we show that an SGLT2 inhibitor ipragliflozin improves hepatic steatosis in high-fat diet-induced and leptin-deficient (ob/ob) obese mice irrespective of body weight reduction. In the obese mice, ipragliflozin-induced hyperphagia occurred to increase energy intake, attenuating body weight reduction with increased epididymal fat mass. There is an inverse correlation between weights of liver and epididymal fat in ipragliflozin-treated obese mice, suggesting that ipragliflozin treatment promotes normotopic fat accumulation in the epididymal fat and prevents ectopic fat accumulation in the liver. Despite increased adiposity, ipragliflozin ameliorates obesity-associated inflammation and insulin resistance in epididymal fat. Clinically, ipragliflozin improves liver dysfunction in patients with T2DM irrespective of body weight reduction. These findings provide new insight into the effects of SGLT2 inhibitors on energy homeostasis and fat accumulation and indicate their potential therapeutic efficacy in T2DM-associated hepatic steatosis.

  13. Cannabis exposure associated with weight reduction and β-cell protection in an obese rat model.

    PubMed

    Levendal, R-A; Schumann, D; Donath, M; Frost, C L

    2012-05-15

    The aim of this study was to investigate the effect of an organic cannabis extract on β-cell secretory function in an in vivo diet-induced obese rat model and determine the associated molecular changes within pancreatic tissue. Diet-induced obese Wistar rats and rats fed on standard pellets were subcutaneously injected with an organic cannabis extract or the vehicle over a 28-day period. The effect of diet and treatment was evaluated using the intraperitoneal glucose tolerance tests (IPGTTs) and qPCR analysis on rat pancreata harvested upon termination of the experiment. The cafeteria diet induced an average weight difference of 32g and an overall increase in body weight in the experimental groups occurred at a significantly slower rate than the control groups, irrespective of diet. Area under the curve for glucose (AUC(g)) in the obese group was significantly lower compared to the lean group (p<0.001), with cannabis treatment significantly reducing the AUC(g) in the lean group (p<0.05), and remained unchanged in the obese group, relative to the obese control group. qPCR analysis showed that the cafeteria diet induced down-regulation of the following genes in the obese control group, relative to lean controls: UCP2, c-MYC and FLIP. Cannabis treatment in the obese group resulted in up-regulation of CB1, GLUT2, UCP2 and PKB, relative to the obese control group, while c-MYC levels were down-regulated, relative to the lean control group. Treatment did not significantly change gene expression in the lean group. These results suggest that the cannabis extract protects pancreatic islets against the negative effects of obesity.

  14. Changes of adiponectin oligomer composition by moderate weight reduction.

    PubMed

    Bobbert, Thomas; Rochlitz, Helmut; Wegewitz, Uta; Akpulat, Suzan; Mai, Knut; Weickert, Martin O; Möhlig, Matthias; Pfeiffer, Andreas F H; Spranger, Joachim

    2005-09-01

    Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 +/- 1.2 to 32.8 +/- 1.1 kg/m(2), P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 +/- 0.5 to 6.1 +/- 0.6 microg/ml (P = 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 +/- 0.07 to 0.4 +/- 0.08 microg/ml, P = 0.042; MMW: 2.3 +/- 0.2 to 2.9 +/- 0.3 microg/ml, P = 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r = -0.695, P = 0.002) and positively with LMW (r = 0.579, P = 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r = 0.665, P = 0.007). Indeed, HMW and free fatty acids before weight reduction predicted approximately 60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol.

  15. Method of glitch reduction in DAC with weight redundancy

    NASA Astrophysics Data System (ADS)

    Azarov, Olexiy D.; Murashchenko, Olexander G.; Chernyak, Olexander I.; Smolarz, Andrzej; Kashaganova, Gulzhan

    2015-12-01

    The appearance of glitches in digital-to-analog converters leads to significant limitations of conversion accuracy and speed, which is critical for DAC and limits their usage. This paper researches the possibility of using the redundant positional number system in order to reduce glitches in DAC. There had been described the usage pattern of number systems with fractional digit weights of bits as well as with the whole number weights of bits. Hereafter there had been suggested the algorithm for glitches reduction in the DAC generation mode of incessant analogue signal. There had also been estimated the efficiency of weight redundancy application with further presentation of the most efficient parameters of number systems. The paper describes a block diagram of a low-glitch DAC based on Fibonacci codes. The simulation results prove the feasibility of weight redundancy application and show a significant reduction of glitches in DAC in comparison with the classical binary system.

  16. Effects of aspartame in young persons during weight reduction.

    PubMed

    Knopp, R H; Brandt, K; Arky, R A

    1976-11-01

    Given the potential use of a low-calorie sweetener during weight reduction, a toxicity study of chronic aspartame ingestion was conducted. Particular attention was given to possible long-term effects of aspartame on the fuel hormonal alterations characteristically caused by weight reduction. As a group mean age was 19.3 yr, body weight was 164.6 lb, and mean height was 65.4 in. Subjects were an average of 33% in excess of ideal body weight. The aspartame dose was 2.7 g/day and was compared on a double-blind randomized basis with a lactose placebo. Both materials were given in gelatin capsules. An average of 6.9 +/- 1.5 lb was lost by the aspartame group during the 13-wk study on a calculated 1,000-calorie diet. The placebo group lost 4.5 +/- 1.2 lb (no significant difference between the two groups). After an overnight fast, reductions in glucose and immunoreactive insulin were seen in both groups, while rising trends in immunoreactive glucagon were observed. These changes are all characteristic of calorie restriction. In no instance was there a detectable effect of the ingested aspartame. No meaningful effect of weight reduction or aspartame was seen on plasma triglyceride and cholesterol, nor on any other parameter of hematologic, hepatic, or renal function that was measured. Similarly, side effects were equally distributed between asparatame and placebo.

  17. Wispy Prosthesis: A Novel Method in Denture Weight Reduction

    PubMed Central

    Anne, Gopinadh; Budeti, Sreedevi; Anche, Sampath Kumar; Zakkula, Srujana; Atla, Jyothi; Jyothula, Ravi Rakesh Dev; Peddinti, Vijaya Kumar

    2016-01-01

    Introduction Stability and retention of the denture becomes at stake with the increase in weight of the denture prosthesis. As a consequence, different materials and methods have been introduced to overcome these issues but denture weight reduction still remains to be a cumbersome and strenuous procedure. Aim To introduce a novel technique for the fabrication of denture prosthesis where in the weight of the denture will not affect the retention and stability of the denture. Materials and Methods Four groups with a sample size of 10 each, were included where in one group was control and other three were study groups. The control group samples were made completely solid and the study group samples were packed with materials like bean balls, cellulose balls and polyacrylic fibers. The weight of all the samples of each study group was measured and compared with the control group. The observations were analyzed statistically by paired t-test. Results It was observed that the bean balls group produced a weight reduction of 31.3%, cellulose balls group 27.4% and polyacrylic fibers group 24.5% when compared to that of the control group. Conclusion This novel technique will eliminate the problems that were associated in creating hollowness and at the same time will reduce the weight of the prosthesis and among all the study groups, bean balls group were found to reduce maximum weight of the prosthesis. PMID:27190947

  18. Calcium intake and reduction in weight or fat mass.

    PubMed

    Teegarden, Dorothy

    2003-01-01

    Obesity is a growing epidemic with subsequent health consequences leading not only to reduced quality of life but also to increased medical costs. Growing evidence supports a relationship between increased calcium intakes and reductions in body weight specific to fat mass. Since the first observations in rats >10 y ago, several recently published clinical studies support this relationship as well. The impact of calcium intake on weight loss or prevention of weight gain has been demonstrated in a wide age range of Caucasian and African-Americans of both genders. This review focuses on the results of clinical trials that have investigated the impact of calcium and dairy products on prevention of weight gain, weight loss or development of the insulin resistance syndrome. The implications of these results are that calcium may play a substantial contributing role in reducing the incidence of obesity and prevalence of the insulin resistance syndrome.

  19. Body Percept Change in Obese Females after Weight Reduction Therapy.

    ERIC Educational Resources Information Center

    Collins, John K.; And Others

    1983-01-01

    Measured video-image representations of body size for 68 females undergoing weight reduction counseling. All judged themselves significantly more obese than they actually were. After therapy, more realistic estimates of their physiques ensued. Dropouts saw themselves as significantly more obese than those who graduated from the program. (JAC)

  20. Arterial stiffening precedes systolic hypertension in diet-induced obesity.

    PubMed

    Weisbrod, Robert M; Shiang, Tina; Al Sayah, Leona; Fry, Jessica L; Bajpai, Saumendra; Reinhart-King, Cynthia A; Lob, Heinrich E; Santhanam, Lakshmi; Mitchell, Gary; Cohen, Richard A; Seta, Francesca

    2013-12-01

    Stiffening of conduit arteries is a risk factor for cardiovascular morbidity. Aortic wall stiffening increases pulsatile hemodynamic forces that are detrimental to the microcirculation in highly perfused organs, such as the heart, brain, and kidney. Arterial stiffness is associated with hypertension but presumed to be due to an adaptive response to increased hemodynamic load. In contrast, a recent clinical study found that stiffness precedes and may contribute to the development of hypertension although the mechanisms underlying hypertension are unknown. Here, we report that in a diet-induced model of obesity, arterial stiffness, measured in vivo, develops within 1 month of the initiation of the diet and precedes the development of hypertension by 5 months. Diet-induced obese mice recapitulate the metabolic syndrome and are characterized by inflammation in visceral fat and aorta. Normalization of the metabolic state by weight loss resulted in return of arterial stiffness and blood pressure to normal. Our findings support the hypothesis that arterial stiffness is a cause rather than a consequence of hypertension.

  1. Metabolic effects of very low calorie weight reduction diets.

    PubMed

    Hoffer, L J; Bistrian, B R; Young, V R; Blackburn, G L; Matthews, D E

    1984-03-01

    A randomized comparison trial of two very low calorie weight reduction diets was carried out for 5 or 8 wk in 17 healthy obese women. One diet provided 1.5 g protein/kg ideal body weight; the other provided 0.8 g protein/kg ideal body weight plus 0.7 g carbohydrate/kg ideal body weight. The diets were isocaloric (500 kcal). Amino acid metabolism was studied by means of tracer infusions of L-[1-13C]leucine and L-[15N]alanine. After 3 wk of adaptation to the diets, nitrogen balance was zero for the 1.5 g protein diet but -2 g N/d for the 0.8 g protein diet. Postabsorptive plasma leucine and alanine flux decreased from base line by an equal extent with both diets by approximately 20 and 40%, respectively. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted, and that nitrogen balance is improved by increasing the protein intake above that level. Basal rates of whole body nitrogen turnover are relatively well maintained, compared with total fasting, at both protein intakes. However, turnover in the peripheral compartment, as evidenced by alanine flux, may be markedly diminished with either diet.

  2. New plant and controller order reduction results with weighted balancing

    NASA Technical Reports Server (NTRS)

    Newman, Brett; Schmidt, David K.

    1991-01-01

    A frequency-response error analysis for frequency-weighted internally balanced (FWIB) truncation is extended and an exact error bound for a case of order reduction by one state is presented. An approximate error bound for a general case of order reduction by more than one state, assuming that only small controllability-observability measures are truncated, is considered. FWIB residualization is presented, and it is shown that a frequency-response error analysis yields results similar to those found for FWIB truncation. It is concluded that FWIB truncation and residualization can be used in a coordinated manner consistent with classical truncation and residualization in order to obtain accuracy higher than that possible from either technique used alone.

  3. Anti-hyperlipidemic activity of Cucumis melo fruit peel extracts in high cholesterol diet induced hyperlipidemia in rats.

    PubMed

    Bidkar, Jayant S; Ghanwat, Dhanaji Dadaso; Bhujbal, Madhuri D; Dama, Ganesh Y

    2012-09-24

    Abstract Cucumis melo Linn. (Cucurbitaceae) fruits have been used, traditionally in Indian traditional system of medicine, for the treatment of various disorders such as liver tonic, cardioprotective, antidiabetic, antiobesity, etc. The aim of the present study was to investigate the possible anti-hyperlipidemic activity of Cucumis melo fruit peel (CMFP) methanolic and aqueous extract in high cholesterol diet induced hyperlipidemia in rats. Treatment with CMFP methanolic and aqueous extract showed significant (P<0.01) reduction in gain in body weight, serum lipid profile like total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) level, atherogenic index and increased the serum high density lipoprotein cholesterol (HDL-C) levels in 28 days treatment when compared to the hyperlipidemic control group. The fecal excretion of bile acids and sterols was further increased upon treatment with CMFP methanolic and aqueous extract and standard drug. Administration of methanolic extract of CMFP at a dose of 500 mg/kg showed higher antihyperlipidemic activity as compared to other extract treated groups. The results concluded that CMFP methanolic extract (500 mg/kg) have potent antihyperlipidemic activity in high cholesterol diet induced hyperlipidemia model and which is equipotent activity when compared with atorvastatin treated group.

  4. Exenatide improves liver mitochondrial dysfunction and insulin resistance by reducing oxidative stress in high fat diet-induced obese mice.

    PubMed

    Wang, Zixuan; Hou, Lin; Huang, Lanhui; Guo, Jun; Zhou, Xinli

    2017-04-22

    Oxidative stress is associated with obesity and may be accompanied by liver insulin resistance and mitochondrial dysfunction. Decreased mitochondrial respiratory chain enzymatic activities and decreased insulin metabolic signaling may promote these maladaptive changes. In this context, exenatide has been reported to reduce hepatic lipid deposition, improve insulin sensitivity and improve mitochondrial dysfunction. We hypothesized that exenatide would attenuate mitochondrial dysfunction by reducing hepatic lipid deposition, blunting oxidant stress and promoting insulin metabolic signaling in a high fat diet-induced model of obesity and insulin resistance. Sixteen-week-old male C57BL/6 diet-induced obese (DIO) mices and age-matched standard diet (STD) mices were treated with exenatide (10 μg/kg twice a day) for 28 days. Compared with untreated STD mice, untreated DIO mice exhibited deposited excessive lipid in liver and produced the oxidative stress in conjunction with insulin resistance, abnormal hepatic cells and mitochondrial histoarchitecture, mitochondrial dysfunction and reduced organism metabolism. Exenatide reduced hepatic steatosis, decreased oxidative stress, and improved insulin resistance in DIO mice, in concert with improvements in the insulin metabolic signaling, mitochondrial respiratory chain enzymatic activation, adenine nucleotide production, organism metabolism and weight gain. Results support the hypothesis that exenatide reduces hepatic cells and mitochondrial structural anomaly and improves insulin resistance in concert with improvements in insulin sensitivity and mitochondrial function activation, concomitantly with reductions in oxidative stress.

  5. A closed-loop synthetic gene circuit for the treatment of diet-induced obesity in mice

    PubMed Central

    Rössger, Katrin; Charpin-El-Hamri, Ghislaine; Fussenegger, Martin

    2013-01-01

    Diet-induced obesity is a lifestyle-associated medical condition that increases the risk of developing cardiovascular disease, type 2 diabetes and certain types of cancer. Here we report the design of a closed-loop genetic circuit that constantly monitors blood fatty acid levels in the setting of diet-associated hyperlipidemia and coordinates reversible and adjustable expression of the clinically licensed appetite-suppressing peptide hormone pramlintide. Grafting of the peroxisome proliferator-activated receptor-α onto the phloretin-responsive repressor TtgR produces a synthetic intracellular lipid-sensing receptor (LSR) that reversibly induces chimeric TtgR-specific promoters in a fatty acid-adjustable manner. Mice with diet-induced obesity in which microencapsulated cells engineered for LSR-driven expression of pramlintide are implanted show significant reduction in food consumption, blood lipid levels and body weight when put on a high-fat diet. Therapeutic designer circuits that monitor levels of pathologic metabolites and link these with the tailored expression of protein pharmaceuticals may provide new opportunities for the treatment of metabolic disorders. PMID:24281397

  6. Diet-Induced Obesity Does Not Alter Tigecycline Treatment Efficacy in Murine Lyme Disease

    PubMed Central

    Pětrošová, Helena; Eshghi, Azad; Anjum, Zoha; Zlotnikov, Nataliya; Cameron, Caroline E.; Moriarty, Tara J.

    2017-01-01

    Obese individuals more frequently suffer from infections, as a result of increased susceptibility to a number of bacterial pathogens. Furthermore, obesity can alter antibiotic treatment efficacy due to changes in drug pharmacokinetics which can result in under-dosing. However, studies on the treatment of bacterial infections in the context of obesity are scarce. To address this research gap, we assessed efficacy of antibiotic treatment in diet-induced obese mice infected with the Lyme disease pathogen, Borrelia burgdorferi. Diet-induced obese C3H/HeN mice and normal-weight controls were infected with B. burgdorferi, and treated during the acute phase of infection with two doses of tigecycline, adjusted to the weights of diet-induced obese and normal-weight mice. Antibiotic treatment efficacy was assessed 1 month after the treatment by cultivating bacteria from tissues, measuring severity of Lyme carditis, and quantifying bacterial DNA clearance in ten tissues. In addition, B. burgdorferi-specific IgG production was monitored throughout the experiment. Tigecycline treatment was ineffective in reducing B. burgdorferi DNA copies in brain. However, diet-induced obesity did not affect antibiotic-dependent bacterial DNA clearance in any tissues, regardless of the tigecycline dose used for treatment. Production of B. burgdorferi-specific IgGs was delayed and attenuated in mock-treated diet-induced obese mice compared to mock-treated normal-weight animals, but did not differ among experimental groups following antibiotic treatment. No carditis or cultivatable B. burgdorferi were detected in any antibiotic-treated group. In conclusion, obesity was associated with attenuated and delayed humoral immune responses to B. burgdorferi, but did not affect efficacy of antibiotic treatment. PMID:28286500

  7. Weight reduction is associated with increased plasma fibrin clot lysis.

    PubMed

    Brzezińska-Kolarz, Beata; Kolarz, Marek; Wałach, Angelika; Undas, Anetta

    2014-11-01

    Obesity is associated with an increased risk of vascular thrombotic events. We sought to investigate how obesity and weight loss affect plasma fibrin clot properties. A total of 29 obese patients were studied before and after 3-month low-fat diet. Plasma fibrin clot parameters, including fibrin clot permeation coefficient (Ks), the lag phase of the turbidity curve, clot lysis time (t 50%), maximum rate of increase in D-dimer levels, and maximum D-dimer concentrations, were determined. Low-fat diet resulted in the reduction of body weight (P < .0001), body mass index (P < .0001), fat mass (P < .0001), total cholesterol (P < .0001), low-density lipoprotein cholesterol (P = .0005), triglycerides (P = .008), and plasminogen activator inhibitor 1 (P = .02), but not in fibrinogen or C-reactive protein. The only change in fibrin clot variables was shorter t 50% (P = .02). Baseline t 50%, but not posttreatment, correlated with waist circumference (r = .44, p = .02). This study demonstrates that weight loss in obese people can increase the efficiency of fibrin clot lysis.

  8. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity

    PubMed Central

    de Melo, T.S.; Lima, P.R.; Carvalho, K.M.M.B.; Fontenele, T.M.; Solon, F.R.N.; Tomé, A.R.; de Lemos, T.L.G.; da Cruz Fonseca, S.G.; Santos, F.A.; Rao, V.S.; de Queiroz, M.G.R.

    2017-01-01

    Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20–25 g (n=6–8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses. PMID:28076453

  9. Ferulic acid lowers body weight and visceral fat accumulation via modulation of enzymatic, hormonal and inflammatory changes in a mouse model of high-fat diet-induced obesity.

    PubMed

    de Melo, T S; Lima, P R; Carvalho, K M M B; Fontenele, T M; Solon, F R N; Tomé, A R; de Lemos, T L G; da Cruz Fonseca, S G; Santos, F A; Rao, V S; de Queiroz, M G R

    2017-01-05

    Previous studies have reported on the glucose and lipid-lowering effects of ferulic acid (FA) but its anti-obesity potential has not yet been firmly established. This study investigated the possible anti-obesitogenic effects of FA in mice fed a high-fat diet (HFD) for 15 weeks. To assess the antiobesity potential of FA, 32 male Swiss mice, weighing 20-25 g (n=6-8 per group) were fed a normal diet (ND) or HFD, treated orally or not with either FA (10 mg/kg) or sibutramine (10 mg/kg) for 15 weeks and at the end of this period, the body weights of animals, visceral fat accumulation, plasma levels of glucose and insulin hormone, amylase and lipase activities, the satiety hormones ghrelin and leptin, and tumor necrosis factor-α (TNF-α) and monocyte chemoattractant protein-1 (MCH-1) were analyzed. Results revealed that FA could effectively suppress the HFD-associated increase in visceral fat accumulation, adipocyte size and body weight gain, similar to sibutramine, the positive control. FA also significantly (P<0.05) decreased the HFD-induced elevations in serum lipid profiles, amylase and lipase activities, and the levels of blood glucose and insulin hormone. The markedly elevated leptin and decreased ghrelin levels seen in HFD-fed control mice were significantly (P<0.05) reversed by FA treatment, almost reaching the values seen in ND-fed mice. Furthermore, FA demonstrated significant (P<0.05) inhibition of serum levels of inflammatory mediators TNF-α, and MCH-1. These results suggest that FA could be beneficial in lowering the risk of HFD-induced obesity via modulation of enzymatic, hormonal and inflammatory responses.

  10. Combinatorial gene construct and non-viral delivery for anti-obesity in diet-induced obese mice.

    PubMed

    Park, Hongsuk; Cho, Sungpil; Han, Yong Hwan; Janat-Amsbury, Margit M; Boudina, Sihem; Bae, You Han

    2015-06-10

    The combinatorial peptidergic therapy of islet amyloid polypeptide (IAPP) and leptin (LEP) analogues was once an optimistic option in treating obese animals and patients. However, the need for frequent administrations and its negative side effects prevent it from being a viable choice. Here, we developed a combinatorial gene therapy of IAPP and LEP, where two genes are inserted into a single plasmid with self-cleaving furin and 2A sites to treat diet-induced obese (DIO) mice. The developed plasmid DNA (pDNA) individually produced both IAPP and LEP peptides in vitro and in vivo. The pDNA was delivered with a non-viral polymeric carrier, and its once-a-week administrations demonstrated a synergistic loss of body weight and significant reductions of fat mass, blood glucose, and lipid levels in DIO mice. The results suggest that the combinatorial gene therapy would have higher potential than the peptidergic approach for future translation due to its improved practicability.

  11. Clinical consequences of diet-induced dysbiosis.

    PubMed

    Chan, Yee Kwan; Estaki, Mehrbod; Gibson, Deanna L

    2013-01-01

    Various disease states are associated with an imbalance of protective and pathogenic bacteria in the gut, termed dysbiosis. Current evidence reveals that dietary factors affect the microbial ecosystem in the gut. Changes to community structure of the intestinal microbiota are not without consequence considering the wide effects that the microbes have on both local and systemic immunity. The goal of this review is to give insight into the importance of gut microbiota in disease development and the possible therapeutic interventions in clinical settings. We introduce the complex tripartite relationship between diet, microbes and the gut epithelium. This is followed by a summary of clinical evidence of diet-induced dysbiosis as a contributing factor in the development of gastrointestinal diseases like inflammatory bowel disease, irritable bowel syndrome and colorectal cancer, as well as systemic diseases like obesity, diabetes, atherosclerosis and nonalcoholic fatty liver disease. Finally, the current dietary and microbial interventions to promote a healthy microbial profile will be reviewed.

  12. Weight reduction potential of automobiles and light trucks: 1980 summary source document. Final report

    SciTech Connect

    Hsia, H.

    1981-06-01

    This report provides an assessment of the potential of weight reduction for passenger cars and light trucks (including pickup trucks, vans, and utility vehicles of GVWR up to 8500 pounds) in the post-1985 period. Vehicle characteristics and weight reduction methodologies, as well as methodologies for determining secondary weight reduction, are presented. Results of four weight reduction scenarios for material substitution, emphasizing high strength steels, fiberglass reinforced plastics, aluminum, and hybrid reinforced plastics, are presented for baseline vehicles.

  13. Chronic rhein treatment improves recognition memory in high-fat diet-induced obese male mice.

    PubMed

    Wang, Sen; Huang, Xu-Feng; Zhang, Peng; Wang, Hongqin; Zhang, Qingsheng; Yu, Shijia; Yu, Yinghua

    2016-10-01

    High-fat (HF) diet modulates gut microbiota and increases plasma concentration of lipopolysaccharide (LPS) which is associated with obesity and its related low-grade inflammation and cognitive decline. Rhein is the main ingredient of the rhubarb plant which has been used as an anti-inflammatory agent for several millennia. However, the potential effects of rhein against HF diet-induced obesity and its associated alteration of gut microbiota, inflammation and cognitive decline have not been studied. In this study, C57BL/6J male mice were fed an HF diet for 8 weeks to induce obesity, and then treated with oral rhein (120 mg/kg body weight/day in HF diet) for a further 6 weeks. Chronic rhein treatment prevented the HF diet-induced recognition memory impairment assessed by the novel object recognition test, neuroinflammation and brain-derived neurotrophic factor (BDNF) deficits in the perirhinal cortex. Furthermore, rhein inhibited the HF diet-induced increased plasma LPS level and the proinflammatory macrophage accumulation in the colon and alteration of microbiota, including decreasing Bacteroides-Prevotella spp. and Desulfovibrios spp. DNA and increasing Bifidobacterium spp. and Lactobacillus spp. DNA. Moreover, rhein also reduced body weight and improved glucose tolerance in HF diet-induced obese mice. In conclusion, rhein improved recognition memory and prevented obesity in mice on a chronic HF diet. These beneficial effects occur via the modulation of microbiota, hypoendotoxinemia, inhibition of macrophage accumulation, anti-neuroinflammation and the improvement of BDNF expression. Therefore, supplementation with rhein-enriched food or herbal medicine could be beneficial as a preventive strategy for chronic HF diet-induced cognitive decline, microbiota alteration and neuroinflammation.

  14. Outcome Expectation Ratings as Predictors of Success in Weight Reduction.

    ERIC Educational Resources Information Center

    And Others; Bradley, Ian

    1980-01-01

    Obese persons about to enter a group program intended to produce "conditioned satiety" were asked to estimate their weight loss. Their outcome expectation correlated significantly with weight loss recorded seven weeks later. However, the magnitude of expected weight loss exceeded the actual amount of weight lost. (Author)

  15. Anti-adipogenic effect of Artemisia annua in diet-induced-obesity mice model

    PubMed Central

    Baek, Hye Kyung; Shim, Hyeji; Lim, Hyunmook; Shim, Minju; Kim, Chul-Kyu; Park, Sang-Kyu; Lee, Yong Seok; Song, Ki-Duk; Kim, Sung-Jo

    2015-01-01

    Obesity has increased continuously in western countries during the last several decades and recently become a problem in developing countries. Currently, anti-obesity drugs originating from natural products are being investigated for their potential to overcome adverse effects associated with chemical drugs. Artemisinic acid, which was isolated from the well-known anti-malaria herb Artemisia annua (AA) L., was recently shown to possess anti-adipogenic effects in vitro. However, the anti-adipogenic effects of AA in animal models have not yet been investigated. Therefore, we conducted daily oral administration with AA water extract in a diet-induced obesity animal model and treated 3T3-L1 cells with AA to confirm the anti-adipogenic effects in the related protein expressions. We then evaluated the physiology, adipose tissue histology and mRNA expressions of many related genes. Inhibition of adipogenesis by the AA water extract was observed in vitro. In the animal model, weight gain was significantly lower in the AA treated group, but there were no changes in food intake volume or calories. Reductions in lipid droplet size and mRNA expression associated with adipogenesis were also observed in animal epididymal fat. This study is the first to report that AA has an anti-obese effects in vivo. PMID:26243598

  16. Inhibition of RXR and PPARγ ameliorates diet-induced obesity and type 2 diabetes

    PubMed Central

    Yamauchi, Toshimasa; Waki, Hironori; Kamon, Junji; Murakami, Koji; Motojima, Kiyoto; Komeda, Kajuro; Miki, Hiroshi; Kubota, Naoto; Terauchi, Yasuo; Tsuchida, Atsuko; Tsuboyama-Kasaoka, Nobuyo; Yamauchi, Naoko; Ide, Tomohiro; Hori, Wataru; Kato, Shigeaki; Fukayama, Masashi; Akanuma, Yasuo; Ezaki, Osamu; Itai, Akiko; Nagai, Ryozo; Kimura, Satoshi; Tobe, Kazuyuki; Kagechika, Hiroyuki; Shudo, Koichi; Kadowaki, Takashi

    2001-01-01

    PPARγ is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARγ by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARγ activity observed in heterozygous PPARγ-deficient mice or the Pro12Ala polymorphism in human PPARγ, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARγ/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARγ antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin’s effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARγ-deficient mice with an RXR antagonist or a PPARγ antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARγ/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes. PMID:11581301

  17. Inhibition of RXR and PPARgamma ameliorates diet-induced obesity and type 2 diabetes.

    PubMed

    Yamauchi, T; Waki, H; Kamon, J; Murakami, K; Motojima, K; Komeda, K; Miki, H; Kubota, N; Terauchi, Y; Tsuchida, A; Tsuboyama-Kasaoka, N; Yamauchi, N; Ide, T; Hori, W; Kato, S; Fukayama, M; Akanuma, Y; Ezaki, O; Itai, A; Nagai, R; Kimura, S; Tobe, K; Kagechika, H; Shudo, K; Kadowaki, T

    2001-10-01

    PPARgamma is a ligand-activated transcription factor and functions as a heterodimer with a retinoid X receptor (RXR). Supraphysiological activation of PPARgamma by thiazolidinediones can reduce insulin resistance and hyperglycemia in type 2 diabetes, but these drugs can also cause weight gain. Quite unexpectedly, a moderate reduction of PPARgamma activity observed in heterozygous PPARgamma-deficient mice or the Pro12Ala polymorphism in human PPARgamma, has been shown to prevent insulin resistance and obesity induced by a high-fat diet. In this study, we investigated whether functional antagonism toward PPARgamma/RXR could be used to treat obesity and type 2 diabetes. We show herein that an RXR antagonist and a PPARgamma antagonist decrease triglyceride (TG) content in white adipose tissue, skeletal muscle, and liver. These inhibitors potentiated leptin's effects and increased fatty acid combustion and energy dissipation, thereby ameliorating HF diet-induced obesity and insulin resistance. Paradoxically, treatment of heterozygous PPARgamma-deficient mice with an RXR antagonist or a PPARgamma antagonist depletes white adipose tissue and markedly decreases leptin levels and energy dissipation, which increases TG content in skeletal muscle and the liver, thereby leading to the re-emergence of insulin resistance. Our data suggested that appropriate functional antagonism of PPARgamma/RXR may be a logical approach to protection against obesity and related diseases such as type 2 diabetes.

  18. Diet-induced obesity in rats leads to a decrease in sperm motility

    PubMed Central

    2011-01-01

    Background Obesity is rapidly becoming a worldwide epidemic that affects children and adults. Some studies have shown a relationship between obesity and infertility, but until now it remains controversial. Thus, the aim of the present study was to investigate the effect of high-fat diet-induced obesity on male reproductive parameters. Methods In a first experiment, male Wistar rats were fed a high-fat diet (HFD) or standard chow (SD) for 15, 30 or 45 weeks, after which they were evaluated by adiposity index, serum leptin levels, reproductive organ weights and sperm counts. In a second experiment, rats received HFD or SD only for 15 weeks, long enough to cause obesity. Sexual hormones and sexual behavior were evaluated in these animals, as well as fertility after natural mating. Another group of rats was submitted to motility analysis and fertility evaluation after in utero insemination. Results After 15, 30 or 45 weeks, HFD-fed animals presented significant increases in obesity index and serum leptin levels. Reproductive organ weights and sperm counts in the testis and epididymis were similar between the two groups at all timepoints studied. Sexual behavior was not altered by the diet regimen, and HFD fertility after natural mating was also similar to SD-fed animals. Intergroup testosterone levels were also comparable, but estradiol levels were increased in HFD rats. Furthermore, sperm quality was reduced in HFD animals as evidenced by their decreased percentage of sperm with progressive movement. This altered motility parameter was followed by a trend toward reduction in fertility potential after artificial in utero insemination. Conclusions The results reported herein showed that obesity can affect sperm quality, by reducing sperm motility, without affecting other sperm parameters. The low sperm quality caused a slight reduction in fertility potential, showing that obesity may lead to impairment in male fertility. PMID:21396114

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

    PubMed

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

    2015-10-28

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

  20. High-fat diet-induced reduction of peroxisome proliferator-activated receptor-γ coactivator-1α messenger RNA levels and oxidative capacity in the soleus muscle of rats with metabolic syndrome.

    PubMed

    Nagatomo, Fumiko; Fujino, Hidemi; Kondo, Hiroyo; Takeda, Isao; Tsuda, Kinsuke; Ishihara, Akihiko

    2012-02-01

    Animal models of type 2 diabetes exhibit reduced peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) messenger RNA (mRNA) levels, which are associated with decreased oxidative capacity, in skeletal muscles. In contrast, animal models with metabolic syndrome show normal PGC-1α mRNA levels. We hypothesized that a high-fat diet decreases PGC-1α mRNA levels in skeletal muscles of rats with metabolic syndrome, reducing muscle oxidative capacity and accelerating metabolic syndrome or inducing type 2 diabetes. We examined mRNA levels and fiber profiles in the soleus muscles of rats with metabolic syndrome (SHR/NDmcr-cp [cp/cp]; CP) fed a high-fat diet. Five-week-old CP rats were assigned to a sedentary group (CP-N) that was fed a standard diet (15.1 kJ/g, 23.6% protein, 5.3% fat, and 54.4% carbohydrates) or a sedentary group (CP-H) that was fed a high-fat diet (21.6 kJ/g, 23.6% protein, 34.9% fat, and 25.9% carbohydrates) and were housed for 10 weeks. Body weight, energy intake, and systolic blood pressure were higher in the CP-H group than in the CP-N group. Nonfasting glucose, triglyceride, total cholesterol, and leptin levels were higher in the CP-H group than in the CP-N group. There was no difference in insulin levels between the CP-N and CP-H groups. Muscle PGC-1α mRNA levels and succinate dehydrogenase activity were lower in the CP-H group than in the CP-N group. We concluded that a high-fat diet reduces PGC-1α mRNA levels and oxidative capacity in skeletal muscles and accelerates metabolic syndrome.

  1. The Effect of Weight Reduction on the Blood and Urine Measurements of College Wrestlers.

    ERIC Educational Resources Information Center

    Segurson, Jack

    It has been suggested that the weight reduction practices of wrestlers results in kidney and liver problems. To observe the effect of wrestlers' weight reduction, diagnostic tests for kidney and liver problems were done on the blood and urine samples of 22 college wrestlers over the course of a wrestling season. Results obtained after reduction to…

  2. Validation of a Weight Reduction Treatment Package for the Retarded.

    ERIC Educational Resources Information Center

    Rotatori, Anthony F.; And Others

    Five studies are reviewed which indicated the effectiveness on weight loss by mentally retarded persons of a treatment program stressing self control. The intervention included procedures which increased the dieter's self awareness of overeating behavior patterns and body weight, reduced food cues, reduced eating rates, increased activity level…

  3. Interventions for Weight Reduction: Facing the Maintenance Problem

    ERIC Educational Resources Information Center

    Anderson, Drew A.; Simmons, Angela M.; Milnes, Suzanne M.

    2005-01-01

    Behavioral treatments are perhaps the cornerstone of modern obesity treatment. Maintenance of weight lost via behavioral treatments has been less than hoped for, however. Weight regain is the result of complex interactions between physiological, behavioral, cognitive, and environmental factors; in this paper we review some of these factors and…

  4. Characteristics influencing weight reduction among veterans in the MOVE!® Program.

    PubMed

    Garvin, Jane T; Marion, Lucy N; Narsavage, Georgia L; Finnegan, Lorna

    2015-01-01

    Obesity is a common health problem for veterans. This study explored background and program characteristics associated with a 5% weight reduction for veterans enrolled in MOVE!(®), a weight management program. For data analysis, 404 veteran records were examined using logistic regression. Background characteristics included socio-demographic variables, comorbidity, body mass index, rurality, and Veterans Administration (VA) priority group. Program characteristics included the program type (group attendee or self-managed) as well as the number and type of provider contacts. Thirteen percent of participants achieved a 5% weight reduction. Age in years (odds ratio [OR] = 1.04) and the number of group visits (OR = 1.05) were significant predictors for achieving a 5% weight reduction. Given the importance of weight reduction, health professionals should consider these significant predictors when planning weight-reduction programs for veterans.

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

    PubMed

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

    2014-07-01

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

  6. Shuttle to Shuttle 2: Subsystem weight reduction potential (estimated 1992 technology readiness date)

    NASA Technical Reports Server (NTRS)

    Macconochie, Ian O.

    1988-01-01

    The objective of this study was to make estimates of the weight savings that might be realized on all the subsystems on an advanced rocket-powered shuttle (designated Shuttle 2) by using advanced technologies having a projected maturity date of 1992. The current Shuttle with external tank was used as a baseline from which to make the estimates of weight savings on each subsystem. The subsystems with the greatest potential for weight reduction are the body shell and the thermal protection system. For the body shell, a reduction of 5.2 percent in the weight of the vehicle at main engine cutoff is projected through the application of new technologies, and an additional configuration-based reduction of 5 percent is projected through simplification of body shape. A reduction of 5 percent is projected for the thermal protection system through experience with the current Space Shuttle and the potential for reducing thermal protection system thicknesses in selected areas. Main propellant tanks are expected to increase slightly in weight. The main propulsion system is also projected to increase in weight because of the requirement to operate engines at derated power levels in order to accommodate one-engine-out capability. The projections for weight reductions through improvements in the remaining subsystems are relatively small. By summing all the technology factors, a projected reduction of 16 percent in the vehicle weight at main engine cutoff is obtained. By summarizing the configurational factors, a potential reduction of 12 percent in vehicle weight is obtained.

  7. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions.

    PubMed

    Beilharz, Jessica E; Maniam, Jayanthi; Morris, Margaret J

    2015-08-12

    It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments.

  8. Diet-Induced Cognitive Deficits: The Role of Fat and Sugar, Potential Mechanisms and Nutritional Interventions

    PubMed Central

    Beilharz, Jessica E.; Maniam, Jayanthi; Morris, Margaret J.

    2015-01-01

    It is of vital importance to understand how the foods which are making us fat also act to impair cognition. In this review, we compare the effects of acute and chronic exposure to high-energy diets on cognition and examine the relative contributions of fat (saturated and polyunsaturated) and sugar to these deficits. Hippocampal-dependent memory appears to be particularly vulnerable to the effects of high-energy diets and these deficits can occur rapidly and prior to weight gain. More chronic diet exposure seems necessary however to impair other sorts of memory. Many potential mechanisms have been proposed to underlie diet-induced cognitive decline and we will focus on inflammation and the neurotrophic factor, brain-derived neurotrophic factor (BDNF). Finally, given supplementation of diets with omega-3 and curcumin has been shown to have positive effects on cognitive function in healthy ageing humans and in disease states, we will discuss how these nutritional interventions may attenuate diet-induced cognitive decline. We hope this approach will provide important insights into the causes of diet-induced cognitive deficits, and inform the development of novel therapeutics to prevent or ameliorate such memory impairments. PMID:26274972

  9. Antiatherosclerotic and Cardioprotective Potential of Acacia senegal Seeds in Diet-Induced Atherosclerosis in Rabbits

    PubMed Central

    Ram, Heera; Jatwa, Rameshwar; Purohit, Ashok

    2014-01-01

    Acacia senegal L. (Fabaceae) seeds are essential ingredient of “Pachkutta,” a specific Rajasthani traditional food. The present study explored antiatherosclerotic and cardioprotective potential of Acacia senegal seed extract, if any, in hypercholesterolemic diet-induced atherosclerosis in rabbits. Atherosclerosis in rabbits was induced by feeding normal diet supplemented with oral administration of cholesterol (500 mg/kg body weight/day mixed with coconut oil) for 15 days. Circulating total cholesterol (TC), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), triglycerides, and VLDL-cholesterol (VLDL-C) levels; atherogenic index (AI); cardiac lipid peroxidation (LPO); planimetric studies of aortal wall; and histopathological studies of heart, aorta, kidney, and liver were performed. Apart from reduced atherosclerotic plaques in aorta (6.34 ± 0.72) and increased lumen volume (51.65 ± 3.66), administration with ethanolic extract of Acacia senegal seeds (500 mg/kg/day, p.o.) for 45 days to atherosclerotic rabbits significantly lowered serum TC, LDL-C, triglyceride, and VLDL-C levels and atherogenic index as compared to control. Atherogenic diet-induced cardiac LPO and histopathological abnormalities in aorta wall, heart, kidney, and liver were reverted to normalcy by Acacia senegal seed extract administration. The findings of the present study reveal that Acacia senegal seed extract ameliorated diet-induced atherosclerosis and could be considered as lead in the development of novel therapeutics. PMID:25544897

  10. Effect of tempol on peripheral neuropathy in diet-induced obese and high fat fed/low dose streptozotocin treated C57Bl6/J mice.

    PubMed

    Obrosov, Alexander; Shevalye, Hanna; Coppey, Lawrence J; Yorek, Mark A

    2017-04-04

    In this study we sought to determine the efficacy of tempol on multiple neuropathic endpoints in a diet-induced obese mouse, a model of pre-diabetes, and a high fat fed low dose streptozotocin treated mouse, a model of type 2 diabetes. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperdine -1-oxyl) is a low molecular weight, water soluble, membrane permeable and metal independent superoxide dismutase mimetic that has been widely used in cellular studies for the removal of intracellular and extracellular superoxide. This in vivo study was designed to be an early intervention. Fourteen weeks post high fat diet (six weeks post hyperglycemia) control, obese and diabetic mice were divided into no treatment and treatment groups. The treated mice received tempol by gavage (150 mg/kg in water) while the untreated mice received vehicle. The diet-induced obese and diabetic mice were maintained on the high fat diet for the duration of the study while the control group was maintained on the standard diet. Obesity and diabetes caused slowing of motor and sensory nerve conduction, reduction in intraepidermal nerve fiber density, thermal hypoalgesia and mechanical allodynia. Treatment with tempol partially or completely protected obese and diabetic mice from these deficits. These studies suggest that tempol or other effective scavengers of reactive oxygen species may be a viable option for treating neural complications associated with obesity or type 2 diabetes.

  11. Ladder-Climbing Training Prevents Bone Loss and Microarchitecture Deterioration in Diet-Induced Obese Rats.

    PubMed

    Tang, Liang; Gao, Xiaohang; Yang, Xiaoying; Liu, Chentao; Wang, Xudan; Han, Yanqi; Zhao, Xinjuan; Chi, Aiping; Sun, Lijun

    2016-01-01

    Resistance exercise has been proved to be effective in improving bone quality in both animal and human studies. However, the issue about whether resistance exercise can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of ladder-climbing training, one of the resistance exercises, on bone mechanical properties and microarchitecture in high-fat (HF) diet-induced obese rats. Twenty-four rats were randomly assigned to the Control, HF + sedentary (HF-S) and HF + ladder-climbing training (HF-LCT) groups. Rats in the HF-LCT group performed ladder-climbing training for 8 weeks. The results showed that ladder-climbing training significantly reduced body and fat weight, and increased muscle mass along with a trend toward enhanced muscle strength in diet-induced obese rats. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by ladder-climbing training, as evidenced by increased trabecular bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor ladder-climbing training had an impact on femoral biomechanical properties. Moreover, ladder-climbing training significantly increased serum adiponectin, decreased serum leptin, TNF-α, IL-6 levels, and downregulated myostatin (MSTN) expression in diet-induced obese rats. Taken together, ladder-climbing training prevents bone loss and microarchitecture deterioration in diet-induced obese rats through multiple mechanisms including increasing mechanical loading on bone due to improved skeletal muscle mass and strength, regulating the levels of myokines and adipokines, and suppressing the release of pro-inflammatory cytokines. It indicates that resistance exercise may be a promising therapy for treating obesity-induced bone loss.

  12. Differences in mechanisms between weight loss-sensitive and -resistant blood pressure reduction in obese subjects.

    PubMed

    Masuo, K; Mikami, H; Ogihara, T; Tuck, M L

    2001-07-01

    This study was conducted to clarify the mechanisms involved in the sensitivity for blood pressure (BP) reduction in response to weight loss. In particular, we focused on the contributions of sympathetic nervous system activity and fasting plasma leptin and insulin levels to BP levels during weight loss in obese subjects with weight loss-sensitive and -resistant BP reduction. Sixty-one young, obese untreated hypertensive men (HT) and 52 obese normotensive men (NT) were enrolled in a weight loss program consisting of a low caloric diet and aerobic exercise over a 24-week period. At entry and at week 24, body mass index (BMI), BP, plasma norepinephrine (NE), leptin and insulin were measured. Successful weight loss and BP reduction were respectively defined as a more than a 10% reduction in BMI or mean BP from baseline at week 24. More than 60% of subjects in either group successfully achieved weight loss by this definition. The percentage of subjects who successfully achieved BP reduction was higher (64%) among those subjects who achieved weight loss than among those who did not (22%). Plasma NE level at entry in subjects who failed to achieve BP reduction despite weight loss was significantly higher than that in subjects who succeeded in BP reduction. Plasma leptin and insulin levels were similar between subjects with and without BP reduction. In addition, the absolute decrement and percent decrement in plasma NE in subjects who succeeded in BP reduction were significantly greater than those in subjects who failed to reduce their BP. Absolute and percent decrements in plasma leptin and insulin were similar in both groups. These results suggest that individuals who are resistant to weight loss-induced BP reduction have more sympathetic overactivity both at the outset of and during weight loss.

  13. The Effect of Weight Reduction on Body Composition and Strength in High School Wrestlers.

    ERIC Educational Resources Information Center

    Hejna, William F.; And Others

    A study assessed the relationship of weight reduction to the strength of various muscle groups in conjunction with a pre-season and in-season training and conditioning program. Twenty-nine high school wrestlers, with an average age of 16 years 4 months, significantly reduced their body weight. In the process, there were losses in lean body weight.…

  14. Neuroprotection in diet-induced ketotic rat brain after focal ischemia.

    PubMed

    Puchowicz, Michelle A; Zechel, Jennifer L; Valerio, Jose; Emancipator, Douglas S; Xu, Kui; Pundik, Svetlana; LaManna, Joseph C; Lust, W David

    2008-12-01

    Neuroprotective properties of ketosis may be related to the upregulation of hypoxia inducible factor (HIF)-1alpha, a primary constituent associated with hypoxic angiogenesis and a regulator of neuroprotective responses. The rationale that the utilization of ketones by the brain results in elevation of intracellular succinate, a known inhibitor of prolyl hydroxylase (the enzyme responsible for the degradation of HIF-1alpha) was deemed as a potential mechanism of ketosis on the upregulation of HIF-1alpha. The neuroprotective effect of diet-induced ketosis (3 weeks of feeding a ketogenic diet), as pretreatment, on infarct volume, after reversible middle cerebral artery occlusion (MCAO), and the upregulation of HIF-1alpha were investigated. The effect of beta-hydroxybutyrate (BHB), as a pretreatment, via intraventricular infusion (4 days of infusion before stroke) was also investigated following MCAO. Levels of HIF-1alpha and Bcl-2 (anti-apoptotic protein) proteins and succinate content were measured. A 55% or 70% reduction in infarct volume was observed with BHB infusion or diet-induced ketosis, respectively. The levels of HIF-1alpha and Bcl-2 proteins increased threefold with diet-induced ketosis; BHB infusions also resulted in increases in these proteins. As hypothesized, succinate content increased by 55% with diet-induced ketosis and fourfold with BHB infusion. In conclusion, the biochemical link between ketosis and the stabilization of HIF-1alpha is through the elevation of succinate, and both HIF-1alpha stabilization and Bcl-2 upregulation play a role in ketone-induced neuroprotection in the brain.

  15. Biomedical engineering and the obesity epidemic: treatments for weight reduction.

    PubMed

    Rutherford, Jesse Jayne

    2010-01-01

    Obesity is becoming increasingly common, with at least 400 million obese adults worldwide and the World Health Organization (WHO) projecting that this statistic will reach 700 million in another five years. Ironically, despite the fact that a majority of adults in developed nations are overweight or obese, society stigmatizes the obese severely. Still, obese people have more than just social motivations for losing weight; obesity commonly goes hand in hand with life-threatening comorbidities like cardiovascular disease and type 2 diabetes and some forms of cancer. It severely threatens quality of life, limiting the ability to move and work, navigate public places, and provide care for others and is a factor in musculoskeletal disorders like osteoarthritis. Both obesity and its comorbidities lead obese patients to hospitals at greater rates than patients of normal weight, and these factors, along with social pressures, motivate patients and their physicians to pursue solutions for obesity, its comorbidities, or both.

  16. Intermittent Hypoxia Exacerbates Metabolic Effects of Diet-Induced Obesity

    PubMed Central

    Drager, Luciano F.; Li, Jianguo; Reinke, Christian; Bevans-Fonti, Shannon; Jun, Jonathan C.; Polotsky, Vsevolod Y.

    2015-01-01

    Obesity causes insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), but the relative contribution of sleep apnea is debatable. The main aim of this study is to evaluate the effects of chronic intermittent hypoxia (CIH), a hallmark of sleep apnea, on IR and NAFLD in lean mice and mice with diet-induced obesity (DIO). Mice (C57BL/6J), 6–8 weeks of age were fed a high fat (n = 18) or regular (n = 16) diet for 12 weeks and then exposed to CIH or control conditions (room air) for 4 weeks. At the end of the exposure, fasting (5 h) blood glucose, insulin, homeostasis model assessment (HOMA) index, liver enzymes, and intraperitoneal glucose tolerance test (1 g/kg) were measured. In DIO mice, body weight remained stable during CIH and did not differ from control conditions. Lean mice under CIH were significantly lighter than control mice by day 28 (P = 0.002). Compared to lean mice, DIO mice had higher fasting levels of blood glucose, plasma insulin, the HOMA index, and had glucose intolerance and hepatic steatosis at baseline. In lean mice, CIH slightly increased HOMA index (from 1.79 ± 0.13 in control to 2.41 ± 0.26 in CIH; P = 0.05), whereas glucose tolerance was not affected. In contrast, in DIO mice, CIH doubled HOMA index (from 10.1 ± 2.1 in control to 22.5 ± 3.6 in CIH; P < 0.01), and induced severe glucose intolerance. In DIO mice, CIH induced NAFLD, inflammation, and oxidative stress, which was not observed in lean mice. In conclusion, CIH exacerbates IR and induces steatohepatitis in DIO mice, suggesting that CIH may account for metabolic dysfunction in obesity. PMID:21799478

  17. Intermittent hypoxia exacerbates metabolic effects of diet-induced obesity.

    PubMed

    Drager, Luciano F; Li, Jianguo; Reinke, Christian; Bevans-Fonti, Shannon; Jun, Jonathan C; Polotsky, Vsevolod Y

    2011-11-01

    Obesity causes insulin resistance (IR) and nonalcoholic fatty liver disease (NAFLD), but the relative contribution of sleep apnea is debatable. The main aim of this study is to evaluate the effects of chronic intermittent hypoxia (CIH), a hallmark of sleep apnea, on IR and NAFLD in lean mice and mice with diet-induced obesity (DIO). Mice (C57BL/6J), 6-8 weeks of age were fed a high fat (n = 18) or regular (n = 16) diet for 12 weeks and then exposed to CIH or control conditions (room air) for 4 weeks. At the end of the exposure, fasting (5 h) blood glucose, insulin, homeostasis model assessment (HOMA) index, liver enzymes, and intraperitoneal glucose tolerance test (1 g/kg) were measured. In DIO mice, body weight remained stable during CIH and did not differ from control conditions. Lean mice under CIH were significantly lighter than control mice by day 28 (P = 0.002). Compared to lean mice, DIO mice had higher fasting levels of blood glucose, plasma insulin, the HOMA index, and had glucose intolerance and hepatic steatosis at baseline. In lean mice, CIH slightly increased HOMA index (from 1.79 ± 0.13 in control to 2.41 ± 0.26 in CIH; P = 0.05), whereas glucose tolerance was not affected. In contrast, in DIO mice, CIH doubled HOMA index (from 10.1 ± 2.1 in control to 22.5 ± 3.6 in CIH; P < 0.01), and induced severe glucose intolerance. In DIO mice, CIH induced NAFLD, inflammation, and oxidative stress, which was not observed in lean mice. In conclusion, CIH exacerbates IR and induces steatohepatitis in DIO mice, suggesting that CIH may account for metabolic dysfunction in obesity.

  18. LEOPARD syndrome-associated SHP2 mutation confers leanness and protection from diet-induced obesity

    PubMed Central

    Tajan, Mylène; Batut, Aurélie; Cadoudal, Thomas; Deleruyelle, Simon; Le Gonidec, Sophie; Saint Laurent, Céline; Vomscheid, Maëlle; Wanecq, Estelle; Tréguer, Karine; De Rocca Serra-Nédélec, Audrey; Vinel, Claire; Marques, Marie-Adeline; Pozzo, Joffrey; Kunduzova, Oksana; Salles, Jean-Pierre; Tauber, Maithé; Raynal, Patrick; Cavé, Hélène; Edouard, Thomas; Valet, Philippe; Yart, Armelle

    2014-01-01

    LEOPARD syndrome (multiple Lentigines, Electrocardiographic conduction abnormalities, Ocular hypertelorism, Pulmonary stenosis, Abnormal genitalia, Retardation of growth, sensorineural Deafness; LS), also called Noonan syndrome with multiple lentigines (NSML), is a rare autosomal dominant disorder associating various developmental defects, notably cardiopathies, dysmorphism, and short stature. It is mainly caused by mutations of the PTPN11 gene that catalytically inactivate the tyrosine phosphatase SHP2 (Src-homology 2 domain-containing phosphatase 2). Besides its pleiotropic roles during development, SHP2 plays key functions in energetic metabolism regulation. However, the metabolic outcomes of LS mutations have never been examined. Therefore, we performed an extensive metabolic exploration of an original LS mouse model, expressing the T468M mutation of SHP2, frequently borne by LS patients. Our results reveal that, besides expected symptoms, LS animals display a strong reduction of adiposity and resistance to diet-induced obesity, associated with overall better metabolic profile. We provide evidence that LS mutant expression impairs adipogenesis, triggers energy expenditure, and enhances insulin signaling, three features that can contribute to the lean phenotype of LS mice. Interestingly, chronic treatment of LS mice with low doses of MEK inhibitor, but not rapamycin, resulted in weight and adiposity gains. Importantly, preliminary data in a French cohort of LS patients suggests that most of them have lower-than-average body mass index, associated, for tested patients, with reduced adiposity. Altogether, these findings unravel previously unidentified characteristics for LS, which could represent a metabolic benefit for patients, but may also participate to the development or worsening of some traits of the disease. Beyond LS, they also highlight a protective role of SHP2 global LS-mimicking modulation toward the development of obesity and associated disorders

  19. Multifoil insulation study for weight reduction. Technical information report

    SciTech Connect

    Glazer, S.D.

    1984-01-01

    The purpose of the present task is to develop high temperature multi-foil insulation suitable for use in the SP-100 thermoelectric converter project. Part of this task involves careful examination of alternative foil and foil spacing materials with the goal of effecting significant weight savings over current state-of-the-art foil insulation. This task involved the determination of the state-of-the-art foils, ascertaining what data is available, what additional data is required, preliminary assessment of the suitability of alternate foil and spacer materials, and specific recommendations for additional tests required to qualify new and existing insulation designs for use in the SP-100.

  20. Mechanisms of Body Weight Reduction by Black Tea Polyphenols.

    PubMed

    Pan, Haibo; Gao, Ying; Tu, Youying

    2016-12-07

    Obesity is one of the most common nutritional diseases worldwide. This disease causes health problems, such as dyslipidemia, hyperglycemia, hypertension and inflammation. There are drugs used to inhibit obesity. However, they have serious side effects outweighing their beneficial effects. Black tea, commonly referred to as "fermented tea", has shown a positive effect on reducing body weight in animal models. Black tea polyphenols are the major components in black tea which reduce body weight. Black tea polyphenols are more effective than green tea polyphenols. Black tea polyphenols exert a positive effect on inhibiting obesity involving in two major mechanisms: (i) inhibiting lipid and saccharide digestion, absorption and intake, thus reducing calorie intake; and (ii) promoting lipid metabolism by activating AMP-activated protein kinase to attenuate lipogenesis and enhance lipolysis, and decreasing lipid accumulation by inhibiting the differentiation and proliferation of preadipocytes; (iii) blocking the pathological processes of obesity and comorbidities of obesity by reducing oxidative stress. Epidemiological studies of the health relevance between anti-obesity and black tea polyphenols consumption remain to be further investigated.

  1. Potential Nociceptive Regulatory Effect of Probiotic Lactobacillus rhamnosus PB01 (DSM 14870) on Mechanical Sensitivity in Diet-Induced Obesity Model

    PubMed Central

    Brandsborg, Erik

    2016-01-01

    Treatments for obesity have been shown to reduce pain secondary to weight loss. Intestinal microbiota, as an endogenous factor, influences obesity and pain sensitivity but the effect of oral probiotic supplementation on musculoskeletal pain perception has not been studied systematically. The present study examined the effect of a single daily oral dose (1 × 109 CFU) of probiotics (Lactobacillus rhamnosus PB01, DSM14870) supplement on mechanical pain thresholds in behaving diet-induced obese (DIO) mice and their normal weight (NW) controls. The mice (N = 24, 6-week-old male) were randomly divided into four groups on either standard or high fat diet with and without probiotic supplementation. Both DIO and NW groups with probiotic supplementation maintained an insignificant weight gain while the control groups gained significant weight (P < 0.05). Similarly, both DIO and NW probiotics supplemented groups demonstrated a significantly (P < 0.05) lower sensitivity to mechanical stimulation compared to their corresponding control. The results of this study suggest a protective effect of probiotics on nociception circuits, which propose a direct result of the weight reduction or an indirect result of anti-inflammatory properties of the probiotics. Deciphering the exact underlying mechanism of the weight loss and lowering nociception effect of the probiotic applied in this study require further investigation. PMID:27647980

  2. Diet-Induced Metabolic Disturbances As Modulators of Brain Homeostasis

    PubMed Central

    Zhang, Le; Bruce-Keller, Annadora J.; Dasuri, Kalavathi; Nguyen, AnhThao; Liu, Dr Ying; Keller, Jeffrey N.

    2009-01-01

    A number of metabolic disturbances occur in response to the consumption of a high fat Western diet. Such metabolic disturbances can include the progressive development of hyperglycemia, hyperinsulemia, obesity, metabolic syndrome, and diabetes. Cumulatively, diet-induced disturbance in metabolism are known to promote increased morbidity and negatively impact life expectancy through a variety of mechanisms. While the impact of metabolic disturbances on the hepatic, endocrine, and cardiovascular systems are well established there remains a noticeable void in understanding the basis by which the central nervous system (CNS) becomes altered in response to diet-induced metabolic dysfunction. In particular, it remains to be fully elucidated which established features of diet-induced pathogenesis (observed in non-CNS tissues) are recapitulated in the brain, and identification as to whether the observed changes in the brain are a direct or indirect effect of peripheral metabolic disturbances. This review will focus on each of these key issues and identify some critical experimental questions which remain to be elucidated experimentally, as well as provide an outline of our current understanding for how diet-induced alterations in metabolism may impact the brain during aging and age-related diseases of the nervous system. PMID:18926905

  3. Beneficial effects of milk oligosaccharides on gut permeability, microbial dysbiosis and the obese phenotype in high-fat diet-induced obesity in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Objective: Microbial dysbiosis and increased intestinal permeability is a target for prevention or reversal of weight gain in high-fat (HF) diet-induced obesity (DIO); however, it is not known whether decreased intestinal permeability is necessary or sufficient for weight loss. Prebiotic milk oligos...

  4. Multivariable frequency weighted model order reduction for control synthesis

    NASA Technical Reports Server (NTRS)

    Schmidt, David K.

    1989-01-01

    Quantitative criteria are presented for model simplification, or order reduction, such that the reduced order model may be used to synthesize and evaluate a control law, and the stability robustness obtained using the reduced order model will be preserved when controlling the full-order system. The error introduced due to model simplification is treated as modeling uncertainty, and some of the results from multivariate robustness theory are brought to bear on the model simplification problem. A numerical procedure developed previously is shown to lead to results that meet the necessary criteria. The procedure is applied to reduce the model of a flexible aircraft. Also, the importance of the control law itself, in meeting the modeling criteria, is underscored. An example is included that demonstrates that an apparently robust control law actually amplifies modest modeling errors in the critical frequency region, and leads to undesirable results. The cause of this problem is associated with the canceling of lightly damped transmission zeroes in the plant. An attempt is made to expand on some of the earlier results and to further clarify the theoretical basis behind the proposed methodology.

  5. Genetic variability to diet-induced hippocampal dysfunction in BXD recombinant inbred (RI) mouse strains

    PubMed Central

    Xue, Yueqiang; Li, JingJing; Yan, Lei; Lu, Lu; Liao, Francesca-Fang

    2016-01-01

    Evidence has emerged suggesting that diet-induced obesity can have a negative effect on cognitive function. Here, we exploited a mouse genetic reference population to look for the linkage between these two processes on a genome-wide scale. The focus of this report is to determine whether the various BXD RI strains exhibited different behavioral performance and hippocampal function under high fat dietary (HFD) condition. We quantified genetic variation in body weight gain and consequent influences on behavioral tests in a cohort of 14 BXD strains of mice (8–12 mice/strain, n=153), for which we have matched data on gene expression and neuroanatomical changes in the hippocampus. It showed that BXD66 was the most susceptible, whereas BXD77 was the least susceptible strain to dietary influences. The performance of spatial reference memory tasks was strongly correlated with body weight gain (P<0.05). The obesity-prone strains displayed more pronounced spatial memory defects compared to the obesity-resistant strains. These abnormalities were associated with neuro inflammation, synaptic dysfunction, and neuronal loss in the hippocampus. The biological relevance of DSCAM gene polymorphism was assessed using the trait correlation analysis tool in Genenet work. Further more, a significant strain-dependent gene expression difference of DSCAM was detected in the hippocampus of obese BXD strains by real-time quantitative PCR. In conclusion, a variety of across-strain hippocampal alterations and genetic predispositions to diet-induced obesity were found in a set of BXD strains. The obesity-prone and obesity-resistant lines we have identified should be highly useful to study the molecular genetics of diet-induced cognitive decline. PMID:26092713

  6. Cafeteria diet-induced obesity causes oxidative damage in white adipose.

    PubMed

    Johnson, Amy R; Wilkerson, Matthew D; Sampey, Brante P; Troester, Melissa A; Hayes, D Neil; Makowski, Liza

    2016-04-29

    Obesity continues to be one of the most prominent public health dilemmas in the world. The complex interaction among the varied causes of obesity makes it a particularly challenging problem to address. While typical high-fat purified diets successfully induce weight gain in rodents, we have described a more robust model of diet-induced obesity based on feeding rats a diet consisting of highly palatable, energy-dense human junk foods - the "cafeteria" diet (CAF, 45-53% kcal from fat). We previously reported that CAF-fed rats became hyperphagic, gained more weight, and developed more severe hyperinsulinemia, hyperglycemia, and glucose intolerance compared to the lard-based 45% kcal from fat high fat diet-fed group. In addition, the CAF diet-fed group displayed a higher degree of inflammation in adipose and liver, mitochondrial dysfunction, and an increased concentration of lipid-derived, pro-inflammatory mediators. Building upon our previous findings, we aimed to determine mechanisms that underlie physiologic findings in the CAF diet. We investigated the effect of CAF diet-induced obesity on adipose tissue specifically using expression arrays and immunohistochemistry. Genomic evidence indicated the CAF diet induced alterations in the white adipose gene transcriptome, with notable suppression of glutathione-related genes and pathways involved in mitigating oxidative stress. Immunohistochemical analysis indicated a doubling in adipose lipid peroxidation marker 4-HNE levels compared to rats that remained lean on control standard chow diet. Our data indicates that the CAF diet drives an increase in oxidative damage in white adipose tissue that may affect tissue homeostasis. Oxidative stress drives activation of inflammatory kinases that can perturb insulin signaling leading to glucose intolerance and diabetes.

  7. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons.

    PubMed

    de Lartigue, Guillaume; Barbier de la Serre, Claire; Espero, Elvis; Lee, Jennifer; Raybould, Helen E

    2011-07-01

    Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.

  8. Effect of phentermine on weight reduction in a pediatric weight management clinic.

    PubMed

    Ryder, J R; Kaizer, A; Rudser, K D; Gross, A; Kelly, A S; Fox, C K

    2017-01-01

    Phentermine is the most widely prescribed obesity medication in adults, yet studies of its use in the pediatric population are limited. We conducted a retrospective chart review of adolescents with obesity treated in a pediatric weight management clinic to examine the weight loss effectiveness of phentermine added to standard of care (SOC) lifestyle modification therapy versus SOC alone. All patients receiving phentermine plus SOC (n=25) were matched with a comparison group receiving only SOC (n=274). Differences at 1, 3 and 6 months were evaluated using generalized estimated equations adjusting for age, sex and baseline body mass index (BMI) and robust variance standard error estimates for confidence intervals and P-values. Phentermine use was associated with a greater percent change in BMI at 1 month (-1.6%; 95% confidence interval (CI): -2.6, -0.6%; P=0.001), 3 months (-2.9%; 95% CI: -4.5, -1.4%; P<0.001) and 6 months (-4.1%; 95% CI: -7.1, -1.0%; P=0.009) compared with SOC alone, with no differences in systolic or diastolic blood pressure between groups. Heart rate was higher at all time-points in the phentermine plus SOC compared with SOC-only group. These data suggest that short-term use of phentermine added to SOC may enhance weight loss in adolescents with obesity in the clinical setting.

  9. Anti-obesity Effect of Fermented Whey Beverage using Lactic Acid Bacteria in Diet-induced Obese Rats

    PubMed Central

    2015-01-01

    High-protein fermented whey beverage (FWB) was manufactured using whey protein concentrate (WPC) and Lactobacillus plantarum DK211 isolated from kimchi. This study was designed to evaluate the anti-obesity activity of FWB in male rats fed a high-fat diet. Male Sprague-Dawley rats were randomly assigned to three groups (n=8 per group). The three groups differed in their diet; one group received a normal diet (ND), another, a high-fat diet (HD), and the third, a HD plus fermented whey beverage (HDFWB), for 4 wk. Supplementation with FWB (the HDFWB group) prevented weight gain and body fat accumulation. The food intake in the HDWFB group was significantly lower (p<0.05) than that of the HD group. The HDWFB group also showed a significant decrease in organ weights (p<0.05), except for the weight of the testis. There was a significant decrease in total cholesterol, LDL-cholesterol, and triglycerides in the HDFWB group compared with the HD group (p<0.05), but there was no significant difference in serum HDL-cholesterol levels among the experimental groups. Rats ingesting FWB (the HDFWB group) also showed a significant decrease in blood glucose levels, and plasma levels of insulin, leptin, and ghrelin compared to HD group (p<0.05). These results indicate that FWB has beneficial effects on dietary control, weight control, and reduction in fat composition and serum lipid level; consequently, it may provide antiobesity and hypolipidemic activity against high fat diet-induced obesity in rats. PMID:26761894

  10. Diet-induced obesity in male mice is associated with reduced fertility and potentiation of acrylamide-induced reproductive toxicity.

    PubMed

    Ghanayem, Burhan I; Bai, Re; Kissling, Grace E; Travlos, Greg; Hoffler, Undi

    2010-01-01

    The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg(-1) day(-1) via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity.

  11. Weight loss improves endothelial function independently of ADMA reduction in severe obesity.

    PubMed

    Rudofsky, G; Roeder, E; Merle, T; Hildebrand, M; Nawroth, P P; Wolfrum, C

    2011-05-01

    This prospective study was performed in order to establish whether improvement of endothelial function after weight reduction can be explained by a decrease of elevated asymmetric dimethyl arginine (ADMA), an inhibitor of endogenous NO-synthase (eNOS). Therefore, 21 obese subjects (BMI: 41.1±6.4 kg/m(2)) were studied at baseline and after 12 weeks of weight reduction with a very low calorie diet. Biochemical and clinical parameters of endothelial function were assessed before and after weight loss. Biochemical parameters were determined by measurement of ADMA and soluble intercellular adhesion molecule (sICAM). Clinical parameters were assessed by pulse wave analysis (PWA). Weight intervention resulted in a 21.4±6.8 kg reduction of body weight from 119.7±12.8 kg at study start to 98.3±11.6 kg at study end (p<0.001). Accordingly, biochemical markers improved under weight reduction (ADMA from 0.47±0.07 mmol/l to 0.42±0.08 mmol/l; p=0.002; ICAM from 276±42 ng/ml to 236±29 ng/ml; p<0.001). Further, clinical parameters of functional endothelial function improved with an increase of deltaRI after salbutamol inhalation from -1% before to -9% after weight reduction (p=0.02). Interestingly, improvement of endothelial function correlated with improved HOMA index only (r=-0.60, p=0.04) but not with reduced ADMA levels, improved hypertension or reduced body weight. In conclusion, weight reduction with a very low calorie diet improves endothelial function measured by pulse wave velocity. The missing correlation with ADMA suggests possible further mechanisms underlying this observed effect, for example, improvement of insulin resistance.

  12. Sleep apnea syndrome in the morbidly obese as an indication for weight reduction surgery.

    PubMed Central

    Peiser, J; Lavie, P; Ovnat, A; Charuzi, I

    1984-01-01

    Fifteen morbidly obese patients with Sleep Apnea Syndrome (SAS) were studied during nocturnal sleep before and between 2 to 4 months after a weight reduction surgery. Six patients were also recorded between 4 to 8 months after surgery. Postoperative recordings revealed a dramatic reduction in the sleep apnea index and an improvement in sleep motility and daytime vigilance levels. A further decrease in apneas and sleep motility was seen in the late post-treatment recording. These results indicate that weight reduction surgery is an effective definitive treatment for obesity associated SAS. PMID:6691724

  13. Ubc13 haploinsufficiency protects against age-related insulin resistance and high-fat diet-induced obesity

    PubMed Central

    Joo, Erina; Fukushima, Toru; Harada, Norio; Reed, John C.; Matsuzawa, Shu-ichi; Inagaki, Nobuya

    2016-01-01

    Obesity is associated with low-grade inflammation that leads to insulin resistance and type 2 diabetes via Toll-like Receptor (TLR) and TNF-family cytokine receptor (TNFR) signaling pathways. Ubc13 is an ubiquitin-conjugating enzyme responsible for non-canonical K63-linked polyubiquitination of TNF receptor-associated factor (TRAF)-family adapter proteins involved in TLR and TNFR pathways. However, the relationship between Ubc13 and metabolic disease remains unclear. In this study, we investigated the role of Ubc13 in insulin resistance and high-fat diet (HFD)-induced obesity. We compared wild-type (WT) and Ubc13 haploinsufficient (ubc13+/−) mice under normal diet (ND) and HFD, since homozygous knockout mice (ubc13−/−) are embryonic lethal. Male and female ubc13+/− mice were protected against age-related insulin resistance under ND and HFD compared to WT mice. Interestingly, only female ubc13+/− mice were protected against HFD-induced obesity and hepatic steatosis. Moreover, only female HFD-fed ubc13+/− mice showed lower expression of inflammatory cytokines that was secondary to reduction in weight gain not present in the other groups. In summary, our results indicate that suppression of Ubc13 activity may play a metabolic role independent of its inflammatory function. Thus, Ubc13 could represent a therapeutic target for insulin resistance, diet-induced obesity, and associated metabolic dysfunctions. PMID:27796312

  14. Diet-induced obesity: dopamine transporter function, impulsivity and motivation

    PubMed Central

    Narayanaswami, V; Thompson, AC; Cassis, LA; Bardo, MT; Dwoskin, LP

    2013-01-01

    OBJECTIVE A rat model of diet-induced obesity (DIO) was used to determine dopamine transporter (DAT) function, impulsivity and motivation as neurobehavioral outcomes and predictors of obesity. DESIGN To evaluate neurobehavioral alterations following the development of DIO induced by an 8-week high-fat diet (HF) exposure, striatal D2-receptor density, DAT function and expression, extracellular dopamine concentrations, impulsivity, and motivation for high- and low-fat reinforcers were determined. To determine predictors of DIO, neurobehavioral antecedents including impulsivity, motivation for high-fat reinforcers, DAT function and extracellular dopamine were evaluated before the 8-week HF exposure. METHODS Striatal D2-receptor density was determined by in vitro kinetic analysis of [3H]raclopride binding. DAT function was determined using in vitro kinetic analysis of [3H]dopamine uptake, methamphetamine-evoked [3H]dopamine overflow and no-net flux in vivo microdialysis. DAT cell-surface expression was determined using biotinylation and western blotting. Impulsivity and food-motivated behavior were determined using a delay discounting task and progressive ratio schedule, respectively. RESULTS Relative to obesity-resistant (OR) rats, obesity-prone (OP) rats exhibited 18% greater body weight following an 8-week HF-diet exposure, 42% lower striatal D2-receptor density, 30% lower total DAT expression, 40% lower in vitro and in vivo DAT function, 45% greater extracellular dopamine and twofold greater methamphetamine-evoked [3H]dopamine overflow. OP rats exhibited higher motivation for food, and surprisingly, were less impulsive relative to OR rats. Impulsivity, in vivo DAT function and extracellular dopamine concentration did not predict DIO. Importantly, motivation for high-fat reinforcers predicted the development of DIO. CONCLUSION Human studies are limited by their ability to determine if impulsivity, motivation and DAT function are causes or consequences of DIO. The

  15. Weight stigmatization and bias reduction: perspectives of overweight and obese adults.

    PubMed

    Puhl, Rebecca M; Moss-Racusin, Corinne A; Schwartz, Marlene B; Brownell, Kelly D

    2008-04-01

    This study employed qualitative methods with a sample of overweight and obese adults to identify and describe their subjective experiences of weight bias. Participants (274 females and 44 males) completed an online battery of self-report questionnaires, including several open-ended questions about weight stigmatization. These questions asked them to describe their worst experiences of weight stigmatization, their perceptions of common weight-based stereotypes, their feelings about being overweight and their suggestions for strategies to reduce weight stigma in our culture. Participants reported experiencing weight stigma across a range of contexts and involving a variety of interpersonal sources. Close relationship partners (such as friends, parents and spouses) were the most common source of their worst stigmatizing encounters. Participants challenged common weight-based stereotypes (notably, that obese individuals are 'lazy') and reported that they would like the public to gain a better understanding of the difficulties of weight loss, the causes of obesity and the emotional consequences of being stigmatized. Education was reported as the most promising avenue for future stigma-reduction efforts. The experiences and opinions expressed were not significantly different for men versus women or overweight versus obese individuals. A minority of participants expressed beliefs suggestive of self-blame and internalization of weight-based stereotypes. These results indicate that while obese individuals experience weight bias across many domains, more stigma-reduction efforts should target stigmatizing encounters in close relationships, including parents, spouses and friends of obese persons.

  16. Protective effect of Caralluma fimbriata against high-fat diet induced testicular oxidative stress in rats.

    PubMed

    Gujjala, Sudhakara; Putakala, Mallaiah; Gangarapu, Venkatanarayana; Nukala, Srinivasulu; Bellamkonda, Ramesh; Ramaswamy, Rajendran; Desireddy, Saralakumari

    2016-10-01

    High-fat diet (HFD) promotes the oxidative stress formation, which in turn has hazardous effects on reproductive system and fertility. The objective of this study was to evaluate the protective effect of Caralluma fimbriata on high-fat diet-induced oxidative stress in the testis of rat. Male Wistar rats were randomly divided into five groups: Control (C), Control treated with CFE (C+ CFE), High fat diet fed (HFD), High fat diet fed treated with CFE (HFD+CFE) and High fat diet fed treated with Metformin (HFD+Met). CFE was orally administered (200mg/kg body weight) for 90days to groups-C+CFE and HFD+CFE rats. The effects of HF-diet on the reproductive organs were determined by measuring relative and absolute testes and epididymal fat pads weights. Regarding testes antioxidant status, high-fat fed rats showed higher levels of lipid peroxidation, protein oxidation, polyol pathway enzymes and lower GSH levels and lower activities of antioxidants, while CFE treatment prevented all these observed abnormalities. The present study clearly indicates that CFE offers a significant protection against HF-diet induced testicular oxidative stress in rats.

  17. Hypolipidemic effect of aqueous extract of Carum carvi (black Zeera) seeds in diet induced hyperlipidemic rats.

    PubMed

    Saghir, Muhammad Rashad; Sadiq, Soban; Nayak, Salma; Tahir, Muhammad Usman

    2012-04-01

    Medicinal plants play a key role in preventing various diseases. Hyperlipidemia is a major contributor to the pathogenesis of cardiovascular diseases. The purpose of the present study was to assess the effect of aqueous extract of Carum carvi seeds in diet induced hyperlipidemia in rats. 2% cholesterol diet were given to rats for six weeks and rats showed high lipid levels were included in the study. Then all rats were divided into, normal control group (A), hyperlipidemia positive control group (B), and the remaining two groups (C and D) served as experimental groups. Group C hyperlipidemic experimental rats received aqueous dried extract of Carum carvi seeds at 60 mg/kg of body weight for eight weeks on daily basis. On the other hand group D rats received simvastatin at 1.0 mg/kg body weight for eight weeks. Blood samples were collected after eight weeks. The hyperlipidemic positive control group rats showed variable increase in serum triglycerides, LDL and total cholesterol levels. Serum HDL levels decreased in hyperlipidemic positive control groups. Carum carvi and simvastatin significantly decreased the levels of these parameters in rats. On comparison Carum carvi reduced lipid levels more, effectively than the simvastatin. Carum carvi constituents, especially flavonoids and carvone have strong anti-oxidant activity which might be involved in hypolipidemia. In conclusion, Carum carvi aqueous seeds extract decrease lipid levels in diet induced hyperlipidemic rats.

  18. Heart energy metabolism impairment in Western-diet induced obese mice.

    PubMed

    Neves, Fabiana A; Cortez, Erika; Bernardo, Amélia F; Mattos, Ana B M; Vieira, Anatalia K; Malafaia, Tayanne de O; Thole, Alessandra A; Rodrigues-Cunha, Alessandra C de S; Garcia-Souza, Erica P; Sichieri, Rosely; Moura, Anibal S

    2014-01-01

    Nutritional transition has contributed to growing obesity, mainly by changing eating habits of the population. The mechanisms by which diet-induced obesity leads to cardiac injury are not completely understood, but it is known that obesity is associated to impaired cardiac function and energy metabolism, increasing morbidity and mortality. Therefore, our study aimed to investigate the mechanisms underlying cardiac metabolism impairment related to Western diet-induced obesity. After weaning, male Swiss mice were fed a Western diet for 16 weeks in order to induce obesity. After this period, the content of proteins involved in heart energy metabolism GLUT1, cytosolic lysate and plasma membrane GLUT4, AMPK, pAMPK, IRβ, IRS-1, PGC-1α, CPT1 and UCP2 was evaluated. Also, the oxidative phosphorylation of myocardial fibers was measured by high-resolution respirometry. Mice in the Western diet group (WG) presented altered biometric parameters compared to those in control group, including higher body weight, increased myocardial lipid deposition and glucose intolerance, which demonstrate the obesogenic role of Western diet. WG presented increased CPT1 and UCP2 contents and decreased IRS-1, plasma membrane GLUT4 and PGC-1α contents. In addition, WG presented cardiac mitochondrial dysfunction and reduced biogenesis, demonstrating a lower capacity of carbohydrates and fatty acid oxidation and also decreased coupling between oxidative phosphorylation and adenosine triphosphate synthesis. Cardiac metabolism impairment related to Western diet-induced obesity is probably due to damaged myocardial oxidative capacity, reduced mitochondrial biogenesis and mitochondria uncoupling, which compromise the bioenergetic metabolism of heart.

  19. Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice

    PubMed Central

    Koza, Robert A; Nikonova, Larissa; Hogan, Jessica; Rim, Jong-Seop; Mendoza, Tamra; Faulk, Christopher; Skaf, Jihad; Kozak, Leslie P

    2006-01-01

    High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity. PMID:16733553

  20. Changes in gene expression foreshadow diet-induced obesity in genetically identical mice.

    PubMed

    Koza, Robert A; Nikonova, Larissa; Hogan, Jessica; Rim, Jong-Seop; Mendoza, Tamra; Faulk, Christopher; Skaf, Jihad; Kozak, Leslie P

    2006-05-01

    High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity.

  1. Diet-induced ketosis improves cognitive performance in aged rats.

    PubMed

    Xu, Kui; Sun, Xiaoyan; Eroku, Bernadette O; Tsipis, Constantinos P; Puchowicz, Michelle A; LaManna, Joseph C

    2010-01-01

    Aging is associated with increased susceptibility to hypoxic/ischemic insult and declines in behavioral function which may be due to attenuated adaptive/defense responses. We investigated if diet-induced ketosis would improve behavioral performance in the aged rats. Fischer 344 rats (3- and 22-month-old) were fed standard (STD) or ketogenic (KG) diet for 3 weeks and then exposed to hypobaric hypoxia. Cognitive function was measured using the T-maze and object recognition tests. Motor function was measured using the inclined-screen test. Results showed that KG diet significantly increased blood ketone levels in both young and old rats. In the aged rats, the KG diet improved cognitive performance under normoxic and hypoxic conditions; while motor performance remained unchanged. Capillary density and HIF-1alpha levels were elevated in the aged ketotic group independent of hypoxic challenge. These data suggest that diet-induced ketosis may be beneficial in the treatment of neurodegenerative conditions.

  2. Deletion of Lkb1 in adult mice results in body weight reduction and lethality.

    PubMed

    Shan, Tizhong; Xiong, Yan; Kuang, Shihuan

    2016-11-08

    Liver kinase B1 (Lkb1) plays crucial roles in development, metabolism and survival. As constitutive knockout of Lkb1 in mice leads to embryonic lethality, whether Lkb1 is required for the growth and survival of adult mice is unclear. Here we address this question using a tamoxifen-inducible Lkb1 knockout (KO) mouse model: Rosa26-Cre(ER): Lkb1(flox/flox) (abbreviated as Rosa-Lkb1). The Rosa-Lkb1 mice exhibited body weight reduction and died within 6 weeks after tamoxifen induction. The body weight reduction was due to reduced weight of various tissues but the brown and white adipose tissues underwent much more pronounced weight reduction relative to the overall body weight reduction. Accordingly, the Rosa-Lkb1 mice had increased blood glucose levels and were intolerant to glucose challenge. Expression levels of adipogenic and lipogenic genes in adipose tissues were also dramatically reduced by Lkb1 deletion. Additionally, Lkb1 deletion reduced lipid deposition and increased expression of mitochondrial (Pgc1a, Cox5b and Cox7a) and hepatic gluconeogenesis related genes (Pepck) in liver. Finally, the Rosa-Lkb1 mice had much reduced oxygen consumption, carbon dioxide production, and energy expenditure. These results demonstrate that Lkb1 plays an important role in maintaining body weight, liver and adipose tissue function, blood glucose homeostasis and survival in adult mice.

  3. Successful weight reduction and maintenance by using a smartphone application in those with overweight and obesity

    PubMed Central

    Chin, Sang Ouk; Keum, Changwon; Woo, Junghoon; Park, Jehwan; Choi, Hyung Jin; Woo, Jeong-taek; Rhee, Sang Youl

    2016-01-01

    A discrepancy exists with regard to the effect of smartphone applications (apps) on weight reduction due to the several limitations of previous studies. This is a retrospective cohort study, aimed to investigate the effectiveness of a smartphone app on weight reduction in obese or overweight individuals, based on the complete enumeration study that utilized the clinical and logging data entered by Noom Coach app users between October 2012 and April 2014. A total of 35,921 participants were included in the analysis, of whom 77.9% reported a decrease in body weight while they were using the app (median 267 days; interquartile range = 182). Dinner input frequency was the most important factor for successful weight loss (OR = 10.69; 95% CI = 6.20–19.53; p < 0.001), and more frequent input of weight significantly decreased the possibility of experiencing the yo-yo effect (OR = 0.59, 95% CI = 0.39–0.89; p < 0.001). This study demonstrated the clinical utility of an app for successful weight reduction in the majority of the app users; the effects were more significant for individuals who monitored their weight and diet more frequently. PMID:27819345

  4. Laxative effects of agarwood on low-fiber diet-induced constipation in rats

    PubMed Central

    2010-01-01

    Background Agarwood (Aquilaria sinensis), well known as incense in Southeast Asia, has been used as a digestive in traditional medicine. We investigated the laxative effects of an ethanol extract of agarwood leaves (EEA) in a rat model of low-fiber diet-induced constipation. Methods A set of rats was bred on a normal diet while another set was placed on a low-fiber diet to induce constipation. The laxative effect of agarwood was then investigated on both sets of rats. Results Pretreatment of normal rats with single dose of EEA (600 mg/kg, p.o.) significantly increased frequency and weight of stools. Also, treatments with EEA (300 and 600 mg/kg, p.o.) for 14 days caused a significant increase in stool frequency and weight. Feeding of the animals with a low-fiber diet resulted in a decrease in stool weight, frequency, and water content and also delayed carmine egestion. A single treatment with EEA (600 mg/kg) or senna (150 and 300 mg/kg) significantly increased stool frequency, weight, and water content and also accelerated carmine egestion in the model rats. Once daily administrations of EEA (150 mg/kg), for 14 days, caused a significant increase in water content of stools. The higher doses of EEA (300 and 600 mg/kg) significantly increased frequency, weight, and water content of the stools while accelerating carmine egestion in the constipated rats. Senna (150 and 300 mg/kg) produced similar effect as the higher doses of EEA but, in addition, induced severe diarrhea. Conclusion These findings indicate that EEA has a laxative effect, without causing diarrhea, in a rat model of low-fiber diet-induced constipation. These findings suggest that EEA may be highly effective on constipation as a complementary medicine in humans suffering from life style-induced constipation. PMID:21078136

  5. Consumption of milk-protein combined with green tea modulates diet-induced thermogenesis.

    PubMed

    Hursel, Rick; Westerterp-Plantenga, Margriet S

    2011-08-01

    Green tea and protein separately are able to increase diet-induced thermogenesis. Although their effects on long-term weight-maintenance were present separately, they were not additive. Therefore, the effect of milk-protein (MP) in combination with green tea on diet-induced thermogenesis (DIT) was examined in 18 subjects (aged 18-60 years; BMI: 23.0 ± 2.1 kg/m(2)). They participated in an experiment with a randomized, 6 arms, crossover design, where energy expenditure and respiratory quotient (RQ) were measured. Green tea (GT)vs. placebo (PL) capsules were either given in combination with water or with breakfasts containing milk protein in two different dosages: 15 g (15 MP) (energy% P/C/F: 15/47/38; 1.7 MJ/500 mL), and 3.5 g (3.5 MP) (energy% P/C/F: 41/59/0; 146.4 kJ/100 mL). After measuring resting energy expenditure (REE) for 30 min, diet-induced energy expenditure was measured for another 3.5 h after the intervention. There was an overall significant difference observed between conditions (p < 0.001). Post-hoc, areas under the curve (AUCs) for diet-induced energy expenditure were significantly different (P ≤ 0.001) for GT + water (41.11 [91.72] kJ·3.5 h) vs. PL + water (10.86 [28.13] kJ·3.5 h), GT + 3.5 MP (10.14 [54.59] kJ·3.5 h) and PL + 3.5 MP (12.03 [34.09] kJ·3.5 h), but not between GT + 3.5 MP, PL + 3.5 MP and PL + water, indicating that MP inhibited DIT following GT. DIT after GT + 15 MP (167.69 [141.56] kJ·3.5 h) and PL + 15 MP (168.99 [186.56] kJ·3.5 h) was significantly increased vs. PL + water (P < 0.001), but these were not different from each other indicating that 15 g MP stimulated DIT, but inhibited the GT effect on DIT. No significant differences in RQ were seen between conditions for baseline and post-treatment. In conclusion, consumption of milk-protein inhibits the effect of green tea on DIT.

  6. The histone acetyltransferase MOF activates hypothalamic polysialylation to prevent diet-induced obesity in mice

    PubMed Central

    Brenachot, Xavier; Rigault, Caroline; Nédélec, Emmanuelle; Laderrière, Amélie; Khanam, Tasneem; Gouazé, Alexandra; Chaudy, Sylvie; Lemoine, Aleth; Datiche, Frédérique; Gascuel, Jean; Pénicaud, Luc; Benani, Alexandre

    2014-01-01

    Overfeeding causes rapid synaptic remodeling in hypothalamus feeding circuits. Polysialylation of cell surface molecules is a key step in this neuronal rewiring and allows normalization of food intake. Here we examined the role of hypothalamic polysialylation in the long-term maintenance of body weight, and deciphered the molecular sequence underlying its nutritional regulation. We found that upon high fat diet (HFD), reduced hypothalamic polysialylation exacerbated the diet-induced obese phenotype in mice. Upon HFD, the histone acetyltransferase MOF was rapidly recruited on the St8sia4 polysialyltransferase-encoding gene. Mof silencing in the mediobasal hypothalamus of adult mice prevented activation of the St8sia4 gene transcription, reduced polysialylation, altered the acute homeostatic feeding response to HFD and increased the body weight gain. These findings indicate that impaired hypothalamic polysialylation contribute to the development of obesity, and establish a role for MOF in the brain control of energy balance. PMID:25161885

  7. Weight reduction potential of automobiles and light trucks: 1979 summary source document. Final report

    SciTech Connect

    Hsia, H.; Kidd, J.A.

    1980-03-01

    The purpose of this report is to provide an assessment of the potential for weight reduction for passenger cars and light trucks (including pickup trucks, vans, and utility vehicles of GVWR up to 8500 pounds) in the 1980 to 2000 model year period. Various aspects of vehicular performance are addressed. Four weight reduction scenarios involving material substitution are presented with increasing technological sophistication. In addition to the baseline data, dominant case assessments for high strength steel, fiber reinforced plastic, aluminum, and hybrid reinforced plastics are provided.

  8. Pharmacological inhibition of soluble epoxide hydrolase ameliorates diet-induced metabolic syndrome in rats.

    PubMed

    Iyer, Abishek; Kauter, Kathleen; Alam, Md Ashraful; Hwang, Sung Hee; Morisseau, Christophe; Hammock, Bruce D; Brown, Lindsay

    2012-01-01

    The signs of metabolic syndrome following chronic excessive macronutrient intake include body weight gain, excess visceral adipose deposition, hyperglycaemia, glucose and insulin intolerances, hypertension, dyslipidaemia, endothelial damage, cardiovascular hypertrophy, inflammation, ventricular contractile dysfunction, fibrosis, and fatty liver disease. Recent studies show increased activity of soluble epoxide hydrolase (sEH) during obesity and metabolic dysfunction. We have tested whether sEH inhibition has therapeutic potential in a rat model of diet-induced metabolic syndrome. In these high-carbohydrate, high-fat-fed rats, chronic oral treatment with trans-4-[4-(3-adamantan-1-ylureido)-cyclohexyloxy]-benzoic acid (t-AUCB), a potent sEH inhibitor, alleviated the signs of metabolic syndrome in vivo including glucose, insulin, and lipid abnormalities, changes in pancreatic structure, increased systolic blood pressure, cardiovascular structural and functional abnormalities, and structural and functional changes in the liver. The present study describes the pharmacological responses to this selective sEH inhibitor in rats with the signs of diet-induced metabolic syndrome.

  9. Cannabinoid receptor 1 antagonist treatment induces glucagon release and shows an additive therapeutic effect with GLP-1 agonist in diet-induced obese mice.

    PubMed

    Patel, Kartikkumar Navinchandra; Joharapurkar, Amit Arvind; Patel, Vishal; Kshirsagar, Samadhan Govind; Bahekar, Rajesh; Srivastava, Brijesh Kumar; Jain, Mukul R

    2014-12-01

    Cannabinoid 1 (CB1) receptor antagonists reduce body weight and improve insulin sensitivity. Preclinical data indicates that an acute dose of CB1 antagonist rimonabant causes an increase in blood glucose. A stable analog of glucagon-like peptide 1 (GLP-1), exendin-4 improves glucose-stimulated insulin secretion in pancreas, and reduces appetite through activation of GLP-1 receptors in the central nervous system and liver. We hypothesized that the insulin secretagogue effect of GLP-1 agonist exendin-4 may synergize with the insulin-sensitizing action of rimonabant. Intraperitoneal as well as intracerebroventricular administration of rimonabant increased serum glucose upon glucose challenge in overnight fasted, diet-induced obese C57 mice, with concomitant rise in serum glucagon levels. Exendin-4 reversed the acute hyperglycemia induced by rimonabant. The combination of exendin-4 and rimonabant showed an additive effect in the food intake, and sustained body weight reduction upon repeated dosing. The acute efficacy of both the compounds was additive for inducing nausea-like symptoms in conditioned aversion test in mice, whereas exendin-4 treatment antagonized the effect of rimonabant on forced swim test upon chronic dosing. Thus, the addition of exendin-4 to rimonabant produces greater reduction in food intake owing to increased aversion, but reduces the other central nervous system side effects of rimonabant. The hyperglucagonemia induced by rimonabant is partially responsible for enhancing the antiobesity effect of exendin-4.

  10. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats.

    PubMed

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R; Taché, Yvette

    2013-09-15

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity.

  11. Weight Reduction in Athletes May Adversely Affect the Phagocytic Function of Monocytes.

    ERIC Educational Resources Information Center

    Kono, Ichiro; And Others

    1988-01-01

    Study of the monocyte phagocytic function in nine competitive athletes before and after a two-week weight reduction (through calorie restriction) program revealed that their pre-program phagocytic activity was higher than in sedentary controls but decreased significantly after the program. This suggests calorie restriction may affect the human…

  12. An Original Behavior Modification Program for Weight Reduction: Minimal Intervention and Permanent Habit Change.

    ERIC Educational Resources Information Center

    Lublin, Irwin; Kirkish, Patricia

    This description of a weight reduction program, based on generalizations derived from eight years of work with overweight persons, discusses the clients' rationalization of overeating behaviors. In this behavior modification program, the client is required to permanently give up one high calorie food and to write down all foods eaten before actual…

  13. A Comparison of Two Weight Reduction Programs for Moderately Retarded Adolescents.

    ERIC Educational Resources Information Center

    Rotatori, Anthony T.; Fox, Robert

    A study of obesity management contrasted the effectiveness for 30 moderately mentally retarded adolescents of a multicomponent behavioral weight reduction program with a more traditional, nutrition based approach. Twelve Ss each were assigned to a behavior therapy (BT) and a social nutrition (SN) group, with the remaining six Ss in a wait-list…

  14. Alliance for a Healthy Border: factors related to weight reduction and glycemic success.

    PubMed

    Wang, Xiaohui; Ghaddar, Suad; Brown, Cynthia; Pagán, José A; Balboa, Marvelia

    2012-04-01

    We examined the factors related to success in achieving weight reduction and glycemic control in Alliance for a Healthy Border (AHB), a chronic disease prevention program implemented from 2006 to 2009 through 12 federally qualified community health centers serving primarily Hispanics in communities located along the US-Mexico border region. We analyzed data from Phase I of AHB using logistic regression to examine the determinants of success in achieving weight reduction and glycemic control among the participants in AHB programs. Factors affecting weight reduction success were sex, age, employment status, income, insurance, diabetes, baseline body mass index (BMI), smoking status, family history of diabetes, session type, program duration, and physical activity changes. Factors affecting achievement of glycemic success included sex, age, employment status, diabetes, baseline BMI, family history of diabetes, program duration, and physical activity changes. We found that the AHB interventions were more successful in reducing participants' HbA1c level than BMI. In addition to sociodemographic factors, participants with better baseline health conditions (ie, participants without diabetes or family history of diabetes, normal BMI, former smokers) were more likely to achieve success after the interventions. Of the 4 key features defining each of the 12 interventions, session type and program duration were associated with success. Within a relatively short time period, physical activity improvements had a stronger effect on weight reduction and glycemic success than improvements in dietary habits. The effectiveness of diabetes and cardiovascular disease prevention programs can be improved substantially by considering these factors during program design and structure.

  15. Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects

    PubMed Central

    Stelmach-Mardas, Marta; Mardas, Marcin; Warchoł, Wojciech; Jamka, Małgorzata; Walkowiak, Jarosław

    2014-01-01

    The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat. PMID:25311271

  16. Successful maintenance of body weight reduction after individualized dietary counseling in obese subjects.

    PubMed

    Stelmach-Mardas, Marta; Mardas, Marcin; Warchoł, Wojciech; Jamka, Małgorzata; Walkowiak, Jarosław

    2014-10-14

    The aim of this study was to describe the effectiveness of individualized dietary counseling in obese subjects based on narrative interview technique on the maintenance of body weight reduction, changes in dietary behaviors, including type of cooking and physical activity. One-hundred subjects out of four-hundred patients met the inclusion criteria. Individually, 45-minute educational program with motivation counseling was performed in 0, 6 and 12 weeks of the study. Patients were advised to follow individually well-balanced diet for 12 weeks. The individuals were asked about the changes in their dietary habits (Food Frequency Questionnaire). The mean percentage of body weight changes from the baseline were as follows: in 6th week- 5.9%, in 12th week - 10.9% and in 52th week - 9.7% (P < 0.0001), however there were no statistically significant changes while comparing body weight in 12th and 52th week. The maintenance of body weight reduction was connected with the dietary habits changes, mainly the type of cooking and increased consumption of vegetable oils. In conclusion, individualized dietary counseling, based on narrative interview technique is an effective intervention for obesity treatment that may help maintain body weight reduction and adapt the pro-healthy changes in type of cooking and sources of dietary fat.

  17. Phloretin Prevents High-Fat Diet-Induced Obesity and Improves Metabolic Homeostasis.

    PubMed

    Alsanea, Sary; Gao, Mingming; Liu, Dexi

    2017-02-14

    Reactive oxygen species generated as a by-product in metabolism play a central role in the development of obesity and obesity-related metabolic complications. The objective of the current study is to explore the possibility to block obesity and improve metabolic homeostasis via phloretin, a natural antioxidant product from apple tree leaves and Manchurian apricot. Both preventive and therapeutic activities of phloretin were assessed using a high-fat diet-induced obesity mouse model. Phloretin was injected intraperitoneally twice weekly into regular and obese mice fed a high-fat diet. The effects of phloretin treatment on body weight and composition, fat content in the liver, glucose and lipid metabolism, and insulin resistance were monitored and compared to the control animals. Phloretin treatment significantly blocks high-fat diet-induced weight gain but did not induce weight loss in obese animals. Phloretin improved glucose homeostasis and insulin sensitivity and alleviated hepatic lipid accumulation. RT-PCR analysis showed that phloretin treatment suppresses expression of macrophage markers (F4/80 and Cd68) and pro-inflammatory genes (Mcp-1 and Ccr2) and enhances adiponectin gene expression in white adipose tissue. In addition, phloretin treatment elevated the expression of fatty acid oxidation genes such as carnitine palmitoyltransferase 1a and 1b (Cpt1a and Cpt1b) and reduced expression of monocyte chemoattractant protein-1 (Mcp-1), de novo lipogenesis transcriptional factor peroxisome proliferator-activated receptor-γ 2 (Pparγ2), and its target monoacylglycerol O-acyltransferase (Mgat-1) genes. These results provide direct evidence to support a possible use of phloretin for mitigation of obesity and maintenance of metabolic homeostasis.

  18. Effects on weight reduction and safety of short-term phentermine administration in Korean obese people.

    PubMed

    Kim, Kyoung Kon; Cho, Hi-Jung; Kang, Hee-Cheol; Youn, Bang-Bu; Lee, Kyu-Rae

    2006-10-31

    The phentermine, an appetite suppressant, has been widely applied in Korea since 2004. However, there have been relatively few reports about the efficacy and the safety of phentermine in Korea. The aim of this study is to verify the effect of phentermine on weight reduction and the safety in Korean patients. This randomized, double-blind, placebo- controlled study had been performed between February and July, 2005, in Seoul on 68 relatively healthy obese adults whose body mass index was 25 kg/m2 or greater. They received phentermine-HCl 37.5 mg or placebo once daily with behavioral therapy for obesity. The primary endpoints were the changes of body weight and waist circumference from the baseline in the intention-to-treat population. Mean decrease of both body weight and waist circumference in phentermine-treated subjects were significantly greater than that of placebo group (weight: -6.7 +/- 2.5 kg, p < 0.001; waist circumference: -6.2 +/- 3.5 cm, p < 0.001). Significant number of subjects in phentermine group accomplished weight reduction of 5% or greater from the baseline and 10% or more (p < 0.001). There were no significant differences in systolic and diastolic blood pressure between the groups (p = 0.122 for systolic BP; p = 0.219 for diastolic BP). Dry mouth and insomnia were the only statistically significant adverse events that occurred more frequently in phentermine group. Most side effects of phentermine were mild to moderate in intensity. Short-term phentermine administration induced significant weight reduction and reduction of waist circumference without clinically problematic adverse events on relatively healthy Korean obese people.

  19. Cuidando El Corazon--a weight-reduction intervention for Mexican Americans.

    PubMed

    Foreyt, J P; Ramirez, A G; Cousins, J H

    1991-06-01

    Cuidando El Corazon (CEC; Taking Care of Your Heart) was designed to assess the effectiveness of a culturally adapted weight-reduction and exercise program for achieving long-term weight loss in Mexican Americans. CEC used a family-oriented approach to achieve lifestyle change in behavior. Participants were assigned to 1) a booklet-only comparison group that received a manual including behavior change, nutrition, and exercise information and traditional recipes modified in fat content; 2) an individual group that received the same manual and attended year-long classes; or 3) a family group that received a manual and attended classes that emphasized techniques for making changes in the family's eating and exercising habits. The family and individual groups had significantly greater weight losses than the information-only group. Weight loss was greatest in the family-involvement group and least in the information-only comparison group.

  20. Effects of dietary fish and weight reduction on ambulatory blood pressure in overweight hypertensives.

    PubMed

    Bao, D Q; Mori, T A; Burke, V; Puddey, I B; Beilin, L J

    1998-10-01

    Obesity is a major factor contributing to hypertension and increased risk of cardiovascular disease. Regular consumption of dietary fish and omega3 fatty acids of marine origin can lower blood pressure (BP) levels and reduce cardiovascular risk. This study examined the potential effects of combining dietary fish rich in omega3 fatty acids with a weight loss regimen in overweight hypertensive subjects, with ambulatory BP levels as the primary end point. Using a factorial design, 69 overweight medication-treated hypertensives were randomized to a daily fish meal (3.65 g omega3 fatty acids), weight reduction, the 2 regimens combined, or a control regimen for 16 weeks. Sixty-three subjects with a mean+/-SEM body mass index of 31.6+/-0.5 kg/m2 completed the study. Weight fell by 5.6+/-0.8 kg with energy restriction. Dietary fish and weight loss had significant independent and additive effects on 24-hour ambulatory BP. Effects were greatest on awake systolic and diastolic BP (P<0.01); relative to control, awake pressures fell 6.0/3.0 mm Hg with dietary fish alone, 5.5/2.2 mm Hg with weight reduction alone, and 13.0/9.3 mm Hg with fish and weight loss combined. These results also remained significant after further adjustment for changes in urinary sodium, potassium, or the sodium/potassium ratio, as well as dietary macronutrients. Dietary fish also significantly reduced 24-hour (-3.1+/-1.4 bpm, P=0.036) and awake (-4.2+/-1.6 bpm, P=0. 013) ambulatory heart rates. Weight reduction had a significant effect on sleeping heart rate only (-3.2+/-1.7 bpm, P=0.037). Combining a daily fish meal with a weight-reducing regimen led to additive effects on ambulatory BP and decreased heart rate. The effects were large, suggesting that cardiovascular risk and antihypertensive drug requirements are likely to be reduced substantially by combining dietary fish meals rich in omega3 fatty acids with weight-loss regimens in overweight medication-treated hypertensives. The reduction in heart

  1. The low density lipoprotein receptor modulates the effects of hypogonadism on diet-induced obesity and related metabolic perturbations

    PubMed Central

    Constantinou, Caterina; Mpatsoulis, Diogenis; Natsos, Anastasios; Petropoulou, Peristera-Ioanna; Zvintzou, Evangelia; Traish, Abdulmaged M.; Voshol, Peter J.; Karagiannides, Iordanes; Kypreos, Kyriakos E.

    2014-01-01

    Here, we investigated how LDL receptor deficiency (Ldlr−/−) modulates the effects of testosterone on obesity and related metabolic dysfunctions. Though sham-operated Ldlr−/− mice fed Western-type diet for 12 weeks became obese and showed disturbed plasma glucose metabolism and plasma cholesterol and TG profiles, castrated mice were resistant to diet-induced obesity and had improved glucose metabolism and reduced plasma TG levels, despite a further deterioration in their plasma cholesterol profile. The effect of hypogonadism on diet-induced weight gain of Ldlr−/− mice was independent of ApoE and Lrp1. Indirect calorimetry analysis indicated that hypogonadism in Ldlr−/− mice was associated with increased metabolic rate. Indeed, mitochondrial cytochrome c and uncoupling protein 1 expression were elevated, primarily in white adipose tissue, confirming increased mitochondrial metabolic activity due to thermogenesis. Testosterone replacement in castrated Ldlr−/− mice for a period of 8 weeks promoted diet-induced obesity, indicating a direct role of testosterone in the observed phenotype. Treatment of sham-operated Ldlr−/− mice with the aromatase inhibitor exemestane for 8 weeks showed that the obesity of castrated Ldlr−/− mice is independent of estrogens. Overall, our data reveal a novel role of Ldlr as functional modulator of metabolic alterations associated with hypogonadism. PMID:24837748

  2. Berberine inhibits adipogenesis in high-fat diet-induced obesity mice.

    PubMed

    Hu, Yueshan; Davies, Gareth E

    2010-07-01

    Our previous studies illustrated that berberine inhibited adipogenesis in murine-derived 3T3-L1 preadipocytes and human white preadipocytes. In this study, the effects of berberine on the adipogenesis of high-fat diet-induced obesity (FD) or normal diet (ND) mice and possible transcriptional impact are investigated. The results demonstrated that in FD mice, berberine reduced mouse weight gain and food intake and serum glucose, triglyceride, and total cholesterol levels accompanied with a down-regulation of PPARgamma expression and an up-regulation of GATA-3 expression. Berberine had no adverse effects on ND mice. These encouraging findings suggest that berberine has excellent pharmacological potential to prevent obesity.

  3. Correlation between nipple elevation and breast resection weight: How to preoperatively plan breast reduction.

    PubMed

    Moio, Mariagrazia; Schonauer, Fabrizio

    2015-08-01

    Breast hypertrophy is often associated with functional limitations. Beyond the aesthetic concerns, breast reduction can improve symptoms and self-esteem. In different countries, health-care system regulations have fixed the threshold for reimbursement in 500 g of predicted tissue resection for each breast. Different preoperative measurements have been proposed to predict breast-tissue weight to be removed, showing a variable correlation with post-operative evaluation. We describe a reliable, simple measurement to predict the quantity of breast reduction in grams, which can be applicable to any surgical technique. A total of 128 patients undergoing bilateral breast reduction were evaluated. The correlation between the preoperative nipple-areola complex (NAC) lift distance and the weight of removed breast tissue was tested with linear regression and Pearson's test. Other anthropometric measurements were tested as a control. The ratio between resected grams and lift distance was explored to find a multiplication coefficient to be used at preoperative planning. The mean resection weight was 686.65 g. The mean NAC-lift distance was 7.6 cm. Positive correlation between the NAC-lift distance and the weight of breast tissue removed was found (r: 0.87; p < 0.001). The mean weight of the removed breast tissue (g) per centimetre of NAC lift was 81 g/cm in the group between 6 and 12 cm and 70 g/cm in the group with >12 cm of lift distance. The NAC-lift distance is a single, objective, repeatable measure that can provide a reliable prediction of breast-tissue grams to be removed; it helps in classifying breast-reduction indications.

  4. Effects of Body Weight Reduction on Serum Irisin and Metabolic Parameters in Obese Subjects

    PubMed Central

    Kurose, Satoshi; Shinno, Hiromi; Thi Thu, Ha Cao; Takao, Nana; Tsutsumi, Hiromi; Hasegawa, Takaaki; Nakajima, Toshiaki; Kimura, Yutaka

    2016-01-01

    Background Irisin is a myokine implicated in lipid and glucose metabolism. The objective of this study is to examine the effect of a body weight reduction on the serum irisin level and physical indicators in obese Japanese patients without diabetes. Methods The subjects were 22 patients (male/female, 5/17; age, 46.1±16.0 years; body mass index [BMI], 36.9±5.0 kg/m2) who completed a 6-month body weight reduction program at our clinic. The program included diet, exercise therapy and cognitive behavioral therapy. Blood parameters, body composition, exercise tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and serum irisin were determined before and after intervention, and relationships among changes in these data were examined. Results There were significant decreases in body weight and BMI after the intervention. Irisin before the intervention was significantly positively correlated with HOMA-IR (r=0.434, P<0.05). The mean irisin level showed no significant change after the intervention in all participants. However, improvements in % body fat, subcutaneous fat area, triglycerides, and fasting glucose were significantly greater in patients with an increase in irisin compared to those with a decrease in irisin after the intervention. Patients with an increase in irisin also had significantly lower fasting insulin (9.7±4.8 vs. 16.4±8.2, P<0.05) and HOMA-IR (2.2±1.1 vs. 3.7±1.6, P<0.05) after the intervention, compared to patients with a decrease in irisin. Conclusion Body weight reduction did not alter irisin levels. However, irisin may play important roles in fat and glucose metabolism and insulin resistance, and the effects of body weight reduction on irisin kinetics may be a key for obesity treatment. PMID:27766246

  5. A Multifactorial Weight Reduction Programme for Children with Overweight and Asthma: A Randomized Controlled Trial

    PubMed Central

    Willeboordse, Maartje; van de Kant, Kim D. G.; Tan, Frans E. S.; Mulkens, Sandra; Schellings, Julia; Crijns, Yvonne; van der Ploeg, Liesbeth; van Schayck, Constant P.; Dompeling, Edward

    2016-01-01

    Background There is increasing evidence that obesity is related to asthma development and severity. However, it is largely unknown whether weight reduction can influence asthma management, especially in children. Objective To determine the effects of a multifactorial weight reduction intervention on asthma management in overweight/obese children with (a high risk of developing) asthma. Methods An 18-month weight-reduction randomized controlled trial was conducted in 87 children with overweight/obesity and asthma. Every six months, measurements of anthropometry, lung function, lifestyle parameters and inflammatory markers were assessed. Analyses were performed with linear mixed models for longitudinal analyses. Results After 18 months, the body mass index-standard deviation score decreased by -0.14±0.29 points (p<0.01) in the intervention group and -0.12±0.34 points (p<0.01) in the control group. This change over time did not differ between groups (p>0.05). Asthma features (including asthma control and asthma-related quality of life) and lung function indices (static and dynamic) improved significantly over time in both groups. The FVC% predicted improved over time by 10.1 ± 8.7% in the intervention group (p<0.001), which was significantly greater than the 6.1 ± 8.4% in the control group (p<0.05). Conclusions & clinical relevance Clinically relevant improvements in body weight, lung function and asthma features were found in both the intervention and control group, although some effects were more pronounced in the intervention group (FVC, asthma control, and quality of life). This implies that a weight reduction intervention could be clinically beneficial for children with asthma. Trial Registration ClinicalTrials.gov NCT00998413 PMID:27294869

  6. Optimization of co-agonism at GLP-1 and glucagon receptors to safely maximize weight reduction in DIO-rodents.

    PubMed

    Day, Jonathan W; Gelfanov, Vasily; Smiley, David; Carrington, Paul E; Eiermann, George; Chicchi, Gary; Erion, Mark D; Gidda, Jas; Thornberry, Nancy A; Tschöp, Matthias H; Marsh, Donald J; SinhaRoy, Ranabir; DiMarchi, Richard; Pocai, Alessandro

    2012-01-01

    The ratio of GLP-1/glucagon receptor (GLP1R/GCGR) co-agonism that achieves maximal weight loss without evidence of hyperglycemia was determined in diet-induced obese (DIO) mice chronically treated with GLP1R/GCGR co-agonist peptides differing in their relative receptor agonism. Using glucagon-based peptides, a spectrum of receptor selectivity was achieved by a combination of selective incorporation of GLP-1 sequences, C-terminal modification, backbone lactam stapling to stabilize helical structure, and unnatural amino acid substitutions at the N-terminal dipeptide. In addition to α-amino-isobutyric acid (Aib) substitution at position two, we show that α,α'-dimethyl imidazole acetic acid (Dmia) can serve as a potent replacement for the highly conserved histidine at position one. Selective site-specific pegylation was used to further minimize enzymatic degradation and provide uniform, extended in vivo duration of action. Maximal weight loss devoid of any sign of hyperglycemia was achieved with a co-agonist comparably balanced for in vitro potency at murine GLP1R and GCGR. This peptide exhibited superior weight loss and glucose lowering compared to a structurally matched pure GLP1R agonist, and to co-agonists of relatively reduced GCGR tone. Any further enhancement of the relative GCGR agonist potency yielded increased weight loss but at the expense of elevated blood glucose. We conclude that GCGR agonism concomitant with GLP1R agonism constitutes a promising approach to treatment of the metabolic syndrome. However, the relative ratio of GLP1R/GCGR co-agonism needs to be carefully chosen for each species to maximize weight loss efficacy and minimize hyperglycemia.

  7. Observation of sympathomimetic effect of ear acupuncture stimulation for body weight reduction.

    PubMed

    Shen, Ein-Yiao; Hsieh, Ching-Liang; Chang, Yung-Hsien; Lin, Jaung-Geng

    2009-01-01

    Ear acupuncture stimulation has been used for body weight reduction as early as the 1970s. Several hypotheses have been proposed in literature regarding its mechanism of action, among which are the effects of the stimulation of the hypothalamic satiety center on decreased neuropeptide Y production. Here, we present another possible mechanism to account for the temporary and short-term effects of ear acupuncture stimulation in the treatment of obesity, the sympathetic effects of the autonomic nervous system. 14 female volunteers underwent a randomized clinical trial of the ear acupuncture stimulation. A prospective, sham-point control, crossover study was performed with two sequential four-week stimulation periods separated by a two-week washout interval. The clinical features of and effects on the autonomic nervous system were recorded and analyzed. Decreased body weight was observed in both the experimental and the control groups in the first 4 weeks of stimulation. Sympathomimetic effects were also noted in both groups. Whereas the sympathomimetic effects and body weight reduction were sustained in the experimental group in the second 4 weeks of stimulation, such effects were not observed in the control group. Some sympathomimetic effects were noted in both the experimental and the control groups initially. This effect remained apparent in the experimental group in sequential stimulation but was lost in the control group. Consequently, we believe that sympathomimetic effects may account for the reduction in body weight by temporarily increasing basal metabolic rate and decreasing appetite, but the body may regain weight after the termination of such effects. Accordingly, the combination of an optimal exercise and diet program with repeated acupoint therapy may be necessary to maintain a healthy body weight.

  8. Enzymatically synthesized glycogen reduces lipid accumulation in diet-induced obese rats.

    PubMed

    Furuyashiki, Takashi; Ogawa, Rui; Nakayama, Yoko; Honda, Kazuhisa; Kamisoyama, Hiroshi; Takata, Hiroki; Yasuda, Michiko; Kuriki, Takashi; Ashida, Hitoshi

    2013-09-01

    Based on a recent study indicating that enzymatically synthesized glycogen (ESG) possesses a dietary, fiber-like action, we hypothesized that ESG can reduce the risk of obesity. In this study, the antiobesity effects of ESG were investigated in a model of diet-induced obesity. Male Sprague-Dawley rats were divided into 4 groups and fed a normal or high-fat diet, with or without 20% ESG, for 4 weeks. Body weight, food intake, lipid deposition in the white adipose tissues and liver, fecal lipid excretion, and plasma lipid profiles were measured. At week 3, the body fat mass was measured using an x-ray computed tomography system, which showed that ESG significantly suppressed the high-fat diet-induced lipid accumulation. Similar results were observed in the weight of the adipose tissue after the experiment. Moreover, ESG significantly suppressed the lipid accumulation in the liver but increased fecal lipid excretion. The plasma concentrations of triacylglycerol and nonesterified fatty acid were lowered after a high-fat diet, whereas the total bile acid concentration was increased by ESG. However, the hepatic messenger RNA (mRNA) levels of enzymes related to lipid metabolism were not affected by ESG. Conversely, the mRNA levels of long-chain acyl-CoA dehydrogenase and medium-chain acyl-CoA dehydrogenase were up-regulated by ESG in the muscle. These results suggest that the combined effects of increased fecal lipid excretion, increased mRNA levels of enzymes that oxidize fatty acids in the muscle, and increased total bile acid concentration in the plasma mediate the inhibitory effect of ESG on lipid accumulation.

  9. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice

    PubMed Central

    Fagman, Johan B.; Wilhelmson, Anna S.; Motta, Benedetta M.; Pirazzi, Carlo; Alexanderson, Camilla; De Gendt, Karel; Verhoeven, Guido; Holmäng, Agneta; Anesten, Fredrik; Jansson, John-Olov; Levin, Malin; Borén, Jan; Ohlsson, Claes; Krettek, Alexandra; Romeo, Stefano; Tivesten, Åsa

    2015-01-01

    Androgens have important cardiometabolic actions in males, but their metabolic role in females is unclear. To determine the physiologic androgen receptor (AR)–dependent actions of androgens on atherogenesis in female mice, we generated female AR-knockout (ARKO) mice on an atherosclerosis-prone apolipoprotein E (apoE)–deficient background. After 8 weeks on a high-fat diet, but not on a normal chow diet, atherosclerosis in aorta was increased in ARKO females (+59% vs. control apoE-deficient mice with intact AR gene). They also displayed increased body weight (+18%), body fat percentage (+62%), and hepatic triglyceride levels, reduced insulin sensitivity, and a marked atherogenic dyslipidemia (serum cholesterol, +52%). Differences in atherosclerosis, body weight, and lipid levels between ARKO and control mice were abolished in mice that were ovariectomized before puberty, consistent with a protective action of ovarian androgens mediated via the AR. Furthermore, the AR agonist dihydrotestosterone reduced atherosclerosis (−41%; thoracic aorta), subcutaneous fat mass (−44%), and cholesterol levels (−35%) in ovariectomized mice, reduced hepatocyte lipid accumulation in hepatoma cells in vitro, and regulated mRNA expression of hepatic genes pivotal for lipid homeostasis. In conclusion, we demonstrate that the AR protects against diet-induced atherosclerosis in female mice and propose that this is mediated by modulation of body composition and lipid metabolism.—Fagman, J. B., Wilhelmson, A. S., Motta, B. M., Pirazzi, C., Alexanderson, C., De Gendt, K., Verhoeven, G., Holmäng, A., Anesten, F., Jansson, J.-O., Levin, M., Borén, J., Ohlsson, C., Krettek, A., Romeo, S., Tivesten, A. The androgen receptor confers protection against diet-induced atherosclerosis, obesity, and dyslipidemia in female mice. PMID:25550469

  10. Ameliorating Effect of Mycoleptodonoides aitchisonii on High-fat Diet-induced Obese Mice

    PubMed Central

    Lee, Mi Ra; Begum, Shahnaz; Oh, Deuk Sil; Wee, An Jin; Yun, Byung Sun; Sung, Chang Keun

    2014-01-01

    The present study investigated the anti-obesity effects of Mycoleptodonoides aitchisonii (MA) in mice fed a high-fat (HF) diet. Two groups were fed either a normal control diet or an HF (45% kcal fat) diet for 12 weeks and three groups were fed an HF diet supplemented with powdered MA (MAP, 1%, 3%, and 5%) for 12 weeks. The anti-obesity effects of MAP supplementation on body weight, fat mass development, and lipid-related markers were assessed. Consumption of an HF diet resulted in increased body weight, serum lipids, relative adipose tissues weight, and liver fat accumulation. However, administration of MAP significantly decreased body weight gain, food intake, food efficiency ratio, hepatic cholesterol level, and adipose tissue weight in a dose-dependent manner. In addition, treatment with MAP significantly reduced the occurrence of fatty liver deposits and steatosis, and inhibited an HF diet-induced increase in adipocyte size. These results suggest that dietary supplementation with MAP exerts anti-obesity effects and indicate that MAP could be used as a functional food to control obesity. PMID:25054104

  11. [Health risks and economic costs associated with obesity requiring a comprehensive weight reduction program].

    PubMed

    Hainer, V; Kunesová, M; Parízková, J; Stunkard, A

    1997-06-12

    defined a comprehensive weight reduction program carried out in weight reduction clubs, out-patient obesity clinics and in specialized departments attached to the university hospitals. In order to provide an integrated knowledge from many different disciplines connected with obesity three week postgraduate course has been organized for physicians involved in obesity management. Even the most spread weight reduction clubs in our country (STOB) are supervised by the trained counselors. The main goal of different weight management programs is to find out optimal approaches leading to long-term beneficial outcome and ameliorating the variety of disorders associated with obesity.

  12. Isotope fractionation of mercury during its photochemical reduction by low-molecular-weight organic compounds.

    PubMed

    Zheng, Wang; Hintelmann, Holger

    2010-04-01

    Photochemical reduction of Hg(II) by various low-molecular-weight organic compounds (LMWOC) was investigated to evaluate the effect of specific functional groups that are typically encountered in natural dissolved organic matters (DOM) on the photoreactivity and isotope fractionation of Hg. LMWOC with reduced sulfur functional groups (e.g., cysteine, glutathione) resulted in slower photochemical reduction of Hg(II) than those without reduced sulfur groups (e.g., serine, oxalic acid). Reduction rate constants were specifically determined for two contrasting LMWOC: dl-serine (0.640 h(-1)) and l-cysteine (0.047 h(-1)). Different mass independent isotope effects of Hg were induced by the two types of LMWOC. S-containing ligands specifically enriched magnetic isotopes ((199)Hg and (201)Hg) in the product (Hg(0)) while sulfurless ligands enriched (199)Hg and (201)Hg in the reactant (Hg(II)), suggesting that opposite magnetic isotope effects were produced by different types of ligands. The nuclear field shift effect was also observed in the photochemical reduction by serine. These isotope effects are related to specific functional groups and reduction mechanisms, and may be used to distinguish between primary and secondary photochemical reduction mechanisms of Hg(II) and to explain isotope fractionation during the photochemical reduction of Hg(II) by natural DOM, which provides mixed bonding conditions.

  13. Anti-Obesity Effect of the CB2 Receptor Agonist JWH-015 in Diet-Induced Obese Mice.

    PubMed

    Verty, A N A; Stefanidis, A; McAinch, A J; Hryciw, D H; Oldfield, Brian

    2015-01-01

    The cannabinoid receptor 2 (CB2) is well known for its immune modulatory role. However, recent localisation of CB2 receptors in metabolically active tissue suggests that the CB2 receptor plays a significant role in energy homeostasis. This study was designed to investigate the impact of chronic CB2 receptor stimulation on food intake, body weight and mood. Lean male C57BL/6 mice were injected i.p. with the selective CB2 receptor agonist, JWH-015 (0.0, 1.0, 5.0 and 10.0 mg kg-1) to establish dose response parameters. Mice made obese following exposure to a diet consisting of 19.4 MJ/kg (4641 Kcal/kg) of energy (19.0% protein, 21.0% total fat, 4.7% crude fiber, and 4.7% AD fiber were given either vehicle or 10 mg/kg JWH-015. Impact on mood, food intake, body weight, plasma metabolites, expression of key metabolic proteins in the brown adipose tissue (BAT) and white adipose tissue (WAT), and markers of inflammation were measured. High dose (10 mg/kg) JWH-015 reduced food intake after 1, 2, 4, and 24 h in lean mice. When given to diet induced obese (DIO) mice, a 10 mg/kg dose of JWH-015 significantly reduced body weight compared to vehicle. This dose led to a shift in markers of lipid metabolism and inflammation in WAT consistent with lipolysis and improved immune response. Furthermore, JWH-015 (10 mg/kg) produced a transient reduction in food intake and significant reduction in fat mass and adipocyte cell size. Importantly, JWH-015 produced an anxiolytic response in the elevated plus maze while having no effect on immobility time in the forced swim test. It should be noted that though the 10 mg/kg dose produced positive effects on the obese state, the possibility that these effects are mediated via non-CB2 receptor mechanisms cannot be ruled out. These results demonstrate a role for CB2 receptors in modulating energy homeostasis and obesity associated metabolic pathologies in the absence of any adverse impact on mood.

  14. Anti-Obesity Effect of the CB2 Receptor Agonist JWH-015 in Diet-Induced Obese Mice

    PubMed Central

    Verty, A. N. A.; Stefanidis, A.; McAinch, A. J.; Hryciw, D. H.; Oldfield, Brian

    2015-01-01

    The cannabinoid receptor 2 (CB2) is well known for its immune modulatory role. However, recent localisation of CB2 receptors in metabolically active tissue suggests that the CB2 receptor plays a significant role in energy homeostasis. This study was designed to investigate the impact of chronic CB2 receptor stimulation on food intake, body weight and mood. Lean male C57BL/6 mice were injected i.p. with the selective CB2 receptor agonist, JWH-015 (0.0, 1.0, 5.0 and 10.0 mg kg-1) to establish dose response parameters. Mice made obese following exposure to a diet consisting of 19.4 MJ/kg (4641 Kcal/kg) of energy (19.0% protein, 21.0% total fat, 4.7% crude fiber, and 4.7% AD fiber were given either vehicle or 10 mg/kg JWH-015. Impact on mood, food intake, body weight, plasma metabolites, expression of key metabolic proteins in the brown adipose tissue (BAT) and white adipose tissue (WAT), and markers of inflammation were measured. High dose (10 mg/kg) JWH-015 reduced food intake after 1, 2, 4, and 24 h in lean mice. When given to diet induced obese (DIO) mice, a 10 mg/kg dose of JWH-015 significantly reduced body weight compared to vehicle. This dose led to a shift in markers of lipid metabolism and inflammation in WAT consistent with lipolysis and improved immune response. Furthermore, JWH-015 (10 mg/kg) produced a transient reduction in food intake and significant reduction in fat mass and adipocyte cell size. Importantly, JWH-015 produced an anxiolytic response in the elevated plus maze while having no effect on immobility time in the forced swim test. It should be noted that though the 10 mg/kg dose produced positive effects on the obese state, the possibility that these effects are mediated via non-CB2 receptor mechanisms cannot be ruled out. These results demonstrate a role for CB2 receptors in modulating energy homeostasis and obesity associated metabolic pathologies in the absence of any adverse impact on mood. PMID:26588700

  15. Advancements in Steel for Weight Reduction of P900 Armor Plate

    DTIC Science & Technology

    2008-12-01

    were investigated as alternatives to MIL-PRF- 32269 steel alloys for application in P900 perforated armor currently used for Army ground combat...ADVANCEMENTS IN STEEL FOR WEIGHT REDUCTION OF P900 ARMOR PLATE R. A. Howell*, J. S. Montgomery Survivability Materials Branch Army Research Lab...Aberdeen Proving Grounds , MD 21001 D.C. Van Aken Missouri University for Science and Technology Rolla, MO 65401 ABSTRACT Ballistic tests

  16. Central pedicled breast reduction technique in male patients after massive weight loss.

    PubMed

    Stoff, Alexander; Velasco-Laguardia, Fernando J; Richter, Dirk F

    2012-03-01

    Male patients after massive weight loss often suffer from redundant skin and soft tissue in the anterior and lateral chest region, causing various deformities of pseudogynecomastia. Techniques with free or pedicled nipple-areola complex (NAC) transposition are widely accepted. The authors present their approach to male breast reduction with preservation of the NAC on a central dermoglandular pedicle and a wide elliptical tissue excision of breast and lateral thorax tissue in combination with liposuction. Male breast reduction was performed on patients after moderate to massive weight loss due to diet or bariatric procedures. Former procedures included free nipple-areola grafts or inferior pedicled techniques for NAC preservation. As a modification, we performed a central pedicled breast reduction on nine male patients with excessive liposuction of the pedicle and a horizontal elliptical skin removal, allowing for sufficient tissue removal at the lateral thorax. From October 2010 until June 2011, nine male patients had central pedicled breast reconstructions after massive weight loss. Mean age was 29.1 years, mean preoperative body mass index was 29.2, and mean preoperative weight loss was 63.9 kg. The chest wall improvement was rated "very good" by eight patients. No major complications occurred in all nine patients. Male chest deformities after massive weight loss can be dealt by several approaches. The optimal scar positioning and the preservation of NAC may be the most challenging aspects of these procedures. Therefore, the preservation of the NAC on a central dermoglandular pedicle with a horizontal submammary scar course may optimize the esthetic outcome.

  17. Electroacupuncture Improves Insulin Resistance by Reducing Neuroprotein Y/Agouti-Related Protein Levels and Inhibiting Expression of Protein Tyrosine Phosphatase 1B in Diet-induced Obese Rats.

    PubMed

    Liu, Xia; He, Jun-Feng; Qu, Ya-Ting; Liu, Zhi-Jun; Pu, Qing-Yang; Guo, Sheng-Tong; Du, Jia; Jiang, Peng-Fei

    2016-04-01

    Electroacupuncture (EA) has been shown to exert beneficial effects on obesity, but the mechanism is unclear. This study investigated the effects of EA on diet-induced obese (DIO) rats. Fifty male Sprague-Dawley rats were randomly divided into low-fat diet (LFD, 10 rats) and high-fat diet (HFD, 40 rats) groups. After the DIO models had been established, successful model rats were randomly divided into HFD, EA, and orlistat (OLST) groups. The EA group received EA at Zusanli (ST36) and Quchi (LI11) for 20 minutes once per day for 28 days. The OLST group was treated with orlistat by gavage. The body weight, homeostasis model assessment-insulin resistance index, adipocyte diameters, and neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B levels were significantly lower in the EA group than in the HFD group. The rats of the OLST group showed watery stools and yellow hairs whereas those of the EA group had regular stools and sleek coats. The effect of EA on weight loss may be related to improved insulin resistance caused by changes in the adipocyte size and by reductions in the expressions of neuroprotein Y/agouti-related protein and protein tyrosine phosphatase 1B. This study indicates that EA may be a better method of alternative therapy for treating obesity and other metabolic diseases.

  18. Hybrid Wing-Body (HWB) Pressurized Fuselage Modeling, Analysis, and Design for Weight Reduction

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, Vivek

    2012-01-01

    This paper describes the interim progress for an in-house study that is directed toward innovative structural analysis and design of next-generation advanced aircraft concepts, such as the Hybrid Wing-Body (HWB) and the Advanced Mobility Concept-X flight vehicles, for structural weight reduction and associated performance enhancement. Unlike the conventional, skin-stringer-frame construction for a cylindrical fuselage, the box-type pressurized fuselage panels in the HWB undergo significant deformation of the outer aerodynamic surfaces, which must be minimized without significant structural weight penalty. Simple beam and orthotropic plate theory is first considered for sizing, analytical verification, and possible equivalent-plate analysis with appropriate simplification. By designing advanced composite stiffened-shell configurations, significant weight reduction may be possible compared with the sandwich and ribbed-shell structural concepts that have been studied previously. The study involves independent analysis of the advanced composite structural concepts that are presently being developed by The Boeing Company for pressurized HWB flight vehicles. High-fidelity parametric finite-element models of test coupons, panels, and multibay fuselage sections, were developed for conducting design studies and identifying critical areas of potential failure. Interim results are discussed to assess the overall weight/strength advantages.

  19. Efficacy of two different materials used in auricular acupressure on weight reduction and abdominal obesity.

    PubMed

    Hsieh, Ching Hsiu; Su, Tsann-Juu; Fang, Yu-Wen; Chou, Pei-Hsuan

    2012-01-01

    The current study was designed to test the efficacy of different materials used in an auricular acupressure program on weight reduction, changes to waist circumference and waist-to-hip ratio. This study used a randomized design with two groups who were treated with auricular acupressure using Semen Vaccariae or the Japanese Magnetic Pearl. Both groups consisted of Asian young adults with a waist circumference ≥ 80 cm in the females and ≥ 90 cm in the males. At completion of the eight-week treatment period, the total sample size was 56 young adults who ranged in age from 18 to 20 years old. Each participant was met with weekly for ten-minute sessions during which ear acupressure treatment was performed. Sessions continued for eight weeks wherein both groups received acupressure with the Japanese Magnetic Pearl or Semen Vaccariae on the ear acupoints. While both groups showed significant reductions (p ≤ 0.05) to body weight and waist circumference after eight weeks of treatments, the group treated with Semen Vaccariae group showed a more effective weight loss over the short term. Given that auricular acupressure is a safe and cost-effective treatment for weight loss, our results suggest that auricular acupressure is a reasonable option for the treatment of overweight and obesity in young adults.

  20. Modulatory effect of green tea extract on hepatic key enzymes of glucose metabolism in streptozotocin and high fat diet induced diabetic rats.

    PubMed

    Sundaram, Ramalingam; Naresh, Rajendran; Shanthi, Palanivelu; Sachdanandam, Panchanatham

    2013-05-15

    The study was undertaken to evaluate the antidiabetic effect of green tea extract on carbohydrate metabolic key enzymes in control and streptozotocin high fat diet -induced diabetic rats. The daily oral treatment of green tea extract (300 mg/kg body weight) to diabetic rats for 30 days resulted in a significant reduction in the levels of plasma glucose, glycosylated hemoglobin (HbA1c) and increase in the levels of insulin and hemoglobin. The altered activities of the key enzymes of carbohydrate metabolism such as hexokinase, pyruvate kinase, lactate dehydrogenase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, glucose-6-phosphate dehydrogenase, glycogen synthase and glycogen phosphorylase in liver of diabetic rats were significantly reverted to near normal levels by the administration of green tea extract. Further, green tea extract administration to diabetic rats improved muscle and hepatic glycogen content suggesting the antihyperglycemic potential of green tea extract in diabetic rats. The obtained results were compared with metformin, a standard oral hypoglycemic drug. Thus, this study indicates that the administration of green tea extract to diabetic rats resulted in alterations in the metabolism of glucose with subsequent reduction in plasma glucose levels.

  1. Serum free thyroxine levels are associated with the efficacy of weight reduction therapy in obese female patients.

    PubMed

    Hashimoto, Koshi; Tagami, Tetsuya; Yamakage, Hajime; Muranaka, Kazuya; Tanaka, Masashi; Odori, Shinji; Kono, Shigeo; Shimatsu, Akira; Ogawa, Yoshihiro; Satoh-Asahara, Noriko

    2016-01-01

    Thyroid function is strongly associated with obesity. The aim of this study is to investigate whether serum free thyroxine (FT4) and/or thyrotropin (TSH) levels are associated with the efficacy of weight reduction therapy in obese patients. We enrolled a total of 283 obese patients and cross-sectionally investigated the association of serum FT4 and/or TSH levels with metabolic features. Furthermore, in 97 obese patients who received 6-month weight reduction therapy, we assessed the relationship of serum FT4 and/or TSH levels to the efficacy of weight reduction therapy. Neither baseline serum FT4 nor TSH levels showed any correlations with body weight (BW) and body mass index (BMI) in these obese patients. However, in 57 obese female patients who underwent weight reduction therapy for six months, serum FT4 levels prior to the therapy was negatively correlated with the degrees of reduction of BW (r = -0.354, p = 0.007) and BMI (r = -0.373, p = 0.004). The correlation between baseline serum FT4 levels with the efficacy of weight reduction therapy was not observed in obese male or postmenopausal female patients. This study demonstrates that baseline serum FT4 levels are associated with weight reduction in obese female premenopausal patients. Therefore, baseline FT4 levels can be used as a clinical, noninvasive, hormonal predictor of weight reduction efficacy in obese patients.

  2. Mice lacking ghrelin receptors resist the development of diet-induced obesity

    PubMed Central

    Zigman, Jeffrey M.; Nakano, Yoshihide; Coppari, Roberto; Balthasar, Nina; Marcus, Jacob N.; Lee, Charlotte E.; Jones, Juli E.; Deysher, Amy E.; Waxman, Amanda R.; White, Ryan D.; Williams, Todd D.; Lachey, Jennifer L.; Seeley, Randy J.; Lowell, Bradford B.; Elmquist, Joel K.

    2005-01-01

    Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor (GHSR; ghrelin receptor). Since its discovery, accumulating evidence has suggested that ghrelin may play a role in signaling and reversing states of energy insufficiency. For example, ghrelin levels rise following food deprivation, and ghrelin administration stimulates feeding and increases body weight and adiposity. However, recent loss-of-function studies have raised questions regarding the physiological significance of ghrelin in regulating these processes. Here, we present results of a study using a novel GHSR-null mouse model, in which ghrelin administration fails to acutely stimulate food intake or activate arcuate nucleus neurons. We show that when fed a high-fat diet, both female and male GHSR-null mice eat less food, store less of their consumed calories, preferentially utilize fat as an energy substrate, and accumulate less body weight and adiposity than control mice. Similar effects on body weight and adiposity were also observed in female, but not male, GHSR-null mice fed standard chow. GHSR deletion also affected locomotor activity and levels of glycemia. These findings support the hypothesis that ghrelin-responsive pathways are an important component of coordinated body weight control. Moreover, our data suggest that ghrelin signaling is required for development of the full phenotype of diet-induced obesity. PMID:16322794

  3. Noise reduction of a tilt-rotor aircraft including effects on weight and performance

    NASA Technical Reports Server (NTRS)

    Gibs, J.; Stepniewski, W. Z.; Spencer, R.; Kohler, G.

    1973-01-01

    Various methods for far-field noise reduction of a tilt-rotor acoustic signature and the performance and weight tradeoffs which result from modification of the noise sources are considered in this report. In order to provide a realistic approach for the investigation, the Boeing tilt-rotor flight research aircraft (Model 222), was selected as the baseline. This aircraft has undergone considerable engineering development. Its rotor has been manufactured and tested in the Ames full-scale wind tunnel. The study reflects the current state-of-the-art of aircraft design for far-field acoustic signature reduction and is not based solely on an engineering feasibility aircraft. This report supplements a previous study investigating reduction of noise signature through the management of the terminal flight trajectory.

  4. Diet-induced obesity promotes myelopoiesis in hematopoietic stem cells

    PubMed Central

    Singer, Kanakadurga; DelProposto, Jennifer; Lee Morris, David; Zamarron, Brian; Mergian, Taleen; Maley, Nidhi; Cho, Kae Won; Geletka, Lynn; Subbaiah, Perla; Muir, Lindsey; Martinez-Santibanez, Gabriel; Nien-Kai Lumeng, Carey

    2014-01-01

    Obesity is associated with an activated macrophage phenotype in multiple tissues that contributes to tissue inflammation and metabolic disease. To evaluate the mechanisms by which obesity potentiates myeloid activation, we evaluated the hypothesis that obesity activates myeloid cell production from bone marrow progenitors to potentiate inflammatory responses in metabolic tissues. High fat diet-induced obesity generated both quantitative increases in myeloid progenitors as well as a potentiation of inflammation in macrophages derived from these progenitors. In vivo, hematopoietic stem cells from obese mice demonstrated the sustained capacity to preferentially generate inflammatory CD11c+ adipose tissue macrophages after serial bone marrow transplantation. We identified that hematopoietic MyD88 was important for the accumulation of CD11c+ adipose tissue macrophage accumulation by regulating the generation of myeloid progenitors from HSCs. These findings demonstrate that obesity and metabolic signals potentiate leukocyte production and that dietary priming of hematopoietic progenitors contributes to adipose tissue inflammation. PMID:25161889

  5. Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

    PubMed Central

    Hankir, Mohammed K.; Patt, Marianne; Patt, Jörg T. W.; Becker, Georg A.; Rullmann, Michael; Kranz, Mathias; Deuther-Conrad, Winnie; Schischke, Kristin; Seyfried, Florian; Brust, Peter; Hesse, Swen; Sabri, Osama; Krügel, Ute; Fenske, Wiebke K.

    2017-01-01

    Brain μ-opioid receptors (MORs) stimulate high-fat (HF) feeding and have been implicated in the distinct long term outcomes on body weight of bariatric surgery and dieting. Whether alterations in fat appetite specifically following these disparate weight loss interventions relate to changes in brain MOR signaling is unknown. To address this issue, diet-induced obese male rats underwent either Roux-en-Y gastric bypass (RYGB) or sham surgeries. Postoperatively, animals were placed on a two-choice diet consisting of low-fat (LF) and HF food and sham-operated rats were further split into ad libitum fed (Sham-LF/HF) and body weight-matched (Sham-BWM) to RYGB groups. An additional set of sham-operated rats always only on a LF diet (Sham-LF) served as lean controls, making four experimental groups in total. Corresponding to a stage of weight loss maintenance for RYGB rats, two-bottle fat preference tests in conjunction with small-animal positron emission tomography (PET) imaging studies with the selective MOR radioligand [11C]carfentanil were performed. Brains were subsequently collected and MOR protein levels in the hypothalamus, striatum, prefrontal cortex and orbitofrontal cortex were analyzed by Western Blot. We found that only the RYGB group presented with intervention-specific changes: having markedly suppressed intake and preference for high concentration fat emulsions, a widespread reduction in [11C]carfentanil binding potential (reflecting MOR availability) in various brain regions, and a downregulation of striatal and prefrontal MOR protein levels compared to the remaining groups. These findings suggest that the suppressed fat appetite caused by RYGB surgery is due to reduced brain MOR signaling, which may contribute to sustained weight loss unlike the case for dieting. PMID:28133443

  6. Birth weight reduction associated with residence near a hazardous waste landfill.

    PubMed Central

    Berry, M; Bove, F

    1997-01-01

    We examined the relationship between birth weight and mother's residence near a hazardous waste landfill. Twenty-five years of birth certificates (1961-1985) were collected for four towns. Births were grouped into five 5-year periods corresponding to hypothesized exposure periods (1971-1975 having the greatest potential for exposure). From 1971 to 1975, term births (37-44 weeks gestation) to parents living closest to the landfill (Area 1A) had a statistically significant lower average birth weight (192 g) and a statistically significant higher proportion of low birth weight [odds ratio (OR) = 5.1; 95% confidence interval (CI), 2.1-12.3] than the control population. Average term birth weights in Area 1A rebounded by about 332 g after 1975. Parallel results were found for all births (gestational age > 27 weeks) in Area 1A during 1971-1975. Area 1A infants had twice the risk of prematurity (OR = 2.1; 95 CI, 1.0-4.4) during 1971-1975 compared to the control group. The results indicate a significant impact to infants born to residents living near the landfill during the period postulated as having the greatest potential for exposure. The magnitude of the effect is in the range of birth weight reduction due to cigarette smoking during pregnancy. Images Figure 1. Figure 2. PMID:9347901

  7. Effects of grape pomace antioxidant extract on oxidative stress and inflammation in diet induced obese mice.

    PubMed

    Hogan, Shelly; Canning, Corene; Sun, Shi; Sun, Xiuxiu; Zhou, Kequan

    2010-11-10

    Norton grape is one of the most important wine grapes in Southern and Midwestern states and generates massive pomace byproducts. The objective of this study is to characterize the antioxidant compounds and activity in Norton grape pomace extract (GPE) and further assess the potential health promoting properties of Norton GPE using an animal disease model. The total phenolic content and anthocyanins in Norton GPE were 475.4 mg of gallic acid equiv/g and 156.9 mg of cyanidin 3-glucoside equiv/g, respectively. Catechin and epicatechin in GPE were 28.6 and 24.5 mg/g, respectively. Other major antioxidants in GPE included quercetin (1.6 mg/g), trans-resveratrol (60 μg/g), gallic acid (867.2 μg/g), coutaric acid (511.8 μg/g), p-hydroxybenzoic acid (408.3 μg/g), and protocatechuic acid (371.5 μg/g). The antioxidant activity of GPE was evaluated by oxygen radical absorbance capacity (ORAC) and was 4133 μmol of Trolox equiv/g. Male diet-induced obese (DIO) mice were randomly divided to three treatment groups (n = 12): a normal diet (ND group), a high fat diet (HF group), and the high fat diet supplemented with GPE (HFGPE group). After 12-week treatment, mice in the high fat diet groups gained 29% more weight than the ND group. The GPE supplementation (estimated 250 mg/kg bw/d) lowered plasma C-reactive protein levels by 15.5% in the high fat diet fed mice (P < 0.05), suggesting a potential anti-inflammatory effect by dietary GPE. However, dietary GPE did not improve oxidative stress in DIO mice as determined by plasma ORAC, glutathione peroxidase, and liver lipid peroxidation. The results showed that GPE contained significant antioxidants and dietary GPE exerted an anti-inflammatory effect in diet induced obesity.

  8. Targeting the NLRP3 Inflammasome to Reduce Diet-Induced Metabolic Abnormalities in Mice

    PubMed Central

    Chiazza, Fausto; Couturier-Maillard, Aurélie; Benetti, Elisa; Mastrocola, Raffaella; Nigro, Debora; Cutrin, Juan C; Serpe, Loredana; Aragno, Manuela; Fantozzi, Roberto; Ryffel, Bernard; Collino, Massimo

    2015-01-01

    Although the molecular links underlying the causative relationship between chronic low-grade inflammation and insulin resistance are not completely understood, compelling evidence suggests a pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3) inflammasome. Here we tested the hypothesis that either a selective pharmacological inhibition or a genetic downregulation of the NLRP3 inflammasome results in reduction of the diet-induced metabolic alterations. Male C57/BL6 wild-type mice and NLRP3−/− littermates were fed control diet or high-fat, high-fructose diet (HD). A subgroup of HD-fed wild-type mice was treated with the NLRP3 inflammasome inhibitor BAY 11-7082 (3 mg/kg intraperitoneally [IP]). HD feeding increased plasma and hepatic lipids and impaired glucose homeostasis and renal function. Renal and hepatic injury was associated with robust increases in profibrogenic markers, while only minimal fibrosis was recorded. None of these metabolic abnormalities were detected in HD-fed NLRP3−/− mice, and they were dramatically reduced in HD-mice treated with the NLRP3 inflammasome inhibitor. BAY 11-7082 also attenuated the diet-induced increase in NLRP3 inflammasome expression, resulting in inhibition of caspase-1 activation and interleukin (IL)-1β and IL-18 production (in liver and kidney). Interestingly, BAY 11-7082, but not gene silencing, inhibited nuclear factor (NF)-κB nuclear translocation. Overall, these results demonstrate that the selective pharmacological modulation of the NLRP3 inflammasome attenuates the metabolic abnormalities and the related organ injury/dysfunction caused by chronic exposure to HD, with effects similar to those obtained by NLRP3 gene silencing. PMID:26623925

  9. Korean solar salts reduce obesity and alter its related markers in diet-induced obese mice

    PubMed Central

    Ju, Jaehyun; Song, Jia-Le; Park, Eui-Seong; Do, Myoung-Sool

    2016-01-01

    BACKGROUND/OBJECTIVES The aim of this experiments was to show anti-obesity effects of Korean solar salt from different salt fields in diet-induced obese mice. SUBJECTS/METHODS Diet-induced obesity (DIO) was induced by a high-fat diet (HFD; 45% cal from fat) in C57BL/6J mice for eight weeks. The mice were fed with the designated diets (chow diet for Normal, HFD for Control, 0.47%-salt-mixed HFD for purified salt (PS), Guerande solar salt from France (SS-G), solar salt from Y salt field (SS-Y), solar salts from T salt field (SS-T) and S salt field (SS-S)) for another eight weeks. We checked body weight, food efficiency ratio (FER) and tissue weights (liver and epididymal adipose tissue (EAT)), and observed serum concentrations of triacylglycerol (TG), total cholesterol (TC), leptin and insulin. We also evaluated gene expressions of adipogenic / lipogenic mRNAs of C/EBPα, PPARγ and FAS and beta-oxidation-related factors (PPARα and CPT-1) in liver and EAT. The mineral composition of salt samples were analyzed using inductively coupled plasma optical emission spectrometry (ICP-OES). RESULTS SS-T and SS-S significantly reduced body weight gain, FER, and weight of EAT compared to control and other samples (P < 0.05). SS-T and SS-S also significantly decreased serum levels of TG, TC, leptin and insulin (P < 0.05). SS-T and SS-S suppressed expressions of adipogenic / lipogenic mRNAs in liver and EAT, while promoting expression of beta-oxidation-related factors. The lowest sodium concentration was observed in SS-T (30.30 ± 0.59%), and the lowest sodium-to-potassium (Na/K) ratio was found in SS-S (17.81). CONCLUSIONS Our study shows that well-processed Korean solar salt may have anti-obesity effects in vivo, probably owing to its differences in mineral composition and other components, presumably resulting from the manufacturing processes. Further research is needed into the mechanism and to explore optimal manufacturing processes. PMID:27909561

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

    PubMed Central

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

    2016-01-01

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

  11. Miglitol prevents diet-induced obesity by stimulating brown adipose tissue and energy expenditure independent of preventing the digestion of carbohydrates.

    PubMed

    Sasaki, Tsutomu; Shimpuku, Mayumi; Kitazumi, Tomoya; Hiraga, Haruna; Nakagawa, Yuko; Shibata, Hiroshi; Okamatsu-Ogura, Yuko; Kikuchi, Osamu; Kim, Hye-jin; Fujita, Yuki; Maruyama, Jun; Susanti, Vina Yanti; Yokota-Hashimoto, Hiromi; Kobayashi, Masaki; Saito, Masayuki; Kitamura, Tadahiro

    2013-01-01

    Miglitol is an alpha-glucosidase inhibitor that improves post-prandial hyperglycemia, and it is the only drug in its class that enters the bloodstream. Anecdotally, miglitol lowers patient body weight more effectively than other alpha-glucosidase inhibitors, but the precise mechanism has not been addressed. Therefore, we analyzed the anti-obesity effects of miglitol in mice and in the HB2 brown adipocyte cell line. Miglitol prevented diet-induced obesity by stimulating energy expenditure without affecting food intake in mice. Long-term miglitol treatment dose-dependently prevented diet-induced obesity and induced mitochondrial gene expression in brown adipose tissue. The anti-obesity effect was independent of preventing carbohydrate digestion in the gastrointestinal tract. Miglitol effectively stimulated energy expenditure in mice fed a high-fat high-monocarbohydrate diet, and intraperitoneal injection of miglitol was sufficient to stimulate energy expenditure in mice. Acarbose, which is a non-absorbable alpha glucosidase inhibitor, also prevented diet-induced obesity, but through a different mechanism: it did not stimulate energy expenditure, but caused indigestion, leading to less energy absorption. Miglitol promoted adrenergic signaling in brown adipocytes in vitro. These data indicate that circulating miglitol stimulates brown adipose tissue and increases energy expenditure, thereby preventing diet-induced obesity. Further optimizing miglitol's effect on brown adipose tissue could lead to a novel anti-obesity drug.

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

    PubMed

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

    2016-06-01

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

  13. Administration of dried Aloe vera gel powder reduced body fat mass in diet-induced obesity (DIO) rats.

    PubMed

    Misawa, Eriko; Tanaka, Miyuki; Nabeshima, Kazumi; Nomaguchi, Kouji; Yamada, Muneo; Toida, Tomohiro; Iwatsuki, Keiji

    2012-01-01

    The aim of the present study was to investigate the anti-obesity effects of Aloe vera gel administration in male Sprague-Dawley (SD) rats with diet-induced obesity (DIO). SD rats at 7 wk of age were fed either a standard diet (10 kcal% fat) (StdD) or high-fat (60 kcal% fat) diet (HFD) during the experimental period. Four weeks after of HFD-feeding, DIO rats (11 wk of age) were orally administered with two doses of Aloe vera gel powder (20 and 200 mg/kg/d) for 90 d. Body weights (g) and body fat (%) of HFD fed rats were significantly higher than those of StdD-fed rats. Although a modest decrease of body weight (g) was observed with the administration of dried Aloe vera gel powder, both subcutaneous and visceral fat weight (g) and body fat (%) were reduced significantly in Aloe vera gel-treated rats. Serum lipid parameters elevated by HFD were also improved by the Aloe vera gel treatment. The oxygen consumption (VO(2)), an index of energy expenditure, was decreased in HFD-fed rats compared with that in StdD-fed rats. Administration of Aloe vera gel reversed the change in VO(2) in the HFD-fed rats. These results suggest that intake of Aloe vera gel reduced body fat accumulation, in part, by stimulation of energy expenditure. Aloe vera gel might be beneficial for the prevention and improvement of diet-induced obesity.

  14. Codonopsis lanceolata Extract Prevents Diet-Induced Obesity in C57BL/6 Mice

    PubMed Central

    Lee, Jong Seok; Kim, Kui-Jin; Kim, Young-Hyun; Kim, Dan-Bi; Shin, Gi-Hae; Cho, Ju-Hyun; Kim, Bong Kyun; Lee, Boo-Yong; Lee, Ok-Hwan

    2014-01-01

    Codonopsis lanceolata extract (CLE) has been used in traditional medicine in the Asian-Pacific region for the treatment of bronchitis, cough, and inflammation. However, it is still unclear whether obesity in mice can be altered by diet supplementation with CLE. To investigate whether CLE could have preventative effects on high fat diet (HFD)-induced obesity, male C57BL/6 mice were placed on either a normal chow diet, 60% HFD, or a HFD supplemented with CLE (60, 180, and 360 mg/kg/day) for 12 weeks. CLE decreased body weight and subcutaneous and visceral fat weights in HFD-induced obese mice. CLE group mice showed lower fat accumulation and a smaller adipocyte area in the adipose tissue compared with the HFD group mice. CLE group mice exhibited lower serum levels of triglycerides, total cholesterol, low density lipoprotein (LDL), glucose, and insulin compared with the HFD group mice. In addition, CLE decreased liver weight and lowered the increase in aspartate aminotransferase (AST) and alanine transaminase (ALT) levels in HFD-induced obese mice. These results indicate that CLE can inhibit the development of diet-induced obesity and hyperlipidemia in C57BL/6 mice. PMID:25353662

  15. Diet-induced obesity skin changes monitored by in vivo SHG and ex vivo CARS microscopy

    PubMed Central

    Haluszka, Dóra; Lőrincz, Kende; Kiss, Norbert; Szipőcs, Róbert; Kuroli, Enikő; Gyöngyösi, Nóra; Wikonkál, Norbert M.

    2016-01-01

    Obesity related metabolic syndrome and type 2 diabetes have severe consequences on our skin. Latest developments in nonlinear microscopy allow the use of noninvasive, label free imaging methods, such as second harmonic generation (SHG) and coherent anti-Stokes Raman scattering (CARS), for early diagnosis of metabolic syndrome-related skin complications by 3D imaging of the skin and the connective tissue. Our aim was to study effects of various types of diet-induced obesity in mice using these methods. We examined mice on different diets for 32 weeks. The collagen morphology was evaluated four times in vivo by SHG microscopy, and adipocytes were examined once at the end of experiment by ex vivo CARS method. A strong correlation was found between the body weight and the adipocyte size, while we found that the SHG intensity of dermal collagen reduces considerably with increasing body weight. Obese mice on high-fat diet showed worse results than those on high-fat - high-fructose diet. Animals on high-fructose diet did not gain more weight than those on ordinary diet despite of the increased calorie intake, but their collagen damage was nonetheless significant. Obesity and high sugar intake damages the skin, mainly the dermal connective tissue and subcutaneous adipose tissue, which efficiently can be monitored by in vivo SHG and ex vivo CARS microscopy. PMID:27895989

  16. Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats.

    PubMed

    Paulino, Gabriel; Barbier de la Serre, Claire; Knotts, Trina A; Oort, Pieter J; Newman, John W; Adams, Sean H; Raybould, Helen E

    2009-04-01

    The vagal afferent pathway is important in short-term regulation of food intake, and decreased activation of this neural pathway with long-term ingestion of a high-fat diet may contribute to hyperphagic weight gain. We tested the hypothesis that expression of genes encoding receptors for orexigenic factors in vagal afferent neurons are increased by long-term ingestion of a high-fat diet, thus supporting orexigenic signals from the gut. Obesity-prone (DIO-P) rats fed a high-fat diet showed increased body weight and hyperleptinemia compared with low-fat diet-fed controls and high-fat diet-induced obesity-resistant (DIO-R) rats. Expression of the type I cannabinoid receptor and growth hormone secretagogue receptor 1a in the nodose ganglia was increased in DIO-P compared with low-fat diet-fed controls or DIO-R rats. Shifts in the balance between orexigenic and anorexigenic signals within the vagal afferent pathway may influence food intake and body weight gain induced by high fat diets.

  17. Increased expression of receptors for orexigenic factors in nodose ganglion of diet-induced obese rats

    PubMed Central

    Paulino, Gabriel; Barbier de la Serre, Claire; Knotts, Trina A.; Oort, Pieter J.; Newman, John W.; Adams, Sean H.; Raybould, Helen E.

    2009-01-01

    The vagal afferent pathway is important in short-term regulation of food intake, and decreased activation of this neural pathway with long-term ingestion of a high-fat diet may contribute to hyperphagic weight gain. We tested the hypothesis that expression of genes encoding receptors for orexigenic factors in vagal afferent neurons are increased by long-term ingestion of a high-fat diet, thus supporting orexigenic signals from the gut. Obesity-prone (DIO-P) rats fed a high-fat diet showed increased body weight and hyperleptinemia compared with low-fat diet-fed controls and high-fat diet-induced obesity-resistant (DIO-R) rats. Expression of the type I cannabinoid receptor and growth hormone secretagogue receptor 1a in the nodose ganglia was increased in DIO-P compared with low-fat diet-fed controls or DIO-R rats. Shifts in the balance between orexigenic and anorexigenic signals within the vagal afferent pathway may influence food intake and body weight gain induced by high fat diets. PMID:19190260

  18. Leptin resistance and diet-induced obesity: central and peripheral actions of leptin.

    PubMed

    Sáinz, Neira; Barrenetxe, Jaione; Moreno-Aliaga, María J; Martínez, José Alfredo

    2015-01-01

    Obesity is a chronic disease that represents one of the most serious global health burdens associated to an excess of body fat resulting from an imbalance between energy intake and expenditure, which is regulated by environmental and genetic interactions. The adipose-derived hormone leptin acts via a specific receptor in the brain to regulate energy balance and body weight, although this protein can also elicit a myriad of actions in peripheral tissues. Obese individuals, rather than be leptin deficient, have in most cases, high levels of circulating leptin. The failure of these high levels to control body weight suggests the presence of a resistance process to the hormone that could be partly responsible of disturbances on body weight regulation. Furthermore, leptin resistance can impair physiological peripheral functions of leptin such as lipid and carbohydrate metabolism and nutrient intestinal utilization. The present document summarizes those findings regarding leptin resistance development and the role of this hormone in the development and maintenance of an obese state. Thus, we focused on the effect of the impaired leptin action on adipose tissue, liver, skeletal muscle and intestinal function and the accompanying relationships with diet-induced obesity. The involvement of some inflammatory mediators implicated in the development of obesity and their roles in leptin resistance development are also discussed.

  19. Adverse events of herbal food supplements for body weight reduction: systematic review.

    PubMed

    Pittler, M H; Schmidt, K; Ernst, E

    2005-05-01

    Herbal weight-loss supplements are marketed with claims of effectiveness. Our earlier systematic review identified data from double-blind, randomized controlled trials for a number of herbal supplements. The aim of this systematic review was to assess all clinical evidence of adverse events of herbal food supplements for body weight reduction for which effectiveness data from rigorous clinical trials exist. We assessed Ephedra sinica, Garcinia cambogia, Paullinia cupana, guar gum, Plantago psyllium, Ilex paraguariensis and Pausinystalia yohimbe. Literature searches were conducted on Medline, Embase, Amed and The Cochrane Library. Data were also requested from the spontaneous reporting scheme of the World Health Organization. We hand-searched relevant medical journals and our own files. There were no restrictions regarding the language of publication. The results show that adverse events including hepatic injury and death have been reported with the use of some herbal food supplements. For herbal ephedra and ephedrine-containing food supplements an increased risk of psychiatric, autonomic or gastrointestinal adverse events and heart palpitations has been reported. In conclusion, adverse events are reported for a number of herbal food supplements, which are used for reducing body weight. Although the quality of the data does not justify definitive attribution of causality in most cases, the reported risks are sufficient to shift the risk-benefit balance against the use of most of the reviewed herbal weight-loss supplements. Exceptions are Garcinia cambogia and yerba mate, which merit further investigation.

  20. Phentermine/topiramate for weight reduction and treatment of adverse metabolic consequences in obesity.

    PubMed

    Bays, H E; Gadde, K M

    2011-12-01

    Phentermine hydrochloride is a noradrenergic sympathetic amine approved for decades by the U.S. Food and Drug Administration (FDA) at doses as high as 37.5 mg/day for the short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide marketed since 1996, and approved by the FDA for seizure disorders at doses up to 400 mg/day and for the prevention of migraine headaches at doses up to 100 mg/day. Clinical trial data suggest topiramate promotes weight loss. The prescribing information of neither agent describes adverse drug interactions with the other. The controlled-release formulation of phentermine and topiramate at low, medium and full doses (with full dose containing 15 mg of phentermine hydrochloride and 92 mg of topiramate) promotes weight reduction, with clinical trial data supporting improvement in adiposopathic consequences leading to metabolic diseases. Reported adverse events with this combination agent are as expected, based upon knowledge of the individual components.

  1. Reduction of weight loss and tumour size in a cachexia model by a high fat diet.

    PubMed Central

    Tisdale, M. J.; Brennan, R. A.; Fearon, K. C.

    1987-01-01

    An attempt has been made to reverse cachexia and to selectively deprive the tumour of metabolic substrates for energy production by feeding a ketogenic regime, since ketone bodies are considered important in maintaining homeostasis during starvation. As a model we have used a transplantable mouse adenocarcinoma of the colon (MAC 16) which produces extensive weight loss without a reduction in food intake. When mice bearing the MAC16 tumour were fed on diets in which up to 80% of the energy was supplied as medium chain triglycerides (MCT) with or without arginine 3-hydroxybutyrate host weight loss was reduced in proportion to the fat content of the diet, and there was also a reduction in the percentage contribution of the tumour to the final body weight. The increase in carcass weight in tumour-bearing mice fed high levels of MCT was attributable to an increase in both the fat and the non-fat carcass mass. Blood levels of free fatty acids (FFA) were significantly reduced by MCT addition. The levels of both acetoacetate and 3-hydroxybutyrate were elevated in mice fed the high fat diets, and tumour-bearing mice fed the normal diet did not show increased plasma levels of ketone bodies over the non-tumour-bearing group despite the loss of carcass lipids. Both blood glucose and plasma insulin levels were reduced in mice bearing the MAC16 tumour and this was not significantly altered by feeding the high fat diets. The elevation in ketone bodies may account for the retention of both the fat and the non-fat carcass mass. This is the first example of an attempt to reverse cachexia by a diet based on metabolic differences between tumour and host tissues, which aims to selectively feed the host at the expense of the tumour. PMID:3620317

  2. Numerical solution for weight reduction model due to health campaigns in Spain

    NASA Astrophysics Data System (ADS)

    Mohammed, Maha A.; Noor, Noor Fadiya Mohd; Siri, Zailan; Ibrahim, Adriana Irawati Nur

    2015-10-01

    Transition model between three subpopulations based on Body Mass Index of Valencia community in Spain is considered. No changes in population nutritional habits and public health strategies on weight reduction until 2030 are assumed. The system of ordinary differential equations is solved using Runge-Kutta method of higher order. The numerical results obtained are compared with the predicted values of subpopulation proportion based on statistical estimation in 2013, 2015 and 2030. Relative approximate error is calculated. The consistency of the Runge-Kutta method in solving the model is discussed.

  3. Thermal Earth Resource Monitoring Instrument (THERMI) size, weight and power reduction

    NASA Astrophysics Data System (ADS)

    Newswander, T.; Bergen, Z.; Hancock, J.; Hansen, S.; Shumway, A.; Stauder, J.; Williams, D.

    2015-09-01

    The Thermal Earth Resource Monitoring Instrument (THERMI) has been designed to meet stringent Landsat heritage requirements with reduced size, weight and power (SWaP). The instrument design provides Earth resource monitoring through the use of two long-wave infrared bands that measure the land surface temperatures. These bands are especially valuable for monitoring water resources and water use. Instrument subsystems, including electronics, cryocooler, thermal management, optical telescope assembly, focal plane module, in-flight calibrator, and scene select mirror were studied and conceptually designed to reduce overall THERMI SWaP. Reductions in SWaP make it possible for THERMI to fit on a small satellite bus with room available for an additional optical instrument. Since mission cost historically correlates well with mass and power on-orbit, it is expected that significant cost savings will result from the predicted SWaP reductions.

  4. A Hamster Model of Diet-Induced Obesity for Preclinical Evaluation of Anti-Obesity, Anti-Diabetic and Lipid Modulating Agents

    PubMed Central

    Hansen, Gitte; Fabricius, Katrine; Hansen, Henrik B.; Jelsing, Jacob; Vrang, Niels

    2015-01-01

    Aim Unlike rats and mice, hamsters develop hypercholesterolemia, and hypertriglyceridemia when fed a cholesterol-rich diet. Because hyperlipidemia is a hallmark of human obesity, we aimed to develop and characterize a novel diet-induced obesity (DIO) and hypercholesterolemia Golden Syrian hamster model. Methods and Results Hamsters fed a highly palatable fat- and sugar-rich diet (HPFS) for 12 weeks showed significant body weight gain, body fat accumulation and impaired glucose tolerance. Cholesterol supplementation to the diet evoked additional hypercholesterolemia. Chronic treatment with the GLP-1 analogue, liraglutide (0.2 mg/kg, SC, BID, 27 days), normalized body weight and glucose tolerance, and lowered blood lipids in the DIO-hamster. The dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin (3.0 mg/kg, PO, QD) also improved glucose tolerance. Treatment with peptide YY3-36 (PYY3-36, 1.0 mg/kg/day) or neuromedin U (NMU, 1.5 mg/kg/day), continuously infused via a subcutaneous osmotic minipump for 14 days, reduced body weight and energy intake and changed food preference from HPFS diet towards chow. Co-treatment with liraglutide and PYY3-36 evoked a pronounced synergistic decrease in body weight and food intake with no lower plateau established. Treatment with the cholesterol uptake inhibitor ezetimibe (10 mg/kg, PO, QD) for 14 days lowered plasma total cholesterol with a more marked reduction of LDL levels, as compared to HDL, indicating additional sensitivity to cholesterol modulating drugs in the hyperlipidemic DIO-hamster. In conclusion, the features of combined obesity, impaired glucose tolerance and hypercholesterolemia in the DIO-hamster make this animal model useful for preclinical evaluation of novel anti-obesity, anti-diabetic and lipid modulating agents. PMID:26266945

  5. A novel and selective melanin-concentrating hormone receptor 1 antagonist ameliorates obesity and hepatic steatosis in diet-induced obese rodent models.

    PubMed

    Kawata, Yayoi; Okuda, Shoki; Hotta, Natsu; Igawa, Hideyuki; Takahashi, Masashi; Ikoma, Minoru; Kasai, Shizuo; Ando, Ayumi; Satomi, Yoshinori; Nishida, Mayumi; Nakayama, Masaharu; Yamamoto, Syunsuke; Nagisa, Yasutaka; Takekawa, Shiro

    2017-02-05

    Melanin-concentrating hormone (MCH), a cyclic neuropeptide expressed predominantly in the lateral hypothalamus, plays an important role in the control of feeding behavior and energy homeostasis. Mice lacking MCH or MCH1 receptor are resistant to diet-induced obesity (DIO) and MCH1 receptor antagonists show potent anti-obesity effects in preclinical studies, indicating that MCH1 receptor is a promising target for anti-obesity drugs. Moreover, recent studies have suggested the potential of MCH1 receptor antagonists for treatment of non-alcoholic fatty liver disease (NAFLD). In the present study, we show the anti-obesity and anti-hepatosteatosis effect of our novel MCH1 receptor antagonist, Compound A. Repeated oral administration of Compound A resulted in dose-dependent body weight reduction and had an anorectic effect in DIO mice. The body weight lowering effect of Compound A was more potent than that of pair-feeding. Compound A also reduced lipid content and the expression level of lipogenesis-, inflammation-, and fibrosis-related genes in the liver of DIO mice. Conversely, intracerebroventricular infusion of MCH caused induction of hepatic steatosis as well as increase in body weight in high-fat diet-fed wild type mice, but not MCH1 receptor knockout mice. The pair-feeding study revealed the MCH-MCH1 receptor system affects hepatic steatosis through a mechanism that is independent of body weight change. Metabolome analysis demonstrated that Compound A upregulated lipid metabolism-related molecules, such as acylcarnitines and cardiolipins, in the liver. These findings suggest that our novel MCH1 receptor antagonist, Compound A, exerts its beneficial therapeutic effect on NAFLD and obesity through a central MCH-MCH1 receptor pathway.

  6. Diet-induced obesity causes long QT and reduces transcription of voltage-gated potassium channels.

    PubMed

    Huang, Haiyan; Amin, Vaibhav; Gurin, Michael; Wan, Elaine; Thorp, Edward; Homma, Shunichi; Morrow, John P

    2013-06-01

    In humans, obesity is associated with long QT, increased frequency of premature ventricular complexes, and sudden cardiac death. The mechanisms of the pro-arrhythmic electrophysiologic remodeling of obesity are poorly understood. We tested the hypothesis that there is decreased expression of voltage-gated potassium channels in the obese heart, leading to long QT. Using implanted telemeters, we found that diet-induced obese (DIO) wild-type mice have impaired cardiac repolarization, demonstrated by long QT, as well as more frequent ventricular ectopy, similar to obese humans. DIO mice have reduced protein and mRNA levels of the potassium channel Kv1.5 caused by a reduction of the transcription factor cyclic AMP response element binding protein (CREB) in DIO hearts. We found that CREB knock-down by siRNA reduces Kv1.5, CREB binds to the Kv1.5 promoter in the heart, and CREB increases transcription of mouse and human Kv1.5 promoters. The reduction in CREB protein during lipotoxicity can be rescued by inhibiting protein kinase D (PKD). Our results identify a mechanism for obesity-induced electrophysiologic remodeling in the heart, namely PKD-induced reduction of CREB, which in turn decreases expression of the potassium channel Kv1.5.

  7. Diet-Induced Obesity in Male Mice Is Associated with Reduced Fertility and Potentiation of Acrylamide-Induced Reproductive Toxicity1

    PubMed Central

    Ghanayem, Burhan I.; Bai, Re; Kissling, Grace E.; Travlos, Greg; Hoffler, Undi

    2009-01-01

    The prevalence of human obesity and related chronic disorders such as diabetes, cardiovascular diseases, and cancer is rapidly increasing. Human studies have shown a direct relationship between obesity and infertility. The objective of the current work was to examine the effect of diet-induced obesity on male fertility and the effect of obesity on susceptibility to chemical-induced reproductive toxicity. From 5 to 30 wk of age, genetically intact male C57Bl/6J mice were fed a normal diet or one in which 60% of the kilocalories were from lard. Obese mice exhibited significant differences in the mRNA of several genes within the testes in comparison to lean males. Pparg was increased 2.2-fold, whereas Crem, Sh2b1, Dhh, Igf1, and Lepr were decreased 6.7, 1.4, 3.2, 1.6, and 7.2-fold, respectively. The fertility of male mice was compared through mating with control females. Acrylamide (AA)-induced reproductive toxicity was assessed in obese or lean males treated with water or 25 mg AA kg−1 day−1 via gavage for 5 days and then mated to control females. Percent body fat and weight were significantly increased in mice fed a high-fat vs. a normal diet. Obesity resulted in significant reduction in plugs and pregnancies of control females partnered with obese vs. lean males. Serum leptin and insulin levels were each approximately 5-fold higher in obese vs. age-matched lean mice. Sperm from obese males exhibited decreased motility and reduced hyperactivated progression vs. lean mice. Treatment with AA exacerbated male infertility of obese and lean mice; however, this effect was more pronounced in obese mice. Further, females partnered with AA-treated obese mice exhibited a further decrease in the percentage of live fetuses, whereas the percentage of resorptions increased. This work demonstrated that diet-induced obesity in mice caused a significant reduction in male fertility and exacerbated AA-induced reproductive toxicity and germ cell mutagenicity. PMID:19696015

  8. Optimization of brain penetrant 11β-hydroxysteroid dehydrogenase type I inhibitors and in vivo testing in diet-induced obese mice.

    PubMed

    Goldberg, Frederick W; Dossetter, Alexander G; Scott, James S; Robb, Graeme R; Boyd, Scott; Groombridge, Sam D; Kemmitt, Paul D; Sjögren, Tove; Gutierrez, Pablo Morentin; deSchoolmeester, Joanne; Swales, John G; Turnbull, Andrew V; Wild, Martin J

    2014-02-13

    11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been widely considered by the pharmaceutical industry as a target to treat metabolic syndrome in type II diabetics. We hypothesized that central nervous system (CNS) penetration might be required to see efficacy. Starting from a previously reported pyrimidine compound, we removed hydrogen-bond donors to yield 3, which had modest CNS penetration. More significant progress was achieved by changing the core to give 40, which combines good potency and CNS penetration. Compound 40 was dosed to diet-induced obese (DIO) mice and gave excellent target engagement in the liver and high free exposures of drug, both peripherally and in the CNS. However, no body weight reduction or effects on glucose or insulin were observed in this model. Similar data were obtained with a structurally diverse thiazole compound 51. This work casts doubt on the hypothesis that localized tissue modulation of 11β-HSD1 activity alleviates metabolic syndrome.

  9. Effect of Green Tea Extract on Systemic Metabolic Homeostasis in Diet-Induced Obese Mice Determined via RNA-Seq Transcriptome Profiles

    PubMed Central

    Choi, Ji-Young; Kim, Ye Jin; Ryu, Ri; Cho, Su-Jung; Kwon, Eun-Young; Choi, Myung-Sook

    2016-01-01

    Green tea (GT) has various health effects, including anti-obesity properties. However, the multiple molecular mechanisms of the effects have not been fully determined. The aim of this study was to elucidate the anti-obesity effects of GT via the analysis of its metabolic and transcriptional responses based on RNA-seq profiles. C57BL/6J mice were fed a normal, high-fat (60% energy as fat), or high-fat + 0.25% (w/w) GT diet for 12 weeks. The GT extract ameliorated obesity, hepatic steatosis, dyslipidemia, and insulin resistance in diet-induced obesity (DIO) mice. GT supplementation resulted in body weight gain reduction than mice fed high-fat through enhanced energy expenditure, and reduced adiposity. The transcriptome profiles of epididymal white adipose tissue (eWAT) suggested that GT augments transcriptional responses to the degradation of branched chain amino acids (BCAAs), as well as AMP-activated protein kinase (AMPK) signaling, which suggests enhanced energy homeostasis. Our findings provide some significant insights into the effects of GT for the prevention of obesity and its comorbidities. We demonstrated that the GT extract contributed to the regulation of systemic metabolic homeostasis via transcriptional responses to not only lipid and glucose metabolism, but also amino acid metabolism via BCAA degradation in the adipose tissue of DIO mice. PMID:27754422

  10. Macrophage Migration Inhibitory Factor (MIF) Knockout Preserves Cardiac Homeostasis through Alleviating Akt-Mediated Myocardial Autophagy Suppression in High Fat Diet-Induced Obesity

    PubMed Central

    Xu, Xihui; Ren, Jun

    2014-01-01

    Background Macrophage migration inhibitory factor (MIF) plays a role in the development of obesity and diabetes. However, whether MIF plays a role in fat diet-induced obesity and associated cardiac anomalies still remains unknown. The aim of this study was to examine the impact of MIF knockout on high fat diet-induced obesity, obesity-associated cardiac anomalies and the underlying mechanisms involved with a focus on Akt-mediated autophagy. Methods Adult male wild-type (WT) and MIF knockout (MIF−/−) mice were placed on 45% high fat diet for 5 months. Oxygen consumption, CO2 production, respiratory exchange ratio (RER), locomotor activity, and heat generation were measured using energy calorimeter. Echocardiographic, cardiomyocyte mechanical and intracellular Ca2+ properties were assessed. Apoptosis was examined using TUNEL staining and western blot analysis. Akt signaling pathway and autophagy markers were evaluated. Cardiomyocytes isolated from WT and MIF−/− mice were treated with recombinant mouse MIF (rmMIF). Results High fat diet feeding elicited increased body weight gain, insulin resistance, and caloric disturbance in WT and MIF−/− mice. High fat diet induced unfavorable geometric, contractile and histological changes in the heart, the effects of which were alleviated by MIF knockout. In addition, fat diet-induced cardiac anomalies were associated with Akt activation and autophagy suppression, which were nullified by MIF deficiency. In cardiomyocytes from WT mice, autophagy was inhibited by exogenous rmMIF through Akt activation. In addition, MIF knockout rescued palmitic acid-induced suppression of cardiomyocyte autophagy, the effect of which was nullified by rmMIF. Conclusions These results indicate that MIF knockout preserved obesity-associated cardiac anomalies without affecting fat diet-induced obesity, probably through restoring myocardial autophagy in an Akt-dependent manner. Our findings provide new insights for the role of MIF in obesity

  11. Diet-Induced Obesity and Circadian Disruption of Feeding Behavior.

    PubMed

    Blancas-Velazquez, Aurea; Mendoza, Jorge; Garcia, Alexandra N; la Fleur, Susanne E

    2017-01-01

    Feeding behavior shows a rhythmic daily pattern, which in nocturnal rodents is observed mainly during the dark period. This rhythmicity is under the influence of the hypothalamic suprachiasmatic nucleus (SCN), the main biological clock. Nevertheless, various studies have shown that in rodent models of obesity, using high-energy diets, the general locomotor activity and feeding rhythms can be disrupted. Here, we review the data on the effects of diet-induced obesity (DIO) on locomotor activity and feeding patterns, as well as the effect on the brain sites within the neural circuitry involved in metabolic and rewarding feeding behavior. In general, DIO may alter locomotor activity by decreasing total activity. On the other hand, DIO largely alters eating patterns, producing increased overall ingestion and number of eating bouts that can extend to the resting period. Furthermore, within the hypothalamic areas, little effect has been reported on the molecular circadian mechanism in DIO animals with ad libitum hypercaloric diets and little or no data exist so far on its effects on the reward system areas. We further discuss the possibility of an uncoupling of metabolic and reward systems in DIO and highlight a gap of circadian and metabolic research that may help to better understand the implications of obesity.

  12. Diet-Induced Obesity and Circadian Disruption of Feeding Behavior

    PubMed Central

    Blancas-Velazquez, Aurea; Mendoza, Jorge; Garcia, Alexandra N.; la Fleur, Susanne E.

    2017-01-01

    Feeding behavior shows a rhythmic daily pattern, which in nocturnal rodents is observed mainly during the dark period. This rhythmicity is under the influence of the hypothalamic suprachiasmatic nucleus (SCN), the main biological clock. Nevertheless, various studies have shown that in rodent models of obesity, using high-energy diets, the general locomotor activity and feeding rhythms can be disrupted. Here, we review the data on the effects of diet-induced obesity (DIO) on locomotor activity and feeding patterns, as well as the effect on the brain sites within the neural circuitry involved in metabolic and rewarding feeding behavior. In general, DIO may alter locomotor activity by decreasing total activity. On the other hand, DIO largely alters eating patterns, producing increased overall ingestion and number of eating bouts that can extend to the resting period. Furthermore, within the hypothalamic areas, little effect has been reported on the molecular circadian mechanism in DIO animals with ad libitum hypercaloric diets and little or no data exist so far on its effects on the reward system areas. We further discuss the possibility of an uncoupling of metabolic and reward systems in DIO and highlight a gap of circadian and metabolic research that may help to better understand the implications of obesity. PMID:28223912

  13. Adaptation to chronic hypoxia during diet-induced ketosis.

    PubMed

    Puchowicz, Michelle A; Emancipator, Douglas S; Xu, Kui; Magness, Danielle L; Ndubuizu, Obinna I; Lust, W David; LaManna, Joseph C

    2005-01-01

    It is recognized that brain oxygen deprivation results in increased glycolysis and lactate accumulation. Moreover, glucose metabolism is altered during starvation or diet, resulting in increased plasma ketones (acetoacetate + beta-hydroxybutyrate; BHB). We investigated glucose and lactate adaptation to hypoxia in concurrence with diet-induced ketosis. Male Wistar rats were fed standard (STD), ketogenic (high fat; KG), or carbohydrate-rich (low fat; CHO) diets for 3 wks and then exposed to hypobaric (0.5 ATM) or normobaric atmosphere for 3 wks while on their diets. Lactate, ketones, and glucose concentrations were measured in plasma (mM) and brain tissue (mmol/g). Plasma and tissue ketone levels were elevated up to 12-fold in the KG fed groups compared with other groups (STD and CHO), with the hypoxic KG group reaching the highest levels (2.6 +/- 1.3 mM and 0.3 +/- 0.1 mmol/g; mean +/- SD). Tissue lactate levels in the hypoxic ketotic rats (4.7 +/- 1.3 mM) were comparable with normoxic STD (5.0 +/- 0.7 mM) and significantly lower (ANOVA P < .05) than the hypoxic STD rats (6.1 +/- 1.0 mM). These data indicate that adaptation to hypoxia did not interfere with ketosis, and that ketosis during hypoxia may lower lactate levels in brain, suggesting decreased glycolysis or increased glucose disposal.

  14. Arginase inhibition restores endothelial function in diet-induced obesity.

    PubMed

    Chung, Ji Hyung; Moon, Jiyoung; Lee, Youn Sue; Chung, Hye-Kyung; Lee, Seung-Min; Shin, Min-Jeong

    2014-08-22

    Arginase may play a major role in the regulation of vascular function in various cardiovascular disorders by impairing nitric oxide (NO) production. In the current study, we investigated whether supplementation of the arginase inhibitor N(ω)-hydroxy-nor-l-arginine (nor-NOHA) could restore endothelial function in an animal model of diet-induced obesity. Arginase 1 expression was significantly lower in the aorta of C57BL/6J mice fed a high-fat diet (HFD) supplemented with nor-NOHA (40mgkg(-1)/day) than in mice fed HFD without nor-NOHA. Arginase inhibition led to considerable increases in eNOS expression and NO levels and significant decreases in the levels of circulating ICAM-1. These findings were further confirmed by the results of siRNA-mediated knockdown of Arg in human umbilical vein endothelial cells. In conclusion, arginase inhibition can help restore dysregulated endothelial function by increasing the eNOS-dependent NO production in the endothelium, indicating that arginase could be a therapeutic target for correcting obesity-induced vascular endothelial dysfunction.

  15. Effects of Astrocaryum aculeatum Meyer (Tucumã) on Diet-Induced Dyslipidemic Rats.

    PubMed

    Craveiro Holanda Malveira Maia, Geórgia; da Silva Campos, Mozer; Barros-Monteiro, Janice; Eduardo Lucas Castillo, Juan; Soares Faleiros, Murilo; Souza de Aquino Sales, Rejane; Moraes Lopes Galeno, Denise; Lira, Edson; das Chagas do Amaral Souza, Francisca; Ortiz, Carmen; Morales, Luisa; Piccolotto Carvalho, Rosany

    2014-01-01

    An in vivo study was conducted to assess the effects of the consumption of Astrocaryum aculeatum Amazon Meyer (tucumã) in the treatment of diet-induced dyslipidemia in sedentary and exercised Wistar rats. With an average weight of 350 grams, 40 male rats were divided into 4 subgroups of 10. The sedentary control group (SCG) was fed with commercial feed, while the sedentary treatment group (STG) was fed with a ration of tucumã. In addition to the sedentary groups, two exercise groups were formed. The Exercised control group (ECG) was fed with commercial food and the exercised treatment group (ETG) was fed with a ration of tucumã. Body weight gain and food intake were monitored during the experiment. Plasma was analyzed for cholesterol, triglycerides, HDL-C, LDL-C, VLDL, total protein, glucose, insulin, and leptin concentrations. Our results show that the ECG group tended to consume more food, while the groups that were fed with tucumã pulp (STG and ETG) presented a greater tendency to gain body mass. ECG group showed a tendency towards a higher concentration of cholesterol in plasma, while STG and ETG presented higher absolute values for triglycerides and VLDL. No hypolipiemic effect was observed related to tucuma ingestion.

  16. Gestational exercise protects adult male offspring from high-fat diet induced hepatic steatosis

    PubMed Central

    Sheldon, Ryan D.; Blaize, A. Nicole; Fletcher, Justin A.; Pearson, Kevin J.; Donkin, Shawn; Newcomer, Sean C.; Rector, R. Scott

    2015-01-01

    Background & Aims Mounting evidence indicates that maternal exercise confers protection to adult offspring against various diseases. Here we hypothesized that maternal exercise during gestation would reduce high fat diet (HFD) induced hepatic steatosis in adult rat offspring. Methods Following conception, pregnant dams were divided into either voluntary wheel running exercise (GE) or wheel-locked sedentary (GS) groups throughout gestation (days 4-21). Post-weaning, offspring received either normal chow diet (ND; 10% fat, 70% carbohydrate, 20% protein) or high-fat diet (HFD; 45% fat, 35% carbohydrate, and 20% protein) until sacrifice at 4-or 8-months of age. Results GE did not affect offspring birth weight or litter size. HFD feeding in offspring increased weight gain, % body fat, and glucose tolerance test area under the curve (GTT-AUC). Male offspring from GE dams had reduced % body fat across all ages (p < 0.05). In addition, 8-mo male offspring from GE dams were protected against HFD-induced hepatic steatosis, which was associated with increased markers of hepatic mitochondrial biogenesis (PGC-1α and TFAM), autophagic potential (ATG12:ATG5 conjugation) and hepatic triacylglycerol secretion (MTTP). Conclusions The current study provides the first evidence that gestational exercise can reduce susceptibility to high fat diet induced hepatic steatosis in adult male offspring. PMID:26325536

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

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

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

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

    PubMed Central

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

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

  19. miR-155 Deletion in Female Mice Prevents Diet-Induced Obesity

    PubMed Central

    Gaudet, Andrew D.; Fonken, Laura K.; Gushchina, Liubov V.; Aubrecht, Taryn G.; Maurya, Santosh K.; Periasamy, Muthu; Nelson, Randy J.; Popovich, Phillip G.

    2016-01-01

    Obesity is a growing epidemic in developed countries. Obese individuals are susceptible to comorbidities, including cardiovascular disease and metabolic disorder. Increasing the ability of adipose tissue to expend excess energy could improve protection from obesity. One promising target is microRNA (miR)-155-5p. We demonstrate that deletion of miR-155 (-5p and -3p) in female mice prevents diet-induced obesity. Body weight gain did not differ between wild-type (WT) and miR-155 knockout (KO) mice fed control diet (CD); however, miR-155 KO mice fed high-fat diet (HFD) gained 56% less body weight and 74% less gonadal white adipose tissue (WAT) than WT mice. Enhanced WAT thermogenic potential, brown adipose tissue differentiation, and/or insulin sensitivity might underlie this obesity resistance. Indeed, miR-155 KO mice on HFD had 21% higher heat release than WT HFD mice. Compared to WT adipocytes, miR-155 KO adipocytes upregulated brown (Ucp1, Cidea, Pparg) and white (Fabp4, Pnpla2, AdipoQ, Fasn) adipogenic genes, and glucose metabolism genes (Glut4, Irs1). miR-155 deletion abrogated HFD-induced adipocyte hypertrophy and WAT inflammation. Therefore, miR-155 deletion increases adipogenic, insulin sensitivity, and energy uncoupling machinery, while limiting inflammation in WAT, which together could restrict HFD-induced fat accumulation. Our results identify miR-155 as a novel candidate target for improving obesity resistance. PMID:26953132

  20. Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth.

    PubMed

    James, Britnie R; Tomanek-Chalkley, Ann; Askeland, Eric J; Kucaba, Tamara; Griffith, Thomas S; Norian, Lyse A

    2012-08-01

    Obesity is a mounting health concern in the United States and is associated with an increased risk for developing several cancers, including renal cell carcinoma (RCC). Despite this, little is known regarding the impact of obesity on antitumor immunity. Because dendritic cells (DC) are critical regulators of antitumor immunity, we examined the combined effects of obesity and tumor outgrowth on DC function. Using a diet-induced obesity (DIO) model, DC function was evaluated in mice bearing orthotopic RCC and in tumor-free controls. Tumor-free DIO mice had profoundly altered serum cytokine and chemokine profiles, with upregulation of 15 proteins, including IL-1α, IL-17, and LIF. Tumor-free DIO mice had elevated percentages of conventional splenic DC that were impaired in their ability to stimulate naive T cell expansion, although they were phenotypically similar to normal weight (NW) controls. In DIO mice, intrarenal RCC tumor challenge in the absence of therapy led to increased local infiltration by T cell-suppressive DC and accelerated early tumor outgrowth. Following administration of a DC-dependent immunotherapy, established RCC tumors regressed in normal weight mice. The same immunotherapy was ineffective in DIO mice and was characterized by an accumulation of regulatory DC in tumor-bearing kidneys, decreased local infiltration by IFN-γ-producing CD8 T cells, and progressive tumor outgrowth. Our results suggest that the presence of obesity as a comorbidity can impair the efficacy of DC-dependent antitumor immunotherapies.

  1. Effects of Astrocaryum aculeatum Meyer (Tucumã) on Diet-Induced Dyslipidemic Rats

    PubMed Central

    Craveiro Holanda Malveira Maia, Geórgia; da Silva Campos, Mozer; Barros-Monteiro, Janice; Eduardo Lucas Castillo, Juan; Soares Faleiros, Murilo; Souza de Aquino Sales, Rejane; Moraes Lopes Galeno, Denise; Lira, Edson; das Chagas do Amaral Souza, Francisca; Ortiz, Carmen

    2014-01-01

    An in vivo study was conducted to assess the effects of the consumption of Astrocaryum aculeatum Amazon Meyer (tucumã) in the treatment of diet-induced dyslipidemia in sedentary and exercised Wistar rats. With an average weight of 350 grams, 40 male rats were divided into 4 subgroups of 10. The sedentary control group (SCG) was fed with commercial feed, while the sedentary treatment group (STG) was fed with a ration of tucumã. In addition to the sedentary groups, two exercise groups were formed. The Exercised control group (ECG) was fed with commercial food and the exercised treatment group (ETG) was fed with a ration of tucumã. Body weight gain and food intake were monitored during the experiment. Plasma was analyzed for cholesterol, triglycerides, HDL-C, LDL-C, VLDL, total protein, glucose, insulin, and leptin concentrations. Our results show that the ECG group tended to consume more food, while the groups that were fed with tucumã pulp (STG and ETG) presented a greater tendency to gain body mass. ECG group showed a tendency towards a higher concentration of cholesterol in plasma, while STG and ETG presented higher absolute values for triglycerides and VLDL. No hypolipiemic effect was observed related to tucuma ingestion. PMID:25165578

  2. Reductions in knee joint forces with weight loss are attenuated by gait adaptations in class III obesity.

    PubMed

    DeVita, Paul; Rider, Patrick; Hortobágyi, Tibor

    2016-03-01

    A consensus exists that high knee joint forces are a precursor to knee osteoarthritis and weight loss reduces these forces. Because large weight loss also leads to increased step length and walking velocity, knee contact forces may be reduced less than predicted by the magnitude of weight loss. The purpose was to determine the effects of weight loss on knee muscle and joint loads during walking in Class III obese adults. We determined through motion capture, force platform measures and biomechanical modeling the effects of weight loss produced by gastric bypass surgery over one year on knee muscle and joint loads during walking at a standard, controlled velocity and at self-selected walking velocities. Weight loss equaling 412 N or 34% of initial body weight reduced maximum knee compressive force by 824 N or 67% of initial body weight when walking at the controlled velocity. These changes represent a 2:1 reduction in knee force relative to weight loss when walking velocity is constrained to the baseline value. However, behavioral adaptations including increased stride length and walking velocity in the self-selected velocity condition attenuated this effect by ∼50% leading to a 392 N or 32% initial body weight reduction in compressive force in the knee joint. Thus, unconstrained walking elicited approximately 1:1 ratio of reduction in knee force relative to weight loss and is more indicative of walking behavior than the standard velocity condition. In conclusion, massive weight loss produces dramatic reductions in knee forces during walking but when patients stride out and walk faster, these favorable reductions become substantially attenuated.

  3. Very low calorie ketogenic weight reduction diet in patients with cirrhosis: a case series.

    PubMed

    Temmerman, J C; Friedman, A N

    2013-11-18

    Weight reduction may be necessary in patients with end-stage liver disease (ESLD) before liver transplantation. Although very low calorie diets (VLCDs) are a highly effective weight loss strategy, they risk inducing protein-calorie malnutrition, sarcopenia and hepatic encephalopathy in ESLD patients. We report for the first time on the use of VCLDs in ESLD. Two severely obese individuals with ESLD underwent a modified VLCD to become eligible for liver transplantation. Patients consumed four protein supplements and one lean meal daily, equivalent to 800 kilocalories (kcal) and were closely monitored during the diet period. Subject 1, a 46-year-old male with alcoholic cirrhosis, lost 44.1 kg after 28 weeks on a modified VLCD. Liver function and MELD (model for end-stage liver disease) scores improved and he currently does not require listing for transplantation. Subject 2, a 64-year-old female with non-alcoholic steatohepatitis, lost 39.7 kg after a 30-week modified VLCD. She is awaiting liver transplantation listing with a stable MELD score. VLCDs were well tolerated by both patients without adverse effects. In conclusion, under close medical supervision VLCDs in patients with ESLD can be safe and effective in reducing weight, facilitating liver transplantation listing, and possibly improving liver damage.

  4. Inactivation of β-catenin results in the reduction of postnatal body weight gain.

    PubMed

    Wang, Hong-Tao; Zeng, Lin; Zhang, Xin; Li, Kui; Zu, Yong; Liu, Ji-wei; Liu, Yong-jie; Zhu, Zhi-chuan; Xiong, Zhi-Qi; Zheng, Jing; Hu, Ze-Lan

    2014-01-01

    Arcuate nucleus of hypothalamus (ARH) is the core component in the regulation circuits of food intake and energy homeostasis. ARH projections to other parts of the hypothalamus and to extrahypothalamic areas are established in the postnatal two weeks, which is a pivotal stage for individual development. β-Catenin, a cell adhesion protein and also the mediator of canonical Wnt signaling pathway, plays an important role in embryonic development and adult homeostasis. However, whether β-catenin plays any roles in the development of hypothalamus is not clear. Here, we report that perinatal conditional knockout of β-catenin by CamKIIα-Cre in forebrain reduces body weight gain from P8 and dramatically shortens life span. Quantitative PCR and in situ hybridization results showed the expression of NPY mRNA in the ARH of β-catenin CKO mice at P15 is obviously increased compared with that of littermate controls, whereas the expression of POMC mRNA is significantly decreased, which suggested the reduction of postnatal body weight gain might be due to the deficiency of food intake. Together, β-catenin might play an important role in the regulation of food intake and postnatal body weight gain probably through affecting the development of ARH circuits.

  5. Anti-apoptotic and Pro-survival Effects of Food Restriction on High-Fat Diet-Induced Obese Hearts.

    PubMed

    Lin, Yi-Yuan; Hsieh, Po-Shiuan; Cheng, Yu-Jung; Cheng, Shiu-Min; Chen, Chiao-Nan Joyce; Huang, Chih-Yang; Kuo, Chia-Hua; Kao, Chung-Lan; Shyu, Woei-Cherng; Lee, Shin-Da

    2017-04-01

    Food restriction and weight loss are known to prevent obesity-related heart diseases. This study investigates whether food restriction elicits anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts. Histopathological analysis, TUNEL assay, and Western blotting were performed on the excised hearts from three groups of Sprague-Dawley rats which were fed with regular chow diet (CON, 13.5 % fat), a high-fat ad libitum diet (HFa, 45 % fat), or a high-fat food-restricted diet (HFr, 45 % fat, maintaining the same weight as CON) for 12 weeks. Body weight, blood pressure, heart weight, triglycerides, insulin, HOMAIR, interstitial spaces, cardiac fibrosis, and cardiac TUNEL-positive apoptotic cells were increased in HFa relative to CON, whereas these parameters were decreased in HFr relative to HFa. The protein levels of cardiac Fas ligand, Fas receptors, Fas-associated death domain (FADD), activated caspase-8, and activated caspase-3 (Fas receptor-dependent apoptotic pathways), as well as t-Bid/Bid, Bax/Bcl-2, Bad/p-Bad, Cytochrome c, activated caspase-9, and activated caspase-3 (mitochondria-dependent apoptotic pathways) in HFr were lower than those in HFa. Moreover, the Bcl-xL and IGF-1-related components of IGF-1, p-PI3 K/PI3 K, p-Akt/Akt in HFr were higher than those in HFa. Our findings suggest that a restricted high-fat diet for maintaining weight control could diminish cardiac Fas receptor-dependent and mitochondria-dependent apoptotic pathways as well as might enhance IGF-1-related pro-survival pathways. In sum, food restriction for maintaining normal weight could elicit anti-apoptotic and pro-survival effects on high-fat diet-induced obese hearts.

  6. Low energy density diet, weight loss maintenance, and risk of cardiovascular disease following a recent weight reduction program: A randomized control trial

    PubMed Central

    Karimi, Golgis; Azadbakht, Leila; Haghighatdoost, Fahimeh; Esmaillzadeh, Ahmad

    2016-01-01

    Background: Little is known about the effects of a low energy dense diet on weight maintenance and cardiovascular risks following a recent weight reduction. Therefore, we assessed if weight maintenance, lipid profiles, and glycemic control differ between low energy density (LED) diet and usual diet consumers following a recent weight reduction. Materials and Methods: In this randomized controlled clinical trial study in a parallel design, we recruited 70 patients with the history of weight reduction in the recent 1 year. LED diet contained 30% fat, 15% protein, and 55% carbohydrate was administered to the test group, and a usual diet including 35% fat, 15% protein, and 50% carbohydrate was prescribed to the control group for 7 months. Dietary intake was assessed by using 3 days food records. Biochemical markers and anthropometric measures were done according to the standard protocol. Results: Weight reduced in LED diet consumers compared to usual diet consumers (−0.3 ± 0.2 vs. 1.3 ± 0.4%, P = 0.002). The results was the same regarding waist circumference (−0.4 ± 0.2 vs. 0.3 ± 0.1%, P = 0.004). Fasting blood sugar also decreased in LED diet group (−9.5 ± 0.8 vs. 0.4 ± 1.0%, P = 0.0001). LED diet group had a drop in percent change of their total cholesterol (−0.4 ± 0.5 vs. 2.05 ± 0.4%, P = 0.04) and low-density lipoprotein-cholesterol (4.8 ± 0.9 vs. −0.3 ± 0.9%, P = 0.002). Conclusion: Our findings confirmed beneficial effects of LED diet on attenuating weight regain in subjects with history of recent weight reduction. It might be derived from higher consumption of fruits, vegetables, and fiber among LED diet than usual diet consumers. PMID:27904578

  7. ARYL HYDROCARBON RECEPTOR DEFICIENCY PROTECTS MICE FROM DIET-INDUCED ADIPOSITY AND METABOLIC DISORDERS THROUGH INCREASED ENERGY EXPENDITURE

    PubMed Central

    Zhang, Zhi-Ming; Jaeger, Cassie D.; Krager, Stacey L.; Bottum, Kathleen M.; Liu, Jianghua; Liao, Duan-Fang; Tischkau, Shelley A.

    2015-01-01

    BACKGROUND/OBJECTIVES Epidemics of obesity and diabetes are escalating. High-calorie/high-fat food is a major cause for these global health issues, but molecular mechanisms underlying high-fat, diet-induced obesity are still not well understood. The aryl hydrocarbon receptor (AhR), a transcription factor that acts as a xenobiotic sensor, mediates environmental toxicant-induced obesity, insulin resistance and development of diabetes. AhR also influences lipid metabolism and diet-induced obesity. The effects of AhR deficiency on diet-induced obesity, hepatic steatosis and insulin resistance were examined. METHODS : Male wild type (WT), AhR null (AhR−/−) and AhR heterozygote (AhR+/−) mice were fed a normal chow diet (NCD, 10% kcal from fat) or a high-fat diet (HFD, 60% kcal from fat) for up to 14 weeks. Adiposity, adipose and liver morphology, insulin signaling, metabolic parameters and gene profiles were assessed. RESULTS AhR deficiency protected against HFD-induced obesity, hepatic steatosis, insulin resistance and inflammation. Moreover, AhR deficiency preserved insulin signaling in major metabolic tissues. These protective effects result from a higher energy expenditure in AhR-deficient mice compared to WT. Levels of transcript for both the thermogenic gene, uncoupling protein 1 (Ucp1), in brown adipose tissue and mitochondrial β-oxidation genes in muscle were significantly higher in AhR−/− and AhR+/− mice compared to WT. CONCLUSIONS This work documents a physiologically relevant function for AhR in regulation of body weight, hepatic fat deposition, insulin sensitivity and energy expenditure under HFD exposure, suggesting that AhR signaling may be developed as a potential therapeutic target for treatment of obesity and metabolic disorders. PMID:25907315

  8. Methionine sulfoxide reductase B1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

    PubMed

    Heo, Jung-Yoon; Cha, Hye-Na; Kim, Ki Young; Lee, Eujin; Kim, Suk-Jeong; Kim, Yong-Woon; Kim, Jong-Yeon; Lee, In-Kyu; Gladyshev, Vadim N; Kim, Hwa-Young; Park, So-Young

    2017-01-01

    Methionine-S-sulfoxide reductase (MsrA) protects against high-fat diet-induced insulin resistance due to its antioxidant effects. To determine whether its counterpart, methionine-R-sulfoxide reductase (MsrB) has similar effects, we compared MsrB1 knockout and wild-type mice using a hyperinsulinemic-euglycemic clamp technique. High-fat feeding for eight weeks increased body weights, fat masses, and plasma levels of glucose, insulin, and triglycerides to similar extents in wild-type and MsrB1 knockout mice. Intraperitoneal glucose tolerance test showed no difference in blood glucose levels between the two genotypes after eight weeks on the high-fat diet. The hyperglycemic-euglycemic clamp study showed that glucose infusion rates and whole body glucose uptakes were decreased to similar extents by the high-fat diet in both wild-type and MsrB1 knockout mice. Hepatic glucose production and glucose uptake of skeletal muscle were unaffected by MsrB1 deficiency. The high-fat diet-induced oxidative stress in skeletal muscle and liver was not aggravated in MsrB1-deficient mice. Interestingly, whereas MsrB1 deficiency reduced JNK protein levels to a great extent in skeletal muscle and liver, it markedly elevated phosphorylation of JNK, suggesting the involvement of MsrB1 in JNK protein activation. However, this JNK phosphorylation based on a p-JNK/JNK level did not positively correlate with insulin resistance in MsrB1-deficient mice. Taken together, our results show that, in contrast to MsrA deficiency, MsrB1 deficiency does not increase high-fat diet-induced insulin resistance in mice.

  9. Susceptibility of Different Mouse Wild Type Strains to Develop Diet-Induced NAFLD/AFLD-Associated Liver Disease

    PubMed Central

    Fengler, Vera H. I.; Macheiner, Tanja; Kessler, Sonja M.; Czepukojc, Beate; Gemperlein, Katja; Müller, Rolf; Kiemer, Alexandra K.; Magnes, Christoph; Haybaeck, Johannes; Lackner, Carolin; Sargsyan, Karine

    2016-01-01

    Although non-alcoholic and alcoholic fatty liver disease have been intensively studied, concerning pathophysiological mechanisms are still incompletely understood. This may be due to the use of different animal models and resulting model-associated variation. Therefore, this study aimed to compare three frequently used wild type mouse strains in their susceptibility to develop diet-induced features of non-alcoholic/alcoholic fatty liver disease. Fatty liver disease associated clinical, biochemical, and histological features in C57BL/6, CD-1, and 129Sv WT mice were induced by (i) high-fat diet feeding, (ii) ethanol feeding only, and (iii) the combination of high-fat diet and ethanol feeding. Hepatic and subcutaneous adipose lipid profiles were compared in CD-1 and 129Sv mice. Additionally hepatic fatty acid composition was determined in 129Sv mice. In C57BL/6 mice dietary regimens resulted in heterogeneous hepatic responses, ranging from pronounced steatosis and inflammation to a lack of any features of fatty liver disease. Liver-related serum biochemistry showed high deviations within the regimen groups. CD-1 mice did not exhibit significant changes in metabolic and liver markers and developed no significant steatosis or inflammation as a response to dietary regimens. Although 129Sv mice showed no weight gain, this strain achieved most consistent features of fatty liver disease, apparent from concentration alterations of liver-related serum biochemistry as well as moderate steatosis and inflammation as a result of all dietary regimens. Furthermore, the hepatic lipid profile as well as the fatty acid composition of 129Sv mice were considerably altered, upon feeding the different dietary regimens. Accordingly, diet-induced non-alcoholic/alcoholic fatty liver disease is most consistently promoted in 129Sv mice compared to C57BL/6 and CD-1 mice. As a conclusion, this study demonstrates the importance of genetic background of used mouse strains for modeling diet-induced

  10. Adult-onset deficiency of acyl CoA:monoacylglycerol acyltransferase 2 protects mice from diet-induced obesity and glucose intolerance[S

    PubMed Central

    Banh, Taylor; Nelson, David W.; Gao, Yu; Huang, Ting-Ni; Yen, Mei-I; Yen, Chi-Liang E.

    2015-01-01

    Acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2 catalyzes triacylglycerol (TAG) synthesis, required in intestinal fat absorption. We previously demonstrated that mice without a functional MGAT2-coding gene (Mogat2−/−) exhibit increased energy expenditure and resistance to obesity induced by excess calories. One critical question raised is whether lacking MGAT2 during early development is required for the metabolic phenotypes in adult mice. In this study, we found that Mogat2−/− pups grew slower than wild-type littermates during the suckling period. To determine whether inactivating MGAT2 in adult mice is sufficient to confer resistance to diet-induced obesity, we generated mice with an inducible Mogat2-inactivating mutation. Mice with adult-onset MGAT2 deficiency (Mogat2AKO) exhibited a transient decrease in food intake like Mogat2−/− mice when fed a high-fat diet and a moderate increase in energy expenditure after acclimatization. They gained less weight than littermate controls, but the difference was smaller than that between wild-type and Mogat2−/− mice. The moderate reduction in weight gain was associated with reduced hepatic TAG and improved glucose tolerance. Similar protective effects were also observed in mice that had gained weight on a high-fat diet before inactivating MGAT2. These findings suggest that adult-onset MGAT2 deficiency mitigates metabolic disorders induced by high-fat feeding and that MGAT2 modulates early postnatal nutrition and may program metabolism later in life. PMID:25535286

  11. Mitochondria-targeted dodecyltriphenylphosphonium (C12TPP) combats high-fat-diet-induced obesity in mice

    PubMed Central

    Kalinovich, A V; Mattsson, C L; Youssef, M R; Petrovic, N; Ost, M; Skulachev, V P; Shabalina, I G

    2016-01-01

    Background: A membrane-penetrating cation, dodecyltriphenylphosphonium (C12TPP), facilitates the recycling of fatty acids in the artificial lipid membrane and mitochondria. C12TPP can dissipate mitochondrial membrane potential and may affect total energy expenditure and body weight in animals and humans. Methods: We investigated the metabolic effects of C12TPP in isolated brown-fat mitochondria, brown adipocyte cultures and mice in vivo. Experimental approaches included the measurement of oxygen consumption, carbon dioxide production, western blotting, magnetic resonance imaging and bomb calorimetry. Results: In mice, C12TPP (50 μmol per (day•kg body weight)) in the drinking water significantly reduced body weight (12%, P<0.001) and body fat mass (24%, P<0.001) during the first 7 days of treatment. C12TPP did not affect water palatability and intake or the energy and lipid content in feces. The addition of C12TPP to isolated brown-fat mitochondria resulted in increased oxygen consumption. Three hours of pretreatment with C12TPP also increased oligomycin-insensitive oxygen consumption in brown adipocyte cultures (P<0.01). The effects of C12TPP on mitochondria, cells and mice were independent of uncoupling protein 1 (UCP1). However, C12TPP treatment increased the mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice. Pair-feeding revealed that one-third of the body weight loss in C12TPP-treated mice was due to reduced food intake. C12TPP treatment elevated the resting metabolic rate (RMR) by up to 18% (P<0.05) compared with pair-fed animals. C12TPP reduced the respiratory exchange ratio, indicating enhanced fatty acid oxidation in mice. Conclusions: C12TPP combats diet-induced obesity by reducing food intake, increasing the RMR and enhancing fatty acid oxidation. PMID:27534841

  12. Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment.

    PubMed

    Slocum, Nikki; Durrant, Jessica R; Bailey, David; Yoon, Lawrence; Jordan, Holly; Barton, Joanna; Brown, Roger H; Clifton, Lisa; Milliken, Tula; Harrington, Wallace; Kimbrough, Carie; Faber, Catherine A; Cariello, Neal; Elangbam, Chandikumar S

    2013-07-01

    Drug-induced weight loss in humans has been associated with undesirable side effects not present in weight loss from lifestyle interventions (caloric restriction or exercise). To investigate the mechanistic differences of weight loss by drug-induced and lifestyle interventions, we examined the gene expression (mRNA) in brown adipose tissue (BAT) and conducted histopathologic assessments in diet-induced obese (DIO) mice given ephedrine (18 mg/kg/day orally), treadmill exercise (10 m/min, 1-h/day), and dietary restriction (DR: 26% dietary restriction) for 7 days. Exercise and DR mice lost more body weight than controls and both ephedrine and exercise reduced percent body fat. All treatments reduced BAT and liver lipid accumulation (i.e., cytoplasmic lipids in brown adipocytes and hepatocytes) and increased oxygen consumption (VO2 ml/kg/h) compared with controls. Mitochondrial biogenesis/function-related genes (TFAM, NRF1 and GABPA) were up-regulated in the BAT of all groups. UCP-1 was up-regulated in exercise and ephedrine groups, whereas MFSD2A was up-regulated in ephedrine and DR groups. PGC-1α up-regulation was observed in exercise and DR groups but not in ephedrine group. In all experimental groups, except for ephedrine, fatty acid transport and metabolism genes were up-regulated, but the magnitude of change was higher in the DR group. PRKAA1 was up-regulated in all groups but not significantly in the ephedrine group. ADRß3 was slightly up-regulated in the DR group only, whereas ESRRA remained unchanged in all groups. Although our data suggest a common pathway of BAT activation elicited by ephedrine treatment, exercise or DR, mRNA changes were indicative of additional nutrient-sensing pathways in exercise and DR.

  13. Effects of a Twelve-Week Weight Reduction Exercise Programme on Selected Spatiotemporal Gait Parameters of Obese Individuals

    PubMed Central

    Adegoke, Babatunde O. A.; Olagbegi, Oladapo M.

    2017-01-01

    Objectives. This study was carried out to investigate the effects of twelve-week weight reduction exercises on selected spatiotemporal gait parameters of obese individuals and compare with their normal weight counterparts. Methods. Sixty participants (30 obese and 30 of normal weight) started but only 58 participants (obese = 30, normal weight = 28) completed the quasi-experimental study. Only obese group had 12 weeks of weight reduction exercise training but both groups had their walking speed (WS), cadence (CD), step length (SL), step width (SW), and stride length (SDL) measured at baseline and at the end of weeks 4, 8, and 12 of the study. Data were analysed using appropriate descriptive and inferential statistics. Results. There was significantly lower WS, SL, and SDL but higher CD and SW in obese group than the normal weight group at baseline and week 12. However, the obese group had significantly higher percentage changes in all selected spatiotemporal parameters than the normal weight group. Conclusion. The 12-week weight reduction exercise programme produced significantly higher percentage changes in all selected spatiotemporal gait parameters in the obese than normal weight individuals and is recommended for improvement of these parameters among the obese individuals with gait related problems. PMID:28168051

  14. Obesity and headache/migraine: the importance of weight reduction through lifestyle modifications.

    PubMed

    Verrotti, Alberto; Di Fonzo, Alessia; Penta, Laura; Agostinelli, Sergio; Parisi, Pasquale

    2014-01-01

    The aim of this study is to determine a possible relationship between prevalence, frequency, and severity of migraine and obesity. All pertinent data from the literature have been critically examined and reviewed in order to assess the possible relationship between obesity and migraine, in particular migraine frequency and disability in children, as well as in adult population studies. Prevalence, frequency, and severity of migraine appear to increase in relation to the body mass index, although this evidence is not supported by all the studies examined. Data from literature suggest that obesity can be linked with migraine prevalence, frequency, and disability both in pediatric and adult subjects. These data have important clinical implications and suggest that clinicians should have a special interest for weight reduction of obese children suffering from migraine, prescribing and supporting intensive lifestyle modifications (dietary, physical activities, and behavioral) for the patient and the entire family.

  15. Obesity and Headache/Migraine: The Importance of Weight Reduction through Lifestyle Modifications

    PubMed Central

    Verrotti, Alberto; Di Fonzo, Alessia; Agostinelli, Sergio

    2014-01-01

    The aim of this study is to determine a possible relationship between prevalence, frequency, and severity of migraine and obesity. All pertinent data from the literature have been critically examined and reviewed in order to assess the possible relationship between obesity and migraine, in particular migraine frequency and disability in children, as well as in adult population studies. Prevalence, frequency, and severity of migraine appear to increase in relation to the body mass index, although this evidence is not supported by all the studies examined. Data from literature suggest that obesity can be linked with migraine prevalence, frequency, and disability both in pediatric and adult subjects. These data have important clinical implications and suggest that clinicians should have a special interest for weight reduction of obese children suffering from migraine, prescribing and supporting intensive lifestyle modifications (dietary, physical activities, and behavioral) for the patient and the entire family. PMID:24800223

  16. Mechanisms of body weight reduction and metabolic syndrome alleviation by tea.

    PubMed

    Yang, Chung S; Zhang, Jinsong; Zhang, Le; Huang, Jinbao; Wang, Yijun

    2016-01-01

    Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been shown to reduce body weight, alleviate metabolic syndrome, and prevent diabetes and cardiovascular diseases in animal models and humans. Such beneficial effects have generally been observed in most human studies when the level of tea consumption was three to four cups (600-900 mg tea catechins) or more per day. Green tea is more effective than black tea. In spite of numerous studies, the fundamental mechanisms for these actions still remain unclear. From a review of the literature, we propose that the two major mechanisms are: (i) decreasing absorption of lipids and proteins by tea constituents in the intestine, thus reducing calorie intake; and (ii) activating AMP-activated protein kinase by tea polyphenols that are bioavailable in the liver, skeletal muscle, and adipose tissues. The relative importance of these two mechanisms depends on the types of tea and diet consumed by individuals. The activated AMP-activated protein kinase would decrease gluconeogenesis and fatty acid synthesis and increase catabolism, leading to body weight reduction and metabolic syndrome alleviation. Other mechanisms and the health relevance of these beneficial effects of tea consumption remain to be further investigated.

  17. Effect of molecular weight reduction by gamma irradiation on chitosan film properties.

    PubMed

    García, Mario A; Pérez, Liliam; de la Paz, Nilia; González, Juan; Rapado, Manuel; Casariego, Alicia

    2015-10-01

    The present work aimed the influence of molecular weight (MW) reduction by irradiation with (60)Co and polymer concentration on some physical properties of chitosan films. Irradiation of chitosan with a MW of 275.221 kDa and 74.74% of deacetylation degree was performed using a (60)Co source to provide doses of 5, 10, 20 and 50 kGy to obtain chitosans with molecular weights of 247.847, 221.563, 126.469 and 77.063 kDa, respectively. Films were prepared via the solution casting method. Film-forming solutions (FFS) of chitosan irradiated or not, were prepared at 1.5 and 2% (w/v) in a solution of lactic acid at 1% (v/v) and 0.1% (v/v) of Tween 80. The FFS were poured into glass plates of 400 cm(2) and dried at 60 °C during 10h without airflow. The decrease of MW and increase of chitosan concentration increased the tensil strength and water vapor permeability while decreased the elongation at break of the films. The chitosan MW did not significantly influence (p>0.05) the water solubility of films within a same polymer concentration. There was a decrease in the films' brightness with the increase of concentration and a decrease of the MW of irradiated chitosan, while the b* values of films increased and there was an increasing tendency of their apparent opacity.

  18. Mechanisms of Body Weight Reduction and Metabolic Syndrome Alleviation by Tea

    PubMed Central

    Yang, Chung S.; Zhang, Jinsong; Zhang, Le; Huang, Jinbao; Wang, Yijun

    2016-01-01

    Tea, a popular beverage made from leaves of the plant Camellia sinensis, has been shown to reduce body weight, alleviate metabolic syndrome, and prevent diabetes and cardiovascular diseases in animal models and humans. Such beneficial effects have generally been observed in most human studies when the level of tea consumption was 3 to 4 cups (600–900 mg tea catechins) or more per day. Green tea is more effective than black tea. In spite of numerous studies, the fundamental mechanisms for these actions still remain unclear. From a review of the literature, we propose that the two major mechanisms are: 1) decreasing absorption of lipids and proteins by tea constituents in the intestine, thus reducing calorie intake; and 2) activating AMPK by tea polyphenols that are bioavailable in the liver, skeletal muscle, and adipose tissues. The relative importance of these two mechanisms depends on the types of tea and diet consumed by individuals. The activated AMPK would decrease gluconeogenesis and fatty acid synthesis and increase catabolism, leading to body weight reduction and MetS alleviation. Other mechanisms and the health relevance of these beneficial effects of tea consumption remain to be further investigated. PMID:26577614

  19. Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions.

    PubMed

    Kelly, Jarod C; Sullivan, John L; Burnham, Andrew; Elgowainy, Amgad

    2015-10-20

    This study examines the vehicle-cycle and vehicle total life-cycle impacts of substituting lightweight materials into vehicles. We determine part-based greenhouse gas (GHG) emission ratios by collecting material substitution data and evaluating that alongside known mass-based GHG ratios (using and updating Argonne National Laboratory's GREET model) associated with material pair substitutions. Several vehicle parts are lightweighted via material substitution, using substitution ratios from a U.S. Department of Energy report, to determine GHG emissions. We then examine fuel-cycle GHG reductions from lightweighting. The fuel reduction value methodology is applied using FRV estimates of 0.15-0.25, and 0.25-0.5 L/(100km·100 kg), with and without powertrain adjustments, respectively. GHG breakeven values are derived for both driving distance and material substitution ratio. While material substitution can reduce vehicle weight, it often increases vehicle-cycle GHGs. It is likely that replacing steel (the dominant vehicle material) with wrought aluminum, carbon fiber reinforced plastic (CRFP), or magnesium will increase vehicle-cycle GHGs. However, lifetime fuel economy benefits often outweigh the vehicle-cycle, resulting in a net total life-cycle GHG benefit. This is the case for steel replaced by wrought aluminum in all assumed cases, and for CFRP and magnesium except for high substitution ratio and low FRV.

  20. Impacts of Vehicle Weight Reduction via Material Substitution on Life-Cycle Greenhouse Gas Emissions

    SciTech Connect

    Kelly, Jarod C.; Sullivan, John L.; Burnham, Andrew; Elgowainy, Amgad

    2015-10-20

    This study examines the vehicle-cycle impacts associated with substituting lightweight materials for those currently found in light-duty passenger vehicles. We determine part-based energy use and greenhouse gas (GHG) emission ratios by collecting material substitution data from both the literature and automotive experts and evaluating that alongside known mass-based energy use and GHG emission ratios associated with material pair substitutions. Several vehicle parts, along with full vehicle systems, are examined for lightweighting via material substitution to observe the associated impact on GHG emissions. Results are contextualized by additionally examining fuel-cycle GHG reductions associated with mass reductions relative to the baseline vehicle during the use phase and also determining material pair breakeven driving distances for GHG emissions. The findings show that, while material substitution is useful in reducing vehicle weight, it often increases vehicle-cycle GHGs depending upon the material substitution pair. However, for a vehicle’s total life cycle, fuel economy benefits are greater than the increased burdens associated with the vehicle manufacturing cycle, resulting in a net total life-cycle GHG benefit. The vehicle cycle will become increasingly important in total vehicle life-cycle GHGs, since fuel-cycle GHGs will be gradually reduced as automakers ramp up vehicle efficiency to meet fuel economy standards.

  1. Relation Between Obesity, Metabolic Syndrome, Successful Long-Term Weight Reduction, and Right Ventricular Function.

    PubMed

    Zeller, Judith; Strack, Christina; Fenk, Sabine; Mohr, Margareta; Loew, Thomas; Schmitz, Gerd; Maier, Lars; Fischer, Marcus; Baessler, Andrea

    2016-07-27

    This study sought to examine the relationships between right ventricular (RV) function and geometry, morbid obesity with and without the metabolic syndrome, and the effect of long-term weight loss. Obese (n = 153, BMI 41.2 ± 8.7 kg/m(2)) and healthy non-obese control subjects (n = 38, BMI 25.5 ± 3.3 kg/m(2)) of similar age and gender distribution were prospectively studied during the course of a 1-year weight reduction program with echocardiography at baseline and after one year of follow up. Function and geometry of the right heart were evaluated by tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TDI S'), RV myocardial performance index (TEI), RV end-diastolic (RVEDD) and end-systolic diameter (RVESD), area of the right atrium (RAA), and systolic pulmonary artery pressure (PAP). Whereas parameters of systolic and diastolic LV function were significantly worse in the obese subjects than those in the non-obese subjects (EF 66 ± 6 versus 69 ± 6%, P = 0.004; E/E' 7.4 ± 2.5 versus 6.3 ± 2.6, P = 0.010), parameters of RV function (TAPSE 25.6 ± 4.5 versus 25.1 ± 3.5 mm, P = 0.528; TDI S' 13.5 ± 2.9 versus 13.8 ± 2.9 mm/second, P = 0.553; TEI 0.25 ± 0.13 versus 0.28 ± 0.09, P = 0.283) as well as geometry measurements were comparable between the obese and non-obese participants and also in obese subjects with full blown metabolic syndrome. Additionally, successful weight reduction did not alter the RV parameters. Nevertheless, in the few obese subjects with RV dysfunction (n = 7), metabolic syndrome parameters were more pronounced than in obese with normal RV function.Morbid obesity with and without the metabolic syndrome is accompanied by an impaired LV systolic and diastolic function. In contrast, RV function appears to be less affected by obesity independent of the presence of the metabolic syndrome.

  2. Statistical CT noise reduction with multiscale decomposition and penalized weighted least squares in the projection domain

    SciTech Connect

    Tang Shaojie; Tang Xiangyang

    2012-09-15

    Purposes: The suppression of noise in x-ray computed tomography (CT) imaging is of clinical relevance for diagnostic image quality and the potential for radiation dose saving. Toward this purpose, statistical noise reduction methods in either the image or projection domain have been proposed, which employ a multiscale decomposition to enhance the performance of noise suppression while maintaining image sharpness. Recognizing the advantages of noise suppression in the projection domain, the authors propose a projection domain multiscale penalized weighted least squares (PWLS) method, in which the angular sampling rate is explicitly taken into consideration to account for the possible variation of interview sampling rate in advanced clinical or preclinical applications. Methods: The projection domain multiscale PWLS method is derived by converting an isotropic diffusion partial differential equation in the image domain into the projection domain, wherein a multiscale decomposition is carried out. With adoption of the Markov random field or soft thresholding objective function, the projection domain multiscale PWLS method deals with noise at each scale. To compensate for the degradation in image sharpness caused by the projection domain multiscale PWLS method, an edge enhancement is carried out following the noise reduction. The performance of the proposed method is experimentally evaluated and verified using the projection data simulated by computer and acquired by a CT scanner. Results: The preliminary results show that the proposed projection domain multiscale PWLS method outperforms the projection domain single-scale PWLS method and the image domain multiscale anisotropic diffusion method in noise reduction. In addition, the proposed method can preserve image sharpness very well while the occurrence of 'salt-and-pepper' noise and mosaic artifacts can be avoided. Conclusions: Since the interview sampling rate is taken into account in the projection domain

  3. Statistical CT noise reduction with multiscale decomposition and penalized weighted least squares in the projection domain

    PubMed Central

    Tang, Shaojie; Tang, Xiangyang

    2012-01-01

    Purposes: The suppression of noise in x-ray computed tomography (CT) imaging is of clinical relevance for diagnostic image quality and the potential for radiation dose saving. Toward this purpose, statistical noise reduction methods in either the image or projection domain have been proposed, which employ a multiscale decomposition to enhance the performance of noise suppression while maintaining image sharpness. Recognizing the advantages of noise suppression in the projection domain, the authors propose a projection domain multiscale penalized weighted least squares (PWLS) method, in which the angular sampling rate is explicitly taken into consideration to account for the possible variation of interview sampling rate in advanced clinical or preclinical applications. Methods: The projection domain multiscale PWLS method is derived by converting an isotropic diffusion partial differential equation in the image domain into the projection domain, wherein a multiscale decomposition is carried out. With adoption of the Markov random field or soft thresholding objective function, the projection domain multiscale PWLS method deals with noise at each scale. To compensate for the degradation in image sharpness caused by the projection domain multiscale PWLS method, an edge enhancement is carried out following the noise reduction. The performance of the proposed method is experimentally evaluated and verified using the projection data simulated by computer and acquired by a CT scanner. Results: The preliminary results show that the proposed projection domain multiscale PWLS method outperforms the projection domain single-scale PWLS method and the image domain multiscale anisotropic diffusion method in noise reduction. In addition, the proposed method can preserve image sharpness very well while the occurrence of “salt-and-pepper” noise and mosaic artifacts can be avoided. Conclusions: Since the interview sampling rate is taken into account in the projection domain

  4. Dual-specificity phosphatase 6 deficiency regulates gut microbiome and transcriptome response against diet-induced obesity in mice.

    PubMed

    Ruan, Jhen-Wei; Statt, Sarah; Huang, Chih-Ting; Tsai, Yi-Ting; Kuo, Cheng-Chin; Chan, Hong-Lin; Liao, Yu-Chieh; Tan, Tse-Hua; Kao, Cheng-Yuan

    2016-11-28

    The gut microbiota plays profound roles in host metabolism and the inflammatory response associated with the development of obesity. Dusp6-deficient mice have been shown to be resistant to diet-induced obesity, but the mechanism behind this remains unclear. 16S ribosomal RNA gene analysis demonstrated that dusp6-deficient mice harbour unique gut microbiota with resistance to diet-induced-obesity-mediated alteration of the gut microbiome. Using a germ-free mouse model, we found that faecal/gut microbiota derived from dusp6-deficient mice significantly increased energy expenditure and reduced weight gain in recipient wild-type mice fed on a high-fat diet. On analysis of the intestinal transcriptome of dusp6-deficient mice, we found that dusp6 deficiency mainly induced biological processes involved in metabolism and the extracellular matrix, particularly the peroxisome proliferator-activated receptor gamma (Pparγ) pathway and tight-junction genes. Furthermore, dusp6-deficient mice have a high-fat-diet-specific transcriptomic response to reverse the expression of genes associated with intestinal barrier functions and mucosal immunity involved in microbiome homeostasis. This study demonstrates that dusp6 deficiency is a strong genetic factor shaping gut microbiota, and that it confers obesity protection by ameliorating the gut microbiota response to diet-mediated stress.

  5. Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice

    PubMed Central

    2016-01-01

    Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice. PMID:27960282

  6. Imidacloprid Promotes High Fat Diet-Induced Adiposity and Insulin Resistance in Male C57BL/6J Mice.

    PubMed

    Sun, Quancai; Xiao, Xiao; Kim, Yoo; Kim, Daeyoung; Yoon, Kyoon Sup; Clark, John M; Park, Yeonhwa

    2016-12-14

    Imidacloprid, a neonicotinoid insecticide widely used in agriculture worldwide, has been reported to promote adipogenesis and cause insulin resistance in vitro. The purpose of the current study was to determine the effects of imidacloprid and its interaction with dietary fat in the development of adiposity and insulin resistance using male C57BL/6J mice. Imidacloprid (0.06, 0.6, or 6 mg/kg bw/day) was mixed in a low-fat (4% w/w) or high-fat (20% w/w) diet and given to mice ad libitum for 12 weeks. Imidacloprid significantly promoted high fat diet-induced body weight gain and adiposity. In addition, imidacloprid treatment with the high fat diet resulted in impaired glucose metabolism. Consistently, there were significant effects of imidacloprid on genes regulating lipid and glucose metabolisms, including the AMP-activated protein kinase-α (AMPKα) pathway in white adipose tissue and liver. These results suggest that imidacloprid may potentiate high fat diet-induced adiposity and insulin resistance in male C57BL/6J mice.

  7. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

    PubMed

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

  8. White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice

    PubMed Central

    Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

    2016-01-01

    Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism. PMID:26914024

  9. The effect of psychological stress on diet-induced thermogenesis and resting metabolic rate.

    PubMed

    Weststrate, J A; Van der Kooy, K; Deurenberg, P; Hautvast, J G

    1990-04-01

    The effect of psychological stress on resting metabolic rate (RMR) and diet-induced thermogenesis (DIT) was assessed in 12 healthy young non-obese men of body weight 70.2 +/- 1.2 kg (mean +/- s.e.m.) and age 25 +/- 0.6 years. Two types of commercially available motion pictures (video films) were shown to the subjects during the measurements, ie stress-inducing horror films and as a control, romantic family films. The study was conducted according to a cross-over design. RMR and respiratory quotients were not significantly influenced by the type of film shown to the subjects. DIT, assessed over 4 h, was significantly increased by the stress-inducing treatment, 0.95 +/- 0.05 kJ/min (mean +/- s.e.m.) versus 0.76 +/- 0.06 kJ/min (control). No significant effect was observed of psychological stress on postprandial substrate oxidation rates, nutrient balances, and urinary catecholamine excretion.

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

    PubMed

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

    2016-01-01

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

  11. A Mouse Model of Diet-Induced Obesity Resembling Most Features of Human Metabolic Syndrome

    PubMed Central

    Della Vedova, Maria C.; Muñoz, Marcos D.; Santillan, Lucas D.; Plateo-Pignatari, Maria G.; Germanó, Maria J.; Rinaldi Tosi, Martín E.; Garcia, Silvina; Gomez, Nidia N.; Fornes, Miguel W.; Gomez Mejiba, Sandra E.; Ramirez, Dario C.

    2016-01-01

    Increased chicken-derived fat and fructose consumption in the human diet is paralleled by an increasing prevalence of obesity and metabolic syndrome (MS). Herein, we aimed at developing and characterizing a mouse model of diet-induced obesity (DIO) resembling most of the key features of the human MS. To accomplish this, we fed male C57BL/6J mice for 4, 8, 12, and 16 weeks with either a low-fat diet (LFD) or a high-chicken-fat diet (HFD) and tap water with or without 10% fructose (F). This experimental design resulted in the following four experimental groups: LFD, LFD + F, HFD, and HFD + F. Over the feeding period, and on a weekly basis, the HFD + F group had more caloric intake and gained more weight than the other experimental groups. Compared to the other groups, and at the end of the feeding period, the HFD + F group had a higher adipogenic index, total cholesterol, low-density lipoprotein cholesterol, fasting basal glycemia, insulin resistance, hypertension, and atherogenic index and showed steatohepatitis and systemic oxidative stress/inflammation. A mouse model of DIO that will allow us to study the effect of MS in different organs and systems has been developed and characterized. PMID:27980421

  12. Fucoidan prevents high-fat diet-induced obesity in animals by suppression of fat accumulation.

    PubMed

    Kim, Mi-Ja; Jeon, Joseph; Lee, Jin-Sil

    2014-01-01

    This study examines the antiobesity effects of fucoidan in an animal model of diet-induced obesity. Mice were fed a standard diet or high-fat diet (HFD) for 5 weeks. After that, the mice were divided into four experimental groups, with 10 mice per group, including a standard diet group, HFD group, HFD containing 1% fucoidan (HFD + FUCO 1%) group and HFD containing 2% fucoidan (HFD + FUCO 2%) group. The fucoidan supplementation group had significantly decreased body-weight gain, food efficiency ratio and relative liver and epididymal fat mass compared with the HFD group. The mice supplemented with fucoidan showed significantly reduced triglyceride, total cholesterol and low-density lipoprotein levels in the plasma. Liver steatosis induced by the HFD improved in the fucoidan-supplemented group. Furthermore, fucoidan affected the down-regulation expression patterns of epididymal adipose tissue genes such as peroxisome proliferator-activated receptor γ, adipose-specific fatty acid binding protein and acetyl CoA carboxylase. Therefore, fucoidan may be considered for use in improving obesity.

  13. Diet-induced obesity alters dendritic cell function in the presence and absence of tumor growth

    PubMed Central

    James, Britnie R.; Tomanek-Chalkley, Ann; Askeland, Eric J.; Kucaba, Tamara; Griffith, Thomas S.; Norian, Lyse A.

    2012-01-01

    Obesity is a mounting health concern in the United States, and is associated with an increased risk for developing several cancers, including renal cell carcinoma (RCC). Despite this, little is known regarding the impact of obesity on antitumor immunity. As dendritic cells (DC) are critical regulators of antitumor immunity, we examined the combined effects of obesity and tumor outgrowth on DC function. Using a diet-induced obesity (DIO) model, DC function was evaluated in mice bearing orthotopic RCC and in tumor-free controls. Tumor-free DIO mice had profoundly altered serum cytokine and chemokine profiles, with upregulation of 15 proteins, including IL-1α, IL-17, and LIF. Tumor-free DIO mice had elevated percentages of conventional splenic DC that were impaired in their ability to stimulate naive T cell expansion, although they were phenotypically similar to normal weight (NW) controls. In DIO mice, intra-renal RCC tumor challenge in the absence of therapy led to increased local infiltration by T cell-suppressive DC and accelerated early tumor outgrowth. Following administration of a DC-dependent immunotherapy, established RCC tumors regressed in NW mice. The same immunotherapy was ineffective in DIO mice, and was characterized by an accumulation of regulatory DC in tumor-bearing kidneys, decreased local infiltration by IFNγ-producing CD8 T cells, and progressive tumor outgrowth. Our results suggest that the presence of obesity as a co-morbidity can impair the efficacy of DC-dependent antitumor immunotherapies. PMID:22745381

  14. Antiatherogenic Potential of Nigella sativa Seeds and Oil in Diet-Induced Hypercholesterolemia in Rabbits.

    PubMed

    Al-Naqeep, Ghanya; Al-Zubairi, Adel S; Ismail, Maznah; Amom, Zulkhairi Hj; Esa, Norhaizan Mohd

    2011-01-01

    Nigella sativa or Black seed (N. sativa L.) is traditionally used for several ailments in many Middle Eastern countries. It is an annual herbaceous plant that belongs to the Ranuculacea family with many beneficial properties as antitumor, antidiabetic, antihypertensive, antioxidative and antibacterial. This work attempted to study the effect of N. sativa seeds powder and oil on atherosclerosis in diet-induced hypercholesterolemic (HC) rabbits in comparison with simvastatin (ST). Twenty-five adult New Zealand male white rabbits, weighing 1.5-2.5 kg, were divided into five groups; normal group (NC, n = 5) and four hypercholesterolemic groups (n = 20): a positive control (PC) and three HC groups force fed diet supplemented with 1000 mg Kg(-1) body weight of N. sativa powder (NSP), 500 mg Kg(-1) body N. sativa oil (NSO) and 10 mg Kg(-1) ST for 8 weeks. Feeding HC rabbits with N. sativa either in powder or oil forms was shown to significantly reduce (P < .05) total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) levels and enhance high-density lipoprotein cholesterol (HDL) levels after treatment for 2, 4, 6 and 8 weeks compared to the PC group. Plaque formation was significantly inhibited while the intima: media ratio was significantly reduced in the NSP and NSO supplemented groups compared to the PC group. In conclusion, treatment of HC rabbits with N. sativa seeds powder or oil showed hypocholesterolemic and antiatherogenic cardioprotective properties.

  15. Popular edible seaweed, Gelidium amansii prevents against diet-induced obesity.

    PubMed

    Kang, Min-Cheol; Kang, Nalae; Kim, Seo-Young; Lima, Inês S; Ko, Seok-Chun; Kim, Young-Tae; Kim, Young-Bum; Jeung, Hee-Do; Choi, Kwang-Sik; Jeon, You-Jin

    2016-04-01

    The popular edible seaweed, Gelidium amansii is broadly used as food worldwide. To determine whether G. amansii extract (GAE) has protective effects on obesity, mice fed a high-fat diet (HFD) treated with GAE (1 and 3 %) were studied. After 12 weeks of GAE treatment, body weight was greatly decreased in mice fed a high-fat diet. This effect could be due to decreased adipogenesis, as evidenced by the fact that GAE suppressed adipogenic gene expression in adipocytes. In addition, blood glucose and serum insulin levels were reduced by GAE treatment in mice fed a high-fat diet, suggesting improvement in glucose metabolism. GAE supplementation also led to a significant decrease in total cholesterol and triglyceride levels. These data are further confirmed by H&E staining. Our findings indicate that Gelidium amansii prevents against the development of diet-induced obesity, and further implicate that GAE supplementation could be the therapeutical option for treatment of metabolic disorder such as obesity.

  16. Hydrodynamic delivery of interleukin 15 gene promotes resistance to high fat diet-induced obesity, fatty liver and improves glucose homeostasis.

    PubMed

    Sun, H; Liu, D

    2015-04-01

    The objective of this study is to examine the effect of hydrodynamic delivery of plasmid containing Il-15 gene on high fat diet-induced obesity and obesity-associated metabolic disorders. We demonstrate that Il-15 gene transfer results in multiple beneficial effects, including blockade of weight gain, alleviation of fatty liver and improvement in glucose homeostasis in mice. These effects are accompanied by suppressed expression of genes involved in lipogenesis and gluconeogenesis including Scd-1, Fas, Pdk4, Pepck and G6p, and enhanced expression of genes responsible for lipolysis and glucose metabolism such as Cpt1-α, Cpt1-β, Acadm, Acadl and Glut-4. Collectively, our results suggest that Il-15 gene transfer is an effective approach in preventing diet-induced obesity and obesity-associated complications.

  17. Hepatoprotective Effect and Synergism of Bisdemethoycurcumin against MCD Diet-Induced Nonalcoholic Fatty Liver Disease in Mice

    PubMed Central

    Lee, Young-Seob; Han, Sin-Hee; Ahn, Young-Sup; Cha, Seon-Woo; Seo, Yun-Soo; Kong, Ryong; Kwon, Dong-Yeul

    2016-01-01

    Nonalcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome, has become one of the most common causes of chronic liver disease over the last decade in developed countries. NAFLD includes a spectrum of pathological hepatic changes, such as steatosis, steatohepatitis, advanced fibrosis, and cirrhosis. Bisdemethoxycurcumin (BDMC) is polyphenolic compounds with a diarylheptanoid skeleton, curcumin close analogues, which is derived from the Curcumae Longae Rhizoma. While the rich bioavailability research of curcumin, BDMC is the poor studies. We investigated whether BDMC has the hepatoprotective effect and combinatory preventive effect with silymarin on methionine choline deficient (MCD)-diet-induced NAFLD in C57BL/6J mice. C57BL/6J mice were divided into five groups of normal (normal diet without any treatment), MCD diet (MCD diet only), MCD + silymarin (SIL) 100 mg/kg group, MCD + BDMC 100 mg/kg group, MCD + SIL 50 mg/kg + BDMC 50 mg/kg group. Body weight, liver weight, liver function tests, histological changes were assessed and quantitative real-time polymerase chain reaction and Western blot analyses were conducted after 4 weeks. Mice lost body weight on the MCD-diet, but BDMC did not lose less than the MCD-diet group. Liver weights decreased from BDMC, but they increased significantly in the MCD-diet groups. All liver function test values decreased from the MCD-diet, whereas those from the BDMC increased significantly. The MCD- diet induced severe hepatic fatty accumulation, but the fatty change was reduced in the BDMC. The BDMC showed an inhibitory effect on liver lipogenesis by reducing associated gene expression caused by the MCD-diet. In all experiments, the combinations of BDMC with SIL had a synergistic effect against MCD-diet models. In conclusion, our findings indicate that BDMC has a potential suppressive effect on NAFLD. Therefore, our data suggest that BDMC may act as a novel and potent therapeutic agent against NAFLD

  18. Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis.

    PubMed

    Bernasconi, Pablo A Scacchi; Cardoso, Nancy P; Reynoso, Roxana; Scacchi, Pablo; Cardinali, Daniel P

    2013-12-01

    Abstract Combinations of fructose- and fat-rich diets in experimental animals can model the human metabolic syndrome (MS). In rats, the increase in blood pressure (BP) after diet manipulation is sex related and highly dependent on testosterone secretion. However, the extent of the impact of diet on rodent hypophysial-testicular axis remains undefined. In the present study, rats drinking a 10% fructose solution or fed a high-fat (35%) diet for 10 weeks had higher plasma levels of luteinizing hormone (LH) and lower plasma levels of testosterone, without significant changes in circulating follicle-stimulating hormone or the weight of most reproductive organs. Diet manipulation brought about a significant increase in body weight, systolic BP, area under the curve (AUC) of glycemia after an intraperitoneal glucose tolerance test (IPGTT), and plasma low-density lipoprotein cholesterol, cholesterol, triglycerides, and uric acid levels. The concomitant administration of melatonin (25 μg/mL of drinking water) normalized the abnormally high LH levels but did not affect the inhibited testosterone secretion found in fructose- or high-fat-fed rats. Rather, melatonin per se inhibited testosterone secretion. Melatonin significantly blunted the body weight and systolic BP increase, the increase in the AUC of glycemia after an IPGTT, and the changes in circulating lipid profile and uric acid found in both MS models. The results are compatible with a primary inhibition of testicular function in diet-induced MS in rats and with the partial effectiveness of melatonin to counteract the metabolic but not the testicular sequelae of rodent MS.

  19. Diet-induced obesity and cardiovascular regulation in C57BL/6J mice.

    PubMed

    Williams, T D; Chambers, J B; Roberts, L M; Henderson, R P; Overton, J M

    2003-10-01

    1. In the present study, we determined the effect of diet-induced obesity on cardiovascular and metabolic regulation in mice at standard laboratory temperatures (ambient temperature (Ta) = 22 degrees C) and during exposure to thermoneutrality (Ta = 30 degrees C). 2. Male C57BL/6J (B6) mice fed a high-fat diet (HFF; n = 17) or chow (CHW; n = 14) for 15 weeks were surgically instrumented with telemetry devices, housed in metabolic chambers and assigned to either control or atenolol treatment (25 mg/kg per day in drinking water) to determine the effects of obesity on baseline cardiovascular function and on the responses to thermoneutrality and 24 h fasting. Mean arterial pressure (MAP), heart rate (HR), arterial pressure and HR variability (time and frequency domain), oxygen consumption (VO2) and locomotor activity were determined. 3. The HFF mice exhibited increased bodyweight (+10.6 +/- 4.1 g), moderate light period hypertension (+8.6 +/- 2.6 mmHg), no difference in HR and increased HR variability at standard laboratory temperature compared with CHW controls. Atenolol produced less of a decrease in HR in HFF mice (-42 +/- 10 b.p.m.) compared with CHW controls (-73 +/- 15 b.p.m.). Acute exposure to thermoneutrality (Ta = 30 degrees C) reduced HR similarly in both HFF and CHW mice (approximately 175 b.p.m.), but reduced MAP less in HFF than in CHW mice (-7.3 +/- 2.5 and -15.2 +/- 1.0 mmHg), respectively. Atenolol treatment had only minor effects on the HR response to thermonuetrality (-114 +/- 13 and -129 +/- 8 b.p.m. in HFF and CHW mice, respectively). The HFF mice displayed greater fasting-induced reductions in light period MAP than did CHW mice (-10.0 +/- 1.1 vs-3.1 +/- 3.5 mmHg, respectively), whereas HR was decreased equally in both groups. Fasting-induced increases in HR variability were attenuated in HFF mice. 4. We conclude that diet-induced obesity produced generally minor changes in cardiovascular regulation in B6 mice at baseline, some of which are distinct

  20. Ghrelin secretion is not reduced by increased fat mass during diet-induced obesity.

    PubMed

    Qi, Xiang; Reed, Jason T; Wang, Guiyun; Han, Song; Englander, Ella W; Greeley, George H

    2008-08-01

    Ghrelin is a stomach hormone that stimulates growth hormone (GH) secretion, adiposity, and food intake. Gastric ghrelin production and secretion are regulated by caloric intake; ghrelin secretion increases during fasting, decreases with refeeding, and is reduced by diet-induced obesity. The aim of the present study was to test the hypotheses that 1) an increase in body adiposity will play an inhibitory role in the reduction of gastric ghrelin synthesis and secretion during chronic ingestion of a high-fat (HF) diet and 2) chronic ingestion of an HF diet will suppress the rise in circulating ghrelin levels in response to acute fasting. Adult male Sprague-Dawley rats were fed a standard AIN-76A (approximately 5-12% of calories from fat) or an HF (approximately 45% of calories from fat) diet. The effect of increased adiposity on gastric ghrelin homeostasis was assessed by comparison of stomach ghrelin production and plasma ghrelin levels in obese and nonobese rats fed the HF diet. HF diet-fed, nonobese rats were generated by administration of triiodothyronine to lower body fat accumulation. Our findings indicate that an increased fat mass per se does not exert an inhibitory effect on ghrelin homeostasis during ingestion of the HF diet. Additionally, the magnitude of change in plasma ghrelin in response to fasting was not blunted, indicating that a presumed, endogenous signal for activation of ingestive behavior remains intact, despite excess stored calories in HF-fed rats.

  1. TRPV1 activation prevents high-salt diet-induced nocturnal hypertension in mice.

    PubMed

    Hao, Xinzhong; Chen, Jing; Luo, Zhidan; He, Hongbo; Yu, Hao; Ma, Liqun; Ma, Shuangtao; Zhu, Tianqi; Liu, Daoyan; Zhu, Zhiming

    2011-03-01

    High dietary salt-caused hypertension is associated with increasing reactive oxygen species generation and reduced nitric oxide (NO) bioavailability. Transient receptor potential vanilloid type 1 (TRPV1), a specific receptor for capsaicin, is proposed to be involved in Dahl salt-sensitive hypertension, as determined in acute or short-term experiments. However, it remains unknown whether activation of TRPV1 by dietary capsaicin could prevent the vascular oxidative stress and hypertension induced by a high-salt diet. Here, we report that consumption of a high-salt diet blunted endothelium-dependent relaxation in mesenteric resistance arteries and elevated nocturnal blood pressure in mice. These effects were associated with increased superoxide anion generation and reduced NO levels in mesenteric vessels in mice on a high-salt diet. However, chronic administration of capsaicin reduced the high-salt diet-induced endothelial dysfunction and nocturnal hypertension in part by preventing the generation of superoxide anions and NO reduction of mesenteric arteries through vascular TRPV1 activation. Our findings provide new insights into the role of TRPV1 channels in the long-term regulation of blood pressure in response to high-salt intake. TRPV1 activation through chronic dietary capsaicin may represent a promising lifestyle intervention in populations with salt-sensitive hypertension.

  2. Dilemmas in the process of weight reduction: Exploring how women experience training as a means of losing weight

    PubMed Central

    Groven, Karen Synne; Engelsrud, Gunn

    2010-01-01

    Patients diagnosed with obesity are usually offered group-based behavior interventions which include dietary advice and exercise programs. In particular, high-intensity training—combining weight lifting with aerobic exercising—has been proven effective for losing weight. Moreover, recent studies have shown that persons participating in high-intensity training are more likely to maintain their weight loss compared to persons with lower levels of physical activity. However, most of the research in the field has made use of quantitative methods focusing on the measurable effect of such interventions. Therefore, the aim of this study was to show how the training is experienced from a first-person perspective, namely the patients themselves. Our hope was to shed some new light on the process of weight loss that concerns more than the measurable “impacts” of the training. A qualitative approach was used based on interviews with five women selected from a primary healthcare clinic in Norway. Our results show that experiences of training are connected to the participants' general experience of being overweight. Both relationships to other people and earlier experiences are important for how the training is carried out and perceived. Five themes were identified supporting this line of argument: (1) the gaze of others; (2) a common ground; (3) dependence of close-follow up; (4) bodily discomfort as painful; and (5) aiming for results—an ambivalent experience. The results highlight the importance of finding the proper context and support for each patient's needs. PMID:20640017

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

    PubMed Central

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

    2013-01-01

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

  4. Dietary supplementation of grape skin extract improves glycemia and inflammation in diet-induced obese mice fed a Western high fat diet.

    PubMed

    Hogan, Shelly; Canning, Corene; Sun, Shi; Sun, Xiuxiu; Kadouh, Hoda; Zhou, Kequan

    2011-04-13

    Dietary antioxidants may provide a cost-effective strategy to promote health in obesity by targeting oxidative stress and inflammation. We recently found that the antioxidant-rich grape skin extract (GSE) also exerts a novel anti-hyperglycemic activity. This study investigated whether 3-month GSE supplementation can improve oxidative stress, inflammation, and hyperglycemia associated with a Western diet-induced obesity. Young diet-induced obese (DIO) mice were randomly divided to three treatment groups (n = 12): a standard diet (S group), a Western high fat diet (W group), and the Western diet plus GSE (2.4 g GSE/kg diet, WGSE group). By week 12, DIO mice in the WGSE group gained significantly more weight (24.6 g) than the W (20.2 g) and S groups (11.2 g); the high fat diet groups gained 80% more weight than the standard diet group. Eight of 12 mice in the W group, compared to only 1 of 12 mice in the WGSE group, had fasting blood glucose levels above 140 mg/dL. Mice in the WGSE group also had 21% lower fasting blood glucose and 17.1% lower C-reactive protein levels than mice in the W group (P < 0.05). However, the GSE supplementation did not affect oxidative stress in diet-induced obesity as determined by plasma oxygen radical absorbance capacity, glutathione peroxidase, and liver lipid peroxidation. Collectively, the results indicated a beneficial role of GSE supplementation for improving glycemic control and inflammation in diet-induced obesity.

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

    PubMed

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

    2015-08-15

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

  6. Weight reduction via life-style modifications results in reverse remodelling and cardiac functional improvement in a patient with obesity.

    PubMed

    Hou, Chang; Zheng, Bo; Yang, Ying; Wang, Xin-Gang; Zhang, Bin; Shi, Qiu-Ping; Chen, Ming

    2017-03-09

    The prevalence of obesity has increased strikingly in recent years. Obesity is associated with increased left ventricular end-diastolic dimension (LVEDD), ventricular wall thickness, left ventricular (LV) mass, left atrial diameter, subtle myocardial systolic as well as diastolic dysfunction and has been identified as an independent predictor of these changes. It's convinced that weight reduction results in cardiac reverse remodelling, while the functional changes after weight reduction are variable. Here, we present a recent case of man with moderate obesity who acquires favourable regression in chamber size, wall thickness and significant improvement in cardiac function. Briefly, after life-style modifications and comprehensive secondary prevention, great amounts of weight loss was achieved simultaneously with decreased LVEDD and increased LV ejection fraction. As dietary intervention and regular physical activity are pivotal for these benefits, this non-invasive approach for weight loss should be advocated in selected patients.

  7. Absence of intestinal microbiota does not protect mice from diet-induced obesity.

    PubMed

    Fleissner, Christine K; Huebel, Nora; Abd El-Bary, Mohamed Mostafa; Loh, Gunnar; Klaus, Susanne; Blaut, Michael

    2010-09-01

    The gut microbiota has been implicated in host nutrient absorption and energy homeostasis. We studied the influence of different diets on body composition in germ-free (GF) and conventional (CV) mice. GF and CV male adult C3H mice were fed ad libitum a semi-synthetic low-fat diet (LFD; carbohydrate-protein-fat ratio: 41:42:17; 19.8 kJ/g), a high-fat diet (HFD; 41:16:43; 21.4 kJ/g) or a commercial Western diet (WD; 41:19:41; 21.5 kJ/g). There was no difference in body weight gain between GF and CV mice on the LFD. On the HFD, GF mice gained more body weight and body fat than CV mice, and had lower energy expenditure. GF mice on the WD gained significantly less body fat than GF mice on the HFD. GF mice on both HFD and WD showed increased intestinal mRNA expression of fasting-induced adipose factor/angiopoietin-like protein 4 (Fiaf/Angptl4), but they showed no major changes in circulating Fiaf/Angptl4 compared with CV mice. The faecal microbiota composition of the CV mice differed between diets: the proportion of Firmicutes increased on both HFD and WD at the expense of the Bacteroidetes. This increase in the Firmicutes was mainly due to the proliferation of one family within this phylum: the Erysipelotrichaceae. We conclude that the absence of gut microbiota does not provide a general protection from diet-induced obesity, that intestinal production of Fiaf/Angptl4 does not play a causal role in gut microbiota-mediated effects on fat storage and that diet composition affects gut microbial composition to larger extent than previously thought.

  8. Diet induced thermogenesis with oral & intravenous feeding in chronically undernourished human subjects.

    PubMed

    Sekhar, R V; Shetty, P S; Kurpad, A V

    1998-12-01

    The parasympathetic nervous system (PNS) has been shown to be important in the mediation of diet induced thermogenesis (DIT). Chronically energy deficient (CED) subjects have a high resting parasympathetic tone, which could lead to a greater than expected DIT. DIT was studied in chronically energy deficient adult men and healthy age-matched volunteers (6 controls, 7 CED subjects) with an isocaloric (600 kcal) meal given by the oral and intravenous (i.v.) routes on two consecutive days, on a crossover basis. The resting metabolic rate (RMR) and the DIT were measured over 6 h, along with cardiovascular, biochemical and anthropometric parameters. Anthropometrically (height, weight, fat free mass, body mass index, mid upper arm circumference and sum of skinfolds), the CED group differed significantly from the well-nourished control group. There were no significant differences between the two groups in the basal state for metabolic (RMR, oxygen consumption, respiratory quotient), cardiovascular [blood pressure (BP), heart rate, cardiac output], and biochemical (plasma glucose, insulin and norepinephrine) parameters. The CED group had a significantly higher DIT response for both meal types when compared to the controls, when expressed as an absolute value and as a percentage response. However, the response was not significant when corrected for the meal size and body weight. There were also no significant differences between the two meal types in each group for the metabolic, cardiovascular and biochemical parameters during the DIT period, although, in general, the oral meal gave a larger DIT response compared to the i.v. meal. Both groups predominantly oxidised fat during the fasted stage and switched to carbohydrate oxidation when fed. It appears that, the previously demonstrated higher tone in the PNS, does not make a significant contribution to the thermic response of a meal in these subjects.

  9. Diet-induced iron deficiency anemia and pregnancy outcome in rhesus monkeys12

    PubMed Central

    Golub, Mari S; Hogrefe, Casey E; Tarantal, Alice F; Germann, Stacey L; Beard, John L; Georgieff, Michael K; Calatroni, Agustin; Lozoff, Betsy

    2006-01-01

    Background Iron deficiency anemia (IDA) is relatively common in the third trimester of pregnancy, but causal associations with low birth weight and compromised neonatal iron status are difficult to establish in human populations. Objective The objective was to determine the effects of diet-induced IDA on intrauterine growth and neonatal iron status in an appropriate animal model for third-trimester IDA in women. Design Hematologic and iron-status measures, pregnancy outcomes, and fetal and neonatal evaluations were compared between pregnant rhesus monkeys (n = 14) fed a diet containing 10 μg Fe/g diet from the time of pregnancy detection (gestation days 28–30) and controls (n = 24) fed 100 μg Fe/g diet. Results By the third trimester, 79% of the iron-deprived dams and 29% of the control monkeys had a hemoglobin concentration <11 g/dL. There were also significant group differences in hematocrit, mean corpuscular volume, transferrin saturation, serum ferritin, and serum iron. At birth, the newborns of monkeys iron-deprived during pregnancy had significantly lower hemoglobin, mean corpuscular volume, and mean corpuscular hemoglobin values and a lower ratio of erythroid to total colony-forming units in bone marrow than did the control newborns. Pregnancy weight gain did not differ significantly between the iron-deprived and control dams, and the fetuses and newborns of the iron-deprived dams were not growth retarded relative to the controls. Gestation length, the number of stillbirths, and neonatal neurobehavioral test scores did not differ significantly by diet group. Conclusion These data indicate that an inadequate intake of iron from the diet during pregnancy in rhesus monkeys can lead to compromised hematologic status of the neonate without indications of growth retardation or impaired neurologic function at birth. PMID:16522913

  10. Resistance to Diet-Induced Obesity and Associated Metabolic Perturbations in Haploinsufficient Monocarboxylate Transporter 1 Mice

    PubMed Central

    Steiner, Nadia; Carneiro, Lionel; Favrod, Céline; Preitner, Frédéric; Thorens, Bernard; Stehle, Jean-Christophe; Dix, Laure; Pralong, François; Magistretti, Pierre J.; Pellerin, Luc

    2013-01-01

    The monocarboxylate transporter 1 (MCT1 or SLC16A1) is a carrier of short-chain fatty acids, ketone bodies, and lactate in several tissues. Genetically modified C57BL/6J mice were produced by targeted disruption of the mct1 gene in order to understand the role of this transporter in energy homeostasis. Null mutation was embryonically lethal, but MCT1+/− mice developed normally. However, when fed high fat diet (HFD), MCT1+/− mice displayed resistance to development of diet-induced obesity (24.8% lower body weight after 16 weeks of HFD), as well as less insulin resistance and no hepatic steatosis as compared to littermate MCT1+/+ mice used as controls. Body composition analysis revealed that reduced weight gain in MCT1+/− mice was due to decreased fat accumulation (50.0% less after 9 months of HFD) notably in liver and white adipose tissue. This phenotype was associated with reduced food intake under HFD (12.3% less over 10 weeks) and decreased intestinal energy absorption (9.6% higher stool energy content). Indirect calorimetry measurements showed ∼ 15% increase in O2 consumption and CO2 production during the resting phase, without any changes in physical activity. Determination of plasma concentrations for various metabolites and hormones did not reveal significant changes in lactate and ketone bodies levels between the two genotypes, but both insulin and leptin levels, which were elevated in MCT1+/+ mice when fed HFD, were reduced in MCT1+/− mice under HFD. Interestingly, the enhancement in expression of several genes involved in lipid metabolism in the liver of MCT1+/+ mice under high fat diet was prevented in the liver of MCT1+/− mice under the same diet, thus likely contributing to the observed phenotype. These findings uncover the critical role of MCT1 in the regulation of energy balance when animals are exposed to an obesogenic diet. PMID:24367518

  11. Reduction from cost-sensitive ordinal ranking to weighted binary classification.

    PubMed

    Lin, Hsuan-Tien; Li, Ling

    2012-05-01

    We present a reduction framework from ordinal ranking to binary classification. The framework consists of three steps: extracting extended examples from the original examples, learning a binary classifier on the extended examples with any binary classification algorithm, and constructing a ranker from the binary classifier. Based on the framework, we show that a weighted 0/1 loss of the binary classifier upper-bounds the mislabeling cost of the ranker, both error-wise and regret-wise. Our framework allows not only the design of good ordinal ranking algorithms based on well-tuned binary classification approaches, but also the derivation of new generalization bounds for ordinal ranking from known bounds for binary classification. In addition, our framework unifies many existing ordinal ranking algorithms, such as perceptron ranking and support vector ordinal regression. When compared empirically on benchmark data sets, some of our newly designed algorithms enjoy advantages in terms of both training speed and generalization performance over existing algorithms. In addition, the newly designed algorithms lead to better cost-sensitive ordinal ranking performance, as well as improved listwise ranking performance.

  12. Cafeteria diet induce changes in blood flow that are more related with heat dissipation than energy accretion

    PubMed Central

    Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Romero, María del Mar; Fernández-López, José Antonio; Alemany, Marià

    2016-01-01

    Background. A “cafeteria” diet is a self-selected high-fat diet, providing an excess of energy, which can induce obesity. Excess of lipids in the diet hampers glucose utilization eliciting insulin resistance, which, further limits amino acid oxidation for energy. Methods. Male Wistar rats were exposed for a month to “cafeteria” diet. Rats were cannulated and fluorescent microspheres were used to determine blood flow. Results. Exposure to the cafeteria diet did not change cardiac output, but there was a marked shift in organ irrigation. Skin blood flow decreased to compensate increases in lungs and heart. Blood flow through adipose tissue tended to increase in relation to controls, but was considerably increased in brown adipose tissue (on a weight basis). Discussion. The results suggest that the cafeteria diet-induced changes were related to heat transfer and disposal. PMID:27547590

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

    PubMed

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

    2016-02-06

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

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

    PubMed Central

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

    2016-01-01

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

  15. Beyond the role of dietary protein and amino acids in the prevention of diet-induced obesity.

    PubMed

    Petzke, Klaus J; Freudenberg, Anne; Klaus, Susanne

    2014-01-20

    High-protein diets have been shown to prevent the development of diet-induced obesity and can improve associated metabolic disorders in mice. Dietary leucine supplementation can partially mimic this effect. However, the molecular mechanisms triggering these preventive effects remain to be satisfactorily explained. Here we review studies showing a connection between high protein or total amino nitrogen intake and obligatory water intake. High amino nitrogen intake may possibly lower lipid storage, and prevent insulin resistance. Suggestions are made for further systematical studies to explore the relationship between water consumption, satiety, and energy expenditure. Moreover, these examinations should better distinguish between leucine-specific and unspecific effects. Research in this field can provide important information to justify dietary recommendations and strategies in promoting long-term weight loss and may help to reduce health problems associated with the comorbidities of obesity.

  16. Size, weight, and power reduction of mercury cadmium telluride infrared detection modules

    NASA Astrophysics Data System (ADS)

    Breiter, Rainer; Ihle, Tobias; Wendler, Joachim C.; Lutz, Holger; Rutzinger, Stefan; Schallenberg, Timo; Hofmann, Karl C.; Ziegler, Johann

    2011-06-01

    Application requirements driving present IR technology development activities are improved capability to detect and identify a threat as well as the need to reduce size weight and power consumption (SWaP) of thermal sights. In addition to the development of 3rd Gen IR modules providing dual-band or dual-color capability, AIM is focused on IR FPAs with reduced pitch and high operating temperature for SWaP reduction. State-of-the-art MCT technology allows AIM the production of mid-wave infrared (MWIR) detectors operating at temperatures exceeding 120 K without any need to sacrifice the 5-μm cut-off wavelength. These FPAs allow manufacturing of low cost IR modules with minimum size, weight, and power for state-of-the-art high performance IR systems. AIM has realized full TV format MCT 640×512 mid-wave and long-wave IR detection modules with a 15-μm pitch to meet the requirements of critical military applications like thermal weapon sights or thermal imagers in unmanned aerial vehicles applications. In typical configurations like an F/4.6 cold shield for the 640×512 MWIR module an noise equivalent temperature difference (NETD) <25 mK @ 5 ms integration time is achieved, while the long-wavelength infrared (LWIR) modules achieve an NETD <38 mK @ F/2 and 180 μs integration time. For the LWIR modules, FPAs with a cut-off up to 10 μm have been realized. The modules are available either with different integral rotary cooler configurations for portable applications that require minimum cooling power or a new split linear cooler providing long lifetime with a mean time to failure (MTTF) > 20000, e.g., for warning sensors in 24/7 operation. The modules are available with optional image processing electronics providing nonuniformity correction and further image processing for a complete IR imaging solution. The latest results and performance of those modules and their applications are presented.

  17. Ski overexpression in skeletal muscle modulates genetic programs that control susceptibility to diet-induced obesity and insulin signaling.

    PubMed

    Diaz, Marianne; Martel, Nick; Fitzsimmons, Rebecca L; Eriksson, Natalie A; Cowin, Gary J; Thomas, Gethin P; Cao, Kim-Anh Lê; Muscat, George E O; Leong, Gary M

    2012-11-01

    Transgenic mice overexpressing chicken Ski (c-Ski) have marked decrease in adipose mass with skeletal muscle hypertrophy. Recent evidence indicates a role for c-Ski in lipogenesis and energy expenditure. In the present study, wild type (WT) and c-Ski mice were challenged on a high-fat (HF) diet to determine whether c-Ski mice were resistant to diet-induced obesity. During the HF feeding WT mice gained significantly more weight than chow-fed animals, while c-Ski mice were partially resistant to the effects of the HF diet on weight. Body composition analysis confirmed the decreased adipose mass in c-Ski mice compared to WT mice. c-Ski mice possess a similar metabolic rate and level of food consumption to WT littermates, despite lower activity levels and on chow diet show mild glucose intolerance relative to WT littermates. On HF diet, glucose tolerance surprisingly remained unchanged in c-Ski mice, while it became worse in WT mice. Skeletal muscle of c-Ski mice exhibit impaired insulin-stimulated Akt phosphorylation and glucose uptake. In concordance, gene expression profiling of skeletal muscle of chow and HF-fed mice indicated that Ski suppresses gene expression associated with insulin signaling and glucose uptake and alters gene pathways involved in myogenesis and adipogenesis. In conclusion, c-Ski mice are partially resistant to diet-induced obesity and display aberrant insulin signaling and glucose homeostasis which is associated with alterations in gene expression that inhibit lipogenesis and insulin signaling. These results suggest Ski plays a major role in skeletal muscle metabolism and adipogenesis and hence influences risk of obesity and diabetes.

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

    PubMed

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

    2014-09-01

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

  19. Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats.

    PubMed

    Conde, Silvia V; Nunes da Silva, Tiago; Gonzalez, Constancio; Mota Carmo, Miguel; Monteiro, Emilia C; Guarino, Maria P

    2012-01-01

    We tested the hypothesis that long-term caffeine intake prevents the development of insulin resistance and hypertension in two pathological animal models: the high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals: control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF; caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin sensitivity was assessed using the insulin tolerance test. Blood pressure, weight gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance and hypertension induced by both the HF and HSu diets. In the HF-fed animals caffeine treatment restored fasting insulin levels to control values and reversed increased weight gain and visceral fat mass. In the HSu group, caffeine reversed fasting hyperglycaemia and restored NEFA to control values. There were no changes either in plasma NO or in hepatic glutathione levels. In contrast, caffeine totally prevented the increase in serum catecholamines induced by HF and HSu diets. To test the hypothesis that inhibition of the sympathetic nervous system prevents the development of diet-induced insulin resistance we administered carvedilol, an antagonist of β1, β2 and also α1 adrenoceptors, to HF and HSu rats. Carvedilol treatment fully prevented diet-induced insulin resistance and hypertension, mimicking the effect of caffeine. We concluded that long-term caffeine intake prevented the development of insulin resistance and hypertension in HF and HSu models and that this effect was related to a decrease in circulating catecholamines.

  20. Yerba mate extract (Ilex paraguariensis) attenuates both central and peripheral inflammatory effects of diet-induced obesity in rats.

    PubMed

    Pimentel, Gustavo D; Lira, Fábio S; Rosa, José C; Caris, Aline V; Pinheiro, Fernanda; Ribeiro, Eliane B; Oller do Nascimento, Cláudia M; Oyama, Lila M

    2013-05-01

    To clarify the effects of natural dietary components on the metabolic consequences of obesity, we examined the effects of yerba mate extract Ilex paraguariensis on both central and peripheral inflammatory effects of diet-induced obesity and correlated the hypothalamic tumor necrosis factor (TNF)-α level with adipose depot weight. Wistar rats were divided into four groups: a control group (CTL) fed with chow diet, a second group fed with chow diet plus yerba mate extract (CTL+E), a third group fed with a high-fat diet rich in saturated fatty acids (HFD) and a fourth group fed with HFD plus yerba mate extract (HFD+E). Enzyme-linked immunosorbent assay, Western blotting, colorimetric method and treatment by gavage were utilized as materials and methods. The HFD groups showed a significant increase in food intake (kcal), body weight, adipose tissue and leptin level in comparison to CTL and CTL+E. HFD leads to increase of both central and peripheral inflammatory effects, and deregulation of insulin pathway. In addition, yerba mate extract intake blunted the proinflammatory effects of diet-induced obesity in rats by reducing the phosphorylation of hypothalamic IKK and NFκBp65 expression and increasing the phosphorylation of IκBα, the expression of adiponectin receptor-1 and consequently the amount of IRS-2. Moreover, the increase in interleukin (IL)-6 levels in the liver and muscle and of the IL-10/TNF-α ratio in groups that received yerba mate extract showed the anti-inflammatory effects of this natural substance. Taken together, our data suggest that the use of yerba mate extract may be useful for reducing low-grade obesity-associated inflammation.

  1. Reduction of structural weight, costs and complexity of a control system in the active vibration reduction of flexible structures

    NASA Astrophysics Data System (ADS)

    Daraji, A. H.; Hale, J. M.

    2014-09-01

    This paper concerns the active vibration reduction of a flexible structure with discrete piezoelectric sensors and actuators in collocated pairs bonded to its surface. In this study, a new fitness and objective function is proposed to determine the optimal number of actuators, based on variations in the average closed loop dB gain margin reduction for all of the optimal piezoelectric pairs and on the modes that are required to be attenuated using the optimal linear quadratic control scheme. The aim of this study is to find the minimum number of optimally located sensor/actuator pairs, which can achieve the same vibration reduction as a greater number, in order to reduce the cost, complexity and power requirement of the control system. This optimization was done using a genetic algorithm. The technique may be applied to any lightly damped structure, and is demonstrated here by attenuating the first six vibration modes of a flat cantilever plate. It is shown that two sensor/actuator pairs, located and controlled optimally, give almost the same vibration reduction as ten pairs. These results are validated by comparing the open and closed loop time responses and actuator feedback voltages for various numbers of piezoelectric pairs using the ANSYS finite element package and a proportional differential control scheme.

  2. Diet-Induced Obesity Is Associated with an Impaired NK Cell Function and an Increased Colon Cancer Incidence

    PubMed Central

    Goritz, Vincent; Doberstein, Henriette; Hiller, Grit Gesine Ruth; Rosenstock, Philip; Jahn, Janine; Pörtner, Ole; Berreis, Tobias; Mueller, Thomas; Spielmann, Julia

    2017-01-01

    Obesity is associated with an increased colon cancer incidence, but underlying mechanisms remained unclear. Previous studies showed altered Natural killer (NK) cell functions in obese individuals. Therefore, we studied the impact of an impaired NK cell functionality on the increased colon cancer risk in obesity. In vitro investigations demonstrated a decreased IFN-γ secretion and cytotoxicity of human NK cells against colon tumor cells after NK cell preincubation with the adipokine leptin. In addition, leptin incubation decreased the expression of activating NK cell receptors. In animal studies, colon cancer growth was induced by injection of azoxymethane (AOM) in normal weight and diet-induced obese rats. Body weight and visceral fat mass were increased in obese animals compared to normal weight rats. AOM-treated obese rats showed an increased quantity, size, and weight of colon tumors compared to the normal weight tumor group. Immunohistochemical analyses demonstrated a decreased number of NK cells in spleen and liver in obesity. Additionally, the expression levels of activating NK cell receptors were lower in spleen and liver of obese rats. The results show for the first time that the decreased number and impaired NK cell function may be one cause for the higher colon cancer risk in obesity. PMID:28357137

  3. Tasting profile affects adoption of caloric beverage reduction in a randomized weight loss intervention

    PubMed Central

    Wang, X.; Popkin, B.; Tate, D. F.

    2016-01-01

    Summary Objective The aim of this study was to examine differences in rates of non‐caloric beverage adoption by participants classified as sweet likers (SLs) or sweet dislikers (measured using a behavioural tasting task). Methods Data are a sub‐study from a 6‐month, three‐group, randomized weight loss trial (CHOICE) (body mass index 36.3 ± 5.8 kg m−2, 84% female, aged 42.2 ± 10.9 years, 53% African‐American) comparing the replacement of caloric beverages with either non‐caloric sweetened beverages (diet) or water (water) compared with a control group. This sub‐study, which included participants within the water (n = 106) and diet (n = 103) groups only, examined whether SLs (n = 33 water; n = 37 diet) varied in their adherence to caloric beverage recommendations compared with sweet dislikers (n = 73 water; n = 76 diet) over the 6‐month study. Results Diet intake and sweet‐liking data collected on 190 (3 months) and 169 participants (6 months) were used for analysis. The interaction between SL status and beverage group (diet vs. water) approached significance (P = 0.06) at 3 months but not 6 months. Caloric beverage intake (% energy) at 3 months was significantly higher in SLs within the water group (9.7 ± 1.4%) compared with SLs in the diet group (5.4 ± 1.0%, P = 0.03). Conclusions Results suggest that SL status may affect the rate in reduction of caloric beverages when water is the recommended substitution. Future studies should explore tailoring beverage recommendations to tasting profile. PMID:28090344

  4. Identification of determinants for weight reduction in overweight and obese children and adolescents.

    PubMed

    Schiel, Ralf; Kaps, Alexander; Bieber, Gerald; Kramer, Guido; Seebach, Henning; Hoffmeyer, André

    2010-01-01

    We conducted a pilot trial of electronic technology integrated into the treatment of children and adolescents who are overweight or obese. A total of 30 patients (mean age 14 years, mean BMI 32.7 kg/m(2)) were admitted to our hospital to participate in a structured treatment and teaching programme (STTP). To assess physical activity and eating habits, a mobile motion sensor board (MoSeBo) or a sensor for physical activity, integrated into a mobile phone with digital camera (DiaTrace) was used. Over an average period of four days of monitoring, the mean intensity (15.4 activity units) and duration of physical activity (267 min/d) were recorded with the mobile sensors. The mean time spent walking was 64 min/d, running 11 min/d, cycling 24 min/d and car driving 21 min/d. There were significant differences (P < 0.001) between self-reported physical activity and objective assessment: in general the duration of physical activity documented by children and adolescents was much higher than the objective assessment. Similarly, the real caloric intake was higher than the self-estimates (P = 0.085). A multivariate analysis showed that the following variables were significantly associated with weight reduction in the hospital STTP (R-squared = 0.59): high motivation, intrafamilial conflicts, duration of physical activity assessed with the MoSeBo/DiaTrace system, and the body fat mass at onset of therapy. All children and adolescents included in the trial completed it. Although the MoSeBo/DiaTrace system was used for a relatively short period in each patient, the high acceptance demonstrated that it could be integrated into therapy easily.

  5. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity

    PubMed Central

    Everard, Amandine; Belzer, Clara; Geurts, Lucie; Ouwerkerk, Janneke P.; Druart, Céline; Bindels, Laure B.; Guiot, Yves; Derrien, Muriel; Muccioli, Giulio G.; Delzenne, Nathalie M.; de Vos, Willem M.; Cani, Patrice D.

    2013-01-01

    Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders. PMID:23671105

  6. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity.

    PubMed

    Everard, Amandine; Belzer, Clara; Geurts, Lucie; Ouwerkerk, Janneke P; Druart, Céline; Bindels, Laure B; Guiot, Yves; Derrien, Muriel; Muccioli, Giulio G; Delzenne, Nathalie M; de Vos, Willem M; Cani, Patrice D

    2013-05-28

    Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.

  7. Diet-induced obesity causes ghrelin resistance in reward processing tasks.

    PubMed

    Lockie, Sarah H; Dinan, Tara; Lawrence, Andrew J; Spencer, Sarah J; Andrews, Zane B

    2015-12-01

    Diet-induced obesity (DIO) causes ghrelin resistance in hypothalamic Agouti-related peptide (AgRP) neurons. However, ghrelin promotes feeding through actions at both the hypothalamus and mesolimbic dopamine reward pathways. Therefore, we hypothesized that DIO would also establish ghrelin resistance in the ventral tegmental area (VTA), a major site of dopaminergic cell bodies important in reward processing. We observed reduced sucrose and saccharin consumption in Ghrelin KO vs Ghrelin WT mice. Moreover, DIO reduced saccharin consumption relative to chow-fed controls. These data suggest that the deletion of ghrelin and high fat diet both cause anhedonia. To assess if these are causally related, we tested whether DIO caused ghrelin resistance in a classic model of drug reward, conditioned place preference (CPP). Chow or high fat diet (HFD) mice were conditioned with ghrelin (1mg/kg in 10ml/kg ip) in the presence or absence of food in the conditioning chamber. We observed a CPP to ghrelin in chow-fed mice but not in HFD-fed mice. HFD-fed mice still showed a CPP for cocaine (20mg/kg), indicating that they maintained the ability to develop conditioned behaviour. The absence of food availability during ghrelin conditioning sessions induced a conditioned place aversion, an effect that was still present in both chow and HFD mice. Bilateral intra-VTA ghrelin injection (0.33μg/μl in 0.5μl) robustly increased feeding in both chow-fed and high fat diet (HFD)-fed mice; however, this was correlated with body weight only in the chow-fed mice. Our results suggest that DIO causes ghrelin resistance albeit not directly in the VTA. We suggest there is impaired ghrelin sensitivity in upstream pathways regulating reward pathways, highlighting a functional role for ghrelin linking appropriate metabolic sensing with reward processing.

  8. Alterations in the hippocampal endocannabinoid system in diet-induced obese mice.

    PubMed

    Massa, Federico; Mancini, Giacomo; Schmidt, Helmut; Steindel, Frauke; Mackie, Ken; Angioni, Carlo; Oliet, Stéphane H R; Geisslinger, Gerd; Lutz, Beat

    2010-05-05

    The endocannabinoid (eCB) system plays central roles in the regulation of food intake and energy expenditure. Its alteration in activity contributes to the development and maintenance of obesity. Stimulation of the cannabinoid receptor type 1 (CB(1) receptor) increases feeding, enhances reward aspects of eating, and promotes lipogenesis, whereas its blockade decreases appetite, sustains weight loss, increases insulin sensitivity, and alleviates dysregulation of lipid metabolism. The hypothesis has been put forward that the eCB system is overactive in obesity. Hippocampal circuits are not directly involved in the neuronal control of food intake and appetite, but they play important roles in hedonic aspects of eating. We investigated the possibility whether or not diet-induced obesity (DIO) alters the functioning of the hippocampal eCB system. We found that levels of the two eCBs, 2-arachidonoyl glycerol (2-AG) and anandamide, were increased in the hippocampus from DIO mice, with a concomitant increase of the 2-AG synthesizing enzyme diacylglycerol lipase-alpha and increased CB(1) receptor immunoreactivity in CA1 and CA3 regions, whereas CB(1) receptor agonist-induced [(35)S]GTPgammaS binding was unchanged. eCB-mediated synaptic plasticity was changed in the CA1 region, as depolarization-induced suppression of inhibition and long-term depression of inhibitory synapses were enhanced. Functionality of CB(1) receptors in GABAergic neurons was furthermore revealed, as mice specifically lacking CB(1) receptors on this neuronal population were partly resistant to DIO. Our results show that DIO-induced changes in the eCB system affect not only tissues directly involved in the metabolic regulation but also brain regions mediating hedonic aspects of eating and influencing cognitive processes.

  9. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles

    PubMed Central

    Xue, Yuan; Xu, Xiaoyang; Zhang, Xue-Qing; Farokhzad, Omid C.; Langer, Robert

    2016-01-01

    The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. PMID:27140638

  10. Yellow pea fiber improves glycemia and reduces Clostridium leptum in diet-induced obese rats.

    PubMed

    Eslinger, Amanda J; Eller, Lindsay K; Reimer, Raylene A

    2014-08-01

    Numerous studies have demonstrated the impact of functional fibers on gut microbiota and metabolic health, but some less well-studied fibers and/or fractions of foods known to be high in fiber still warrant examination. The aim of this study was to assess the effect of yellow pea-derived fractions varying in fiber and protein content on metabolic parameters and gut microbiota in diet-induced obese rats. We hypothesized that the yellow pea fiber (PF) fraction would improve glycemia and alter gut microbiota. Rats were randomized to 1 of 5 isoenergetic dietary treatments for 6 weeks: (1) control; (2) oligofructose (OFS); (3) yellow PF; (4) yellow pea flour (PFL); or (5) yellow pea starch (PS). Glycemia, plasma gut hormones, body composition, hepatic triglyceride content, gut microbiota, and messenger RNA expression of genes related to hepatic fat metabolism were examined. Pea flour attenuated weight gain compared with control, PF, and PS (P < .05). Pea flour, PS, and OFS had significantly lower final percent body fat compared with control. Oligofructose but not the pea fraction diets reduced food intake compared with control (P < .05). Pea fiber resulted in lower fasting glucose and glucose area under the curve compared with control. Changes in gut microbiota were fraction specific and included a decrease in Firmicutes (percent) for OFS, PF, and PFL compared with control (P < .05). The Firmicutes/Bacteroidetes ratio was reduced with OFS, PF, and PFL when compared with PS (P < .05). Taken together, this work suggests that yellow pea-derived fractions are able to distinctly modulate metabolic parameters and gut microbiota in obese rats.

  11. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin.

    PubMed

    Tilton, Susan C; Waters, Katrina M; Karin, Norman J; Webb-Robertson, Bobbie-Jo M; Zangar, Richard C; Lee, K Monica; Bigelow, Diana J; Pounds, Joel G; Corley, Richard A

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  12. Mineralocorticoid receptor blockade prevents Western diet-induced diastolic dysfunction in female mice.

    PubMed

    Bostick, Brian; Habibi, Javad; DeMarco, Vincent G; Jia, Guanghong; Domeier, Timothy L; Lambert, Michelle D; Aroor, Annayya R; Nistala, Ravi; Bender, Shawn B; Garro, Mona; Hayden, Melvin R; Ma, Lixin; Manrique, Camila; Sowers, James R

    2015-05-01

    Overnutrition/obesity predisposes individuals, particularly women, to diastolic dysfunction (DD), an independent predictor of future cardiovascular disease. We examined whether low-dose spironolactone (Sp) prevents DD associated with consumption of a Western Diet (WD) high in fat, fructose, and sucrose. Female C57BL6J mice were fed a WD with or without Sp (1 mg·kg(-1)·day(-1)). After 4 mo on the WD, mice exhibited increased body weight and visceral fat, but similar blood pressures, compared with control diet-fed mice. Sp prevented the development of WD-induced DD, as indicated by decreased isovolumic relaxation time and an improvement in myocardial performance (diet-induced DD in women. Mineralocorticoid antagonism; low-dose spironolactone; aldosterone;high-fat diet; high-fructose diet; oxidative stress

  13. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.

    PubMed

    Trinko, Joseph R; Land, Benjamin B; Solecki, Wojciech B; Wickham, Robert J; Tellez, Luis A; Maldonado-Aviles, Jaime; de Araujo, Ivan E; Addy, Nii A; DiLeone, Ralph J

    2016-01-01

    The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.

  14. Diet-Induced Obesity Reprograms the Inflammatory Response of the Murine Lung to Inhaled Endotoxin

    SciTech Connect

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, Monika K.; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures.

  15. Diet-induced obesity reprograms the inflammatory response of the murine lung to inhaled endotoxin

    SciTech Connect

    Tilton, Susan C.; Waters, Katrina M.; Karin, Norman J.; Webb-Robertson, Bobbie-Jo M.; Zangar, Richard C.; Lee, K. Monica; Bigelow, Diana J.; Pounds, Joel G.; Corley, Richard A.

    2013-03-01

    The co-occurrence of environmental factors is common in complex human diseases and, as such, understanding the molecular responses involved is essential to determine risk and susceptibility to disease. We have investigated the key biological pathways that define susceptibility for pulmonary infection during obesity in diet-induced obese (DIO) and regular weight (RW) C57BL/6 mice exposed to inhaled lipopolysaccharide (LPS). LPS induced a strong inflammatory response in all mice as indicated by elevated cell counts of macrophages and neutrophils and levels of proinflammatory cytokines (MDC, MIP-1γ, IL-12, RANTES) in the bronchoalveolar lavage fluid. Additionally, DIO mice exhibited 50% greater macrophage cell counts, but decreased levels of the cytokines, IL-6, TARC, TNF-α, and VEGF relative to RW mice. Microarray analysis of lung tissue showed over half of the LPS-induced expression in DIO mice consisted of genes unique for obese mice, suggesting that obesity reprograms how the lung responds to subsequent insult. In particular, we found that obese animals exposed to LPS have gene signatures showing increased inflammatory and oxidative stress response and decreased antioxidant capacity compared with RW. Because signaling pathways for these responses can be common to various sources of environmentally induced lung damage, we further identified biomarkers that are indicative of specific toxicant exposure by comparing gene signatures after LPS exposure to those from a parallel study with cigarette smoke. These data show obesity may increase sensitivity to further insult and that co-occurrence of environmental stressors result in complex biosignatures that are not predicted from analysis of individual exposures. - Highlights: ► Obesity modulates inflammatory markers in BAL fluid after LPS exposure. ► Obese animals have a unique transcriptional signature in lung after LPS exposure. ► Obesity elevates inflammatory stress and reduces antioxidant capacity in the lung

  16. High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats.

    PubMed

    Milagro, F I; Campión, J; García-Díaz, D F; Goyenechea, E; Paternain, L; Martínez, J A

    2009-03-01

    Leptin is an adipokine involved in body weight and food intake regulation whose promoter region presents CpG islands that could be subject to dynamic methylation. This methylation process could be affected by environmental (e.g. diet) or endogenous (e.g., adipocyte differentiation, inflammation, hypoxia) factors, and could influence adipocyte leptin gene expression. The aim of this article was to study whether a high-energy diet may affect leptin gene promoter methylation in rats. A group of eleven male Wistar rats were assigned into two dietary groups, one fed on a control diet for 11 weeks and the other on a high-fat cafeteria diet. Rats fed a high-energy diet become overweight and hyperleptinemic as compared to the controls. DNA isolated from retroperitoneal adipocytes was treated with bisulfite and a distal portion of leptin promoter (from -694 to -372 bp) including 13 CpG sites was amplified by PCR and sequenced. The studied promoter portion was slightly more methylated in the cafeteria-fed animals, which was statistically significant (p < 0.05) for one of the CpG sites (located at the position -443). In obese rats, such methylation was associated to lower circulating leptin levels, suggesting that this position could be important in the regulation of leptin gene expression, probably by being a target sequence of different transcription factors. Our findings reveal, for the first time, that leptin methylation pattern can be influenced by diet-induced obesity, and suggest that epigenetic mechanisms could be involved in obesity by regulating the expression of important epiobesigenic genes.

  17. Western-style diet induces insulin insensitivity and hyperactivity in adolescent male rats.

    PubMed

    Marwitz, Shannon E; Woodie, Lauren N; Blythe, Sarah N

    2015-11-01

    The prevalence of obesity in children and adolescents has increased rapidly over the past 30 years, as has the incidence of attention deficit hyperactivity disorder (ADHD). In 2012, it was found that overweight children have a twofold higher chance of developing ADHD than their normal weight counterparts. Previous work has documented learning and memory impairments linked to consumption of an energy-dense diet in rats, but the relationship between diet and ADHD-like behaviors has yet to be explored using animal models. Therefore, the purpose of this study was to explore the role of diet in the etiology of attention and hyperactivity disorders using a rat model of diet-induced obesity. Male Sprague-Dawley rats were fed either a control diet or a Western-style diet (WSD) for ten weeks, and specific physiological and behavioral effects were examined. Tail blood samples were collected to measure fasting blood glucose and insulin levels in order to assess insulin insensitivity. Rats also performed several behavioral tasks, including the open field task, novel object recognition test, and attentional set-shifting task. Rats exposed to a WSD had significantly higher fasting insulin levels than controls, but both groups had similar glucose levels. The quantitative insulin sensitivity check index (QUICKI) indicated the development of insulin resistance in WSD rats. Performance in the open field test indicated that WSD induced pronounced hyperactivity and impulsivity. Further, control diet animals were able to discriminate between old and novel objects, but the WSD animals were significantly impaired in object recognition. However, regardless of dietary condition, rats were able to perform the attentional set-shifting paradigm. While WSD impaired episodic memory and induced hyperactivity, attentional set-shifting capabilities are unaffected. With the increasing prevalence of both obesity and ADHD, understanding the potential links between the two conditions is of clinical

  18. Cafeteria diet-induced insulin resistance is not associated with decreased insulin signaling or AMPK activity and is alleviated by physical training in rats.

    PubMed

    Brandt, Nina; De Bock, Katrien; Richter, Erik A; Hespel, Peter

    2010-08-01

    Excess energy intake via a palatable low-fat diet (cafeteria diet) is known to induce obesity and glucose intolerance in rats. However, the molecular mechanisms behind this adaptation are not known, and it is also not known whether exercise training can reverse it. Male Wistar rats were assigned to 12-wk intervention groups: chow-fed controls (CON), cafeteria diet (CAF), and cafeteria diet plus swimming exercise during the last 4 wk (CAF(TR)). CAF feeding led to increased body weight (16%, P < 0.01) and increased plasma glucose (P < 0.05) and insulin levels (P < 0.01) during an IVGTT, which was counteracted by training. In the perfused hindlimb, insulin-stimulated glucose transport in red gastrocnemius muscle was completely abolished in CAF and rescued by exercise training. Apart from a tendency toward an approximately 20% reduction in both basal and insulin-stimulated Akt Ser(473) phosphorylation (P = 0.051) in the CAF group, there were no differences in insulin signaling (IR Tyr(1150/1151), PI 3-kinase activity, Akt Thr(308), TBC1D4 Thr(642), GSK3-alpha/beta Ser(21/9)) or changes in AMPKalpha1 or -alpha2, GLUT4, Munc18c, or syntaxin 4 protein expression or in phosphorylation of AMPK Thr(172) among the groups. In conclusion, surplus energy intake of a palatable but low-fat cafeteria diet resulted in obesity and insulin resistance that was rescued by exercise training. Interestingly, insulin resistance was not accompanied by major defects in the insulin-signaling cascade or in altered AMPK expression or phosphorylation. Thus, compared with previous studies of high-fat feeding, where insulin signaling is significantly impaired, the mechanism by which CAF diet induces insulin resistance seems different.

  19. Pregnancy restores insulin secretion from pancreatic islets in cafeteria diet-induced obese rats.

    PubMed

    Vanzela, E C; Ribeiro, R A; de Oliveira, C A Machado; Rodrigues, F B; Bonfleur, M L; Carneiro, E M; Souza, K L A; Boschero, A C

    2010-02-01

    Insulin resistance during pregnancy is counteracted by enhanced insulin secretion. This condition is aggravated by obesity, which increases the risk of gestational diabetes. Therefore, pancreatic islet functionality was investigated in control nonpregnant (C) and pregnant (CP), and cafeteria diet-fed nonpregnant (Caf), and pregnant (CafP) obese rats. Isolated islets were used for measurements of insulin secretion (RIA), NAD(P)H production (MTS), glucose oxidation ((14)CO(2) production), intracellular Ca(2+) levels (fura-2 AM), and gene expression (real-time PCR). Impaired glucose tolerance was clearly established in Caf and CafP rats at the 14th wk on a diet. Insulin secretion induced by direct depolarizing agents such as KCl and tolbutamide and increasing concentrations of glucose was significantly reduced in Caf, compared with C islets. This reduction was not observed in islets from CP and CafP rats. Accordingly, the glucose oxidation and production of reduced equivalents were increased in CafP islets. The glucose-induced Ca(2+) increase was significantly lower in Caf and higher in CafP, compared with all other groups. CP and CafP islets demonstrated an increased Ca(2+) oscillation frequency, compared with both C and Caf islets, and the amplitude of oscillations was augmented in CafP, compared with Caf islets. In addition, Ca(v)alpha1.2 and SERCA2a mRNA levels were reduced in Caf islets. Ca(v)alpha1.2, but not SERCA2a, mRNA was normalized in CafP islets. In conclusion, cafeteria diet-induced obesity impairs insulin secretion. This alteration is related to the impairment of Ca(2+) handling in pancreatic islets, in especial Ca(2+) influx, a defect that is reversed during pregnancy allowing normalization of insulin secretion.

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

    PubMed Central

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

    2015-01-01

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

  1. Beta-aminoisobutyric acid prevents diet-induced obesity in mice with partial leptin deficiency.

    PubMed

    Begriche, Karima; Massart, Julie; Abbey-Toby, Adjé; Igoudjil, Anissa; Lettéron, Philippe; Fromenty, Bernard

    2008-09-01

    Beta-Aminoisobutyric acid (BAIBA), a thymine catabolite, increases fatty acid oxidation (FAO) in liver and reduces the gain of body fat mass in Swiss (lean) mice fed a standard chow. We determined whether BAIBA could prevent obesity and related metabolic disorders in different murine models. To this end, BAIBA (100 or 500 mg/kg/day) was administered for 4 months in mice totally deficient in leptin (ob/ob). BAIBA (100 mg/kg/day) was also given for 4 months in wild-type (+/+) mice and mice partially deficient in leptin (ob/+) fed a high-calorie (HC) diet. BAIBA did not limit obesity and hepatic steatosis in ob/ob mice, but reduced liver cytolysis and inflammation. In ob/+ mice fed the HC diet, BAIBA fully prevented, or limited, the gain of body fat, steatosis and necroinflammation, glucose intolerance, and hypertriglyceridemia. Plasma beta-hydroxybutyrate was increased, whereas expression of carnitine palmitoyltransferase-1 was augmented in liver and white adipose tissue. Acetyl-CoA carboxylase was more phosphorylated, and de novo lipogenesis was less induced in liver. These favorable effects of BAIBA in ob/+ mice were associated with a restoration of plasma leptin levels. The reduction of body adiposity afforded by BAIBA was less marked in +/+ mice. Finally, BAIBA significantly stimulated the secretion of leptin in isolated ob/+ adipose cells, but not in +/+ cells. Thus, BAIBA could limit triglyceride accretion in tissues through a leptin-dependent stimulation of FAO. As partial leptin deficiency is not uncommon in the general population, supplementation with BAIBA may help to prevent diet-induced obesity and related metabolic disorders in low leptin secretors.

  2. Effects of Maternal Linseed Oil Supplementation on Metabolic Parameters in Cafeteria Diet-induced Obese Rats.

    PubMed

    Benaissa, Nawel; Merzouk, Hafida; Merzouk, Sid Ahmed; Narce, Michel

    2015-04-01

    Because linseed oil may influence maternal and fetal metabolisms, we investigated its role in the modulation of lipid metabolism in cafeteria diet-induced obese rats and their offspring. Female Wistar rats were fed control or cafeteria food, which were either supplemented or not supplemented with linseed oil (5%) for 1 month before and during gestation. At parturition, serum and tissue lipids and enzyme activities were analyzed. Cafeteria diet induced adverse metabolic alterations in both mothers and offspring. Linseed oil improved metabolic status. In conclusion, linseed oil displayed health benefits by modulating tissue enzyme activities in both obese mothers and their newborns.

  3. Examination of the tissue ghrelin expression of rats with diet-induced obesity using radioimmunoassay and immunohistochemical methods.

    PubMed

    Aydin, Suleyman; Sahin, Ibrahim; Ozkan, Yusuf; Dag, Ersel; Gunay, Ahmet; Guzel, Saadet Pilten; Catak, Zekiye; Ozercan, Mehmet Resat

    2012-06-01

    Currently, obesity is an important health problem in all countries, both developed and developing. Dietary habits and neurohormonal imbalances play a critical role in obesity. Circulating amounts of ghrelin, which is a neurohormonal hormone, decrease with obesity and increase with weight loss. Although it is known that both mRNA and peptide version of the ghrelin hormone are expressed in almost all tissues of both humans and animals, it is not known how obesity changes the expression of this hormone in the tissues, with the exception of the gastrointestinal system tissues. Therefore, the objective of the present study is to show how diet-induced obesity in rats changes ghrelin expression in all system tissues, and thus, to shed light on the etiopathology of obesity. The study included 12 male and 12 female 2-month-old Wistar albino species rats. The animals in the control group were fed on standard rat pellet, while those in the experiment group were fed ad libitum on a cafeteria-style diet for 2 months. When their body mass index reached 1 g/cm(2), diet-induced obese (DIO) rats were sacrificed in a sterile environment after one night fasting. Ghrelin localizations in the tissues were studied immunohistochemically using avidin-biotin-peroxidase complex (ABC) method, while tissue ghrelin amounts were analyzed using radioimmunoassay (RIA) method. When the ghrelin amounts in the urogenital system (with the exception of kidney tissues), sensory organs, respiratory system, immune system, skeletal muscle system, cardiovascular system, nervous system, and adipose tissue of rats analyzed by RIA method were compared to those in the control group, tissue ghrelin amounts in the DIO group were found lower. Immunohistochemical findings which showed a similar fall in ghrelin concentrations in the tissues were parallel to RIA results. In addition, ghrelin was shown to be synthesized in the cardiovascular system, heart muscle cells, tails of the sperms, hair follicles, lacrimal

  4. Randomised controlled trial and economic analysis of an internet-based weight management programme: POWeR+ (Positive Online Weight Reduction).

    PubMed Central

    Little, Paul; Stuart, Beth; Hobbs, Fd Richard; Kelly, Jo; Smith, Emily R; Bradbury, Katherine J; Hughes, Stephanie; Smith, Peter Wf; Moore, Michael V; Lean, Mike Ej; Margetts, Barrie M; Byrne, Christopher D; Griffin, Simon; Davoudianfar, Mina; Hooper, Julie; Yao, Guiqing; Zhu, Shihua; Raftery, James; Yardley, Lucy

    2017-01-01

    BACKGROUND Behavioural counselling with intensive follow-up for obesity is effective, but in resource-constrained primary care settings briefer approaches are needed. OBJECTIVES To estimate the clinical effectiveness and cost-effectiveness of an internet-based behavioural intervention with regular face-to-face or remote support in primary care, compared with brief advice. DESIGN Individually randomised three-arm parallel trial with health economic evaluation and nested qualitative interviews. SETTING Primary care general practices in the UK. PARTICIPANTS Patients with a body mass index of ≥ 30 kg/m(2) (or ≥ 28 kg/m(2) with risk factors) identified from general practice records, recruited by postal invitation. INTERVENTIONS Positive Online Weight Reduction (POWeR+) is a 24-session, web-based weight management intervention completed over 6 months. Following online registration, the website randomly allocated participants using computer-generated random numbers to (1) the control intervention (n = 279), which had previously been demonstrated to be clinically effective (brief web-based information that minimised pressure to cut down foods, instead encouraging swaps to healthier choices and increasing fruit and vegetables, plus 6-monthly nurse weighing); (2) POWeR+F (n = 269), POWeR+ supplemented by face-to-face nurse support (up to seven contacts); or (3) POWeR+R (n = 270), POWeR+ supplemented by remote nurse support (up to five e-mails or brief telephone calls). MAIN OUTCOME MEASURES The primary outcome was a modelled estimate of average weight reduction over 12 months, assessed blind to group where possible, using multiple imputation for missing data. The secondary outcome was the number of participants maintaining a 5% weight reduction at 12 months. RESULTS A total of 818 eligible individuals were randomised using computer-generated random numbers. Weight change, averaged over 12 months, was documented in 666 out of 818 participants (81

  5. High-fat diet induces leptin resistance in leptin-deficient mice.

    PubMed

    Koch, C E; Lowe, C; Pretz, D; Steger, J; Williams, L M; Tups, A

    2014-02-01

    immunoreactivity in vehicle-treated Lep(ob/ob) mice that was unaffected by leptin treatment, suggesting central leptin resistance. Negating central inflammation by co-administering a c-Jun n-terminal kinase (JNK) inhibitor reinstated the glucose-lowering effects of leptin. These findings demonstrate that Lep(ob/ob) mice develop leptin resistance on a HFD independent of hyperleptinaemia and also indicate that the JNK inflammatory pathway plays a key role in the induction of diet-induced glucose intolerance.

  6. The effects of forskolin and rolipram on cAMP, cGMP and free fatty acid levels in diet induced obesity.

    PubMed

    Doseyici, S; Mehmetoglu, I; Toker, A; Yerlikaya, F H; Erbay, E

    2014-07-01

    Obesity is a major health problem. We investigated the effects of forskolin and rolipram in the diet of animals in which obesity had been induced. We used 50 female albino Wistar rats that were assigned randomly into five groups as follows: group 1, control; group 2, high fat diet; group 3, high fat diet + forskolin; group 4, high fat diet + rolipram; and group 5, high fat diet + rolipram + forskolin. The rats were fed for 10 weeks and rolipram and forskolin were administered during last two weeks. The animals were sacrificed and blood samples were obtained. Serum cAMP, cGMP and free fatty acids (FFA) levels were measured using ELISA assays. We also measured weight gain during the 10 week period. cAMP and FFA levels of groups 3, 4 and 5 were significantly higher than those of groups 1 and 2. We found no significant differences in serum cGMP levels among the groups. The weight gain in groups 3, 4 and 5 was significantly less than for group 2. We also found that the weight gain in group 5 was significantly less than in groups 3 and 4. We found that both forskolin and rolipram stimulated lipolysis and inhibited body weight increase by increasing cAMP levels. Also, combination therapy using the two agents may be more effective in preventing diet induced obesity than either agent alone. We found also that these agents did not effect cellular cGMP levels in diet induced obesity.

  7. Genetic deletion and pharmacological inhibition of phosphodiesterase 10A protects mice from diet-induced obesity and insulin resistance.

    PubMed

    Nawrocki, Andrea R; Rodriguez, Carlos G; Toolan, Dawn M; Price, Olga; Henry, Melanie; Forrest, Gail; Szeto, Daphne; Keohane, Carol Ann; Pan, Yie; Smith, Karen M; Raheem, Izzat T; Cox, Christopher D; Hwa, Joyce; Renger, John J; Smith, Sean M

    2014-01-01

    Phosphodiesterase 10A (PDE10A) is a novel therapeutic target for the treatment of schizophrenia. Here we report a novel role of PDE10A in the regulation of caloric intake and energy homeostasis. PDE10A-deficient mice are resistant to diet-induced obesity (DIO) and associated metabolic disturbances. Inhibition of weight gain is due to hypophagia after mice are fed a highly palatable diet rich in fats and sugar but not a standard diet. PDE10A deficiency produces a decrease in caloric intake without affecting meal frequency, daytime versus nighttime feeding behavior, or locomotor activity. We tested THPP-6, a small molecule PDE10A inhibitor, in DIO mice. THPP-6 treatment resulted in decreased food intake, body weight loss, and reduced adiposity at doses that produced antipsychotic efficacy in behavioral models. We show that PDE10A inhibition increased whole-body energy expenditure in DIO mice fed a Western-style diet, achieving weight loss and reducing adiposity beyond the extent seen with food restriction alone. Therefore, chronic THPP-6 treatment conferred improved insulin sensitivity and reversed hyperinsulinemia. These data demonstrate that PDE10A inhibition represents a novel antipsychotic target that may have additional metabolic benefits over current medications for schizophrenia by suppressing food intake, alleviating weight gain, and reducing the risk for the development of diabetes.

  8. Phenolic compounds from Rosemary (Rosmarinus officinalis L.) attenuate oxidative stress and reduce blood cholesterol concentrations in diet-induced hypercholesterolemic rats

    PubMed Central

    2013-01-01

    Background Phenolic compounds combine antioxidant and hypocholesterolemic activities and, consequently, are expected to prevent or minimize cardiometabolic risk. Methods To evaluate the effect of an aqueous extract (AQ) and non-esterified phenolic fraction (NEPF) from rosemary on oxidative stress in diet-induced hypercholesterolemia, 48 male 4-week old Wistar rats were divided into 6 groups: 1 chow diet group (C) and 5 hypercholesterolemic diet groups, with 1 receiving water (HC), 2 receiving AQ at concentrations of 7 and 140 mg/kg body weight (AQ70 and AQ140, respectively), and 2 receiving NEPF at concentrations of 7 and 14 mg/kg body weight (NEPF7 and NEPF14, respectively) by gavage for 4 weeks. Results In vitro, both AQ and NEPF had remarkable antioxidant activity in the 2,2-diphenyl-1-picrylhydrazyl (DPPH●) assay, which was similar to BHT. In vivo, the group that received AQ at 70 mg/kg body weight had lower serum total cholesterol (−39.8%), non-HDL-c (−44.4%) and thiobarbituric acid reactive substance (TBARS) levels (−37.7%) compared with the HC group. NEPF (7 and 14 mg/kg) reduced the tissue TBARS levels and increased the activity of tissular antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). Neither AQ nor NEPF was able to ameliorate the alterations in the hypercholesterolemic diet-induced fatty acid composition in the liver. Conclusions These data suggest that phenolic compounds from rosemary ameliorate the antioxidant defense in different tissues and attenuate oxidative stress in diet-induced hypercholesterolemic rats, whereas the serum lipid profile was improved only in rats that received the aqueous extract. PMID:23374457

  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. The effect of isorhamnetin glycosides extracted from Opuntia ficus-indica in a mouse model of diet induced obesity.

    PubMed

    Rodríguez-Rodríguez, César; Torres, Nimbe; Gutiérrez-Uribe, Janet A; Noriega, Lilia G; Torre-Villalvazo, Iván; Leal-Díaz, Ana M; Antunes-Ricardo, Marilena; Márquez-Mota, Claudia; Ordaz, Guillermo; Chavez-Santoscoy, Rocío A; Serna-Saldivar, Sergio O; Tovar, Armando R

    2015-03-01

    A diet rich in polyphenols can ameliorate some metabolic alterations associated with obesity and type 2 diabetes. Opuntia ficus-indica (OFI) is a plant rich in isorhamnetin glycosides and is highly consumed in Mexico. The purpose of this research was to determine the metabolic effect of an OFI extract on a mouse model of diet-induced obesity and in isolated pancreatic islets. OFI extract was added to a high fat (HF) diet at a low (0.3%) or high (0.6%) dose and administered to C57BL/6 mice for 12 weeks. Mice fed the HF diet supplemented with the OFI extract gained less body weight and exhibited significantly lower circulating total cholesterol, LDL cholesterol and HDL cholesterol compared to those fed the HF diet alone. The HF-OFI diet fed mice presented lower glucose and insulin concentration than the HF diet fed mice. However, the HF-OFI diet fed mice tended to have higher insulin concentration than control mice. The OFI extract stimulated insulin secretion in vitro, associated with increased glucose transporter 2 (GLUT2) and peroxisome proliferator-activated receptor gamma (PPARγ) mRNA content. Furthermore, the OFI extract improved glucose tolerance, and additionally increased energy expenditure. These metabolic improvements were associated with reduced adipocyte size, increased hepatic IRS1 tyr-608 and S6 K thr-389 phosphorylation. OFI isorhamnetin glycosides also diminished the hepatic lipid content associated with reduced mRNA expression of the endoplasmic reticulum stress markers and lipogenic enzymes and increased mRNA expression of genes related to fatty acid oxidation. Overall, the OFI extract prevented the development of metabolic abnormalities associated with diet-induced obesity.

  11. Role of human pregnane X receptor in high fat diet-induced obesity in pre-menopausal female mice

    PubMed Central

    Spruiell, Krisstonia; Jones, Dominique Z.; Cullen, John M.; Awumey, Emmanuel M.; Gonzalez, Frank J.; Gyamfi, Maxwell A.

    2014-01-01

    Obesity is a complex metabolic disorder that is more prevalent among women. Until now, the only relevant rodent models of diet-induced obesity were via the use of ovariectomized (“postmenopausal”) females. However, recent reports suggest that the xenobiotic nuclear receptor pregnane X receptor (PXR) may contribute to obesity. Therefore, we compared the roles of mouse and human PXRs in diet-induced obesity between wild type (WT) and PXR-humanized (hPXR) transgenic female mice fed either control or high-fat diets (HFD) for 16 weeks. HFD-fed hPXR mice gained weight more rapidly than controls, exhibited hyperinsulinemia, and impaired glucose tolerance. Fundamental differences were observed between control-fed hPXR and WT females: hPXR mice possessed reduced estrogen receptor α (ERα) but enhanced uncoupling protein 1 (UCP1) protein expression in white adipose tissue (WAT); increased protein expression of the hepatic cytochrome P450 3A11 (CYP3A11) and key gluconeogenic enzymes phosphoenolpyruvate carboxykinase and glucose 6-phosphatase, and increased total cholesterol. Interestingly, HFD ingestion induced both UCP1 and glucokinase protein expression in WT mice, but inhibited these enzymes in hPXR females. Unlike WT mice, CYP3A11 protein, serum 17β-estradiol levels, and WAT ERα expression were unaffected by HFD in hPXR females. Together, these studies indicate that the hPXR gene promotes obesity and metabolic syndrome by dysregulating lipid and glucose homeostasis while inhibiting UCP1 expression. Furthermore, our studies indicate that the human PXR suppresses the protective role of estrogen in metabolic disorders. Finally, these data identify PXR-humanized mice as a promising in vivo research model for studying obesity and diabetes in women. PMID:24721462

  12. Data reduction framework for standard atomic weights and isotopic compositions of the elements

    NASA Astrophysics Data System (ADS)

    Meija, Juris; Possolo, Antonio

    2017-04-01

    We outline a general framework to compute consensus reference values of standard atomic weights, isotope ratios, and isotopic abundances, and to evaluate associated uncertainties using modern statistical methods for consensus building that can handle mutually inconsistent measurement results. The multivariate meta-regression approach presented here is directly relevant to the work of the IUPAC Commission on Isotopic Abundances and atomic weights (CIAAW), and we illustrate the proposed method in meta-analyses of the isotopic abundances and atomic weights of zinc, platinum, antimony, and iridium.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. CD11c expression in adipose tissue and blood and its role in diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To examine CD11c, a beta(2)-integrin, on adipose tissue (AT) leukocytes, and blood monocytes and its role in diet-induced obesity. High-fat diet-induced obese C57BL/6 mice, CD11c-deficient mice, and obese humans were studied. CD11c, leukocytes, and chemokines/cytokines were examined in AT and/or blo...

  15. Time of day: A vital determinant in diet-induced cardiometabolic syndrome development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Excess caloric intake is strongly associated with the development of obesity, type 2 diabetes mellitus, and cardiovascular disease (CVD). Research efforts have focused attention primarily on the quality (i.e., nutritional content) and/or quantity of calories as potential causes for diet-induced path...

  16. Appropriateness of the hamster as a model to study diet-induced atherosclerosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Golden-Syrian hamsters have been used as an animal model to assess diet-induced atherosclerosis since the early 1980s. Advantages appeared to include a low rate of endogenous cholesterol synthesis, receptor-mediated uptake of LDL cholesterol, cholesteryl ester transfer protein activity, hepatic apo...

  17. Increased hepatic CD36 expression contributes to dyslipidemia associated with diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The etiology of type 2 diabetes often involves diet-induced obesity (DIO), which is associated with elevated plasma fatty acids and lipoprotein associated triglycerides. Since aberrant hepatic fatty acid uptake may contribute to this, we investigated whether increased expression of a fatty acid tran...

  18. Speckle reduction in medical ultrasound: a novel scatterer density weighted nonlinear diffusion algorithm implemented as a neural-network filter.

    PubMed

    Badawi, Ahmed M; Rushdi, Muhammad A

    2006-01-01

    This paper proposes a novel algorithm for speckle reduction in medical ultrasound imaging while preserving the edges with the added advantages of adaptive noise filtering and speed. We propose a nonlinear image diffusion algorithm that incorporates two local parameters of image quality, namely, scatterer density and texture-based contrast in addition to gradient, to weight the nonlinear diffusion process. The scatterer density is proposed to replace the existing traditional measures of quality of the ultrasound diffusion process such as MSE, RMSE, SNR, and PSNR. This novel diffusion filter was then implemented using back propagation neural network for fast parallel processing of volumetric images. The experimental results show that weighting the image diffusion with these parameters produces better noise reduction and produces a better edge detection quality with reasonable computational cost. The proposed filter can be used as a preprocessing phase before applying any ultrasound segmentation or active contour model processes.

  19. Effect of recovery from muscle strength imbalance in lower limb using four point weight bearing reduction system.

    PubMed

    Yu, Chang Ho; Kang, Seung Rok; Jeong, Ho Choon; Kim, Kyung; Kwon, Tae Kyu

    2014-01-01

    This study was performed to assess the improvement of muscle strength imbalance in the lower limbs using a four point weight bearing reduction system with a two-belt treadmill. Participants, each having differences in muscle function of the left and right legs of over 20%, were divided into two groups of ten. The participants were involved in experiments progressing 40 minutes per day, 3 days per week, during a period of 4 weeks. The maximal peak torque and average power were measured for testing joint torque in the hip, knee and ankle. The results showed the improvement of muscle imbalance as assessed by the maximal muscle strength was the most effective in the hip joint, while the improvement of muscular reaction was the most effective in the knee joint. We suggest that the method of weight bearing reduction could be sufficient to reduce muscle imbalance in the lower limbs.

  20. Curcumin ameliorates high-fat diet-induced spermatogenesis dysfunction

    PubMed Central

    Mu, Yang; Yan, Wen-Jie; Yin, Tai-Lang; Yang, Jing

    2016-01-01

    Curcumin, a type of natural active ingredient, is derived from rhizoma of Curcuma, which possesses antioxidant, antitumorigenic and anti-inflammatory activities. The present study aimed to investigate whether treatment with curcumin reduced high-fat diet (HFD)-induced spermatogenesis dysfunction. Sprague-Dawley rats fed a HFD were treated with or without curcumin for 8 weeks. The testis/body weight, histological analysis and serum hormone levels were used to evaluate the effects of curcumin treatment on spermatogenesis dysfunction induced by the HFD. In addition, the expression levels of apoptosis associated proteins, Fas, B-cell lymphoma (Bcl)-xl, Bcl-associated X protein (Bax) and cleaved-caspase 3, were determined in the testis. The results of the present study suggested that curcumin treatment attenuated decreased testis/body weight and abnormal hormone levels. Morphological changes induced by a HFD were characterized as atrophied seminiferous tubules, decreased spermatogenetic cells and interstitial cells were improved by curcumin treatment. In addition, curcumin treatment reduced apoptosis in the testis, and decreased expression of Fas, Bax and cleaved-caspase 3, as well as increased expression of Bcl-xl. In conclusion, the present study revealed that curcumin treatment reduced HFD-induced spermatogenesis dysfunction in male rats. PMID:27600729

  1. Some cyclin-dependent kinase inhibitors-related genes are regulated by vitamin C in a model of diet-induced obesity.

    PubMed

    Boqué, Noemí; Campión, Javier; Milagro, Fermín Ignacio; Moreno-Aliaga, Maria-Jesús; Martinez, José Alfredo

    2009-08-01

    The aim of this research was to investigate differential gene expression of cyclin-dependent kinase inhibitors (CKIs) in white adipose tissue (WAT) and liver from high-fat fed male Wistar rats with or without vitamin C (VC) supplementation (750 mg/kg of body weight). After 56 d of experimentation, animals fed on a cafeteria diet increased significantly body weights and total body fat. Reverse transcription-polymerase chain reaction (RT-PCR) studies showed that cafeteria diet decreased p21 and p57 mRNA expression in subcutaneous WAT and increased p21 mRNA in liver. Overall, these data provide new information about the role of high fat intake on mRNA levels of several CKIs with implications in adipogenesis, cell metabolism and weight homeostasis. Interestingly, VC supplementation partially prevented diet-induced adiposity and increased p27 mRNA in liver without any changes in the other tissues and genes analyzed. Thus, hepatic mRNA changes induced by ascorbic acid indicate a possible role of these genes in diet-induced oxidative stress processes.

  2. Zonisamide for Weight Reduction in Obese Adults A 1-Year Randomized Controlled Trial

    PubMed Central

    Gadde, Kishore M.; Kopping, Mariko F.; Wagner, H. Ryan; Yonish, Gretchen M.; Allison, David B.; Bray, George A.

    2013-01-01

    SUMMARY Background Obese individuals who have failed to achieve adequate weight loss with lifestyle changes have limited non-surgical therapeutic options. We evaluated the efficacy and tolerability of zonisamide, an antiepileptic drug, for enhancing weight loss in obese patients receiving diet and lifestyle guidance. Methods This was a 1-year randomized, double-blind, placebo-controlled trial conducted between January 2006 and September 2011 at Duke University Medical Center. Patients were 225 obese (mean [SD] body mass index 37.6 [4.9]) women (134 [59.6%]) and men (91 [40.4%]) without diabetes. Interventions were daily dosing with placebo (n=74), zonisamide 200 mg (n=76), orzonisamide 400 mg (n=75), in addition to diet and lifestyle counseling by a dietitian for 1 year. Primary outcome was change in body weight at 1-year. Results Of the 225 randomized patients, 218 (97%) provided 1-year follow-up assessments. Change(least-squares mean) in body weight was -4.0 kg (−3.7%; 95% CI, −5.8 kg to −2.3 kg) for placebo, −4.4 kg (−3.9%; −6.1 to −2.6, P=.79vs placebo) for zonisamide 200 mg, and −7.3 kg (−6.8%; −9.0 to −5.6, P=.009vs placebo) for zonisamide 400 mg. In the categorical analysis,23 (31%) on placebo, 26 (34%; P=.71) on zonisamide 200 mg, and 41 (55%; P=.007) onzonisamide 400 mg achieved ≥5% weight loss; for ≥10% weight loss, the corresponding numbers were 6 (8%), 17 (22%; P=.022), and 24 (32%; P=.001). Gastrointestinal, nervous system and psychiatric adverse events occurred at a higher incidence with zonisamide than with placebo. Conclusion Zonisamide 400 mg/d moderately enhanced weight loss achieved with diet and lifestyle counseling, but had a high incidence of adverse events. PMID:23147455

  3. Diet-induced hyperphagia in the rat is influenced by sex and exercise.

    PubMed

    Eckel, Lisa A; Moore, Shelley R

    2004-11-01

    Caloric intake is increased in rats fed a diet containing greater fat or sugar than that found in laboratory chow. Because such diet-induced hyperphagia has been studied primarily in sedentary male rats, our goal here was to investigate the effects of sex and exercise on caloric intake of a diet (chow supplemented with sweet milk) chosen for its ability to stimulate hyperphagia. Rats were housed individually in cages that provided access to running wheels, and daily caloric intake of chow alone and then chow plus sweet milk was monitored during sedentary and active conditions. In sedentary rats, chow intake was greater in males compared with females. Wheel running produced similar decreases in chow intake in both sexes. Availability of the chow plus milk diet increased caloric intake compared with that observed in chow-fed rats. This diet-induced hyperphagia was significantly greater in sedentary females (35.7 +/- 3.1% increase) relative to sedentary males (9.1 +/- 2.2% increase). In addition, 35% of sedentary females consuming the chow plus milk diet developed estrous cycle disruptions. Wheel running decreased intake of the chow plus milk diet in both sexes. In active males, diet-induced hyperphagia was abolished; caloric intake was reduced to that observed during chow feeding. In active female rats, diet-induced hyperphagia was attenuated but not abolished; caloric intake of the chow plus milk diet remained greater than that observed during chow feeding. We conclude that female rats are more vulnerable than male rats to this form of diet-induced hyperphagia.

  4. Enhanced cocaine-induced locomotor sensitization and intrinsic excitability of NAc medium spiny neurons in adult but not adolescent rats susceptible to diet-induced obesity

    PubMed Central

    Oginsky, Max F.; Maust, Joel D.; Corthell, John T.; Ferrario, Carrie R.

    2015-01-01

    Rationale Basal and diet-induced differences in mesolimbic function, particularly within the nucleus accumbens (NAc), may contribute to human obesity; these differences may be more pronounced in susceptible populations. Objectives We determined whether there are differences in cocaine-induced behavioral plasticity in rats that are susceptible vs. resistant to diet-induced obesity, and basal differences in the striatal neuron function in adult and adolescent obesity-prone and obesity-resistant rats. Methods Susceptible and resistant outbred rats were identified based on “junk-food” diet-induced obesity. Then, the induction and expression of cocaine-induced locomotor sensitization, which is mediated by enhanced striatal function and is associated with increased motivation for rewards and reward-paired cues, were evaluated. Basal differences in mesolimbic function were examined in selectively bred obesity-prone and obesity-resistant rats (P70-80 and P30-40) using both cocaine induced locomotion and whole-cell patch clamping approaches in NAc core medium spiny neurons (MSNs). Results In rats that became obese after eating “junk-food”, the expression of locomotor sensitization was enhanced compared to non-obese rats, with similarly strong responses to 7.5 and 15 mg/kg cocaine. Without diet manipulation, obesity-prone rats were hyper-responsive to the acute locomotor-activating effects of cocaine, and the intrinsic excitability of NAc core MSNs was enhanced by ~60% at positive and negative potentials. These differences were present in adult, but not adolescent rats. Post-synaptic glutamatergic transmission was similar between groups. Conclusions Mesolimbic systems, particularly NAc MSNs, are hyper-responsive in obesity-prone individuals; and interactions between predisposition and experience influence neurobehavioral plasticity in ways that may promote weight gain and hamper weight loss in susceptible rats. PMID:26612617

  5. Lifestyle modification and weight reduction among low-income patients with the metabolic syndrome: the CHARMS randomized controlled trial.

    PubMed

    Chirinos, Diana A; Goldberg, Ronald B; Llabre, Maria M; Gellman, Marc; Gutt, Miriam; McCalla, Judith; Mendez, Armando; Schneiderman, Neil

    2016-06-01

    Although weight is an important intervention target among patients with metabolic syndrome, few trials have recruited low-income minority populations. The Community Health and Risk-reduction for Metabolic Syndrome randomized controlled trial aimed to examine the effects of a lifestyle intervention on weight and metabolic syndrome components among low-income minority adults. We randomized 120 adults with metabolic syndrome to standard medical care (N = 60) or a lifestyle intervention (N = 60). Using an intent-to-treat approach, we found significant intervention effects on weight [B = -0.452; SE = 0.122; 95 % confidence intervals (CI) -0.653 to -0.251) and glucose levels at 6-months (B = -0.522, SE = 0.234, 95 % CI -0.907 to -0.138). These changes were maintained through the 12-month assessment. No significant effects were observed on insulin resistance or other metabolic syndrome components. Our intervention was successful in achieving modest but significant weight loss and reduction in fasting glucose among low-income minority subjects with metabolic syndrome.

  6. The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors.

    PubMed

    Hulmi, Juha J; Isola, Ville; Suonpää, Marianna; Järvinen, Neea J; Kokkonen, Marja; Wennerström, Annika; Nyman, Kai; Perola, Markus; Ahtiainen, Juha P; Häkkinen, Keijo

    2016-01-01

    Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35-50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3-4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35-50% decrease in body fat in previously normal-weight females can recover within 3-4 months of increased energy intake.

  7. The Effects of Intensive Weight Reduction on Body Composition and Serum Hormones in Female Fitness Competitors

    PubMed Central

    Hulmi, Juha J.; Isola, Ville; Suonpää, Marianna; Järvinen, Neea J.; Kokkonen, Marja; Wennerström, Annika; Nyman, Kai; Perola, Markus; Ahtiainen, Juha P.; Häkkinen, Keijo

    2017-01-01

    Worries about the potential negative consequences of popular fat loss regimens for aesthetic purposes in normal weight females have been surfacing in the media. However, longitudinal studies investigating these kinds of diets are lacking. The purpose of the present study was to investigate the effects of a 4-month fat-loss diet in normal weight females competing in fitness-sport. In total 50 participants finished the study with 27 females (27.2 ± 4.1 years) dieting for a competition and 23 (27.7 ± 3.7 years) acting as weight-stable controls. The energy deficit of the diet group was achieved by reducing carbohydrate intake and increasing aerobic exercise while maintaining a high level of protein intake and resistance training in addition to moderate fat intake. The diet led to a ~12% decrease in body weight (P < 0.001) and a ~35–50% decrease in fat mass (DXA, bioimpedance, skinfolds, P < 0.001) whereas the control group maintained their body and fat mass (diet × group interaction P < 0.001). A small decrease in lean mass (bioimpedance and skinfolds) and in vastus lateralis muscle cross-sectional area (ultrasound) were observed in diet (P < 0.05), whereas other results were unaltered (DXA: lean mass, ultrasound: triceps brachii thickness). The hormonal system was altered during the diet with decreased serum concentrations of leptin, triiodothyronine (T3), testosterone (P < 0.001), and estradiol (P < 0.01) coinciding with an increased incidence of menstrual irregularities (P < 0.05). Body weight and all hormones except T3 and testosterone returned to baseline during a 3–4 month recovery period including increased energy intake and decreased levels aerobic exercise. This study shows for the first time that most of the hormonal changes after a 35–50% decrease in body fat in previously normal-weight females can recover within 3–4 months of increased energy intake. PMID:28119632

  8. Case report of hemoglobin a1c and weight reduction in integrative health coaching.

    PubMed

    Moore, Cynthia

    2013-05-01

    Integrative health coaching (IHC) offers significant health improvement in biometric measures without pharmaceuticals. In this case of newly diagnosed impaired glucose tolerance (IGT) with obesity, IHC used the patient's strengths to reverse IGT, prevent frank diabetes, and reduce weight by 40 lbs or 21% of her original weight. This intervention included a client self-assessment and 14 in-person health coaching sessions over 11 months. IHC provides a framework to accomplish short-term goals and identify and overcome barriers while drawing on the strengths and aims of the individual.

  9. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

    PubMed Central

    Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

    2016-01-01

    Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II−/−) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II−/− mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II−/− mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II−/− mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development. PMID:27920727

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

    PubMed

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

    2016-01-01

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

  11. Autoimmunity to HSP60 during diet induced obesity in mice

    PubMed Central

    Şelli, M E; Wick, G; Wraith, D C; Newby, A C

    2017-01-01

    Adaptive immunity has been implicated in adipose tissue inflammation, obesity and its adverse metabolic consequences. No obesity-related autoantigen has yet been identified, although heat shock protein 60 (HSP60) has been implicated in other autoimmune diseases. We investigated whether feeding a high-fat diet to C57BL/6J mice would cause autoimmunity to HSP60 and whether immunomodulation with peptides from HSP60 would reverse the resulting obesity or metabolic dysfunction. Obese mice had higher circulating levels of HSP60 associated with increased T-lymphocyte proliferation responses and the emergence of circulating IgG1 and IgG2c antibody levels against HSP60. Treatment with escalating doses of a mixture of three proven immunomodulatory HSP60 peptides did not reduce weight but completely reversed the increase in VLDL/LDL levels and partially reversed the glucose intolerance in obese mice. Obese mice mount an autoimmune response to HSP60, which partly underlies the resulting metabolic disturbances. PMID:27899808

  12. Serotonin Improves High Fat Diet Induced Obesity in Mice

    PubMed Central

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

    2016-01-01

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

  13. Effect of weight reduction on leptin, total ghrelin and obestatin concentrations in prepubertal children.

    PubMed

    Arrigo, T; Gitto, E; Ferraù, V; Munafò, C; Alibrandi, A; Marseglia, G L; Salpietro, A; Miraglia Del Giudice, M; Leonardi, S; Ciprandi, G; Salpietro, C

    2012-01-01

    The aim of the study was to evaluate fasting levels of glucose, insulin, leptin, total ghrelin, and obestatin in a group of prepubescent obese children before and after weight loss. We enrolled 64 prepubescent obese children, but only 35 completed the study (mean age 7.6 +- 0.9 years, 19 females) and 20 normal-weight prepubescent children as controls. Fasting plasma concentration of glucose, insulin, Homeostasis Model assessment for insulin resistance (HOMA-IR), and leptin, total ghrelin, and obestatin levels were measured at baseline and after a 6-month lifestyle intervention (i.e. improved nutrition and increased physical activity). At baseline, obese children showed significantly (p less than 0.001) higher leptin and obestatin levels, and lower total ghrelin concentrations than control subjects. Weight loss significantly (p less than 0.001) diminished plasma leptin and insulin levels and increased ghrelin and obestatin concentrations. Weight loss in prepubescent children is associated with a significant change in leptin, ghrelin and obestatin concentrations. These results confirm the hypothesis that levels of these hormones are closely associated with obesity in childhood and might take part, as consequence but not as a cause, in glucose, fat, and energy metabolism.

  14. A Weight-Reduction Program for Schizophrenic Patients on a Token Economy Unit: Two Case Studies

    ERIC Educational Resources Information Center

    Upper, Dennis; Newton, Judith G.

    1971-01-01

    Overweight patients on a token economy psychiatric ward were reinforced with tokens, off ward privileges and social approval for meeting a weight loss criterion of three pounds per week. The progress of two subjects, both chronic paranoid schizophrenics, is described. The procedure appears to be effective. (Author)

  15. Effect of Methanolic Leaf Extract of Talinum triangulare (Jacq). Willd. on Biochemical Parameters in Diet induced Dyslipidemia Wistar Rats

    PubMed Central

    Olorunnisola, Olubukola Sinbad; Adetutu, Adewale; Afolayan, Anthony Jide; Owoade, Abiodun Olusoji

    2016-01-01

    Objective: To investigate the effect of methanolic leaf extract of Talinum triangulare on hematological parameters, enzymatic and non-enzymatic antioxidant status, and serum lipid in Wistar rats fed standard laboratory, or 2% cholesterol-enrich diet. Material and Methods: Wistar rats (180-210g) divided into six groups of six animals (males) each were fed 2% cholesterol-enriched diet and orally treated with 0.9% saline or extract of Talinum triangulare (250, 500, and 1000 mg/kg per body weight) daily for eight weeks. Lipid profile, lipid peroxidation (MDA), hematological parameters, and their functional indices and serum antioxidant enzymes (catalase, glutathione -S-transferase, and superoxide dismutase) activities and glutathione status were assessed in normal and diet-induced hypercholesterolemic extract treated rats and compared with the rats treated with 100 mg/kg per bwt standard drug gemfibrozil. Results: A significant (P < 0.05) increase in lipid profile (total glyceride, total cholestrol, low-density lipoprotein, and very low-density lipoprotein), MDA and reduction (P < 0.05) in enzymatic and nonenzymatic antioxidant status coupled with alterations in hematological parameters was observed in the serum of hypercholesterolemic rats when compared with animals on a normal diet. Coadministration of methanolic leaf extracts of Talinum triangulare or gemfibrozil significantly (P < 0.05) restored the elevated serum lipid profile, MDA, and the deranged hematological parameters to near normal. The extract also protected against hypercholesterolemic-induced diminished enzymatic and nonenzymatic antioxidant status. The activities of the plant extract are dose (250, 500, and 1000 mg/kg) dependent and it compared favorably with the standard drug gemfibrozil. Conclusion: The present study suggested that the extract of Talinum triangulare might protect against hypercholesterolemic-induced altered lipid profiles, oxidative stress, and also improve the status of antioxidant

  16. Improved Function With Enhanced Protein Intake per Meal: A Pilot Study of Weight Reduction in Frail, Obese Older Adults

    PubMed Central

    Pieper, Carl F.; Orenduff, Melissa C.; McDonald, Shelley R.; McClure, Luisa B.; Zhou, Run; Payne, Martha E.; Bales, Connie W.

    2016-01-01

    Background: Obesity is a significant cause of functional limitations in older adults; yet, concerns that weight reduction could diminish muscle along with fat mass have impeded progress toward an intervention. Meal-based enhancement of protein intake could protect function and/or lean mass but has not been studied during geriatric obesity reduction. Methods: In this 6-month randomized controlled trial, 67 obese (body mass index ≥30kg/m2) older (≥60 years) adults with a Short Physical Performance Battery score of 4–10 were randomly assigned to a traditional (Control) weight loss regimen or one with higher protein intake (>30g) at each meal (Protein). All participants were prescribed a hypo-caloric diet, and weighed and provided dietary guidance weekly. Physical function (Short Physical Performance Battery) and lean mass (BOD POD), along with secondary measures, were assessed at 0, 3, and 6 months. Results: At the 6-month endpoint, there was significant (p < .001) weight loss in both the Control (−7.5±6.2kg) and Protein (−8.7±7.4kg) groups. Both groups also improved function but the increase in the Protein (+2.4±1.7 units; p < .001) was greater than in the Control (+0.9±1.7 units; p < .01) group (p = .02). Conclusion: Obese, functionally limited older adults undergoing a 6-month weight loss intervention with a meal-based enhancement of protein quantity and quality lost similar amounts of weight but had greater functional improvements relative to the Control group. If confirmed, this dietary approach could have important implications for improving the functional status of this vulnerable population (ClinicalTrials.gov identifier: NCT01715753). PMID:26786203

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

    PubMed

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

    2012-01-01

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

  18. Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease.

    PubMed

    Pacana, Tommy; Cazanave, Sophie; Verdianelli, Aurora; Patel, Vaishali; Min, Hae-Ki; Mirshahi, Faridoddin; Quinlivan, Eoin; Sanyal, Arun J

    2015-01-01

    Methionine metabolism plays a central role in methylation reactions, production of glutathione and methylarginines, and modulating homocysteine levels. The mechanisms by which these are affected in NAFLD are not fully understood. The aim is to perform a metabolomic, molecular and epigenetic analyses of hepatic methionine metabolism in diet-induced NAFLD. Female 129S1/SvlmJ;C57Bl/6J mice were fed a chow (n = 6) or high-fat high-cholesterol (HFHC) diet (n = 8) for 52 weeks. Metabolomic study, enzymatic expression and DNA methylation analyses were performed. HFHC diet led to weight gain, marked steatosis and extensive fibrosis. In the methionine cycle, hepatic methionine was depleted (30%, p< 0.01) while s-adenosylmethionine (SAM)/methionine ratio (p< 0.05), s-adenosylhomocysteine (SAH) (35%, p< 0.01) and homocysteine (25%, p< 0.01) were increased significantly. SAH hydrolase protein levels decreased significantly (p <0.01). Serine, a substrate for both homocysteine remethylation and transsulfuration, was depleted (45%, p< 0.01). In the transsulfuration pathway, cystathionine and cysteine trended upward while glutathione decreased significantly (p< 0.05). In the transmethylation pathway, levels of glycine N-methyltransferase (GNMT), the most abundant methyltransferase in the liver, decreased. The phosphatidylcholine (PC)/ phosphatidylethanolamine (PE) ratio increased significantly (p< 0.01), indicative of increased phosphatidylethanolamine methyltransferase (PEMT) activity. The protein levels of protein arginine methytransferase 1 (PRMT1) increased significantly, but its products, monomethylarginine (MMA) and asymmetric dimethylarginine (ADMA), decreased significantly. Circulating ADMA increased and approached significance (p< 0.06). Protein expression of methionine adenosyltransferase 1A, cystathionine β-synthase, γ-glutamylcysteine synthetase, betaine-homocysteine methyltransferase, and methionine synthase remained unchanged. Although gene expression of the DNA

  19. Diet-induced obesity differentially regulates behavioral, biomechanical, and molecular risk factors for osteoarthritis in mice

    PubMed Central

    2010-01-01

    Introduction Obesity is a major risk factor for the development of osteoarthritis in both weight-bearing and nonweight-bearing joints. The mechanisms by which obesity influences the structural or symptomatic features of osteoarthritis are not well understood, but may include systemic inflammation associated with increased adiposity. In this study, we examined biomechanical, neurobehavioral, inflammatory, and osteoarthritic changes in C57BL/6J mice fed a high-fat diet. Methods Female C57BL/6J mice were fed either a 10% kcal fat or a 45% kcal fat diet from 9 to 54 weeks of age. Longitudinal changes in musculoskeletal function and inflammation were compared with endpoint neurobehavioral and osteoarthritic disease states. Bivariate and multivariate analyses were conducted to determine independent associations with diet, percentage body fat, and knee osteoarthritis severity. We also examined healthy porcine cartilage explants treated with physiologic doses of leptin, alone or in combination with IL-1α and palmitic and oleic fatty acids, to determine the effects of leptin on cartilage extracellular matrix homeostasis. Results High susceptibility to dietary obesity was associated with increased osteoarthritic changes in the knee and impaired musculoskeletal force generation and motor function compared with controls. A high-fat diet also induced symptomatic characteristics of osteoarthritis, including hyperalgesia and anxiety-like behaviors. Controlling for the effects of diet and percentage body fat with a multivariate model revealed a significant association between knee osteoarthritis severity and serum levels of leptin, adiponectin, and IL-1α. Physiologic doses of leptin, in the presence or absence of IL-1α and fatty acids, did not substantially alter extracellular matrix homeostasis in healthy cartilage explants. Conclusions These results indicate that diet-induced obesity increases the risk of symptomatic features of osteoarthritis through changes in

  20. Cashew apple extract inhibition of fat storage and insulin resistance in the diet-induced obesity mouse model.

    PubMed

    Beejmohun, Vickram; Mignon, Cyril; Mazollier, Aude; Peytavy-Izard, Marie; Pallet, Dominique; Dornier, Manuel; Chapal, Nicolas

    2015-01-01

    The cashew apple is an unvalued by-product from the cashew nut industry, of which millions of tonnes are simply discarded globally. Interestingly, however, cashew apple nutrients may have beneficial effects for health even if these are still poorly described. The present study was designed to evaluate the effect of a hydro-alcoholic extract of cashew apple (cashew apple extract; CAE; Cashewin(™)) on obesity and diabetes, in two experimental designs using the diet-induced obesity (DIO) mouse model. First, in the preventive design, mice were treated orally with the CAE at the dose of 200 mg/kg body weight from the first day under a high-fat diet (HFD) and during 8 weeks thereafter. Second, in the curative design, the animals were first maintained under the HFD for 4 weeks and then treated with the CAE for a further 4 weeks under the same regimen. For both experimental designs, body weight, peri-epididymal adipose tissue, liver weight, food consumption, glycaemia, insulinaemia and insulin resistance were assessed. In both designs, the CAE significantly reduced body-weight gain and fat storage in both the peri-epididymal adipose tissue and the liver for mice under the HFD. This was achieved without modifying their energy consumption. Furthermore, glycaemia, insulinaemia and insulin resistance (homeostasis model assessment-insulin resistance) of the DIO mice were significantly lowered compared with the control group. Thus, a well-designed hydro-alcoholic extract of cashew apple could provide an attractive nutritional food ingredient to help support the management of body weight and associated metabolic parameters such as blood glucose and insulin levels.

  1. Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats.

    PubMed

    Goularte, Jéferson F; Ferreira, Maria B C; Sanvitto, Gilberto L

    2012-10-28

    Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

  2. The crude extract from puerariae flower exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice.

    PubMed

    Kamiya, Tomoyasu; Sameshima-Kamiya, Mayu; Nagamine, Rika; Tsubata, Masahito; Ikeguchi, Motoya; Takagaki, Kinya; Shimada, Tsutomu; Aburada, Masaki

    2012-01-01

    Kudzu, a leguminous plant, has long been used in folk medicine. In particular, its flowers are used in Japanese and Chinese folk medicine for treating hangovers. We focused on the flower of Kudzu (Puerariae thomsonii), and we previously reported the antiobesity effect of Puerariae thomsonii flower extract (PFE) in humans. In this study, we conducted an animal study to investigate the effect of PFE on visceral fat and hepatic lipid levels in mice with diet-induced obesity. In addition, we focused on gene expression profiles to investigate the antiobesity mechanism of PFE. Male C57BL/6J mice were fed a high-fat diet (HFD) or an HFD supplemented with 5% PFE for 14 days. PFE supplementation significantly reduced body weight and white adipose tissue (WAT) weight. Moreover, in the histological analysis, PFE supplementation improved fatty liver. Hepatic reverse transcription-polymerase chain reaction revealed that PFE supplementation downregulated acetyl-CoA carboxylase expression. For adipose tissue, the expressions of hormone-sensitive lipase in WAT and uncoupling protein 1 in brown adipose tissue (BAT) were significantly upregulated. These results suggest that PFE exerts antiobesity and antifatty liver effects in high-fat diet-induced obese mice through suppressing lipogenesis in the liver, stimulating lipolysis in WAT, and promoting thermogenesis in BAT.

  3. Xanthohumol improves dysfunctional glucose and lipid metabolism in diet-induced obese C57BL/6J mice.

    PubMed

    Miranda, Cristobal L; Elias, Valerie D; Hay, Joshua J; Choi, Jaewoo; Reed, Ralph L; Stevens, Jan F

    2016-06-01

    Xanthohumol (XN) is a prenylated flavonoid found in hops (Humulus lupulus) and beer. The dose-dependent effects of XN on glucose and lipid metabolism in a preclinical model of metabolic syndrome were the focus of our study. Forty-eight male C57BL/6J mice, 9 weeks of age, were randomly divided into three XN dose groups of 16 animals. The mice were fed a high-fat diet (60% kcal as fat) supplemented with XN at dose levels of 0, 30, or 60 mg/kg body weight/day, for 12 weeks. Dietary XN caused a dose-dependent decrease in body weight gain. Plasma levels of glucose, total triglycerides, total cholesterol, and MCP-1 were significantly decreased in mice on the 60 mg/kg/day treatment regimen. Treatment with XN at 60 mg/kg/day resulted in reduced plasma LDL-cholesterol (LDL-C), IL-6, insulin and leptin levels by 80%, 78%, 42%, and 41%, respectively, compared to the vehicle control group. Proprotein Convertase Subtilisin Kexin 9 (PCSK-9) levels were 44% lower in the 60 mg/kg dose group compared to the vehicle control group (p ≤ 0.05) which may account for the LDL-C lowering activity of XN. Our results show that oral administration of XN improves markers of systemic inflammation and metabolic syndrome in diet-induced obese C57BL/6J mice.

  4. Monocarboxylate transporters: new players in body weight regulation.

    PubMed

    Carneiro, L; Pellerin, L

    2015-02-01

    Over the last two decades, several genes have been identified that appear to play a role in the regulation of energy homeostasis and body weight. For a small subset of them, a reduction or an absence of expression confers a resistance to the development of obesity. Recently, a knockin mouse for a member of the monocarboxylate transporter (MCT) family, MCT1, was demonstrated to exhibit a typical phenotype of resistance to diet-induced obesity and a protection from its associated metabolic perturbations. Such findings point out at MCTs as putatively new therapeutic targets in the context of obesity. Here, we will review what is known about MCTs and their possible metabolic roles in different organs and tissues. Based on the description of the phenotype of the MCT1 knockin mouse, we will also provide some insights about their putative roles in weight gain regulation.

  5. Weight reduction among people with severe and persistent mental illness after health behavior counseling and monitoring.

    PubMed

    Katekaru, Matthew; Minn, Carol E; Pobutsky, Ann M

    2015-04-01

    The high prevalence of obesity and associated chronic conditions in persons with severe and persistent mental illness has contributed to a mortality rate that is nearly two times higher than the overall population. In 2008, the Central O'ahu Community Mental Health Center of the Hawai'i State Department of Health, Adult Mental Health Division began an unfunded, health counseling intervention pilot project to address such concerns for the health of persons with severe and persistent mental illness. This article reviews the results of this intervention. Forty-seven persons with schizophrenia or related disorders were included in the intervention which involved health counseling and monitoring of weight as a risk factor for chronic disease. After five years of counseling and monitoring, medical chart reviews were conducted for each person for data on weight change. Analysis showed weight loss and improvements in body mass index. The results of this project show potential for long-term counseling and monitoring as an intervention for obesity in persons with severe and persistent mental illness.

  6. Weight loss and brown adipose tissue reduction in rat model of sleep apnea

    PubMed Central

    Martinez, Denis; Vasconcellos, Luiz FT; de Oliveira, Patricia G; Konrad, Signorá P

    2008-01-01

    Background - Obesity is related to obstructive sleep apnea-hypopnea syndrome (OSAHS), but its roles in OSAHS as cause or consequence are not fully clarified. Isocapnic intermittent hypoxia (IIH) is a model of OSAHS. We verified the effect of IIH on body weight and brown adipose tissue (BAT) of Wistar rats. Methods Nine-month-old male breeders Wistar rats of two groups were studied: 8 rats submitted to IIH and 5 control rats submitted to sham IIH. The rats were weighed at the baseline and at the end of three weeks, after being placed in the IIH apparatus seven days per week, eight hours a day, in the lights on period, simulating an apnea index of 30/hour. After experimental period, the animals were weighed and measured as well as the BAT, abdominal, perirenal, and epididymal fat, the heart, and the gastrocnemius muscle. Results Body weight of the hypoxia group decreased 17 ± 7 grams, significantly different from the variation observed in the control group (p = 0,001). The BAT was 15% lighter in the hypoxia group and reached marginally the alpha error probability (p = 0.054). Conclusion Our preliminary results justify a larger study for a longer time in order to confirm the effect of isocapnic intermittent hypoxia on body weight and BAT. PMID:18671859

  7. Rosiglitazone improves insulin sensitivity and baroreflex gain in rats with diet-induced obesity.

    PubMed

    Zhao, Ding; McCully, Belinda H; Brooks, Virginia L

    2012-10-01

    Obesity decreases baroreflex gain (BRG); however, the mechanisms are unknown. We tested the hypothesis that impaired BRG is related to the concurrent insulin resistance, and, therefore, BRG would be improved after treatment with the insulin-sensitizing drug rosiglitazone. Male rats fed a high-fat diet diverged into obesity-prone (OP) and obesity-resistant (OR) groups after 2 weeks. Then, OP and OR rats, as well as control (CON) rats fed a standard diet, were treated daily for 2 to 3 weeks with rosiglitazone (3 or 6 mg/kg) or its vehicle by gavage. Compared with OR and CON rats, conscious OP rats exhibited reductions in BRG (OP, 2.9 ± 0.1 bpm/mm Hg; OR, 4.0 ± 0.2 bpm/mm Hg; CON, 3.9 ± 0.2 bpm/mm Hg; P < 0.05) and insulin sensitivity (hyperinsulinemic euglycemic clamp; OP, 6.8 ± 0.9 mg/kg · min; OR, 22.2 ± 1.2 mg/kg · min; CON, 17.7 ± 0.8 mg/kg · min; P < 0.05), which were well correlated (r(2) = 0.49; P < 0.01). In OP rats, rosiglitazone dose-dependently improved (P < 0.05) insulin sensitivity (12.8 ± 0.6 mg/kg · min at 3 mg/kg; 16.0 ± 1.5 mg/kg · min at 6 mg/kg) and BRG (3.8 ± 0.4 bpm/mm Hg at 3 mg/kg; 5.3 ± 0.7 bpm/mm Hg at 6 mg/kg). However, 6 mg/kg rosiglitazone also increased BRG in OR rats without increasing insulin sensitivity, disrupted the correlation between BRG and insulin sensitivity (r(2) = 0.08), and, in OP and OR rats, elevated BRG relative to insulin sensitivity (analysis of covariance; P < 0.05). Moreover, in OP rats, stimulation of the aortic depressor nerve, to activate central baroreflex pathways, elicited markedly reduced decreases in heart rate and arterial pressure, but these responses were not improved by rosiglitazone. In conclusion, diet-induced obesity impairs BRG via a central mechanism that is related to the concurrent insulin resistance. Rosiglitazone normalizes BRG, but not by improving brain baroreflex processing or insulin sensitivity.

  8. Purple Tea and Its Extract Suppress Diet-induced Fat Accumulation in Mice and Human Subjects by Inhibiting Fat Absorption and Enhancing Hepatic Carnitine Palmitoyltransferase Expression.

    PubMed

    Shimoda, Hiroshi; Hitoe, Shoketsu; Nakamura, Seikou; Matsuda, Hisashi

    2015-06-01

    A number of clinical trials have been completed using green tea and black tea to investigate their effect in controlling weight in overweight adults. The results of these investigations, however, have often been contradictory, with some trials reporting positive effects of tea supplementation and some trials reporting no effect. As a result, the use of these teas for weight loss is controversial. Purple tea is a variety of green tea developed in Kenya (called TRFK306), which in addition to certain tea constituents found in green tea, also contains anthocyanins. The major constituents in the leaves of purple tea are caffeine, theobromine, epigallocatechin (ECG), epigallocatechin gallate (EGCG) and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (GHG). We investigated the efficacy of purple tea extract (PTE) on diet-induced fat accumulation in mice. PTE administration (200 mg/kg) significantly suppressed body weight gain, liver weight, abdominal fat and triglycerides in serum and liver. Protein expression of carnitine palmitoyltransferase (CPT) 1A was also enhanced. In olive oil loaded mice, PTE (100 mg/kg) and caffeine (25 mg/kg) suppressed fat absorption. PTE (10 μg/mL) and GHG (10 μg/mL) also enhanced protein expression of CPT1A in HepG2 hepatoma. Moreover, 4-week daily consumption of purple tea drink in humans improved obesity parameters compared to baseline, including body weight (79.9 ± 3.1 kg vs 80.8 ± 3.2, p<0.05), body mass index (BMI) (26.8 ± 0.6 vs 27.0 ± 0.6, p<0.05) and body fat mass (21.0 ± 1.4 kg vs 21.8 ± 1.5, p<0.01). In conclusion, PTE could control diet-induced weight gain by suppression of fat absorption and enhancement of hepatic fat metabolism.

  9. Purple Tea and Its Extract Suppress Diet-induced Fat Accumulation in Mice and Human Subjects by Inhibiting Fat Absorption and Enhancing Hepatic Carnitine Palmitoyltransferase Expression

    PubMed Central

    Shimoda, Hiroshi; Hitoe, Shoketsu; Nakamura, Seikou; Matsuda, Hisashi

    2015-01-01

    A number of clinical trials have been completed using green tea and black tea to investigate their effect in controlling weight in overweight adults. The results of these investigations, however, have often been contradictory, with some trials reporting positive effects of tea supplementation and some trials reporting no effect. As a result, the use of these teas for weight loss is controversial. Purple tea is a variety of green tea developed in Kenya (called TRFK306), which in addition to certain tea constituents found in green tea, also contains anthocyanins. The major constituents in the leaves of purple tea are caffeine, theobromine, epigallocatechin (ECG), epigallocatechin gallate (EGCG) and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-β-D-glucose (GHG). We investigated the efficacy of purple tea extract (PTE) on diet-induced fat accumulation in mice. PTE administration (200 mg/kg) significantly suppressed body weight gain, liver weight, abdominal fat and triglycerides in serum and liver. Protein expression of carnitine palmitoyltransferase (CPT) 1A was also enhanced. In olive oil loaded mice, PTE (100 mg/kg) and caffeine (25 mg/kg) suppressed fat absorption. PTE (10 μg/mL) and GHG (10 μg/mL) also enhanced protein expression of CPT1A in HepG2 hepatoma. Moreover, 4-week daily consumption of purple tea drink in humans improved obesity parameters compared to baseline, including body weight (79.9 ± 3.1 kg vs 80.8 ± 3.2, p<0.05), body mass index (BMI) (26.8 ± 0.6 vs 27.0 ± 0.6, p<0.05) and body fat mass (21.0 ± 1.4 kg vs 21.8 ± 1.5, p<0.01). In conclusion, PTE could control diet-induced weight gain by suppression of fat absorption and enhancement of hepatic fat metabolism PMID:26199579

  10. Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity

    PubMed Central

    Higgins, Guy A; Desnoyer, Jill; Van Niekerk, Annalise; Silenieks, Leo B; Lau, Winnie; Thevarkunnel, Sandy; Izhakova, Julia; DeLannoy, Ines AM; Fletcher, Paul J; DeLay, Josepha; Dobson, Howard

    2015-01-01

    The 5-HT2C receptor agonist lorcaserin (Belviq®) has been Food and Drug Administration (FDA) approved for the treatment of obesity. The present study is a back translational investigation into the effect of 28-day lorcaserin treatment in a diet-induced obesity (DIO) model using male, Sprague–Dawley rats. An assessment of drug effect on efficacy and multiple safety endpoints including cardiac function was undertaken. Lorcaserin (1–2 mg/kg SC b.i.d.) significantly reduced percentage body weight gain compared to vehicle-treated controls (VEH: 10.6 ± 0.4%; LOR 1: 7.6 ± 1.2%; LOR 2: 5.4 ± 0.6%). Measurement of body composition using quantitative magnetic resonance (QMR) imaging indicated this change was due to the selective reduction in body fat mass. Modest effects on food intake were recorded. At the completion of the treatment phase, echocardiography revealed no evidence for valvulopathy, that is, no aortic or mitral valve regurgitation. The pharmacokinetics of the present treatment regimen was determined over a 7-day treatment period; plasma Cmin and Cmax were in the range 13–160 ng/mL (1 mg/kg b.i.d.) and 34–264 ng/mL (2 mg/kg b.i.d.) with no evidence for drug accumulation. In sum, these studies show an effect of lorcaserin in the DIO model, that in the context of the primary endpoint measure of % body weight change was similar to that reported clinically (i.e., 3.0–5.2% vs. 3.2%). The present studies highlight the translational value of obesity models such as DIO, and suggest that assuming consideration is paid to nonspecific drug effects such as malaise, the DIO model has reasonable forward translational value to help predict clinical outcomes of a new chemical entity. PMID:25692009

  11. Over-Expression of Leptin Receptors in Hypothalamic POMC Neurons Increases Susceptibility to Diet-Induced Obesity

    PubMed Central

    Gamber, Kevin M.; Huo, Lihong; Ha, Sangdeuk; Hairston, Joyce E.; Greeley, Sarah; Bjørbæk, Christian

    2012-01-01

    Diet-induced obesity (DIO) in rodents is characterized by impaired activation of signal-transducer and activator of transcription 3 (STAT3) by leptin receptors (LepRb) within the hypothalamic arcuate nucleus. This signaling defect likely plays an important role in development of DIO. However, the neuro-chemical identity of the leptin-STAT3 resistant arcuate neurons has not been determined and the underlying mechanisms responsible for development of cellular leptin resistance remain unclear. To investigate this, we first measured arcuate gene expression of known key signaling components of the LepRb signaling pathway and tested whether specifically the critical arcuate pro-opiomelanocortin (POMC) neurons are resistant to LepRb-STAT3 signaling in mice given a high-fat-diet (HFD) compared to mice provided a low-fat control diet (LFD). We found that leptin-dependent STAT3 phosphorylation was decreased within POMC neurons of HFD mice. In addition, Leprb mRNA and suppressor of cytokine signaling 3 (Socs3) mRNA were elevated in the arcuate of HFD mice. To investigate whether increased LepRb expression per se in POMC neurons can influence development of DIO and Socs3 expression, we created mice that over-express LepRb selectively in POMC neurons (POMC-LepRb). No differences in body weight, fat mass or food intake were found between LFD POMC-LepRb mice and LFD controls. Surprisingly, body weight, fat mass and caloric intake of HFD POMC-LepRb mice was markedly higher than HFD control mice. In addition, arcuate Socs3 mRNA was increased in HFD POMC-LepRb mice compared to HFD controls. These data show that specifically POMC neurons of DIO mice are resistant to STAT3 activation by leptin, indicating that those cells might play a role in development of DIO. Furthermore, over-expression of LepRb selectively in POMC neurons increases susceptibility to the development of DIO. We propose a model where over-reactivity of the leptin-LepRb signaling system in arcuate neurons may play

  12. Keeping Weight Off: study protocol of an RCT to investigate brain changes associated with mindfulness-based stress reduction

    PubMed Central

    Siegel, Julia A; Allison, Jeroan; Rosal, Milagros C; Brewer, Judson; King, Jean A

    2016-01-01

    Introduction Obesity is a growing epidemic fuelled by unhealthy behaviours and associated with significant comorbidities and financial costs. While behavioural interventions produce clinically meaningful weight loss, weight loss maintenance is challenging. This may partially be due to failure to target stress and emotional reactivity. Mindfulness-based stress reduction (MBSR) reduces stress and emotional reactivity and may be a useful tool for behaviour change maintenance. This study seeks to provide a mechanistic understanding for clinical trials of the benefits of MBSR for weight loss maintenance by examining changes in functional connectivity (FC) and the association of these changes with clinical outcomes. Methods and analysis Community-dwelling individuals (n=80) who intentionally lost ≥5% of their body weight in the past year will be recruited and randomised to an MBSR programme or educational control. FC using resting-state functional MRI will be measured at baseline and 8 weeks. Psychological factors, health behaviours, body mass index and waist circumference will be measured at baseline, 8 weeks and 6 months post intervention. A 12-month telephone follow-up will assess self-reported weight. Analyses will characterise FC changes in response to MBSR in comparison with a control condition, assess the relationship between baseline FC status and pre–post MBSR changes in FC and investigate the association of FC change with changes in psychological factors and weight loss maintenance. Ethics and dissemination The University of Massachusetts Medical School Institutional Review Board has approved this study, Declaration of Helsinki protocols are being followed, and patients will give written informed consent. The Independent Monitoring Committee will monitor protocol adherence. Results from the study will be disseminated to the medical community at conferences and submitted for publication in peer-reviewed journals when the last patient included has been

  13. Overexpression of apolipoprotein A5 in mice is not protective against body weight gain and aberrant glucose homeostasis.

    PubMed

    Pamir, Nathalie; McMillen, Timothy S; Li, Yu-I; Lai, Ching-Mei; Wong, Howard; LeBoeuf, Renée C

    2009-04-01

    Apolipoprotein A5 (APOA5) is expressed primarily in the liver and modulates plasma triglyceride levels in mice and humans. Mice overexpressing APOA5 exhibit reduced plasma triglyceride levels. Because there is a tight association between plasma triglyceride concentration and traits of the metabolic syndrome, we used transgenic mice overexpressing human APOA5 to test the concept that these mice would be protected from diet-induced obesity and insulin resistance. Male and female transgenic and wild-type mice on the FVB/N genetic background were fed standard rodent chow or a diet rich in fat and sucrose for 18 weeks, during which time clinical phenotypes associated with obesity and glucose homeostasis were measured. We found that APOA5 transgenic (A5tg) mice were resistant to diet-induced changes in plasma triglyceride but not total cholesterol levels. Body weights were similar between the genotypes for females and males, although male A5tg mice showed a modest but significant increase in the relative size of inguinal fat pads. Although male A5tg mice showed a significantly increased ratio of plasma glucose to insulin, profiles of glucose clearance as evaluated after injections of glucose or insulin failed to reveal any differences between genotypes. Overall, our data showed that there was no advantage to responses to diet-induced obesity with chronic reduction of plasma triglyceride levels as mediated by overexpression of APOA5.

  14. Diet-Induced Obesity in Mice Reduces the Maintenance of Influenza-Specific CD8+ Memory T Cells12

    PubMed Central

    Karlsson, Erik A.; Sheridan, Patricia A.; Beck, Melinda A.

    2010-01-01

    Obesity has been associated with increasing the risk for type 2 diabetes and heart disease, but its influence on the immune response to viral infection is understudied. Memory T cells generated during a primary influenza infection are important for protection against subsequent influenza exposures. Previously, we have demonstrated that diet-induced obese (DIO) mice have increased morbidity and mortality following secondary influenza infection compared with lean mice. To determine whether the problem resided in a failure to maintain functional, influenza-specific CD8+ memory T cells, male DIO and lean mice were infected with influenza X-31. At 84 d postinfection, DIO mice had a 10% reduction in memory T cell numbers. This reduction may have resulted from significantly reduced memory T cell expression of interleukin 2 receptor β (IL-2R β, CD122), but not IL-7 receptor α (CD127), which are both required for memory cell maintenance. Peripheral leptin resistance in the DIO mice may be a contributing factor to the impairment. Indeed, leptin receptor mRNA expression was significantly reduced in the lungs of obese mice, whereas suppressor of cytokine signaling (Socs)1 and Socs3 mRNA expression were increased. It is imperative to understand how the obese state alters memory T cells, because impairment in maintenance of functional memory responses has important implications for vaccine efficacy in an obese population. PMID:20592105

  15. Influence of Term of Exposure to High-Fat Diet-Induced Obesity on Myocardial Collagen Type I and III

    PubMed Central

    da Silva, Danielle Cristina Tomaz; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; de Campos, Dijon Henrique Salomé; do Nascimento, André Ferreira; de Oliveira, Sílvio Assis; Padovani, Carlos Roberto; Cicogna, Antonio Carlos

    2014-01-01

    Background Obesity is a risk factor for many medical complications; medical research has shown that hemodynamic, morphological and functional abnormalities are correlated with the duration and severity of obesity. Objective Present study determined the influence of term of exposure to high-fat diet-induced obesity on myocardial collagen type I and III. Methods Thirty-day-old male Wistar rats were randomly distributed into two groups: a control (C) group fed a standard rat chow and an obese (Ob) group alternately fed one of four palatable high-fat diets. Each diet was changed daily, and the rats were maintained on their respective diets for 15 (C15 and Ob15) and 30 (C30 and Ob30) consecutive weeks. Obesity was determined by adiposity index. Results The Ob15 group was similar to the C15 group regarding the expression of myocardial collagen type I; however, expression in the Ob30 group was less than C30 group. The time of exposure to obesity was associated with a reduction in collagen type I in Ob30 when compared with Ob15. Obesity did not affect collagen type III expression. Conclusion This study showed that the time of exposure to obesity for 30 weeks induced by unsaturated high-fat diet caused a reduction in myocardial collagen type I expression in the obese rats. However, no effect was seen on myocardial collagen type III expression. PMID:24676371

  16. Weight loss and blood pressure reduction in obese subjects in response to nutritional guidance using information communication technology.

    PubMed

    Ueki, Kanako; Sakurai, Nozomi; Tochikubo, Osamu

    2009-05-01

    The metabolic syndrome caused by visceral-fat obesity is a major risk factor for atherosclerosis. This study used a new information communication technology (ICT) to investigate body weight (BW) and blood pressure (BP) changes in response to nutritional guidance. Obese subjects with hypertension, hyperlipidemia, or impaired glucose tolerance received guidance with the ICT method (n = 13) or face-to-face according to conventional methods (n = 39). The effects of the methods were compared. After 12 weeks, significant weight loss and BP reduction were observed in the ICT group. Also, significant higher improvements were observed in total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, and HbA(1c) in the ICT-group compared with those groups using the conventional method. The effectiveness of the ICT method in reducing BW, BP, total and LDL cholesterol, and HbA(1c) was demonstrated.

  17. High carbohydrate diet induces nonalcoholic steato-hepatitis (NASH) in a desert gerbil.

    PubMed

    Semiane, Nesrine; Foufelle, Fabienne; Ferré, Pascal; Hainault, Isabelle; Ameddah, Souad; Mallek, Aicha; Khalkhal, Ali; Dahmani, Yasmina

    2017-01-01

    A high intake of sugars has been linked to diet-induced health problems. The aim of this study was to assess whether the long-term consumption of a high-carbohydrate diet (HCD) would cause the hepatic histopathological and metabolic abnormalities that characterize nonalcoholic steatohepatitis (NASH) in a desert gerbil, Gerbillus gerbillus. Compared to natural diet, HCD leads to several metabolic disorders including adiposity, dyslipidemia, insulin resistance, ectopic fat deposition in the liver, which were associated with higher levels of transcripts of genes involved with fat synthesis, endoplasmic reticulum (ER) stress, and fibrosis. In the same way, the experimented animals showed enhanced oxidative stress. Taken together, these results demonstrate that HCD consumption in gerbils induces metabolic disorders and damaged liver, which are key contributors to NASH development. These results suggest that this rodent represents a valuable natural model for human diet-induced metabolic disorders and nonalcoholic fatty liver disease (NAFLD).

  18. Altered Hepatic Transport by Fetal Arsenite Exposure in Diet-Induced Fatty Liver Disease.

    PubMed

    Ditzel, Eric J; Li, Hui; Foy, Caroline E; Perrera, Alec B; Parker, Patricia; Renquist, Benjamin J; Cherrington, Nathan J; Camenisch, Todd D

    2016-07-01

    Non-alcoholic fatty liver disease can result in changes to drug metabolism and disposition potentiating adverse drug reactions. Furthermore, arsenite exposure during development compounds the severity of diet-induced fatty liver disease. This study examines the effects of arsenite potentiated diet-induced fatty liver disease on hepatic transport in male mice. Changes were detected for Mrp2/3/4 hepatic transporter gene expression as well as for Oatp1a4/2b1/1b2. Plasma concentrations of Mrp and Oatp substrates were increased in arsenic exposure groups compared with diet-only controls. In addition, murine embryonic hepatocytes and adult primary hepatocytes show significantly altered transporter expression after exposure to arsenite alone: a previously unreported phenomenon. These data indicate that developmental exposure to arsenite leads to changes in hepatic transport which could increase the risk for ADRs during fatty liver disease.

  19. Lifestyle interventions for cardiovascular disease risk reduction: a systematic review of the effects of diet composition, food provision, and treatment modality on weight loss.

    PubMed

    Dutton, Gareth R; Laitner, Melissa H; Perri, Michael G

    2014-10-01

    The purpose of this systematic review was to evaluate, synthesize, and interpret findings from recent randomized controlled trials (RCTs) of dietary and lifestyle weight loss interventions examining the effects of (1) diet composition, (2) use of food provision, and (3) modality of treatment delivery on weight loss. Trials comparing different dietary approaches indicated that reducing carbohydrate intake promoted greater initial weight loss than other approaches but did not appear to significantly improve long-term outcomes. Food provision appears to enhance adherence to reduction in energy intake and produce greater initial weight losses. The long-term benefits of food provision are less clear. Trials comparing alternative treatment modalities suggest that phone-based treatment produce short- and long-term weight reductions equivalent to face-to-face interventions. The use of Internet and mobile technologies are associated with smaller reductions in body weight than face-to-face interventions. Based on this review, clinical implications and future research directions are provided.

  20. Improved high-fat diet-induced glucose intolerance by an oral administration of phytosphingosine.

    PubMed

    Murakami, Itsuo; Mitsutake, Susumu; Kobayashi, Naoyuki; Matsuda, Junko; Suzuki, Akemi; Shigyo, Tatsuro; Igarashi, Yasuyuki

    2013-01-01

    We have previously reported that phytoceramide and phytosphingosine (PHS) stimulated the transcriptional activity of peroxisome proliferator-activated receptor γ (PPARγ) in cells. PPARγ is a therapeutic target for type 2 diabetes. We found in this study that an oral administration of PHS improved diet-induced glucose intolerance in mice. Since PHS is highly expressed in yeast, PHS in fermented foods may improve diabetes.

  1. Long-term voluntary running improves diet-induced adiposity in young adult mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of long-term voluntary running on diet-induced adiposity in male C57BL/6 mice. Four-week old mice (n = 15 per group) were fed the AIN93G diet or a 45% high-fat diet (% kcal.) with or without access to in-cage activity wheels for 14 weeks. The high-fat die...

  2. Effect of at-the-source noise reduction on performance and weights of a tilt-rotor aircraft

    NASA Technical Reports Server (NTRS)

    Gibs, J.; Stepniewski, W. Z.; Spencer, R.

    1975-01-01

    Reduction of far-field acoustic signature through modification of basic design parameters (tip speed, number of blades, disc loading and rotor blade area) was examined, using a tilt-rotor flight research aircraft as a baseline configuration. Of those design parameters, tip speed appeared as the most important. Next, preliminary design of two aircraft was performed, postulating the following reduction of noise level from that of the baseline machine, at 500 feet from the spot of OGE hover. In one aircraft, the PNL was lowered by 10 PNdB and in the other, OASPL decreased by 10 dB. The resulting weight and performance penalties were examined. Then, PNL and EPNL aspects of terminal operation were compared for the baseline and quieter aircraft.

  3. Determining residual reduction algorithm kinematic tracking weights for a sidestep cut via numerical optimization.

    PubMed

    Samaan, Michael A; Weinhandl, Joshua T; Bawab, Sebastian Y; Ringleb, Stacie I

    2016-12-01

    Musculoskeletal modeling allows for the determination of various parameters during dynamic maneuvers by using in vivo kinematic and ground reaction force (GRF) data as inputs. Differences between experimental and model marker data and inconsistencies in the GRFs applied to these musculoskeletal models may not produce accurate simulations. Therefore, residual forces and moments are applied to these models in order to reduce these differences. Numerical optimization techniques can be used to determine optimal tracking weights of each degree of freedom of a musculoskeletal model in order to reduce differences between the experimental and model marker data as well as residual forces and moments. In this study, the particle swarm optimization (PSO) and simplex simulated annealing (SIMPSA) algorithms were used to determine optimal tracking weights for the simulation of a sidestep cut. The PSO and SIMPSA algorithms were able to produce model kinematics that were within 1.4° of experimental kinematics with residual forces and moments of less than 10 N and 18 Nm, respectively. The PSO algorithm was able to replicate the experimental kinematic data more closely and produce more dynamically consistent kinematic data for a sidestep cut compared to the SIMPSA algorithm. Future studies should use external optimization routines to determine dynamically consistent kinematic data and report the differences between experimental and model data for these musculoskeletal simulations.

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  6. Blended-Wing-Body (BWB) Fuselage Structural Design for Weight Reduction

    NASA Technical Reports Server (NTRS)

    Mukhopadhyay, V.

    2005-01-01

    Structural analysis and design of efficient pressurized fuselage configurations for the advanced Blended-Wing-Body (BWB) flight vehicle is a challenging problem. Unlike a conventional cylindrical pressurized fuselage, stress level in a box type BWB fuselage is an order of magnitude higher, because internal pressure primarily results in bending stress instead of skin-membrane stress. In addition, resulting deformation of aerodynamic surface could significantly affect performance advantages provided by lifting body. The pressurized composite conformal multi-lobe tanks of X-33 type space vehicle also suffered from similar problem. In the earlier BWB design studies, Vaulted Ribbed Shell (VLRS), Flat Ribbed Shell (FRS); Vaulted shell Honeycomb Core (VLHC) and Flat sandwich shell Honeycomb Core (FLHC) concepts were studied. The flat and vaulted ribbed shell concepts were found most efficient. In a recent study, a set of composite sandwich panel and cross-ribbed panel were analyzed. Optimal values of rib and skin thickness, rib spacing, and panel depth were obtained for minimal weight under stress and buckling constraints. In addition, a set of efficient multi-bubble fuselage (MBF) configuration concept was developed. The special geometric configuration of this concept allows for balancing internal cabin pressure load efficiently, through membrane stress in inner-stiffened shell and inter-cabin walls, while the outer-ribbed shell prevents buckling due to external resultant compressive loads. The initial results from these approximate finite element analyses indicate progressively lower maximum stresses and deflections compared to the earlier study. However, a relative comparison of the FEM weight per unit floor area of the segment unit indicates that the unit weights are still relatively higher that the conventional B777 type cylindrical or A380 type elliptic fuselage design. Due to the manufacturing concern associated with multi-bubble fuselage, a Y braced box

  7. Differences in Birth Weight Associated with the 2008 Beijing Olympics Air Pollution Reduction: Results from a Natural Experiment

    PubMed Central

    Liu, Kaibo; Zhang, Jinliang; Thurston, Sally W.; Stevens, Timothy P.; Pan, Ying; Kane, Cathleen; Weinberger, Barry; Ohman-Strickland, Pamela; Woodruff, Tracey J.; Duan, Xiaoli; Assibey-Mensah, Vanessa; Zhang, Junfeng

    2015-01-01

    , Thurston SW, Stevens TP, Pan Y, Kane C, Weinberger B, Ohman-Strickland P, Woodruff TJ, Duan X, Assibey-Mensah V, Zhang J. 2015. Differences in birth weight associated with the 2008 Beijing Olympics air pollution reduction: results from a natural experiment. Environ Health Perspect 123:880–887; http://dx.doi.org/10.1289/ehp.1408795 PMID:25919693

  8. Development of Novel Methods for the Reduction of Noise and Weight in Helicopter Transmissions

    NASA Astrophysics Data System (ADS)

    Dimofte, Florin; Keith, Theo G., Jr.

    2003-01-01

    Over the 70-year evolution of the helicopter, man's understanding of vibration control has greatly increased. However, in spite of the increased performance, the extent of helicopter vibration problems has not significantly diminished. Crew vibration and noise remains important factors in the design of all current helicopters. With more complex and critical demands being placed on aircrews, it is essential that vibration and noise not impair their performance. A major source of helicopter cabin noise (which has been measured at a sound pressure level of over 100 dB) is the gearbox. Reduction of this noise has been a goal of NASA and the U.S. Army. Gear mesh noise is typically in the frequency range of 1000 to 3000 Hz, a range important for speech. A requirement for U.S. Army/NASA Advanced Rotorcraft Transmission project has been a 10-dB reduction compared to current designs. A combined analytical/experimental effort has been underway, since the end of the 80's, to study effects of design parameters on noise production. The noise generated by the gear mesh can be transmitted to the surrounding media through the bearings that support the gear shaft. Therefore, the use of fluid film bearings instead of rolling element bearings could reduce the transmission noise by 10 dB. In addition, the fluid film bearings that support the gear shaft can change the dynamics of the gear assembly by providing damping to the system and by being softer than rolling element bearings. Wave bearings can attenuate, and filter, the noise generated by a machine component due to the dynamic stiffness and damping coefficients. The attenuation ratio could be as large as 35-40 dB. The noise components at higher frequencies than a synchronous frequency can be almost eliminated.

  9. Effects of carbohydrate refeeding on physiological responses and psychological and physical performance following acute weight reduction in collegiate wrestlers.

    PubMed

    Finn, Kevin J; Dolgener, Forrest A; Williams, Richard B

    2004-05-01

    The purpose of this study was to determine the effects of carbohydrate refeeding on intermittent sprint exercise, blood lactate response, and mood following a typical weight-reduction program practiced by college wrestlers. Fifteen collegiate wrestlers from the University of Northern Iowa completed 3 trials of intermittent arm cranking and a mood inventory prior to weigh-ins (baseline), after weigh-ins, and 1 hour postconsumption of either 1.5 g carbohydrate (CHO)/kg body mass carbohydrate beverage (25% solution) or placebo taken within 1 hour after weigh-ins. Blood lactate responses were determined with each trial. Repeated measures analysis of variance indicated no significant interaction between group and trial for total work (p = 0.08), blood lactate (p = 0.29), positive mood (p = 0.49), or negative mood (p = 0.78). Simple effects analysis indicated a significant difference in lactate response between trials (p = 0.002); however, no difference for work (p = 0.75), positive mood (p = 0.13), or negative mood (p = 0.08). The results of this study suggest that intermittent sprint exercise, blood lactate response, and mood were not positively affected by ingestion of CHOs following an acute weight-reduction period.

  10. The effects of low-fat, high-carbohydrate diets on plasma lipoproteins, weight loss, and heart disease risk reduction.

    PubMed

    Schaefer, Ernst J; Gleason, Joi A; Dansinger, Michael L

    2005-11-01

    Although there is consensus about restriction of dietary saturated and trans fatty acids, cholesterol, and sugars, there is debate about what the optimal total fat and carbohydrate content of the diet should be for weight loss and coronary heart disease (CHD) risk reduction. The overall evidence that dietary composition plays an important role in determining caloric intake is limited. Three recent randomized trials have indicated that low-carbohydrate diets are more effective in promoting weight loss in overweight and obese subjects over 4 to 6 months, but not over 1 year. In our own randomized trial no such differences were noted, and compliance with extreme diets was limited. Moreover little attempt has been made to control for the type of carbohydrate used in the low-fat, high-carbohydrate arms of these trials. Available evidence suggests that restriction of sugars and carbohydrates having a high glycemic index would be preferable to total carbohydrate restriction, and that an increased intake of fiber and essential fats (especially omega-3 fatty acids) is also important for overall heart disease risk reduction.

  11. Demonstration of improved vehicle fuel efficiency through innovative tire design, materials, and weight reduction technologies

    SciTech Connect

    Donley, Tim

    2014-12-31

    Cooper completed an investigation into new tire technology using a novel approach to develop and demonstrate a new class of fuel efficient tires using innovative materials technology and tire design concepts. The objective of this work was to develop a new class of fuel efficient tires, focused on the “replacement market” that would improve overall passenger vehicle fuel efficiency by 3% while lowering the overall tire weight by 20%. A further goal of this project was to accomplish the objectives while maintaining the traction and wear performance of the control tire. This program was designed to build on what has already been accomplished in the tire industry for rolling resistance based on the knowledge and general principles developed over the past decades. Cooper’s CS4 (Figure #1) premium broadline tire was chosen as the control tire for this program. For Cooper to achieve the goals of this project, the development of multiple technologies was necessary. Six technologies were chosen that are not currently being used in the tire industry at any significant level, but that showed excellent prospects in preliminary research. This development was divided into two phases. Phase I investigated six different technologies as individual components. Phase II then took a holistic approach by combining all the technologies that showed positive results during phase one development.

  12. Electromagnet weight reduction in a magnetic levitation system for contactless delivery applications.

    PubMed

    Hong, Do-Kwan; Woo, Byung-Chul; Koo, Dae-Hyun; Lee, Ki-Chang

    2010-01-01

    This paper presents an optimum design of a lightweight vehicle levitation electromagnet, which also provides a passive guide force in a magnetic levitation system for contactless delivery applications. The split alignment of C-shaped electromagnets about C-shaped rails has a bad effect on the lateral deviation force, therefore, no-split positioning of electromagnets is better for lateral performance. This is verified by simulations and experiments. This paper presents a statistically optimized design with a high number of the design variables to reduce the weight of the electromagnet under the constraint of normal force using response surface methodology (RSM) and the kriging interpolation method. 2D and 3D magnetostatic analysis of the electromagnet are performed using ANSYS. The most effective design variables are extracted by a Pareto chart. The most desirable set is determined and the influence of each design variable on the objective function can be obtained. The generalized reduced gradient (GRG) algorithm is adopted in the kriging model. This paper's procedure is validated by a comparison between experimental and calculation results, which shows that the predicted performance of the electromagnet designed by RSM is in good agreement with the simulation results.

  13. MyD88 signaling in the CNS is required for development of fatty acid induced leptin resistance and diet-induced obesity

    PubMed Central

    Kleinridders, André; Schenten, Dominik; Könner, A. Christine; Belgardt, Bengt F.; Mauer, Jan; Okamura, Tomoo; Wunderlich, F. Thomas; Medzhitov, Ruslan; Brüning, Jens C.

    2014-01-01

    Summary Obesity-associated activation of inflammatory pathways represents a key step in the development of insulin resistance in peripheral organs, partially via activation of TLR-4 signaling by fatty acids. Here we demonstrate that palmitate acting in the central nervous system (CNS) inhibits leptin-induced anorexia and Stat-3 activation. To determine the functional significance of TLR signaling in the CNS in the development of leptin resistance and diet-induced obesity in vivo, we have characterized mice deficient for the TLR adaptor molecule MyD88 in the CNS (MyD88ΔCNS). Compared to control mice, MyD88ΔCNS mice are protected from high-fat diet (HFD)-induced weight gain, from the development of HFD-induced leptin resistance and from the induction of leptin resistance by acute central application of palmitate. Moreover, CNS-restricted MyD88 deletion protects from HFD- and icv palmitate-induced impairment of peripheral glucose metabolism. Thus, we define neuronal MyD88-dependent signaling as a key regulator of diet-induced leptin and insulin resistance in vivo. PMID:19808018

  14. Intestine-specific Deletion of Acyl-CoA:Monoacylglycerol Acyltransferase (MGAT) 2 Protects Mice from Diet-induced Obesity and Glucose Intolerance*

    PubMed Central

    Nelson, David W.; Gao, Yu; Yen, Mei-I; Yen, Chi-Liang Eric

    2014-01-01

    The absorption of dietary fat involves the re-esterification of digested triacylglycerol in the enterocytes, a process catalyzed by acyl-CoA:monoacylglycerol acyltransferase (MGAT) 2. Mice without a functional gene encoding MGAT2 (Mogat2−/−) are protected from diet-induced obesity. Surprisingly, these mice absorb normal amounts of dietary fat but increase their energy expenditure. MGAT2 is expressed in tissues besides intestine, including adipose tissue in both mice and humans. To test the hypothesis that intestinal MGAT2 regulates systemic energy balance, we generated and characterized mice deficient in MGAT2 specifically in the small intestine (Mogat2IKO). We found that, like Mogat2−/− mice, Mogat2IKO mice also showed a delay in fat absorption, a decrease in food intake, and a propensity to use fatty acids as fuel when first exposed to a high fat diet. Mogat2IKO mice increased energy expenditure although to a lesser degree than Mogat2−/− mice and were protected against diet-induced weight gain and associated comorbidities, including hepatic steatosis, hypercholesterolemia, and glucose intolerance. These findings illustrate that intestinal lipid metabolism plays a crucial role in the regulation of systemic energy balance and may be a feasible intervention target. In addition, they suggest that MGAT activity in extraintestinal tissues may also modulate energy metabolism. PMID:24784138

  15. Treating Diet-Induced Diabetes and Obesity with Human Embryonic Stem Cell-Derived Pancreatic Progenitor Cells and Antidiabetic Drugs

    PubMed Central

    Bruin, Jennifer E.; Saber, Nelly; Braun, Natalie; Fox, Jessica K.; Mojibian, Majid; Asadi, Ali; Drohan, Campbell; O’Dwyer, Shannon; Rosman-Balzer, Diana S.; Swiss, Victoria A.; Rezania, Alireza; Kieffer, Timothy J.

    2015-01-01

    Summary Human embryonic stem cell (hESC)-derived pancreatic progenitor cells effectively reverse hyperglycemia in rodent models of type 1 diabetes, but their capacity to treat type 2 diabetes has not been reported. An immunodeficient model of type 2 diabetes was generated by high-fat diet (HFD) feeding in SCID-beige mice. Exposure to HFDs did not impact the maturation of macroencapsulated pancreatic progenitor cells into glucose-responsive insulin-secreting cells following transplantation, and the cell therapy improved glucose tolerance in HFD-fed transplant recipients after 24 weeks. However, since diet-induced hyperglycemia and obesity were not fully ameliorated by transplantation alone, a second cohort of HFD-fed mice was treated with pancreatic progenitor cells combined with one of three antidiabetic drugs. All combination therapies rapidly improved body weight and co-treatment with either sitagliptin or metformin improved hyperglycemia after only 12 weeks. Therefore, a stem cell-based therapy may be effective for treating type 2 diabetes, particularly in combination with antidiabetic drugs. PMID:25801507

  16. The Anti-Inflammatory Effect of Prunus yedoensis Bark Extract on Adipose Tissue in Diet-Induced Obese Mice

    PubMed Central

    Kang, Hee; Kwak, Tae-Kyung; Kim, Bo-Geun; Lee, Kyung-Jin

    2015-01-01

    Chronic, low-grade inflammatory responses occur in obese adipose tissue and play a crucial role in the development of insulin resistance. Macrophages exposed to high glucose upregulate the expression of SRA, a macrophage-specific scavenger receptor. The present study investigated whether Prunus yedoensis (PY) bark extract affects the inflammatory response and scavenger receptor gene expression observed in a diet-induced obesity model in vivo. Oral administration of PY extract significantly reduced fasting blood glucose levels without a change in body weight in mice fed a high fat diet for 17 weeks. PY extract significantly suppressed expression of inflammatory and macrophage genes such as tumor necrosis factor-α, interleukin-6, and F4/80 in epididymal adipose tissue. Among scavenger receptor genes, SRA expression was significantly reduced. The inhibitory responses of PY extract and its fractions were determined through evaluation of scavenger receptor expression in THP-1 cells. PY extract and its ethyl acetate fraction decreased the levels of SRA mRNA and phospho-ERK1/2 during monocyte differentiation. Our data indicate that the anti-inflammatory effects of PY extract and its downregulation of SRA seem to account for its hypoglycemic effects. PMID:26413130

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2012-09-01

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

  19. Effects of Murine Norovirus Infection on a Mouse Model of Diet-Induced Obesity and Insulin Resistance

    PubMed Central

    Paik, Jisun; Fierce, Yvette; Drivdahl, Rolf; Treuting, Piper M; Seamons, Audrey; Brabb, Thea; Maggio-Price, Lillian

    2010-01-01

    Murine norovirus (MNV) is prevalent in SPF mouse facilities in the United States, and we currently lack sufficient data to determine whether it should be eliminated. It is generally accepted that the virus does not cause clinical symptoms in immunocompetent mice. However, we previously reported that MNV infection alters the phenotype of a mouse model of bacteria-induced inflammatory bowel disease in part through its effects on dendritic cells. The tropism of MNV toward macrophages and dendritic cells makes MNV a potential intercurrent variable in murine models of macrophage-driven inflammatory diseases, such as obesity, insulin resistance, and atherosclerosis. Therefore, we determined whether MNV infection altered obesity and insulin resistance phenotypes in C57BL/6 mice, a widely used model of diet-induced obesity. We found that MNV did not alter weight gain, food intake, and glucose metabolism in this model, but it did induce subtle changes in lymphoid tissue. Further studies using other models of metabolic diseases are needed to provide additional information on the potential role this ‘subclinical’ virus might have on disease progression in mouse models of inflammatory diseases. PMID:20579433

  20. Long-term supplementation of umbelliferone and 4-methylumbelliferone alleviates high-fat diet induced hypertriglyceridemia and hyperglycemia in mice.

    PubMed

    Sim, Mi-Ok; Ham, Ju Ri; Lee, Hae-In; Seo, Kwon-Il; Lee, Mi-Kyung

    2014-06-05

    This study was conducted to evaluate the effects of umbelliferone (UF) and 4-methylumbelliferone (mUF) on high-fat diet-induced hypertriglyceridemia and hyperglycemia in mice. The mice were assigned to normal control, high-fat control, and high-fat with UF or mUF groups. For UF or mUF groups, the high-fat diet was supplemented with UF or mUF at 0.02% (wt/wt) for 12weeks. Both UF and mUF significantly decreased plasma triglyceride, free fatty acid and glucose levels, adipocyte size, white adipose tissue weights, and hepatic phosphatidate phosphohydrolase activity and significantly increased plasma adiponectin levels and hepatic fatty acid β-oxidation activity compared with the high-fat control group. UF and mUF improved glucose intolerance and hepatic steatosis in the high-fat fed mice. Long-term high-fat diet intake induced an increase in hepatic CYP2E1 activity and lipid peroxide and cytosolic hydrogen peroxide contents and suppressed superoxide dismutase and glutathione peroxidase activities, which were reversed by UF and mUF supplementation. These results indicate that UF and mUF similarly ameliorate hypertriglyceridemia and hyperglycemia partly by modulating hepatic lipid metabolism and the antioxidant defense system along with increasing adiponectin levels.

  1. Myricetin protects against diet-induced obesity and ameliorates oxidative stress in C57BL/6 mice*

    PubMed Central

    Su, Hong-ming; Feng, Li-na; Zheng, Xiao-dong; Chen, Wei

    2016-01-01

    Background: Myricetin is a naturally occurring antioxidant commonly found in various plants. However, little information is available with respect to its direct anti-obesity effects. Objective: This study was undertaken to investigate the effect of myricetin on high-fat diet (HFD)-induced obesity in C57BL/6 mice. Results: Administration of myricetin dramatically reduced the body weight of diet-induced obese mice compared with solely HFD-induced mice. Several parameters related to obesity including serum glucose, triglyceride, and cholesterol were significantly decreased in myricetin-treated mice. Moreover, obesity-associated oxidative stress (glutathione peroxidase (GPX) activity, total antioxidant capacity (T-AOC), and malondialdehyde (MDA)) and inflammation (tumor necrosis factor-α (TNF-α)) were ameliorated in myricetin-treated mice. Further investigation revealed that the protective effect of myricetin against HFD-induced obesity in mice appeared to be partially mediated through the down-regulation of mRNA expression of adipogenic transcription factors peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), and lipogenic transcription factor sterol regulatory element-binding protein 1c (SREBP-1c). Conclusions: Consumption of myricetin may help to prevent obesity and obesity-related metabolic complications. PMID:27256677

  2. Two-generation diet-induced obesity model producing mice with increased amount of body fat in early adulthood.

    PubMed

    Kubandová, J; Fabian, D; Burkuš, J; Cikoš, Š; Czikková, S; Mozeš, Š; Šefčíková, Z; Koppel, J

    2014-01-01

    The aim of our study was to develop a model producing obese mice in early adulthood (4-6 weeks) based on their over-nutrition during fetal and early postnatal development. The fertilized dams of the parental generation were fed the standard diet supplemented with high-energy nutritional product Ensure Plus during gestation and lactation. Delivered weanlings were then fed with standard or supplemented diet and assessed for body fat deposits using EchoMRI at the time of early and late adulthood. Maternal over-feeding during the period before weaning had the most significant effect on obesity development in the filial generation. In weanlings, significantly higher body fat deposits and average body weight were recorded. Later, further significant increase in percentage of body fat in both male and female mice was observed. Withdrawal of the Ensure Plus supplement caused a decrease in the percentage of body fat in part of the filial generation. In offspring fed the standard diet, higher fat deposits persisted till the time of late adulthood. We conclude that this diet-induced obesity model might be used in exploration of the effects of elevated body fat on physiological functions of various organ systems during juvenile and early adulthood periods of life of a human being.

  3. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats

    PubMed Central

    Paul, Heather A.; Bomhof, Marc R.; Vogel, Hans J.; Reimer, Raylene A.

    2016-01-01

    Maternal obesity and overnutrition during pregnancy and lactation can program an increased risk of obesity in offspring. In this context, improving maternal metabolism may help reduce the intergenerational transmission of obesity. Here we show that, in Sprague-Dawley rats, selectively altering obese maternal gut microbial composition with prebiotic treatment reduces maternal energy intake, decreases gestational weight gain, and prevents increased adiposity in dams and their offspring. Maternal serum metabolomics analysis, along with satiety hormone and gut microbiota analysis, identified maternal metabolic signatures that could be implicated in programming offspring obesity risk and highlighted the potential influence of maternal gut microbiota on maternal and offspring metabolism. In particular, the metabolomic signature of insulin resistance in obese rats normalized when dams consumed the prebiotic. In summary, prebiotic intake during pregnancy and lactation improves maternal metabolism in diet-induced obese rats in a manner that attenuates the detrimental nutritional programming of offspring associated with maternal obesity. Overall, these findings contribute to our understanding of the maternal mechanisms influencing the developmental programming of offspring obesity and provide compelling pre-clinical evidence for a potential strategy to improve maternal and offspring metabolic outcomes in human pregnancy. PMID:26868870

  4. Phlorizin Supplementation Attenuates Obesity, Inflammation, and Hyperglycemia in Diet-Induced Obese Mice Fed a High-Fat Diet.

    PubMed

    Shin, Su-Kyung; Cho, Su-Jung; Jung, Un Ju; Ryu, Ri; Choi, Myung-Sook

    2016-02-16

    Obesity, along with its related complications, is a serious health problem worldwide. Many studies reported the anti-diabetic effect of phlorizin, while little is known about its anti-obesity effect. We investigated the beneficial effects of phlorizin on obesity and its complications, including diabetes and inflammation in obese animal. Male C57BL/6J mice were divided into three groups and fed their respective experimental diets for 16 weeks: a normal diet (ND, 5% fat, w/w), high-fat diet (HFD, 20% fat, w/w), or HFD supplemented with phlorizin (PH, 0.02%, w/w). The findings revealed that the PH group had significantly decreased visceral and total white adipose tissue (WAT) weights, and adipocyte size compared to the HFD. Plasma and hepatic lipids profiles also improved in the PH group. The decreased levels of hepatic lipids in PH were associated with decreased activities of enzymes involved in hepatic lipogenesis, cholesterol synthesis and esterification. The PH also suppressed plasma pro-inflammatory adipokines levels such as leptin, adipsin, tumor necrosis factor-α, monocyte chemoattractant protein-1, interferon-γ, and interleukin-6, and prevented HFD-induced collagen accumulation in the liver and WAT. Furthermore, the PH supplementation also decreased plasma glucose, insulin, glucagon, and homeostasis model assessment of insulin resistance levels. In conclusion, phlorizin is beneficial for preventing diet-induced obesity, hepatic steatosis, inflammation, and fibrosis, as well as insulin resistance.

  5. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

    PubMed Central

    Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

    2015-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  6. [Reduction of dielectric properties of rat gastrocnemius induced by loss of weight].

    PubMed

    Tang, Zhiynan; Zhao, Weihong; Wang, Lin; Ma, Qing

    2009-10-01

    In this experimental study, the AC impedance of isolated gastrocnemius was measured with an impendance analyzer of Agilent 4294A, and the effect of simulated weightlessness on the dielectric properties of the cells in isolated rat sural muscle was investigated by analyzing the dielectric numerical characters with the use of dielectric spectroscopy, the Cole-Cole plots, the spectrum of loss factor and loss tangent, as well as the spectrum of conductivity imaginary part. The results demonstrated that 10 weeks' simulated weightlessness caused some changes; for example, both permittivity at low frequency (epsilonL) and permittivity increment (deltaepsilon) were reduced, and conductivity at high frequency (kappa(h)) was also reduced; at the same time, conductivity increment (deltakappa) was reduced, too. The first characteristic frequency (f(C1)) decreased, while the second characteristic frequency(f(C2)) increased. All of the peak of loss factor, the peak of loss tangent, and the maximum of conductivity imaginary part were reduced. These data indicated that the reduction of dielectric properties of skeletal muscles was induced by weightlessness.

  7. Differential effects of prenatal stress on metabolic programming in diet-induced obese and dietary-resistant rats

    PubMed Central

    Balasubramanian, Priya; Varde, Pratibha A.; Abdallah, Simon Labib; Najjar, Sonia M.; MohanKumar, P. S.

    2015-01-01

    Stress during pregnancy is a known contributing factor for the development of obesity in the offspring. Since maternal obesity is on the rise, we wanted to identify the effects of prenatal stress in the offspring of diet-induced obese (DIO) rats and compare them with the offspring of dietary-resistant (DR) rats. We hypothesized that prenatal stress would make both DIO and DR offspring susceptible to obesity, but the effect would be more pronounced in DIO rats. Pregnant DIO and DR rats were divided into two groups: nonstressed controls (control) and prenatal stress (subjected to restraint stress, three times/day from days 14 to 21 of gestation). After recording birth weight and weaning weight, male offspring were weaned onto a chow diet for 9 wk and shifted to a high-fat (HF) diet for 1 wk. At the end of the 10th wk the animals were euthanized, and visceral adipose mass, blood glucose, serum insulin, and C-peptide levels were measured. Prenatal stress resulted in hyperinsulinemia and higher C-peptide levels without altering caloric intake, body weight gain, or fat mass in the DIO offspring after 1 wk of HF intake, but not in DR offspring. To determine the mechanism underlying the hyperinsulinemia, we measured the levels of CEACAM1 that are responsible for insulin clearance. CEACAM1 levels in the liver were reduced in prenatally stressed DIO offspring after the HF challenge, suggesting that preexisting genetic predisposition in combination with prenatal stress increases the risk for obesity in adulthood, especially when offspring are fed a HF diet. PMID:26219866

  8. Thrombospondin-1 regulates adiposity and metabolic dysfunction in diet-induced obesity enhancing adipose inflammation and stimulating adipocyte proliferation

    PubMed Central

    Kong, Ping; Gonzalez-Quesada, Carlos; Li, Na; Cavalera, Michele; Lee, Dong-Wook

    2013-01-01

    As a typical matricellular protein, thrombospondin (TSP)-1, binds to the structural matrix and regulates cellular behavior by modulating growth factor and cytokine signaling. Obesity and diabetes are associated with marked upregulation of TSP-1 in adipose tissue. We hypothesized that endogenous TSP-1 may play an important role in the pathogenesis of diet-induced obesity and metabolic dysfunction. Accordingly, we examined the effects of TSP-1 gene disruption on weight gain, adiposity, and adipose tissue inflammation in mice receiving a high-fat diet (HFD: 60% fat, 20% carbohydrate) or a high-carbohydrate low-fat diet (HCLFD: 10% fat, 70% carbohydrate). HFD mice had significantly higher TSP-1 expression in perigonadal adipose tissue; TSP-1 was predominantly localized in the adipose interstitium. TSP-1 loss attenuated weight gain and fat accumulation in HFD and HCLFD groups. Compared with corresponding wild-type animals, TSP-1-null mice had decreased insulin levels but exhibited elevated free fatty acid and triglyceride levels, suggesting impaired fatty acid uptake. TSP-1 loss did not affect adipocyte size and had no effect on adipose vascular density. However, TSP-1-null mice exhibited attenuated tumor necrosis factor-α mRNA expression and reduced macrophage infiltration, suggesting a role for TSP-1 in mediating obesity-associated inflammation. In vitro, TSP-1 enhanced proliferation of 3T3-L1 preadipocytes but did not modulate inflammatory cytokine and chemokine synthesis. In conclusion, TSP-1 upregulation contributes to weight gain, adipose growth, and the pathogenesis of metabolic dysfunction. The effects of TSP-1 may involve stimulation of adipocyte proliferation, activation of inflammatory signaling, and facilitated fatty acid uptake by adipocytes. PMID:23757408

  9. Gelidium amansii extract ameliorates obesity by down-regulating adipogenic transcription factors in diet-induced obese mice

    PubMed Central

    Kang, Ji-Hye; Lee, Hyun-Ah; Kim, Hak-Ju

    2017-01-01

    BACKGROUND/OBJECTIVES In this study, we investigated whether Gelidium amansii extract (GAE) ameliorates obesity in diet-induced obese (DIO) mice. MATERIALS/METHODS The mice were maintained on a high-fat diet (HD) for 5 weeks to generate the DIO mouse model. And then mice fed HD plus 0.5% (GAE1), 1% (GAE2) or 2% (GAE3) for 8 weeks. RESULTS After the experimental period, GAE-supplemented groups were significantly lower than the HD group in body weight gain and liver weight. GAE supplemented groups were significantly lower than the HD group in both epididymal and mesenteric adipose tissue mass. The plasma leptin level was significantly higher in the HD group than in GAE-supplemented groups. The leptin level of HD+GAE3 group was significantly lower than that of the HD+conjugated linoleic acid (CLA) group. In contrast, plasma adiponectin level of the HD group was significantly lower than those of HD+GAE2 and HD+GAE3 groups. The expression levels of adipogenic proteins such as fatty acid synthase, sterol regulatory element-binding protein-1c, peroxisome proliferator-activated receptor γ, and CCAAT/enhancer binding protein α in the GAE supplemented groups were significantly decreased than those in HD group, respectively. In addition, the expression levels of HD+GAE2 and HD+GAE3 groups are significantly decreased compared to those of HD+CLA group. On the contrary, the expression levels of hormone-sensitive lipase and phospho-AMP-activated protein kinase, proteins associated with lipolysis, were significantly increased in the GAE supplemented groups compared to those in the HD group. HD+GAE3 group showed the highest level among the GAE supplemented groups. CONCLUSIONS These results suggested that GAE supplementation stimulated the expressions of lipid metabolic factors and reduced weight gain in HD-fed C57BL/6J obese mice. PMID:28194261

  10. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats.

    PubMed

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V; Gydesen, Sofie; Ottosen, Ida; Henriksen, Jan Erik; Beck-Nielsen, Henning; Christiansen, Claus; Karsdal, Morten A; Henriksen, Kim

    2014-08-15

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma glucoregulatory hormones and pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced anorectic action during the 7 days lead-in period and markedly reduced food intake and body weight in conjunction with improved glucose homeostasis. During the maintenance period, oral sCT normalized food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes.

  11. Macrophage-Specific ApoE Gene Repair Reduces Diet-Induced Hyperlipidemia and Atherosclerosis in Hypomorphic Apoe Mice

    PubMed Central

    Gaudreault, Nathalie; Kumar, Nikit; Olivas, Victor R.; Eberlé, Delphine; Rapp, Joseph H.; Raffai, Robert L.

    2012-01-01

    Background Apolipoprotein (apo) E is best known for its ability to lower plasma cholesterol and protect against atherosclerosis. Although the liver is the major source of plasma apoE, extra-hepatic sources of apoE, including from macrophages, account for up to 10% of plasma apoE levels. This study examined the contribution of macrophage-derived apoE expression levels in diet-induced hyperlipidemia and atherosclerosis. Methodology/Principal Findings Hypomorphic apoE (Apoeh/h) mice expressing wildtype mouse apoE at ∼2–5% of physiological levels in all tissues were derived by gene targeting in embryonic stem cells. Cre-mediated gene repair of the Apoeh/h allele in Apoeh/hLysM-Cre mice raised apoE expression levels by 26 fold in freshly isolated peritoneal macrophages, restoring it to 37% of levels seen in wildtype mice. Chow-fed Apoeh/hLysM-Cre and Apoeh/h mice displayed similar plasma apoE and cholesterol levels (55.53±2.90 mg/dl versus 62.70±2.77 mg/dl, n = 12). When fed a high-cholesterol diet (HCD) for 16 weeks, Apoeh/hLysM-Cre mice displayed a 3-fold increase in plasma apoE and a concomitant 32% decrease in plasma cholesterol when compared to Apoeh/h mice (602.20±22.30 mg/dl versus 888.80±24.99 mg/dl, n = 7). On HCD, Apoeh/hLysM-Cre mice showed increased apoE immunoreactivity in lesional macrophages and liver-associated Kupffer cells but not hepatocytes. In addition, Apoeh/hLysM-Cre mice developed 35% less atherosclerotic lesions in the aortic root than Apoeh/h mice (167×103±16×103 µm2 versus 259×103±56×103 µm2, n = 7). This difference in atherosclerosis lesions size was proportional to the observed reduction in plasma cholesterol. Conclusions/Significance Macrophage-derived apoE raises plasma apoE levels in response to diet-induced hyperlipidemia and by such reduces atherosclerosis proportionally to the extent to which it lowers plasma cholesterol levels. PMID:22606237

  12. Ghrelin, Sleep Reduction and Evening Preference: Relationships to CLOCK 3111 T/C SNP and Weight Loss

    PubMed Central

    Garaulet, Marta; Sánchez-Moreno, Carmen; Smith, Caren E.; Lee, Yu-Chi; Nicolás, Francisco; Ordovás, Jose M.

    2011-01-01

    Background Circadian Locomotor Output Cycles Kaput (CLOCK), an essential element of the positive regulatory arm in the human biological clock, is involved in metabolic regulation. The aim was to investigate the behavioral (sleep duration, eating patterns and chronobiological characteristics) and hormonal (plasma ghrelin and leptin concentrations) factors which could explain the previously reported association between the CLOCK 3111T/C SNP and weight loss. Methodology/Principal Findings We recruited 1495 overweight/obese subjects (BMI: 25–40 kg/m2) of 20–65 y. who attended outpatient obesity clinics in Murcia, in southeastern Spain. We detected an association between the CLOCK 3111T/C SNP and weight loss, which was particularly evident after 12–14 weeks of treatment (P = 0.038). Specifically, carriers of the minor C allele were more resistant to weight loss than TT individuals (Mean±SEM) (8.71±0.59 kg vs 10.4±0.57 kg) C and TT respectively. In addition, our data show that minor C allele carriers had: 1. shorter sleep duration Mean ± SEM (7.0±0.05 vs 7.3±0.05) C and TT respectively (P = 0.039), 2. higher plasma ghrelin concentrations Mean ± SEM (pg/ml) (1108±49 vs 976±47)(P = 0.034); 3. delayed breakfast time; 4. evening preference and 5. less compliance with a Mediterranean Diet pattern, as compared with TT homozygotes. Conclusions/Significance Sleep reduction, changes in ghrelin values, alterations of eating behaviors and evening preference that characterized CLOCK 3111C carriers could be affecting weight loss. Our results support the hypothesis that the influence of the CLOCK gene may extend to a broad range of variables linked with human behaviors. PMID:21386998

  13. Xanthohumol Improves Diet-induced Obesity and Fatty Liver by Suppressing Sterol Regulatory Element-binding Protein (SREBP) Activation.

    PubMed

    Miyata, Shingo; Inoue, Jun; Shimizu, Makoto; Sato, Ryuichiro

    2015-08-14

    Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that stimulate the expression of genes involved in fatty acid and cholesterol biosynthesis. Here, we demonstrate that a prenylated flavonoid in hops, xanthohumol (XN), is a novel SREBP inactivator that reduces the de novo synthesis of fatty acid and cholesterol. XN independently suppressed the maturation of SREBPs of insulin-induced genes in a manner different from sterols. Our results suggest that XN impairs the endoplasmic reticulum-to-Golgi translocation of the SREBP cleavage-activating protein (SCAP)-SREBP complex by binding to Sec23/24 and blocking SCAP/SREBP incorporation into common coated protein II vesicles. Furthermore, in diet-induced obese mice, dietary XN suppressed SREBP-1 target gene expression in the liver accompanied by a reduction of the mature form of hepatic SREBP-1, and it inhibited the development of obesity and hepatic steatosis. Altogether, our data suggest that XN attenuates the function of SREBP-1 by repressing its maturation and that it has the potential of becoming a nutraceutical food or pharmacological agent for improving metabolic syndrome.

  14. Xanthohumol Improves Diet-induced Obesity and Fatty Liver by Suppressing Sterol Regulatory Element-binding Protein (SREBP) Activation*

    PubMed Central

    Miyata, Shingo; Inoue, Jun; Shimizu, Makoto; Sato, Ryuichiro

    2015-01-01

    Sterol regulatory element-binding proteins (SREBPs) are key transcription factors that stimulate the expression of genes involved in fatty acid and cholesterol biosynthesis. Here, we demonstrate that a prenylated flavonoid in hops, xanthohumol (XN), is a novel SREBP inactivator that reduces the de novo synthesis of fatty acid and cholesterol. XN independently suppressed the maturation of SREBPs of insulin-induced genes in a manner different from sterols. Our results suggest that XN impairs the endoplasmic reticulum-to-Golgi translocation of the SREBP cleavage-activating protein (SCAP)-SREBP complex by binding to Sec23/24 and blocking SCAP/SREBP incorporation into common coated protein II vesicles. Furthermore, in diet-induced obese mice, dietary XN suppressed SREBP-1 target gene expression in the liver accompanied by a reduction of the mature form of hepatic SREBP-1, and it inhibited the development of obesity and hepatic steatosis. Altogether, our data suggest that XN attenuates the function of SREBP-1 by repressing its maturation and that it has the potential of becoming a nutraceutical food or pharmacological agent for improving metabolic syndrome. PMID:26140926

  15. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity.

    PubMed

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-09-30

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction.

  16. Lactobacillus plantarum HAC01 regulates gut microbiota and adipose tissue accumulation in a diet-induced obesity murine model.

    PubMed

    Park, Soyoung; Ji, Yosep; Jung, Hoe-Yune; Park, Hyunjoon; Kang, Jihee; Choi, Sang-Haeng; Shin, Heuynkil; Hyun, Chang-Kee; Kim, Kyong-Tai; Holzapfel, Wilhelm H

    2017-02-01

    The functional features of Lactobacillus plantarum HAC01 (HAC01), isolated from fermented Korean kimchi, were studied with regard to the fat mass, immunometabolic biomarkers and dysbiosis in a diet-induced obesity (DIO) murine model. L. rhamnosus GG (LGG) served as reference strain and a PBS-treated group as control. The administration of L. plantarum HAC01 resulted in reduction of the mesenteric adipose depot, the conjunctive tissue closely associated with the gastrointestinal tract, where lipid oxidative gene expression was upregulated compared to the control group. Metagenome analysis of intestinal microbiota showed that both strains HAC01 and LGG influenced specific bacterial families such as the Lachnospiraceae and Ruminococcaceae rather than the phyla Firmicutes and Bacteroidetes as a whole. The relative abundance of the Lachnospiraceae (phylum Firmicutes) was significantly higher in both LAB-treated groups than in the control. Comparing the impact of the two Lactobacillus strains on microbial composition in the gut also suggests strain-specific effects. The study emphasises the need for deeper studies into functional specificity of a probiotic organism at the strain level. Alleviation of obesity-associated dysbiosis by modulation of the gut microbiota appears to be associated with "indicator" bacterial taxa such as the family Lachnospiraceae. This may provide further insight into mechanisms basic to the mode of probiotic action against obesity and associated dysbiosis.

  17. Nebivolol Ameliorates Cardiac NLRP3 Inflammasome Activation in a Juvenile-Adolescent Animal Model of Diet-Induced Obesity

    PubMed Central

    Xie, Qihai; Wei, Tong; Huang, Chenglin; Liu, Penghao; Sun, Mengwei; Shen, Weili; Gao, Pingjin

    2016-01-01

    NLRP3 is involved in obesity-induced cardiac remodeling and dysfunction. In this study, we evaluated whether the cardiac protective effects of nebivolol relied on attenuating NLRP3 activation in a juvenile-adolescent animal model of diet-induced obesity. Weaning male Sprague-Dawley rats were fed with either a standard chow diet (ND) or a high-fat diet (HFD) for 8 weeks. The obese rats were subsequently subdivided into three groups: 1) HFD control group; 2) HFD with low-dose nebivolol (5 mg/kg/d); 3) HFD with high-dose nebivolol (10 mg/kg/d). Treatment with nebivolol prevented HFD-induced obesity associated excess cardiac lipid accumulation as well as myocardial mitochondrial dysfunction. Nebivolol attenuated pro-inflammatory cytokines secretion and NLRP3 inflammasome activation in myocardium of obese rats. In parallel, nebivolol treatment of obese animals increased cardiac β3-AR expression, reversing the reduction of endothelial nitric oxide synthase (eNOS). In vitro, nebivolol treatment of palmitate-incubated H9C2 cells suppressed autophagy, restored mitochondrial biogenesis, leading to decreased mitochondrial reactive oxygen species (mtROS) generation, and suppressed NLRP3 inflammasome activation. Meanwhile the presence of shRNA against β3-AR or against eNOS deteriorated the protective effects of nebivolol. These data suggest the beneficial effect of nebivolol on myocardial lipotoxicity contributing to inhibiting NLRP3 inflammasome activation possibly via improved mitochondrial dysfunction. PMID:27686325

  18. Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice.

    PubMed

    Kodo, Kazuki; Sugimoto, Satoru; Nakajima, Hisakazu; Mori, Jun; Itoh, Ikuyo; Fukuhara, Shota; Shigehara, Keiichi; Nishikawa, Taichiro; Kosaka, Kitaro; Hosoi, Hajime

    2017-01-01

    Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO's anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO's suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT's endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO

  19. Erythropoietin (EPO) ameliorates obesity and glucose homeostasis by promoting thermogenesis and endocrine function of classical brown adipose tissue (BAT) in diet-induced obese mice

    PubMed Central

    Kodo, Kazuki; Sugimoto, Satoru; Mori, Jun; Itoh, Ikuyo; Fukuhara, Shota; Shigehara, Keiichi; Nishikawa, Taichiro; Kosaka, Kitaro; Hosoi, Hajime

    2017-01-01

    Erythropoietin (EPO), clinically used as a hematopoietic drug, has received much attention due to its nonhematopoietic effects. EPO reportedly has beneficial effects on obesity and diabetes mellitus. We investigated whether interscapular brown adipose tissue (iBAT: main part of classical BAT) could play a role in EPO’s anti-obesity and anti-diabetic effects in diet-induced obese mice. Four-week-old male C57BL/6J mice were fed a high-fat diet (HFD-Con), and half were additionally given an intraperitoneal injection of recombinant human EPO (200 IU/kg) (HFD-EPO) thrice a week for four weeks. At 8 weeks, EPO-injected mice showed significantly reduced body weight with reduced epididymal and subcutaneous white fat mass and unchanged caloric intake and locomotor activity. HOMA-IR (insulin resistance index) and glucose levels during intraperitoneal glucose tolerance test (IPGTT) were significantly lower in HFD-EPO mice than in HFD-Con mice. EPO-injected mice also showed increased oxygen consumption, indicative of metabolic rate, and skin temperature around iBAT tissue masses. EPO significantly upregulated the PRD1-BF1-RIZ1 homologous domain containing 16 (PRDM16), a transcriptional factor with a crucial role in brown adipocyte differentiation. EPO significantly increased phosphorylated signal transducer and activator of transcription 3 (STAT3), which is downstream of erythropoietin receptor (EpoR) and known to stabilize PRDM16. EPO’s suppression of myocyte enhancer factor 2c (Mef2c) and microRNA-133a (miR-133a) via β3-adrenergic receptor caused PRDM16 upregulation. EPO-mediated enhancement of EpoR/STAT3 and β-adrenergic receptor/Mef2c/miR-133 pathways dramatically increases total uncoupling protein 1 (UCP1), an essential enzyme for BAT thermogenesis. Furthermore, EPO activated BAT’s endocrine functions. EPO facilitated fibroblast growth factor 21 (FGF21) production and excretion in iBAT, associated with reduction of liver gluconeogenesis-related genes. Thus, EPO

  20. Synthesis and characterization of high molecular weight water-soluble polymers to study the role of extensional viscosity in polymeric drag reduction

    NASA Astrophysics Data System (ADS)

    Cowan, Martin E.

    Several high molecular weight water-soluble acrylamide copolymers identified as efficient drag reducers have been synthesized, characterized, and examined for drag reduction effectiveness. Commercially supplied poly(ethylene oxide) polymers of varying molecular weight were also characterized and studied for comparison. The resistance to polymer extension was measured using a screen extensional rheometer allowing for the local extensional viscosity of each polymer to be quantified. Copolymer composition was determined using 13C NMR. Dilute solution properties and molecular weights were determined from zero shear intrinsic viscosity measurements and multi-angle laser light scattering experiments respectively. Molecular weights ranged from 0.55 to 4.3 million grams per mole. Drag reduction measurements were performed using a rotating disk instrument. Drag reduction data were analyzed by several theoretical models. The best correlation was found using the energy model of Walsh. Empirically, drag reduction was found to be directly related to the local extensional viscosity of each polymer sample. A model is presented explaining drag reduction in terms of increased local viscosity leading to decreased turbulence characterized with a decreased local Reynolds number. Molecular weight was found to be the most important molecular parameter of the polymers studied with polymers of greater molecular weight showing superior drag reduction properties.

  1. Psychological and sociodemographic predictors of premature discontinuation of a 1-year multimodal outpatient weight-reduction program: an attrition analysis

    PubMed Central

    Ahnis, Anne; Riedl, Andrea; Figura, Andrea; Steinhagen-Thiessen, Elisabeth; Liebl, Max E; Klapp, Burghard F

    2012-01-01

    Objective Attrition rates of up to 77% have been reported in conservative weight-reduction programs for the treatment of obesity. In view of the cost of such programs to the health system, there is a need to identify the variables that predict premature discontinuation of treatment. Previous studies have focused mainly on somatic and sociodemographic parameters. The prospective influence of psychological factors has not been systematically investigated to date. Methods A total of 164 patients (138 of whom were women) with a mean age of 45 years and a mean body mass index of 39.57 participated in a 1-year outpatient weight-reduction program at the Charité – Universitätsmedizin Berlin University Hospital. The program included movement therapy, dietary advice, psychoeducational and behavioral interventions, relaxation procedures, and consultations with a specialist in internal medicine and a psychologist. Patients also underwent regular laboratory and psychological testing. The results were evaluated using a t-test, χ2-test, and logistic regression analysis. Results Seventy-one of the 164 patients (61 women, mean age = 43 years, mean body mass index = 39.53) withdrew before the end of the program (attrition rate = 43.3%). While there were no differences between the somatic and metabolic characteristics of those who withdrew and those who remained, the sociodemographic and psychological factors had some relevance. In particular, “expectation of self-efficacy” (Fragebogen zu Selbstwirksamkeit, Optimismus und Pessimismus [SWOP]), “not working,” “tiredness” (Berliner Stimmungsfragebogen [BSF]), “pessimism” (SWOP) and “positive reframing” (Brief-COPE) were found to play a role in whether participants subsequently dropped out of the treatment. “Support coping” (Brief-COPE) and “older age” prior to the start of treatment were identified as variables that promoted treatment adherence. Conclusion The results are discussed in light of previous

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

    PubMed

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

    2007-06-01

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

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

    SciTech Connect

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

    2010-10-08

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

  4. Omentin-1 plasma levels and cholesterol metabolism in obese patients with diabetes mellitus type 1: impact of weight reduction

    PubMed Central

    Lesná, J; Tichá, A; Hyšpler, R; Musil, F; Bláha, V; Sobotka, L; Zadák, Z; Šmahelová, A

    2015-01-01

    Background: Omentin-1 is an anti-inflammatory adipokine produced preferentially by visceral adipose tissue. Plasma levels of omentin-1 are decreased in obesity and other insulin-resistant states. Insulin resistance contributes to the changes of cholesterol synthesis and absorption as well. The aim of this study was to characterise omentin-1 plasma levels in obese patients with diabetes mellitus type 1 during weight reduction, and to elucidate the relationship between cholesterol metabolism and omentin-1. Methods: Plasma levels of omentin-1 were measured in obese type 1 diabetics (n=14, body mass index >30 kg m−2, age 29–62 years) by enzyme-linked immunosorbent assay (BioVendor). Gas chromatography with flame ionisation detector (Fisons Plc.,) was used to measure squalene and non-cholesterol sterols—markers of cholesterol synthesis and absorption (phase I). Measurements were repeated after 1 month (phase II; 1 week of fasting in the hospital setting and 3 weeks on a diet containing 150 g saccharides per day) and after 1 year (phase III) on a diet with 225 g saccharides per day. Results: Omentin-1 plasma levels were stable during phases I and II, but significantly increased (P<0.001) during phase III. Omentin-1 plasma dynamics were significantly associated with plasma levels of high-density lipoprotein (P=0.005) and triacylglycerols (P=0.01), as well as with lathosterol (P=0.03). Conclusion: Omentin-1 plasma levels significantly increased during the weight reduction programme. Omentin-1 plasma dynamics suggest a close relationship with cholesterol metabolism. PMID:26524638

  5. Effects of Diet-Induced Obesity on Motivation and Pain Behavior in an Operant Assay

    PubMed Central

    Rossi, Heather L.; Luu, Anthony K.S.; Kothari, Sunny D.; Kuburas, Adisa; Neubert, John K.; Caudle, Robert M.; Recober, Ana

    2013-01-01

    Obesity has been associated with multiple chronic pain disorders, including migraine. We hypothesized that diet-induced obesity would be associated with a reduced threshold for thermal nociception in the trigeminal system. In this study, we sought to examine the effect of diet-induced obesity on facial pain behavior. Mice of two different strains were fed high-fat or regular diet and tested using a well-established operant facial pain assay. We found that the effects of diet on behavior in this assay were strain and reward dependent. Obesity prone C57BL/6J mice fed high-fat diet display lower number of licks of a caloric, palatable reward (33% sweetened condensed milk or 30% sucrose) than control mice. This occurred at all temperatures, in both sexes, and was evident even before the onset of obesity. This diminished reward-seeking behavior was not observed in obesity resistant SKH1E mice. These findings suggest that diet and strain interact to modulate reward-seeking behavior. Furthermore, we observed a difference between diet groups in operant behavior with caloric, palatable rewards, but not with a non-caloric neutral reward (water). Importantly, we found no effect of diet-induced obesity on acute thermal nociception in the absence of inflammation or injury. This indicates that thermal sensation in the face is not affected by obesity-associated peripheral neuropathy as it occurs when studying pain behaviors in the rodent hindpaw. Future studies using this model may reveal whether obesity facilitates the development of chronic pain after injury or inflammation. PMID:23333672

  6. CRP, but not TNF-α or IL-6, decreases after weight loss in patients with morbid obesity exposed to intensive weight reduction and balneological treatment*

    PubMed Central

    Rość, Danuta; Adamczyk, Przemysław; Boinska, Joanna; Szafkowski, Robert; Ponikowska, Irena; Stankowska, Katarzyna; Góralczyk, Barbara; Ruszkowska-Ciastek, Barbara

    2015-01-01

    Objective: The aim of this study was to evaluate the concentrations of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and the degree of homeostasis model assessment-insulin resistance (HOMA-IR) in patients with morbid obesity exposed to a three-week low-calorie diet and balneotherapy. Methods: The study included 33 patients (25 females and 8 males; mean age 46 years) with body mass index (BMI) values of >40 kg/m2. Evaluations of CRP, IL-6, TNF-α, lipid profile, HOMA-IR, and fasting glucose were carried out before (baseline data) and three weeks after the treatment. The control group consisted of 20 healthy volunteers (15 females and 5 males) with a mean age of 39 years and BMI values of ≤24.9 kg/m2. Results: In the blood of patients with morbid obesity we found significantly elevated levels of CRP, TNF-α, triglycerides, HOMA-IR and fasting glucose, but a decreased level of high density lipoprotein (HDL)-cholesterol, compared with the healthy individuals. The treatment resulted in about a 9.4% reduction in body weight from 122.5 to 111.0 kg and a significant decrease in the concentration of CRP, but no change in TNF-α or IL-6. HOMA-IR was significantly reduced. Conclusions: The decrease in CRP level without changes in TNF-α or IL-6 concentrations after the low-calorie diet and balneological treatment, suggests that an essential amount of adipose tissue must be removed before proper adipocyte function is restored. The decrease in HOMA-IR indicates an improvement in insulin sensitivity, which is beneficial in obese patients. PMID:25990058

  7. Perinatal Protein Malnutrition Affects Mitochondrial Function in Adult and Results in a Resistance to High Fat Diet-Induced Obesity

    PubMed Central

    Jousse, Céline; Muranishi, Yuki; Parry, Laurent; Montaurier, Christophe; Even, Patrick; Launay, Jean-Marie; Carraro, Valérie; Maurin, Anne-Catherine; Averous, Julien; Chaveroux, Cédric; Bruhat, Alain; Mallet, Jacques; Morio, Béatrice; Fafournoux, Pierre

    2014-01-01

    Epidemiological findings indicate that transient environmental influences during perinatal life, especially nutrition, may have deleterious heritable health effects lasting for the entire life. Indeed, the fetal organism develops specific adaptations that permanently change its physiology/metabolism and that persist even in the absence of the stimulus that initiated them. This process is termed “nutritional programming”. We previously demonstrated that mothers fed a Low-Protein-Diet (LPD) during gestation and lactation give birth to F1-LPD animals presenting metabolic consequences that are different from those observed when the nutritional stress is applied during gestation only. Compared to control mice, adult F1-LPD animals have a lower body weight and exhibit a higher food intake suggesting that maternal protein under-nutrition during gestation and lactation affects the energy metabolism of F1-LPD offspring. In this study, we investigated the origin of this apparent energy wasting process in F1-LPD and demonstrated that minimal energy expenditure is increased, due to both an increased mitochondrial function in skeletal muscle and an increased mitochondrial density in White Adipose Tissue. Importantly, F1-LPD mice are protected against high-fat-diet-induced obesity. Clearly, different paradigms of exposure to malnutrition may be associated with differences in energy expenditure, food intake, weight and different susceptibilities to various symptoms associated with metabolic syndrome. Taken together these results demonstrate that intra-uterine environment is a major contributor to the future of individuals and disturbance at a critical period of development may compromise their health. Consequently, understanding the molecular mechanisms may give access to useful knowledge regarding the onset of metabolic diseases. PMID:25118945

  8. A novel cystine based antioxidant attenuates oxidative stress and hepatic steatosis in diet-induced obese mice

    PubMed Central

    Sinha-Hikim, Indrani; Sinha-Hikim, Amiya P.; Shen, Ruoqing; Kim, H.; French, Samuel W.; Vazari, Nostrola D.; Crum, Albert; Rajavashisth, Tripathi B.; Norris, Keith C.

    2011-01-01

    Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver pathologies and is associated with obesity and the metabolic syndrome. Here, we investigated the molecular mechanisms by which a novel cystine based glutathione precursor with added selenomethionine (F1) prevents hepatic steatosis in a moderate high fat dietary model of NAFLD. Adult (8 weeks old), male apolipoprotein E (ApoE)−/− mice were fed with a normal diet (ND) or high fat diet (HFD), consisting of 21% fat and 0.21% cholesterol, with or without dietary supplementation of F1 (3 g/kg food) for 16 weeks. Compared with ApoE−/− mice fed with ND with or without F1, ApoE−/− mice fed with HFD exhibited significant weight gain, hepatomegaly, and increased serum cholesterol and triglycerides levels with no change in serum albumin levels. High resolution light and electron microscopy revealed micro-and macro-vesicular steatosis in ApoE−/− mice fed on a HFD. HFD- induced obesity also led to increased lipogenesis, oxidative stress, activation of c-Jun-NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), perturbation of the BAX/BCL-2 rheostat, hepatocyte apoptosis, and activation of caspases 9 and 3. F1 fully prevented the adverse effects of HFD on serum triglyceride levels, body and liver weights, and hepatic steatosis and substantially attenuated HFD-induced increase in lipogenesis, oxidative stress, kinase activation, apoptotic signaling, and hepatocyte ultrastructural abnormalities. These results demonstrate that administration of F1, a glutathione precursor, ameliorates HFD-induced hepatic steatosis in ApoE−/− mice and emphasizes the role of oxidative stress in diet-induced obesity and hepatic steatosis. PMID:21570964

  9. Effects of diet-induced obesity and voluntary wheel running on the microstructure of the murine distal femur

    PubMed Central

    2011-01-01

    Background Obesity and osteoporosis, two possibly related conditions, are rapidly expanding health concerns in modern society. Both of them are associated with sedentary life style and nutrition. To investigate the effects of diet-induced obesity and voluntary physical activity we used high resolution micro-computed tomography (μCT) together with peripheral quantitative computed tomography (pQCT) to examine the microstructure of the distal femoral metaphysis in mice. Methods Forty 7-week-old male C57BL/6J mice were assigned to 4 groups: control (C), control + running (CR), high-fat diet (HF), and high-fat diet + running (HFR). After a 21-week intervention, all the mice were sacrificed and the left femur dissected for pQCT and μCT measurements. Results The mice fed the high-fat diet showed a significant weight gain (over 70% for HF and 60% for HFR), with increased epididymal fat pad mass and impaired insulin sensitivity. These obese mice had significantly higher trabecular connectivity density, volume, number, thickness, area and mass, and smaller trabecular separation. At the whole bone level, they had larger bone circumference and cross-sectional area and higher density-weighted maximal, minimal, and polar moments of inertia. Voluntary wheel running decreased all the cortical bone parameters, but increased the trabecular mineral density, and decreased the pattern factor and structure model index towards a more plate-like structure. Conclusions The results suggest that in mice the femur adapts to obesity by improving bone strength both at the whole bone and micro-structural level. Adaptation to running exercise manifests itself in increased trabecular density and improved 3D structure, but in a limited overall bone growth PMID:21241467

  10. Effect of Peucedanum japonicum Thunb extract on high-fat diet-induced obesity and gene expression in mice.

    PubMed

    Nukitrangsan, Natthanan; Okabe, Takafumi; Toda, Takayoshi; Inafuku, Masashi; Iwasaki, Hironori; Oku, Hirosuke

    2012-01-01

    Supplementation of the diet with Peucedanum japonicum Thunb (PJT) powder inhibits high-fat diet-induced obesity in mice. Either the fiber component or other bioactive components in the PJT powder may inhibit obesity. This study, therefore, was an attempt to identify the components, fiber or other phytochemicals of PJT that were responsible for the anti-obesity activity, and also studied the modulation of obesity-related gene expression in C57BL/6 mice. Animals were fed a modified-AIN76 diet supplemented with PJT powder or extracts of PJT in water, 50 % ethanol, or ethanol. Body weight gain, tissue weight, serum biochemical parameters, liver lipid concentrations, and gene expression in tissues were compared between the control and treatment groups. Of the extracts, the ethanol extract of PJT decreased fat accumulation and adipocyte size, reduced serum and liver triglyceride concentrations, and inhibited obesity. This finding clearly demonstrates the presence of anti-obesity phytochemicals in PJT. Ethanol extract of PJT inhibited lipase activity in vitro. Modulation of gene expression by PJT ethanol extract was largely similar to that by PJT powder in the hepatic and adipose tissues: RORC and PBEF1 were upregulated and DUSP1, INSIG2, and SERPINA12 were downregulated in the liver; FXRα and PPARγ were upregulated and PEG1/MEST, the size-marker of adipocytes, was downregulated in the adipose tissue. Furthermore, PJT ethanol extract increased the expression of the UCP3 gene in muscle. These results suggest that the anti-obesity phytochemicals in PJT lower lipid levels by inhibiting fat absorption and by modulating obesity-related gene expression in the liver, adipose tissue, and muscle.

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

    PubMed

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

    2016-01-05

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

  12. Proanthocyanidins potentiate hypothalamic leptin/STAT3 signalling and Pomc gene expression in rats with diet-induced obesity

    PubMed Central

    Ibars, M; Ardid-Ruiz, A; Suárez, M; Muguerza, B; Bladé, C; Aragonès, G

    2017-01-01

    Objective: Dietary obesity is usually linked with hypothalamic leptin resistance, in which the primary impact is an interference in the homeostatic control of body weight and appetite. Notably, proanthocyanidins (PACs), which are the most abundant phenolic compounds present in human diet, modulate adiposity and food intake. The aim of this study was to assess whether PACs could re-establish appropriate leptin signalling in both the hypothalamus and peripheral tissues. Design: Male Wistar rats were fed either a standard chow diet (STD group, n=7) or a cafeteria diet (CD) for 13 weeks. The CD-fed rats were treated with either grape-seed PAC extract (GSPE) at 25 mg  per kg of body weight per day (CD+GSPE group, n=7) or with the vehicle (CD group, n=7) for the last 21 days of the study period. Specific markers for intracellular leptin signalling, inflammation and endoplasmic reticulum stress in the hypothalamus, liver, mesenteric white adipose tissue and skeletal muscle were analysed using immunoblotting and quantitative PCR. Results: GSPE treatment significantly reduced the food intake but did not reverse the hyperleptinemia and body wt gain assessed. However, the animals treated with GSPE exhibited greater hypothalamic activation of signal transducer and activator of transcription-3, which was associated with a rise in the Pomc mRNA levels compared with the CD group. In addition, this restoration of leptin responsiveness was accompanied by lower local inflammation and increased Sirt1 gene expression. The effects of the GSPE treatment in the peripheral tissues were not as evident as those in the hypothalamus, although the GSPE treatment significantly restored the mRNA levels of Socs3 and Ptp1b in the skeletal muscle. Conclusions: The use of GSPE reduces hyperphagia and improves the central and peripheral leptin resistance associated with diet-induced obesity. Our results suggest that GSPE could exert these effects partially by increasing Sirt1 expression and

  13. Adipocyte-specific deletion of Ip6k1 reduces diet-induced obesity by enhancing AMPK-mediated thermogenesis

    PubMed Central

    Zhu, Qingzhang; Ghoshal, Sarbani; Rodrigues, Ana; Gao, Su; Asterian, Alice; Kamenecka, Theodore M.; Barrow, James C.

    2016-01-01

    Enhancing energy expenditure (EE) is an attractive strategy to combat obesity and diabetes. Global deletion of Ip6k1 protects mice from diet-induced obesity (DIO) and insulin resistance, but the tissue-specific mechanism by which IP6K1 regulates body weight is unknown. Here, we have demonstrated that IP6K1 regulates fat accumulation by modulating AMPK-mediated adipocyte energy metabolism. Cold exposure led to downregulation of Ip6k1 in murine inguinal and retroperitoneal white adipose tissue (IWAT and RWAT) depots. Adipocyte-specific deletion of Ip6k1 (AdKO) enhanced thermogenic EE, which protected mice from high-fat diet–induced weight gain at ambient temperature (23°C), but not at thermoneutral temperature (30°C). AdKO-induced increases in thermogenesis also protected mice from cold-induced decreases in body temperature. UCP1, PGC1α, and other markers of browning and thermogenesis were elevated in IWAT and RWAT of AdKO mice. Cold-induced activation of sympathetic signaling was unaltered, whereas AMPK was enhanced, in AdKO IWAT. Moreover, beige adipocytes from AdKO IWAT displayed enhanced browning, which was diminished by AMPK depletion. Furthermore, we determined that IP6 and IP6K1 differentially regulate upstream kinase-mediated AMPK stimulatory phosphorylation in vitro. Finally, treating mildly obese mice with the IP6K inhibitor TNP enhanced thermogenesis and inhibited progression of DIO. Thus, IP6K1 regulates energy metabolism via a mechanism that could potentially be targeted in obesity. PMID:27701146

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

    PubMed Central

    Oh, Ji-Hyun; Kim, Jaehoon

    2016-01-01

    BACKGROUND/OBJECTIVES Seaweeds have been reported to have various health beneficial effects. In this study, we investigated the potential anti-obesity and anti-inflammatory effects of four types of domestic brown seaweeds in a high-fat diet-induced obese mouse model and bone marrow-derived macrophages (BMDM). MATERIALS/METHODS Male C57BL/6N mice were fed low-fat diet (LFD), high-fat diet (HFD) or HFD containing Undaria Pinnatifida, HFD containing Laminaria Japonica (LJ), HFD containing Sargassum Fulvellum, or HFD containing Hizikia Fusiforme (HF) for 16 weeks. RESULTS Brown seaweed supplementation did not affect long-term HFD-associated changes in body weight or adiposity, although mice fed HFD + LJ or HFD + HF gained slightly less body weight compared with those fed HFD at the beginning of feeding. Despite being obese, mice fed HFD + LJ