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Sample records for diet-induced weight reduction

  1. 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

  2. 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

  3. 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

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

    PubMed

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

    2016-08-01

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

  5. Using personality as a predictor of diet induced weight loss and weight management

    PubMed Central

    2011-01-01

    Background A major challenge for successful weight management is tailoring weight loss programs to individual needs. The aim of this study was to investigate whether personality traits could be used to match individuals to a compatible weight loss program that would maximize weight loss. Method Two different weight loss trials were conducted, both with a weight loss greater than 5% the measure of success. Fifty-four individuals, BMI 30-40 kg/m2, either followed a slow, healthy eating weight loss diet (HEWLD) of 5000-6000 kJ/day for 12 weeks (n = 22), or a fast, very low energy diet (VLED) of 3000 kJ/day for 4 weeks (n = 32). Anthropometric measurements were recorded at baseline, at the end of the weight loss period and, for VLED, at the end of 10 weeks of weight maintenance. Personality traits were measured at baseline using the Tangney Self Control Scale plus 3 of the scales from the Five Factor Model - Neuroticism, Conscientiousness and Extraversion. Results The percentage weight loss was significantly greater in VLED (-7.38%) compared to HEWLD (-4.11%), (p < 0.001). Weight loss in HEWLD was positively correlated with Anxiety, a facet of Neuroticism. Weight loss in VLED was positively correlated with Neuroticism (r = 0.5, p < 0.01), and negatively correlated with Dutifulness and Discipline, facets of Conscientiousness, (p < 0.05 for both). No link was observed between weight loss and the personality trait, Self Control, in either HEWLD or VLED. Conclusion The personality factor, Neuroticism, was linked to successful weight loss (that is ≥ 5%) with a particular weight loss treatment, suggesting that there is a potential to use measures of personality to identify appropriate weight loss/management strategies for individuals. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12611000716965 PMID:22112231

  6. Weight Loss Decreases Inherent and Allergic Methacholine Hyperresponsiveness in Mouse Models of Diet-Induced Obese Asthma.

    PubMed

    Ather, Jennifer L; Chung, Michael; Hoyt, Laura R; Randall, Matthew J; Georgsdottir, Anna; Daphtary, Nirav A; Aliyeva, Minara I; Suratt, Benjamin T; Bates, Jason H T; Irvin, Charles G; Russell, Sheila R; Forgione, Patrick M; Dixon, Anne E; Poynter, Matthew E

    2016-08-01

    Obese asthma presents with inherent hyperresponsiveness to methacholine or augmented allergen-driven allergic asthma, with an even greater magnitude of methacholine hyperresponsiveness. These physiologic parameters and accompanying obese asthma symptoms can be reduced by successful weight loss, yet the underlying mechanisms remain incompletely understood. We implemented mouse models of diet-induced obesity, dietary and surgical weight loss, and environmental allergen exposure to examine the mechanisms and mediators of inherent and allergic obese asthma. We report that the methacholine hyperresponsiveness in these models of inherent obese asthma and obese allergic asthma manifests in distinct anatomical compartments but that both are amenable to interventions that induce substantial weight loss. The inherent obese asthma phenotype, with characteristic increases in distal airspace tissue resistance and tissue elastance, is associated with elevated proinflammatory cytokines that are reduced with dietary weight loss. Surprisingly, bariatric surgery-induced weight loss further elevates these cytokines while reducing methacholine responsiveness to levels similar to those in lean mice or in formerly obese mice rendered lean through dietary intervention. In contrast, the obese allergic asthma phenotype, with characteristic increases in central airway resistance, is not associated with increased adaptive immune responses, yet diet-induced weight loss reduces methacholine hyperresponsiveness without altering immunological variables. Diet-induced weight loss is effective in models of both inherent and allergic obese asthma, and our examination of the fecal microbiome revealed that the obesogenic Firmicutes/Bacteroidetes ratio was normalized after diet-induced weight loss. Our results suggest that structural, immunological, and microbiological factors contribute to the manifold presentations of obese asthma. PMID:27064658

  7. 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. PMID:22128019

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

    PubMed Central

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

    2011-01-01

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

  9. 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. PMID:21565212

  10. 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. PMID:23922646

  11. Rapid response of the steatosis-sensing hepatokine LECT2 during diet-induced weight cycling in mice.

    PubMed

    Chikamoto, Keita; Misu, Hirofumi; Takayama, Hiroaki; Kikuchi, Akihiro; Ishii, Kiyo-Aki; Lan, Fei; Takata, Noboru; Tajima-Shirasaki, Natsumi; Takeshita, Yumie; Tsugane, Hirohiko; Kaneko, Shuichi; Matsugo, Seiichi; Takamura, Toshinari

    2016-09-23

    Dieting often leads to body weight cycling involving repeated weight loss and regain. However, little information is available regarding rapid-response serum markers of overnutrition that predict body weight alterations during weight cycling. Here, we report the rapid response of serum leukocyte cell-derived chemotaxin 2 (LECT2), a hepatokine that induces insulin resistance in skeletal muscle, during diet-induced weight cycling in mice. A switch from a high-fat diet (HFD) to a regular diet (RD) in obese mice gradually decreased body weight but rapidly decreased serum LECT2 levels within 10 days. In contrast, a switch from a RD to a HFD rapidly elevated serum LECT2 levels. Serum LECT2 levels showed a positive correlation with liver triglyceride contents but not with adipose tissue weight. This study demonstrates the rapid response of LECT2 preceding body weight alterations during weight cycling in mice and suggests that measurement of serum LECT2 may be clinically useful in the management of obesity. PMID:27562717

  12. The Effect of PPARα, PPARδ, PPARγ, and PPARpan Agonists on Body Weight, Body Mass, and Serum Lipid Profiles in Diet-Induced Obese AKR/J Mice

    PubMed Central

    Harrington, W. Wallace; S. Britt, Christy; G. Wilson, Joan; O. Milliken, Naphtali; G. Binz, Jane; C. Lobe, David; R. Oliver, William; C. Lewis, Michael; M. Ignar, Diane

    2007-01-01

    Activation of peroxisome proliferator-activated receptor (PPAR) α, δ, and γ subtypes increases expression of genes involved in fatty acid transport and oxidation and alters adiposity in animal models of obesity and type-2 diabetes. PPARpan agonists which activate all three receptor subtypes have antidiabetic activity in animal models without the weight gain associated with selective PPARγ agonists. Herein we report the effects of selective PPAR agonists (GW9578, a PPARα agonist, GW0742, a PPARδ agonist, GW7845, a PPARγ agonist), combination of PPARα and δ agonists, and PPARpan (PPARα/γ/δ) activators (GW4148 or GW9135) on body weight (BW), body composition, food consumption, fatty acid oxidation, and serum chemistry of diet-induced obese AKR/J mice. PPARα or PPARδ agonist treatment induced a slight decrease in fat mass (FM) while a PPARγ agonist increased BW and FM commensurate with increased food consumption. The reduction in BW and food intake after cotreatment with PPARα and δ agonists appeared to be synergistic. GW4148, a PPARpan agonist, induced a significant and sustained reduction in BW and FM similar to an efficacious dose of rimonabant, an antiobesity compound. GW9135, a PPARpan agonist with weak activity at PPARδ, induced weight loss initially followed by rebound weight gain reaching vehicle control levels by the end of the experiment. We conclude that PPARα and PPARδ activations are critical to effective weight loss induction. These results suggest that the PPARpan compounds may be expected to maintain the beneficial insulin sensitization effects of a PPARγ agonist while either maintaining weight or producing weight loss. PMID:17710237

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  15. 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

  16. 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

  17. 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

  18. 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

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

    PubMed

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

    2016-04-01

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

  20. 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. PMID:25051449

  1. Effect of physical activity on weight loss, energy expenditure and energy intake during diet induced weight loss

    PubMed Central

    DeLany, James P.; Kelley, David E.; Hames, Kazanna C.; Jakicic, John M.; Goodpaster, Bret H.

    2016-01-01

    Objective Objective measurements of physical activity (PA), energy expenditure (EE) and energy intake can provide valuable information regarding appropriate strategies for successful sustained weight loss. Design and methods We examined total EE by doubly labeled water, resting metabolic rate, PA with activity monitors, and energy intake by the Intake/Balance technique in 116 severely obese undergoing intervention with diet alone (DO) or diet plus PA (D-PA). Results Weight loss of 9.6±6.8 kg resulted in decreased EE which was not minimized in the D-PA group. Comparing the highest and lowest quartiles of increase in PA revealed a lower decrease in TDEE (−122±319 vs. −376±305 kcal/d), elimination of the drop in AEE (83±279 vs. −211±284 kcal/d) and greater weight loss (13.0±7.0 vs. 8.1±6.3 kg). Increased PA was associated with greater adherence to energy restriction and maintenance of greater weight loss during months 7–12. Conclusion Noncompliance to prescribed PA in the DO and D-PA groups partially masked the effects of PA to increase weight loss and to minimize the reduced EE. Increased PA was also associated with improved adherence to prescribed caloric restriction. A strong recommendation needs to be made to improve interventions that promote PA within the context of behavioral weight loss interventions. PMID:23804562

  2. Effect of diet-induced weight loss on muscle strength in adults with overweight or obesity - a systematic review and meta-analysis of clinical trials.

    PubMed

    Zibellini, J; Seimon, R V; Lee, C M Y; Gibson, A A; Hsu, M S H; Sainsbury, A

    2016-08-01

    We conducted a systematic review and meta-analysis to identify how diet-induced weight loss in adults with overweight or obesity impacts on muscle strength. Twenty-seven publications, including 33 interventions, most of which were 8-24 weeks in duration, were included. Meta-analysis of seven interventions measuring knee extensor strength by isokinetic dynamometry in 108 participants found a significant decrease following diet-induced weight loss (-9.0 [95% confidence interval: -13.8, -4.1] N/m, P < 0.001), representing a 7.5% decrease from baseline values. Meta-analysis of handgrip strength from 10 interventions in 231 participants showed a non-significant decrease (-1.7 [-3.6, 0.1] kg, P = 0.070), with significant heterogeneity (I(2)  = 83.9%, P < 0.001). This heterogeneity may have been due to diet type, because there was a significant decrease in handgrip strength in seven interventions in 169 participants involving moderate energy restriction (-2.4 [-4.8, -0.0] kg, P = 0.046), representing a 4.6% decrease from baseline values, but not in three interventions in 62 participants involving very-low-energy diet (-0.4 [-2.0, 1.2] kg, P = 0.610). Because of variability in methodology and muscles tested, no other data could be meta-analyzed, and qualitative assessment of the remaining interventions revealed mixed results. Despite varying methodologies, diets and small sample sizes, these findings suggest a potential adverse effect of diet-induced weight loss on muscle strength. While these findings should not act as a deterrent against weight loss, due to the known health benefits of losing excess weight, they call for strategies to combat strength loss - such as weight training and other exercises - during diet-induced weight loss. © 2016 World Obesity. PMID:27126087

  3. 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

  4. Exercise but not diet-induced weight loss decreases skeletal muscle inflammatory gene expression in frail obese elderly persons.

    PubMed

    Lambert, Charles P; Wright, Nicole R; Finck, Brian N; Villareal, Dennis T

    2008-08-01

    Many obese elderly persons have impaired physical function associated with an increased chronic inflammatory response. We evaluated 12 wk of exercise (aerobic and resistance) or 12 wk of weight loss (approximately 7% reduction) on skeletal muscle mRNAs for toll-like receptor-4 (TLR-4), mechanogrowth factor (MGF), TNF-alpha, and IL-6 in 16 obese (body mass index 38+/-2 kg/m2) older (69+/-1 yr) physically frail individuals. Vastus lateralis muscle biopsies were obtained at 0 and 12 wk and analyzed by real-time RT-PCR. Body composition was assessed by dual-energy x-ray absorptiometry. Body weight decreased (-7.5+/-1.2 kg, P=0.001) in the weight loss group but not in the exercise group (-0.3+/-0.8 kg, P=0.74). Fat-free mass (FFM) decreased (-2.9+/-0.6 kg, P=0.010) in the weight loss group and increased (1.6+/-0.6 kg, P=0.03) in the exercise group. Exercise resulted in a 37% decrease in TLR-4 mRNA (P<0.05) while weight loss had no significant effect. Additionally, exercise led to a significant (50%) decrease in IL-6 and TNF-alpha mRNA (P<0.05) while weight loss had no effect. Exercise increased MGF mRNA (approximately 2 fold, P<0.05), but weight loss had no effect. In conclusion, exercise but not weight loss had a beneficial effect on markers of muscle inflammation and anabolism in frail obese elderly individuals. PMID:18535122

  5. Rhein Reduces Fat Weight in db/db Mouse and Prevents Diet-Induced Obesity in C57Bl/6 Mouse through the Inhibition of PPARγ Signaling

    PubMed Central

    Zhang, Yu; Fan, Shengjie; Hu, Na; Gu, Ming; Chu, Chunxiao; Li, Yiming; Lu, Xiong; Huang, Cheng

    2012-01-01

    Rheum palmatum has been used most frequently in the weight-reducing formulae in traditional Chinese medicine. However, the components of Rheum palmatum that play the antiobesity role are still uncertain. Here, we tested the weight-reducing effect of two major Rheum palmatum compounds on db/db mouse. We found that rhein (100 mg kg−1 day−1), but not emodin, reduced the fat weight in db/db mouse. Using diet-induced obese (DIO) C57BL/6 mice, we identified that rhein blocked high-fat diet-induced obesity, decreased fat mass and the size of white and brown adipocytes, and lowered serum cholesterol, LDL cholesterol, and fasting blood glucose levels in the mice. To elucidate the underlying mechanisms, we used reporter assay and gene expression analysis and found that rhein inhibited peroxisome proliferator-activated receptor γ (PPARγ) transactivity and the expression of its target genes, suggesting that rhein may act as a PPARγ antagonist. Our data indicate that rhein may be a promising choice for antiobesity therapy. PMID:23049539

  6. Functional characterization of a promoter polymorphism that drives ACSL5 gene expression in skeletal muscle and associates with diet-induced weight loss.

    PubMed

    Teng, Allen C T; Adamo, Kristi; Tesson, Frédérique; Stewart, Alexandre F R

    2009-06-01

    Diet-induced weight loss is affected by a wide range of factors, including genetic variation. Identifying functional polymorphisms will help to elucidate mechanisms that account for variation in dietary metabolism. Previously, we reported a strong association between a common single nucleotide polymorphism (SNP) rs2419621 (C>T) in the promoter of acyl-CoA synthetase long chain 5 (ACSL5), rapid weight loss in obese Caucasian females, and elevated ACSL5 mRNA levels in skeletal muscle biopsies. Here, we showed by electrophoretic mobility shift assay (EMSA) that the T allele creates a functional cis-regulatory E-box element (CANNTG) that is recognized by the myogenic regulatory factor MyoD. The T allele promoted MyoD-dependent activation of a 1089-base pair ACSL5 promoter fragment in nonmuscle CV1 cells. Differentiation of skeletal myoblasts significantly elevated expression of the ACSL5 promoter. The T allele sustained promoter activity 48 h after differentiation, whereas the C allele showed a significant decline. These results reveal a mechanism for elevated transcription of ACSL5 in skeletal muscle of carriers of the rs2419621(T) allele, associated with more rapid diet-induced weight loss. Natural selection favoring promoter polymorphisms that reduced expression of catabolic genes in skeletal muscle likely accounts for the resistance of obese individuals to dietary intervention. PMID:19218499

  7. Exercise training versus diet-induced weight-loss on metabolic risk factors and inflammatory markers in obese subjects: a 12-week randomized intervention study.

    PubMed

    Christiansen, Tore; Paulsen, Søren K; Bruun, Jens M; Pedersen, Steen B; Richelsen, Bjørn

    2010-04-01

    The purpose of this study was to investigate the effect of exercise training and diet-induced weight loss alone or in combination on inflammatory markers in circulation, in adipose tissue (AT) and in skeletal muscle (SM) in obese subjects. Seventy-nine obese subjects were randomized into a 12-wk intervention: 1) exercise only (EXO), 2) diet-induced weight loss using a very low energy diet (DIO), and 3) exercise and diet-induced weight-loss combined (DEX). Blood samples (metabolic and inflammatory markers) and AT and SM biopsies (mRNA expression) were collected at baseline and after 12 wk. In the EXO group the weight loss was 3.5 kg and in the DIO and DEX groups it was 12 kg in both. Vo(2max) was increased by 14-18% in the EXO and DEX groups with no changes in the DIO group. In the DIO and DEX groups, circulating levels of MCP-1, MIP-1alpha, IL-15, and IL-18 were decreased, and adiponectin was increased (P < 0.05 for all). In the EXO group, MCP-1 was decreased with 10% (P = 0.06). By combining the weight loss in all three groups, we found a correlation between the degree of weight loss and improvement in several of the inflammatory markers (P < 0.05). In AT biopsies, subjects in the DIO and DEX groups achieved a general beneficial but nonsignificant effect on the gene expression of inflammatory markers. In the EXO group, no changes in AT adipokine mRNA were found except for an increment of adiponectin (P < 0.05). In SM, the only observed change was that the gene expression of IL-6 was increased in all three groups (P < 0.05). In conclusion, rather large weight losses (>5-7%) were found to have beneficial effects on circulating inflammatory markers in these obese subjects. Aerobic exercise for 12 wk, which increased Vo(2max), was found to have no effects on circulating inflammatory markers in these obese patients. It is suggested that more intensive exercise may be necessary to affect systemic inflammation. PMID:20086201

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

    PubMed

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

    2016-02-01

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

  9. 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. PMID:16407735

  10. Lactobionic acid reduces body weight gain in diet-induced obese rats by targeted inhibition of galectin-1.

    PubMed

    Mukherjee, Rajib; Yun, Jong Won

    2015-08-01

    Galectin-1 (GAL1), an animal lectin with a carbohydrate recognition domain, is known for its roles in cancer, tumor progression, as well as obesity and related complications. Here, we investigated the anti-obesity effect of lactobionic acid (LBA), a GAL1 inhibitor, both in vitro and in vivo. LBA treatment significantly reduced lipogenic capacity of both 3T3-L1 and HIB1B adipocytes through down-regulation of major adipogenic transcription factors at both mRNA and protein levels. Moreover, oral administration and intraperitoneal injection of LBA in Sprague-Dawley male rats fed a high fat diet caused marked reduction of body weight gain as well as improvement of related metabolic parameters. Important lipogenic transcription factors were also down-regulated in LBA-treated rats, resulting in attenuated lipogenesis and fat accumulation. Collectively, pharmaceutical targeting of GAL1 using LBA would be a novel therapeutic approach for the treatment of obesity. PMID:26116537

  11. Chronic treatment with a melanocortin-4 receptor agonist causes weight loss, reduces insulin resistance, and improves cardiovascular function in diet-induced obese rhesus macaques.

    PubMed

    Kievit, Paul; Halem, Heather; Marks, Daniel L; Dong, Jesse Z; Glavas, Maria M; Sinnayah, Puspha; Pranger, Lindsay; Cowley, Michael A; Grove, Kevin L; Culler, Michael D

    2013-02-01

    The melanocortin-4 receptor (MC4R) is well recognized as an important mediator of body weight homeostasis. Activation of MC4R causes dramatic weight loss in rodent models, and mutations in human are associated with obesity. This makes MC4R a logical target for pharmacological therapy for the treatment of obesity. However, previous studies in rodents and humans have observed a broad array of side effects caused by acute treatment with MC4R agonists, including increased heart rate and blood pressure. We demonstrate that treatment with a highly-selective novel MC4R agonist (BIM-22493 or RM-493) resulted in transient decreases in food intake (35%), with persistent weight loss over 8 weeks of treatment (13.5%) in a diet-induced obese nonhuman primate model. Consistent with weight loss, these animals significantly decreased adiposity and improved glucose tolerance. Importantly, we observed no increases in blood pressure or heart rate with BIM-22493 treatment. In contrast, treatment with LY2112688, an MC4R agonist previously shown to increase blood pressure and heart rate in humans, caused increases in blood pressure and heart rate, while modestly decreasing food intake. These studies demonstrate that distinct melanocortin peptide drugs can have widely different efficacies and side effects. PMID:23048186

  12. Diet-induced thermogenesis in patients with gastrointestinal cancer cachexia.

    PubMed

    Weston, P M; King, R F; Goode, A W; Williams, N S

    1989-08-01

    1. Indirect calorimetry has been used to measure resting energy expenditure (REE) and the thermogenic response to a test meal (diet-induced thermogenesis) in groups of weight-stable and weight-losing patients with gastrointestinal adenocarcinoma. Average daily intakes of energy and protein were computed from dietary assessment for the week before hospitalization. Results were compared with a control group of patients with benign gastrointestinal disease. 2. Weight-losing cancer patients had a significantly reduced mean total energy and protein intake. 3. There was no significant difference in REE between the groups when results were normalized in terms of metabolic body size (kJ/kg 0.75) and lean body mass (kJ/kg). 4. Diet-induced thermogenesis was reduced in weight-losing cancer patients. 5. It is suggested that the reduction of diet-induced thermogenesis in weight-losing cancer patients is another element of starvation adaptation, subsequent to their weight loss, and that altered thermogenesis does not contribute to the weight loss seen in cancer cachexia. PMID:2766653

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

    PubMed

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

    2013-04-01

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

  14. 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

  15. Effects of diet-induced weight gain and turnout to pasture on insulin sensitivity in moderately insulin resistant horses.

    PubMed

    Lindåse, Sanna S; Nostell, Katarina E; Müller, Cecilia E; Jensen-Waern, Marianne; Bröjer, Johan T

    2016-03-01

    OBJECTIVE To quantify insulin sensitivity and monitor glucose, insulin, and lipid concentrations in a group of moderately insulin-resistant horses during induction of obesity by use of a forage diet supplemented with fat and during subsequent turnout to pasture. ANIMALS 9 adult Standardbred mares (11 to 20 years old). PROCEDURES Weight gain of horses was induced during 22 weeks by use of a forage diet supplemented with fat fed in gradually increasing amounts, followed by feeding of that fat-supplemented diet at 2.5 times the daily maintenance requirements. Horses were then turned out to pasture. Insulin sensitivity was measured with the euglycemic hyperinsulinemic clamp method before and after weight gain and after 4 weeks at pasture. Body weight, body condition score, and cresty neck score as well as fasting and postprandial concentrations of plasma insulin, plasma glucose, serum triglyceride, and serum nonesterified fatty acids were measured during the study. RESULTS Body weight typically increased by 10%, and body condition score (scale, 1 to 9) increased by > 1.5 from the start to the end of the weight-gain period. There was no difference in insulin sensitivity or metabolic clearance rate of insulin during the weight-gain period. Four weeks at pasture generally improved insulin sensitivity and metabolic clearance rate of insulin by 54% and 32%, respectively, but there was no change in body weight or body condition score. CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that dietary composition played a more important role than did short-term weight gain on alterations in insulin sensitivity of horses. PMID:26919602

  16. 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

  17. 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 Central

    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. PMID:26444289

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

    PubMed

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

    2016-09-01

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

  19. 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

  20. Effect of Lactobacillus plantarum FH185 on the Reduction of Adipocyte Size and Gut Microbial Changes in Mice with Diet-induced Obesity

    PubMed Central

    2015-01-01

    This study aimed to investigate the effects of Lactobacillus plantarum FH185 on the reduction of adipocyte size and gut microbial changes in mice with diet-induced obesity. The strain was found to have a lipase inhibitory activity of 70.09±2.04% and inhibited adipocyte differentiation of 3T3-L1 cells (18.63±0.98%) at a concentration of 100 µg/mL. To examine the effect of the strain supplementation on gut microbial changes in mice with diet-induced obesity, male C57BL/6J mice were fed on four different diets (i.e., A, normal diet (ND); B, high-fat diet (HFD); C, HFD with ABT-3 (109 CFU/day); and D, HFD with L. plantarum FH185 (109 CFU/day)) for 6 wk. According to the results of fecal pyrosequencing, the ratio of Firmicutes to Bacteroidetes in groups C and D was lower than in the control groups at the phylum level. At the family level, Lactobacillaceae in groups C and D was observed to dominate, while Lachnospiraceae in groups A and B was observed to dominate. At the genus level, Lactobacillus in groups C and D was comparatively higher than in groups A and B. To examine the effects of strain supplementation on the reduction of adipocyte size, the left and right epididymal fat pads were quickly isolated after the animals were sacrificed, and the adipocyte sizes were measured. In groups A, C and D, the percentage of 2,000 m2 of adipocyte was higher than in the other size of adipocyte, while the percentage of over 5,000 m2 of adipocyte was highest in group B. The mean adipocyte size of group D was significantly larger than that of group A, but smaller than that of group B. PMID:26761825

  1. 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. PMID:26295369

  2. 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

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

    PubMed

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

    2016-02-01

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

  4. Weight reduction, fertility and contraception.

    PubMed

    Van Der Spuy, Z M; Jacobs, H S

    1983-10-01

    The significance of weight and body composition with regard to the fertile menstrual cycle has excited much interest. There is global imbalance of resources and problems of widespread chronic malnutrition in many 3rd world countries. This emphasizes the great importance of the possible effects of diet, body weight, and body composition on fecundity (ability to reproduce), fertility (reproductive performance), and pregnancy outcome. Frisch and Revelle suggested that a critical body weight is required for a girl to progress through puberty, menstruate, and finally develop ovulatory cycles. They postulated a direct relationship between weight and menarche and suggested that before menarche will occur at least 17% of the body weight needs to be made up of fat. The Frisch hypothesis is not universally accepted, and it seems highly unlikely that a single age unrelated body weight is always the trigger for menarche. Many of the data used in Frische's original studies were derived rather than directly observed. It seems likely that both body weight and composition are important and that the peripheral conversion of androgens to estrogens in fat plays a role in pubertal development, but the actual signal whcih triggers the hypothalamic events leading eventually through puberty to menstruation and ovulation remains unkown. Acute malnutrition, as seen during famine, is assoicated with a dramatic decrease in fertility. It is usually secondary to amenorrhea and annovulation. In developing countries weight related amenorrhea and delayed menarche are largely the result of nutritonal deprivation and the demands of lactation on women of boderline body weight, but a different pattern is seen in Western countries. The outstanding example of weight reduction resulting in infertility is seen in patients with anorexia nervosa. These women have extreme self imposed weight loss, a distorted perception of their body image, and disturbance in their attitude towards their feelings of hunger

  5. 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...

  6. Obese gene expression: reduction by fasting and stimulation by insulin and glucose in lean mice, and persistent elevation in acquired (diet-induced) and genetic (yellow agouti) obesity.

    PubMed Central

    Mizuno, T M; Bergen, H; Funabashi, T; Kleopoulos, S P; Zhong, Y G; Bauman, W A; Mobbs, C V

    1996-01-01

    Mutations in the obese (ob) gene lead to obesity. This gene has been recently cloned, but the factors regulating its expression have not been elucidated. To address the regulation of the ob gene with regard to body weight and nutritional factors, Northern blot analysis was used to assess ob mRNA in adipose tissue from mice [lean, obese due to diet, or genetically (yellow agouti) obese] under different nutritional conditions. ob mRNA was elevated in both forms of obesity, compared to lean controls, correlated with elevations in plasma insulin and body weight, but not plasma glucose. In lean C57BL/6J mice, but not in mice with diet-induced obesity, ob mRNA decreased after a 48-hr fast. Similarly, in lean C57BL/6J controls, but not in obese yellow mice, i.p. glucose injection significantly increased ob mRNA. For up to 30 min after glucose injection, ob mRNA in lean mice significantly correlated with plasma glucose, but not with plasma insulin. In a separate study with only lean mice, ob mRNA was inhibited >90% by fasting, and elevated approximately 2-fold 30 min after i.p. injection of either glucose or insulin. These results suggest that in lean animals glucose and insulin enhance ob gene expression. In contrast to our results in lean mice, in obese animals ob mRNA is elevated and relatively insensitive to nutritional state, possibly due to chronic exposure to elevated plasma insulin and/or glucose. Images Fig. 1 Fig. 4 PMID:8622953

  7. 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

  8. 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

    2016-01-01

    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

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

    PubMed Central

    Park, Soyoung; Lim, Yeseo; Shin, Sunhye

    2013-01-01

    Korean pine nut oil (PNO) has been reported to have favorable effects on lipid metabolism and appetite control. We investigated whether PNO consumption could influence weight gain, and whether the PNO-induced effect would result in an improvement of immune function in high-fat diet (HFD)-induced obese mice. C57BL/6 mice were fed control diets with 10% energy fat from either PNO or soybean oil (SBO), or HFDs with 45% energy fat from 10% PNO or SBO and 35% lard, 20% PNO or SBO and 25% lard, or 30% PNO or SBO and 15% lard for 12 weeks. The proliferative responses of splenocytes upon stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS), Con A-stimulated production of interleukin (IL)-2 and interferon (IFN)-γ, and LPS-stimulated production of IL-6, IL-1β, and prostaglandin E2 (PGE2) by splenocytes were determined. Consumption of HFDs containing PNO resulted in significantly less weight gain (17% less, P < 0.001), and lower weight gain was mainly due to less white adipose tissue (18% less, P = 0.001). The reduction in weight gain did not result in the overall enhancement in splenocyte proliferation. Overall, PNO consumption resulted in a higher production of IL-1β (P = 0.04). Replacement of SBO with PNO had no effect on the production of IL-2, IFN-γ, IL-6, or PGE2 in mice fed with either the control diets or HFDs. In conclusion, consumption of PNO reduced weight gain in mice fed with HFD, but this effect did not result in the overall improvement in immune responses. PMID:24133613

  10. Impaired vascular responses to relaxin in diet-induced overweight female rats.

    PubMed

    van Drongelen, Joris; van Koppen, Arianne; Pertijs, Jeanne; Gooi, Jonathan H; Parry, Laura J; Sweep, Fred C G J; Lotgering, Frederik K; Smits, Paul; Spaanderman, Marc E A

    2012-03-01

    Relaxin mediates renal and mesenteric vascular adaptations to pregnancy by increasing endothelium-dependent vasodilation and compliance and decreasing myogenic reactivity. Diet-induced overweight and obesity are associated with impaired endothelial dysfunction and vascular remodeling leading to a reduction in arterial diameter. In this study, we tested the hypothesis that local vascular responses to relaxin are impaired in diet-induced overweight female rats on a high-fat cafeteria-style diet for 9 wk. Rats were chronically infused with either relaxin or placebo for 5 days, and vascular responses were measured in isolated mesenteric arteries and the perfused kidney. Diet-induced overweight significantly increased sensitivity to phenylephrine (by 17%) and vessel wall thickness, and reduced renal perfusion flow (RPFF; by 16%), but did not affect flow-mediated vasodilation, myogenic reactivity, and vascular compliance. In the normal weight rats, relaxin treatment significantly enhanced flow-mediated vasodilation (2.67-fold), decreased myogenic reactivity, and reduced sensitivity to phenylephrine (by 28%), but had no effect on compliance or RPFF. NO blockade by l-NAME diminished most relaxin-mediated effects. In diet-induced overweight rats, the vasodilator effects of relaxin were markedly reduced for flow-mediated vasodilation, sensitivity to phenylephrine, and myogenic response compared with the normal diet rats, mostly persistent under l-NAME. Our data demonstrate that some of the vasodilator responses to in vivo relaxin administration are impaired in isolated mesenteric arteries and the perfused kidney in diet-induced overweight female rats. This does not result from a decrease in Rxfp1 (relaxin family peptide receptor) expression but is likely to result from downstream disruption to endothelial-dependent mechanisms in diet-induced overweight animals. PMID:22174401

  11. 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

  12. Theaflavin Synthesized in a Selective, Domino-Type, One-Pot Enzymatic Biotransformation Method with Camellia sinensis Cell Culture Inhibits Weight Gain and Fat Accumulation to High-Fat Diet-Induced Obese Mice.

    PubMed

    Takemoto, Masumi; Takemoto, Hiroaki; Saijo, Ryoyasu

    2016-08-01

    The polyphenolic compound theaflavin, which is the main red pigment present in black tea, is reported to elicit various physiological effects. Because of the extremely low concentration of theaflavin present in black tea, its extraction from black tea leaves in quantities sufficient for use in medical studies has been difficult. We have developed a simple, inexpensive, selective, domino-type, one-pot enzymatic biotransformation method for the synthesis of theaflavin that is suitable for use in medical studies. Subsequent administration of this synthetic theaflavin to high-fat diet-induced obese mice inhibited both body weight gain and visceral fat accumulation, with no significant difference in the amount of faeces between the experimental and control mice. PMID:27237789

  13. 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...

  14. WITHDRAWN BY AUTHOR: 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 Central

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

    2014-01-01

    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. PMID:24773342

  15. 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 Central

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

    2015-01-01

    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. PMID:25549049

  16. Putting the diet back into diet-induced obesity: diet-induced hypothalamic gene expression.

    PubMed

    Mercer, Julian G; Archer, Zoë A

    2008-05-01

    A wealth of detailed mechanistic information relating to obesity and body weight regulation has emerged from study of single gene mutation models, and continues to be generated by engineered rodent models targeting specific genes. However, as an early step in translational research, many researchers are turning to models of diet-induced obesity. Interpretation of data generated from such models is not aided by the variety of diets and rodent strains employed in these studies and a strong case could be made for rationalisation. Differences in experimental protocol, which may deploy a single obligatory solid diet, a choice of solid diets, or liquid/solid combinations, and which may or may not allow a preferred macronutrient composition to be selected, mean that different models of diet-induced obesity achieve that obesity by different routes. The priority should be to mimic the palatability- and choice-driven over-consumption that probably underlies the majority of human obesity. Some of the hypothalamic energy balance genes apparently 'recognise' developing diet-induced obesity as indicated by counter-regulatory changes in expression levels. However, substantial changes in gene expression on long-term exposure to obesogenic diets are not able to prevent weight gain. Forebrain reward systems are widely assumed to be overriding hypothalamic homeostatic energy balance systems under these circumstances. More mechanism-based research at the homeostatic/reward/diet interface may enable diets to be manipulated with therapeutic benefit, or define the contribution of these interactions to susceptibility to diet-induced obesity. PMID:18342851

  17. Rice koji reduced body weight gain, fat accumulation, and blood glucose level in high-fat diet-induced obese mice

    PubMed Central

    Yoshizaki, Yumiko; Kawasaki, Chihiro; Cheng, Kai-Chun; Ushikai, Miharu; Amitani, Haruka; Asakawa, Akihiro; Okutsu, Kayu; Sameshima, Yoshihiro; Takamine, Kazunori

    2014-01-01

    Rice koji is considered a readily accessible functional food that may have health-promoting effects. We investigated whether white, yellow, and red koji have the anti-obesity effect in C57BL/6J mice fed a high-fat diet (HFD), which is a model for obesity. Mice were fed HFD containing 10% (w/w) of rice koji powder or steamed rice for 4 weeks. Weight gain, epididymal white adipose tissue, and total adipose tissue weight were significantly lower in all rice koji groups than in the HFD-rice group after 4 weeks. Feed efficiency was significantly reduced in the yellow koji group. Blood glucose levels were significantly lower in the white and red koji groups with HOMA-R and leptin levels being reduced in the white koji group. White and red koji increased glucose uptake and GLUT4 protein expression in L6 myotube cells. These results showed that all rice koji have the anti-obesity or anti-diabetes effects although the mechanisms may differ depending on the type of rice koji consumed. PMID:25237599

  18. 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

  19. 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

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

    PubMed

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

    2015-05-01

    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/m(2)) 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-(13)C6]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

  1. 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

  2. Simple noise reduction for diffusion weighted images.

    PubMed

    Konishi, Yuto; Kanazawa, Yuki; Usuda, Takatoshi; Matsumoto, Yuki; Hayashi, Hiroaki; Matsuda, Tsuyoshi; Ueno, Junji; Harada, Masafumi

    2016-07-01

    Our purpose in this study was to reduce the noise in order to improve the SNR of Dw images with high b-value by using two correction schemes. This study was performed with use of phantoms made from water and sucrose at different concentrations, which were 10, 30, and 50 weight percent (wt%). In noise reduction for Dw imaging of the phantoms, we compared two correction schemes that are based on the Rician distribution and the Gaussian distribution. The highest error values for each concentration with use of the Rician distribution scheme were 7.3 % for 10 wt%, 2.4 % for 30 wt%, and 0.1 % for 50 wt%. The highest error values for each concentration with use of the Gaussian distribution scheme were 20.3 % for 10 wt%, 11.6 % for 30 wt%, and 3.4 % for 50 wt%. In Dw imaging, the noise reduction makes it possible to apply the correction scheme of Rician distribution. PMID:26984734

  3. Empagliflozin Protects against Diet-Induced NLRP-3 Inflammasome Activation and Lipid Accumulation.

    PubMed

    Benetti, Elisa; Mastrocola, Raffaella; Vitarelli, Giovanna; Cutrin, Juan Carlos; Nigro, Debora; Chiazza, Fausto; Mayoux, Eric; Collino, Massimo; Fantozzi, Roberto

    2016-10-01

    The aim of this study was to evaluate the effects of chronic treatment with empagliflozin, a potent and selective sodium glucose cotransporter-2 inhibitor, in a murine model of diet-induced obesity and insulin resistance, focusing on drug effects on body weight reduction and nucleotide-binding domain, leucine-rich repeat containing protein (NLRP)-3 inflammasome activation, which have never been investigated to date. Male C57BL/6 mice were fed control or a high fat-high sugar (HFHS) diet for 4 months. Over the last 2 months, subsets of animals were treated with empagliflozin (1-10 mg/kg) added to the diet. Empagliflozin evoked body weight reduction (P < 0.001 for the highest dose) and positive effects on fasting glycemia and homeostasis model assessment of insulin resistance. In addition, the drug was able to reduce renal tubular damage and liver triglycerides level in a dose-dependent manner. Interestingly, empagliflozin also decreased cardiac lipid accumulation. Moreover, diet-induced activation of NLRP-3 in kidney and liver (not observed in the heart) was dose-dependently attenuated by empagliflozin. Our results clearly demonstrate the ability of empagliflozin to counteract the deleterious effects evoked by chronic exposure to HFHS diet. Most notably, empagliflozin treatment was associated with NLRP-3 inflammasome signaling modulation, suggesting that this inhibition may contribute to the drug therapeutic effects. PMID:27440421

  4. Relative Contributions of Afferent Vagal Fibers to Resistance to Diet-Induced Obesity

    PubMed Central

    Stearns, A. T.; Balakrishnan, A.; Radmanesh, A.; Ashley, S. W.; Rhoads, D. B.

    2014-01-01

    Background We previously demonstrated vagal neural pathways, specifically subdiaphragmatic afferent fibers, regulate expression of the intestinal sodium-glucose cotransporter SGLT1, the intestinal transporter responsible for absorption of dietary glucose. We hypothesized targeting this pathway could be a novel therapy for obesity. We therefore tested the impact of disrupting vagal signaling by total vagotomy or selective vagal de-afferentation on weight gain and fat content in diet-induced obese rats. Methods Male Sprague–Dawley rats (n = 5–8) underwent truncal vagotomy, selective vagal de-afferentation with capsaicin, or sham procedure. Animals were maintained for 11 months on a high-caloric Western diet. Abdominal visceral fat content was assessed by magnetic resonance imaging together with weight of fat pads at harvest. Glucose homeostasis was assessed by fasting blood glucose and HbA1C. Jejunal SGLT1 gene expression was assessed by qPCR and immunoblotting and function by glucose uptake in everted jejunal sleeves. Results At 11-months, vagotomized rats weighed 19% less (P = 0.003) and de-afferented rats 7% less (P = 0.19) than shams. Vagotomized and de-afferented animals had 52% (P < 0.0001) and 18% reduction (P = 0.039) in visceral abdominal fat, respectively. There were no changes in blood glucose or glycemic indexes. SGLT1 mRNA, protein and function were unchanged across all cohorts at 11-months postoperatively. Conclusions Truncal vagotomy led to significant reductions in both diet-induced weight gain and visceral abdominal fat deposition. Vagal de-afferentation led to a more modest, but clinically and statistically significant, reduction in visceral abdominal fat. As increased visceral abdominal fat is associated with excess morbidity and mortality, vagal de-afferentation may be a useful adjunct in bariatric surgery. PMID:22138962

  5. Further weight reduction of applications in long glass reinforced polymers

    NASA Astrophysics Data System (ADS)

    Yanev, A.; Schijve, W.; Martin, C.; Brands, D.

    2014-05-01

    Long glass reinforced materials are broadly used in the automotive industry due to their good mechanical performance, competitive price and options for functional integration in order to reduce weight. With rapidly changing environmental requirements, a demand for further weight reduction is growing constantly. Designs in LGF-PP can bring light weight solutions in combination with system cost improvement. There are quite some possibilities for applying weight reduction technologies nowadays. These technologies have to be evaluated based on weight reduction potential, but also on mechanical performance of the end application, where the latter is often the key to success. Different weight reduction technologies are applied to SABIC®STAMAX{trade mark, serif} material, a long glass fiber reinforced polypropylene (LGF-PP), in order to investigate and define best application performance. These techniques include: chemical foaming, physical foaming and thin wall applications. Results from this research will be presented, giving a guideline for your development.

  6. 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. PMID:26977813

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

    PubMed Central

    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. PMID:26977813

  8. 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.

  9. 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. PMID:796476

  10. 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

  11. Weight bias reduction in health professionals: a systematic review.

    PubMed

    Alberga, A S; Pickering, B J; Alix Hayden, K; Ball, G D C; Edwards, A; Jelinski, S; Nutter, S; Oddie, S; Sharma, A M; Russell-Mayhew, S

    2016-06-01

    Innovative and coordinated strategies to address weight bias among health professionals are urgently needed. We conducted a systematic literature review of empirical peer-reviewed published studies to assess the impact of interventions designed to reduce weight bias in students or professionals in a health-related field. Combination sets of keywords based on three themes (1: weight bias/stigma; 2: obesity/overweight; 3: health professional) were searched within nine databases. Our search yielded 1447 individual records, of which 17 intervention studies satisfied the inclusion criteria. Most studies (n = 15) included medical, dietetic, health promotion, psychology and kinesiology students, while the minority included practicing health professionals (n = 2). Studies utilized various bias-reduction strategies. Many studies had methodological weaknesses, including short assessment periods, lack of randomization, lack of control group and small sample sizes. Although many studies reported changes in health professionals' beliefs and knowledge about obesity aetiology, evidence of effectiveness is poor, and long-term effects of intervention strategies on weight bias reduction remain unknown. The findings highlight the lack of experimental research to reduce weight bias among health professionals. Although changes in practice will likely require multiple strategies in various sectors, well-designed trials are needed to test the impact of interventions to decrease weight bias in healthcare settings. PMID:27166133

  12. 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

  13. Immunity-Based Evolutionary Interpretation of Diet-Induced Thermogenesis.

    PubMed

    Liao, Wan-Hui; Henneberg, Maciej; Langhans, Wolfgang

    2016-06-14

    Diet-induced thermogenesis (DIT) has often been argued to be a physiological defense against obesity, but no empirical proof of its effectiveness in limiting human body weight gain is available. We here propose an immune explanation of DIT-i.e., that it results from the coevolution of host and gut microbiota (especially Firmicutes) that ferment ingested food and proliferate, causing periodic, vagally mediated increases in thermogenesis aimed at curtailing their expansion. Because of this evolutionary adaptive significance related to the immune system, DIT is not effective as an "adaptation" to maintain a certain body mass. Were DIT an effective adaptation to prevent obesity, the current obesity epidemic might not have occurred. PMID:27304499

  14. Optimal model reduction and frequency-weighted extension

    NASA Technical Reports Server (NTRS)

    Spanos, J. T.; Milman, M. H.; Mingori, D. L.

    1990-01-01

    In this paper the quadratically optimal model reduction problem for single-input, single-output systems is considered. The reduced order model is determined by minimizing the integral of the magnitude-squared of the transfer function error. It is shown that the numerator coefficients of the optimal approximant satisfy a weighted least squares problem and, on this basis, a two-step iterative algorithm is developed combining a least squares solver with a gradient minimizer. The existence of globally optimal stable solutions to the optimization problem is established, and convergence of the algorithm to stationary values of the cost function is proved. The formulation is extended to handle the frequency-weighted optimal model reduction problem. Three examples demonstrate the optimization algorithm.

  15. Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

    PubMed Central

    Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Mathai, Michael L.

    2016-01-01

    Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. Conclusion Ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. PMID:27058737

  16. Appetite suppression and weight reduction by a centrally active aminosterol.

    PubMed

    Ahima, Rexford S; Patel, Hiralben R; Takahashi, Nobuhiko; Qi, Yong; Hileman, Stanley M; Zasloff, Michael A

    2002-07-01

    The rise in obesity and its complications has generated enormous interest in the regulation of feeding and body weight. We show that a spermine metabolite of cholesterol (MSI-1436) decreases body weight, specifically fat, by suppressing feeding and preventing the reduction in energy expenditure, hormonal changes, and patterns of neuropeptide expression normally associated with weight loss. MSI-1436 enters the brain after peripheral injection and is more potent when injected into the cerebral ventricle (intracerebroventricular [ICV]). Systemic or ICV MSI-1436 administration induced similar patterns of Fos immunoreactivity in the brain, especially the paraventricular hypothalamic nucleus (PVN). This brain region integrates neural signals from hypothalamic and brain stem nuclei and regulates feeding behavior, autonomic function, and neuroendocrine function. Microinjection of MSI-1436 into the PVN potently suppressed feeding and reduced body weight for several days. Unlike caloric restriction, MSI-1436 decreased mRNA levels of agouti-related peptide and neuropeptide Y in the hypothalamus. These findings indicate that MSI-1436 acts in the brain to regulate food intake and energy expenditure, likely through suppression of orexigenic hypothalamic pathways. PMID:12086938

  17. Speckle reduction by phase-based weighted least squares.

    PubMed

    Zhu, Lei; Wang, Weiming; Qin, Jing; Heng, Pheng-Ann

    2014-01-01

    Although ultrasonography has been widely used in clinical applications, the doctor suffers great difficulties in diagnosis due to the artifacts of ultrasound images, especially the speckle noise. This paper proposes a novel framework for speckle reduction by using a phase-based weighted least squares optimization. The proposed approach can effectively smooth out speckle noise while preserving the features in the image, e.g., edges with different contrasts. To this end, we first employ a local phase-based measure, which is theoretically intensity-invariant, to extract the edge map from the input image. The edge map is then incorporated into the weighted least squares framework to supervise the optimization during despeckling, so that low contrast edges can be retained while the noise has been greatly removed. Experimental results in synthetic and clinical ultrasound images demonstrate that our approach performs better than state-of-the-art methods. PMID:25570846

  18. Low-Fat Versus Low-Carbohydrate Weight Reduction Diets

    PubMed Central

    Bradley, Una; Spence, Michelle; Courtney, C. Hamish; McKinley, Michelle C.; Ennis, Cieran N.; McCance, David R.; McEneny, Jane; Bell, Patrick M.; Young, Ian S.; Hunter, Steven J.

    2009-01-01

    OBJECTIVE Low-fat hypocaloric diets reduce insulin resistance and prevent type 2 diabetes in those at risk. Low-carbohydrate, high-fat diets are advocated as an alternative, but reciprocal increases in dietary fat may have detrimental effects on insulin resistance and offset the benefits of weight reduction. RESEARCH DESIGN AND METHODS We investigated a low-fat (20% fat, 60% carbohydrate) versus a low-carbohydrate (60% fat, 20% carbohydrate) weight reduction diet in 24 overweight/obese subjects ([mean ± SD] BMI 33.6 ± 3.7 kg/m2, aged 39 ± 10 years) in an 8-week randomized controlled trial. All food was weighed and distributed, and intake was calculated to produce a 500 kcal/day energy deficit. Insulin action was assessed by the euglycemic clamp and insulin secretion by meal tolerance test. Body composition, adipokine levels, and vascular compliance by pulse-wave analysis were also measured. RESULTS Significant weight loss occurred in both groups (P < 0.01), with no difference between groups (P = 0.40). Peripheral glucose uptake increased, but there was no difference between groups (P = 0.28), and suppression of endogenous glucose production was also similar between groups. Meal tolerance–related insulin secretion decreased with weight loss with no difference between groups (P = 0.71). The change in overall systemic arterial stiffness was, however, significantly different between diets (P = 0.04); this reflected a significant decrease in augmentation index following the low-fat diet, compared with a nonsignificant increase within the low-carbohydrate group. CONCLUSIONS This study demonstrates comparable effects on insulin resistance of low-fat and low-carbohydrate diets independent of macronutrient content. The difference in augmentation index may imply a negative effect of low-carbohydrate diets on vascular risk. PMID:19720791

  19. Energy density in cafeteria diet induced hyperphagia in the rat.

    PubMed

    Shafat, Amir; Murray, Brenda; Rumsey, David

    2009-02-01

    Rats that are fed cafeteria diet (CD) are a widely used model of obesity. Presenting a varied and energy-dense diet often leads to hyperphagia and weight gain. However, the exact macronutrient composition of ingested food remains difficult to measure accurately. The current investigation aims to improve the accuracy of food intake calculations using a novel compensation for water evaporation, and to examine the role of energy density in CD-induced hyperphagia. Seven rats were presented daily with four foods, on rotation from a list of 36 different items, for a period of 43 days and compared to chow-fed controls (n=6). Correcting for evaporation corrected an overestimation by 8% of energy intake in rats fed CD. Rats consumed 25% more food by weight when fed CD as compared to controls. Similar to human studies, exposure to CD resulted in a 58% increase in energy intake. Energy density was positively correlated with energy intake in rats fed CD. Body weight gain was significantly elevated from day 20 onwards, suggesting the onset of obesity. This study removes evaporation bias from measurements of food intake in CD and supports the conclusion that a varied, energetically dense diet induces hyperphagia and obesity in the rat. PMID:18680774

  20. 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

  1. Utilizing the Health Belief Model to predicting female middle school students' behavioral intention of weight reduction by weight status

    PubMed Central

    2011-01-01

    Weight reduction behavior is common among adolescent girls. The present study examined the status of weight reduction behavior and factors affecting the behavioral intention of weight reduction using the Health Belief Model (HBM) for female middle school students by weight category. Survey data was collected from three girl's middle schools in Gyeongju, Korea. A total of 299 female middle school students participated in this study. The questionnaire had questions about general characteristics, weight reduction behavior, and variables of HBM (perceived threat, perceived benefits, perceived barriers, cues to action, self-efficacy in dietary life and exercise, and behavioral intention of weight reduction). Descriptive statistics, Chi-square tests, ANOVA, and multiple regression analysis were applied to analyze the variables. A higher percentage of students in the overweight group attempted weight reduction than those in the underweight and the normal weight groups (P < 0.001). Among students who had attempted weight reduction, 73% tried diet therapy, while 78% tried exercise. Students in the normal and overweight groups showed significantly higher threat (P < 0.01) and cues to action (P < 0.001) than those in the underweight group. As for perceived benefits, barriers, and self-efficacy in dietary life and exercise, there were no significant differences among weight groups. Students in the overweight group showed the strongest intention of weight reduction and there were significant differences among the three weight groups (P < 0.001). Perceive threat (P < 0.01), cues to action (P < 0.001), and perceived self-efficacy (P < 0.01) were significantly associated to behavioral intention of weight reduction for all respondents. For the underweight group, perceived threat (P < 0.05) and perceived self-efficacy (P < 0.01) were the significant variables. For the overweight group, cue to action was the significant variable (P < 0.05). PMID:21994529

  2. 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

  3. Biodrying for municipal solid waste: volume and weight reduction.

    PubMed

    Bilgin, Melayib; Tulun, Şevket

    2015-01-01

    Biodrying is a variation of aerobic decomposition used for the mechanical-biological treatment organic substances to dry and partially stabilize residual municipal waste. This study focuses on the volume and weight reduction biodegradation of the biodrying process using municipal solid waste and the appearance of a stable, final product. The materials were placed in a reactor with invariant airflow rates of 50 L/h and initial moisture contents of 48.49-50.00%. The laboratory-scale experiments were implemented using a 36-L biodrying reactor equipped with an air supply system, a biomass temperature sensor and air sensors. To determine the effect of temperature on biodrying, the process was repeated at various temperatures between 30 °C and 50 °C. The results obtained indicated that after 13 days, biodrying reduced the volume content of waste by 32% and the final product had a high calorific value (4680 kcal/kg). PMID:25571768

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

    PubMed

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

    2015-10-28

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

  5. Effect of Weight-Reduction in Obese Mice Lacking Toll-Like Receptor 5 and C57BL/6 Mice Fed a Low-Fat Diet

    PubMed Central

    Wu, Shao-Chun; Rau, Cheng-Shyuan; Lu, Tsu-Hsiang; Tzeng, Siou-Ling; Wu, Yi-Chan; Wu, Chia-Jung; Lin, Chia-Wei; Hsieh, Ching-Hua

    2015-01-01

    Background. This study aims to investigate the effect of feeding low-fat diet (LFD) to diet-induced obesity (DIO) mice lacking TLR5 (TLR5−/−), which have a tendency to develop glucose intolerance with increased adiposity, compared to that in C57BL/6 mice. Results. TLR5−/− and C57BL/6 male mice were divided into three subgroups: (1) control, mice were fed a standard AIN-76A (fat: 11.5 kcal%) diet for 12 weeks; (2) DIO, mice were fed a 58 kcal% high-fat diet (HFD) for 12 weeks; and (3) diet, mice were fed a HFD for 8 weeks to induce obesity and then switched to a 10.5 kcal% LFD for 4 weeks. The glucose intolerance in DIO TLR5−/− mice was more significant than that in DIO C57BL/6 mice and was not attenuated by a switch to the LFD. Weight-reduction with LFD had significantly decreased the epididymal fat mass in C57BL/6 mice but not in TLR5−/− mice. In addition, the LFD-fed TLR5−/− mice showed significantly higher expression of ghrelin in the serum and resistin in the epididymal fat than that in C57BL/6 mice. Conclusions. This study demonstrated that TLR5 gene knockout impairs some effects of weight-reduction in DIO. PMID:26681840

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

    PubMed

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

    2014-07-01

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

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

    PubMed Central

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

    2014-01-01

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

  8. 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…

  9. 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

  10. 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

  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. PMID:26410845

  12. Rapid Rather than Gradual Weight Reduction Impairs Hemorheological Parameters of Taekwondo Athletes through Reduction in RBC-NOS Activation

    PubMed Central

    Yang, Woo Hwi; Heine, Oliver; Pauly, Sebastian; Kim, Pilsang; Bloch, Wilhelm; Mester, Joachim; Grau, Marijke

    2015-01-01

    Purpose Rapid weight reduction is part of the pre-competition routine and has been shown to negatively affect psychological and physiological performance of Taekwondo (TKD) athletes. This is caused by a reduction of the body water and an electrolyte imbalance. So far, it is unknown whether weight reduction also affects hemorheological properties and hemorheology-influencing nitric oxide (NO) signaling, important for oxygen supply to the muscles and organs. Methods For this purpose, ten male TKD athletes reduced their body weight by 5% within four days (rapid weight reduction, RWR). After a recovery phase, athletes reduced body weight by 5% within four weeks (gradual weight reduction, GWR). Each intervention was preceded by two baseline measurements and followed by a simulated competition. Basal blood parameters (red blood cell (RBC) count, hemoglobin concentration, hematocrit, mean corpuscular volume, mean cellular hemoglobin and mean cellular hemoglobin concentration), RBC-NO synthase activation, RBC nitrite as marker for NO synthesis, RBC deformability and aggregation parameters were determined on a total of eight investigation days. Results Basal blood parameters were not affected by the two interventions. In contrast to GWR, RWR decreased activation of RBC-NO synthase, RBC nitrite, respective NO concentration and RBC deformability. Additionally, RWR increased RBC aggregation and disaggregation threshold. Conclusion The results point out that a rapid weight reduction negatively affects hemorheological parameters and NO signaling in RBC which might limit performance capacity. Thus, GWR should be preferred to achieve the desired weight prior to a competition to avoid these negative effects. PMID:25875585

  13. 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…

  14. 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…

  15. Hypoglycemic effects of brassinosteroid in diet-induced obese mice.

    PubMed

    Esposito, Debora; Kizelsztein, Pablo; Komarnytsky, Slavko; Raskin, Ilya

    2012-09-01

    The prevalence of obesity is increasing globally, and obesity is a major risk factor for metabolic diseases such as type 2 diabetes. Previously, we reported that oral administration of homobrassinolide (HB) to healthy rats triggered a selective anabolic response that was associated with lower blood glucose. Therefore, the aim of this study was to evaluate the effects of HB administration on glucose metabolism, insulin sensitivity, body composition, and gluconeogenic gene expression profiles in liver of C57BL/6J high-fat diet-induced obese mice. Acute oral administration of 50-300 mg/kg HB to obese mice resulted in a dose-dependent decrease in fasting blood glucose within 3 h of treatment. Daily chronic administration of HB (50 mg/kg for 8 wk) ameliorated hyperglycemia and improved oral glucose tolerance associated with obesity without significantly affecting body weight or body composition. These changes were accompanied by lower expression of two key gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G-6-Pase), and increased phosphorylation of AMP-activated protein kinase in the liver and muscle tissue. In vitro, HB treatment (1-15 μM) inhibited cyclic AMP-stimulated but not dexamethasone-stimulated upregulation of PEPCK and G-6-Pase mRNA levels in H4IIE rat hepatoma cells. Among a series of brassinosteroid analogs related to HB, only homocastasterone decreased glucose production in cell culture significantly. These results indicate the antidiabetic effects of brassinosteroids and begin to elucidate their putative cellular targets both in vitro and in vivo. PMID:22785239

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

    PubMed

    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

    2014-10-21

    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

  17. 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

  18. Brown fat and the myth of diet-induced thermogenesis.

    PubMed

    Kozak, Leslie P

    2010-04-01

    The notion that brown adipose tissue (BAT) in mice or humans maintains energy balance by burning off excess calories seems incompatible with evolutionary biology. Studies in obese rats and mice lacking UCP1 indicate that diet-induced thermogenesis by BAT is unlikely. PMID:20374958

  19. Effects of weight-reduction on obesity-associated diseases.

    PubMed

    Liebermeister, Hermann

    2003-01-01

    Even moderate, but persistent weight-loss ameliorates most of the related diseases in obesity. Besides the consequences of the metabolic syndrome, this includes less well-known obesity-associated changes, such as impaired fertility, menstrual disorders, psychic changes, total leucocyte-count as a parameter of immunity and the impaired pulmonary function in asthma and sleep-apnoea. Life-expectancy is prolonged by diminution of visceral fat depots, whilst weight-loss by shrinking of fat-free body-mass seems to have a contrary effect. PMID:19675702

  20. Effects of weight-reduction on obesity-associated diseases

    PubMed Central

    Liebermeister, Hermann

    2003-01-01

    Even moderate, but persistent weight-loss ameliorates most of the related diseases in obesity. Besides the consequences of the metabolic syndrome, this includes less well-known obesity-associated changes, such as impaired fertility, menstrual disorders, psychic changes, total leucocyte-count as a parameter of immunity and the impaired pulmonary function in asthma and sleep-apnoea. Life-expectancy is prolonged by diminution of visceral fat depots, whilst weight-loss by shrinking of fat-free body-mass seems to have a contrary effect. PMID:19675702

  1. 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.…

  2. 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. PMID:27033600

  3. Determinants of Successful Weight Loss After Using a Commercial Web-Based Weight Reduction Program for Six Months: Cohort Study

    PubMed Central

    Postrach, Elisa; Aspalter, Rosa; Elbelt, Ulf; Koller, Michael; Longin, Rita; Schulzke, Jörg-Dieter

    2013-01-01

    weight entries were independent predictors for 6-month weight reduction (all P<.001) explaining 52% of the variance in weight reduction. Sensitivity analysis by baseline carried forward method confirmed all independent predictors of 6-month weight loss and reduced the model fit by only 11%. The high success group lost weight faster and maintained weight loss more efficiently than the other groups (P<.001). Early weight loss was associated with weight maintenance after 1 year and 2 years (both P<.001). Weight dynamics did not differ between men and women over 6 months when adjusted for baseline and usage parameters (P=.91). The percentage of male long-term users was unusually high (42.2%). Conclusions Our results suggest that early weight loss and close program adherence (ie, 5 dietary protocols per week and weekly entering of current weight), especially in the early phase of program usage, can improve weight loss outcome. PMID:24126250

  4. 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

  5. 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.

  6. 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. PMID:25817008

  7. 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

  8. Reduced capacity for fatty acid oxidation in rats with inherited susceptibility to diet-induced obesity.

    PubMed

    Ji, Hong; Friedman, Mark I

    2007-08-01

    High-fat, energy-dense diets promote weight gain and obesity in humans and other animals, but the mechanisms underlying such diet-induced obesity remain elusive. To determine whether a reduced capacity to oxidize fat is involved in the etiology of diet-induced obesity, we examined different measures of fatty acid oxidation in rats selectively bred for susceptibility (DIO) or resistance (DR) to dietary obesity before and after they were fed a high-fat diet and became obese. DIO rats eating a low-fat diet oxidized less dietary fatty acid in vivo and had lower levels of plasma ketone bodies during fasting compared with DR rats. Lean DIO rats fed a low-fat diet showed reduced liver messenger RNA expression of CD36, which transports fatty acids across cell membranes, and long-chain acyl-coenzyme A dehydrogenase (ACADL), which catalyzes the first step in the mitochondrial beta-oxidation of fatty acids. The deficit in CD36 and ACADL messenger RNA expression was also seen in obese DIO rats that had been eating a high-fat diet and, in addition, was accompanied by reduced expression of liver carnitine palmitoyl transferase I, the enzyme that mediates transport of long-chain fatty acids into mitochondria. No differences were found in the expression of liver enzymes involved in fat synthesis; however, in muscle, DIO rats fed the low-fat, but not high-fat, diet showed greater expression of diacylglycerol O-acyltransferase 1 and lipoprotein lipase than did DR rats. Expression of muscle enzymes involved in fatty acid oxidation was similar in the 2 groups. These findings provide a metabolic mechanism for the development of diet-induced obesity and thus suggest potential targets for intervention strategies to treat or prevent it. PMID:17618960

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

    PubMed

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

    2012-04-01

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

  10. Short-Chain Fructo-Oligosaccharides Modulate Intestinal Microbiota and Metabolic Parameters of Humanized Gnotobiotic Diet Induced Obesity Mice

    PubMed Central

    Respondek, Frederique; Gerard, Philippe; Bossis, Mathilde; Boschat, Laura; Bruneau, Aurélia; Rabot, Sylvie; Wagner, Anne; Martin, Jean-Charles

    2013-01-01

    Prebiotic fibres like short-chain fructo-oligosaccharides (scFOS) are known to selectively modulate the composition of the intestinal microbiota and especially to stimulate Bifidobacteria. In parallel, the involvement of intestinal microbiota in host metabolic regulation has been recently highlighted. The objective of the study was to evaluate the effect of scFOS on the composition of the faecal microbiota and on metabolic parameters in an animal model of diet-induced obesity harbouring a human-type microbiota. Forty eight axenic C57BL/6J mice were inoculated with a sample of faecal human microbiota and randomly assigned to one of 3 diets for 7 weeks: a control diet, a high fat diet (HF, 60% of energy derived from fat)) or an isocaloric HF diet containing 10% of scFOS (HF-scFOS). Mice fed with the two HF gained at least 21% more weight than mice from the control group. Addition of scFOS partially abolished the deposition of fat mass but significantly increased the weight of the caecum. The analysis of the taxonomic composition of the faecal microbiota by FISH technique revealed that the addition of scFOS induced a significant increase of faecal Bifidobacteria and the Clostridium coccoides group whereas it decreased the Clostridium leptum group. In addition to modifying the composition of the faecal microbiota, scFOS most prominently affected the faecal metabolome (e.g. bile acids derivatives, hydroxyl monoenoic fatty acids) as well as urine, plasma hydrophilic and plasma lipid metabolomes. The increase in C. coccoides and the decrease in C. leptum, were highly correlated to these metabolic changes, including insulinaemia, as well as to the weight of the caecum (empty and full) but not the increase in Bifidobacteria. In conclusion scFOS induce profound metabolic changes by modulating the composition and the activity of the intestinal microbiota, that may partly explain their effect on the reduction of insulinaemia. PMID:23951074

  11. 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

  12. 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.

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

    PubMed

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

    2011-07-01

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

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

    PubMed Central

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

    2011-01-01

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

  15. CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction

    PubMed Central

    Peterson, Jonathan M.; Wei, Zhikui; Seldin, Marcus M.; Byerly, Mardi S.; Aja, Susan

    2013-01-01

    CTRP9 is a secreted multimeric protein of the C1q family and the closest paralog of the insulin-sensitizing adipokine, adiponectin. The metabolic function of this adipose tissue-derived plasma protein remains largely unknown. Here, we show that the circulating levels of CTRP9 are downregulated in diet-induced obese mice and upregulated upon refeeding. Overexpressing CTRP9 resulted in lean mice that dramatically resisted weight gain induced by a high-fat diet, largely through decreased food intake and increased basal metabolism. Enhanced fat oxidation in CTRP9 transgenic mice resulted from increases in skeletal muscle mitochondrial content, expression of enzymes involved in fatty acid oxidation (LCAD and MCAD), and chronic AMPK activation. Hepatic and skeletal muscle triglyceride levels were substantially decreased in transgenic mice. Consequently, CTRP9 transgenic mice had a greatly improved metabolic profile with markedly reduced fasting insulin and glucose levels. The high-fat diet-induced obesity, insulin resistance, and hepatic steatosis observed in wild-type mice were prevented in transgenic mice. Consistent with the in vivo data, recombinant protein significantly enhanced fat oxidation in L6 myotubes via AMPK activation and reduced lipid accumulation in H4IIE hepatocytes. Collectively, these data establish CTRP9 as a novel metabolic regulator and a new component of the metabolic network that links adipose tissue to lipid metabolism in skeletal muscle and liver. PMID:23842676

  16. ATF7 ablation prevents diet-induced obesity and insulin resistance.

    PubMed

    Liu, Yang; Maekawa, Toshio; Yoshida, Keisuke; Furuse, Tamio; Kaneda, Hideki; Wakana, Shigeharu; Ishii, Shunsuke

    2016-09-16

    The activating transcription factor (ATF)2 family of transcription factors regulates a variety of metabolic processes, including adipogenesis and adaptive thermogenesis. ATF7 is a member of the ATF2 family, and mediates epigenetic changes induced by environmental stresses, such as social isolation and pathogen infection. However, the metabolic role of ATF7 remains unknown. The aim of the present study is to examine the role of ATF7 in metabolism using ATF7-dificeint mice. Atf7(-/-) mice exhibited lower body weight and resisted diet-induced obesity. Serum triglycerides, resistin, and adipose tissue mass were all significantly lower in ATF7-deficient mice. Fasting glucose levels and glucose tolerance were unaltered, but systemic insulin sensitivity was increased, by ablation of ATF7. Indirect calorimetry revealed that oxygen consumption by Atf7(-/-) mice was comparable to that of wild-type littermates on a standard chow diet, but increased energy expenditure was observed in Atf7(-/-) mice on a high-fat diet. Hence, ATF7 ablation may impair the development and function of adipose tissue and result in elevated energy expenditure in response to high-fat-feeding obesity and insulin resistance, indicating that ATF7 is a potential therapeutic target for diet-induced obesity and insulin resistance. PMID:27498002

  17. Deficiency and pharmacological stabilization of mast cells reduce diet-induced obesity and diabetes in mice

    PubMed Central

    Liu, Jian; Divoux, Adeline; Sun, Jiusong; Zhang, Jie; Clément, Karine; Glickman, Jonathan N.; Sukhova, Galina K.; Wolters, Paul J.; Du, Juan; Gorgun, Cem Z.; Doria, Alessandro; Libby, Peter; Blumberg, Richard S.; Kahn, Barbara B.; Hotamisligil, Gokhan S.; Shi, Guo-Ping

    2009-01-01

    Although mast cell functions classically relate to allergic responses1–3, recent studies indicate that these cells contribute to other common diseases such as multiple sclerosis, rheumatoid arthritis, atherosclerosis, aortic aneurysm, and cancer4–8. This study presents evidence that mast cells contribute importantly to diet-induced obesity and diabetes. White adipose tissues (WAT) from obese humans and mice contain more mast cells than WAT from their lean counterparts. Genetically determined mast cell deficiency and pharmacological stabilization of mast cells in mice reduce body weight gain and levels of inflammatory cytokines, chemokines, and proteases in serum and WAT, in concert with improved glucose homeostasis and energy expenditure. Mechanistic studies reveal that mast cells contribute to WAT and muscle angiogenesis and associated cell apoptosis and cathepsin activity. Adoptive transfer of cytokine-deficient mast cells established that these cells contribute to mice adipose tissue cysteine protease cathepsin expression, apoptosis, and angiogenesis, thereby promoting diet-induced obesity and glucose intolerance by production of IL6 and IFN-γ. Mast cell stabilizing agents in clinical use reduced obesity and diabetes in mice, suggesting the potential of developing novel therapies for these common human metabolic disorders. PMID:19633655

  18. Effects of sprint interval training and body weight reduction on power to weight ratio in experienced cyclists.

    PubMed

    Lunn, William R; Finn, Joan A; Axtell, Robert S

    2009-07-01

    The purpose of this study was to determine the effect of supramaximal sprint interval training (SIT), body weight reduction, and a combination of both treatments on peak and average anaerobic power to weight ratio (PPOan:Wt, APOan:Wt) by manipulating peak and average anaerobic power output (PPOan, APOan) and body weight (BW) in experienced cyclists. Participants (N = 34, age = 38.0 +/- 7.1 years) were assigned to 4 groups for a 10-week study. One group performed twice-weekly SIT sessions on a cycle ergometer while maintaining body weight (SIT). A second group did not perform SIT but intentionally reduced body weight (WR). A third group simultaneously performed SIT sessions and reduced body weight (SIT+WR). A control group cycled in their normal routine and maintained body weight (CON). The 30-second Wingate Test assessed pretest and posttest POan:Wt scores. There was a significant mean increase (p < 0.05) from pretest to posttest in PPOan:Wt and APOan:Wt (W x kg(-1)) scores in both SIT (10.82 +/- 1.71 to 11.92 +/- 1.77 and 8.05 +/- 0.64 to 8.77 +/- 0.64, respectively) and WR (10.33 +/- 2.91 to 11.29 +/- 2.80 and 7.04 +/- 1.45 to 7.62 +/- 1.24, respectively). PPOan and APOan (W) increased significantly only in SIT (753.7 +/- 121.0 to 834.3 +/- 150.1 and 561.3 +/- 62.5 to 612.7 +/- 69.0, respectively). Body weight (kg) decreased significantly in WR and SIT + WR (80.3 +/- 13.7 to 75.3 +/- 11.9 and 78.9 +/- 10.8 to 73.4 +/- 10.8, respectively). The results demonstrate that cyclists can use SIT sessions and body weight reduction as singular training interventions to effect significant increases in anaerobic power to weight ratio, which has been correlated to enhanced aerobic cycling performance. However, the treatments were not effective as combined interventions, as there was no significant change in either PPOan:Wt or APOan:Wt in SIT + WR. PMID:19568031

  19. Loss of FXR Protects against Diet-Induced Obesity and Accelerates Liver Carcinogenesis in ob/ob Mice

    PubMed Central

    Ge, Xuemei; Heemstra, Lydia A.; Chen, Wei-Dong; Xu, Jiesi; Smith, Joseph L.; Ma, Huiyan; Kasim, Neda; Edwards, Peter A.; Novak, Colleen M.

    2012-01-01

    Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr−/− mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr−/−) mice, the Ldlr−/−Fxr−/− double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr−/− background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr−/− mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr−/− mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob−/−Fxr−/− mice that were deficient in both Leptin and Fxr. On a chow diet, ob−/−Fxr−/− mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob−/−Fxr−/− mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions. PMID:22261820

  20. Loss of FXR protects against diet-induced obesity and accelerates liver carcinogenesis in ob/ob mice.

    PubMed

    Zhang, Yanqiao; Ge, Xuemei; Heemstra, Lydia A; Chen, Wei-Dong; Xu, Jiesi; Smith, Joseph L; Ma, Huiyan; Kasim, Neda; Edwards, Peter A; Novak, Colleen M

    2012-02-01

    Farnesoid X receptor (FXR) is known to play important regulatory roles in bile acid, lipid, and carbohydrate metabolism. Aged (>12 months old) Fxr(-/-) mice also develop spontaneous liver carcinomas. In this report, we used three mouse models to investigate the role of FXR deficiency in obesity. As compared with low-density lipoprotein receptor (Ldlr) knockout (Ldlr(-/-)) mice, the Ldlr(-/-)Fxr(-/-) double-knockout mice were highly resistant to diet-induced obesity, which was associated with increased expression of genes involved in energy metabolism in the skeletal muscle and brown adipose tissue. Such a striking effect of FXR deficiency on obesity on an Ldlr(-/-) background led us to investigate whether FXR deficiency alone is sufficient to affect obesity. As compared with wild-type mice, Fxr(-/-) mice showed resistance to diet-induced weight gain. Interestingly, only female Fxr(-/-) mice showed significant resistance to diet-induced obesity, which was accompanied by increased energy expenditure in these mice. Finally, we determined the effect of FXR deficiency on obesity in a genetically obese and diabetic mouse model. We generated ob(-/-)Fxr(-/-) mice that were deficient in both Leptin and Fxr. On a chow diet, ob(-/-)Fxr(-/-) mice gained less body weight and had reduced body fat mass as compared with ob/ob mice. In addition, we observed liver carcinomas in 43% of young (<11 months old) Ob(-/-)Fxr(-/-) mice. Together these data indicate that loss of FXR prevents diet-induced or genetic obesity and accelerates liver carcinogenesis under diabetic conditions. PMID:22261820

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

    PubMed Central

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

    2013-01-01

    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. PMID:23883680

  2. αB-crystallin and HspB2 deficiency is protective from diet-induced glucose intolerance.

    PubMed

    Toft, Daniel J; Fuller, Miles; Schipma, Matthew; Chen, Feng; Cryns, Vincent L; Layden, Brian T

    2016-09-01

    Emerging evidence suggests molecular chaperones have a role in the pathogenesis of obesity and diabetes. As αB-crystallin and HspB2 are molecular chaperones and data suggests their expression is elevated in the skeletal muscle of diabetic and obese animals, we sought to determine if αB-crystallin and HspB2 collectively play a functional role in the metabolic phenotype of diet-induced obesity. Using αB-crystallin/HspB2 knockout and littermate wild-type controls, it was observed that mice on the high fat diet gained more weight as compared to the normal chow group and genotype did not impact this weight gain. To test if the genotype and/or diet influenced glucose homeostasis, intraperitoneal glucose challenge was performed. While similar on normal chow diet, wild-type mice on the high fat diet exhibited higher glucose levels during the glucose challenge compared to the αB-crystallin/HspB2 knockout mice. Although wild-type mice had higher glucose levels, insulin levels were similar for both genotypes. Insulin tolerance testing revealed that αB-crystallin/HspB2 knockout mice were more sensitive to insulin, leading to lower glucose levels over time, which is indicative of a difference in insulin sensitivity between the genotypes on a high fat diet. Transcriptome analyses of skeletal muscle in αB-crystallin/HspB2 knockout and wild-type mice on a normal or high fat diet revealed reductions in cytokine pathway genes in αB-crystallin/HspB2 knockout mice, which may contribute to their improved insulin sensitivity. Collectively, these data reveal that αB-crystallin/HspB2 plays a role in development of insulin resistance during a high fat diet challenge. PMID:27330996

  3. Metabolic Effects of Sleeve Gastrectomy in a Female Rat Model of Diet-Induced Obesity

    PubMed Central

    Brinckerhoff, Tatiana Z.; Bondada, Sandhya; Lewis, Catherine E.; French, Sam; DeUgarte, Daniel A.

    2011-01-01

    Background While females disproportionately undergo bariatric surgery, rodent models investigating mechanisms of bariatric surgery have been limited to males. Female rodent models can also potentially allow us to understand the effects of surgical intervention on future generations of offspring. Sleeve gastrectomy is an attractive weight loss procedure for reproductive-age female patients as it avoids the malabsorption associated with intestinal bypass. Objectives We sought to evaluate the impact of sleeve gastrectomy on young female rats with diet-induced obesity. Settings David Geffen School of Medicine at UCLA Methods Sprague Dawley female rats were fed a 60% high-fat diet. At 12 weeks of age, animals underwent either sleeve gastrectomy or sham surgery. Animals were sacrificed four weeks after surgery. A chemistry panel was performed, and serum adipokines and gut hormones were assayed. Homeostasis model assessment score (HOMA) was calculated. Liver histology was graded for steatosis. Two-sample t-test was used to compare groups. Results Sleeve gastrectomy was associated with significant weight loss (5±6% vs. −4±6%; p<0.001), lower leptin levels (1.3±1.2 vs. 3.5±2.3 ng/ml; p<0.01), and higher adiponectin levels (0.43 ± 0.19 vs. 0.17 ± 0.14 ng/ml; p<0.004) when compared to sham animals. There were no significant differences in fasting ghrelin. Furthermore, we did not observe evidence of insulin resistance or steatohepatitis after 11 weeks of high-fat diet. Despite these limitations, further gender-specific studies are warranted given that the majority of bariatric surgeries are performed in females. Conclusion Sleeve gastrectomy appears to result in weight loss and improvements in adiponectin and leptin via mechanisms independent of ghrelin in a female model of diet-induced obesity. PMID:22093377

  4. Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy (Slc13a5)

    PubMed Central

    Pesta, Dominik H.; Perry, Rachel J.; Guebre-Egziabher, Fitsum; Zhang, Dongyan; Jurczak, Michael; Fischer-Rosinsky, Antje; Daniels, Martin A.; Willmes, Diana M.; Bhanot, Sanjay; Bornstein, Stefan R.; Knauf, Felix; Samuel, Varman T.; Shulman, Gerald I.; Birkenfeld, Andreas L.

    2015-01-01

    Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and insulin resistance in mice. The organ specific contribution to this phenotype is unknown. We examined the impact of selective inducible hepatic knockdown of mIndy on whole body lipid and glucose metabolism using 2′-O-methoxyethyl chimeric anti-sense oligonucleotides (ASOs) in high-fat fed rats. 4-week treatment with 2′-O-methoxyethyl chimeric ASO reduced mIndy mRNA expression by 91% (P<0.001) compared to control ASO. Besides similar body weights between both groups, mIndy-ASO treatment lead to a 74% reduction in fasting plasma insulin concentrations as well as a 35% reduction in plasma triglycerides. Moreover, hepatic triglyceride content was significantly reduced by the knockdown of mIndy, likely mediating a trend to decreased basal rates of endogenous glucose production as well as an increased suppression of hepatic glucose production by 25% during a hyperinsulinemic-euglycemic clamp. Together, these data suggest that inducible liver-selective reduction of mIndy in rats is able to ameliorate hepatic steatosis and insulin resistance, conditions occurring with high calorie diets and during aging. PMID:26647160

  5. Prevention of diet-induced hepatic steatosis and hepatic insulin resistance by second generation antisense oligonucleotides targeted to the longevity gene mIndy (Slc13a5).

    PubMed

    Pesta, Dominik H; Perry, Rachel J; Guebre-Egziabher, Fitsum; Zhang, Dongyan; Jurczak, Michael; Fischer-Rosinsky, Antje; Daniels, Martin A; Willmes, Diana M; Bhanot, Sanjay; Bornstein, Stefan R; Knauf, Felix; Samuel, Varman T; Shulman, Gerald I; Birkenfeld, Andreas L

    2015-12-01

    Reducing the expression of the Indy (I'm Not Dead Yet) gene in lower organisms extends life span by mechanisms resembling caloric restriction. Similarly, deletion of the mammalian homolog, mIndy (Slc13a5), encoding for a plasma membrane tricarboxylate transporter, protects from aging- and diet-induced adiposity and insulin resistance in mice. The organ specific contribution to this phenotype is unknown. We examined the impact of selective inducible hepatic knockdown of mIndy on whole body lipid and glucose metabolism using 2'-O-methoxyethyl chimeric anti-sense oligonucleotides (ASOs) in high-fat fed rats. 4-week treatment with 2'-O-methoxyethyl chimeric ASO reduced mIndy mRNA expression by 91% (P=0.001) compared to control ASO. Besides similar body weights between both groups, mIndy-ASO treatment lead to a 74% reduction in fasting plasma insulin concentrations as well as a 35% reduction in plasma triglycerides. Moreover, hepatic triglyceride content was significantly reduced by the knockdown of mIndy, likely mediating a trend to decreased basal rates of endogenous glucose production as well as an increased suppression of hepatic glucose production by 25% during a hyperinsulinemic-euglycemic clamp. Together, these data suggest that inducible liver-selective reduction of mIndy in rats is able to ameliorate hepatic steatosis and insulin resistance, conditions occurring with high calorie diets and during aging. PMID:26647160

  6. 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

  7. Integrin-Linked Kinase in Muscle Is Necessary for the Development of Insulin Resistance in Diet-Induced Obese Mice.

    PubMed

    Kang, Li; Mokshagundam, Shilpa; Reuter, Bradley; Lark, Daniel S; Sneddon, Claire C; Hennayake, Chandani; Williams, Ashley S; Bracy, Deanna P; James, Freyja D; Pozzi, Ambra; Zent, Roy; Wasserman, David H

    2016-06-01

    Diet-induced muscle insulin resistance is associated with expansion of extracellular matrix (ECM) components, such as collagens, and the expression of collagen-binding integrin, α2β1. Integrins transduce signals from ECM via their cytoplasmic domains, which bind to intracellular integrin-binding proteins. The integrin-linked kinase (ILK)-PINCH-parvin (IPP) complex interacts with the cytoplasmic domain of β-integrin subunits and is critical for integrin signaling. In this study we defined the role of ILK, a key component of the IPP complex, in diet-induced muscle insulin resistance. Wild-type (ILK(lox/lox)) and muscle-specific ILK-deficient (ILK(lox/lox)HSAcre) mice were fed chow or a high-fat (HF) diet for 16 weeks. Body weight was not different between ILK(lox/lox) and ILK(lox/lox)HSAcre mice. However, HF-fed ILK(lox/lox)HSAcre mice had improved muscle insulin sensitivity relative to HF-fed ILK(lox/lox) mice, as shown by increased rates of glucose infusion, glucose disappearance, and muscle glucose uptake during a hyperinsulinemic-euglycemic clamp. Improved muscle insulin action in the HF-fed ILK(lox/lox)HSAcre mice was associated with increased insulin-stimulated phosphorylation of Akt and increased muscle capillarization. These results suggest that ILK expression in muscle is a critical component of diet-induced insulin resistance, which possibly acts by impairing insulin signaling and insulin perfusion through capillaries. PMID:27207548

  8. Diet-induced obesity alters bone remodeling leading to decreased femoral trabecular bone mass in mice.

    PubMed

    Cao, Jay J; Sun, Li; Gao, Hongwei

    2010-03-01

    Obesity-derived body mass may be detrimental to bone health through not well-defined mechanisms. In this study we determined changes in bone structure and serum cytokines related to bone metabolism in diet-induced obese mice. Mice fed a high-fat diet (HFD) had higher serum tartrate-resistant acid phosphatase (TRAP) and leptin but lower osteocalcin concentrations than those fed the normal-fat diet. The HFD increased multinucleated TRAP-positive osteoclasts in bone marrow compared to the control diet. Despite being much heavier, mice fed the HFD had lower femoral bone volume, trabecular number, and connectivity density and higher trabecular separation than mice on the control diet. These findings suggest that obesity induced by a HFD increases bone resorption that may blunt any positive effects of increased body weight on bone. PMID:20392249

  9. Weighted G0-and G1-multi-degree reduction of Bézier curves

    NASA Astrophysics Data System (ADS)

    Rababah, Abedallah; Ibrahim, Salisu

    2016-06-01

    In this paper, weighted G0-and G1-multi-degree reduction of Bézier curves are considered. The degree reduction of a given Bézier curve of degree n is used to write it as a Bézier curve of degree m, m < n. Exact degree reduction is not possible, and, therefore approximation methods are used. The weight function w[t] = 2t(1 - t), t ∈ [0, 1] is used with the L2 -norm in multi degree reduction with G0- and G1- continuity at the end points of the curve. Numerical results and comparisons show that the new methods suggests smaller approximation errors in the interior of the domain and proves to be competative in applications.

  10. Effects of (-)-epicatechin on a diet-induced rat model of cardiometabolic risk factors.

    PubMed

    Gutiérrez-Salmeán, Gabriel; Ortiz-Vilchis, Pilar; Vacaseydel, Claudia Maria; Garduño-Siciliano, Leticia; Chamorro-Cevallos, German; Meaney, Eduardo; Villafaña, Santiago; Villarreal, Francisco; Ceballos, Guillermo; Ramírez-Sánchez, Israel

    2014-04-01

    Overweight and obesity have been associated with increase in cardiometabolic risk. Therapeutics include lifestyle changes and/or pharmacologic agents. However, such interventions are often limited by poor compliance and/or significant side effects. The consumption of certain dietary products, such as cocoa, exerts positive effects on cardiometabolic risk factors. (-)-Epicatechin (EPI), the most abundant flavonoid in cacao has been reported to replicate such effects. However its mechanisms of action have not been fully elucidated.In a rat model of high-fat diet-induced obesity and its associated cardiometabolic risk factors, we administered 1mg/kg of EPI, by gavage, for 2 weeks. Endpoints included weight-gain, glycemia, triglyceridemia, and systolic blood pressure. We also assessed food intake and fecal excretion. Mitochondrial function and structure related proteins were measured by Westerns.Obesity, hyperglycemia, hypertriglyceridemia, and systolic hypertension were developed after the administration of the high-fat diet for five weeks. EPI significantly decreased the rate of weight gain, glycemia and hypertriglyceridemia. The ratio between energy intake and excretion was not significantly modified by treatment. EPI restored the obesity-induced decreases in the levels of skeletal muscle and abdominal tissue sirtuins (SIRTs), peroxisome proliferator-activated receptor coactivator (PGC-1α), mitofilin, transcription factor A mitochondrial (TFAM), uncoupling protein 1 (UCP1), and deiodinase.EPI treatment yielded beneficial effects on high fat diet-induced endpoints thus may be considered as a potential agent for the treatment of obesity and its cardiometabolic associated abnormalities. Mechanism of action may be attributed to the modulation of cellular/mitochondrial function, thus improving overall metabolism. PMID:24491839

  11. 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

  12. 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

  13. 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. PMID:27079226

  14. Anti-obesity Effect of Yogurt Fermented by Lactobacillus plantarum Q180 in Diet-induced Obese Rats

    PubMed Central

    2016-01-01

    This study aimed to investigate the anti-obesity effects of yogurt fermented by Lactobacillus plantarum Q180 in diet-induced obese rats. To examine the effects, male Sprague-Dawley rats were fed on six different diets, as follows: Group A was fed an ND and orally administrated saline solution; Group B, an HFD and orally administrated saline solution; Group C, an HFD and orally administrated yogurt fermented by ABT-3 and L. plantarum Q180; Group D, an HFD and orally administrated yogurt with added Garcinia cambogia extract, fermented by ABT-3 and L. plantarum Q180; Group E, an HFD and orally administrated yogurt fermented by L. plantarum Q180; and Group F, an HFD and orally administrated yogurt with added Garcinia cambogia extract, fermented by L. plantarum Q180 for eight weeks. After eight weeks, the rate of increase in bodyweight was 5.14%, 6.5%, 3.35% and 10.81% lower in groups C, D, E and F, respectively, compared with group B; the epididymal fat weight of groups E and F was significantly lower than that of group B; and the level of triglyceride and leptin was significantly reduced in groups C, D, E and F compared to group B. In addition, the level of AST was reduced in group C compared to the other groups. To examine the effects of yogurt on the reduction of adipocyte size, the adipocyte sizes were measured. The number of large-size adipose tissue was less distributed in groups A, C, D, E and F than in group B. PMID:27499667

  15. Use of a truss to maintain inguinal hernia reduction in a very low birth weight infant.

    PubMed

    Ruderman, J W; Schick, J B; Sherman, M; Reagan, Y; Hanks, G; Weitzman, J J

    1995-01-01

    Trusses are not usually used in management of inguinal hernia of the very low birth weight infant. A potential benefit of this therapy is maintenance of hernia reduction, thus delaying operative repair until the infant is larger and healthier. We designed a safe and effective truss with supplies found in most neonatal intensive care units. PMID:7595774

  16. 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…

  17. 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…

  18. 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…

  19. The development of a rating scale for the prediction of success in weight reduction.

    PubMed

    Dash, J D; Brown, R A

    1977-07-01

    A valid and reliable rating instrument was developed that has predictive value with regard to the ability to lose weight. The major constructs that the test was intended to measure were knowledge of the pragmatics of weight reduction and obesity and the role of fantasy in weight loss. Test items were drawn from research findings in the obesity literature and from subject matter experts in the fields of nutrition, internal medicine and clinical psychology. Test-retest reliability coefficients for the new instrument range from .64 to .95. Construct validity was ascertained through administration of the scale to groups of high school students (N=20), college nutrition students (N=30) and successful and unsuccessful dieters (Ns=28 and 20, respectively). It appears that the scale, The Dash-Brown Survey of Fact and Fiction in Weight Reduction (DBS), may be employed usefully to assess the remediability of obesity for potential dieters. The data further suggest that cognitive awareness of diet-related issues is significant in weight reduction. PMID:893707

  20. 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

    2014-01-01

    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

  1. 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

  2. Inhibition of hypothalamic Foxo1 expression reduced food intake in diet-induced obesity rats

    PubMed Central

    Ropelle, Eduardo R; Pauli, José R; Prada, Patrícia; Cintra, Dennys E; Rocha, Guilherme Z; Moraes, Juliana C; Frederico, Marisa J S; da Luz, Gabrielle; Pinho, Ricardo A; Carvalheira, José B C; Velloso, Licio A; Saad, Mario A; De Souza, Cláudio T

    2009-01-01

    Insulin signalling in the hypothalamus plays a role in maintaining body weight. The forkhead transcription factor Foxo1 is an important mediator of insulin signalling in the hypothalamus. Foxo1 stimulates the transcription of the orexigenic neuropeptide Y and Agouti-related protein through the phosphatidylinositol-3-kinase/Akt signalling pathway, but the role of hypothalamic Foxo1 in insulin resistance and obesity remains unclear. Here, we identify that a high-fat diet impaired insulin-induced hypothalamic Foxo1 phosphorylation and degradation, increasing the nuclear Foxo1 activity and hyperphagic response in rats. Thus, we investigated the effects of the intracerebroventricular (i.c.v.) microinfusion of Foxo1-antisense oligonucleotide (Foxo1-ASO) and evaluated the food consumption and weight gain in normal and diet-induced obese (DIO) rats. Three days of Foxo1-ASO microinfusion reduced the hypothalamic Foxo1 expression by about 85%. i.c.v. infusion of Foxo1-ASO reduced the cumulative food intake (21%), body weight change (28%), epididymal fat pad weight (22%) and fasting serum insulin levels (19%) and increased the insulin sensitivity (34%) in DIO but not in control animals. Collectively, these data showed that the Foxo1-ASO treatment blocked the orexigenic effects of Foxo1 and prevented the hyperphagic response in obese rats. Thus, pharmacological manipulation of Foxo1 may be used to prevent or treat obesity. PMID:19332486

  3. Diet-Induced Obesity in the Selenocysteine Lyase Knockout Mouse

    PubMed Central

    Gilman, Christy L.; Hashimoto, Ann C.; Ogawa-Wong, Ashley N.; Berry, Marla J.

    2015-01-01

    Abstract Aims: Selenocysteine lyase (Scly) mediates selenocysteine decomposition. It was previously demonstrated that, upon adequate caloric intake (12% kcal fat) and selenium deficiency, disruption of Scly in mice leads to development of metabolic syndrome. In this study, we investigate the effect of a high-fat (45% kcal) selenium-adequate diet in Scly knockout (KO) mice on development of metabolic syndrome. Involvement of selenoproteins in energy metabolism after Scly disruption was also examined in vitro in the murine hepatoma cell line, Hepa1-6, following palmitate treatment. Results: Scly KO mice were more susceptible to diet-induced obesity than their wild-type counterparts after feeding a high-fat selenium-adequate diet. Scly KO mice had aggravated hyperinsulinemia, hypercholesterolemia, glucose, and insulin intolerance, but unchanged inflammatory cytokines and expression of most selenoproteins, except increased serum selenoprotein P (Sepp1). Scly KO mice also exhibited enhanced hepatic levels of pyruvate and enzymes involved in the regulation of pyruvate cycling, such as pyruvate carboxylase (Pcx) and pyruvate dehydrogenase (Pdh). However, in vitro silencing of Scly in Hepa1-6 cells led to diminished Sepp1 expression, and concomitant palmitate treatment decreased Pdh expression. Innovation: The role of selenium in lipid metabolism is recognized, but specific selenium-dependent mechanisms leading to obesity are unclear. This study uncovers that Scly has a remarkable effect on obesity and metabolic syndrome development triggered by high-fat exposure, independent of the expression of most selenoproteins. Conclusion: Diet-induced obesity in Scly KO mice is aggravated, with effects on pyruvate levels and consequent activation of energy metabolism independent of selenoprotein levels. Antioxid. Redox Signal. 23, 761–774. PMID:26192035

  4. Overexpression of lecithin:cholesterol acyltransferase in transgenic rabbits prevents diet-induced atherosclerosis.

    PubMed Central

    Hoeg, J M; Santamarina-Fojo, S; Bérard, A M; Cornhill, J F; Herderick, E E; Feldman, S H; Haudenschild, C C; Vaisman, B L; Hoyt, R F; Demosky, S J; Kauffman, R D; Hazel, C M; Marcovina, S M; Brewer, H B

    1996-01-01

    Lecithin:cholesterol acyltransferase (LCAT) is a key plasma enzyme in cholesterol and high density lipoprotein (HDL) metabolism. Transgenic rabbits overexpressing human LCAT had 15-fold greater plasma LCAT activity that nontransgenic control rabbits. This degree of overexpression was associated with a 6.7-fold increase in the plasma HDL cholesterol concentration in LCAT transgenic rabbits. On a 0.3% cholesterol diet, the HDL cholesterol concentrations increased from 24 +/- 1 to 39 +/- 3 mg/dl in nontransgenic control rabbits (n = 10; P < 0.05) and increased from 161 +/- 5 to 200 +/- 21 mg/dl (P < 0.001) in the LCAT transgenic rabbits (n = 9). Although the baseline non-HDL concentrations of control (4 +/- 3 mg/dl) and transgenic rabbits (18 +/- 4 mg/dl) were similar, the cholesterol-rich diet raised the non-HDL cholesterol concentrations, reflecting the atherogenic very low density, intermediate density, and low density lipoprotein particles observed by gel filtration chromatography. The non-HDL cholesterol rose to 509 +/- 57 mg/dl in controls compared with only 196 +/- 14 mg/dl in the LCAT transgenic rabbits (P < 0.005). The differences in the plasma lipoprotein response to a cholesterol-rich diet observed in the transgenic rabbits paralleled the susceptibility to developing aortic atherosclerosis. Compared with nontransgenic controls, LCAT transgenic rabbits were protected from diet-induced atherosclerosis with significant reductions determined by both quantitative planimetry (-86%; P < 0.003) and quantitative immunohistochemistry (-93%; P < 0.009). Our results establish the importance of LCAT in the metabolism of both HDL and apolipoprotein B-containing lipoprotein particles with cholesterol feeding and the response to diet-induced atherosclerosis. In addition, these findings identify LCAT as a new target for therapy to prevent atherosclerosis. Images Fig. 2 Fig. 3 Fig. 4 PMID:8876155

  5. 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

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

    PubMed

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

    2016-06-01

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

  7. 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

  8. 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

  9. 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. PMID:25997557

  10. 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. PMID:22878390

  11. 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

  12. [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. PMID:9333508

  13. Fuel Consumption Reduction and Weight Estimate of an Intercooled-Recuperated Turboprop Engine

    NASA Astrophysics Data System (ADS)

    Andriani, Roberto; Ghezzi, Umberto; Ingenito, Antonella; Gamma, Fausto

    2012-09-01

    The introduction of intercooling and regeneration in a gas turbine engine can lead to performance improvement and fuel consumption reduction. Moreover, as first consequence of the saved fuel, also the pollutant emission can be greatly reduced. Turboprop seems to be the most suitable gas turbine engine to be equipped with intercooler and heat recuperator thanks to the relatively small mass flow rate and the small propulsion power fraction due to the exhaust nozzle. However, the extra weight and drag due to the heat exchangers must be carefully considered. An intercooled-recuperated turboprop engine is studied by means of a thermodynamic numeric code that, computing the thermal cycle, simulates the engine behavior at different operating conditions. The main aero engine performances, as specific power and specific fuel consumption, are then evaluated from the cycle analysis. The saved fuel, the pollution reduction, and the engine weight are then estimated for an example case.

  14. 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

  15. 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. PMID:22506803

  16. 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

  17. 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.

  18. 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.

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

    PubMed

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

    PubMed

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

    2011-05-01

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

  1. Antiobesity effect of Safoof Mohazzil, a polyherbal formulation, in cafeteria diet induced obesity in rats.

    PubMed

    Gupta, Pooja; Mehla, Jogender; Gupta, Yogendra Kumar

    2012-11-01

    Obesity is reaching epidemic proportions all over the world yet it lacks adequate treatment. Most of the drugs have failed either due to ineffectiveness or adverse effects. Complementary and alternative system of medicine is being used since ancient times. However, many of them have not been tested for efficacy and safety using modern scientific methods. Therefore, the antiobesity effect of Safoof Mohazzil, a polyherbal formulation, was evaluated in cafeteria diet induced obesity in female Sprague Dawley rats. Animals weighing 100-150 g were divided into four groups (n = 8) i.e. standard pellet diet, cafeteria diet control, cafeteria diet + Safoof Mohazzil and standard pellet diet plus Safoof Mohazzil. The formulation was administered orally at a dose of 1 g/kg/day for 14 weeks. At the end of study, cafeteria diet significantly increased body weight, Lee's index, lipid profile (cholesterol and triglycerides), insulin and leptin levels as compared to standard pellet diet control group. Fourteen week treatment with Safoof Mohazzil significantly prevented the increase in body weight, Lee's index, lipid profile, insulin and leptin levels as compared to cafeteria diet control group without affecting food and water intake. Safoof Mohazzil had no adverse effect on hepatic transaminases, locomotor activity and motor coordination. The study provides evidence for antiobesity effect of Safoof Mohazzil. PMID:23305028

  2. 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

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

    PubMed

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

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

  4. 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

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

    PubMed

    Ma, Yongjie; Gao, Mingming; Liu, Dexi

    2016-01-01

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

  6. 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

  7. Meta-chlorophenylpiperazine enhances leptin sensitivity in diet-induced obese mice

    PubMed Central

    Yan, Chunling; Yang, Yongjie; Saito, Kenji; Xu, Pingwen; Wang, Chunmei; Hinton Jr, Antentor Othrell; Yan, Xiaofeng; Wu, Qi; Tong, Qingchun; Elmquist, Joel K; Fukuda, Makoto; Xu, Yong

    2015-01-01

    Background and Purpose Most forms of human obesity are characterized by impaired leptin sensitivity and, therefore, the effectiveness of anti-obesity leptin therapy in these leptin-resistant obese patients is marginal. Hence, the development of strategies to increase leptin sensitivity is of high priority in the field of obesity research. Experimental Approach We first examined the effects of co-administration of leptin and meta-chlorophenylpiperazine (mCPP), an agonist of 5-HT2C and 5-HT1B receptors, on energy balance in leptin-resistant diet-induced obese (DIO) mice. We further assessed leptin-induced phosphorylation of the STAT-3 (pSTAT3) in various brain regions of DIO mice pretreated with mCPP or in mice genetically lacking 5-HT2C receptors. Results Co-administration of mCPP with leptin had an additive effect on reducing body weight in DIO mice. Furthermore, mCPP pretreatment in DIO mice enhanced leptin-induced pSTAT3 in the arcuate nucleus, the ventromedial hypothalamic nucleus, and the ventral premammillary nucleus. Finally, deletion of 5-HT2C receptors significantly blunted leptin-induced pSTAT3 in these same hypothalamic regions. Conclusions and Implications Our study provides evidence that drugs, which activate 5-HT2C receptors, could function as leptin sensitizers and be used in combination with leptin to provide additional weight loss in DIO. PMID:25817043

  8. 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

  9. 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

  10. Retrospective Long-Term Comparison of Naturopathic Fasting Therapy and Weight Reduction Diet in Overweight Patients

    PubMed Central

    Ismar, Lena Elisabeth; Wessely, Dominik Karl; Pötschke, Tanja; Weidner, Beate; Wiebelitz, Karl Rüdiger

    2014-01-01

    In a follow-up study overweight and obese patients fasting according to Buchinger (modified) and a control group treated by a weight reduction diet in the context of an inpatient naturopathic complex treatment were compared using a questionnaire developed for a standardized phone interview 6.8 ± 1.1 years after inpatient treatment. During the inpatient treatment the fasting patients significantly more body weight, but at the time of the interview significantly more weight was gained again. 10.7% of the fasting patients and 31.9% of the control group lowered their weight at least 5% of their initial weight up to the interview. 42% of the fasting and 74% of the control group persistently changed their diet. The control group followed a significantly higher number of trained nutritional aspects. 21% of the fasting and 40% of the control group increased their leisure activity permanently. Continued improvement in quality of life was achieved by 16% of the fasting patients and 28% of the control group. The fasting therapy, carried out as part of the inpatient naturopathic complex treatment, turned out to be less suitable for the treatment of overweight and obesity compared to standard therapy. One likely determinant is the minor poststationary lifestyle modification. PMID:25126098

  11. Ketogenesis prevents diet-induced fatty liver injury and hyperglycemia

    PubMed Central

    Cotter, David G.; Ercal, Baris; Huang, Xiaojing; Leid, Jamison M.; d’Avignon, D. André; Graham, Mark J.; Dietzen, Dennis J.; Brunt, Elizabeth M.; Patti, Gary J.; Crawford, Peter A.

    2014-01-01

    Nonalcoholic fatty liver disease (NAFLD) spectrum disorders affect approximately 1 billion individuals worldwide. However, the drivers of progressive steatohepatitis remain incompletely defined. Ketogenesis can dispose of much of the fat that enters the liver, and dysfunction in this pathway could promote the development of NAFLD. Here, we evaluated mice lacking mitochondrial 3-hydroxymethylglutaryl CoA synthase (HMGCS2) to determine the role of ketogenesis in preventing diet-induced steatohepatitis. Antisense oligonucleotide–induced loss of HMGCS2 in chow-fed adult mice caused mild hyperglycemia, increased hepatic gluconeogenesis from pyruvate, and augmented production of hundreds of hepatic metabolites, a suite of which indicated activation of the de novo lipogenesis pathway. High-fat diet feeding of mice with insufficient ketogenesis resulted in extensive hepatocyte injury and inflammation, decreased glycemia, deranged hepatic TCA cycle intermediate concentrations, and impaired hepatic gluconeogenesis due to sequestration of free coenzyme A (CoASH). Supplementation of the CoASH precursors pantothenic acid and cysteine normalized TCA intermediates and gluconeogenesis in the livers of ketogenesis-insufficient animals. Together, these findings indicate that ketogenesis is a critical regulator of hepatic acyl-CoA metabolism, glucose metabolism, and TCA cycle function in the absorptive state and suggest that ketogenesis may modulate fatty liver disease. PMID:25347470

  12. 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

  13. Inhibiting myostatin signaling prevents femoral trabecular bone loss and microarchitecture deterioration in diet-induced obese rats.

    PubMed

    Tang, Liang; Yang, Xiaoying; Gao, Xiaohang; Du, Haiping; Han, Yanqi; Zhang, Didi; Wang, Zhiyuan; Sun, Lijun

    2016-02-01

    Besides resulting in a dramatic increase in skeletal muscle mass, myostatin (MSTN) deficiency has a positive effect on bone formation. However, the issue about whether blocking MSTN can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of MSTN blocking on bone quality in high-fat (HF), diet-induced obese rats using a prepared polyclonal antibody for MSTN (MsAb). Twenty-four rats were randomly assigned to the Control, HF and HF + MsAb groups. Rats in the HF + MsAb group were injected once a week with purified MsAb for eight weeks. The results showed that MsAb significantly reduced body and fat weight, and increased muscle mass and strength in the HF group. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by MsAb treatment, as evidenced by increased 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 MsAb treatment had an impact on femoral biomechanical properties including maximum load, stiffness, energy absorption and elastic modulus. Moreover, MsAb significantly increased adiponectin concentrations, and decreased TNF-α and IL-6 levels in diet-induced obese rats. Taken together, blocking MSTN by MsAb improves bone quality in diet-induced obese rats through a mechanotransduction pathway from skeletal muscle, and the accompanying changes occurring in the levels of circulating adipokines and pro-inflammatory cytokines may also be involved in this process. It indicates that the administration of MSTN antagonists may be a promising therapy for treating obesity and obesity-induced bone loss. PMID:26438721

  14. β-Catenin Links Hepatic Metabolic Zonation with Lipid Metabolism and Diet-Induced Obesity in Mice

    PubMed Central

    Behari, Jaideep; Li, Huanan; Liu, Shiguang; Stefanovic-Racic, Maja; Alonso, Laura; O'Donnell, Christopher P.; Shiva, Sruti; Singamsetty, Srikanth; Watanabe, Yoshio; Singh, Vijay P.; Liu, Qing

    2015-01-01

    β-catenin regulates the establishment of hepatic metabolic zonation. To elucidate the functional significance of liver metabolic zonation in the chronically overfed state in vivo, we fed a high-fat diet (HFD) to hepatocyte-specific β-catenin transgenic (TG) and knockout (KO) mice. Chow-fed TG and KO mice had normal liver histologic findings and body weight. However, HFD-fed TG mice developed prominent perivenous steatosis with periportal sparing. In contrast, HFD-fed KO mice had increased lobular inflammation and hepatocyte apoptosis. HFD-fed TG mice rapidly developed diet-induced obesity and systemic insulin resistance, but KO mice were resistant to diet-induced obesity. However, β-catenin did not directly affect hepatic insulin signaling, suggesting that the metabolic effects of β-catenin occurred via a parallel pathway. Hepatic expression of key glycolytic and lipogenic genes was higher in HFD-fed TG and lower in KO mice compared with wild-type mice. KO mice also exhibited defective hepatic fatty acid oxidation and fasting ketogenesis. Hepatic levels of hypoxia inducible factor-1α, an oxygen-sensitive transcriptional regulator of glycolysis and a known β-catenin binding partner, were higher in HFD-fed TG and lower in KO mice. KO mice had attenuated perivenous hypoxia, suggesting disruption of the normal sinusoidal oxygen gradient, a major determinant of liver carbohydrate and liver metabolism. Canonical Wnt signaling in hepatocytes is essential for the development of diet-induced fatty liver and obesity. PMID:25300578

  15. Initial Response to Program, Program Participation, and Weight Reduction Among 375 MOVE! Participants, Augusta, Georgia, 2008–2010

    PubMed Central

    Hardy, Dale; Xu, Hongyan

    2016-01-01

    Introduction Obesity management guidelines specify initial goals for participation and weight reduction for the first 6 months of a weight-reduction intervention, but guidelines do not specify when to assess early response and make adjustments. We aimed to determine whether very early or early weight reduction in the weight-reduction program MOVE! predicted later participation or achievement of weight-reduction goals. Methods Using clinical data from 375 MOVE! participants enrolled from July 2008 through May 2010, we examined program participation and weight reduction. Very early response was defined as achieving a weight reduction of 0.5% or more at week 2, and early response was defined as achieving weight reduction of 1.0% or more at week 4. Success, or achievement of weight-reduction goal, at 6 months, 1 year, and 2 years was defined as a weight reduction of 5% or more. Participation was assessed according to the number of sessions attended within the first 6 months of program enrollment; attendance of 14 or more sessions was classified as high-intensity participation. Results Very early responders were more than 5 times as likely (odds ratio [OR] = 5.46; 95% confidence interval [CI], 1.69–17.71; P = .005) and early responders were more than 10 times as likely (OR = 10.76; 95% CI, 2.64–43.80; P = .001) to achieve the 6-month weight-reduction goal as participants who were not very early responders or early responders, respectively. Early responders were almost 7 times as likely to achieve the 1-year weight-reduction goal (OR = 6.96; 95% CI, 1.85–26.13; P = .004). Neither very early nor early response predicted participation, high-intensity participation, or success at 2 years. Conclusion This research supports the predictive value of very early response and early response to MOVE! on weight-reduction success at 6 months; early response also predicted 1-year success, suggesting that the 2-week point may be an ideal time to assess initial response and make

  16. Alcohol-free fermented blueberry-blackberry beverage phenolic extract attenuates diet-induced obesity and blood glucose in C57BL/6J mice.

    PubMed

    Johnson, Michelle H; Wallig, Matthew; Luna Vital, Diego A; de Mejia, Elvira G

    2016-05-01

    The aim of this study was to determine the potential of phenolic compounds from a fermented blackberry-blueberry beverage to reduce diet-induced obesity and hyperglycemia in mice fed a 60% high-fat diet (HFD) for 10weeks after 1week of pretreatment. C57BL/6J mice were randomized into six groups and allowed to drink (ad libitum) an alcohol-free blackberry-blueberry beverage [alcohol-free fermented beverage (AFFB), 8.4mg anthocyanin (ANC)/kg body weight (BW)/day]; three doses of a phenolic extract [postamberlite extract (PAE)] from AFFB at 0.1×, 1× and 2× ANC concentrations; sitagliptin (hypoglycemic positive control); or water (negative control). Weight and fat mass gain were attenuated in mice receiving the highest doses of PAE (18.9mg ANC/kg BW/day, P<.05). There were also reductions (P<.05) in percent fat mass, epididymal fat pad weights, mean adipocyte diameters and plasma triglycerides and cholesterol associated with PAE treatments. By the end of the study, fasting blood glucose for mice receiving 9mg (1×) or 18.9mg (2×) ANC/kg BW/day was significantly lower than in the water and the sitagliptin groups (P<.05). Histological and histochemical analyses revealed an unexpected change in liver of mice fed ANC at 1× or 2× doses consisting of liver enlargement and increased lipid deposition. PAE also induced the most differential gene expression changes, including highly significant downstream effects at all doses to reduce d-glucose concentrations. Overall, phenolic compounds from the fermented blueberry-blackberry beverage had an impact to attenuate the development of obesity and fasting blood glucose in C57BL/6J mice. PMID:27133423

  17. Effect of Acupuncture on Body Weight Reduction and Inflammatory Mediators in Egyptian Obese Patients

    PubMed Central

    Ismail, Laila Ahmed Abou; Ibrahim, Alshaymaa Ahmed; Abdel-Latif, Ghada A.; El-Haleem, Dalia Adel Abd; Helmy, Ghada; Labib, Lylah M.; El-Masry, M. Kadry

    2015-01-01

    AIM: Aim of this study was to examine the effectiveness of body acupuncture on body weight loss, routine laboratory tests and pro-inflammatory markers. METHODOLOGY: The study was performed on eighty obese patients. They were divided into three groups according to their body mass index. Subjects received acupuncture for three- six months in combination with a low-calorie diet. They were assessed pre and post acupuncture, by anthropometric measurement, routine laboratory tests and, tumor necrosis factor- alpha (TNF-α), interleukin- 6 (IL-6), and high sensitivity C-reactive protein (hsCRP) levels in serum. RESULTS: The pre-acupuncture results showed significant difference between the three grades of obesity and the controls regarding TNFα, IL-6 and hsCRP. We found significant reduction in anthropometric measurement of adiposity after acupuncture. In comparing the pre &post acupuncture results of TNF-α, IL-6 and hsCRP showed high significant reduction after acupuncture. There are highly significant decrease in kidney function (creatinine and uric acid) and lipid profile (cholesterol and triglycerides) and fasting blood glucose, but there was no significant difference in urea, SGPT, SGOT, HDL and LDL. CONCLUSION: Body acupuncture in combination with diet restriction was found to be effective for weight loss and also reduction of the inflammatory reactions. Acupuncture could be used as a synergistic treatment option for obesity control.

  18. Female mice target deleted for the neuromedin B receptor have partial resistance to diet-induced obesity.

    PubMed

    Paula, Gabriela Silva Monteiro; Souza, Luana Lopes; Cabanelas, Adriana; Bloise, Flavia Fonseca; Mello-Coelho, Valéria; Wada, Etsuko; Ortiga-Carvalho, Tania Maria; Oliveira, Karen Jesus; Pazos-Moura, Carmen Cabanelas

    2010-05-01

    Previous studies have proposed a role for neuromedin B (NB), a bombesin-like peptide, in the control of body weight homeostasis. However, the nature of this role is unclear. The actions of NB are mediated preferentially by NB-preferring receptors (NBRs). Here we examined the consequences of targeted deletion of NBRs in female mice on body weight homeostasis in mice fed a normolipid diet (ND) or a high-fat diet (HFD) for 13 weeks. Body weight and food ingestion of neuromedin B receptor knockout (NBR-KO) mice fed a normolipid diet showed no difference in relation to wild-type (WT). However, the high-fat diet induced an 8.9- and 4.8-fold increase in body weight of WT and NBR-KO, respectively, compared to their controls maintained with a normolipid diet, even though the mice ingested the same amount of calories, regardless of genotype. Comparing mice fed the high-fat diet, NBR-KO mice accumulated approximately 45% less fat depot mass than WT, exhibited a lower percentage of fat in their carcasses (19.2 vs. 31.3%), and their adipocytes were less hypertrophied. Serum leptin and leptin mRNA in inguinal and perigonadal fat were lower in HFD NBR-KO than HFD WT, and serum adiponectin was similar among HFD groups and unaltered in comparison to ND-fed mice. HFD-fed WT mice developed glucose intolerance but not the HFD-fed NBR-KO mice, although they had similar glycaemia and insulinaemia. NBR-KO and WT mice on the normolipid diet showed no differences in any parameters, except for a trend to lower insulin levels. Therefore, disruption of the neuromedin B receptor pathway did not change body weight homeostasis in female mice fed a normolipid diet; however, it did result in partial resistance to diet-induced obesity. PMID:20211980

  19. Female mice target deleted for the neuromedin B receptor have partial resistance to diet-induced obesity

    PubMed Central

    Paula, Gabriela Silva Monteiro; Souza, Luana Lopes; Cabanelas, Adriana; Bloise, Flavia Fonseca; Mello-Coelho, Valéria; Wada, Etsuko; Ortiga-Carvalho, Tania Maria; Oliveira, Karen Jesus; Pazos-Moura, Carmen Cabanelas

    2010-01-01

    Previous studies have proposed a role for neuromedin B (NB), a bombesin-like peptide, in the control of body weight homeostasis. However, the nature of this role is unclear. The actions of NB are mediated preferentially by NB-preferring receptors (NBRs). Here we examined the consequences of targeted deletion of NBRs in female mice on body weight homeostasis in mice fed a normolipid diet (ND) or a high-fat diet (HFD) for 13 weeks. Body weight and food ingestion of neuromedin B receptor knockout (NBR-KO) mice fed a normolipid diet showed no difference in relation to wild-type (WT). However, the high-fat diet induced an 8.9- and 4.8-fold increase in body weight of WT and NBR-KO, respectively, compared to their controls maintained with a normolipid diet, even though the mice ingested the same amount of calories, regardless of genotype. Comparing mice fed the high-fat diet, NBR-KO mice accumulated approximately 45% less fat depot mass than WT, exhibited a lower percentage of fat in their carcasses (19.2 vs. 31.3%), and their adipocytes were less hypertrophied. Serum leptin and leptin mRNA in inguinal and perigonadal fat were lower in HFD NBR-KO than HFD WT, and serum adiponectin was similar among HFD groups and unaltered in comparison to ND-fed mice. HFD-fed WT mice developed glucose intolerance but not the HFD-fed NBR-KO mice, although they had similar glycaemia and insulinaemia. NBR-KO and WT mice on the normolipid diet showed no differences in any parameters, except for a trend to lower insulin levels. Therefore, disruption of the neuromedin B receptor pathway did not change body weight homeostasis in female mice fed a normolipid diet; however, it did result in partial resistance to diet-induced obesity. PMID:20211980

  20. A model for determining total ketogenic ratio (TKR) for evaluating the ketogenic property of a weight-reduction diet.

    PubMed

    Cohen, I A

    2009-09-01

    Ketogenic weight-reduction dieting methods have existed since antiquity. Recent research has demonstrated their value in controlling type 2 diabetes. Although research done in the 1920s provided a mathematical model of non-weight-reduction ketogenic clinical diets using the concept of a ketogenic ratio (KR), little has been done to evaluate the ketogenic nature of purported ketogenic weight-reduction diets. The mathematical model of Woodyatt is valid only under isocaloric conditions where dietary energy intake is balanced by energy use. It is hypothesised that under certain conditions of weight loss, energy deficit can predict utilization of stored lipid so that a modified formula for total ketogenic ratio (TKR) may be derived. Such a predictive mathematical model may be a useful tool in predicting the efficacy of weight-reduction diets and adapting such diets to individual patient needs. PMID:19410378

  1. Personalized Weight Management Interventions for Cardiovascular Risk Reduction: A Viable Option for African-American Women.

    PubMed

    Franklin, Nina C; Arena, Ross

    2016-01-01

    Obesity is an independent contributor to cardiovascular disease (CVD) and a major driving force behind racial/ethnic and gender disparities in risk. Due to a multitude of interrelating factors (i.e., personal, social, cultural, economic and environmental), African-American (AA) women are disproportionately obese and twice as likely to succumb to CVD, yet they are significantly underrepresented in behavioral weight management interventions. In this selective review we highlight components of the limited interventions shown to enhance weight loss outcomes in this population and make a case for leveraging Web-based technology and artificial intelligence techniques to deliver personalized programs aimed at obesity treatment and CVD risk reduction. Although many of the approaches discussed are generally applicable across populations burdened by disparate rates of obesity and CVD, we specifically focus on AA women due to the disproportionate impact of these non-communicable diseases and the general paucity of interventions targeted to this high-risk group. PMID:26908050

  2. Acupoint Stimulation on Weight Reduction for Obesity: A Randomized Sham-Controlled Study.

    PubMed

    Yeh, Mei-Ling; Chu, Nain-Feng; Hsu, Man-Ying F; Hsu, Chin-Che; Chung, Yu-Chu

    2015-12-01

    Auricular acupoint stimulation has become a popular weight loss method. However, its efficacy for obesity treatment has not been fully studied. This study aimed to investigate the effect of a 10-week intervention of auricular electrical stimulation combined with auricular acupressure on weight reduction in obese outpatients. In this single-blind randomized sham-controlled study, 134 participants were randomly assigned to an experimental group receiving stimulation at true acupoints, or a sham group receiving stimulation delivered in the same manner but at sham acupoints. Each participant received nutrition counseling by a nutritionist weekly. The results showed significant differences in body mass index, blood pressure, total cholesterol, triglyceride, and leptin or adiponectin over time within the group, but not between the groups. This study could not exclude the effect of placebo and dietary consultation. Further study that adds a control group receiving no treatment is therefore needed to confirm the effects of auricular acupressure. PMID:25183702

  3. 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

  4. Verification of the history-score moment equations for weight-window variance reduction

    SciTech Connect

    Solomon, Clell J; Sood, Avneet; Booth, Thomas E; Shultis, J. Kenneth

    2010-12-06

    The history-score moment equations that describe the moments of a Monte Carlo score distribution have been extended to weight-window variance reduction, The resulting equations have been solved deterministically to calculate the population variance of the Monte Carlo score distribution for a single tally, Results for one- and two-dimensional one-group problems are presented that predict the population variances to less than 1% deviation from the Monte Carlo for one-dimensional problems and between 1- 2% for two-dimensional problems,

  5. 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.

  6. Size, weight, and power reduction regimes in achromatic gradient-index singlets.

    PubMed

    Campbell, Sawyer D; Brocker, Donovan E; Nagar, Jogender; Werner, Douglas H

    2016-05-01

    By analyzing the limitations that achromatic gradient-index (GRIN) lens solutions in the radial and axial extremes place on lens thickness and surface curvature, a radial-axial hybrid GRIN theory is developed in order to overcome these restrictions and expose a larger solution space. With the achromatic hybrid GRIN theory, the trade-offs between thickness, curvature, and GRIN type can be directly studied in the context of size, weight, and power (SWaP) reduction. Finally, the achromatic solution space of a silicon-germanium-based material system is explored, and several designs are verified with ray tracing. PMID:27140376

  7. Diet-induced obesity attenuates endotoxin-induced cognitive deficits

    PubMed Central

    Setti, Sharay E.; Littlefield, Alyssa M.; Johnson, Samantha W.; Kohman, Rachel A.

    2015-01-01

    Activation of the immune system can impair cognitive function, particularly on hippocampus dependent tasks. Several factors such as normal aging and prenatal experiences can modify the severity of these cognitive deficits. One additional factor that may modulate the behavioral response to immune activation is obesity. Prior work has shown that obesity alters the activity of the immune system. Whether diet-induced obesity (DIO) influences the cognitive deficits associated with inflammation is currently unknown. The present study explored whether DIO alters the behavioral response to the bacterial endotoxin, lipopolysaccharide (LPS). Female C57BL/6J mice were fed a high-fat (60% fat) or control diet (10% fat) for a total of five months. After consuming their respective diets for four months, mice received an LPS or saline injection and were assessed for alterations in spatial learning. One month later, mice received a second injection of LPS or saline and tissue samples were collected to assess the inflammatory response within the periphery and central nervous system (CNS). Results showed that LPS administration impaired spatial learning in the control diet mice, but had no effect in DIO mice. This lack of a cognitive deficit in the DIO female mice is likely due to a blunted inflammatory response within the brain. While cytokine production within the periphery (i.e., plasma, adipose, and spleen) was similar between the DIO and control mice, the DIO mice failed to show an increase in IL-6 and CD74 in the brain following LPS administration. Collectively, these data indicate that DIO can reduce aspects of the neuroinflammatory response as well as blunt the behavioral reaction to an immune challenge. PMID:25542778

  8. CD47 Deficiency Protects Mice From Diet-induced Obesity and Improves Whole Body Glucose Tolerance and Insulin Sensitivity

    PubMed Central

    Maimaitiyiming, Hasiyeti; Norman, Heather; Zhou, Qi; Wang, Shuxia

    2015-01-01

    CD47 is a transmembrane protein with several functions including self-recognition, immune cell communication, and cell signaling. Although it has been extensively studied in cancer and ischemia, CD47 function in obesity has never been explored. In this study, we utilized CD47 deficient mice in a high-fat diet induced obesity model to study for the first time whether CD47 plays a role in the development of obesity and metabolic complications. Male CD47 deficient and wild type (WT) control mice were fed with either low fat (LF) or high fat (HF) diets for 16 weeks. Interestingly, we found that CD47 deficient mice were protected from HF diet-induced obesity displaying decreased weight gain and reduced adiposity. This led to decreased MCP1/CCR2 dependent macrophage infiltration into adipose tissue and reduced inflammation, resulting in improved glucose tolerance and insulin sensitivity. In addition, CD47 deficiency stimulated the expression of UCP1 and carnitine palmitoyltransferase 1b (CPT1b) levels in brown adipose tissue, leading to increased lipid utilization and heat production. This contributes to the increased energy utilization and reduced adiposity observed in these mice. Taken together, these data revealed a novel role for CD47 in the development of obesity and its related metabolic complications. PMID:25747123

  9. 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. PMID:26914024

  10. 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

  11. Transcriptome analysis of anti-fatty liver action by Campari tomato using a zebrafish diet-induced obesity model

    PubMed Central

    2011-01-01

    Background High dietary intake of vegetable products is beneficial against obesity and its related diseases such as dyslipidemia, nonalcoholic fatty liver disease, and cancer. We previously developed a diet-induced obesity model of zebrafish (DIO-zebrafish) that develops visceral adiposity, dyslipidemia, and liver steatosis. Zebrafish is a polyphagous animal; thus we hypothesized that DIO-zebrafish could be used for transcriptome analysis of anti-obesity effects of vegetables. Results Each vegetable exhibited different effects against obesity. We focused on "Campari" tomato, which suppressed increase of body weight, plasma TG, and lipid droplets in livers of DIO-zebrafish. Campari tomato decreased srebf1 mRNA by increase of foxo1 gene expression, which may depend on high contents of β-carotene in this strain. Conclusions Campari tomato ameliorates diet-induced obesity, especially dyslipidemia and liver steatosis via downregulation of gene expression related to lipogenesis. DIO-zebrafish can discriminate the anti-obesity effects of different strains of vegetables, and will become a powerful tool to assess outcomes and find novel mechanisms of anti-obesity effects of natural products. PMID:22152339

  12. Weight and blood pressure reduction among participants engaged in a cancer awareness and prevention program

    PubMed Central

    Carter, Vivian L.; Dawkins, Norma L.; Howard, Barbara

    2015-01-01

    Objectives African–Americans consume a diet high in fat, salt and sugar; such dietary habits increase the risks of cancer and other chronic diseases. The objective of this study was to engage rural communities in a nutrition and physical activity behavior modification program to promote cancer awareness and risk reduction. Methods Focus group discussions were conducted to generate information for the development of a nutrition and physical activity program. African Americans (N = 62) from two rural counties (Bullock and Macon) in Alabama participated in a year-long intervention program in 2012 and 2013. Weight loss and blood pressure were evaluated to measure the impact of the intervention. Results Themes emerged for the focus group discussions were: nutrition, health, family, environment, and resource access. In Macon County participants lost weight irrespective of the exercise regimen, with those involved in floor exercise losing the most weight (− 22.4 lbs, or − 11.18% change), while in Bullock county walking was most effective in weight loss (6.1 lbs or − 3.40% change) p < 0.05. Systolic and diastolic pressure decreased from 5.3 to 10.5 mm Hg; − 2.0 to − 6.4 mm Hg, respectively, for Bullock county, except for the walking group. In Macon County, both systolic and diastolic pressure % change ranged from − 8.94 to 12.66 and − 5.34 to 12.66 mm Hg respectively, irrespective of physical activity respectively. Conclusion In this study, changes in weight lost and blood pressure were observed among individuals engaged in a nutrition education and physical activity program. PMID:26601053

  13. 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

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

    PubMed

    Kim, Sung-Bae; Kang, Ok-Hwa; 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

  15. Effects of diet-induced ketosis in rats with hypoglycaemia due to a serially transplantable insulinoma.

    PubMed

    Flatt, P R; Swanston-Flatt, S K; Snell, K; Tan, K S; Marks, V

    1987-01-01

    In view of the ability of ketones to partially replace glucose as an alternative fuel in the brain, the potential protective effects of diet-induced ketosis were examined in male NEDH rats with hypoglycaemia due to a serially transplantable radiation-induced insulinoma. Ketosis was induced by daily oral administration of medium chain triglycerides to normal rats and to insulinoma-bearing rats 1 day after subcutaneous subscapular implantation of tumours fragments. All rats treated with medium chain triglycerides became ketotic within 72 hours, and plasma 3-hydroxybutyrate concentrations remained 5-10 fold elevated at 24 days. Untreated insulinoma-bearing rats became moderately hyperinsuliaemic and hypoglycaemic by 17 days, with the later manifestation of more marked hyperinsulineamia (21.6 +/- 0.8 ng/ml, mean +/- SEM) severe hypoglycaemia (1.5 +/- 0.1 mmol/l) and death by 24-28 (26 +/- 1) days. Induction and maintenance of hyperketonaemia did not affect the development of hyperinsulineamia, hypoglycaemia or the exaggerated fall of plasma glucose produced by an 8 hour fast in these rats. However by day 21, the severity of hypoglycaemia was greater in insulinoma-bearing rats receiving medium chain triglycerides, culminating in accelerated death by 22-25 (23 +/- 1) days and an accompanying 50% decrease in final tumour weight. These results demonstrate that induction of ketosis in the face of marked hyperinsulinaemia did not afford protection against the profound hypoglycaemia produced by a serially transplantable rat insulinoma. PMID:2828127

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

    PubMed

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

    2016-01-01

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

  17. 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. PMID:21792359

  18. Liquid enteral diets induce bacterial translocation by increasing cecal flora without changing intestinal motility.

    PubMed

    Haskel, Y; Udassin, R; Freund, H R; Zhang, J M; Hanani, M

    2001-01-01

    The aim of this study was to determine the contribution of intestinal motility and cecal bacterial overgrowth to liquid diet-induced bacterial translocation (BT). Three different commercially available liquid diets were offered to mice for 1 week. BT to the mesenteric lymph nodes (MLN), spleen, and liver were examined as well as cecal bacterial counts and populations, small bowel length and weight, and histopathologic changes in the ileal and jejunal mucosa. In addition, the effect of the various diets on intestinal motility was measured by the transit index of a charcoal mixture introduced into the stomach. The incidence of BT to the mesenteric lymph nodes was significantly and similarly increased (p < .05) in mice fed Vivonex (30%), Ensure (30%), and Osmolite (33%) compared with chow-fed controls (0%). Compared with chow-fed controls, all three liquid diets were associated with the development of cecal bacterial overgrowth (p < .01). There were no significant changes in the transit index for the three liquid diet groups compared with the chow-fed controls. BT to the MLN was induced by all three liquid diets tested, casting some doubts as to their role in preventing BT in clinical use. BT was associated with a statistically significant increase in cecal bacterial count but was not associated with gut motility changes in this model. In fact, no significant changes in intestinal motility were noted in all groups tested. PMID:11284471

  19. 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. PMID:26911551

  20. 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. PMID:25436751

  1. 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

  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 412N or 34% of initial body weight reduced maximum knee compressive force by 824N 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 392N 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. PMID:26979878

  3. Acute exercise modulates the Foxo1/PGC-1α pathway in the liver of diet-induced obesity rats

    PubMed Central

    Ropelle, Eduardo R; Pauli, José R; Cintra, Dennys E; Frederico, Marisa J S; de Pinho, Ricardo A; Velloso, Lício A; De Souza, Cláudio T

    2009-01-01

    PGC-1α expression is a tissue-specific regulatory feature that is extremely relevant to diabetes. Several studies have shown that PGC-1α activity is atypically activated in the liver of diabetic rodents and contributes to hepatic glucose production. PGC-1α and Foxo1 can physically interact with one another and represent an important signal transduction pathway that governs the synthesis of glucose in the liver. However, the effect of physical activity on PGC-1α/Foxo1 association is unknown. Here we investigate the expression of PGC-1α and the association of PGC-1α/Foxo1 in the liver of diet-induced obese rats after acute exercise. Wistar rats swam for two 3 h-long bouts, separated by a 45 min rest period. Eight hours after the acute exercise protocol, the rats were submitted to an insulin tolerance test (ITT) and biochemical and molecular analysis. Results demonstrate that acute exercise improved insulin signalling, increasing insulin-stimulated Akt and Foxo1 phosphorylation and decreasing PGC-1α expression and PGC-1α/Foxo1 interaction in the liver of diet-induced obesity rats under fasting conditions. These phenomena are accompanied by a reduction in the expression of gluconeogenesis genes, such as phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphate (G6Pase). Thus, these results provide new insights into the mechanism by which exercise could improve fasting hyperglycaemia. PMID:19273580

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

    PubMed

    Temmerman, J C; Friedman, A N

    2013-01-01

    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. PMID:24247485

  5. Burst noise reduction of image by decimation and adaptive weighted median filter

    NASA Astrophysics Data System (ADS)

    Nakayama, Fumitaka; Meguro, Mitsuhiko; Hamada, Nozomu

    2000-12-01

    The removal of noise in image is one of the important issues, and useful as a preprocessing for edge detection, motion estimation and so on. Recently, many studies on the nonlinear digital filter for impulsive noise reduction have been reported. The median filter, the representative of the nonlinear filters, is very effective for removing impulsive noise and preserving sharp edge. In some cases, burst (i.e., successive) impulsive noise is added to image, and this type of noise is difficult to remove by using the median filter. In this paper, we propose an Adaptive Weighted Median (AWM) filter with Decimation (AWM-D filter) for burst noise reduction. This method can also be applied to recover large destructive regions, such as blotch and scratch. The proposed filter is an extension of the Decimated Median (DM) filter, which is useful for reducing successive impulsive noise. The DM filter can split long impulsive noise sequences into short ones, and remove burst noise in spite of the short filter window. Nevertheless, the DM filter also has two disadvantages. One is that the signals without added noise is unnecessary filtered. The other is that the position information in the window is not considered in the weight determinative process, as common in the median type filter. To improve detail-preserving property of the DM filter, we use the noise detection procedure and the AWM-D filter, which can be tuned by Least Mean Absolute (LMA) algorithm. The AWM-D filter preserves details more precisely than the median-type filter, because the AWM-D filter has the weights that can control the filter output. Through some simulations, the higher performance of the proposed filter is shown compared with the simple median, the WM filter, and the DM filter.

  6. 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. PMID:18495830

  7. Genetic Ablation of CD38 Protects against Western Diet-Induced Exercise Intolerance and Metabolic Inflexibility

    PubMed Central

    Chiang, Shian-Huey; Harrington, W. Wallace; Luo, Guizhen; Milliken, Naphtali O.; Ulrich, John C.; Chen, Jing; Rajpal, Deepak K.; Qian, Ying; Carpenter, Tiffany; Murray, Rusty; Geske, Robert S.; Stimpson, Stephen A.; Kramer, Henning F.; Haffner, Curt D.; Becherer, J. David; Preugschat, Frank; Billin, Andrew N.

    2015-01-01

    Nicotinamide adenine dinucleotide (NAD+) is a key cofactor required for essential metabolic oxidation-reduction reactions. It also regulates various cellular activities, including gene expression, signaling, DNA repair and calcium homeostasis. Intracellular NAD+ levels are tightly regulated and often respond rapidly to nutritional and environmental changes. Numerous studies indicate that elevating NAD+ may be therapeutically beneficial in the context of numerous diseases. However, the role of NAD+ on skeletal muscle exercise performance is poorly understood. CD38, a multi-functional membrane receptor and enzyme, consumes NAD+ to generate products such as cyclic-ADP-ribose. CD38 knockout mice show elevated tissue and blood NAD+ level. Chronic feeding of high-fat, high-sucrose diet to wild type mice leads to exercise intolerance and reduced metabolic flexibility. Loss of CD38 by genetic mutation protects mice from diet-induced metabolic deficit. These animal model results suggest that elevation of tissue NAD+ through genetic ablation of CD38 can profoundly alter energy homeostasis in animals that are maintained on a calorically-excessive Western diet. PMID:26287487

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-08-15

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

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

    PubMed

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

    2015-12-31

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

  11. Assessment of the relationship between box weight and trunk kinematics: does a reduction in box weight necessarily correspond to a decrease in spinal loading?

    PubMed

    Davis, K G; Marras, W S

    2000-01-01

    Typically, the simplest and most cost-efficient ergonomic solution to offset the rising costs of low back injuries is to reduce the box weight that is lifted. However, there is limited research on how a worker interacts with the box. In the present study, we quantify the utility of reducing the weight that is lifted - specifically, how changes in the box weight affect trunk kinematics, trunk moments, and ultimately, spinal loads. In the experiment, 15 participants lifted a variety of box weights (from 9.1 to 41.7 kg) from knee height, carried it a distance of 5 feet (1.5 m), and placed it on a shelf at elbow height. For the lower weights, small increases in box weight (3-9 kg) were offset by the trunk dynamics (sagittal velocity), resulting in no difference in spinal loads. At the same time, spinal loads were found to be significantly higher for weights above 25 kg. Thus, when making ergonomic changes (reduction of box weight), it is important to consider how workers will interact with the box. These results indicate that purely weight-based ergonomic controls might not sufficiently reduce the risk of low back disorders. Furthermore, this study provides additional evidence of the utility of using more complex spinal load models (dynamic, multiple muscle models) when evaluating highly dynamic and complex tasks. PMID:11022880

  12. Fatty acid-binding protein 5 regulates diet-induced obesity via GIP secretion from enteroendocrine K cells in response to fat ingestion.

    PubMed

    Shibue, Kimitaka; Yamane, Shunsuke; Harada, Norio; Hamasaki, Akihiro; Suzuki, Kazuyo; Joo, Erina; Iwasaki, Kanako; Nasteska, Daniela; Harada, Takanari; Hayashi, Yoshitaka; Adachi, Yasuhiro; Owada, Yuji; Takayanagi, Ryoichi; Inagaki, Nobuya

    2015-04-01

    Gastric inhibitory polypeptide (GIP) is an incretin released from enteroendocrine K cells in response to nutrient intake, especially fat. GIP is one of the contributing factors inducing fat accumulation that results in obesity. A recent study shows that fatty acid-binding protein 5 (FABP5) is expressed in murine K cells and is involved in fat-induced GIP secretion. We investigated the mechanism of fat-induced GIP secretion and the impact of FABP5-related GIP response on diet-induced obesity (DIO). Single oral administration of glucose and fat resulted in a 40% reduction of GIP response to fat but not to glucose in whole body FABP5-knockout (FABP5(-/-)) mice, with no change in K cell count or GIP content in K cells. In an ex vivo experiment using isolated upper small intestine, oleic acid induced only a slight increase in GIP release, which was markedly enhanced by coadministration of bile and oleic acid together with attenuated GIP response in the FABP5(-/-) sample. FABP5(-/-) mice exhibited a 24% reduction in body weight gain and body fat mass under a high-fat diet compared with wild-type (FABP5(+/+)) mice; the difference was not observed between GIP-GFP homozygous knock-in (GIP(gfp/gfp))-FABP5(+/+) mice and GIP(gfp/gfp)-FABP5(-/-) mice, in which GIP is genetically deleted. These results demonstrate that bile efficiently amplifies fat-induced GIP secretion and that FABP5 contributes to the development of DIO in a GIP-dependent manner. PMID:25628425

  13. 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

  14. The PGE2 EP3 Receptor Regulates Diet-Induced Adiposity in Male Mice.

    PubMed

    Ceddia, Ryan P; Lee, DaeKee; Maulis, Matthew F; Carboneau, Bethany A; Threadgill, David W; Poffenberger, Greg; Milne, Ginger; Boyd, Kelli L; Powers, Alvin C; McGuinness, Owen P; Gannon, Maureen; Breyer, Richard M

    2016-01-01

    Mice carrying a targeted disruption of the prostaglandin E2 (PGE2) E-prostanoid receptor 3 (EP3) gene, Ptger3, were fed a high-fat diet (HFD), or a micronutrient matched control diet, to investigate the effects of disrupted PGE2-EP3 signaling on diabetes in a setting of diet-induced obesity. Although no differences in body weight were seen in mice fed the control diet, when fed a HFD, EP3(-/-) mice gained more weight relative to EP3(+/+) mice. Overall, EP3(-/-) mice had increased epididymal fat mass and adipocyte size; paradoxically, a relative decrease in both epididymal fat pad mass and adipocyte size was observed in the heaviest EP3(-/-) mice. The EP3(-/-) mice had increased macrophage infiltration, TNF-α, monocyte chemoattractant protein-1, IL-6 expression, and necrosis in their epididymal fat pads as compared with EP3(+/+) animals. Adipocytes isolated from EP3(+/+) or EP3(-/-) mice were assayed for the effect of PGE2-evoked inhibition of lipolysis. Adipocytes isolated from EP3(-/-) mice lacked PGE2-evoked inhibition of isoproterenol stimulated lipolysis compared with EP3(+/+). EP3(-/-) mice fed HFD had exaggerated ectopic lipid accumulation in skeletal muscle and liver, with evidence of hepatic steatosis. Both blood glucose and plasma insulin levels were similar between genotypes on a control diet, but when fed HFD, EP3(-/-) mice became hyperglycemic and hyperinsulinemic when compared with EP3(+/+) fed HFD, demonstrating a more severe insulin resistance phenotype in EP3(-/-). These results demonstrate that when fed a HFD, EP3(-/-) mice have abnormal lipid distribution, developing excessive ectopic lipid accumulation and associated insulin resistance. PMID:26485614

  15. 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

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

    PubMed

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

    2009-07-01

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

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

    PubMed

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

    2015-01-01

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

  18. Reversion of steatosis by SREBP-1c antisense oligonucleotide did not improve hepatic insulin action in diet-induced obesity mice.

    PubMed

    Vitto, M F; Luz, G; Luciano, T F; Marques, S O; Souza, D R; Pinho, R A; Lira, F S; Cintra, D E; De Souza, C T

    2012-11-01

    The literature has associated hepatic insulin action with NAFLD. In this sense, treatments to revert steatosis and improve hepatic insulin action become important. Our group has demonstrated that inhibition of Sterol Regulatory Element Binding Proteins-1c (SREBP-1c) reverses hepatic steatosis. However, insulin signals after NAFLD reversion require better investigation. Thus, in this study, we investigated if the reversal of NAFLD by SREBP-1c inhibitor results in improvement in the hepatic insulin signal in obesity mice. After installation/achievement of diet-induced obesity and insulin resistance, Swiss mice were divided into 3 groups: i) Lean, ii) D-IHS, diet-induced hepatic steatosis [no treatment with antisense oligonucleotide (ASO)], and iii) RD-IHS, reversion of diet-induced hepatic steatosis (treated with ASO). The mice were treated with ASO SREBP-1c as previously described by our group. After ASO treatment, one set of animals was anesthetized and used for in vivo test, and another mice set was anesthetized and used for histology and Western blot analysis. Reversion of diet-induced hepatic steatosis did not change blood glucose, glucose decay constant (k(ITT)), body weight, or serum insulin levels. In addition, results showed that the protocol did not improve insulin pathway signaling, as confirmed by the absence of changes in IR, IRS1, Akt and Foxo1 phosphorylation in hepatic tissue. In parallel, no alterations were observed in proinflammatory molecules. Thus, our results suggest that the inhibition of SREBP-1c reverts steatosis, but without improving insulin hepatic resistance. PMID:22932913

  19. Triterpene alcohols and sterols from rice bran lower postprandial glucose-dependent insulinotropic polypeptide release and prevent diet-induced obesity in mice.

    PubMed

    Fukuoka, Daisuke; Okahara, Fumiaki; Hashizume, Kohjiro; Yanagawa, Kiyotaka; Osaki, Noriko; Shimotoyodome, Akira

    2014-12-01

    Obesity is now a worldwide health problem. Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone that is secreted following the ingestion of food and modulates energy metabolism. Previous studies reported that lowering diet-induced GIP secretion improved energy homeostasis in animals and humans, and attenuated diet-induced obesity in mice. Therefore, food-derived GIP regulators may be used in the development of foods that prevent obesity. Rice bran oil and its components are known to have beneficial effects on health. Therefore, the aim of the present study was to clarify the effects of the oil-soluble components of rice bran on postprandial GIP secretion and obesity in mice. Triterpene alcohols [cycloartenol (CA) and 24-methylene cycloartanol (24Me)], β-sitosterol, and campesterol decreased the diet-induced secretion of GIP in C57BL/6J mice. Mice fed a high-fat diet supplemented with a triterpene alcohol and sterol preparation (TASP) from rice bran for 23 wk gained less weight than control mice. Indirect calorimetry revealed that fat utilization was higher in TASP-fed mice than in control mice. Fatty acid oxidation-related gene expression in the muscles of mice fed a TASP-supplemented diet was enhanced, whereas fatty acid synthesis-related gene expression in the liver was suppressed. The treatment of HepG2 cells with CA and 24Me decreased the gene expression of sterol regulatory element-binding protein (SREBP)-1c. In conclusion, we clarified for the first time that triterpene alcohols and sterols from rice bran prevented diet-induced obesity by increasing fatty acid oxidation in muscles and decreasing fatty acid synthesis in the liver through GIP-dependent and GIP-independent mechanisms. PMID:25257874

  20. 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. PMID:26577614

  1. Phytosterols protect against diet-induced hypertriglyceridemia in Syrian golden hamsters

    PubMed Central

    2014-01-01

    Background In addition to lowering LDL-C, emerging data suggests that phytosterols (PS) may reduce blood triglycerides (TG), however, the underlying mechanisms are not known. Methods We examined the TG-lowering mechanisms of dietary PS in Syrian golden hamsters randomly assigned to a high fat (HF) diet or the HF diet supplemented with PS (2%) for 6 weeks (n = 12/group). An additional subset of animals (n = 12) was provided the HF diet supplemented with ezetimibe (EZ, 0.002%) as a positive control as it is a cholesterol-lowering agent with known TG-lowering properties. Results In confirmation of diet formulation and compound delivery, both the PS and EZ treatments lowered (p < 0.05) intestinal cholesterol absorption (24 and 31%, respectively), blood non-HDL cholesterol (61 and 66%, respectively), and hepatic cholesterol (45 and 55%, respectively) compared with the HF-fed animals. Blood TG concentrations were lower (p < 0.05) in the PS (49%) and EZ (68%)-treated animals compared with the HF group. The TG-lowering response in the PS-supplemented group was associated with reduced (p < 0.05) intestinal SREBP1c mRNA (0.45 fold of HF), hepatic PPARα mRNA (0.73 fold of HF), hepatic FAS protein abundance (0.68 fold of HD), and de novo lipogenesis (44%) compared with the HF group. Similarly, lipogenesis was lower in the EZ-treated animals, albeit through a reduction in the hepatic protein abundance of ACC (0.47 fold of HF). Conclusions Study results suggest that dietary PS are protective against diet-induced hypertriglyceridemia, likely through multiple mechanisms that involve modulation of intestinal fatty acid metabolism and a reduction in hepatic lipogenesis. PMID:24393244

  2. Beyond the role of dietary protein and amino acids in the prevention of diet-induced obesity.

    PubMed

    Petzke, Klaus J; Freudenberg, Anne; Klaus, Susanne

    2014-01-01

    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. PMID:24447927

  3. 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

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

    PubMed

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

    2009-06-18

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

  5. 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

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

    PubMed

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

    2015-03-01

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

  7. Cafeteria diet induce changes in blood flow that are more related with heat dissipation than energy accretion.

    PubMed

    Sabater, David; Agnelli, Silvia; Arriarán, Sofía; Romero, María Del Mar; Fernández-López, José Antonio; Alemany, Marià; Remesar, Xavier

    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

  8. 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. PMID:26393414

  9. 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.

  10. 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

  11. Central orexin sensitivity, physical activity, and obesity in diet-induced obese and diet-resistant rats.

    PubMed

    Novak, Colleen M; Kotz, Catherine M; Levine, James A

    2006-02-01

    Nonexercise activity thermogenesis (NEAT), the most variable component of energy expenditure, can account for differential capacities for human weight gain. Also highly variable, spontaneous physical activity (SPA) may similarly affect weight balance in animals. In the following study, we utilized the rat model of obesity, the diet-induced obese (DIO) rat, as well as the diet-resistant (DR) rat strain, to investigate how access to a high-fat diet alters SPA and the associated energy expenditure (i.e., NEAT). DIO and DR rats showed no differences in the amount of SPA before access to the high-fat diet. After 29 days on a high-fat diet, the DIO rats showed significant decreases in SPA, whereas the DR rats did not. Next, we wanted to determine whether the DIO and DR rats showed differential sensitivity to microinjections of orexin into the paraventricular nucleus of the hypothalamus (PVN). Unilateral guide cannulae were implanted, aimed at the PVN. Orexin A (0, 0.125, 0.25, and 1.0 nmol in 500 nl) was microinjected through the guide cannula into the PVN, then SPA and energy expenditure were measured for 2 h. Using the response to vehicle as a baseline, the DR rats showed significantly greater increase in NEAT compared with the DIO rats. These data indicate that diet-induced obesity is associated with decreases in SPA and a lack of increase in NEAT. A putative mechanism for changes in NEAT that accompany obesity is a decreased sensitivity to the NEAT-activating effects of neuropeptides such as orexin. PMID:16188908

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

    PubMed Central

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

    2013-01-01

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

  13. 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. PMID:22841395

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

    PubMed

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

    2014-09-01

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

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

    PubMed Central

    Jang, Woong Sun; Choung, Se Young

    2013-01-01

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

  16. 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

  17. Culturally-sensitive weight loss program produces significant reduction in weight, blood pressure, and cholesterol in eight weeks.

    PubMed Central

    Ard, J. D.; Rosati, R.; Oddone, E. Z.

    2000-01-01

    Dietary and behavioral needs of special populations are rarely considered in traditional weight loss programs. This study assessed the impact of culturally-sensitive modifications to the Duke University Rice Diet weight loss program for African-American dieters. The study was a randomized modified cross-over study in which volunteers received either early or delayed weight loss intervention. Final outcomes were measured at 8 weeks. At the onset of the study, there were 56 African American participants, however, only 44 (79%) completed the study. The eight-week intervention was a modified 1000-calorie/day version of the Rice Diet. Modifications to the program included decreased cost, culturally-sensitive recipes, addressing attitudes about exercise, and including family members in weight loss efforts. Average weight loss for subjects completing the program was 14.8 pounds (SD = 6.8 pounds). BMI decreased from 37.8 kg/m2 to 35.3 kg/m2 (p < 0.01). Total cholesterol levels decreased from 199.2 mg/dL to 185.4 mg/dL (p < 0.01); systolic and diastolic blood pressure decreased by 4.3 mmHg (p < 0.01) and 2.4 mmHg (p < 0.05), respectively. The control group showed no significant change in any outcome measures. We found that diet programs can be successfully tailored to incorporate the needs of African-Americans. Most importantly, these dietary program changes can lead to significant improvement in clinical parameters. Additional studies are necessary to determine the permanence of these short-term changes. PMID:11152083

  18. 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. PMID:25156790

  19. 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

  20. 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

  1. 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.

  2. 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. PMID:27257625

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

    PubMed Central

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

    2014-01-01

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

  4. Diet-induced obesity promotes altered remodeling and exacerbated cardiac hypertrophy following pressure overload

    PubMed Central

    Holzem, Katherine M; Marmerstein, Joseph T; Madden, Eli J; Efimov, Igor R

    2015-01-01

    Heart failure (HF) is the end stage of cardiovascular disease, in which hypertrophic remodeling no longer meets cardiac output demand. Established animal models of HF have provided insights into disease pathogenesis. However, these models are developed on dissimilar metabolic backgrounds from humans – patients with HF are frequently overweight or obese, whereas animal models of HF are typically lean. Thus, we aimed to develop and investigate model for cardiac hypertrophy and failure that also recapitulates the cardiometabolic state of HF in humans. We subjected mice with established diet-induced obesity (DIO) to cardiac pressure overload provoked by transverse aortic constriction (TAC). Briefly, we fed WT male mice a normal chow or high-fat diet for 10 weeks prior to sham/TAC procedures and until surgical follow-up. We then analyzed cardiac hypertrophy, mechanical function, and electrophysiology at 5–6 weeks after surgery. In DIO mice with TAC, hypertrophy and systolic dysfunction were exacerbated relative to chow TAC animals, which showed minimal remodeling with our moderate constriction intensity. Normalized heart weight was 55.8% greater and fractional shortening was 30.9% less in DIO TAC compared with chow TAC hearts. However, electrophysiologic properties were surprisingly similar between DIO sham and TAC animals. To examine molecular pathways activated by DIO and TAC, we screened prohypertrophic signaling cascades, and the exacerbated remodeling was associated with early activation of the c-Jun-N-terminal kinase (JNK1/2) signaling pathway. Thus, DIO aggravates the progression of hypertrophy and HF caused by pressure overload, which is associated with JNK1/2 signaling, and cardiometabolic state can significantly modify HF pathogenesis. PMID:26290533

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

    PubMed

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

    2015-03-01

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

  6. Diet-Induced Obesity Model: Abnormal Oocytes and Persistent Growth Abnormalities in the Offspring

    PubMed Central

    Jungheim, Emily S.; Schoeller, Erica L.; Marquard, Kerri L.; Louden, Erica D.; Schaffer, Jean E.; Moley, Kelle H.

    2010-01-01

    Associations between maternal obesity and adverse fetal outcomes are well documented, but the mechanisms involved are largely unknown. Most previous work has focused on postconceptional events, however, our laboratory has shown pre- and periconceptional aberrations in maternal glucose metabolism have adverse effects on oocytes and embryos that carry on to the fetus. To demonstrate effects of maternal obesity in the pre- and periconceptional periods, we compared reproductive tissues from diet-induced obese female mice to those of control mice. Ovaries were either stained for follicular apoptosis or dissected and evaluated for oocyte size and meiotic maturation. Mice were also mated and followed for reproductive outcomes including preimplantation embryonic IGF-I receptor (IGF-IR) immunostaining, midgestation fetal growth, and midgestational placental IGF receptor 2 (Igf2r) mRNA. Delivered pups were followed for growth and development of markers of metabolic syndrome. Compared with controls, obese mice had significantly more apoptotic ovarian follicles, smaller and fewer mature oocytes, decreased embryonic IGF-IR staining, smaller fetuses, increased placental Igf2r mRNA, and smaller pups. All weaned pups were fed a regular diet. At 13 wk pups delivered from obese mice were significantly larger, and these pups demonstrated glucose intolerance and increased cholesterol and body fat suggesting early development of a metabolic-type syndrome. Together, our findings suggest maternal obesity has adverse effects as early as the oocyte and preimplantation embryo stage and that these effects may contribute to lasting morbidity in offspring, underscoring the importance of optimal maternal weight and nutrition before conception. PMID:20573727

  7. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles.

    PubMed

    Xue, Yuan; Xu, Xiaoyang; Zhang, Xue-Qing; Farokhzad, Omid C; Langer, Robert

    2016-05-17

    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

  8. Alterations in the hippocampal endocannabinoid system in diet-induced obese mice

    PubMed Central

    Massa, Federico; Mancini, Giacomo; Schmidt, Helmut; Steindel, Frauke; Mackie, Ken; Angioni, Carlo; Oliet, Stéphane H.R.; Geisslinger, Gerd; Lutz, Beat

    2010-01-01

    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 (CB1 receptor) increases feeding, enhances reward aspects of eating and promotes lipogenesis, while 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 over-active 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-α and increased CB1 receptor immunoreactivity in CA1 and CA3 regions, while CB1 receptor agonist-induced GTPγS binding was unchanged. eCB-mediated synaptic plasticity was changed in the CA1 region, as depolarization-induced suppression of inhibition (DSI) and long-term depression of inhibitory synapses (I-LTD) were enhanced. Functionality of CB1 receptors in GABAergic neurons was furthermore revealed, as mice specifically lacking CB1 receptors on this neuronal population were partly resistant to DIO. Our results showed that DIO-induced changes in the eCB system does not affect only tissues directly involved in the metabolic regulation, but also brain regions mediating hedonic aspects of eating and influencing cognitive processes. PMID:20445053

  9. Reduction of body-weight gain enhances in vitro embryo production in overfed superovulated dairy heifers.

    PubMed

    Freret, S; Grimard, B; Ponter, A A; Joly, C; Ponsart, C; Humblot, P

    2006-04-01

    The aim of our study was to test whether a reduction in dietary intake could improve in vitro embryo production in superovulated overfed dairy heifers. Cumulus-oocyte complexes of 16 Prim' Holstein heifers (14 +/- 1 months old) were collected by ovum pick-up (OPU), every 2 weeks following superovulation treatment with 250 microg FSH, before being matured and fertilized in vitro. Embryos were cultured in Synthetic Oviduct Fluid medium for 7 days. Heifers were fed with hay, soybean meal, barley, minerals and vitamins. From OPU 1 to 4 (period 1), all heifers received individually for 8 weeks a diet formulated for a 1000 g/day live-weight gain. From OPU 5 to 8 (period 2), the heifers were allocated to one of two diets (1000 or 600 g/day) for 8 weeks. Heifers' growth rates were monitored and plasma concentrations of metabolites, metabolic and reproductive hormones were measured each week. Mean live-weight gain observed during period 1 was 950 +/- 80 g/day (n = 16). In period 2 it was 730 +/- 70 (n = 8) and 1300 +/- 70 g/day (n = 8) for restricted and overfed groups respectively. When comparing period 1 and period 2 within groups, significant differences were found. In the restricted group, a higher blastocyst rate, greater proportions of grade 1-3 and grade 1 embryos, associated with higher estradiol at OPU and lower glucose and beta-hydroxybutyrate, were observed in period 2 compared with period 1. Moreover, after 6 weeks of dietary restriction (OPU 7), numbers of day 7 total embryos, blastocysts and grade 1-3 embryos had significantly increased. On the contrary, in the overfed group, we observed more <8 mm follicles 2 days before superovulation treatment, higher insulin and IGF-I and lower nonesterified fatty acids in period 2 compared with period 1 (no significant difference between periods for embryo production). After 6 weeks of 1300 g/day live-weight gain (OPU 7), embryo production began to decrease. Whatever the group, oocyte collection did not differ between

  10. MCD diet-induced steatohepatitis is associated with alterations in asymmetric dimethylarginine (ADMA) and its transporters.

    PubMed

    Di Pasqua, Laura G; Berardo, Clarissa; Rizzo, Vittoria; Richelmi, Plinio; Croce, Anna Cleta; Vairetti, Mariapia; Ferrigno, Andrea

    2016-08-01

    Using an experimental model of NASH induced by a methionine-choline-deficient (MCD) diet, we investigated whether changes occur in serum and tissue levels of asymmetric dimethylarginine (ADMA). Male Wistar rats underwent NASH induced by 8-week feeding with an MCD diet. Serum and hepatic biopsies at 2, 4 and 8 weeks were taken, and serum enzymes, ADMA and nitrate/nitrite (NOx), were evaluated. Hepatic biopsies were used for mRNA and protein expression analysis of dimethylarginine dimethylaminohydrolase-1 (DDAH-1) and protein methyltransferases (PRMT-1), enzymes involved in ADMA metabolism and synthesis, respectively, and ADMA transporters (CAT-1, CAT-2A and CAT-2B). Lipid peroxides (TBARS), glutathione, ATP/ADP and DDAH activity were quantified. An increase in serum AST and ALT was detected in MCD animals. A time-dependent decrease in serum and tissue ADMA and increase in mRNA expression of DDAH-1 and PRMT-1 as well as higher rates of mRNA expression of CAT-1 and lower rates of CAT-2A and CAT-2B were found after 8-week MCD diet. An increase in serum NOx and no changes in protein expression in DDAH-1 and CAT-1 and higher content in CAT-2 and PRMT-1 were found at 8 weeks. Hepatic DDAH activity decreased with a concomitant increase in oxidative stress, as demonstrated by high TBARS levels and low glutathione content. In conclusion, a decrease in serum and tissue ADMA levels in the MCD rats was found associated with a reduction in DDAH activity due to the marked oxidative stress observed. Changes in ADMA levels and its transporters are innovative factors in the onset and progression of hepatic alterations correlated with MCD diet-induced NASH. PMID:27357826

  11. 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

  12. Suppression of diet-induced atherosclerosis in low density lipoprotein receptor knockout mice overexpressing lipoprotein lipase.

    PubMed Central

    Shimada, M; Ishibashi, S; Inaba, T; Yagyu, H; Harada, K; Osuga, J I; Ohashi, K; Yazaki, Y; Yamada, N

    1996-01-01

    Lipoprotein lipase (LPL) is a key enzyme in the hydrolysis of triglyceride-rich lipoproteins. Conflicting results have been reported concerning its role in atherogenesis. To determine the effects of the overexpressed LPL on diet-induced atherosclerosis, we have generated low density lipoprotein receptor (LDLR) knockout mice that overexpressed human LPL transgene (LPL/LDLRKO) and compared their plasma lipoproteins and atherosclerosis with those in nonexpressing LDLR-knockout mice (LDLRKO). On a normal chow diet, LPL/LDLRKO mice showed marked suppression of mean plasma triglyceride levels (32 versus 236 mg/dl) and modest decrease in mean cholesterol levels (300 versus 386 mg/dl) as compared with LDLRKO mice. Larger lipoprotein particles of intermediate density lipoprotein (IDL)/LDL were selectively reduced in LPL/LDLRKO mice. On an atherogenic diet, both mice exhibited severe hypercholesterolemia. But, mean plasma cholesterol levels in LPL/ LDLRKO mice were still suppressed as compared with that in LDLRKO mice (1357 versus 2187 mg/dl). Marked reduction in a larger subfraction of IDL/LDL, which conceivably corresponds to remnant lipoproteins, was observed in the LPL/LDLRKO mice. LDLRKO mice developed severe fatty streak lesions in the aortic sinus after feeding with the atherogenic diet for 8 weeks. In contrast, mean lesion area in the LPL/LDLRKO mice was 18-fold smaller than that in LDLRKO mice. We suggest that the altered lipoprotein profile, in particular the reduced level of remnant lipoproteins, is mainly responsible for the protection by LPL against atherosclerosis. Images Fig. 1 Fig. 3 PMID:8692976

  13. 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

  14. Disrupted Leptin Signaling in the Lateral Hypothalamus and Ventral Premammillary Nucleus Alters Insulin and Glucagon Secretion and Protects Against Diet-Induced Obesity.

    PubMed

    Denroche, Heather C; Glavas, Maria M; Tudurí, Eva; Karunakaran, Subashini; Quong, Whitney L; Philippe, Marion; Britton, Heidi M; Clee, Susanne M; Kieffer, Timothy J

    2016-07-01

    Leptin signaling in the central nervous system, and particularly the arcuate hypothalamic nucleus, is important for regulating energy and glucose homeostasis. However, the roles of extra-arcuate leptin responsive neurons are less defined. In the current study, we generated mice with widespread inactivation of the long leptin receptor isoform in the central nervous system via Synapsin promoter-driven Cre (Lepr(flox/flox) Syn-cre mice). Within the hypothalamus, leptin signaling was disrupted in the lateral hypothalamic area (LHA) and ventral premammillary nucleus (PMV) but remained intact in the arcuate hypothalamic nucleus and ventromedial hypothalamic nucleus, dorsomedial hypothalamic nucleus, and nucleus of the tractus solitarius. To investigate the role of LHA/PMV neuronal leptin signaling, we examined glucose and energy homeostasis in Lepr(flox/flox) Syn-cre mice and Lepr(flox/flox) littermates under basal and diet-induced obese conditions and tested the role of LHA/PMV neurons in leptin-mediated glucose lowering in streptozotocin-induced diabetes. Lepr(flox/flox) Syn-cre mice did not have altered body weight or blood glucose levels but were hyperinsulinemic and had enhanced glucagon secretion in response to experimental hypoglycemia. Surprisingly, when placed on a high-fat diet, Lepr(flox/flox) Syn-cre mice were protected from weight gain, glucose intolerance, and diet-induced hyperinsulinemia. Peripheral leptin administration lowered blood glucose in streptozotocin-induced diabetic Lepr(flox/flox) Syn-cre mice as effectively as in Lepr(flox/flox) littermate controls. Collectively these findings suggest that leptin signaling in LHA/PMV neurons is not critical for regulating glucose levels but has an indispensable role in the regulation of insulin and glucagon levels and, may promote the development of diet-induced hyperinsulinemia and weight gain. PMID:27183315

  15. EMP acupoint stimulation conducive to increase the effect of weight reduction through aerobic exercise

    PubMed Central

    Jiao, Chun; Zhu, Ximei; Zhang, Hongyu; Du, Xiaowei

    2015-01-01

    Purpose: to observe whether weight reduction through aerobic exercise is more effective with the intervention of electromagnetic pulse (EMP) Acupoint stimulation. Method: based on the need of this study, we choose 48 young and middle-aged obese patients and randomly divide them into Experimental Group and Control Group with each group consisting of 24 of them. The Control Group has an aerobic endurance running each day with each running lasting for about 45 minutes and covering about 6 KM; the Experimental Group has the same exercise as the CG, but, after their running, stimulation by electromagnetic pulse meter is given to their Sanyinjiao Acupoint and Zushanli Acupoint. Then the content of body fat and the lipid indexes of the two groups before the treatment are compared with their counterparts after the said treatment. Result: after 6 weeks of treatment, the various indexes of the two groups are improved to different degrees (P<0.05); the effect on lipid indexes of the Experimental Group is obviously better than that of the Control Group (P<0.05), but the content of their body fat shows no conspicuous difference (P>0.05). Conclusion: after 6 weeks of treatment, the intervention of EMP acupoint stimulation can more evidently improve the lipid indexes than it has done to the group only having aerobic exercise; but it has little effect in terms of the improvement of the body fat content, which may be because of the short time of such intervention. PMID:26379942

  16. 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. PMID:25588195

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

    PubMed

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

    2013-10-01

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

  18. 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

  19. Aeronautical fuel conservation possibilities for advanced subsonic transports. [application of aeronautical technology for drag and weight reduction

    NASA Technical Reports Server (NTRS)

    Braslow, A. L.; Whitehead, A. H., Jr.

    1973-01-01

    The anticipated growth of air transportation is in danger of being constrained by increased prices and insecure sources of petroleum-based fuel. Fuel-conservation possibilities attainable through the application of advances in aeronautical technology to aircraft design are identified with the intent of stimulating NASA R and T and systems-study activities in the various disciplinary areas. The material includes drag reduction; weight reduction; increased efficiency of main and auxiliary power systems; unconventional air transport of cargo; and operational changes.

  20. Apple-Derived Pectin Modulates Gut Microbiota, Improves Gut Barrier Function, and Attenuates Metabolic Endotoxemia in Rats with Diet-Induced Obesity

    PubMed Central

    Jiang, Tingting; Gao, Xuejin; Wu, Chao; Tian, Feng; Lei, Qiucheng; Bi, Jingcheng; Xie, Bingxian; Wang, Hong Yu; Chen, Shuai; Wang, Xinying

    2016-01-01

    This study was aimed at determining potential effects of apple-derived pectin on weight gain, gut microbiota, gut barrier and metabolic endotoxemia in rat models of diet-induced obesity. The rats received a standard diet (control; Chow group; n = 8) or a high-fat diet (HFD; n = 32) for eight weeks to induce obesity. The top 50th percentile of weight-gainers were selected as diet induced obese rats. Thereafter, the Chow group continued on chow, and the diet induced obese rats were randomly divided into two groups and received HFD (HF group; n = 8) or pectin-supplemented HFD (HF-P group; n = 8) for six weeks. Compared to the HF group, the HF-P group showed attenuated weight gain (207.38 ± 7.96 g vs. 283.63 ± 10.17 g, p < 0.01) and serum total cholesterol level (1.46 ± 0.13 mmol/L vs. 2.06 ± 0.26 mmol/L, p < 0.01). Compared to the Chow group, the HF group showed a decrease in Bacteroidetes phylum and an increase in Firmicutes phylum, as well as subordinate categories (p < 0.01). These changes were restored to the normal levels in the HF-P group. Furthermore, compared to the HF group, the HF-P group displayed improved intestinal alkaline phosphatase (0.57 ± 0.20 vs. 0.30 ± 0.19, p < 0.05) and claudin 1 (0.76 ± 0.14 vs. 0.55 ± 0.18, p < 0.05) expression, and decreased Toll-like receptor 4 expression in ileal tissue (0.76 ± 0.58 vs. 2.04 ± 0.89, p < 0.01). The HF-P group also showed decreased inflammation (TNFα: 316.13 ± 7.62 EU/mL vs. 355.59 ± 8.10 EU/mL, p < 0.01; IL-6: 51.78 ± 2.35 EU/mL vs. 58.98 ± 2.59 EU/mL, p < 0.01) and metabolic endotoxemia (2.83 ± 0.42 EU/mL vs. 0.68 ± 0.14 EU/mL, p < 0.01). These results suggest that apple-derived pectin could modulate gut microbiota, attenuate metabolic endotoxemia and inflammation, and consequently suppress weight gain and fat accumulation in diet induced obese rats. PMID:26938554

  1. Weight regain after sustained weight reduction is accompanied by suppressed oxidation of dietary fat and adipocyte hyperplasia.

    PubMed

    Jackman, Matthew R; Steig, Amy; Higgins, Janine A; Johnson, Ginger C; Fleming-Elder, Brooke K; Bessesen, Daniel H; MacLean, Paul S

    2008-04-01

    A dual-tracer approach (dietary 14C-palmitate and intraperitoneal 3H-H2O) was used to assess the trafficking of dietary fat and net retention of carbon in triglyceride depots during the first 24 h of weight regain. Obesity-prone male Wistar rats were allowed to mature under obesogenic conditions for 16 wk. One group was switched to ad libitum feeding of a low-fat diet for 10 wk (Obese group). The remaining rats were switched to an energy-restricted, low-fat diet for 10 wk that reduced body weight by 14% and were then assessed in energy balance (Reduced group), with free access to the low-fat diet (Relapse-Day1 group), or with a provision that induced a minor imbalance (+10 kcal) equivalent to that observed in obese rats (Gap-Matched group). Fat oxidation remained at a high, steady rate throughout the day in Obese rats, but was suppressed in Reduced, Gap-Matched, and Relapse-Day1 rats though 9, 18, and 24 h, respectively. The same caloric excess in Obese and Gap-Matched rats led to less fat oxidation over the day and greater trafficking of dietary fat to visceral depots in the latter. In addition to trafficking nutrients to storage, Relapse-Day1 rats had more small, presumably new, adipocytes at the end of 24 h. Dietary fat oxidation at 24 h was related to the phosphorylation of skeletal muscle acetyl-CoA carboxylase and fatty acid availability. These observations provide evidence of adaptations in the oxidation and trafficking of dietary fat that extend beyond the energy imbalance, which facilitate rapid, efficient regain during the relapse to obesity. PMID:18287221

  2. 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...

  3. 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...

  4. 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.

  5. 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...

  6. Effects of diet-induced obesity on secondary tumor development and plasma cytokine expression in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of diet-induced obesity on secondary tumor development and expression of plasma cytokines in mice. Three-wk old male C57BL/6 mice were fed the AIN-93G diet or a 45% fat diet (kcal %; n=25/group) for 7 wks before they were subcutaneously injected with 2.5 x ...

  7. 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...

  8. Toll Like Receptor-4 Mediates Vascular Inflammation and Insulin Resistance in Diet-Induced Obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vascular dysfunction is a major complication of metabolic disorders such as diabetes and obesity. The current studies were undertaken to determine if inflammatory responses are activated in the vasculature of mice with diet-induced obesity (DIO), and if so, whether Toll Like Receptor-4 (TLR4), a ke...

  9. 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...

  10. Is Western Diet-Induced Nonalcoholic Steatohepatitis in Ldlr-/- Mice Reversible?

    PubMed Central

    Lytle, Kelli A.; Jump, Donald B.

    2016-01-01

    Background Nonalcoholic fatty liver disease (NAFLD) is a major public health burden in western societies. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), is characterized by hepatosteatosis, inflammation, oxidative stress, and hepatic damage that can progress to fibrosis and cirrhosis; risk factors for hepatocellular carcinoma. Given the scope of NASH, validating treatment protocols (i.e., low fat diets and weight loss) is imperative. Methods We evaluated the efficacy of two diets, a non-purified chow (NP) and purified (low-fat low-cholesterol, LFLC) diet to reverse western diet (WD)-induced NASH and fibrosis in Ldlr-/- mice. Results Mice fed WD for 22–24 weeks developed robust hepatosteatosis with mild fibrosis, while mice maintained on the WD an additional 7–8 weeks developed NASH with moderate fibrosis. Returning WD-fed mice to the NP or LFLC diets significantly reduced body weight and plasma markers of metabolic syndrome (dyslipidemia, hyperglycemia) and hepatic gene expression markers of inflammation (Mcp1), oxidative stress (Nox2), fibrosis (Col1A, LoxL2, Timp1) and collagen crosslinking (hydroxyproline). Time course analyses established that plasma triglycerides and hepatic Col1A1 mRNA were rapidly reduced following the switch from the WD to the LFLC diet. However, hepatic triglyceride content and fibrosis did not return to normal levels 8 weeks after the change to the LFLC diet. Time course studies further revealed a strong association (r2 ≥ 0.52) between plasma markers of inflammation (TLR2 activators) and hepatic fibrosis markers (Col1A, Timp1, LoxL2). Inflammation and fibrosis markers were inversely associated (r2 ≥ 0.32) with diet-induced changes in hepatic ω3 and ω6 polyunsaturated fatty acids (PUFA) content. Conclusion These studies establish a temporal link between plasma markers of inflammation and hepatic PUFA and fibrosis. Low-fat low-cholesterol diets promote reversal of many, but not all, features associated with WD

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

    PubMed Central

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

    2016-01-01

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

  12. Weight reduction and pioglitazone ameliorate polycystic ovary syndrome after removal of a Sertoli-stromal cell tumor

    PubMed Central

    Baba, Tsuyoshi; Endo, Toshiaki; Ikeda, Keiko; Shimizu, Ayumi; Morishita, Miyuki; Kuno, Yoshika; Honnma, Hiroyuki; Kiya, Tamotsu; Ishioka, Shin-ichi; Saito, Tsuyoshi

    2012-01-01

    This report presents an unusual case of Sertoli-stromal cell tumor and polycystic ovary syndrome successfully treated with weight reduction and an insulin-sensitizing agent. A 22-year-old woman, gravida 0, para 0, visited our hospital for the first time with a 12-year history of secondary amenorrhea and hypertrichosis. Transvaginal ultrasonography revealed a solid tumor in the right ovary. Right salpingo-oophorectomy was performed and pathological examination confirmed a Sertoli-stromal cell tumor. The patient’s serum androgen levels declined postoperatively, but remained above normal. Pioglitazone treatment for 6 months also significantly reduced serum androgen levels, but they still remained above normal. However, after losing 12 kg of body weight, the patient’s serum androgen levels declined to normal, and spontaneous menstruation became regular. Weight reduction with pioglitazone is an effective means of treating hyperandrogenism. PMID:23226075

  13. Analysis of energy expenditure in diet-induced obese rats

    PubMed Central

    Assaad, Houssein; Yao, Kang; Tekwe, Carmen D.; Feng, Shuo; Bazer, Fuller W.; Zhou, Lan; Carroll, Raymond J.; Meininger, Cynthia J.; Wu, Guoyao

    2014-01-01

    Development of obesity in animals is affected by energy intake, dietary composition, and metabolism. Useful models for studying this metabolic problem are Sprague-Dawley rats fed low-fat (LF) or high-fat (HF) diets beginning at 28 days of age. Through experimental design, their dietary intakes of energy, protein, vitamins, and minerals per kg body weight (BW) do not differ in order to eliminate confounding factors in data interpretation. The 24-h energy expenditure of rats is measured using indirect calorimetry. A regression model is constructed to accurately predict BW gain based on diet, initial BW gain, and the principal component scores of respiratory quotient and heat production. Time-course data on metabolism (including energy expenditure) are analyzed using a mixed effect model that fits both fixed and random effects. Cluster analysis is employed to classify rats as normal-weight or obese. HF-fed rats are heavier than LF-fed rats, but rates of their heat production per kg non-fat mass do not differ. We conclude that metabolic conversion of dietary lipids into body fat primarily contributes to obesity in HF-fed rats. PMID:24896330

  14. Timing of prenatal smoking cessation or reduction and infant birth weight: evidence from the United Kingdom Millennium Cohort Study.

    PubMed

    Yan, Ji; Groothuis, Peter A

    2015-03-01

    Smoking during pregnancy is a key contributor to poor infant health. Our study presents a dynamic relationship between the timing of prenatal smoking cessation or reduction and infant birth weight. Using a large representative dataset of a birth cohort in the United Kingdom, we apply regression analysis to examine the influences of cessation in smoking or reduction in smoking intensity at different months or trimesters on infant birth weight. For robustness checks, we use a rich set of additional covariates, a series of variable selection procedures, alternative birth outcome measures, and stratified samples. We find robust evidence that mothers who quit smoking by the third month of pregnancy or the end of the first trimester have infants of the same weight as those infants of nonsmokers. However, we find smoking cessation in the fourth month or any time beyond is associated with substantially lower infant birth weights. Two-thirds of the total adverse smoking impact on infant birth weight occurs in the second trimester. Our study also shows mothers who smoke throughout pregnancy but cut smoking intensity by the third month in pregnancy deliver infants of the same weight as those infants born to persistent light smokers. Our research suggests the efficacy of prenatal smoking cessation services can be significantly improved, if health professionals can encourage more pregnant women to quit smoking or reduce smoking intensity timely by the end of the first trimester. PMID:24889113

  15. 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.

  16. Pharmacological glycerol-3-phosphate acyltransferase inhibition decreases food intake and adiposity and increases insulin sensitivity in diet-induced obesity

    PubMed Central

    Kuhajda, Francis P.; Tu, Yajun; Han, Wan Fang; Medghalchi, Susan M.; El Meskini, Rajaa; Landree, Leslie E.; Peterson, Jonathan M.; Daniels, Khadija; Wong, Kody; Wydysh, Edward A.; Townsend, Craig A.; Ronnett, Gabriele V.

    2011-01-01

    Storage of excess calories as triglycerides is central to obesity and its associated disorders. Glycerol-3-phosphate acyltransferases (GPATs) catalyze the initial step in acylglyceride syntheses, including triglyceride synthesis. We utilized a novel small-molecule GPAT inhibitor, FSG67, to investigate metabolic consequences of systemic pharmacological GPAT inhibition in lean and diet-induced obese (DIO) mice. FSG67 administered intraperitoneally decreased body weight and energy intake, without producing conditioned taste aversion. Daily FSG67 (5 mg/kg, 15.3 μmol/kg) produced gradual 12% weight loss in DIO mice beyond that due to transient 9- to 10-day hypophagia (6% weight loss in pair-fed controls). Continued FSG67 maintained the weight loss despite return to baseline energy intake. Weight was lost specifically from fat mass. Indirect calorimetry showed partial protection by FSG67 against decreased rates of oxygen consumption seen with hypophagia. Despite low respiratory exchange ratio due to a high-fat diet, FSG67-treated mice showed further decreased respiratory exchange ratio, beyond pair-fed controls, indicating enhanced fat oxidation. Chronic FSG67 increased glucose tolerance and insulin sensitivity in DIO mice. Chronic FSG67 decreased gene expression for lipogenic enzymes in white adipose tissue and liver and decreased lipid accumulation in white adipose, brown adipose, and liver tissues without signs of damage. RT-PCR showed decreased gene expression for orexigenic hypothalamic neuropeptides AgRP or NPY after acute and chronic systemic FSG67. FSG67 given intracerebroventricularly (100 and 320 nmol icv) produced 24-h weight loss and feeding suppression, indicating contributions from direct central nervous system sites of action. Together, these data point to GPAT as a new potential therapeutic target for the management of obesity and its comorbidities. PMID:21490364

  17. Mice with a Targeted Deletion of the Type 2 Deiodinase Are Insulin Resistant and Susceptible to Diet Induced Obesity

    PubMed Central

    Marsili, Alessandro; Aguayo-Mazzucato, Cristina; Chen, Ting; Kumar, Aditi; Chung, Mirra; Lunsford, Elaine P.; Harney, John W.; Van-Tran, Thuy; Gianetti, Elena; Ramadan, Waile; Chou, Cyril; Bonner-Weir, Susan; Larsen, Philip Reed; Silva, Jorge Enrique; Zavacki, Ann Marie

    2011-01-01

    Background The type 2 iodothyronine deiodinase (D2) converts the pro-hormone thyroxine into T3 within target tissues. D2 is essential for a full thermogenic response of brown adipose tissue (BAT), and mice with a disrupted Dio2 gene (D2KO) have an impaired response to cold. BAT is also activated by overfeeding. Methodology/Principal Findings After 6-weeks of HFD feeding D2KO mice gained 5.6% more body weight and had 28% more adipose tissue. Oxygen consumption (V02) was not different between genotypes, but D2KO mice had an increased respiratory exchange ratio (RER), suggesting preferential use of carbohydrates. Consistent with this, serum free fatty acids and β-hydroxybutyrate were lower in D2KO mice on a HFD, while hepatic triglycerides were increased and glycogen content decreased. Neither genotype showed glucose intolerance, but D2KO mice had significantly higher insulin levels during GTT independent of diet. Accordingly, during ITT testing D2KO mice had a significantly reduced glucose uptake, consistent with insulin resistance. Gene expression levels in liver, muscle, and brown and white adipose tissue showed no differences that could account for the increased weight gain in D2KO mice. However, D2KO mice have higher PEPCK mRNA in liver suggesting increased gluconeogenesis, which could also contribute to their apparent insulin resistance. Conclusions/Significance We conclude that the loss of the Dio2 gene has significant metabolic consequences. D2KO mice gain more weight on a HFD, suggesting a role for D2 in protection from diet-induced obesity. Further, D2KO mice appear to have a greater reliance on carbohydrates as a fuel source, and limited ability to mobilize and to burn fat. This results in increased fat storage in adipose tissue, hepatic steatosis, and depletion of liver glycogen in spite of increased gluconeogenesis. D2KO mice are also less responsive to insulin, independent of diet-induced obesity. PMID:21698184

  18. Transgenerational inheritance of diet-induced genome rearrangements in Drosophila.

    PubMed

    Aldrich, John C; Maggert, Keith A

    2015-04-01

    Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila genome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenerationally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet. PMID:25885886

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

    PubMed

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

    2016-01-01

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

  20. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    PubMed

    Schafer, Marissa J; White, Thomas A; Evans, Glenda; Tonne, Jason M; Verzosa, Grace C; Stout, Michael B; Mazula, Daniel L; Palmer, Allyson K; Baker, Darren J; Jensen, Michael D; Torbenson, Michael S; Miller, Jordan D; Ikeda, Yasuhiro; Tchkonia, Tamara; van Deursen, Jan M; Kirkland, James L; LeBrasseur, Nathan K

    2016-06-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span. PMID:26983960

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

    PubMed

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

    2012-01-01

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

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

    PubMed

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

    2016-05-18

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed Central

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

    2014-01-01

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

  5. Luteolin attenuates hepatic steatosis and insulin resistance through the interplay between the liver and adipose tissue in mice with diet-induced obesity.

    PubMed

    Kwon, Eun-Young; Jung, Un Ju; Park, Taesun; Yun, Jong Won; Choi, Myung-Sook

    2015-05-01

    The flavonoid luteolin has various pharmacological activities. However, few studies exist on the in vivo mechanism underlying the actions of luteolin in hepatic steatosis and obesity. The aim of the current study was to elucidate the action of luteolin on obesity and its comorbidity by analyzing its transcriptional and metabolic responses, in particular the luteolin-mediated cross-talk between liver and adipose tissue in diet-induced obese mice. C57BL/6J mice were fed a normal, high-fat, and high-fat + 0.005% (weight for weight) luteolin diet for 16 weeks. In high fat-fed mice, luteolin improved hepatic steatosis by suppressing hepatic lipogenesis and lipid absorption. In adipose tissue, luteolin increased PPARγ protein expression to attenuate hepatic lipotoxicity, which may be linked to the improvement in circulating fatty acid (FA) levels by enhancing FA uptake genes and lipogenic genes and proteins in adipose tissue. Interestingly, luteolin also upregulated the expression of genes controlling lipolysis and the tricarboxylic acid (TCA) cycle prior to lipid droplet formation, thereby reducing adiposity. Moreover, luteolin improved hepatic insulin sensitivity by suppressing SREBP1 expression that modulates Irs2 expression through its negative feedback and gluconeogenesis. Luteolin ameliorates the deleterious effects of diet-induced obesity and its comorbidity via the interplay between liver and adipose tissue. PMID:25524918

  6. The combined action of omega-3 polyunsaturated fatty acids and grape proanthocyanidins on a rat model of diet-induced metabolic alterations.

    PubMed

    Ramos-Romero, Sara; Molinar-Toribio, Eunice; Pérez-Jiménez, Jara; Taltavull, Núria; Dasilva, Gabriel; Romeu, Marta; Medina, Isabel; Torres, Josep Lluís

    2016-08-10

    It has been suggested that food components such as ω-3 polyunsaturated fatty acids (ω-3 PUFAs) and (poly)phenols counteract diet-induced metabolic alterations by common or complementary mechanisms. To examine the effects of a combination of ω-3 PUFAs and (poly)phenols on such alterations, adult Wistar-Kyoto rats were fed an obesogenic high-fat high-sucrose diet supplemented, or not, for 24 weeks with: eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) 1 : 1 (16.6 g kg(-1) feed); proanthocyanidin-rich grape seed extract (GSE, 0.8 g kg(-1) feed); or EPA/DHA 1 : 1 + GSE. Body weight, feed intake, and plasma glucose were evaluated every 6 weeks, while adipose tissue weight, insulin, glucagon, ghrelin, leptin, adiponectin, cholesterol, and triglycerides were evaluated at the end of the experiment. ω-3 PUFAs reduced plasma leptin and cholesterol levels, but did not modify diet-induced perigonadal fat or plasma insulin levels; while GSE increased plasma triglyceride levels. The combined action of ω-3 PUFAs and the proanthocyanidins reduced plasma insulin and leptin, as well as partially prevented perigonadal fat accumulation. While separate supplementation with ω-3 PUFAs or grape proanthocyanidins may not counteract all the key metabolic changes induced by a high-energy-dense diet, the combination of both supplements reverts altered insulin, leptin and triglyceride levels to normal. PMID:27418399

  7. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    PubMed Central

    Boon, Mariëtte R.; van den Berg, Sjoerd A. A.; Wang, Yanan; van den Bossche, Jan; Karkampouna, Sofia; Bauwens, Matthias; De Saint-Hubert, Marijke; van der Horst, Geertje; Vukicevic, Slobodan; de Winther, Menno P. J.; Havekes, Louis M.; Jukema, J. Wouter; Tamsma, Jouke T.; van der Pluijm, Gabri; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Background/Aims Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. Methods and Results High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21°C or 28°C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21°C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28°C. Additionally, BMP7 resulted in extensive ‘browning’ of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. Conclusion Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to

  8. Dysregulated Hepatic Methionine Metabolism Drives Homocysteine Elevation in Diet-Induced Nonalcoholic Fatty Liver Disease

    PubMed Central

    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

  9. Transgenerational Inheritance of Diet-Induced Genome Rearrangements in Drosophila

    PubMed Central

    Aldrich, John C.; Maggert, Keith A.

    2015-01-01

    Ribosomal RNA gene (rDNA) copy number variation modulates heterochromatin formation and influences the expression of a large fraction of the Drosophila ge-nome. This discovery, along with the link between rDNA, aging, and disease, high-lights the importance of understanding how natural rDNA copy number variation arises. Pursuing the relationship between rDNA expression and stability, we have discovered that increased dietary yeast concentration, emulating periods of dietary excess during life, results in somatic rDNA instability and copy number reduction. Modulation of Insulin/TOR signaling produces similar results, indicating a role for known nutrient sensing signaling pathways in this process. Furthermore, adults fed elevated dietary yeast concentrations produce offspring with fewer rDNA copies demonstrating that these effects also occur in the germline, and are transgenera-tionally heritable. This finding explains one source of natural rDNA copy number variation revealing a clear long-term consequence of diet. PMID:25885886

  10. 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. PMID:26976708

  11. Silencing of OB-RGRP in mouse hypothalamic arcuate nucleus increases leptin receptor signaling and prevents diet-induced obesity

    PubMed Central

    Couturier, Cyril; Sarkis, Chamsy; Séron, Karin; Belouzard, Sandrine; Chen, Patty; Lenain, Aude; Corset, Laetitia; Dam, Julie; Vauthier, Virginie; Dubart, Anne; Mallet, Jacques; Froguel, Philippe; Rouillé, Yves; Jockers, Ralf

    2007-01-01

    Obesity is a major public health problem and is often associated with type 2 diabetes mellitus, cardiovascular disease, and metabolic syndrome. Leptin is the crucial adipostatic hormone that controls food intake and body weight through the activation of specific leptin receptors (OB-R) in the hypothalamic arcuate nucleus (ARC). However, in most obese patients, high circulating levels of leptin fail to bring about weight loss. The prevention of this “leptin resistance” is a major goal for obesity research. We report here a successful prevention of diet-induced obesity (DIO) by silencing a negative regulator of OB-R function, the OB-R gene-related protein (OB-RGRP), whose transcript is genetically linked to the OB-R transcript. We provide in vitro evidence that OB-RGRP controls OB-R function by negatively regulating its cell surface expression. In the DIO mouse model, obesity was prevented by silencing OB-RGRP through stereotactic injection of a lentiviral vector encoding a shRNA directed against OB-RGRP in the ARC. This work demonstrates that OB-RGRP is a potential target for obesity treatment. Indeed, regulators of the receptor could be more appropriate targets than the receptor itself. This finding could serve as the basis for an approach to identifying potential new therapeutic targets for a variety of diseases, including obesity. PMID:18042720

  12. 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. PMID:26688724

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

    PubMed Central

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

    2015-01-01

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

  14. 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. PMID:26199579

  15. 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

  16. 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

  17. Characterization of the 5-HT2C receptor agonist lorcaserin on efficacy and safety measures in a rat model of diet-induced obesity.

    PubMed

    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

    2015-02-01

    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 C min and C max 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

  18. Long-Term Follow-Up of the Telemonitoring Weight-Reduction Program “Active Body Control”

    PubMed Central

    Stumm, Gabriele; Blaik, Alexandra; Kropf, Siegfried; Westphal, Sabine; Hantke, Tanja Katrin; Luley, Claus

    2016-01-01

    The Active Body Control (ABC) weight-reduction program is based on telemonitoring of physical activity and nutrition together with telecoaching by weekly counseling letters sent by post or by e-mail. The study presented here reports the results of a 1-year follow-up of 49 patients with the metabolic syndrome who had lost weight with the aid of the ABC program in the preceding year. The weight regain after the second year in patients not receiving any further care (“ABC discontinued” group; n = 24) and the potential benefit of continuing with the ABC program with monthly counseling letters (“ABC continued” group; n = 25) were investigated. The relative weight changes after the first year had been, respectively, −13.4% and −11.4% in the “ABC discontinued” and “ABC continued” groups, and after the second year they decreased by, respectively, 4.4 and 2.8%. However, this difference in weight regains between the two groups was not statistically significant. It is concluded that three-quarters of the weight loss after 1 year is maintained after the second year. The decision whether to continue with the ABC program after 1 year should be made individually. PMID:27088096

  19. Sexually dimorphic myeloid inflammatory and metabolic responses to diet-induced obesity.

    PubMed

    Griffin, C; Lanzetta, N; Eter, L; Singer, K

    2016-08-01

    It is well known in clinical and animal studies that women and men have different disease risk as well as different disease physiology. Women of reproductive age are protected from metabolic and cardiovascular disease compared with postmenopausal women and men. Most murine studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of similar protection in female mice. We have investigated dietary obesity in a mouse model and have directly compared inflammatory responses in males and females. In this review we will summarize what is known about sex differences in diet-induced inflammation and will summarize our data on this topic. It is clear that sex differences in high-fat diet-induced inflammatory activation are due to cell intrinsic differences in hematopoietic responses to obesogenic cues, but further research is needed to understand what leads to sexually dimorphic responses. PMID:27252473

  20. 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

  1. 3,5-Diiodo-L-Thyronine (3,5-T2) Exerts Thyromimetic Effects on Hypothalamus-Pituitary-Thyroid Axis, Body Composition, and Energy Metabolism in Male Diet-Induced Obese Mice

    PubMed Central

    Lietzow, Julika; Wohlgemuth, Franziska; Hoefig, Carolin S.; Wiedmer, Petra; Schweizer, Ulrich; Köhrle, Josef; Schürmann, Annette

    2015-01-01

    Effective and safe antiobesity drugs are still needed in face of the obesity pandemic worldwide. Recent interventions in rodents revealed 3,5-diiodo-L-thyronine (3,5-T2) as a metabolically active iodothyronine affecting energy and lipid metabolism without thyromimetic side effects typically associated with T3 administration. Accordingly, 3,5-T2 has been proposed as a potential hypolipidemic agent for treatment of obesity and hepatic steatosis. In contrast to other observations, our experiments revealed dose-dependent thyromimetic effects of 3,5-T2 akin to those of T3 in diet-induced obese male C57BL/6J mice. 3,5-T2 treatment exerted a negative feedback regulation on the hypothalamus-pituitary-thyroid axis, similar to T3. This is demonstrated by decreased expression of genes responsive to thyroid hormones (TH) in pituitary resulting in a suppressed thyroid function with lower T4 and T3 concentrations in serum and liver of 3,5-T2-treated mice. Analyses of hepatic TH target genes involved in lipid metabolism revealed T3-like changes in gene expression and increased type I-deiodinase activity after application of 3,5-T2 (2.5 μg/g body weight). Reduced hepatic triglyceride and serum cholesterol concentrations reflected enhanced lipid metabolism. Desired increased metabolic rate and reduction of different fat depots were, however, compromised by increased food intake preventing significant body weight loss. Moreover, enlarged heart weights indicate potential cardiac side effects of 3,5-T2 beyond hepatic thyromimetic actions. Altogether, the observed thyromimetic effects of 3,5-T2 in several mouse TH target tissues raise concern about indiscriminate administration of 3,5-T2 as powerful natural hormone for the treatment of hyperlipidemia and pandemic obesity. PMID:25322465

  2. 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...

  3. Aldose Reductase Is Involved in the Development of Murine Diet-Induced Nonalcoholic Steatohepatitis

    PubMed Central

    Qiu, Longxin; Lin, Jianhui; Ying, Miao; Chen, Weiqiang; Yang, Jinmei; Deng, Tiantian; Chen, Jinfeng; Shi, Duanyu; Yang, James Y.

    2013-01-01

    Hepatic aldose reductase (AR) expression is known to be induced in liver diseases, including hepatitis and hepatocellular carcinoma. However, the role of AR in the development of these diseases remains unclear. We performed this current study to determine whether and how AR might be involved in the development of diet-induced nonalcoholic steatohepatitis. Our results showed that the level of AR protein expression was significantly higher in db/db mice fed the methionine-choline-deficient (MCD) diet than in mice fed the control diet. In parallel with the elevation in AR, steatohepatitis was observed in MCD diet-fed mice, and this diet-induced steatohepatitis was significantly attenuated by lentiviral-mediated knock-down of the AR gene. This suppressive effect of AR knock-down was associated with repressed levels of serum alanine aminotransferase and hepatic lipoperoxides, reduced mRNA and protein expression of hepatic cytochrome P450 2E1 (CYP2E1), and decreased mRNA expression of pro-inflammatory tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6). Moreover, AR-induced elevations on the level of CYP2E1 expression, reactive oxygen species, mRNA expression of TNF-α and IL-6 were confirmed in AML12 hepatocytes. Further, lentiviral-mediated knock-down of AR ameliorated MCD diet-induced collagen deposition in the livers of db/db mice. With the improvement in liver fibrosis, the mRNA levels of tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-2 (MMP-2), two genes involved in hepatic fibrogenesis, were found to be significantly suppressed, while TIMP-2 and MMP-13 were unaffected. Together these data indicate that inhibition of AR alleviates the MCD diet-induced liver inflammation and fibrosis in db/db mice, probably through dampening CYP2E1 mediated-oxidative stress and ameliorating the expression of pro-inflammatory cytokines. PMID:24066058

  4. 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. PMID:26846133

  5. 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

  6. 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

  7. Cardiovascular and renal effects of weight reduction in obesity and the metabolic syndrome.

    PubMed

    Cohen, Jordana B; Cohen, Debbie L

    2015-05-01

    Obesity is a critical public health issue worldwide. Patients with obesity have markedly increased morbidity and mortality compared to the general population. The increased health risks of obesity in part are due to its close association with each of the other components of the metabolic syndrome, including hypertension, dyslipidemia, and insulin resistance. Accordingly, obese individuals are at particularly increased risk of cardiovascular disease and chronic kidney disease. Modest weight loss results in improvements in serum cholesterol levels, blood pressure, and glycemic profiles. Lifestyle interventions for weight loss have long been the mainstay of treatment in obesity. However, the existing literature demonstrates limited weight loss sustainability and inconsistent cardiovascular and renal benefits using these modalities. In addition to improvements in intermediate risk factors, surgical interventions provide a more lasting impact on long-term cardiovascular and renal outcomes, though carry higher short-term risks due to perioperative complications. PMID:25833456

  8. Weight loss for reduction of proteinuria in diabetic nephropathy: Comparison with angiotensin-converting enzyme inhibitor therapy

    PubMed Central

    Patil, M. R.; Mishra, A.; Jain, N.; Gutch, M.; Tewari, R.

    2013-01-01

    Reduction of weight in obese type 2 diabetes mellitus (T2DM) individuals is emerging as a significant strategy in the reduction of proteinuria in diabetic nephropathy along with control of hyperglycemia, hypertension, and dyslipidemia. The objective was to evaluate the reduction in 24-h proteinuria in T2DM patients with nephropathy by weight loss, with conventional therapy (angiotensin-converting enzyme [ACE] inhibitors) as the control arm. A prospective, randomized controlled trial was conducted between June 2010 and May 2011. T2DM patients with confirmed nephropathy by 24-h urinary protein estimation with a body mass index (BMI) of >25 kg/m2 were studied. Patients who had nondiabetic nephropathy, uncontrolled hypertension (>125/75 mmHg) irrespective of antihypertensive drugs, excess weight due to edema or obesity due to other specific diseases, alcoholics, smokers, and patients who were on hemodialysis were excluded from the study. The patients were divided into three groups, namely, group A, patients on ACE inhibitor therapy; group B, patients on lifestyle modifications for weight loss; and group C, patients on an antiobesity drug (orlistat) and lifestyle modifications. At the end of 6 months, all the three groups were compared. Data were analyzed using software SPSS version 15.0. This study encompassed a total of 88 patients; 12 patients were dropped during the study period and 76 (group A: 22, group B: 23, and group C: 31) patients remained. The mean age of the patients was 58.36 ± 10.87 years (range: 30-70 years). At baseline, age, gender, mean BMI, waist-to-hip ratio (WHR), and 24-h proteinuria did not vary significantly among the three groups. At 6 months, the mean BMI significantly decreased in group C (P < 0.001) compared to that in the other two groups. Among the parameters BMI and WHR, the proportional form of BMI correlated well with the degree of reduction in proteinuria (r = 0.397, P = 0.01). Reduction in weight using lifestyle modifications and

  9. Reduction of bias in neutron multiplicity assay using a weighted point model

    SciTech Connect

    Geist, W. H.; Krick, M. S.; Mayo, D. R.

    2004-01-01

    Accurate assay of most common plutonium samples was the development goal for the nondestructive assay technique of neutron multiplicity counting. Over the past 20 years the technique has been proven for relatively pure oxides and small metal items. Unfortunately, the technique results in large biases when assaying large metal items. Limiting assumptions, such as unifoh multiplication, in the point model used to derive the multiplicity equations causes these biases for large dense items. A weighted point model has been developed to overcome some of the limitations in the standard point model. Weighting factors are detemiined from Monte Carlo calculations using the MCNPX code. Monte Carlo calculations give the dependence of the weighting factors on sample mass and geometry, and simulated assays using Monte Carlo give the theoretical accuracy of the weighted-point-model assay. Measured multiplicity data evaluated with both the standard and weighted point models are compared to reference values to give the experimental accuracy of the assay. Initial results show significant promise for the weighted point model in reducing or eliminating biases in the neutron multiplicity assay of metal items. The negative biases observed in the assay of plutonium metal samples are caused by variations in the neutron multiplication for neutrons originating in various locations in the sample. The bias depends on the mass and shape of the sample and depends on the amount and energy distribution of the ({alpha},n) neutrons in the sample. When the standard point model is used, this variable-multiplication bias overestimates the multiplication and alpha values of the sample, and underestimates the plutonium mass. The weighted point model potentially can provide assay accuracy of {approx}2% (1 {sigma}) for cylindrical plutonium metal samples < 4 kg with {alpha} < 1 without knowing the exact shape of the samples, provided that the ({alpha},n) source is uniformly distributed throughout the

  10. High and Low Activity Rats: Elevated intrinsic physical activity drives resistance to diet induced obesity in non-bred rats

    PubMed Central

    Perez-Leighton, Claudio E.; Boland, Kelsey; Billington, Charles; Kotz, Catherine M.

    2012-01-01

    Humans and rodents show large variability in their individual sensitivity to diet-induced obesity, which has been associated with differences in intrinsic spontaneous physical activity (SPA). Evidence from genetic and out-bred rat obesity models shows that higher activity of the orexin peptides results in higher intrinsic SPA and protection against diet-induced obesity. Based on this, we hypothesized that naturally occurring variation in SPA and orexin signaling activity is sufficient to drive differences in sensitivity to diet-induced obesity. We analyzed orexin activity and sensitivity to diet-induced obesity in non-manipulated male Sprague Dawley rats selected for high and low intrinsic SPA. Our results defined a new model of differential DIO sensitivity, the high-activity and low activity-rats, and suggest that naturally occurring variations in intrinsic SPA cause differences in energy expenditure that are mediated by orexin signaling and alter DIO sensitivity. PMID:23404834

  11. The Impact of a Long-Term Reduction in Dietary Energy Density on Body Weight Within a Randomized Diet Trial

    PubMed Central

    Saquib, Nazmus; Natarajan, Loki; Rock, Cheryl L.; Flatt, Shirley W.; Madlensky, Lisa; Kealey, Sheila; Pierce, John P.

    2008-01-01

    We examined the effect of dietary energy density change on body weight in participants of a randomized trial. Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat. Participants were 2,718 breast cancer survivors, aged 26−74 yr, with baseline mean body mass index of 27.3 kg/m2 (SD = 6.3). We assessed dietary intake by sets of four 24-h dietary recalls and validated with plasma carotenoid concentrations. Weight and height were measured at baseline, 1 yr, and 4 yr. Dietary energy density was calculated using food but excluding beverages. Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr—both in cross-sectional (P < 0.0001) and longitudinal (Group × Time interaction, P < 0.0001) analyses. Total energy intake or physical activity did not vary between groups. The intervention group had a small but significant weight loss at 1 yr (Group × Time interaction, P < 0.0001), but no between-group weight difference was observed at 4 yr. Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient to promote long-term weight loss in a free-living population. PMID:18444133

  12. The impact of a long-term reduction in dietary energy density on body weight within a randomized diet trial.

    PubMed

    Saquib, Nazmus; Natarajan, Loki; Rock, Cheryl L; Flatt, Shirley W; Madlensky, Lisa; Kealey, Sheila; Pierce, John P

    2008-01-01

    We examined the effect of dietary energy density change on body weight in participants of a randomized trial. Intervention participants markedly increased fruit and vegetable intake while reducing energy intake from fat. Participants were 2,718 breast cancer survivors, aged 26-74 yr, with baseline mean body mass index of 27.3 kg/m(2) (SD = 6.3). We assessed dietary intake by sets of four 24-h dietary recalls and validated with plasma carotenoid concentrations. Weight and height were measured at baseline, 1 yr, and 4 yr. Dietary energy density was calculated using food but excluding beverages. Intervention participants significantly reduced dietary energy density compared to controls and maintained it over 4 yr -- both in cross-sectional (P < 0.0001) and longitudinal (Group x Time interaction, P < 0.0001) analyses. Total energy intake or physical activity did not vary between groups. The intervention group had a small but significant weight loss at 1 yr (Group x Time interaction, P < 0.0001), but no between-group weight difference was observed at 4 yr. Our study showed that reducing dietary energy density did not result in a reduction in total energy intake and suggests that this strategy alone is not sufficient to promote long-term weight loss in a free-living population. PMID:18444133

  13. Leptin deficient ob/ob mice and diet-induced obese mice responded differently to Roux-en-Y bypass surgery

    PubMed Central

    Hao, Z; Münzberg, H; Rezai-Zadeh, K; Keenan, M; Coulon, D; Lu, H; Berthoud, H-R; Ye, J

    2015-01-01

    OBJECTIVE Weight regain contributes to the therapeutic failure in 15–20% of type 2 diabetic patients after Roux-en-Y gastric bypass surgery (RYGB), and the mechanism remains largely unknown. This study was conducted to explore the mechanism of weight regain. RESEARCH DESIGN Wild-type (WT) diet-induced obese (DIO) mice were used to mimic human obesity, and ob/ob mice were used for leptin deficiency-induced obesity. Two groups of mice were compared in weight regain for 10 months after RYGB. Weight loss, food intake, fecal energy loss and energy expenditure were monitored in the study of weight regain. Fasting insulin, insulin tolerance and homeostatic model assessment-insulin resistance were tested for insulin sensitivity under the weight regain. Weight loss from RYGB and calorie restriction was compared for the impact in insulin sensitivity. RESULTS In WT mice, RYGB induced a sustained weight loss and insulin sensitization over the sham operation in this 10-month study. However, RYGB failed to generate the same effects in leptin-deficient ob/ob mice, which suffered a weight regain over the pre-surgery level. In ob/ob mice, body weight was reduced by RYGB transiently in the first week, recovered in the second week and increased over the baseline thereafter. Weight loss was induced by RYGB relative to that of sham mice, but the loss was not sufficient to keep body weight below the pre-surgery levels. In addition, insulin sensitivity was not improved by the weight loss. The response to RYGB was improved in ob/ob mice by 2 weeks of leptin treatment. Weight loss from calorie restriction had an equivalent effect on insulin sensitization compared with that of RYGB. CONCLUSION Those data demonstrate that ob/ob mice and DIO mice responded differently to RYGB surgery, suggesting that leptin may be one of the factors required for RYGB to prevent weight regain and diabetes recurrence. PMID:25349056

  14. Weight Reduction and Maintenance for Overweight, Mentally Retarded Students, Ages 9-17.

    ERIC Educational Resources Information Center

    Nelson, Evelyn C.; And Others

    1983-01-01

    This article reports on a study undertaken to determine if overweight, mentally retarded students could safely lose weight and maintain their individual losses through a given time period (six months). School personnel and parents instituted minor changes in nutrition and a simple activity program. (Authors/JMK)

  15. Oscillating signal components of a dead-weight force-standard machine and reduction techniques

    NASA Astrophysics Data System (ADS)

    Park, Yon-Kyu; Kang, Dae-Im

    1999-08-01

    This paper describes the dynamic behaviour of a dead-weight force-standard machine at the Korea Research Institute of Standards and Science (KRISS). When a build-up system is set into a dead-weight machine, the signals from the force transducers in the build-up system consist of a dc component and oscillating signal components. The dominant oscillating components are due to pendulum motions of the dead weights and bounce-mode oscillation. The oscillation frequencies are about 0.19-0.23 Hz for the pendulum motions and 0.67-1.42 Hz for the bounce-mode oscillation. The frequencies decrease as the weights loaded are increased. The time-averaging technique is the simplest method for reducing the ac components. However, it has some limitations in that the averaging time must be re-adjusted according to the loading conditions. Other methods of reducing the ac components are therefore required. We introduced an infinite-impulse-response (IIR) low-pass filter, which reduced the oscillating components dramatically for all loading conditions. The results obtained by using IIR filtering were compared with those of time averaging and shown to be better.

  16. 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)

  17. Fenugreek with reduced bitterness prevents diet-induced metabolic disorders in rats

    PubMed Central

    2012-01-01

    difference of food intake was observed, while the 1.2% FRB group alone showed nearly the same effects on glucose and lipid metabolism as in the experiment 1. Conclusions Thus we have demonstrated that FRB (1.2 ~ 4.8%) prevents diet-induced metabolic disorders such as insulin resistance, dyslipidemia and fatty liver. PMID:22642742

  18. 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

  19. 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

  20. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity.

    PubMed

    Verdeguer, Francisco; Soustek, Meghan S; Hatting, Maximilian; Blättler, Sharon M; McDonald, Devin; Barrow, Joeva J; Puigserver, Pere

    2016-01-01

    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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2013-12-01

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

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

    PubMed

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

    2012-09-01

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

  5. CGI-58 knockdown in mice causes hepatic steatosis but prevents diet-induced obesity and glucose intolerance[S

    PubMed Central

    Brown, J. Mark; Betters, Jenna L.; Lord, Caleb; Ma, Yinyan; Han, Xianlin; Yang, Kui; Alger, Heather M.; Melchior, John; Sawyer, Janet; Shah, Ramesh; Wilson, Martha D.; Liu, Xiuli; Graham, Mark J.; Lee, Richard; Crooke, Rosanne; Shulman, Gerald I.; Xue, Bingzhong; Shi, Hang; Yu, Liqing

    2010-01-01

    Mutations of Comparative Gene Identification-58 (CGI-58) in humans cause triglyceride (TG) accumulation in multiple tissues. Mice genetically lacking CGI-58 die shortly after birth due to a skin barrier defect. To study the role of CGI-58 in integrated lipid and energy metabolism, we utilized antisense oligonucleotides (ASOs) to inhibit CGI-58 expression in adult mice. Treatment with two distinct CGI-58-targeting ASOs resulted in ∼80–95% knockdown of CGI-58 protein expression in both liver and white adipose tissue. In chow-fed mice, ASO-mediated depletion of CGI-58 did not alter weight gain, plasma TG, or plasma glucose, yet raised hepatic TG levels ∼4-fold. When challenged with a high-fat diet (HFD), CGI-58 ASO-treated mice were protected against diet-induced obesity, but their hepatic contents of TG, diacylglycerols, and ceramides were all elevated, and intriguingly, their hepatic phosphatidylglycerol content was increased by 10-fold. These hepatic lipid alterations were associated with significant decreases in hepatic TG hydrolase activity, hepatic lipoprotein-TG secretion, and plasma concentrations of ketones, nonesterified fatty acids, and insulin. Additionally, HFD-fed CGI-58 ASO-treated mice were more glucose tolerant and insulin sensitive. Collectively, this work demonstrates that CGI-58 plays a critical role in limiting hepatic steatosis and maintaining hepatic glycerophospholipid homeostasis and has unmasked an unexpected role for CGI-58 in promoting HFD-induced obesity and insulin resistance. PMID:20802159

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

    PubMed Central

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

    2015-01-01

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

  7. Diet-induced changes in maternal gut microbiota and metabolomic profiles influence programming of offspring obesity risk in rats.

    PubMed

    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

  8. 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

  9. Antiobesity Effect of Garlic Extract Fermented by Lactobacillus plantarum BL2 in Diet-Induced Obese Mice.

    PubMed

    Lee, Hee-Seop; Lim, Won-Chul; Lee, Sung-Jin; Lee, Seung-Hyun; Lee, Jin-Hyup; Cho, Hong-Yon

    2016-09-01

    Obesity is viewed as a serious public health problem. This study aimed to investigate the antiobesity effects of fermented garlic extract by lactic acid bacteria (LAFGE) on obesity. Male C57BL/6J mice were fed with high-fat diet (HFD) to induce obesity. The HFD-induced obese mice were orally administrated with 250 or 500 mg/kg LAFGE for 8 weeks. Feeding HFD-fed mice with 250 or 500 mg/kg LAFGE reduced body weight by 14% and 18%, respectively, compared to HFD. HFD-fed mice with 500 mg/kg LAFGE administration had lower epididymal, retroperitoneal, and mesenteric adipose tissue mass by 36%, 44%, and 63%, respectively, compared to HFD. The concentration of plasma triacylglyceride and total cholesterol was significantly lower in the HFD-fed mice with LAFGE administration. Moreover, LAFGE supplementation suppressed adipogenesis by downregulation in mRNA and protein expression of PPARγ, C/EBPα, and lipogenic proteins, including SREBP-1c, FAS, and SCD-1. Based on these findings, LAFGE may ameliorate diet-induced obesity by inhibiting adipose tissue hypertrophy by suppressing adipogenesis. PMID:27627701

  10. Dual melanocortin-4 receptor and GLP-1 receptor agonism amplifies metabolic benefits in diet-induced obese mice

    PubMed Central

    Clemmensen, Christoffer; Finan, Brian; Fischer, Katrin; Tom, Robby Zachariah; Legutko, Beata; Sehrer, Laura; Heine, Daniela; Grassl, Niklas; Meyer, Carola W; Henderson, Bart; Hofmann, Susanna M; Tschöp, Matthias H; Van der Ploeg, Lex HT; Müller, Timo D

    2015-01-01

    We assessed the efficacy of simultaneous agonism at the glucagon-like peptide-1 receptor (GLP-1R) and the melanocortin-4 receptor (MC4R) for the treatment of obesity and diabetes in rodents. Diet-induced obese (DIO) mice were chronically treated with either the long-acting GLP-1R agonist liraglutide, the MC4R agonist RM-493 or a combination of RM-493 and liraglutide. Co-treatment of DIO mice with RM-493 and liraglutide improves body weight loss and enhances glycemic control and cholesterol metabolism beyond what can be achieved with either mono-therapy. The superior metabolic efficacy of this combination therapy is attributed to the anorectic and glycemic actions of both drugs, along with the ability of RM-493 to increase energy expenditure. Interestingly, compared to mice treated with liraglutide alone, hypothalamic Glp-1r expression was higher in mice treated with the combination therapy after both acute and chronic treatment. Further, RM-493 enhanced hypothalamic Mc4r expression. Hence, co-dosing with MC4R and GLP-1R agonists increases expression of each receptor, indicative of minimized receptor desensitization. Together, these findings suggest potential opportunities for employing combination treatments that comprise parallel MC4R and GLP-1R agonism for the treatment of obesity and diabetes. PMID:25652173

  11. 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

  12. Treating diet-induced diabetes and obesity with human embryonic stem cell-derived pancreatic progenitor cells and antidiabetic drugs.

    PubMed

    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

    2015-04-14

    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

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

    PubMed

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

    2015-08-01

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

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

    PubMed

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

    2011-01-01

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

  15. 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. PMID:24182339

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

    PubMed

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

    2016-08-01

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2009-12-01

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

  19. Diet-induced obesity resistance of Kv1.3−/− mice is olfactory bulb dependent

    PubMed Central

    Tucker, Kristal; Overton, J. Michael; Fadool, Debra Ann

    2012-01-01

    Gene-targeted deletion of the voltage-gated potassium channel, Kv1.3 (Kv1.3−/−), increases olfactory sensitivity and discriminatory ability, and causes resistance to diet-induced obesity (DIO) in mice. The objective of the present study was to determine if the enhanced olfactory ability of the Kv1.3−/− mouse contributes to the resistance to DIO. Kv1.3+/+ and Kv1.3−/− mice were subject to bilateral olfactory bulbectomy (OBX) or sham surgery at 9 weeks of age and placed on either a control chow diet (CF) or a 32% moderately high-fat diet (MHF). Caloric and water intake, locomotor activity, and oxygen consumption were monitored after 5 weeks of diet treatment. At the end of 26 weeks of diet treatment, fat pad weight and blood chemistry were evaluated. Kv1.3+/+ mice exhibited a significant increase in weight, adiposity, fasting glucose and fasting leptin in response to the MHF-diet, with or without OBX. When treated with a MHF-diet, Kv1.3−/− mice gained significantly less weight than Kv1.3 +/+ mice and exhibited a significant increase in light phase metabolism. OBX of Kv1.3−/− mice prevented the resistance to DIO and concomitant upregulation of light phase metabolism while decreasing dark phase metabolism and total energy expenditure. These findings suggest that pathways activated in Kv1.3 −/− that increased energy expenditure and led to resistance to DIO are olfactory bulb dependent. Thus, these findings add to a growing body of evidence suggesting that the olfactory system can modulate pathways involved in the regulation of energy balance. PMID:22435906

  20. Loss of ADAMTS4 reduces high fat diet-induced atherosclerosis and enhances plaque stability in ApoE−/− mice

    PubMed Central

    Kumar, Saran; Chen, Mo; Li, Yan; Wong, Fiona H. S.; Thiam, Chung Wee; Hossain, Md Zakir; Poh, Kian Keong; Hirohata, Satoshi; Ogawa, Hiroko; Angeli, Véronique; Ge, Ruowen

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease characterized by formation of lipid-rich plaques on the inner walls of arteries. ADAMTS4 (a disintegrin-like and metalloproteinase with thrombospondin motifs-4) is a secreted proteinase that regulates versican turnover in the arterial wall and atherosclerotic plaques. Recent reports indicated elevated ADAMTS4 level in human atherosclerotic plaques and in the plasma of acute coronary syndrome patients. Nevertheless, whether increased ADAMTS4 is a consequence of atherosclerosis or ADAMTS4 has a causal role in atherogenesis remains unknown. In this work, we investigated the role of ADAMTS4 in diet induced atherosclerosis using apolipoprotein E deficient (ApoE−/−) and Adamts4 knockout mice. We show that ADAMTS4 expression increases in plaques as atherosclerosis progresses in ApoE−/− mice. ApoE−/−Adamts4−/− double knockout mice presented a significant reduction in plaque burden at 18 weeks of age. Loss of ADAMTS4 lead to a more stable plaque phenotype with a significantly reduced plaque vulnerability index characterized by reduced lipid content and macrophages accompanied with a significant increase in smooth muscle cells, collagen deposition and fibrotic cap thickness. The reduced atherosclerosis is accompanied by an altered plasma inflammatory cytokine profile. These results demonstrate for the first time that ADAMTS4 contributes to diet induced atherosclerosis in ApoE−/− mice. PMID:27491335

  1. Cinnamomum camphora Seed Kernel Oil Improves Lipid Metabolism and Enhances β3-Adrenergic Receptor Expression in Diet-Induced Obese Rats.

    PubMed

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Wen, Xuefang; Yu, Ping; Gong, Deming

    2016-06-01

    The effects of dietary Cinnamomum camphora seed kernel oil (CCSKO) containing medium-chain triacylglycerols on lipid metabolism and mRNA and protein expression of β-3 adrenergic receptor in adipose tissue were studied in diet-induced obese rats. High fat food-induced obese rats were randomly divided into CCSKO group, Lard group, Soybean oil (SOY) group and naturally restoring group (n = 10). Rats fed with low fat food were used as a normal control group. Significant decreases in body mass and abdominal fat mass/body mass after 12 weeks were found in CCSKO group as compared with Lard and SOY groups (p < 0.05). Levels of blood total cholesterol (TC), triglyceride, free fatty acid, fasting insulin and insulin resistance in the CCSKO group were decreased significantly, and noradrenaline level and insulin sensitivity index in the CCSKO group were significantly higher than other groups. Meanwhile liver TC and triglyceride levels in the CCSKO group were also decreased markedly. Expression levels of β3-adrenergic receptor mRNA and protein were higher in CCSKO group than in Lard and SOY groups. These results suggest that CCSKO may contribute to reduction of the body fat mass, promote lipid metabolism and up-regulate β3-adrenergic receptor expression in high fat diet-induced obese rats. PMID:27068065

  2. Application of SEM-based contours for OPC model weighting and sample plan reduction

    NASA Astrophysics Data System (ADS)

    Miller, Marshal; Hitomi, Keiichiro; Halle, Scott; Graur, Ioana; Bailey, Todd

    2015-03-01

    Continued improvements in SEM contour extraction capabilities have enabled calibrating more accurate OPC models for advanced technology nodes using a hybrid approach, combining CDs for 1D structures and full contour measurements for more complex 2D patterns. Previous work has addressed various components of contour modeling including alignment, edge detection, CD to contour consistency, and image parameter space coverage. This study covers weighting strategies for CDs compared to contours. Additionally the total number of structures in a sample plan can be reduced by incorporating contours for model calibration due to the increased number of evaluation points they provide. Repeated measurements of the same structure at separate locations are used to extract SEM contours across several instances. The average measurements from these locations can then be used for OPC model calibration. Using 14nm process data, it is shown that including more contours in hybrid OPC model calibration leads to improved model verification. Within an appropriate range, higher weight on the contour patterns leads to improved model verification on measurement sites unseen by the calibration set. Calibrating a model with fewer contour structures, but at higher weight shows improvement over standard CD only model calibration.

  3. 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

  4. Astaxanthin prevents and reverses diet-induced insulin resistance and steatohepatitis in mice: A comparison with vitamin E

    PubMed Central

    Ni, Yinhua; Nagashimada, Mayumi; Zhuge, Fen; Zhan, Lili; Nagata, Naoto; Tsutsui, Akemi; Nakanuma, Yasuni; Kaneko, Shuichi; Ota, Tsuguhito

    2015-01-01

    Hepatic insulin resistance and nonalcoholic steatohepatitis (NASH) could be caused by excessive hepatic lipid accumulation and peroxidation. Vitamin E has become a standard treatment for NASH. However, astaxanthin, an antioxidant carotenoid, inhibits lipid peroxidation more potently than vitamin E. Here, we compared the effects of astaxanthin and vitamin E in NASH. We first demonstrated that astaxanthin ameliorated hepatic steatosis in both genetically (ob/ob) and high-fat-diet-induced obese mice. In a lipotoxic model of NASH: mice fed a high-cholesterol and high-fat diet, astaxanthin alleviated excessive hepatic lipid accumulation and peroxidation, increased the proportion of M1-type macrophages/Kupffer cells, and activated stellate cells to improve hepatic inflammation and fibrosis. Moreover, astaxanthin caused an M2-dominant shift in macrophages/Kupffer cells and a subsequent reduction in CD4+ and CD8+ T cell recruitment in the liver, which contributed to improved insulin resistance and hepatic inflammation. Importantly, astaxanthin reversed insulin resistance, as well as hepatic inflammation and fibrosis, in pre-existing NASH. Overall, astaxanthin was more effective at both preventing and treating NASH compared with vitamin E in mice. Furthermore, astaxanthin improved hepatic steatosis and tended to ameliorate the progression of NASH in biopsy-proven human subjects. These results suggest that astaxanthin might be a novel and promising treatment for NASH. PMID:26603489

  5. 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

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

  8. Determination of prostate adenoma weight reduction due to vaporisation process occurring during transurethral resection of the prostate

    PubMed Central

    Szopinski, Tomasz; Chlosta, Piotr; Borówka, Andrzej

    2014-01-01

    Introduction Transurethral resection of the prostate (TURP) is regarded as the gold standard surgical treatment for benign prostatic hyperplasia (BPH). The completeness of TURP may be assessed indirectly by estimation of the weight of glandular tissue removed. This parameter is often lower than expected. Tissue vaporisation in the course of TURP could be a contributory cause. Aim To quantitatively evaluate tissue vaporisation occurring in the course of transurethral resection of the prostate and electrovaporisation of the prostate (EVAP) performed under experimental conditions. Material and methods The study was performed on 26 prostate glands removed during retropubic prostatectomy. Immediately following surgery all adenomas were halved and TURP or EVAP were carried out on both halves of each gland for period of 5 min. The amount of prostate tissue which vaporised during EVAP and TURP were calculated. Results The mean weight (± standard deviation) of the adenoma lost due to resection and vaporisation in the TURP group was 10.00 ±2.92 g and 4.26 ±1.59 g, respectively. The latter accounted for 30.10 ±7.71% of total prostate weight reduction. The mean prostate weight lost in the course of EVAP was 5.03 ±1.58 g. Conclusions The vaporisation significantly contributes to the prostate tissue loss occurring during transurethral resection of the prostate. PMID:25337165

  9. Reduction of speckle noise from optical coherence tomography images using multi-frame weighted nuclear norm minimization method

    NASA Astrophysics Data System (ADS)

    Thapa, Damber; Raahemifar, Kaamran; Lakshminarayanan, Vasudevan

    2015-12-01

    In this paper, we propose a speckle noise reduction method for spectral-domain optical coherence tomography (SD-OCT) images called multi-frame weighted nuclear norm minimization (MWNNM). This method is a direct extension of weighted nuclear norm minimization (WNNM) in the multi-frame framework since an adequately denoised image could not be achieved with single-frame denoising methods. The MWNNM method exploits multiple B-scans collected from a small area of a SD-OCT volumetric image, and then denoises and averages them together to obtain a high signal-to-noise ratio B-scan. The results show that the image quality metrics obtained by denoising and averaging only five nearby B-scans with MWNNM method is considerably better than those of the average image obtained by registering and averaging 40 azimuthally repeated B-scans.

  10. The effects of auricular acupuncture on weight reduction and feeding-related cytokines: a pilot study

    PubMed Central

    Ito, Hisayuki; Yamada, Osamu; Kira, Yuji; Tanaka, Takeshi; Matsuoka, Rumiko

    2015-01-01

    Objective Auricular acupuncture is a common therapy used to control appetite; however, the underlying mechanism(s) of action is unclear. The present study examined changes in feeding behaviour and in the levels of several appetite-related hormones in response to auricular acupuncture, and attempted to identify the mechanism(s) by which this traditional medical treatment exerts its effects. Methods Ten healthy adult volunteers (nine female and one male) were recruited by the KOSAI Oriental Healthcare Center. The participants were randomly assigned to one of two groups (n=5 per group): an acupuncture group and a placebo group. Each received detention needle stimulus on a weekly basis for 1 month. Changes in diet, body weight, blood pressure and blood biochemistry were evaluated before treatment and at 1 week after the start of treatment. Results The difference in weight before treatment and after 1 week of treatment was significant for all participants in the acupuncture group (p=0.02). The percentage changes in active ghrelin in the acupuncture group were no significant changes observed in active ghrelin levels at 1 week after acupuncture in any individual participant (p=0.89). By contrast, the percentage changes in active ghrelin levels in the placebo group at 1 week after the start of acupuncture were significant (p=0.04). The insulin, adrenocorticotropic hormone, leptin and adiponectin levels did not change significantly in either group. Conclusions There was a statistically significant difference in the percentage change in body weight and active ghrelin levels in each individual participant in auricular acupuncture groups. This is a pilot study and the sample number is small; however, auricular acupuncture may reduce appetite by suppressing ghrelin production. PMID:26462269

  11. Reduction of artifacts in T2-weighted PROPELLER in high-field preclinical imaging

    PubMed Central

    Pandit, Prachi; Qi, Yi; King, Kevin F.; Johnson, G. Allan

    2010-01-01

    A simple technique is implemented for correction of artifacts arising from non-uniform T2-weighting of k-space data in FSE-based PROPELLER (Periodically Rotated Overlapping ParallEL Lines with Enhanced Reconstruction). An additional blade with no phase-encoding gradients is acquired to generate the scaling factor used for the correction. Results from simulations and phantom experiments, as well as in vivo experiments in free-breathing mice, demonstrate the advantages of the proposed method. This technique is developed specifically for high-field imaging applications where T2 decay is rapid. PMID:20928875

  12. 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.

  13. 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.

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

    PubMed

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

    2007-06-01

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

  15. 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

  16. Effects of diet-induced obesity on motivation and pain behavior in an operant assay.

    PubMed

    Rossi, H L; Luu, A K S; Kothari, S D; Kuburas, A; Neubert, J K; Caudle, R M; Recober, A

    2013-04-01

    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 (RD) 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 a high-fat diet (HFD) 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 SKH1-E (SK) 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

  17. Diet-Induced Alterations in Total and Metabolically Active Microbes within the Rumen of Dairy Cows

    PubMed Central

    Lettat, Abderzak; Benchaar, Chaouki

    2013-01-01

    DNA-based techniques are widely used to study microbial populations; however, this approach is not specific to active microbes, because DNA may originate from inactive and/or dead cells. Using cDNA and DNA, respectively, we aimed to discriminate the active microbes from the total microbial community within the rumen of dairy cows fed diets with increasing proportions of corn silage (CS). Nine multiparous lactating Holstein cows fitted with ruminal cannulas were used in a replicated 3×3 Latin square (32-d period; 21-d adaptation) design to investigate diet-induced shifts in microbial populations by targeting the rDNA gene. Cows were fed a total mixed ration with the forage portion being either barley silage (0% CS), a 50∶50 mixture of barley silage and corn silage (50% CS), or corn silage (100% CS). No differences were found for total microbes analyzed by quantitative PCR, but changes were observed within the active ones. Feeding more CS to dairy cows was accompanied by an increase in Prevotella rRNA transcripts (P = 0.10) and a decrease in the protozoal rRNA transcripts (P<0.05). Although they were distributed differently among diets, 78% of the amplicons detected in DNA- and cDNA-based fingerprints were common to total and active bacterial communities. These may represent a bacterial core of abundant and active cells that drive the fermentation processes. In contrast, 10% of amplicons were specific to total bacteria and may represent inactive or dead cells, whereas 12% were only found within the active bacterial community and may constitute slow-growing bacteria with high metabolic activity. It appears that cDNA-based analysis is more discriminative to identify diet-induced shifts within the microbial community. This approach allows the detection of diet-induced changes in the microbial populations as well as particular bacterial amplicons that remained undetected using DNA-based methods. PMID:23593365

  18. 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

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

    PubMed

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

    2016-01-01

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

  20. A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice.

    PubMed

    Ohyama, Kana; Nogusa, Yoshihito; Suzuki, Katsuya; Shinoda, Kosaku; Kajimura, Shingo; Bannai, Makoto

    2015-02-15

    Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT. PMID:25516550

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

    PubMed Central

    Oh, Ji-Hyun; Kim, Jaehoon

    2016-01-01

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

  2. Rhein ameliorates fatty liver disease through negative energy balance, hepatic lipogenic regulation, and immunomodulation in diet-induced obese mice.

    PubMed

    Sheng, Xiaoyan; Wang, Min; Lu, Meng; Xi, Beili; Sheng, Hongguang; Zang, Ying Qin

    2011-05-01

    Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and inflammatory disorders. In this study, we tested the effect of rhein, a lipophilic anthraquinone derived from a traditional Chinese herbal medicine Rheum palmatum L., on NAFLD-associated hepatic steatosis, insulin resistance, and the T helper (Th)1/Th2 cytokine imbalance in high-fat diet-induced obese (DIO) mice. We found that oral administration of rhein for 40 days significantly increased energy expenditure, reduced body weight, particularly body fat content, improved insulin resistance, and lowered circulating cholesterol levels in DIO mice without affecting food intake. Rhein treatment also reduced liver triglyceride levels, reversed hepatic steatosis, and normalized alanine aminotransferase (ALT) levels in these mice. Gene analysis and Western blot showed that rhein markedly suppressed the expression of the lipogenic enzyme sterol regulatory element-binding protein-1c (SREBP-1c) and its target genes in the liver. Luciferase reporter assay revealed that rhein suppressed the transcriptional activity of SREBP-1c through its upstream regulator, liver X receptor (LXR). This suggests that rhein exerts its effects by targeting LXR, which is also supported by its inability to reduce body weight in LXR knockout mice. Moreover, multiplex ELISA displayed a downregulated Th1 response after rhein treatment. Rhein shifted the Th1/Th2 responses by inhibiting T-box expressed in T-cells (T-bet) expression and enhancing GATA-binding protein-3 (GATA-3) expression through increased signal transducer and activator of transcription 6 (STAT6) phosphorylation. These data indicate that rhein ameliorated NAFLD and associated disorders through LXR-mediated negative energy balance, metabolic regulatory pathways, and immunomodulatory activities involved in hepatic steatosis. The combined effects of rhein to target hepatic metabolic and immune pathways may be beneficial for complex metabolic

  3. Development of Novel Methods for the Reduction of Noise and Weight in Helicopter Transmissions

    NASA Technical Reports Server (NTRS)

    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.

  4. Identification of Predictors for Weight Reduction in Children and Adolescents with Overweight and Obesity (IDA-Insel Survey)

    PubMed Central

    Schiel, Ralf; Kaps, Alexander; Stein, Günter; Steveling, Antje

    2016-01-01

    Introduction: Worldwide, overweight and obesity are known as posing serious health risks. Successful methods of prevention and therapy for overweight and obesity have remained elusive. It was the aim of the present trial to identify parameters and determinants to guarantee long-term weight reduction. Patients and methods: In total 143/159 children and adolescents (90%) with overweight and obesity completed the prospective, multicenter trial (age 13.9 ± 2.4 years, BMI 31.2 ± 5.4 kg/m2, BMI-SDS 2.51 ± 0.57). During a six-week rehabilitation patients participated in a structured treatment and teaching program (STTP). Following the inpatient treatment the children and adolescents were monitored over a period of 24 months (physical examination, measurements of BMI, BMI-SDS, body composition, carotid intima-media thickness, laboratory parameters, blood pressure, and standardized questionnaires to assess socio-demographic, socio-economic parameters, eating behavior, well-being, quality of life, intelligence, intrafamilial conflicts, self-efficacy, resilience, sense of coherence, stress-management, social support, and actual body shape). Results: 66% of the children and adolescents showed non-normal laboratory parameters as well as higher blood pressure and/or an increased carotid intima-media thickness. Mean thickness of carotid intima-media was 0.53 ± 0.09 mm (range, 0.40–0.80); 15% of the patients showed a normal range (<0.45 mm), 40% slightly elevated (0.45–0.50 mm) and 45% an elevated (>0.50 mm) thickness. After an inpatient treatment lasting 40.4 ± 4.1 (range, 28–49) days, children and adolescents reached a mean weight reduction of 5.52 ± 3.94 (0.4–13.3) kg (p < 0.01) accompanied by a reduction of body fat mass. Performing multivariate analyses, the most important psychological factors associated with long-term weight reduction were identified (R-square = 0.53): Well-being (β = −0.543), resilience (β = 0.434) and intrafamilial conflicts (β = 0

  5. Six-week Diet Correction for Body Weight Reduction and Its Subsequent Changes of Gut Microbiota: A Case Report

    PubMed Central

    2016-01-01

    Impact of intestinal microbes on obesity and health is a new topic recently started to get attention. Comparing to the global concern and research trends, there are few research on the association between intestinal bacteria and life style disease in Korean. One voluntary case (female) was reported to show the change in gut microbiota and weight by diet intervention. She was overweight (BMI 23.2 kg/m2) and has abnormal liver function, and the causes of overweight were frequent drinking and meat consumption at the late evening hours. For 47 days, she was administered an improved diet on breakfast and dinner with reduction of meat consumption frequency by 50%. Alcohol consumption was reduced to once a week. As a result, she lost 3 kilograms of body weight. Her fecal sample was collected before and after the intervention, and gut microbiota change was compared using a high-throughput sequencing technique. After diet correction, the shift of gut microbiota was clearly observed with decreased proportion of Firmicutes (from 75.7% to 47.3% in total microbiota) but increased proportion of Bacteroidetes upto 47.7%. After incorporating the diet intervention, it is meaningful to confirm the changes in dominant gut microbiota and weight loss. PMID:27152303

  6. Six-week Diet Correction for Body Weight Reduction and Its Subsequent Changes of Gut Microbiota: A Case Report.

    PubMed

    Oh, Bumjo; Kim, Jong Seung; Kweon, Meera; Kim, Bong-Soo; Huh, In Sil

    2016-04-01

    Impact of intestinal microbes on obesity and health is a new topic recently started to get attention. Comparing to the global concern and research trends, there are few research on the association between intestinal bacteria and life style disease in Korean. One voluntary case (female) was reported to show the change in gut microbiota and weight by diet intervention. She was overweight (BMI 23.2 kg/m(2)) and has abnormal liver function, and the causes of overweight were frequent drinking and meat consumption at the late evening hours. For 47 days, she was administered an improved diet on breakfast and dinner with reduction of meat consumption frequency by 50%. Alcohol consumption was reduced to once a week. As a result, she lost 3 kilograms of body weight. Her fecal sample was collected before and after the intervention, and gut microbiota change was compared using a high-throughput sequencing technique. After diet correction, the shift of gut microbiota was clearly observed with decreased proportion of Firmicutes (from 75.7% to 47.3% in total microbiota) but increased proportion of Bacteroidetes upto 47.7%. After incorporating the diet intervention, it is meaningful to confirm the changes in dominant gut microbiota and weight loss. PMID:27152303

  7. Depot-specific effects of treadmill running and rutin on white adipose tissue function in diet-induced obese mice.

    PubMed

    Chen, Neng; Lei, Ting; Xin, Lili; Zhou, Lingmei; Cheng, Jinbo; Qin, Liqiang; Han, Shufen; Wan, Zhongxiao

    2016-09-01

    White adipose tissue (WAT) is a critical organ involved in regulating metabolic homeostasis under obese condition. Strategies that could positively affect WAT function would hold promise for fighting against obesity and its complications. The aim of the present study is to explore the effects of treadmill exercise training and rutin intervention on adipose tissue function from diet-induced obese (DIO) mice and whether fat depot-specific effects existed. In epididymal adipose tissue, high-fat diet (HFD) resulted in reduction in adiponectin mRNA expression, peroxisome proliferator-activated receptors (PPAR)-γ and DsbA-L protein expression, elevation in endoplasmic reticulum (ER) stress markers including 78 kDa glucose-regulated protein (GRP-78), C/EBP homologous protein (CHOP) and p-c-Jun N-terminal kinase (JNK). Isoproterenol-stimulated lipolysis and insulin stimulated Akt phosphorylation ex vivo were blunted from HFD group. The combination of rutin with exercise (HRE) completely restored GRP78 and p-JNK protein expression to normal levels, as well as blunted signaling ex vivo. In inguinal adipose tissue, HFD led to increased adiponectin mRNA expression, PPAR-γ, GRP78, and p-JNK protein expression, and reduction in DsbA-L. HRE is effective for restoring p-JNK, PPAR-γ, and DsbA-L. In conclusion, depot-specific effects may exist in regard to the effects of rutin and exercise on key molecules involved in regulating adipose tissue function (i.e., ER stress markers, PPAR-γ and DsbA-L, adiponectin expression, and secretion, ex vivo catecholamine stimulated lipolysis and insulin stimulated Akt phosphorylation) from DIO mice. PMID:27192989

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

    PubMed Central

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

    2015-01-01

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

  9. 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.

  10. Electromagnet Weight Reduction in a Magnetic Levitation System for Contactless Delivery Applications

    PubMed Central

    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. PMID:22163572

  11. 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. PMID:22163572

  12. Loss of Nlrp3 Does Not Protect Mice from Western Diet-Induced Adipose Tissue Inflammation and Glucose Intolerance.

    PubMed

    Ringling, Rebecca E; Gastecki, Michelle L; Woodford, Makenzie L; Lum-Naihe, Kelly J; Grant, Ryan W; Pulakat, Lakshmi; Vieira-Potter, Victoria J; Padilla, Jaume

    2016-01-01

    We tested the hypothesis that loss of Nlrp3 would protect mice from Western diet-induced adipose tissue (AT) inflammation and associated glucose intolerance and cardiovascular complications. Five-week old C57BL6J wild-type (WT) and Nlrp3 knockout (Nlrp3-/-) mice were randomized to either a control diet (10% kcal from fat) or Western diet (45% kcal from fat and 1% cholesterol) for 24 weeks (n = 8/group). Contrary to our hypothesis that obesity-mediated white AT inflammation is Nlrp3-dependent, we found that Western diet-induced expression of AT inflammatory markers (i.e., Cd68, Cd11c, Emr1, Itgam, Lgals, Il18, Mcp1, Tnf, Ccr2, Ccl5 mRNAs, and Mac-2 protein) were not accompanied by increased caspase-1 cleavage, a hallmark feature of NLRP3 inflammasome activation. Furthermore, Nlrp3 null mice were not protected from Western diet-induced white or brown AT inflammation. Although Western diet promoted glucose intolerance in both WT and Nlrp3-/- mice, Nlrp3-/- mice were protected from Western diet-induced aortic stiffening. Additionally, Nlrp3-/- mice exhibited smaller cardiomyocytes and reduced cardiac fibrosis, independent of diet. Collectively, these findings suggest that presence of the Nlrp3 gene is not required for Western diet-induced AT inflammation and/or glucose intolerance; yet Nlrp3 appears to play a role in potentiating arterial stiffening, cardiac hypertrophy and fibrosis. PMID:27583382

  13. Effects of thiol antioxidant β-mercaptoethanol on diet-induced obese mice

    PubMed Central

    Wong, Siu; Kirkland, James L.; Schwanz, Heidi A.; Simmons, Amber L.; Hamilton, James A.; Corkey, Barbara E.; Guo, Wen

    2014-01-01

    Aims Obesity and insulin resistance are associated with increased oxidant stress. However, treatments of obese subjects with different types of antioxidants often give mixed outcomes. In this work, we sought to determine if long-term supplementation of a thiol antioxidant, β-mercaptoethanol, to diet-induced obese mice may improve their health conditions. Main Methods Middle-age mice with pre-existing diet-induced obesity were provided with low concentration β-mercaptoethanol (BME) in drinking water for six months. Animals were assessed for body composition, gripping strength, spontaneous physical and metabolic activities, as well as insulin and pyruvate tolerance tests. Markers of inflammation were assessed in plasma, fat tissue, and liver. Key findings BME-treated mice gained less fat mass and more lean mass than the control animals. They also showed increased nocturnal locomotion and respiration, as well as greater gripping strength. BME reduced plasma lipid peroxidation, decreased abdominal fat tissue inflammation, reduced fat infiltration into muscle and liver, and reduced liver and plasma C-reactive protein. However, BME was found to desensitize insulin signaling in vivo, an effect also confirmed by in vitro experiments. Conclusion Long-term supplementation of low dose thiol antioxidant BME improved functional outcomes in animals with pre-existing obesity. Additional studies are needed to address the treatment impact on insulin sensitivity if a therapeutic value is to be explored. PMID:24802126

  14. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome.

    PubMed

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L; Ward, Leigh C; Mouatt, Peter; Brown, Lindsay

    2015-09-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  15. Green and Black Cardamom in a Diet-Induced Rat Model of Metabolic Syndrome

    PubMed Central

    Bhaswant, Maharshi; Poudyal, Hemant; Mathai, Michael L.; Ward, Leigh C.; Mouatt, Peter; Brown, Lindsay

    2015-01-01

    Both black (B) and green (G) cardamom are used as flavours during food preparation. This study investigated the responses to B and G in a diet-induced rat model of human metabolic syndrome. Male Wistar rats were fed either a corn starch-rich diet (C) or a high-carbohydrate, high-fat diet with increased simple sugars along with saturated and trans fats (H) for 16 weeks. H rats showed signs of metabolic syndrome leading to visceral obesity with hypertension, glucose intolerance, cardiovascular remodelling and nonalcoholic fatty liver disease. Food was supplemented with 3% dried B or G for the final eight weeks only. The major volatile components were the closely related terpenes, 1,8-cineole in B and α-terpinyl acetate in G. HB (high-carbohydrate, high-fat + black cardamom) rats showed marked reversal of diet-induced changes, with decreased visceral adiposity, total body fat mass, systolic blood pressure and plasma triglycerides, and structure and function of the heart and liver. In contrast, HG (high-carbohydrate, high-fat + green cardamom) rats increased visceral adiposity and total body fat mass, and increased heart and liver damage, without consistent improvement in the signs of metabolic syndrome. These results suggest that black cardamom is more effective in reversing the signs of metabolic syndrome than green cardamom. PMID:26378573

  16. Diet-induced hypercholesterolemia imparts structure-function changes to erythrocyte chondroitin sulphate/dermatan sulphate.

    PubMed

    Kiran, G; Srikanth, C B; Salimath, P V; Nandini, C D

    2015-09-01

    Hypercholesterolemia is one of the factors contributing to cardiovascular problems. Erythrocytes are known to contribute its cholesterol to atherosclerotic plaque. Our earlier study showed that erythrocytes overexpress chondroitin sulphate/dermatan sulphate (CS/DS), a linear co-polymer, during diabetes which resulted in increased cytoadherence to extracellular matrix (ECM) components. This study was carried out to determine whether diet-induced hypercholesterolemia had any effect on erythrocyte CS/DS and impacted cytoadherence to ECM components. Unlike in diabetes, diet-induced hypercholesterolemia did not show quantitative changes in erythrocyte CS/DS but showed difference in proportion of un-sulphated and 4-O-sulphated disaccharides. Erythrocytes from hypercholesterolemic rats showed increased adhesion to ECM components which was abrogated to various extents when subjected to chondroitinase ABC digestion. However, isolated CS/DS chains showed a different pattern of binding to ECM components indicating that orientation of CS/DS chains could be playing a role in binding. PMID:25862809

  17. Decreased carbon shunting from glucose towards oxidative metabolism in diet-induced ketotic rat brain

    PubMed Central

    Zhang, Yifan; Zhang, Shenghui; Marin-Valencia, Isaac; Puchowicz, Michelle A.

    2014-01-01

    The mechanistic link of ketosis to neuroprotection under certain pathological conditions continues to be explored. We investigated whether chronic ketosis induced by ketogenic diet results in the partitioning of ketone bodies towards oxidative metabolism in brain. We hypothesized that diet-induced ketosis results in increased shunting of ketone bodies towards citric acid cycle (CAC) and amino acids with decreased carbon shunting from glucose. Rats were fed standard (STD) or ketogenic (KG) diets for 3.5 weeks and then infused with [U-13C]glucose or [U-13C]acetoacetate tracers. Concentrations and 13C-labeling pattern of CAC intermediates and amino acids were analyzed from brain homogenates using stable isotopomer mass spectrometry analysis. The contribution of [U-13C]glucose to acetyl-CoA and amino acids decreased by ~30% in the KG group vs STD, whereas [U-13C]acetoacetate contributions were more than 2-fold higher. The concentration of GABA remained constant across all groups; however, the 13C-labeling of GABA was markedly increased in the KG group infused with [U-13C]acetoacetate compared to STD. This study reveals that there is a significant contribution of ketone bodies to oxidative metabolism and GABA in diet-induced ketosis. We propose that this represents a fundamental mechanism of neuroprotection under pathological conditions. PMID:25314677

  18. Decreased carbon shunting from glucose toward oxidative metabolism in diet-induced ketotic rat brain.

    PubMed

    Zhang, Yifan; Zhang, Shenghui; Marin-Valencia, Isaac; Puchowicz, Michelle A

    2015-02-01

    The mechanistic link of ketosis to neuroprotection under certain pathological conditions continues to be explored. We investigated whether chronic ketosis induced by ketogenic diet results in the partitioning of ketone bodies toward oxidative metabolism in brain. We hypothesized that diet-induced ketosis results in increased shunting of ketone bodies toward citric acid cycle and amino acids with decreased carbon shunting from glucose. Rats were fed standard (STD) or ketogenic (KG) diets for 3.5 weeks and then infused with [U-(13) C]glucose or [U-(13) C]acetoacetate tracers. Concentrations and (13) C-labeling pattern of citric acid cycle intermediates and amino acids were analyzed from brain homogenates using stable isotopomer mass spectrometry analysis. The contribution of [U-(13) C]glucose to acetyl-CoA and amino acids decreased by ~ 30% in the KG group versus STD, whereas [U-(13) C]acetoacetate contributions were more than two-fold higher. The concentration of GABA remained constant across groups; however, the (13) C labeling of GABA was markedly increased in the KG group infused with [U-(13) C]acetoacetate compared to STD. This study reveals that there is a significant contribution of ketone bodies to oxidative metabolism and GABA in diet-induced ketosis. We propose that this represents a fundamental mechanism of neuroprotection under pathological conditions. PMID:25314677

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

    PubMed

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

    2016-04-01

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

  20. The Amplifying Pathway of the β-Cell Contributes to Diet-induced Obesity.

    PubMed

    Vetterli, Laurène; Carobbio, Stefania; Frigerio, Francesca; Karaca, Melis; Maechler, Pierre

    2016-06-17

    Efficient energy storage in adipose tissues requires optimal function of the insulin-producing β-cell, whereas its dysfunction promotes diabetes. The associated paradox related to β-cell efficiency is that excessive accumulation of fat in adipose tissue predisposes for type 2 diabetes. Insulin exocytosis is regulated by intracellular metabolic signal transduction, with glutamate dehydrogenase playing a key role in the amplification of the secretory response. Here, we used mice with β-cell-selective glutamate dehydrogenase deletion (βGlud1(-/-)), lacking an amplifying pathway of insulin secretion. As opposed to control mice, βGlud1(-/-) animals fed a high calorie diet maintained glucose tolerance and did not develop diet-induced obesity. Islets of βGlud1(-/-) mice did not increase their secretory response upon high calorie feeding, as did islets of control mice. Inhibited adipose tissue expansion observed in knock-out mice correlated with lower expression of genes responsible for adipogenesis. Rather than being efficiently stored, lipids were consumed at a higher rate in βGlud1(-/-) mice compared with controls, in particular during food intake periods. These results show that reduced β-cell function prior to high calorie feeding prevented diet-induced obesity. PMID:27137930

  1. Cinnamomum camphora Seed Kernel Oil Ameliorates Oxidative Stress and Inflammation in Diet-Induced Obese Rats.

    PubMed

    Fu, Jing; Zeng, Cheng; Zeng, Zheling; Wang, Baogui; Gong, Deming

    2016-05-01

    Cinnamomum camphora seed kernel oil (CCSKO) was found to reduce body fat deposition and improve blood lipid in both healthy and obese rats. The study was aimed to investigate the antioxidative stress and anti-inflammatory effects of CCSKO in high-fat-diet-induced obese rats. The obese rats were treated with CCSKO, lard, and soybean oil, respectively, for 12 wk. The level of total antioxidant capacity (T-AOC), activities of superoxide dismutase (SOD), glutathione peroxidase, and catalase, and levels of malondialdehyde (MDA), tumor necrosis factor (TNF)-α, peroxisome proliferator-activated receptor (PPAR)-γ, interleukin (IL)-6, and P65 were compared among CCSKO, lard, and soybean oil groups. Our results showed that the level of T-AOC and activities of SOD and catalase were significantly increased and the level of MDA was significantly decreased in CCSKO group. In addition, CCSKO treatment reduced the activities of serum glutamic oxaloacetic transaminase and glutamate-pyruvate transaminase, and levels of serum TNF-α, IL-6, and P65 through raising the level of PPAR-γ. In conclusion, CCSKO has, for the first time, been found to ameliorate oxidative stress and inflammation in high-fat-diet-induced obese rats. PMID:27003858

  2. Spatial disturbances in altered mucosal and luminal gut viromes of diet-induced obese mice.

    PubMed

    Kim, Min-Soo; Bae, Jin-Woo

    2016-05-01

    Gut microbial biogeography is a key feature of host-microbe relationships. In gut viral ecology, biogeography and responses to dietary intervention remain poorly understood. Here, we conducted a metagenomic study to determine the composition of the mucosal and luminal viromes of the gut and to evaluate the impact of a Western diet on gut viral ecology. We found that mucosal and luminal viral assemblages comprised predominantly temperate phages. The mucosal virome significantly differed from the luminal virome in low-fat diet-fed lean mice, where spatial variation correlated with bacterial microbiota from the mucosa and lumen. The mucosal and luminal viromes of high-fat, high-sucrose 'Western' diet-fed obese mice were significantly enriched with temperate phages of the Caudovirales order. Interestingly, this community alteration occurred to a greater extent in the mucosa than lumen, leading to loss of spatial differences; however, these changes recovered after switching to a low-fat diet. Temperate phages enriched in the Western diet-induced obese mice were associated with the Bacilli, Negativicutes and Bacteroidia classes and temperate phages from the Bacteroidia class particularly encoded stress and niche-specific functions advantageous to bacterial host adaptation. This study illustrates a biogeographic view of the gut virome and phage-bacterial host connections under the diet-induced microbial dysbiosis. PMID:26690305

  3. Maternal Diet-Induced Obesity Alters Mitochondrial Activity and Redox Status in Mouse Oocytes and Zygotes

    PubMed Central

    Igosheva, Natalia; Abramov, Andrey Y.; Poston, Lucilla; Eckert, Judith J.; Fleming, Tom P.; Duchen, Michael R.; McConnell, Josie

    2010-01-01

    The negative impact of obesity on reproductive success is well documented but the stages at which development of the conceptus is compromised and the mechanisms responsible for the developmental failure still remain unclear. Recent findings suggest that mitochondria may be a contributing factor. However to date no studies have directly addressed the consequences of maternal obesity on mitochondria in early embryogenesis. Using an established murine model of maternal diet induced obesity and a live cell dynamic fluorescence imaging techniques coupled with molecular biology we have investigated the underlying mechanisms of obesity-induced reduced fertility. Our study is the first to show that maternal obesity prior to conception is associated with altered mitochondria in mouse oocytes and zygotes. Specifically, maternal diet-induced obesity in mice led to an increase in mitochondrial potential, mitochondrial DNA content and biogenesis. Generation of reactive oxygen species (ROS) was raised while glutathione was depleted and the redox state became more oxidised, suggestive of oxidative stress. These altered mitochondrial properties were associated with significant developmental impairment as shown by the increased number of obese mothers who failed to support blastocyst formation compared to lean dams. We propose that compromised oocyte and early embryo mitochondrial metabolism, resulting from excessive nutrient exposure prior to and during conception, may underlie poor reproductive outcomes frequently reported in obese women. PMID:20404917

  4. RNA-mediated paternal heredity of diet-induced obesity and metabolic disorders

    PubMed Central

    Grandjean, Valérie; Fourré, Sandra; De Abreu, Diana Andrea Fernandes; Derieppe, Marie-Alix; Remy, Jean-Jacques; Rassoulzadegan, Minoo

    2015-01-01

    The paternal heredity of obesity and diabetes induced by a high-fat and/or high-sugar diet (Western-like diet) has been demonstrated through epidemiological analysis of human cohorts and experimental analysis, but the nature of the hereditary vector inducing this newly acquired phenotype is not yet well defined. Here, we show that microinjection of either testis or sperm RNA of male mice fed a Western-like diet into naive one-cell embryos leads to the establishment of the Western-like diet-induced metabolic phenotype in the resulting progenies, whereas RNAs prepared from healthy controls did not. Among multiple sequence differences between the testis transcriptomes of the sick and healthy fathers, we noted that several microRNAs had increased expression, which was of interest because this class of noncoding RNA is known to be involved in epigenetic control of gene expression. When microinjected into naive one-cell embryos, one of these small RNA, i.e., the microRNA miR19b, induced metabolic alterations that are similar to the diet-induced phenotype. Furthermore, this pathological phenotype was inherited by the offspring after crosses with healthy partners. Our results indicate that acquired food-induced trait inheritance might be enacted by RNA signalling. PMID:26658372

  5. Lipidomics Biomarkers of Diet-Induced Hyperlipidemia and Its Treatment with Poria cocos.

    PubMed

    Miao, Hua; Zhao, Yu-Hui; Vaziri, Nosratola D; Tang, Dan-Dan; Chen, Hua; Chen, Han; Khazaeli, Mahyar; Tarbiat-Boldaji, Mehrdokht; Hatami, Leili; Zhao, Ying-Yong

    2016-02-01

    Hyperlipidemia is a major cause of atherosclerotic cardiovascular disease. Poria cocos (PC) is a medicinal product widely used in Asia. This study was undertaken to define the alterations of lipid metabolites in rats fed a high-fat diet to induce hyperlipidemia and to explore efficacy and mechanism of action of PC in the treatment of diet-induced hyperlipidemia. Plasma samples were then analyzed using UPLC-HDMS. The untreated rats fed a high-fat diet exhibited significant elevation of plasma triglyceride and total and low-density lipoprotein (LDL) cholesterol concentrations. This was associated with marked changes in plasma concentrations of seven fatty acids (palmitic acid, hexadecenoic acid, hexanoylcarnitine, tetracosahexaenoic acid, cervonoyl ethanolamide, 3-hydroxytetradecanoic acid, and 5,6-DHET) and five sterols [cholesterol ester (18:2), cholesterol, hydroxytestosterone, 19-hydroxydeoxycorticosterone, and cholic acid]. These changes represented disorders of biosynthesis and metabolism of the primary bile acids, steroids, and fatty acids and mitochondrial fatty acid elongation pathways in diet-induced hyperlipidemia. Treatment with PC resulted in significant improvements of hyperlipidemia and the associated abnormalities of the lipid metabolites. PMID:26758241

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

    PubMed Central

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

    2013-01-01

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

  7. Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis

    PubMed Central

    Hiramitsu, Masanori; Shimada, Yasuhito; Kuroyanagi, Junya; Inoue, Takashi; Katagiri, Takao; Zang, Liqing; Nishimura, Yuhei; Nishimura, Norihiro; Tanaka, Toshio

    2014-01-01

    Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32 mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. PMID:24424211

  8. On the use of antenna weight functions in field strength prediction and interference reduction

    NASA Astrophysics Data System (ADS)

    van de Griendt, M. A. J.; van Dooren, G. A. J.

    1993-10-01

    In this paper two methods for calculating the received electromagnetic field by a single-parabolic reflector antenna in the shadow region behind a finite-width screen are proposed and analysed. The first one is referred to as the far-field approach and treats the obstacle and reflector antenna diffraction separately. The antenna simply is replaced by a point source having the receiving properties of the reflector antenna considered. The second method is called the near-field approach and considers the combined effect of obstacle and antenna diffraction. It is shown that considerable differences between the results of both methods may exist, even for an obstacle-antenna separation large compared to the Rayleigh distance of the antenna, and both for a CW and broadband analysis of the communications channel. It is concluded that the near-field method gives the best results and can be applied to many practical problems such as interference reduction and searching the optimal position of VSATs in urban environments.

  9. Evidence that diet-induced hyperleptinemia, but not hypothalamic gliosis, causes ghrelin resistance in NPY/AgRP neurons of male mice.

    PubMed

    Briggs, Dana I; Lockie, Sarah H; Benzler, Jonas; Wu, Qunli; Stark, Romana; Reichenbach, Alex; Hoy, Andrew J; Lemus, Moyra B; Coleman, Harold A; Parkington, Helena C; Tups, Alex; Andrews, Zane B

    2014-07-01

    High-fat diet (HFD) feeding causes ghrelin resistance in arcuate neuropeptide Y (NPY)/Agouti-related peptide neurons. In the current study, we investigated the time course over which this occurs and the mechanisms responsible for ghrelin resistance. After 3 weeks of HFD feeding, neither peripheral nor central ghrelin increased food intake and or activated NPY neurons as demonstrated by a lack of Fos immunoreactivity or whole-cell patch-clamp electrophysiology. Pair-feeding studies that matched HFD calorie intake with chow calorie intake show that HFD exposure does not cause ghrelin resistance independent of body weight gain. We observed increased plasma leptin in mice fed a HFD for 3 weeks and show that leptin-deficient obese ob/ob mice are still ghrelin sensitive but become ghrelin resistant when central leptin is coadministered. Moreover, ob/ob mice fed a HFD for 3 weeks remain ghrelin sensitive, and the ability of ghrelin to induce action potential firing in NPY neurons was blocked by leptin. We also examined hypothalamic gliosis in mice fed a chow diet or HFD, as well as in ob/ob mice fed a chow diet or HFD and lean controls. HFD-fed mice exhibited increased glial fibrillary acidic protein-positive cells compared with chow-fed mice, suggesting that hypothalamic gliosis may underlie ghrelin resistance. However, we also observed an increase in hypothalamic gliosis in ob/ob mice fed a HFD compared with chow-fed ob/ob and lean control mice. Because ob/ob mice fed a HFD remain ghrelin sensitive, our results suggest that hypothalamic gliosis does not underlie ghrelin resistance. Further, pair-feeding a HFD to match the calorie intake of chow-fed controls did not increase body weight gain or cause central ghrelin resistance; thus, our evidence suggests that diet-induced hyperleptinemia, rather than diet-induced hypothalamic gliosis or HFD exposure, causes ghrelin resistance. PMID:24742194

  10. Extensive impact of saturated fatty acids on metabolic and cardiovascular profile in rats with diet-induced obesity: a canonical analysis

    PubMed Central

    2013-01-01

    Background Although hypercaloric interventions are associated with nutritional, endocrine, metabolic, and cardiovascular disorders in obesity experiments, a rational distinction between the effects of excess adiposity and the individual roles of dietary macronutrients in relation to these disturbances has not previously been studied. This investigation analyzed the correlation between ingested macronutrients (including sucrose and saturated and unsaturated fatty acids) plus body adiposity and metabolic, hormonal, and cardiovascular effects in rats with diet-induced obesity. Methods Normotensive Wistar-Kyoto rats were submitted to Control (CD; 3.2 Kcal/g) and Hypercaloric (HD; 4.6 Kcal/g) diets for 20 weeks followed by nutritional evaluation involving body weight and adiposity measurement. Metabolic and hormonal parameters included glycemia, insulin, insulin resistance, and leptin. Cardiovascular analysis included systolic blood pressure profile, echocardiography, morphometric study of myocardial morphology, and myosin heavy chain (MHC) protein expression. Canonical correlation analysis was used to evaluate the relationships between dietary macronutrients plus adiposity and metabolic, hormonal, and cardiovascular parameters. Results Although final group body weights did not differ, HD presented higher adiposity than CD. Diet induced hyperglycemia while insulin and leptin levels remained unchanged. In a cardiovascular context, systolic blood pressure increased with time only in HD. Additionally, in vivo echocardiography revealed cardiac hypertrophy and improved systolic performance in HD compared to CD; and while cardiomyocyte size was unchanged by diet, nuclear volume and collagen interstitial fraction both increased in HD. Also HD exhibited higher relative β-MHC content and β/α-MHC ratio than their Control counterparts. Importantly, body adiposity was weakly associated with cardiovascular effects, as saturated fatty acid intake was directly associated with most

  11. 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

  12. Effects of antibodies to adipocytes on body weight, food intake, and adipose tissue cellularity in obese rats.

    PubMed

    Flint, D J

    1998-11-01

    Female Wistar rats were fed on a high fat diet for 18 weeks, during which their energy intake increased by 25% and body weight by 50% due to a doubling of adipose tissue tissue stores. Animals were then treated with increasing doses of a sheep polyclonal antiserum to rat adipocytes on days 1-4 and 7 after which they remained untreated for 14 weeks. Antibody treatment reduced body weight by 10% and the weight of parametrial and subcutaneous adipose tissue by 30-40%. This decrease was explicable entirely in terms of a decrease in the number of adipocytes presumably due to adipocyte lysis. These favourable changes in body fat mass were accompanied by improvement in at least one metabolic factor associated with obesity - serum leptin concentrations were significantly reduced in treated animals compared with high fat controls. Genetically obese Zucker rats also showed decreases in the number of adipocytes after treatment with antibodies but in contrast to diet-induced obese rats, they showed a compensatory increase in adipocyte volume which attenuated the effects on body fat mass. These results demonstrate for the first time, the potential to treat diet-induced obesity with antibodies to adipocytes by producing long-term reductions in the number of adipocytes, with minimal side-effects. PMID:9813180

  13. Diet-induced obesity mediates a proinflammatory response in pancreatic β cell via toll-like receptor 4

    PubMed Central

    Li, Juan; Chen, Shufen; Qiang, Juan; Wang, Xin; Chen, Lei

    2014-01-01

    Toll-like receptor 4 has an important role in inflammation and immunity. Whether TLR4 signaling contributes to the link between insulin resistance and islet β cell dysfunction is an unanswered question. Here, we show that in the face of the same high-fat continuous stimulation for 24 weeks, in TLR4–/– HF mice, the weight, fraction of the liver, epididymal fat pad fraction, as well as blood glucose and insulin levels were lower than in the WT HF group. In TLR4–/– HF mice, the O2 consumption, CO2 production and activities were higher than in the WT HF group. Glucose tolerance test, insulin tolerance test and insulin release test suggest that the impaired insulin secretion was significantly improved in TLR4–/– HF mice, compared with the WT HF group. In TLR4–/– HF mice, islet β cell ultrastructure was not damaged in the face of the same high-fat continuous stimulation, compared to that in the WT HF group. By detecting glucose-stimulated insulin secretion in the primary islet, insulin secretion of TLR4–/– HF mice was better than that of the WT HF group, and in the TLR4–/– HF group, at the mRNA level, islet interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and monocyte chemotactic protein 1 (MCP-1) were significantly lower than in the WT HF group. There was the islet macrophage infiltration in the WT HF group, but no significant macrophage infiltration in the TLR4–/– HF group. These data suggest that the damaged islet functions of the high fat diet-induced obesity mice may be linked to the TLR4 expression level, and the recruitment of macrophages into the islets. PMID:26155140

  14. Properties of myenteric neurones and mucosal functions in the distal colon of diet-induced obese mice

    PubMed Central

    Reichardt, François; Baudry, Charlotte; Gruber, Lisa; Mazzuoli, Gemma; Moriez, Raphaël; Scherling, Christian; Kollmann, Patrick; Daniel, Hannelore; Kisling, Sigrid; Haller, Dirk; Neunlist, Michel; Schemann, Michael

    2013-01-01

    Colonic transit and mucosal integrity are believed to be impaired in obesity. However, a comprehensive assessment of altered colonic functions, inflammatory changes and neuronal signalling of obese animals is missing. In mice, we studied the impact of diet-induced obesity (DIO) on: (i) in vivo colonic transit; (ii) signalling in the myenteric plexus by recording responses to nicotine and 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), together with the expression of tryptophan hydroxylase (TPH) 1 and 2, serotonin reuptake transporter, choline acetyltransferase and the paired box gene 4; and (iii) expression of proinflammatory cytokines, epithelial permeability and density of macrophages, mast cells and enterochromaffin cells. Compared with controls, colon transit and neuronal sensitivity to nicotine and 2-methyl-5-HT were enhanced in DIO mice fed for 12 weeks. This was associated with increased tissue acetylcholine and 5-hydroxytryptamine (5-HT) content, and increased expression of TPH1 and TPH2. In DIO mice, upregulation of proinflammatory cytokines was found in fat tissue, but not in the gut wall. Accordingly, mucosal permeability or integrity was unaltered without signs of immune cell infiltration in the gut wall. Body weight showed positive correlations with adipocyte markers, tissue levels of 5-HT and acetylcholine, and the degree of neuronal sensitization. DIO mice fed for 4 weeks showed no neuronal sensitization, had no signs of gut wall inflammation and showed a smaller increase in leptin, interleukin-6 and monocyte chemoattractant protein 1 expression in fat tissue. DIO is associated with faster colonic transit and impacts on acetylcholine and 5-HT metabolism with enhanced responsiveness of enteric neurones to both mediators after 12 weeks of feeding. Our study demonstrates neuronal plasticity in DIO prior to the development of a pathological histology or abnormal mucosal functions. This questions the common assumption that increased mucosal inflammation and

  15. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle

    PubMed Central

    Arrabal, Sergio; Lucena, Miguel Angel; Canduela, Miren Josune; Ramos-Uriarte, Almudena; Rivera, Patricia; Serrano, Antonia; Pavón, Francisco Javier; Decara, Juan; Vargas, Antonio; Baixeras, Elena; Martín-Rufián, Mercedes; Márquez, Javier; Fernández-Llébrez, Pedro; De Roos, Baukje; Grandes, Pedro; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg-1, 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle—regulated by both diet and CB1 receptor activity—through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD. PMID:26671069

  16. Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption123

    PubMed Central

    Land, Benjamin B.; Wickham, Robert J.; Maldonado-Aviles, Jaime; de Araujo, Ivan E.; Addy, Nii A.

    2016-01-01

    Abstract 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. PMID:27257625

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

    PubMed Central

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

    2013-01-01

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

  18. Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

    PubMed

    Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

    2016-04-01

    Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. PMID:27012634

  19. Low-Dose Aspartame Consumption Differentially Affects Gut Microbiota-Host Metabolic Interactions in the Diet-Induced Obese Rat

    PubMed Central

    Palmnäs, Marie S. A.; Cowan, Theresa E.; Bomhof, Marc R.; Su, Juliet; Reimer, Raylene A.; Vogel, Hans J.; Hittel, Dustin S.; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5–7 mg/kg/d in drinking water) treatments for 8 week (n = 10–12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

  20. Maintenance of the thyroid axis during diet-induced obesity in rodents is controlled at the central level

    PubMed Central

    Perello, Mario; Çakir, Isin; Cyr, Nicole E.; Romero, Amparo; Stuart, Ronald C.; Chiappini, Franck; Hollenberg, Anthony N.

    2010-01-01

    The hypothalamic-pituitary-thyroid (HPT) axis is a major contributor in maintaining energy expenditure and body weight, and the adipocyte hormone leptin regulates this axis by increasing TRH levels in the fed state. Leptin stimulates TRH directly in the hypothalamic paraventricular nucleus (PVN; direct pathway) and indirectly by regulating proopiomelnocortin neurons in the hypothalamic arcuate nucleus (ARC; indirect pathway). Whereas the indirect pathway is fully functional in lean animals, it is inactive during diet-induced obesity (DIO) because of the establishment of leptin resistance. Despite this, the HPT axis activity in obese humans and rodents remains within the normal levels or slightly higher. Therefore, in this study, we aimed to determine the mechanism(s) by which the HPT axis is still active despite leptin resistance. With a combination of using the Sprague-Dawley rat physiological model and the Zuker rat that bears a mutation in the leptin receptor, we were able to demonstrate that under DIO conditions the HPT axis is regulated at the central level, but only through the direct pathway of leptin action on TRH neurons. Deiodinase enzymes, which are present in many tissues and responsible for converting thyroid hormones, were not statistically different between lean and DIO animals. These data suggest that the increase in T4/3 seen in obese animals is due mostly to central leptin action. We also found that T3 feedback inhibition on the prepro-TRH gene is controlled partially by leptin-induced pSTAT3 signaling via the TRH promoter. This interactive relationship between T3 and pSTAT3 signaling appears essential to maintain the HPT axis at normal levels in conditions such as obesity. PMID:20858755

  1. Pharmacological Blockade of Cannabinoid CB1 Receptors in Diet-Induced Obesity Regulates Mitochondrial Dihydrolipoamide Dehydrogenase in Muscle.

    PubMed

    Arrabal, Sergio; Lucena, Miguel Angel; Canduela, Miren Josune; Ramos-Uriarte, Almudena; Rivera, Patricia; Serrano, Antonia; Pavón, Francisco Javier; Decara, Juan; Vargas, Antonio; Baixeras, Elena; Martín-Rufián, Mercedes; Márquez, Javier; Fernández-Llébrez, Pedro; De Roos, Baukje; Grandes, Pedro; Rodríguez de Fonseca, Fernando; Suárez, Juan

    2015-01-01

    Cannabinoid CB1 receptors peripherally modulate energy metabolism. Here, we investigated the role of CB1 receptors in the expression of glucose/pyruvate/tricarboxylic acid (TCA) metabolism in rat abdominal muscle. Dihydrolipoamide dehydrogenase (DLD), a flavoprotein component (E3) of α-ketoacid dehydrogenase complexes with diaphorase activity in mitochondria, was specifically analyzed. After assessing the effectiveness of the CB1 receptor antagonist AM251 (3 mg kg(-1), 14 days) on food intake and body weight, we could identified seven key enzymes from either glycolytic pathway or TCA cycle--regulated by both diet and CB1 receptor activity--through comprehensive proteomic approaches involving two-dimensional electrophoresis and MALDI-TOF/LC-ESI trap mass spectrometry. These enzymes were glucose 6-phosphate isomerase (GPI), triosephosphate isomerase (TPI), enolase (Eno3), lactate dehydrogenase (LDHa), glyoxalase-1 (Glo1) and the mitochondrial DLD, whose expressions were modified by AM251 in hypercaloric diet-induced obesity. Specifically, AM251 blocked high-carbohydrate diet (HCD)-induced expression of GPI, TPI, Eno3 and LDHa, suggesting a down-regulation of glucose/pyruvate/lactate pathways under glucose availability. AM251 reversed the HCD-inhibited expression of Glo1 and DLD in the muscle, and the DLD and CB1 receptor expression in the mitochondrial fraction. Interestingly, we identified the presence of CB1 receptors at the membrane of striate muscle mitochondria. DLD over-expression was confirmed in muscle of CB1-/- mice. AM251 increased the pyruvate dehydrogenase and glutathione reductase activity in C2C12 myotubes, and the diaphorase/oxidative activity in the mitochondria fraction. These results indicated an up-regulation of methylglyoxal and TCA cycle activity. Findings suggest that CB1 receptors in muscle modulate glucose/pyruvate/lactate pathways and mitochondrial oxidative activity by targeting DLD. PMID:26671069

  2. Nootkatone, a characteristic constituent of grapefruit, stimulates energy metabolism and prevents diet-induced obesity by activating AMPK.

    PubMed

    Murase, Takatoshi; Misawa, Koichi; Haramizu, Satoshi; Minegishi, Yoshihiko; Hase, Tadashi

    2010-08-01

    AMP-activated protein kinase (AMPK) is a serine/threonine kinase that is implicated in the control of energy metabolism and is considered to be a molecular target for the suppression of obesity and the treatment of metabolic syndrome. Here, we identified and characterized nootkatone, a constituent of grapefruit, as a naturally occurring AMPK activator. Nootkatone induced an increase in AMPKalpha1 and -alpha2 activity along with an increase in the AMP/ATP ratio and an increase the phosphorylation of AMPKalpha and the downstream target acetyl-CoA carboxylase (ACC), in C(2)C(12) cells. Nootkatone-induced activation of AMPK was possibly mediated both by LKB1 and Ca(2+)/calmodulin-dependent protein kinase kinase. Nootkatone also upregulated PPARgamma coactivator-1alpha in C(2)C(12) cells and C57BL/6J mouse muscle. In addition, administration of nootkatone (200 mg/kg body wt) significantly enhanced AMPK activity, accompanied by LKB1, AMPK, and ACC phosphorylation in the liver and muscle of mice. Whole body energy expenditure evaluated by indirect calorimetry was also increased by nootkatone administration. Long-term intake of diets containing 0.1% to 0.3% (wt/wt) nootkatone significantly reduced high-fat and high-sucrose diet-induced body weight gain, abdominal fat accumulation, and the development of hyperglycemia, hyperinsulinemia, and hyperleptinemia in C57BL/6J mice. Furthermore, endurance capacity, evaluated as swimming time to exhaustion in BALB/c mice, was 21% longer in mice fed 0.2% nootkatone than in control mice. These findings indicate that long-term intake of nootkatone is beneficial toward preventing obesity and improving physical performance and that these effects are due, at least in part, to enhanced energy metabolism through AMPK activation in skeletal muscle and liver. PMID:20501876

  3. Low-dose aspartame consumption differentially affects gut microbiota-host metabolic interactions in the diet-induced obese rat.

    PubMed

    Palmnäs, Marie S A; Cowan, Theresa E; Bomhof, Marc R; Su, Juliet; Reimer, Raylene A; Vogel, Hans J; Hittel, Dustin S; Shearer, Jane

    2014-01-01

    Aspartame consumption is implicated in the development of obesity and metabolic disease despite the intention of limiting caloric intake. The mechanisms responsible for this association remain unclear, but may involve circulating metabolites and the gut microbiota. Aims were to examine the impact of chronic low-dose aspartame consumption on anthropometric, metabolic and microbial parameters in a diet-induced obese model. Male Sprague-Dawley rats were randomized into a standard chow diet (CH, 12% kcal fat) or high fat (HF, 60% kcal fat) and further into ad libitum water control (W) or low-dose aspartame (A, 5-7 mg/kg/d in drinking water) treatments for 8 week (n = 10-12 animals/treatment). Animals on aspartame consumed fewer calories, gained less weight and had a more favorable body composition when challenged with HF compared to animals consuming water. Despite this, aspartame elevated fasting glucose levels and an insulin tolerance test showed aspartame to impair insulin-stimulated glucose disposal in both CH and HF, independently of body composition. Fecal analysis of gut bacterial composition showed aspartame to increase total bacteria, the abundance of Enterobacteriaceae and Clostridium leptum. An interaction between HF and aspartame was also observed for Roseburia ssp wherein HF-A was higher than HF-W (P<0.05). Within HF, aspartame attenuated the typical HF-induced increase in the Firmicutes:Bacteroidetes ratio. Serum metabolomics analysis revealed aspartame to be rapidly metabolized and to be associated with elevations in the short chain fatty acid propionate, a bacterial end product and highly gluconeogenic substrate, potentially explaining its negative affects on insulin tolerance. How aspartame influences gut microbial composition and the implications of these changes on the development of metabolic disease require further investigation. PMID:25313461

  4. Response to diet-induced obesity produces time-dependent induction and progression of metabolic osteoarthritis in rat knees.

    PubMed

    Collins, Kelsey H; Hart, David A; Reimer, Raylene A; Seerattan, Ruth A; Herzog, Walter

    2016-06-01

    Obesity, and corresponding chronic-low grade inflammation, is associated with the onset and progression of knee OA. The origin of this inflammation is poorly understood. Here, the effect of high fat, high sucrose (HFS) diet induced obesity (DIO) on local (synovial fluid), and systemic (serum) inflammation is evaluated after a 12-week obesity induction and a further 16-week adaptation period. For 12-weeks of obesity induction, n = 40 DIO male Sprague-Dawley rats consumed a HFS diet while the control group (n = 14) remained on chow. DIO rats were allocated to prone (DIO-P, top 33% based on weight change) or resistant (DIO-R, bottom 33%) groups at 12-weeks. Animals were euthanized at 12- and after an additional 16-weeks on diet (28-weeks). At sacrifice, body composition and knee joints were collected and assessed. Synovial fluid and sera were profiled using cytokine array analysis. At 12-weeks, DIO-P animals demonstrated increased Modified Mankin scores compared to DIO-R and chow (p = 0.026), and DIO-R had higher Mankin scores compared to chow (p = 0.049). While numerous systemic and limited synovial fluid inflammatory markers were increased at 12-weeks in DIO animals compared to chow, by 28-weeks there were limited systemic differences but marked increases in local synovial fluid inflammatory marker concentrations. Metabolic OA may manifest from an initial systemic inflammatory disturbance. Twelve weeks of obesity induction leads to a unique inflammatory profile and induction of metabolic OA which is altered after a further 16-weeks of obesity and HFS diet intake, suggesting that obesity is a dynamic, progressive process. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1010-1018, 2016. PMID:26572064

  5. Antiobesity Effects of an Edible Halophyte Nitraria retusa Forssk in 3T3-L1 Preadipocyte Differentiation and in C57B6J/L Mice Fed a High Fat Diet-Induced Obesity

    PubMed Central

    Zar Kalai, Feten; Han, Junkyu; Ksouri, Riadh; El Omri, Abdelfatteh; Abdelly, Chedly; Isoda, Hiroko

    2013-01-01

    Nitraria retusa is an edible halophyte, used in Tunisia for several traditional medicine purposes. The present study investigated the antiobesity effects of Nitraria retusa ethanol extract (NRE) in 3T3-L1 cells using different doses and in high-fat diet-induced obesity in mice. Male C57B6J/L mice were separately fed a normal diet (ND) or a high-fat diet (HFD) and daily administrated with NRE (50, 100 mg/kg) or one for 2 days with Naringenin (10 mg/kg). NRE administration significantly decreased body weight gain, fat pad weight, serum glucose, and lipid levels in HFD-induced obese mice. To elucidate the mechanism of action of NRE, the expression of genes involved in lipid and carbohydrate metabolism were measured in liver. Results showed that mice treated with NRE demonstrated a significant decrease in cumulative body weight and fat pad weight, a significant lowering in glucose and triglycerides serum levels, and an increase in the HDL-cholesterol serum level. Moreover mRNA expression results showed an enhancement of the expression of genes related to liver metabolism. Our findings suggest that NRE treatment had a protective or controlling effect against a high fat diet-induced obesity in C57B6J/L mice through the regulation of expression of genes involved in lipolysis and lipogenesis and thus the enhancement of the lipid metabolism in liver. PMID:24367387

  6. Increased Plasma Citrulline in Mice Marks Diet-Induced Obesity and May Predict the Development of the Metabolic Syndrome

    PubMed Central

    Sailer, Manuela; Dahlhoff, Christoph; Giesbertz, Pieter; Eidens, Mena K.; de Wit, Nicole; Rubio-Aliaga, Isabel; Boekschoten, Mark V.; Müller, Michael; Daniel, Hannelore

    2013-01-01

    In humans, plasma amino acid concentrations of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) increase in states of obesity, insulin resistance and diabetes. We here assessed whether these putative biomarkers can also be identified in two different obesity and diabetic mouse models. C57BL/6 mice with diet-induced obesity (DIO) mimic the metabolic impairments of obesity in humans characterized by hyperglycemia, hyperinsulinemia and hepatic triglyceride accumulation. Mice treated with streptozotocin (STZ) to induce insulin deficiency were used as a type 1 diabetes model. Plasma amino acid profiling of two high fat (HF) feeding trials revealed that citrulline and ornithine concentrations are elevated in obese mice, while systemic arginine bioavailability (ratio of plasma arginine to ornithine + citrulline) is reduced. In skeletal muscle, HF feeding induced a reduction of arginine levels while citrulline levels were elevated. However, arginine or citrulline remained unchanged in their key metabolic organs, intestine and kidney. Moreover, the intestinal conversion of labeled arginine to ornithine and citrulline in vitro remained unaffected by HF feeding excluding the intestine as prime site of these alterations. In liver, citrulline is mainly derived from ornithine in the urea cycle and DIO mice displayed reduced hepatic ornithine levels. Since both amino acids share an antiport mechanism for mitochondrial import and export, elevated plasma citrulline may indicate impaired hepatic amino acid handling in DIO mice. In the insulin deficient mice, plasma citrulline and ornithine levels also increased and additionally these animals displayed elevated BCAA and AAA levels like insulin resistant and diabetic patients. Therefore, type 1 diabetic mice but not DIO mice show the “diabetic fingerprint” of plasma amino acid changes observed in humans. Additionally, citrulline may serve as an early indicator of the obesity-dependent metabolic impairments. PMID

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

    PubMed Central

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

    2015-01-01

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

  8. Impaired intestinal afferent nerve satiety signalling and vagal afferent excitability in diet induced obesity in the mouse.

    PubMed

    Daly, Donna M; Park, Sung Jin; Valinsky, William C; Beyak, Michael J

    2011-06-01

    Gastrointestinal vagal afferents transmit satiety signals to the brain via both chemical and mechanical mechanisms. There is indirect evidence that these signals may be attenuated in obesity. We hypothesized that responses to satiety mediators and distension of the gut would be attenuated after induction of diet induced obesity. Obesity was induced by feeding a high fat diet (60% kcal from fat). Low fat fed mice (10% kcal from fat) served as a control. High fat fed mice were obese, with increased visceral fat, but were not hyperglycaemic. Recordings from jejunal afferents demonstrated attenuated responses to the satiety mediators cholecystokinin (CCK, 100 nm) and 5-hydroxytryptamine (5-HT, 10 μm), as was the response to low intensity jejunal distension, while responses to higher distension pressures were preserved. We performed whole cell patch clamp recordings on nodose ganglion neurons, both unlabelled, and those labelled by fast blue injection into the wall of the jejunum. The cell membrane of both labelled and unlabelled nodose ganglion neurons was less excitable in HFF mice, with an elevated rheobase and decreased number of action potentials at twice rheobase. Input resistance of HFF neurons was also significantly decreased. Calcium imaging experiments revealed reduced proportion of nodose ganglion neurons responding to CCK and 5-HT in obese mice. These results demonstrate a marked reduction in afferent sensitivity to satiety related stimuli after a chronic high fat diet. A major mechanism underlying this change is reduced excitability of the neuronal cell membrane. This may explain the development of hyperphagia when a high fat diet is consumed. Improving sensitivity of gastrointestinal afferent nerves may prove useful to limit food intake in obesity. PMID:21486762

  9. Feasibility of simultaneous PET/MR in diet-induced atherosclerotic minipig: a pilot study for translational imaging

    PubMed Central

    Pedersen, Sune F; Ludvigsen, Trine P; Johannesen, Helle H; Löfgren, Johan; Ripa, Rasmus S; Hansen, Adam E; Ettrup, Anders J; Christoffersen, Berit Ø; Pedersen, Henrik D; Olsen, Lisbeth H; Højgaard, Liselotte; Kjær, Andreas

    2014-01-01

    Novel hybrid 18-fluoro-deoxy-D-glucose (18F-FDG) based positron emission tomography (PET) and magnetic resonance imaging (MRI) has shown promise for characterization of atherosclerotic plaques clinically. The purpose of this study was to evaluate the method in a pre-clinical model of diet-induced atherosclerosis, based on the Göttingen minipig. Using 18F-FDG PET/MRI the goal was to develop and create a new imaging method in an in vivo animal model for translational studies of atherosclerosis. We used a strategy of multisequence MRI for optimal anatomical imaging of the abdominal aortas of the pigs (n=4): T1-weighted turbo spin-echo (T1-TSE), T2-weighted turbo spin-echo (T2-TSE) and proton density imaging with and without fat saturation. 18F-FDG PET emission data were collected from a single bed position of the abdominal aorta in 3D mode for either 10 (n=4) or 10 and 20 minutes (n=2) to measure glycolysis as given by standardized uptake values (SUV). Ex vivo en face evaluation of aortas from an atherosclerotic animal illustrated plaque distribution macroscopically, compared to a lean control animal. Although T2-TSE weighted imaging was most consistent, no one MRI sequence was preferable and superior to another for visualization and identification of the abdominal aorta. We found poor correlation between SUVs obtained from 10 and 20 minutes of reconstructed PET emission data. This can most likely be ascribed to intestinal movement. In conclusion multisequence MRI is recommended for optimal imaging of the abdominal aorta using MRI. Furthermore we found that 10 minutes of PET emission data seems adequate. This is the first study to demonstrate that the method of 18F-FDG PET/MRI is feasible in minipig models of atherosclerosis, and therefore relevant in larger prospective studies. Perspectives of the method include correlation to e.g. aortic immunohistochemistry findings and a range of genomic and proteomic analyses. PMID:25143863

  10. Diet-induced obesity mediated by the JNK/DIO2 signal transduction pathway

    PubMed Central

    Vernia, Santiago; Cavanagh-Kyros, Julie; Barrett, Tamera; Jung, Dae Young; Kim, Jason K.; Davis, Roger J.

    2013-01-01

    The cJun N-terminal kinase (JNK) signaling pathway is a key mediator of metabolic stress responses caused by consuming a high-fat diet, including the development of obesity. To test the role of JNK, we examined diet-induced obesity in mice with targeted ablation of Jnk genes in the anterior pituitary gland. These mice exhibited an increase in the pituitary expression of thyroid-stimulating hormone (TSH), an increase in the blood concentration of thyroid hormone (T4), increased energy expenditure, and markedly reduced obesity compared with control mice. The increased amount of pituitary TSH was caused by reduced expression of type 2 iodothyronine deiodinase (Dio2), a gene that is required for T4-mediated negative feedback regulation of TSH expression. These data establish a molecular mechanism that accounts for the regulation of energy expenditure and the development of obesity by the JNK signaling pathway. PMID:24186979

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2013-08-01

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

  13. Neuron-Specific Deletion of Peroxisome Proliferator-Activated Receptor Delta (PPARδ) in Mice Leads to Increased Susceptibility to Diet-Induced Obesity

    PubMed Central

    Kocalis, Heidi E.; Turney, Maxine K.; Printz, Richard L.; Laryea, Gloria N.; Muglia, Louis J.; Davies, Sean S.; Stanwood, Gregg D.; McGuinness, Owen P.; Niswender, Kevin D.

    2012-01-01

    Central nervous system (CNS) lipid accumulation, inflammation and resistance to adipo-regulatory hormones, such as insulin and leptin, are implicated in the pathogenesis of diet-induced obesity (DIO). Peroxisome proliferator-activated receptors (PPAR α, δ, γ) are nuclear transcription factors that act as environmental fatty acid sensors and regulate genes involved in lipid metabolism and inflammation in response to dietary and endogenous fatty acid ligands. All three PPAR isoforms are expressed in the CNS at different levels. Recent evidence suggests that activation of CNS PPARα and/or PPARγ may contribute to weight gain and obesity. PPARδ is the most abundant isoform in the CNS and is enriched in the hypothalamus, a region of the brain involved in energy homeostasis regulation. Because in peripheral tissues, expression of PPARδ increases lipid oxidative genes and opposes inflammation, we hypothesized that CNS PPARδ protects against the development of DIO. Indeed, genetic neuronal deletion using Nes-Cre loxP technology led to elevated fat mass and decreased lean mass on low-fat diet (LFD), accompanied by leptin resistance and hypothalamic inflammation. Impaired regulation of neuropeptide expression, as well as uncoupling protein 2, and abnormal responses to a metabolic challenge, such as fasting, also occur in the absence of neuronal PPARδ. Consistent with our hypothesis, KO mice gain significantly more fat mass on a high-fat diet (HFD), yet are surprisingly resistant to diet-induced elevations in CNS inflammation and lipid accumulation. We detected evidence of upregulation of PPARγ and target genes of both PPARα and PPARγ, as well as genes of fatty acid oxidation. Thus, our data reveal a previously underappreciated role for neuronal PPARδ in the regulation of body composition, feeding responses, and in the regulation of hypothalamic gene expression. PMID:22916190

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

    PubMed

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

    2015-04-01

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

  15. Paradoxical resistance to diet-induced obesity in UCP1-deficient mice

    PubMed Central

    Liu, Xiaotuan; Rossmeisl, Martin; McClaine, Jennifer; Kozak, Leslie P.

    2003-01-01

    The availability of mice lacking the mitochondrial uncoupling protein UCP1, has provided an opportunity to analyze the relationship between the capacity for energy expenditure and the development of obesity in response to a high-fat, high-sucrose diet. Congenic UCP1-deficient mice on a C57BL/6J genetic background show a temperature-dependent resistance to diet-induced obesity when compared with wild-type mice. This resistance, which occurs at 20°C, is quickly reversed when the ambient temperature is increased to 27°C. At 20°C, total oxygen consumption and physical activity of mutant and wild-type mice are indistinguishable; however, body temperature is higher in UCP1-deficient mice by 0.1–0.3°C, and respiratory quotient is slightly reduced. A reduced respiratory quotient, together with elevated β-hydroxybutyrate and reduced plasma fatty acid levels, suggests that the mutants oxidize a greater proportion of fat than wild-type mice, and that this possibly accounts for the resistance to diet-induced obesity. Although shivering is one alternative mechanism of thermogenesis that is probably used in UCP1-deficient mice, whether there are others remains to be determined. Nevertheless, our study underscores the paradox that elimination of the major thermogenic mechanism in the animal reduces rather than increases metabolic efficiency. We propose that in the absence of nonshivering thermogenesis, alternative, calorically more costly pathways of metabolism must be used to maintain body temperature. PMID:12569166

  16. Use of hamster as a model to study diet-induced atherosclerosis

    PubMed Central

    2010-01-01

    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 apoB-100 and intestinal apoB-48 secretion, and uptake of the majority of LDL cholesterol via the LDL receptor pathway. Early work suggested hamsters fed high cholesterol and saturated fat diets responded similarly to humans in terms of lipoprotein metabolism and aortic lesion morphology. Recent work has not consistently replicated these findings. Reviewed was the literature related to controlled hamster feeding studies that assessed the effect of strain, background diet (non-purified, semi-purified) and dietary perturbation (cholesterol and/or fat) on plasma lipoprotein profiles and atherosclerotic lesion formation. F1B hamsters fed a non-purified cholesterol/fat-supplemented diet had more atherogenic lipoprotein profiles (nHDL-C > HDL-C) than other hamster strains or hamsters fed cholesterol/fat-supplemented semi-purified diets. However, fat type; saturated (SFA), monounsaturated or n-6 polyunsaturated (PUFA) had less of an effect on plasma lipoprotein concentrations. Cholesterol- and fish oil-supplemented semi-purified diets yielded highly variable results when compared to SFA or n-6 PUFA, which were antithetical to responses observed in humans. Dietary cholesterol and fat resulted in inconsistent effects on aortic lipid accumulation. No hamster strain was reported to consistently develop lesions regardless of background diet, dietary cholesterol or dietary fat type amount. In conclusion, at this time the Golden-Syrian hamster does not appear to be a useful model to determine the mechanism(s) of diet-induced development of atherosclerotic lesions. PMID:21143982

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

    PubMed Central

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

    2016-01-01

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

  18. β-Cryptoxanthin Alleviates Diet-Induced Nonalcoholic Steatohepatitis by Suppressing Inflammatory Gene Expression in Mice

    PubMed Central

    Kobori, Masuko; Ni, Yinhua; Takahashi, Yumiko; Watanabe, Natsumi; Sugiura, Minoru; Ogawa, Kazunori; Nagashimada, Mayumi; Kaneko, Shuichi; Naito, Shigehiro; Ota, Tsuguhito

    2014-01-01

    Recent nutritional epidemiological surveys showed that serum β-cryptoxanthin inversely associates with the risks for insulin resistance and liver dysfunction. Consumption of β-cryptoxanthin possibly prevents nonalcoholic steatohepatitis (NASH), which is suggested to be caused by insulin resistance and oxidative stress from nonalcoholic fatty liver disease. To evaluate the effect of β-cryptoxanthin on diet-induced NASH, we fed a high-cholesterol and high-fat diet (CL diet) with or without 0.003% β-cryptoxanthin to C56BL/6J mice for 12 weeks. After feeding, β-cryptoxanthin attenuated fat accumulation, increases in Kupffer and activated stellate cells, and fibrosis in CL diet-induced NASH in the mice. Comprehensive gene expression analysis showed that although β-cryptoxanthin histochemically reduced steatosis, it was more effective in inhibiting inflammatory gene expression change in NASH. β-Cryptoxanthin reduced the alteration of expression of genes associated with cell death, inflammatory responses, infiltration and activation of macrophages and other leukocytes, quantity of T cells, and free radical scavenging. However, it showed little effect on the expression of genes related to cholesterol and other lipid metabolism. The expression of markers of M1 and M2 macrophages, T helper cells, and cytotoxic T cells was significantly induced in NASH and reduced by β-cryptoxanthin. β-Cryptoxanthin suppressed the expression of lipopolysaccharide (LPS)-inducible and/or TNFα-inducible genes in NASH. Increased levels of the oxidative stress marker thiobarbituric acid reactive substances (TBARS) were reduced by β-cryptoxanthin in NASH. Thus, β-cryptoxanthin suppresses inflammation and the resulting fibrosis probably by primarily suppressing the increase and activation of macrophages and other immune cells. Reducing oxidative stress is likely to be a major mechanism of inflammation and injury suppression in the livers of mice with NASH. PMID:24858832

  19. A diet-induced animal model of non-alcoholic fatty liver disease and hepatocellular cancer

    PubMed Central

    Asgharpour, Amon; Cazanave, Sophie C.; Pacana, Tommy; Seneshaw, Mulugeta; Vincent, Robert; Banini, Bubu A.; Kumar, Divya Prasanna; Daita, Kalyani; Min, Hae-Ki; Mirshahi, Faridoddin; Bedossa, Pierre; Sun, Xiaochen; Hoshida, Yujin; Koduru, Srinivas V.; Contaifer, Daniel; Warncke, Urszula Osinska; Wijesinghe, Dayanjan S.; Sanyal, Arun J.

    2016-01-01

    Background & Aims The lack of a preclinical model of progressive non-alcoholic steatohepatitis (NASH) that recapitulates human disease is a barrier to therapeutic development. Methods A stable isogenic cross between C57BL/6J (B6) and 129S1/SvImJ (S129) mice were fed a high fat diet with ad libitum consumption of glucose and fructose in physiologically relevant concentrations and compared to mice fed a chow diet and also to both parent strains. Results Following initiation of the obesogenic diet, B6/129 mice developed obesity, insulin resistance, hypertriglyceridemia and increased LDL-cholesterol. They sequentially also developed steatosis (4–8 weeks), steatohepatitis (16–24 weeks), progressive fibrosis (16 weeks onwards) and spontaneous hepatocellular cancer (HCC). There was a strong concordance between the pattern of pathway activation at a transcriptomic level between humans and mice with similar histological phenotypes (FDR 0.02 for early and 0.08 for late time points). Lipogenic, inflammatory and apoptotic signaling pathways activated in human NASH were also activated in these mice. The HCC gene signature resembled the S1 and S2 human subclasses of HCC (FDR 0.01 for both). Only the B6/129 mouse but not the parent strains recapitulated all of these aspects of human NAFLD. Conclusions We here describe a diet-induced animal model of non-alcoholic fatty liver disease (DIAMOND) that recapitulates the key physiological, metabolic, histologic, transcriptomic and cell-signaling changes seen in humans with progressive NASH. Lay summary We have developed a diet-induced mouse model of non-alcoholic steatohepatitis (NASH) and hepatic cancers in a cross between two mouse strains (129S1/SvImJ and C57Bl/6J). This model mimics all the physiological, metabolic, histological, transcriptomic gene signature and clinical endpoints of human NASH and can facilitate preclinical development of therapeutic targets for NASH. PMID:27261415

  20. Hepatic overexpression of bovine scavenger receptor type I in transgenic mice prevents diet-induced hyperbetalipoproteinemia.

    PubMed Central

    Wölle, S; Via, D P; Chan, L; Cornicelli, J A; Bisgaier, C L

    1995-01-01

    Hepatic scavenger receptors (SR) may play a protective role by clearing modified lipoproteins before they target the artery wall. To gain insight into this hypothesized function, transgenic mice expressing hepatic bovine SR (TgSR) were created and studied when fed chow, and during diet-induced hyperlipidemia. SR overexpression resulted in extensive hepatic parenchymal cell uptake of fluorescently labeled acetylated human low density lipoprotein (DiI ac-hLDL) and a twofold increase in 125I-acetylated-LDL clearance. Food intake and cholesterol absorption was indistinguishable between control and TgSR mice. In chow-fed mice, lipoprotein cholesterol was similar in control and TgSR mice. However, on a 3-wk high fat/cholesterol (HFHC) diet, the rise in apoB containing lipoproteins was suppressed in TgSR+/- and TgSR+/+ mice. The rise in HDL was similar in control and TgSR+/- mice, but significantly elevated in the TgSR+/+ mice. Overall, on chow, the ratio of apo-B containing lipoprotein cholesterol to HDL cholesterol was similar for all groups (control = 0.33; TgSR+/- = 0.32; TgSR+/+ = 0.38). However, after 3 wk on the HFHC diet, this ratio was markedly higher in control (2.34 +/- 0.21) than in either TgSR+/- (1.00 +/- 0.24) or TgSR+/+ (1.00 +/- 0.19) mice. In TgSR+/- mice, hepatic cholesteryl esters were reduced by 59%, 7 alpha-hydroxylase mRNA levels were elevated twofold, and a significant increase in fecal bile acid flux was observed after the 3-wk HFHC diet. These results suggest SR may play a protective role in liver by preventing diet-induced increases in apoB containing lipoproteins. Images PMID:7615795

  1. Amelioration of diet-induced diabetes mellitus by removal of visceral fat.

    PubMed

    Pitombo, Cid; Araújo, Eliana P; De Souza, Cláudio T; Pareja, José C; Geloneze, Bruno; Velloso, Lício A

    2006-12-01

    The effect of visceral fat removal upon glucose homeostasis, insulin signal transduction, and serum adipokine levels in an animal model of diet-induced obesity and diabetes mellitus (DIO) was evaluated. Swiss mice were initially divided into two groups fed with regular rodent chow or with chow containing 24 g% saturated fat (DIO). DIO mice became obese and overtly diabetic after 8 weeks. DIO mice were then divided into three groups: control, sham, and visceral (epididymal and perinephric) fat removal. All groups were submitted to evaluation of basal glucose and insulin levels and i.p. insulin tolerance test. Insulin signal transduction in muscle was evaluated by immunoprecipitation and immunoblot, and serum adipokine levels were determined by ELISA. DIO mice became diabetic (228 versus 115 mg/dl), hyperinsulinemic (7.59 versus 3.15 ng/ml) and insulin resistant (K(itt) 2.88 versus 4.97%/min) as compared with control. Visceral fat removal partially reverted all parameters (147 mg/dl glucose; 3.82 ng/ml insulin; and 4.20%/min K(itt)). In addition, visceral fat removal completely reversed the impairment of insulin signal transduction through insulin receptor, insulin receptor substrate (IRS)-1, IRS-2 and Akt in muscle. Finally, serum levels of the pro-inflammatory cytokines tumour necrosis factor-alpha, interleukin (IL)-1beta and IL-6 were significantly increased, while adiponectin levels were significantly reduced in DIO mice. After visceral fat removal the levels of adipokines returned to near control levels. The present study shows that removal of visceral fat improves insulin signal transduction and glucose homeostasis in an animal model of diet-induced obesity and diabetes mellitus and these metabolic and molecular outcomes are accompanied by the restoration of adipokine levels. PMID:17170226

  2. Weight Loss, Dietary Intake and Pulse Wave Velocity.

    PubMed

    Petersen, Kristina; Blanch, Natalie; Keogh, Jennifer; Clifton, Peter

    2015-09-01

    We have recently conducted a meta-analysis to determine the effect of weight loss achieved by an energy-restricted diet with or without exercise, anti-obesity drugs or bariatric surgery on pulse wave velocity (PWV) measured at all arterial segments. Twenty studies, including 1,259 participants, showed that modest weight loss (8% of the initial body weight) caused a reduction in PWV measured at all arterial segments. However, due to the poor methodological design of the included studies, the results of this meta-analysis can only be regarded as hypothesis generating and highlight the need for further research in this area. In the future, well-designed randomised controlled trials are required to determine the effect of diet-induced weight loss on PWV and the mechanisms involved. In addition, there is observational evidence that dietary components such as fruit, vegetables, dairy foods, sodium, potassium and fatty acids may be associated with PWV, although evidence from well-designed intervention trials is lacking. In the future, the effect of concurrently improving dietary quality and achieving weight loss should be assessed in randomised controlled trials. PMID:26587462

  3. Weight Loss, Dietary Intake and Pulse Wave Velocity

    PubMed Central

    Petersen, Kristina; Blanch, Natalie; Keogh, Jennifer; Clifton, Peter

    2015-01-01

    We have recently conducted a meta-analysis to determine the effect of weight loss achieved by an energy-restricted diet with or without exercise, anti-obesity drugs or bariatric surgery on pulse wave velocity (PWV) measured at all arterial segments. Twenty studies, including 1,259 participants, showed that modest weight loss (8% of the initial body weight) caused a reduction in PWV measured at all arterial segments. However, due to the poor methodological design of the included studies, the results of this meta-analysis can only be regarded as hypothesis generating and highlight the need for further research in this area. In the future, well-designed randomised controlled trials are required to determine the effect of diet-induced weight loss on PWV and the mechanisms involved. In addition, there is observational evidence that dietary components such as fruit, vegetables, dairy foods, sodium, potassium and fatty acids may be associated with PWV, although evidence from well-designed intervention trials is lacking. In the future, the effect of concurrently improving dietary quality and achieving weight loss should be assessed in randomised controlled trials. PMID:26587462

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

    PubMed Central

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

    2014-01-01

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

  5. Weight and Glucose Reduction Observed with a Combination of Nutritional Agents in Rodent Models Does Not Translate to Humans in a Randomized Clinical Trial with Healthy Volunteers and Subjects with Type 2 Diabetes

    PubMed Central

    Hodge, Rebecca J.; Paulik, Mark A.; Walker, Ann; Boucheron, Joyce A.; McMullen, Susan L.; Gillmor, Dawn S.; Nunez, Derek J.

    2016-01-01

    Background Nutritional agents have modest efficacy in reducing weight and blood glucose in animal models and humans, but combinations are less well characterized. GSK2890457 (GSK457) is a combination of 4 nutritional agents, discovered by the systematic assessment of 16 potential components using the diet-induced obese mouse model, which was subsequently evaluated in a human study. Nonclinical Results In the diet-induced obese mouse model, GSK457 (15% w/w in chow) given with a long-acting glucagon-like peptide -1 receptor agonist, exendin-4 AlbudAb, produced weight loss of 30.8% after 28 days of treatment. In db/db mice, a model of diabetes, GSK457 (10% w/w) combined with the exendin-4 AlbudAb reduced glucose by 217 mg/dL and HbA1c by 1.2% after 14 days. Clinical Results GSK457 was evaluated in a 6 week randomized, placebo-controlled study that enrolled healthy subjects and subjects with type 2 diabetes to investigate changes in weight and glucose. In healthy subjects, GSK457 well tolerated when titrated up to 40 g/day, and it reduced systemic exposure of metformin by ~ 30%. In subjects with diabetes taking liraglutide 1.8 mg/day, GSK457 did not reduce weight, but it slightly decreased mean glucose by 0.356 mmol/L (95% CI: -1.409, 0.698) and HbAlc by 0.065% (95% CI: -0.495, 0.365), compared to placebo. In subjects with diabetes taking metformin, weight increased in the GSK457-treated group [adjusted mean % increase from baseline: 1.26% (95% CI: -0.24, 2.75)], and mean glucose and HbA1c were decreased slightly compared to placebo [adjusted mean glucose change from baseline: -1.22 mmol/L (95% CI: -2.45, 0.01); adjusted mean HbA1c change from baseline: -0.219% (95% CI: -0.910, 0.472)]. Conclusions Our data demonstrate remarkable effects of GSK457 in rodent models of obesity and diabetes, but a marked lack of translation to humans. Caution should be exercised with nutritional agents when predicting human efficacy from rodent models of obesity and diabetes. Trial

  6. Effects of voluntary running and soy supplementation on diet-induced metabolic disturbances and inflammation in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of voluntary running and soy supplementation on diet-induced metabolic disturbance and inflammation in male C57BL/6 mice using a 2x2x2 design in which the effects of diet (AIN93G or its modification with 45% calories from fat), activity level (sedentary or ...

  7. Inflammation status in adipose tissue and peritoneal macrophages of young and old mice in diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity causes a low grade inflammation. We have shown that aging is also associated with upregulated inflammation in adipose tissue. In this study, we investigated effect of diet-induced obesity on inflammation status in young and old mice. Young (2-mo) and old (19-mo) C57BL/6 mice were fed low fat...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  10. A Rat Model to Study the Effects of Diet-Induced Obesity on Radiation-Induced Mammary Carcinogenesis.

    PubMed

    Imaoka, Tatsuhiko; Nishimura, Mayumi; Daino, Kazuhiro; Morioka, Takamitsu; Nishimura, Yukiko; Uemura, Hiroji; Akimoto, Kenta; Furukawa, Yuki; Fukushi, Masahiro; Wakabayashi, Keiji; Mutoh, Michihiro; Shimada, Yoshiya

    2016-05-01

    A detailed understanding of the relationship between radiation-induced breast cancer and obesity is needed for appropriate risk management and to prevent the development of a secondary cancer in patients who have been treated with radiation. Our goal was to develop an animal model to study the relationship by combining two existing Sprague-Dawley rat models of radiation-induced mammary carcinogenesis and diet-induced obesity. Female rats were fed a high-fat diet for 4 weeks and categorized as obesity prone or obesity resistant based on their body weight at 7 weeks of age, at which time the rats were irradiated with 4 Gy. Control rats were fed a standard diet and irradiated at the same time and in the same manner. All rats were maintained on their initial diets and assessed for palpable mammary cancers once a week for the next 30 weeks. The obesity-prone rats were heavier than those in the other groups. The obesity-prone rats were also younger than the other animals at the first detection of mammary carcinomas and their carcinoma weights were greater. A tendency toward higher insulin and leptin blood levels were observed in the obesity-prone rats compared to the other two groups. Blood angiotensin II levels were elevated in the obesity-prone and obesity-resistant rats. Genes related to translation and oxidative phosphorylation were upregulated in the carcinomas of obesity-prone rats. Expression profiles from human breast cancers were used to validate this animal model. As angiotensin is potentially an important factor in obesity-related morbidities and breast cancer, a second set of rats was fed in a similar manner, irradiated and then treated with an angiotensin-receptor blocker, losartan and candesartan. Neither blocker altered mammary carcinogenesis; analyses of losartan-treated animals indicated that expression of renin in the renal cortex and of Agtr1a (angiotensin II receptor, type 1) in cancer tissue was significantly upregulated, suggesting the presence of

  11. Dietary Silicon Deficiency Does Not Exacerbate Diet-Induced Fatty Lesions in Female ApoE Knockout Mice123

    PubMed Central

    Jugdaohsingh, Ravin; Kessler, Katharina; Messner, Barbara; Stoiber, Martin; Pedro, Liliana D; Schima, Heinrich; Laufer, Günther; Powell, Jonathan J; Bernhard, David

    2015-01-01

    Background: Dietary silicon has been positively linked with vascular health and protection against atherosclerotic plaque formation, but the mechanism of action is unclear. Objectives: We investigated the effect of dietary silicon on 1) serum and aorta silicon concentrations, 2) the development of aortic lesions and serum lipid concentrations, and 3) the structural and biomechanic properties of the aorta. Methods: Two studies, of the same design, were conducted to address the above objectives. Female mice, lacking the apolipoprotein E (apoE) gene, and therefore susceptible to atherosclerosis, were separated into 3 groups of 10–15 mice, each exposed to a high-fat diet (21% wt milk fat and 1.5% wt cholesterol) but with differing concentrations of dietary silicon, namely: silicon-deprived (−Si; <3-μg silicon/g feed), silicon-replete in feed (+Si-feed; 100-μg silicon/g feed), and silicon-replete in drinking water (+Si-water; 115-μg silicon/mL) for 15–19 wk. Silicon supplementation was in the form of sodium metasilicate (feed) or monomethylsilanetriol (drinking water). Results: The serum silicon concentration in the −Si group was significantly lower than in the +Si-feed (by up to 78%; P < 0.003) and the +Si-water (by up to 84%; P < 0.006) groups. The aorta silicon concentration was also lower in the −Si group than in the +Si-feed group (by 65%; P = 0.025), but not compared with the +Si-water group. There were no differences in serum and aorta silicon concentrations between the silicon-replete groups. Body weights, tissue wet weights at necropsy, and structural, biomechanic, and morphologic properties of the aorta were not affected by dietary silicon; nor were the development of fatty lesions and serum lipid concentrations. Conclusions: These findings suggest that dietary silicon has no effect on atherosclerosis development and vascular health in the apoE mouse model of diet-induced atherosclerosis, contrary to the reported findings in the cholesterol

  12. Effects of a multidisciplinary body weight reduction program on static and dynamic thoraco-abdominal volumes in obese adolescents.

    PubMed

    LoMauro, Antonella; Cesareo, Ambra; Agosti, Fiorenza; Tringali, Gabriella; Salvadego, Desy; Grassi, Bruno; Sartorio, Alessandro; Aliverti, Andrea

    2016-06-01

    The objective of this study was to characterize static and dynamic thoraco-abdominal volumes in obese adolescents and to test the effects of a 3-week multidisciplinary body weight reduction program (MBWRP), entailing an energy-restricted diet, psychological and nutritional counseling, aerobic physical activity, and respiratory muscle endurance training (RMET), on these parameters. Total chest wall (VCW), pulmonary rib cage (VRC,p), abdominal rib cage (VRC,a), and abdominal (VAB) volumes were measured on 11 male adolescents (Tanner stage: 3-5; BMI standard deviation score: >2; age: 15.9 ± 1.3 years; percent body fat: 38.4%) during rest, inspiratory capacity (IC) maneuver, and incremental exercise on a cycle ergometer at baseline and after 3 weeks of MBWRP. At baseline, the progressive increase in tidal volume was achieved by an increase in end-inspiratory VCW (p < 0.05) due to increases in VRC,p and VRC,a with constant VAB. End-expiratory VCW decreased with late increasing VRC,p, dynamically hyperinflating VRC,a (p < 0.05), and progressively decreasing VAB (p < 0.05). After MBWRP, weight loss was concentrated in the abdomen and total IC decreased. During exercise, abdominal rib cage hyperinflation was delayed and associated with 15% increased performance and reduced dyspnea at high workloads (p < 0.05) without ventilatory and metabolic changes. We conclude that otherwise healthy obese adolescents adopt a thoraco-abdominal operational pattern characterized by abdominal rib cage hyperinflation as a form of lung recruitment during incremental cycle exercise. Additionally, a short period of MBWRP including RMET is associated with improved exercise performance, lung and chest wall volume recruitment, unloading of respiratory muscles, and reduced dyspnea. PMID:27175804

  13. Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

    PubMed Central

    Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K. N.; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S. Sendhil

    2016-01-01

    Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID:27197769

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

    PubMed Central

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

    2014-01-01

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

  15. Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats.

    PubMed

    Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K N; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S Sendhil

    2016-01-01

    Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID:27197769

  16. In vivo imaging of lipid storage and regression in diet-induced obesity during nutrition manipulation.

    PubMed

    Bidar, Abdel Wahad; Ploj, Karolina; Lelliott, Christopher; Nelander, Karin; Winzell, Maria Sörhede; Böttcher, Gerhard; Oscarsson, Jan; Storlien, Leonard; Hockings, Paul D

    2012-12-01

    Changes in adipose tissue distribution and ectopic fat storage in, liver and skeletal muscle tissue impact whole body insulin sensitivity in both humans and experimental animals. Numerous mouse models of obesity, insulin resistance, and diabetes exist; however, current methods to assess mouse phenotypes commonly involve direct harvesting of the tissues of interest, precluding the possibility of repeated measurements in the same animal. In this study, we demonstrate that whole body 3-D imaging of body fat composition can be used to analyze distribution as well as redistribution of fat after intervention by repeated assessment of intrahepatocellular lipids (IHCL), intra-abdominal, subcutaneous, and total adipose tissue (IAT, SAT, and TAT) and brown adipose tissue (BAT). C57BL/6J mice fed a cafeteria diet for 16 wk were compared with mice fed standard chow for 16 wk and mice switched from café diet to standard chow after 12 wk. MRI determinations were made at 9 and 15 wk, and autopsy was performed at 16 wk. There was a strong correlation between MRI-calculated weights in vivo at 15 wk and measured weights at 16 wk ex vivo for IAT (r = 0.99), BAT (r = 0.93), and IHCL (r = 0.97). IHCL and plasma insulin increased steeply relative to body weight at body weights above 45 g. This study demonstrates that the use of 3-D imaging to assess body fat composition may allow substantial reductions in animal usage. The dietary interventions indicated that a marked metabolic deterioration occurred when the mice had gained a certain fat mass. PMID:23032688

  17. Independent but Coordinated Trials: Insights from the Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group

    PubMed Central

    Yeh, Hsin-Chieh; Clark, Jeanne M.; Emmons, Karen M.; Moore, Renee H.; Bennett, Gary G; Warner, Erica T.; Sarwer, Davis B.; Jerome, Gerald J; Miller, Edgar R; Volger, Sheri; Louis, Thomas A.; Wells, Barbara; Wadden, Thomas A.; Colditz, Graham A.; Appel, Lawrence J.

    2011-01-01

    Background The National Heart, Lung, and Blood Institute (NHLBI) funded three institutions to conduct effectiveness trials of weight loss interventions in primary care settings. Unlike traditional multi-center clinical trials, each study was established as an independent trial with a distinct protocol. Still, efforts were made to coordinate and standardize several aspects of the trials. The three trials formed a collaborative group, the “Practice Based Opportunities for Weight Reduction (POWER) Trials Collaborative Research Group.” Purpose We describe the common and distinct features of the three trials, the key characteristics of the collaborative group, and the lessons learned from this novel organizational approach. Methods The Collaborative Research Group consists of three individual studies: “Be Fit, Be Well“(Washington University in St. Louis/Harvard University), “POWER Hopkins” (Johns Hopkins), and “POWER-UP” (University of Pennsylvania). There are a total of 15 participating clinics with ~1,100 participants. The common primary outcome is change in weight at 24 months of follow-up, but each protocol has trial-specific elements including different interventions and different secondary outcomes. A Resource Coordinating Unit at Johns Hopkins provides administrative support. Results The Collaborative Research Group established common components to facilitate potential cross-site comparisons. The main advantage of this approach is to develop and evaluate several interventions, when there is insufficient evidence to test one or two approaches, as would be done in a traditional multi-center trial. Limitations The challenges of the organizational design include the complex decision making process, the extent of potential data pooling, time intensive efforts to standardize reports, and the additional responsibilities of the DSMB to monitor three distinct protocols. Conclusions The POWER Trials Collaborative Research Group is a case study of an

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

    PubMed Central

    Dinan, Timothy G.; Cryan, John F.

    2016-01-01

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

  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 Central

    Laitner, Melissa H.; Perri, Michael G.

    2014-01-01

    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. PMID:25092578

  20. 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. PMID:25092578

  1. Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/Prevotella in Diet-Induced Obese Mice

    PubMed Central

    Neyrinck, Audrey M.; Possemiers, Sam; Druart, Céline; Van de Wiele, Tom; De Backer, Fabienne; Cani, Patrice D.; Larondelle, Yvan; Delzenne, Nathalie M.

    2011-01-01

    Background Alterations in the composition of gut microbiota - known as dysbiosis - has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice. Methodology/Principal Findings Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters. Conclusions/Significance Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti

  2. Increased adiposity on normal diet, but decreased susceptibility to diet-induced obesity in μ-opioid receptor-deficient mice

    PubMed Central

    Zuberi, Aamir R.; Townsend, Leigh; Patterson, Laurel; Zheng, Huiyuan; Berthoud, Hans-Rudi

    2008-01-01

    The mu-opioid receptor encoded by the Oprm1 gene plays a crucial role in the mediation of food reward and drug-induced positive reinforcement, but its genetic deletion has been shown to provide food intake-independent, partial protection from diet-induced obesity. We hypothesized that mu-opioid receptor-deficient mice would show an even greater, intake-dependent, resistance to high fat diet-induced obesity if the diet comprises a sweet component. We generated an F2 population by crossing the heterozygous offspring of homozygous female Oprm1-/- mice (on a mixed C57BL/6 and BALB/c genetic background) with male inbred C57BL/6 mice. Groups of genotyped wildtype (WT) and homozygous mutant (KO) males and females were fed either control chow or a high caloric palatable diet consisting of sweet, liquid chocolate-flavored Ensure together with a solid high fat diet. Food intake, body weight, and body composition was measured over a period of 16 weeks. Unexpectedly, male, and to a lesser extent female, KO mice fed chow for the entire period showed progressively increased body weight and adiposity while eating significantly more chow. In contrast, when exposed to the sweet plus high-fat diet, male, and to a lesser extent female, KO mice gained significantly less body weight and fat mass compared to WT mice when using chow fed counterparts for reference values. Male KO mice consumed 33% less of the sweet liquid diet but increased intake of high-fat pellets, so that total calorie intake was not different from WT animals. These results demonstrate a dissociation of the role of μ-opioid receptors in the control of adiposity for different diets and sex. On a bland diet, normal receptor function appears to confer a slightly catabolic predisposition, but on a highly palatable diet, it confers an anabolic metabolic profile, favoring fat accretion. Because of the complexity of μ-opioid gene regulation and tissue distribution, more selective and targeted approaches will be necessary

  3. The effect of aspirin on atherogenic diet-induced diabetes mellitus.

    PubMed

    Sethi, Apoorva; Parmar, Hamendra S; Kumar, Anil

    2011-06-01

    Exploration of atherogenic diet-induced diabetes mellitus and the evaluation of antidiabetic potential of aspirin were carried out in this study. Male albino Wistar rats were divided into three groups of seven each (1, 2 and 3). Animals of groups 2 and 3 received CCT diet (normal rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5%, 2-thiouracil), whereas the animals of group 1 received normal feed and served as control. In addition to CCT, animals of group 3 (CCT + Asp) also received aspirin (8 gm/kg), commencing from day 8 till the end of study (day 15). In another experiment (exp. 2), aspirin-supplemented normal rat chow (Asp) was fed to the animals for 7 days and compared with the normal rat chow-fed control group. In experiment 3, an in vitro nitric oxide radical-scavenging potential of aspirin at three different doses (25, 50 and 100 μg/ml) was evaluated. In response to CCT diet, a decrease in serum insulin, α-amylase activity, hepatic glycogen, pancreatic calcium with a concomitant increase in serum glucose, lipid profile (except high-density lipoprotein cholesterol (HDL-C)), pancreatic nitrite and lipid peroxidation and the size of adipocytes along with macrophages infiltration were observed. Aspirin administration to CCT diet-fed animals (CCT + Asp) reverted all the studied biochemical and histological changes towards normality. In experiment 2, aspirin administration decreased the serum glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C) and VLDL-C with concomitantly increased HDL-C and insulin; however, it increased hepatic glycogen and pancreatic calcium concentration with a decrease in pancreatic and adipose lipid peroxidation. In vitro assay revealed the nitric oxide radical-scavenging potential of aspirin in all the studied doses. It is concluded that CCT diet-induced diabetes mellitus might be the outcome of nitric oxide radical-induced oxidative stress in pancreatic tissue, as well as diminished

  4. Diet high in oat β-glucan activates the gut-hypothalamic (PYY₃₋₃₆-NPY) axis and increases satiety in diet-induced obesity in mice.

    PubMed

    Huang, Xu-Feng; Yu, Yinghua; Beck, Eleanor J; South, Tim; Li, Yulin; Batterham, Marijka J; Tapsell, Linda C; Chen, Jiezhong

    2011-07-01

    This study tested the effects of (1→3),(1→4) β-D-glucan from oats, on activation of the gut-hypothalamic (PYY₃₋₃₆-NPY) axis, satiety, and weight loss in diet-induced obesity (DIO) mice. DIO mice were fed standard lab chow diets or varied doses of β-glucan for 6 weeks. Energy intake, satiety, body weight changes and peptide Y-Y₃₋₃₆ (PYY₃₋₃₆) were measured together with a satiety test and measurement of neuropeptide Y (NPY) mRNA expression in the hypothalamic arcuate nucleus (Arc). The average energy intake (-13%, p<0.05) and body weight gain was lower with increasing β-glucan over 6 wk with acute suppression of energy intake over 4 h. The highest β-glucan diet significantly increased plasma PYY₃₋₃₆, with suppression of Arc NPY mRNA. PMID:21688388

  5. Treadmill Intervention Attenuates the Cafeteria Diet-Induced Impairment of Stress-Coping Strategies in Young Adult Female Rats

    PubMed Central

    Cigarroa, Igor; Lalanza, Jaume F.; Caimari, Antoni; del Bas, Josep M.; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M.

    2016-01-01

    The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy

  6. Treadmill Intervention Attenuates the Cafeteria Diet-Induced Impairment of Stress-Coping Strategies in Young Adult Female Rats.

    PubMed

    Cigarroa, Igor; Lalanza, Jaume F; Caimari, Antoni; del Bas, Josep M; Capdevila, Lluís; Arola, Lluís; Escorihuela, Rosa M

    2016-01-01

    The current prevalence of diet-induced overweight and obesity in adolescents and adults is continuously growing. Although the detrimental biochemical and metabolic consequences of obesity are widely studied, its impact on stress-coping behavior and its interaction with specific exercise doses (in terms of intensity, duration and frequency) need further investigation. To this aim, we fed adolescent rats either an obesogenic diet (cafeteria diet, CAF) or standard chow (ST). Each group was subdivided into four subgroups according to the type of treadmill intervention as follows: a sedentary group receiving no manipulation; a control group exposed to a stationary treadmill; a low-intensity treadmill group trained at 12 m/min; and a higher intensity treadmill group trained at 17 m/min. Both the diet and treadmill interventions started at weaning and lasted for 8 weeks. Subjects were tested for anxiety-like behavior in the open field test and for coping strategies in the two-way active avoidance paradigm at week 7 and were sacrificed at week 8 for biometric and metabolic characterization. CAF feeding increased the weight gain, relative retroperitoneal white adipose tissue (RWAT %), and plasma levels of glucose, insulin, triglycerides and leptin and decreased the insulin sensitivity. Treadmill intervention partially reversed the RWAT% and triglyceride alterations; at higher intensity, it decreased the leptin levels of CAF-fed animals. CAF feeding decreased the motor activity and impaired the performance in a two-way active avoidance assessment. Treadmill intervention reduced defecation in the shuttle box, suggesting diminished anxiety. CAF feeding combined with treadmill training at 17 m/min increased the time spent in the center of the open field and more importantly, partially reversed the two-way active avoidance deficit. In conclusion, this study demonstrates that at doses that decreased anxiety-like behavior, treadmill exercise partially improved the coping strategy

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

    PubMed

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

    2013-03-14

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

  8. Morphological differences in adipose tissue and changes in BDNF/Trkb expression in brain and gut of a diet induced obese zebrafish model.

    PubMed

    Montalbano, Giuseppe; Mania, Manuela; Guerrera, Maria Cristina; Abbate, Francesco; Laurà, Rosaria; Navarra, Michele; Vega, Jose A; Ciriaco, Emilia; Germanà, Antonino

    2016-03-01

    Obesity is a multifactorial disease generated by an alteration in balance between energy intake and expenditure, also dependent on genetic and non-genetic factors. Moreover, various nuclei of the hypothalamus receive and process peripheral stimuli from the gastrointestinal tract, controlling food intake and therefore energy balance. Among anorexigenic molecules, brain-derived neurotrophic factor (BDNF) acts through the tyrosine-kinase receptor TrkB. Numerous data demonstrate that the BDNF/TrkB system has a fundamental role in the control of food intake and body weight. Quantitative PCR and immunohistochemistry for both BDNF and TrkB were used to determine changes in levels in the brain and gastro-intestinal tract of an experimental zebrafish model of diet-induced obesity. Overfed animals showed increased weight and body mass index as well as accumulation of adipose tissue in the visceral, subcutaneous and hepatic areas. These changes were concomitant with decreased levels of BDNF mRNA in the gastro-intestinal tract and increased expression of TrkB mRNA in the brain. Overfeeding did not change the density of cells displaying immunoreactivity for BDNF or TrkB in the brain although both were significantly diminished in the gastro-intestinal tract. These results suggest an involvement of the BDNF/TrkB system in the regulation of food intake and energy balance in zebrafish, as in mammals. PMID:26617157

  9. Effects of diet supplementation with Camu-camu (Myrciaria dubia HBK McVaugh) fruit in a rat model of diet-induced obesity.

    PubMed

    Nascimento, Ozanildo V; Boleti, Ana P A; Yuyama, Lucia K O; Lima, Emerson S

    2013-03-01

    Amazonian Camu-camu fruit (Myrciaria dubia HBK Mc Vaugh) has attracted interest from food and cosmetics industries because of its rich content of vitamin C, flavonoids and anthocyanins. The goal of this study was investigates the antiobesity action of the ingestion of the Camu-camu pulp in a rat model of diet-induced obesity. Wistar rats with obesity induced by subcutaneous injection of monosodium glutamate receiving diet ad libitum. The rats were divided in two groups: an experimental group that ingested 25 mL/day of Camu-camu pulp (CCG) and a non treated group (CG). After 12 weeks, the animals were sacrificed. Blood, liver, heart, white adipose tissues were collected and weighted, biochemical and inflammatory profiles were determinate as well. Animals that received the pulp of Camu-camu reduced their weights of the fat in white adipose tissues, glucose, total cholesterol, triglycerides, LDL-c and insulin blood levels. There was an increase in HDL-c levels. No change was observed in inflammatory markers and liver enzymes. Camu-camu pulp was able to improve the biochemical profile of obesity in rats suggesting that this Amazonian fruit can be further used such a functional food ingredient in control of chronic diseases linked to obesity. PMID:23460435

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

    PubMed Central

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

    2015-01-01

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

  11. Inflammation-induced microvascular insulin resistance is an early event in diet-induced obesity

    PubMed Central

    Zhao, Lina; Fu, Zhuo; Wu, Jing; Aylor, Kevin W.; Barrett, Eugene J.; Cao, Wenhong

    2015-01-01

    Endothelial dysfunction and vascular insulin resistance usually coexist and chr