scholarly journals The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery

Author(s):  
Brandon Boland ◽  
Michael B. Mumphrey ◽  
Zheng Hao ◽  
Benji Gill ◽  
R. Leigh Townsend ◽  
...  

Background/Goals: The gut hormone PYY secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, HOMA-IR, and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as GLP-1 remain to be investigated.

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 585 ◽  
Author(s):  
Brandon Boland ◽  
Michael Mumphrey ◽  
Zheng Hao ◽  
Benji Gill ◽  
R. Townsend ◽  
...  

Background/Goals: The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. Methods: Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet. Results: Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. Conclusions: PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.


Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 302
Author(s):  
Ahtesham Hussain ◽  
Jin Sook Cho ◽  
Jong-Seok Kim ◽  
Young Ik Lee

Background: Currently, obesity is a global health challenge due to its increasing prevalence and associated health risk. It is associated with various metabolic diseases, including diabetes, hypertension, cardiovascular disease, stroke, certain forms of cancer, and non-alcoholic liver diseases (NAFLD). Objective: The aim of this study to evaluate the effects of polyphenol enriched herbal complex (Rubus crataegifolius/ellagic acid, Crataegus pinnatifida Bunge/vitexin, chlorogenic acid, Cinnamomum cassiaa/cinnamic acid) on obesity and obesity induced NAFLD in the high-fat diet (HFD)-induced obese mouse model. Methods: Obesity was induced in male C57BL/6 mice using HFD. After 8 weeks, the mice were treated with HFD+ plants extract for 8 weeks. Body weight, food intake weekly, and blood sugar level were measured. After sacrifice, changes in the treated group’s liver weight, fat weight, serum biochemical parameters, hormone levels, and enzyme levels were measured. For histological analysis, tissues were stained with hematoxylin-eosin (H&E) and Oil Red-O. Results: Our results showed that the herbal complex ameliorated body weight and liver weight gain, and decreased total body fat in HFD-fed animals. Post prandial blood glucose (PBG) and fasting blood glucose (FBG) were lower in the herbal complex-treated group than in the HFD control group. Additionally, herbal formulation treatment significantly increased HDL levels in serum and decreased TC, TG, AST, ALT, deposition of fat droplets in the liver, and intima media thickness (IMT) in the aorta. Herbal complex increased serum adiponectin and decreased serum leptin. Herbal complex also increased carnitine palmityl transferase (CPT) activity and significantly decreased enzyme activity of beta-hydroxy beta methyl glutamyl-CoA (HMG-CoA) reductase, and fatty acid synthase (FAS). Conclusions: The results of this study demonstrated that the herbal complex is an effective herbal formulation in the attenuation of obesity and obesity-induced metabolic dysfunction including NAFLD in HFD-induced mouse model.


2014 ◽  
Vol 5 (3) ◽  
pp. 229-239 ◽  
Author(s):  
K. M. Platt ◽  
R. J. Charnigo ◽  
K. J. Pearson

Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10–11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10–11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.


2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Rosa Martha Perez Gutierrez ◽  
Diana Madrigales Ahuatzi ◽  
Maria del Carmen Horcacitas ◽  
Efren Garcia Baez ◽  
Teresa Cruz Victoria ◽  
...  

Obesity is one of the major factors to increase various disorders like diabetes. The present paper emphasizes study related to the antiobesity effect ofPhalaris canariensisseeds hexane extract (Al-H) in high-fat diet- (HFD-) induced obese CD1 mice and in streptozotocin-induced mild diabetic (MD) and severely diabetic (SD) mice.AL-H was orally administered to MD and SD mice at a dose of 400 mg/kg once a day for 30 days, and a set of biochemical parameters were studied: glucose, cholesterol, triglycerides, lipid peroxidation, liver and muscle glycogen, ALP, SGOT, SGPT, glucose-6-phosphatase, glucokinase, hexokinase, SOD, CAT, GSH, GPX activities, and the effect on insulin level. HS-H significantly reduced the intake of food and water and body weight loss as well as levels of blood glucose, serum cholesterol, triglyceride, lipoprotein, oxidative stress, showed a protective hepatic effect, and increased HDL-cholesterol, serum insulin in diabetic mice. The mice fed on the high-fat diet and treated with AL-H showed inhibitory activity on the lipid metabolism decreasing body weight and weight of the liver and visceral adipose tissues and cholesterol and triglycerides in the liver. We conclude that AL-H can efficiently reduce serum glucose and inhibit insulin resistance, lipid abnormalities, and oxidative stress in MD and SD mice. Our results demonstrate an antiobesity effect reducing lipid droplet accumulation in the liver, indicating that its therapeutic properties may be due to the interaction plant components soluble in the hexane extract, with any of the multiple targets involved in obesity and diabetes pathogenesis.


2016 ◽  
Vol 61 (3) ◽  
pp. 1600716 ◽  
Author(s):  
Sandra Steensels ◽  
Leen Cools ◽  
Bert Avau ◽  
Laurien Vancleef ◽  
Ricard Farré ◽  
...  

Author(s):  
Shirish S. Joshi ◽  
Firoz M. Tadavi ◽  
Amit R. Birajdar ◽  
Snehalata V. Gajbhiye ◽  
Anagha A. Shende

Background: Obesity is not only affecting the affluent society but also affecting developing countries like India. The incidence of obesity is rapidly increasing throughout the world. However, the current anti-obesity drugs have numerous limitations.Methods: The obesity was induced in male wistar rats by giving high-fat diet over 12 weeks. The variables assessed were body weight, abdominal girth, blood triglyceride level, liver weight and fat mass and histopathology of liver. Aqueous and alcoholic extracts of Lagenaria siceraria (200mg/kg and 400mg/kg Doses) were compared to orlistat (treatment control) and high-fat diet group (disease control) for different variables.Results: Alcoholic and aqueous extracts high dose (400mg/kg) of Lagenaria siceraria significantly reduced total body weight (p<0.05), abdominal girth (p <0.05) at week 10 and 12 compared to high fat diet group. Alcoholic extract (400mg/kg) significantly reduced total blood triglyceride level (p <0.05) and total liver weight (p <0.05) compared to high-fat diet group. None of the study drugs reduced % liver weight. Alcoholic extract high dose (p <0.05) has shown improvement in histopathological score. Both aqueous and alcoholic extracts have shown reduced fat mass compared to high-fat diet group.Conclusions: The alcoholic extract (400mg/kg) of Lagenaria siceraria alleviated high fat diet induced obesity and dyslipidemic changes in rats. The alcoholic extract of Lagenaria siceraria is having better anti-obesity potential than aqueous extract.


Obesity ◽  
2014 ◽  
Vol 22 (10) ◽  
pp. 2147-2155 ◽  
Author(s):  
Yongbin Yang ◽  
Daniel L. Smith ◽  
Karen D. Keating ◽  
David B. Allison ◽  
Tim R. Nagy

Drug Research ◽  
2018 ◽  
Vol 68 (11) ◽  
pp. 637-647 ◽  
Author(s):  
Mohammad Haque ◽  
H. Ansari

AbstractArq zeera is a distillate product that prepared from four different herbs namely Trachyspermum ammi L., apiaceae, Zingiber officinale Roxb., zingiberaceae, Carum carvi L.,apiaceae and Cuminum cyminum L., apiaceae. The present study aims to determine the antiobesity effect of arq zeera and its main components thymol and cuminaldehyde in high fat diet induced obese rats and to explore its mechanism of action. In current study, orlistat was used as positive controls. Male Wistar rats were fed with HFD for 42 days to induce obesity. HFD-fed rats were administered with arq zeera, thymol, cumic aldehyde, thymol + cuminaldehyde and orlistat for 28 days. During the course of treatment, body weight and food intake frequently observed and after end of treatments, liver weight, visceral fat pad weight, plasma lipid proflie, alanine aminotransferase, aspartate aminotransferase, glucose, insulin, leptin levels and pancreatic lipase activity were studied on all treated obese rats. The histopathology of liver was also studied. After the treatments of arq zeera and its main components, body weight, food intake, liver weight, visceral fat pad weight and the level of lipid profile, alanine aminotransferase, aspartate aminotranferase, glucose, insulin, and leptin were found to be decreased and pancreatic lipase inhibition were increased. Arq zeera showed more potential antiobesity effect than orlistat. According to our present findings, arq zeera and its main components possessed potent antiobesity effect on high fat diet -induced obese rats and excreted anti-obesity effect partly via hypolipidemic, hypoglycemic, hypoinsulinemic, hypoleptinemic and pancreatic lipase inhibition action.


2014 ◽  
Vol 306 (1) ◽  
pp. R34-R44 ◽  
Author(s):  
Beatriz de Carvalho Borges ◽  
Rodrigo Rorato ◽  
Ernane Torres Uchoa ◽  
Paula Marangon ◽  
Glauber S. F. da Silva ◽  
...  

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


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