scholarly journals PARP1 deficiency exacerbates diet-induced obesity in mice

2010 ◽  
Vol 205 (3) ◽  
pp. 243-252 ◽  
Author(s):  
Kishor Devalaraja-Narashimha ◽  
Babu J Padanilam
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Food Intake ◽  
Heat Production ◽  
Diet Induced Obesity ◽  
Insulin Tolerance ◽  
Protein Functions ◽  
Normal Chow ◽  
Obesity In Mice ◽  
Fat Reabsorption

Poly (ADP-ribose) polymerase-1 (PARP1) regulates gene expression as a transcriptional cofactor and protein functions via poly (ADP-ribosyl)ation. This study was aimed to determine the effect of Parp1 gene deficiency on diet-induced obesity and energy metabolism. Parp1-knockout (Parp-KO) and wild-type (WT) mice on the same genetic background were fed either normal chow or high-fat (HF) diet. Food intake and weight gain were monitored weekly. Plasma levels of glucose, leptin, and insulin were monitored monthly. At 19 weeks, locomotor activity, body composition, respiratory quotient and heat production, glucose and insulin tolerance, and fat reabsorption were analyzed. Parp-KO mice are highly susceptible to diet-induced obesity, accumulation of fat tissue, and they develop hyperleptinemia and insulin resistance and glucose intolerance compared with their WT counterparts. The increased weight gain is due to decreased metabolic rate, heat production, and total energy expenditure (EE). Paradoxically, food intake is less, and the motor activity and oxidation of fat are higher in Parp-KO mice. Absorption of fatty acids is not altered between the groups after HF diet. These results suggest that malfunction of PARP1 signaling exacerbates diet-induced obesity, hyperleptinemia, and insulin resistance, and that it decreases EE in 129 mice.

scholarly journals Diet-Induced Obesity in Mice Overexpressing Neuropeptide Y in Noradrenergic Neurons

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Suvi T. Ruohonen ◽  
Laura H. Vähätalo ◽  
Eriika Savontaus
Keyword(s):  
Weight Gain ◽  
Neuropeptide Y ◽  
Transgenic Mouse Model ◽  
Noradrenergic Neurons ◽  
Fat Depots ◽  
Diet Induced Obesity ◽  
Cholesterol Levels ◽  
Insulin Tolerance ◽  
Normal Chow ◽  
Obesity In Mice

Neuropeptide Y (NPY) is a neurotransmitter associated with feeding and obesity. We have constructed an NPY transgenic mouse model (OE- mouse), where targeted overexpression leads to increased levels of NPY in noradrenergic and adrenergic neurons. We previously showed that these mice become obese on a normal chow. Now we aimed to study the effect of a Western-type diet in OE- and wildtype (WT) mice, and to compare the genotype differences in the development of obesity, insulin resistance, and diabetes. Weight gain, glucose, and insulin tolerance tests, fasted plasma insulin, and cholesterol levels were assayed. We found that female OE- mice gained significantly more weight without hyperphagia or decreased activity, and showed larger white and brown fat depots with no difference in UCP-1 levels. They also displayed impaired glucose tolerance and decreased insulin sensitivity. OE- and WT males gained weight robustly, but no difference in the degree of adiposity was observed. However, 40% of but none of the WT males developed hyperglycaemia while on the diet. The present study shows that female OE- mice were not protected from the obesogenic effect of the diet suggesting that increased NPY release may predispose females to a greater risk of weight gain under high caloric conditions.

scholarly journals ADAR1 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2020 ◽  
Author(s):  
Xiaobing Cui ◽  
Jia Fei ◽  
Sisi Chen ◽  
Gaylen L. Edwards ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Food Intake ◽  
High Fat Diet ◽  
Peptide Yy ◽  
Tolerance Test ◽  
Chow Diet ◽  
High Fat ◽  
Blood Biochemical ◽  
Insulin Tolerance ◽  
Normal Chow

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases, and many other chronic diseases. The objective of this study was to determine the role of adenosine deaminase acting on RNA 1 (ADAR1) in the development of obesity and insulin resistance. Wild-type (WT) and heterozygous ADAR1-deficient (Adar1+/-) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Adar1+/- mice fed with HFD exhibited a lean phenotype with reduced fat mass compared with WT controls, although no difference was found under chow diet conditions. Blood biochemical analysis and insulin tolerance test showed that Adar1+/- improved HFD-induced dyslipidemia and insulin resistance. Metabolic studies showed that food intake was decreased in Adar1+/- mice compared with the WT mice under HFD conditions. Paired feeding studies further demonstrated that Adar1+/- protected mice from HFD-induced obesity through decreased food intake. Furthermore, Adar1+/- restored the increased ghrelin expression in stomach and the decreased serum peptide YY levels under HFD conditions. These data indicate that ADAR1 may contribute to diet-induce obesity, at least partially, through modulating the ghrelin and peptide YY expression and secretion.

scholarly journals Role of Ventromedial Hypothalamus in Sucrose-Induced Obesity on Metabolic Parameters

2021 ◽  
pp. 097275312110057
Author(s):  
Archana Gaur ◽  
G.K. Pal ◽  
Pravati Pal
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Food Intake ◽  
Ventromedial Hypothalamus ◽  
Female Rats ◽  
Metabolic Parameters ◽  
Male Rats ◽  
Significant Weight Gain ◽  
The Metabolic Syndrome

Background: Obesity is because of excessive fat accumulation that affects health adversely in the form of various diseases such as diabetes, hypertension, cardiovascular diseases, and many other disorders. Our Indian diet is rich in carbohydrates, and hence the sucrose-induced obesity is an apt model to mimic this. Ventromedial hypothalamus (VMH) is linked to the regulation of food intake in animals as well as humans. Purpose: To understand the role of VMHin sucrose-induced obesity on metabolic parameters. Methods: A total of 24 adult rats were made obese by feeding them on a 32% sucrose solution for 10 weeks. The VMH nucleus was ablated in the experimental group and sham lesions were made in the control group. Food intake, body weight, and biochemical parameters were compared before and after the lesion. Results: Male rats had a significant weight gain along with hyperphagia, whereas female rats did not have a significant weight gain inspite of hyperphagia. Insulin resistance and dyslipidemia were seen in both the experimental and control groups. Conclusion: A sucrose diet produces obesity which is similar to the metabolic syndrome with insulin resistance and dyslipidemia, and a VMH lesion further exaggerates it. Males are more prone to this exaggeration.

scholarly journals Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats

2011 ◽  
Vol 107 (1) ◽  
pp. 86-95 ◽  
Author(s):  
Silvia V. Conde ◽  
Tiago Nunes da Silva ◽  
Constancio Gonzalez ◽  
Miguel Mota Carmo ◽  
Emilia C. Monteiro ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Visceral Fat ◽  
Tolerance Test ◽  
Caffeine Intake ◽  
Insulin Tolerance ◽  
Hepatic Glutathione ◽  
Chronic Caffeine ◽  
High Sucrose

We tested the hypothesis that long-term caffeine intake prevents the development of insulin resistance and hypertension in two pathological animal models: the high-fat (HF) and the high-sucrose (HSu) diet rat. We used six groups of animals: control; caffeine-treated (Caff; 1 g/l in drinking water during 15 d); HF; caffeine-treated HF (HFCaff); HSu; caffeine-treated HSu (HSuCaff). Insulin sensitivity was assessed using the insulin tolerance test. Blood pressure, weight gain, visceral fat, hepatic glutathione, plasma caffeine, insulin and NO, and serum NEFA and catecholamines were measured. Caffeine reversed insulin resistance and hypertension induced by both the HF and HSu diets. In the HF-fed animals caffeine treatment restored fasting insulin levels to control values and reversed increased weight gain and visceral fat mass. In the HSu group, caffeine reversed fasting hyperglycaemia and restored NEFA to control values. There were no changes either in plasma NO or in hepatic glutathione levels. In contrast, caffeine totally prevented the increase in serum catecholamines induced by HF and HSu diets. To test the hypothesis that inhibition of the sympathetic nervous system prevents the development of diet-induced insulin resistance we administered carvedilol, an antagonist of β1, β2 and also α1 adrenoceptors, to HF and HSu rats. Carvedilol treatment fully prevented diet-induced insulin resistance and hypertension, mimicking the effect of caffeine. We concluded that long-term caffeine intake prevented the development of insulin resistance and hypertension in HF and HSu models and that this effect was related to a decrease in circulating catecholamines.

scholarly journals Freeze-dried jaboticaba peel powder improves insulin sensitivity in high-fat-fed mice

2013 ◽  
Vol 110 (3) ◽  
pp. 447-455 ◽  
Author(s):  
Nathalia R. V. Dragano ◽  
Anne y Castro Marques ◽  
Dennys E. C. Cintra ◽  
Carina Solon ◽  
Joseane Morari ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Receptor ◽  
Tolerance Test ◽  
Protective Role ◽  
High Fat ◽  
Protein Levels ◽  
Diet Induced Obesity ◽  
Forkhead Box ◽  
Insulin Tolerance ◽  
Freeze Dried

The peel of the native Brazilian fruit jaboticaba is rich in anthocyanins, which are known for their anti-obesity effects in animal models. The aim of the present study was to evaluate the effects of freeze-dried jaboticaba peel powder (FDJPP) on a number of metabolic parameters in a model of diet-induced obesity. Mice (n 8 per group) were initially fed on a high-fat diet (HFD, 35 % w/w) for 4 weeks and then switched to a HFD supplemented with FDJPP (1, 2 or 4 % w/w) for an additional 6 weeks. Energy intake, weight loss, glucose tolerance, insulin resistance and lipid profile were determined, and the results were evaluated using ANOVA and Tukey's tests. The FDJPP exerted no protective effect on HFD-induced weight gain, hyperleptinaemia and glucose intolerance. However, the supplementation was effective to reduce insulin resistance, as evidenced in the insulin tolerance test, and subsequently confirmed by improved signal transduction through the insulin receptor/insulin receptor substrate-1/Akt/forkhead box protein pathway and by the attenuation of HFD-induced inflammation in the liver, verified by lower expressions of IL-1β and IL-6 and decreased phosphorylated IκB-α protein levels in all jaboticaba-treated mice. These results suggest that FDJPP may exert a protective role against obesity-associated insulin resistance.

scholarly journals SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake

Endocrinology ◽  
2006 ◽  
Vol 147 (10) ◽  
pp. 4542-4549 ◽  
Author(s):  
Bassil M. Kublaoui ◽  
J. Lloyd Holder ◽  
Kristen P. Tolson ◽  
Terry Gemelli ◽  
Andrew R. Zinn
Keyword(s):  
Food Intake ◽  
Energy Expenditure ◽  
Transgenic Mice ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Enhanced Sensitivity ◽  
Diet Induced Obesity ◽  
Melanocortin 4 Receptor ◽  
Obesity In Mice

Single-minded 1 (SIM1) mutations are associated with obesity in mice and humans. Haploinsufficiency of mouse Sim1 causes hyperphagic obesity with increased linear growth and enhanced sensitivity to a high-fat diet, a phenotype similar to that of agouti yellow and melanocortin 4 receptor knockout mice. To investigate the effects of increased Sim1 dosage, we generated transgenic mice that overexpress human SIM1 and examined their phenotype. Compared with wild-type mice, SIM1 transgenic mice had no obvious phenotype on a low-fat chow diet but were resistant to diet-induced obesity on a high-fat diet due to reduced food intake with no change in energy expenditure. The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated. Our results indicate that the melanocortin 4 receptor signals through Sim1 or its transcriptional targets in controlling food intake but not energy expenditure.

scholarly journals Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice

2014 ◽  
Vol 306 (7) ◽  
pp. E779-E790 ◽  
Author(s):  
Zhikui Wei ◽  
Xia Lei ◽  
Pia S. Petersen ◽  
Susan Aja ◽  
G. William Wong
Keyword(s):  
Food Intake ◽  
Hepatic Steatosis ◽  
Knockout Mice ◽  
Caloric Intake ◽  
Physiological Role ◽  
Lipogenic Genes ◽  
Diet Induced Obesity ◽  
Insulin Tolerance ◽  
Hepatic Insulin Signaling ◽  
Physiological Relevance

Transgenic overexpression of CTRP9, a secreted hormone downregulated in obesity, confers striking protection against diet-induced obesity and type 2 diabetes. However, the physiological relevance of this adiponectin-related plasma protein remains undefined. Here, we used gene targeting to establish the metabolic function of CTRP9 in a physiological context. Mice lacking CTRP9 were obese and gained significantly more body weight when fed standard laboratory chow. Increased food intake, due in part to upregulated expression of hypothalamic orexigenic neuropeptides, contributed to greater adiposity in CTRP9 knockout mice. Although the frequency of food intake remained unchanged, CTRP9 knockout mice increased caloric intake by increasing meal size and decreasing satiety ratios. The absence of CTRP9 also resulted in peripheral tissue insulin resistance, leading to increased fasting insulin levels, impaired hepatic insulin signaling, and reduced insulin tolerance. Increased expression of lipogenic genes, combined with enhanced caloric intake, contributed to hepatic steatosis in CTRP9 knockout mice. Loss of CTRP9 also resulted in reduced skeletal muscle AMPK activation and mitochondrial content. Together, these results provide the genetic evidence for a physiological role of CTRP9 in controlling energy balance via central and peripheral mechanisms.

scholarly journals Inactivation of Ppp1r15a minimises weight gain and insulin resistance during caloric excess in mice

2018 ◽  
Author(s):  
Vruti Patel ◽  
Guillaume Bidault ◽  
Joseph E. Chambers ◽  
Stefania Carobbio ◽  
Angharad J. T. Everden ◽  
...  
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Translation Initiation Factor ◽  
Initiation Factor ◽  
Standard Diet ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Caloric Excess ◽  
Deficient Mice

AbstractPhosphorylation of the translation initiation factor eIF2α within the mediobasal hypothalamus is known to suppress food intake, but the role of the eIF2α phosphatases in regulating body weight is poorly understood. Mice deficient in active PPP1R15A, a stress-inducible eIF2α phosphatase, are healthy and more resistant to endoplasmic reticulum stress than wild type controls. We report that when Ppp1r15a mutant mice are fed a high fat diet they gain less weight than wild type littermates owing to reduced food intake. This results in healthy leaner Ppp1r15a mutant animals with reduced hepatic steatosis and improved insulin sensitivity, albeit with a modest defect in insulin secretion. By contrast, no weight differences are observed between wild type and Ppp1r15a deficient mice fed a standard diet. We conclude that mice lacking the C-terminal PP1-binding domain of PPP1R15A show reduced dietary intake and preserved glucose tolerance. Our data indicate that this results in reduced weight gain and protection from diet-induced obesity.

scholarly journals Choline Deficiency Attenuates Body Weight Gain and Improves Glucose Tolerance in ob/ob Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Gengshu Wu ◽  
Liyan Zhang ◽  
Tete Li ◽  
Gary Lopaschuk ◽  
Dennis E. Vance ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Fat Mass ◽  
Body Weight Gain ◽  
Genetic Defect ◽  
Plasma Glucagon ◽  
Choline Deficiency ◽  
Deficient Diet ◽  
Insulin Tolerance

Previous studies demonstrated that choline supply is directly linked to high-fat-diet-induced obesity and insulin resistance in mice. The aim of this study was to evaluate if choline supply could also modulate obesity and insulin resistance caused by a genetic defect. Eight-week-old male ob/ob mice were fed for two months with either choline-deficient or choline-supplemented diet. Tissue weight including fat mass and lean mass was assessed. Intracellular signaling, plasma glucagon and insulin, and glucose and insulin tolerance tests were also investigated. The choline-deficient diet slowed body weight gain and decreased fat mass. Choline deficiency also decreased plasma glucose level and improved glucose and insulin tolerance although fatty liver was exacerbated. Increased adipose lipolytic activity, decreased plasma glucagon and reduced expression of hepatic glucagon receptor were also observed with the choline-deficient diet. Our results demonstrate that a choline-deficient diet can decrease fat mass and improve glucose tolerance in obese and diabetic mice caused by a genetic defect.

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