Timing of food intake is more potent than habitual voluntary exercise to prevent diet-induced 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.

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Moo1 obesity quantitative trait locus in BTBR T+ Itpr3tf/J mice increases food intake

Physiological Genomics ◽

10.1152/physiolgenomics.00159.2012 ◽

2013 ◽

Vol 45 (5) ◽

pp. F191-F199 ◽

Cited By ~ 2

Author(s):

Subashini Karunakaran ◽

Akiff Manji ◽

Chenhua Serena Yan ◽

Zi-Jun John Wu ◽

Susanne M. Clee

Keyword(s):

Quantitative Trait Locus ◽

Food Intake ◽

Quantitative Trait ◽

Factors Affecting ◽

New Therapeutic Approaches ◽

Diet Induced Obesity ◽

Clinical Consequences ◽

Prevalence Of Obesity ◽

Obesity In Mice ◽

Trait Locus

The rising prevalence of obesity is one of the greatest health challenges facing the world today. Discovery of genetic factors affecting obesity risk will provide important insight to its etiology that could suggest new therapeutic approaches. We have previously identified the Modifier of obese 1 ( Moo1) quantitative trait locus (QTL) in a cross between leptin-deficient BTBR T+ Itpr3tf/J (BTBR) and C57BL/6J (B6) mice. Understanding the mechanism by which this locus acts will aid in the identification of candidate genes. Here we refined the location of this QTL and sought to determine the mechanism by which Moo1 affects body weight. We found that the effects of Moo1 also alter high fat diet-induced obesity in mice having functional leptin. In detailed metabolic analyses we determined that this locus acts by increasing food intake in BTBR mice, without affecting energy expenditure. The expression levels of the main molecular mediators of food intake in the hypothalamus were not altered, suggesting this locus affects an independent pathway, consistent with its identification in mice lacking functional leptin. Finally, we show that the increased adiposity resulting from Moo1 is sufficient to affect glucose tolerance. These studies show that the Moo1 obesity QTL affects food intake, likely through a novel mechanism, and indicate that modulation of the underlying pathway may not only ameliorate obesity but also its clinical consequences.

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PARP1 deficiency exacerbates diet-induced obesity in mice

Journal of Endocrinology ◽

10.1677/joe-09-0402 ◽

2010 ◽

Vol 205 (3) ◽

pp. 243-252 ◽

Cited By ~ 37

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.

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Antiobesity Effect of a Melanin-Concentrating Hormone 1 Receptor Antagonist in Diet-Induced Obese Mice

Endocrinology ◽

10.1210/en.2004-1150 ◽

2005 ◽

Vol 146 (7) ◽

pp. 3080-3086 ◽

Cited By ~ 57

Author(s):

Satoshi Mashiko ◽

Akane Ishihara ◽

Akira Gomori ◽

Ryuichi Moriya ◽

Makoto Ito ◽

...

Keyword(s):

Food Intake ◽

Body Weight Gain ◽

Physiological Role ◽

Obese Mice ◽

Sprague Dawley ◽

Diet Induced Obesity ◽

Intracerebroventricular Infusion ◽

Orexigenic Peptide ◽

Melanin Concentrating Hormone ◽

Obesity In Mice

Abstract Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus, which plays an important role in regulating energy balance. To elucidate the physiological role of MCH in obesity development, the present study examined the effect of a selective MCH1 receptor (MCH1R) antagonist in the diet-induced obesity mouse model. The MCH1R antagonist has high affinity and selectivity for MCH-1R and potently inhibits intracerebroventricularly injected MCH-induced food intake in Sprague Dawley rats. Chronic intracerebroventricular infusion of the MCH1R antagonist (7.5 μg/d) completely suppressed body weight gain in diet-induced obese mice during the treatment periods and significantly decreased cumulative food intake, by 14%. Carcass analysis showed that the MCH1R antagonist resulted in a selective decrease of body fat in the diet-induced obese mice. In addition, the MCH1R antagonist ameliorated the obesity-related hypercholesterolemia, hyperinsulinemia, hyperglycemia, and hyperleptinemia. These results indicate that MCH has a major role in the development of diet-induced obesity in mice and that a MCH1R antagonist might be a useful candidate as an antiobesity agent.

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Resistance to Diet-Induced Obesity in Mice Lacking OPA1 in Adipose Tissue Occurs Independently of Fat-Derived FGF-21 and BAT Function

Diabetes ◽

10.2337/db18-276-lb ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 276-LB ◽

Cited By ~ 2

Author(s):

RENATA PEREIRA ◽

ANGELA C. OLVERA ◽

ALEX A. MARTI ◽

RANA HEWEZI ◽

WILLIAM A. BUI TRAN ◽

...

Keyword(s):

Adipose Tissue ◽

Diet Induced Obesity ◽

Obesity In Mice

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

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718187688.793487756 ◽

2013 ◽

Author(s):

D John Doyle ◽

Joseph Morgan MD

Keyword(s):

Closed Loop ◽

Synthetic Gene ◽

Gene Circuit ◽

Diet Induced Obesity ◽

Obesity In Mice

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Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice

Scientific Reports ◽

10.1038/s41598-021-93224-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Enrique Calvo ◽

Noelia Keiran ◽

Catalina Núñez-Roa ◽

Elsa Maymó-Masip ◽

Miriam Ejarque ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Therapeutic Option ◽

Metabolic Activation ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Obesity In Mice ◽

Treatment Of Obesity ◽

Visceral Adipose

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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Different Short-Term Mild Exercise Modalities Lead to Differential Effects on Body Composition in Healthy Prepubertal Male Rats

BioMed Research International ◽

10.1155/2015/404201 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

D. M. Sontam ◽

M. H. Vickers ◽

J. M. O’Sullivan ◽

M. Watson ◽

E. C. Firth

Keyword(s):

Body Composition ◽

Food Intake ◽

Vital Role ◽

Voluntary Exercise ◽

Bone Architecture ◽

Male Rats ◽

Short Term ◽

Cross Sectional ◽

Impact Exercise ◽

Prepubertal Rats

Physical activity has a vital role in regulating and improving bone strength. Responsiveness of bone mass to exercise is age dependent with the prepubertal period suggested to be the most effective stage for interventions. There is a paucity of data on the effects of exercise on bone architecture and body composition when studied within the prepubertal period. We examined the effect of two forms of low-impact exercise on prepubertal changes in body composition and bone architecture. Weanling male rats were assigned to control (CON), bipedal stance (BPS), or wheel exercise (WEX) groups for 15 days until the onset of puberty. Distance travelled via WEX was recorded, food intake measured, and body composition quantified. Trabecular and cortical microarchitecture of the femur were determined by microcomputed tomography. WEX led to a higher lean mass and reduced fat mass compared to CON. WEX animals had greater femoral cortical cross-sectional thickness and closed porosity compared to CON. The different exercise modalities had no effect on body weight or food intake, but WEX significantly altered body composition and femoral microarchitecture. These data suggest that short-term mild voluntary exercise in normal prepubertal rats can alter body composition dependent upon the exercise modality.

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