Nicotinamide Protects Against Diet‐Induced Body Weight Gain, Increases Energy Expenditure and Induces White Adipose Tissue Beiging

Neonatal nutritional changes induce long-lasting effects on energy homeostasis. Adiponectin influences food intake and body weight. The aim of this study was to investigate the effects of neonatal nutritional programming on the central stimulation of adiponectin. Male Wistar rats were divided on postnatal (PN) day 3 in litters of 3 (small litter, SL), 10 (normal litter, NL), or 16 pups/dam (large litter, LL). We assessed body weight gain for 60 days, adiponectin concentration, and white adipose tissue weight. We examined the response of SL, NL, and LL rats on body weight gain, food intake, oxygen consumption (V̇o2), respiratory exchange ratio (RER), calorimetry, locomotor activity, phosphorylated-AMP-activated protein kinase (AMPK) expression in the hypothalamus, and uncoupling protein (UCP)-1 in the brown adipose tissue after central stimulus with adiponectin. After weaning, SL rats maintained higher body weight gain despite similar food intake compared with NL rats. LL rats showed lower body weight at weaning, with a catch up afterward and higher food intake. Both LL and SL groups had decreased plasma concentrations of adiponectin at PN60. SL rats had increased white adipose tissue. Central injection of adiponectin decreased body weight and food intake and increased V̇o2, RER, calorimetry, p-AMPK and UCP- 1 expression in NL rats, but it had no effect on SL and LL rats, compared with the respective vehicle groups. In conclusion, neonatal under- and overfeeding induced an increase in body weight gain in juvenile and early adult life. Unresponsiveness to central effects of adiponectin contributes to the imbalance of the energy homeostasis in adult life induced by neonatal nutritional programming.

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Individual housing of male C57BL/6J mice after weaning impairs growth and predisposes for obesity

10.1101/834416 ◽

2019 ◽

Author(s):

Lidewij Schipper ◽

Steffen van Heijningen ◽

Giorgio Karapetsas ◽

Eline M. van der Beek ◽

Gertjan van Dijk

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Intake ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Tissue Mass ◽

Individual Housing ◽

Adipose Tissue Mass ◽

Obesogenic Diet

AbstractIndividual housing from weaning onwards resulted in reduced growth rate during adolescence in male C57Bl/6J mice that were housed individually, while energy intake and energy expenditure were increased compared to socially housed counterparts. At 6 weeks of age, these mice had reduced lean body mass, but significantly higher white adipose tissue mass compared to socially housed mice. Body weight gain of individually housed animals exceeded that of socially housed mice during adulthood, with elevations in both energy intake and expenditure. At 18 weeks of age, individually housed mice showed higher adiposity and higher mRNA expression of UCP-1 in inguinal white adipose tissue. Exposure to an obesogenic diet starting at 6 weeks of age further amplified body weight gain and adipose tissue deposition. This study shows that post-weaning individual housing of male mice results in impaired adolescent growth and higher susceptibility to obesity in adulthood. Mice are widely used to study obesity and cardiometabolic comorbidities. For (metabolic) research models using mice, (social) housing practices should be carefully considered and regarded as a potential confounder due to their modulating effect on metabolic health outcomes.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00354.2014 ◽

2015 ◽

Vol 308 (4) ◽

pp. E315-E323 ◽

Cited By ~ 37

Author(s):

Kana Ohyama ◽

Yoshihito Nogusa ◽

Katsuya Suzuki ◽

Kosaku Shinoda ◽

Shingo Kajimura ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

Body Weight Gain ◽

Whole Body ◽

Voluntary Running ◽

Running Wheel Exercise ◽

Body Energy

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.

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Dorsomedial hypothalamic BDNF neurons integrate thermal afferent signals to control energy expenditure

10.1101/2021.04.11.439314 ◽

2021 ◽

Author(s):

Wei L Shen ◽

Hongbin Sun ◽

Qian Zhou ◽

Hao Bian ◽

Mengting Wang ◽

...

Keyword(s):

Physical Activity ◽

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

Body Weight Gain ◽

Dorsomedial Hypothalamus ◽

Brown Adipose ◽

Thermoregulatory System ◽

Bdnf Signaling

Mutations in the gene brain-derived neurotrophic factor (BDNF) cause obesity in humans. BDNF signaling and its expressing neurons in the hypothalamus help control feeding, energy expenditure (EE), and physical activity. However, whether the BDNF neurons interact with another EE-regulating system, the thermoregulation circuitry, remains unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMH) are activated by environmental cooling and sufficient to induce body temperature increases and brown adipose tissue (BAT) thermogenesis. Conversely, blocking these neurons impairs BAT thermogenesis and cold defense, causing body weight gain and glucose intolerance. DMH BDNF neurons are therefore an important type of thermoregulatory neuron, integrating thermal afferent signals to control EE during cold defense. This reveals a critical intersection between the BDNF circuitry and the thermoregulatory system.

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Mice deleted for GPAT3 have reduced GPAT activity in white adipose tissue and altered energy and cholesterol homeostasis in diet-induced obesity

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00666.2013 ◽

2014 ◽

Vol 306 (10) ◽

pp. E1176-E1187 ◽

Cited By ~ 29

Author(s):

Jingsong Cao ◽

Sylvie Perez ◽

Bryan Goodwin ◽

Qingcong Lin ◽

Haibing Peng ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Energy Expenditure ◽

White Adipose Tissue ◽

High Fat Diet ◽

Cholesterol Metabolism ◽

Body Weight Gain ◽

Cholesterol Homeostasis ◽

High Fat

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first step in the synthesis of glycerolipids and glycerophospholipids. Microsomal GPAT, the major GPAT activity, is encoded by at least two closely related genes, GPAT3 and GPAT4. To investigate the in vivo functions of GPAT3, we generated Gpat3-deficient ( Gpat3 −/−) mice. Total GPAT activity in white adipose tissue of Gpat3 −/− mice was reduced by 80%, suggesting that GPAT3 is the predominant GPAT in this tissue. In liver, GPAT3 deletion had no impact on total GPAT activity but resulted in a 30% reduction in N-ethylmaleimide-sensitive GPAT activity. The Gpat3 −/− mice were viable and fertile and exhibited no obvious metabolic abnormalities on standard laboratory chow. However, when fed a high-fat diet, female Gpat3 −/− mice showed decreased body weight gain and adiposity and increased energy expenditure. Increased energy expenditure was also observed in male Gpat3 −/− mice, although it was not accompanied by a significant change in body weight. GPAT3 deficiency lowered fed, but not fasted, glucose levels and tended to improve glucose tolerance in diet-induced obese male and female mice. On a high-fat diet, Gpat3 −/− mice had enlarged livers and displayed a dysregulation in cholesterol metabolism. These data establish GPAT3 as the primary GPAT in white adipose tissue and reveal an important role of the enzyme in regulating energy, glucose, and lipid homeostasis.

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Energy balance and brown adipose tissue thermogenesis during chronic endotoxemia in rats

Journal of Applied Physiology ◽

10.1152/jappl.1989.66.4.1970 ◽

1989 ◽

Vol 66 (4) ◽

pp. 1970-1975 ◽

Cited By ~ 5

Author(s):

J. Arnold ◽

R. A. Little ◽

N. J. Rothwell

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Energy Balance ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Body Weight Gain ◽

Male Rats ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

The effects of continuously administered endotoxin on 7-day energy balance were investigated in male rats. Three groups of rats were implanted with osmotic pumps; two groups received saline-filled pumps, whereas the third received endotoxin. One of the saline groups was pair fed to match the food intake of the endotoxemic rats. After 7 days, body energy and protein and fat contents of rats were determined together with the energy content of food and feces. Endotoxin infusion not only induced fever, but it also suppressed appetite and significantly decreased body weight gain. Metabolizable energy intake was reduced by approximately 20% in infected rats. Although protein and fat gains were lowest in the endotoxin group, there appeared to be a selective loss of protein when considered as percent of body weight. Percent body fat was unaltered between the groups. Energy expenditure considered in absolute (kJ) or body weight-independent (kJ/kg0.67) terms yielded similar patterns of results; expenditure (kJ) was 10 and 20% (P less than 0.05, P less than 0.01) lower in the endotoxemic and pair-fed rats, respectively, compared with controls. Hence, compared with pair-fed rats, endotoxin-infused animals had a 10% rise in their expenditure. Brown adipose tissue thermogenesis was assessed by mitochondrial binding of guanosine 5′-diphosphate, and results showed that binding was greatest in endotoxemic rats and lowest in the pair-fed animals. The present results suggest that in this endotoxemic model appetite suppression exacerbates changes in energy balance. However, the reduction in body weight gain is also dependent on a decrease in metabolic efficiency and an increase in total energy expenditure.(ABSTRACT TRUNCATED AT 250 WORDS)

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A Functional Leptin System Is Essential for Sodium Tungstate Antiobesity Action

Endocrinology ◽

10.1210/en.2008-0881 ◽

2009 ◽

Vol 150 (2) ◽

pp. 642-650 ◽

Cited By ~ 10

Author(s):

Ignasi Canals ◽

María C. Carmona ◽

Marta Amigó ◽

Albert Barbera ◽

Analía Bortolozzi ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Food Intake ◽

Energy Expenditure ◽

Energy Homeostasis ◽

Sodium Tungstate ◽

Body Weight Gain ◽

Dependent Manner ◽

Leptin System

Sodium tungstate is a novel agent in the treatment of obesity. In diet-induced obese rats, it is able to reduce body weight gain by increasing energy expenditure. This study evaluated the role of leptin, a key regulator of energy homeostasis, in the tungstate antiobesity effect. Leptin receptor-deficient Zucker fa/fa rats and leptin-deficient ob/ob mice were treated with tungstate. In lean animals, tungstate administration reduced body weight gain and food intake and increased energy expenditure. However, in animals with deficiencies in the leptin system, treatment did not modify these parameters. In ob/ob mice in which leptin deficiency was restored through adipose tissue transplantation, treatment restored the tungstate-induced body weight gain and food intake reduction as well as energy expenditure increase. Furthermore, in animals in which tungstate administration increased energy expenditure, changes in the expression of key genes involved in brown adipose tissue thermogenesis were detected. Finally, the gene expression of the hypothalamic neuropeptides, Npy, Agrp, and Cart, involved in the leptin regulation of energy homeostasis, was also modified by tungstate in a leptin-dependent manner. In summary, the results indicate that the effectiveness of tungstate in reducing body weight gain is completely dependent on a functional leptin system. Anti-obesity activity of tungstate is due to an increase in thermogenesis and a reduction in food intake and depends entirely on a functional leptin system.

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Time-Restricted Feeding Improves Body Weight Gain, Lipid Profiles, and Atherogenic Indices in Cafeteria-Diet-Fed Rats: Role of Browning of Inguinal White Adipose Tissue

Nutrients ◽

10.3390/nu12082185 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2185

Author(s):

Samira Aouichat ◽

Meriem Chayah ◽

Souhila Bouguerra-Aouichat ◽

Ahmad Agil

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

White Adipose Tissue ◽

Body Weight Gain ◽

Density Lipoprotein ◽

Cafeteria Diet ◽

Restricted Feeding ◽

Diet Induced Obesity ◽

Atherogenic Indices

Time-restricted feeding (TRF) showed a potent effect in preventing obesity and improving metabolicoutcomes in several animal models of obesity. However, there is, as of yet, scarce evidence concerning its effectiveness against obesogenic challenges that more accurately mimic human Western diets, such as the cafeteria diet. Moreover, the mechanism for its efficacy is poorly understood. White adipose browning has been linked to body weight loss. Herein, we tested whether TRF has the potential to induce browning of inguinal white adipose tissue (iWAT) and to attenuate obesity and associated dyslipidemia in a cafeteria-diet-induced obesity model. Male Wistar rats were fed normal laboratory chow (NC) or cafeteria diet (CAF) for 16 weeks and were subdivided into two groups that were subjected to either ad libitum (ad lib, A) or TRF (R) for 8 h per day. Rats under the TRF regimen had a lower body weight gain and adiposity than the diet-matchedad lib rats, despite equivalent levels of food intake and locomotor activity. In addition, TRF improved the deranged lipid profile (total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-c), low-density lipoprotein (LDL-c)) and atherogenic indices (atherogenic index of plasma (AIP), atherogenic coefficient (AC), coronary risk index (CRI) in CAF-fed rats. Remarkably, TRF resulted in decreased size of adipocytes and induced emergence of multilocular brown-like adipocytes in iWAT of NC- and CAF-fed rats. Protein expression of browning markers, such as uncoupling protein-1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α), were also up-regulated in the iWAToftime-restricted NC- or CAF-fed rats. These findings suggest that a TRF regimen is an effective strategy to improve CAF diet-induced obesity, probably via a mechanismthe involving WAT browning process.

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Phytohemagglutinin ameliorates HFD-induced obesity by increasing energy expenditure

Journal of Molecular Endocrinology ◽

10.1530/jme-20-0349 ◽

2021 ◽

Author(s):

Yunxia Zhang ◽

Jin Li ◽

Hui-hui Wang ◽

Jiao Li ◽

Yue Yu ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Weight Gain ◽

Body Temperature ◽

Energy Expenditure ◽

Glucose Homeostasis ◽

Body Weight Gain ◽

The Body ◽

Brown Adipose ◽

Study Results

Despite all modern advances in medicine, there are few reports of effective and safe drugs to treat obesity. Our objective was to screen anti-obesity natural compounds, and to verify whether they can reduce the body weight gain and investigate their molecular mechanisms. By using drug-screening methods, Phytohemagglutinin (PHA) was found to be the most anti-obesity candidate natural compound. Six-week-old C57BL/6J mice were fed with high-fat diet (HFD) and intraperitoneally injected with 0.25mg/kg PHA every day for 8 weeks. The body weight, glucose homeostasis, oxygen consumption and physical activity were assessed. We also measured the heat intensity, body temperature and the gene expression of key regulators of energy expenditure. Prevention study results showed PHA treatment not only reduced the body weight gain, but also maintained glucose homeostasis in HFD-fed mice. Further study indicated energy expenditure and uncoupling protein 1 (UCP-1) expression of brown adipose tissue (BAT) and white adipose tissue (WAT) in HFD-fed mice were significantly improved by PHA. In the therapeutic study, the similar effect was observed. PHA inhibited lipid droplet formation and up-regulated mitochondrial related genes expression during adipogenesis in vitro. UCP-1 KO mice displayed no differences in body weight, glucose homeostasis and core body temperature between PHA and control groups. Our results suggest that PHA prevent and treat obesity by increasing energy expenditure though up-regulation of BAT thermogenesis.

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