High-fat diet induces site-specific unresponsiveness to LPS-stimulated STAT3 activation in the hypothalamus

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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The effects of enterostatin intake on food intake and energy expenditure

British Journal Of Nutrition ◽

10.1079/bjn2003871 ◽

2003 ◽

Vol 90 (1) ◽

pp. 207-214 ◽

Cited By ~ 15

Author(s):

Eva M. R. Kovacs ◽

Manuela P. G. M. Lejeune ◽

Margriet S. Westerterp-Plantenga

Keyword(s):

Body Weight ◽

Food Intake ◽

Energy Expenditure ◽

High Fat Diet ◽

Resting Metabolic Rate ◽

Body Weight Loss ◽

Negative Energy ◽

High Fat ◽

Double Blind ◽

Diet Induced Thermogenesis

Enterostatin (ENT) has been found to inhibit food intake and selectively inhibit fat intake in rats. Both peripheral and central mechanisms have been proposed. It also has been suggested that ENT may increase thermogenesis. The present study investigated the effects of oral ENT administration on food intake, energy expenditure and body weight in subjects with a preference for a high-fat diet. In a double-blind, placebo-controlled, randomized and crossover design, nine female and three male healthy subjects (age 34 (sd 11) years, BMI 24·5 (sd 2·5) kg/m2) with a preference for a high-fat diet ingested ENT (3 × 15 mg/d) or placebo (PLA) while consuming a high-fat diet ad libitum for 4d. Eight subjects ended each intervention with a 36h stay in the respiration chamber, continuing the diet and treatment. Body-weight loss was significant (ENT 0·8 (se 0·3) kg, P<0·05; PLA 1·3 (se 0·3) kg, P<0·001), but not different between treatments. There was no difference between treatments in total energy intake (ENT 37·1 (se 2·6), PLA 35·9 (se 3·2) MJ), macronutrient composition, hunger, satiety and hedonic scores during the 4d high-fat diet. Energy expenditure (24h) (ENT 9·6 (se 0·4), PLA 9·5 (se 0·4) MJ), sleeping and resting metabolic rate, diet-induced thermogenesis, activity-induced energy expenditure and 24h RQ (ENT 0·77 (se 0·01), PLA 0·77 (se 0·01)) were similar for both treatments. We conclude that oral ENT administration did not affect food intake, energy expenditure or body weight in subjects with a preference for a high-fat diet experiencing a negative energy and fat balance.

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AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet

Endocrinology ◽

10.1210/en.2015-1430 ◽

2016 ◽

Vol 157 (4) ◽

pp. 1457-1466 ◽

Cited By ~ 13

Author(s):

Miyuki Shibata ◽

Ryoichi Banno ◽

Mariko Sugiyama ◽

Takashi Tominaga ◽

Takeshi Onoue ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Energy Expenditure ◽

Glucocorticoid Receptor ◽

High Fat Diet ◽

Uncoupling Protein ◽

Chow Diet ◽

Wild Type ◽

High Fat ◽

Brown Adipose

Abstract Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

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A Low-Protein High-Fat Diet Leads to Loss of Body Weight and White Adipose Tissue Weight via Enhancing Energy Expenditure in Mice

Metabolites ◽

10.3390/metabo11050301 ◽

2021 ◽

Vol 11 (5) ◽

pp. 301

Author(s):

Yifeng Rang ◽

Sihui Ma ◽

Jiao Yang ◽

Huan Liu ◽

Katsuhiko Suzuki ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Adipose Tissue ◽

Energy Expenditure ◽

White Adipose Tissue ◽

High Fat Diet ◽

Acid Oxidation ◽

High Fat ◽

Plasma Biomarkers ◽

Low Protein

Obesity has become a worldwide health problem over the past three decades. During obesity, metabolic dysfunction of white adipose tissue (WAT) is a key factor increasing the risk of type 2 diabetes. A variety of diet approaches have been proposed for the prevention and treatment of obesity. The low-protein high-fat diet (LPHF) is a special kind of high-fat diet, characterized by the intake of a low amount of protein, while compared to typical high-fat diet, may induce weight loss and browning of WAT. Physical activity is another effective intervention to treat obesity by reducing WAT mass, inducing browning of WAT. In order to determine whether an LPHF, along with exercise enhanced body weight loss and body fat loss as well as the synergistic effect of an LPHF and exercise on energy expenditure in a mice model, we combined a 10-week LPHF with an 8-week forced treadmill training. Meanwhile, a traditional high-fat diet (HPHF) containing the same fat and relatively more protein was introduced as a comparison. In the current study, we further analyzed energy metabolism-related gene expression, plasma biomarkers, and related physiological changes. When comparing to HPHF, which induced a dramatic increase in body weight and WAT weight, the LPHF led to considerable loss of body weight and WAT, without muscle mass and strength decline, while it exhibited a risk of liver and pancreas damage. The mechanism underlying the LPHF-induced loss of body weight and WAT may be attributed to the synergistically upregulated expression of Ucp1 in WAT and Fgf21 in the liver, which may enhance energy expenditure. The 8-week training did not further enhance weight loss and increased plasma biomarkers of muscle damage when combined with LPHF. Furthermore, LPHF reduced the expression of fatty acid oxidation-related genes in adipose tissues, muscle tissues, and liver. Our results indicated that an LPHF has potential for obesity treatment, while the physiological condition should be monitored during application.

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Effect of repeated stress on body weight and body composition of rats fed low- and high-fat diets

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1998.275.6.r1928 ◽

1998 ◽

Vol 275 (6) ◽

pp. R1928-R1938 ◽

Cited By ~ 34

Author(s):

Ruth B. S. Harris ◽

Jun Zhou ◽

Bradley D. Youngblood ◽

Igor I. Rybkin ◽

Gennady N. Smagin ◽

...

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

High Fat Diet ◽

Corn Oil ◽

Coconut Oil ◽

High Fat ◽

Adult Rats ◽

Reduced Body ◽

Fat Diets

Exposure to the moderate stressor of 3-h restraint for 3 consecutive days causes a temporary drop in food intake but a permanent reduction in body weight in adult rats. Young rats did not show the same response. Food intake of adult rats exposed to repeated restraint was significantly lower than that of controls for 4 days after the end of stress, and there was no rebound hyperphagia. Body weight remained significantly lower for at least 40 days after stress. When the rats were fed a high-fat diet of 80% chow and 20% vegetable shortening (48% kcal fat, 16% protein), lean body mass accounted for all of the weight loss in stressed rats. When the experiment was repeated with a purified high-fat diet containing corn oil and coconut oil as the source of fat (41% kcal fat, 16% protein), weight loss consisted of both lean and fat tissue. There were no sustained changes in single time point measures of corticosterone, insulin, or leptin that could account for the reduced body weight in these rats.

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Cannabinoid Type 1 (CB1) Receptors on Sim1-Expressing Neurons Regulate Energy Expenditure in Male Mice

Endocrinology ◽

10.1210/en.2014-1437 ◽

2014 ◽

Vol 156 (2) ◽

pp. 411-418 ◽

Cited By ~ 27

Author(s):

Pierre Cardinal ◽

Luigi Bellocchio ◽

Omar Guzmán-Quevedo ◽

Caroline André ◽

Samantha Clark ◽

...

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Food Intake ◽

Energy Expenditure ◽

High Fat Diet ◽

Cb1 Receptor ◽

Cb1 Receptors ◽

High Fat ◽

Brown Adipose

The paraventricular nucleus of the hypothalamus (PVN) regulates energy balance by modulating not only food intake, but also energy expenditure (EE) and brown adipose tissue thermogenesis. To test the hypothesis that cannabinoid type 1 (CB1) receptor in PVN neurons might control these processes, we used the Cre/loxP system to delete CB1 from single-minded 1 (Sim1) neurons, which account for the majority of PVN neurons. On standard chow, mice lacking CB1 receptor in Sim1 neurons (Sim1-CB1-knockout [KO]) had food intake, body weight, adiposity, glucose metabolism, and EE comparable with wild-type (WT) (Sim1-CB1-WT) littermates. However, maintenance on a high-fat diet revealed a gene-by-diet interaction whereby Sim1-CB1-KO mice had decreased adiposity, improved insulin sensitivity, and increased EE, whereas feeding behavior was similar to Sim1-CB1-WT mice. Additionally, high-fat diet-fed Sim1-CB1-KO mice had increased mRNA expression of the β3-adrenergic receptor, as well as of uncoupling protein-1, cytochrome-c oxidase subunit IV and mitochondrial transcription factor A in the brown adipose tissue, all molecular changes suggestive of increased thermogenesis. Pharmacological studies using β-blockers suggested that modulation of β-adrenergic transmission play an important role in determining EE changes observed in Sim1-CB1-KO. Finally, chemical sympathectomy abolished the obesity-resistant phenotype of Sim1-CB1-KO mice. Altogether, these findings reveal a diet-dependent dissociation in the CB1 receptor control of food intake and EE, likely mediated by the PVN, where CB1 receptors on Sim1-positive neurons do not impact food intake but hinder EE during dietary environmental challenges that promote body weight gain.

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A Berberis Microphylla Extract Prevents Obesity, Modulates Inflammation and Promotes Thermogenesis in Mice Fed on a High Fat Diet (P06-055-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.p06-055-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Lissette Duarte ◽

Luis Amanda Ramirez ◽

Javier Quezada ◽

Carlos Poblete ◽

Francisca Concha ◽

...

Keyword(s):

Body Weight ◽

Energy Expenditure ◽

High Fat Diet ◽

Control Diet ◽

Obese Mice ◽

High Fat ◽

Final Body Weight ◽

Funding Sources ◽

Tnf Α ◽

Body Weight Increase

Abstract Objectives To evaluate the effect of a polyphenol-rich berberis microphylla (Calafate, a Chilean native berry) extract in obese mice. Methods 40 8-week old C57BL6 mice were divided (n = 10 each) in 4 treatments for 4 months: Control diet (C; 11% fat), Control diet/Calafate (CC), High fat diet (HF; 58% fat), and High fat diet/Calafate (HFC). Animals received food and water ad libitum. CC and HFC were treated with a daily dose of 50 mg total polyphenols/kg weight of Calafate extract. IPGTT and indirect calorimetry were performed at month 2 and 3 respectively. At month 4, animals were euthanized and final body weight were recorded, and samples of interscapular brown (BAT), epididymal white (eWAT) and inguinal white (iWAT) adipose tissues were obtained. Gene expression of inflammatory markers (MCP-1, TNF-α, Leptina, ADIPOQ and F4/80) on eWAT and thermogenic markers (UCP-1, PGC1α, SIRT1, PRDM16, PPARα/γ, DIO2) on BAT and iWAT were analyzed. 2x2 ANOVA statistical analysis was applied. Results HF presented higher body weight than HFC mice (p < 0.001), from day 40 of treatment. Also, BAT weight was increased (p < 0.05). Basal glycemia was higher in HF than C (p < 0.05), but not than HFC. Energy expenditure was higher in HFC (p < 0.05). Differential expression of MCP-1, leptin and F4/80 on eWAT was detected. In BAT, UCP-1, PGC1α, PPARα and SIRT1 expression were higher in HFC than HF (p < 0.05). In iWAT, expression of PGC1α, PPARα, PRDM16, SIRT1, y DIO2 were also increased (p < 0.05). Conclusions a polyphenol-rich Calafate extract decrease body weight increase, augment BAT mass, modulate inflammation, and promote energy expenditure, which was related to higher expression of thermogenic genes in obese mice. Funding Sources FONDECYT 1171550 (CONICYT, CHILE).

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Leptin prevents obesity induced by a high-fat diet after diet-induced weight loss in the marsupial S. crassicaudata

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00240.2003 ◽

2004 ◽

Vol 286 (4) ◽

pp. R734-R739 ◽

Cited By ~ 3

Author(s):

Gary A. Wittert ◽

Helen Turnbull ◽

Perdita Hope ◽

John E. Morley ◽

Michael Horowitz

Keyword(s):

Weight Loss ◽

Body Weight ◽

Food Intake ◽

Caloric Restriction ◽

High Fat Diet ◽

High Fat ◽

Fat Stores ◽

Ad Libitum ◽

Standard Laboratory Diet ◽

Ad Libitum Feeding

The aims of this study were to determine in the marsupial Sminthopsis crassicaudata, the effects of leptin on food intake, body weight, tail width (a reflection of fat stores), and leptin mRNA, after caloric restriction followed by refeeding ad libitum with either a standard or high-fat preferred diet. S. crassicaudata ( n = 32), were fed standard laboratory diet (LabD; 1.01 kcal/g, 20% fat) ad libitum for 3 days. On days 4-10, animals received LabD at 75% of basal intake and then ( days 11-25) were fed either LabD or a choice of LabD and mealworms (MW; 2.99 kcal/g, 30% fat); during this time, half the animals ( n = 8) in each group received either leptin (2.5 mg/kg) or PBS intraperitoneally two times daily. On day 26, animals were killed and fat was removed for assay of leptin mRNA. At baseline, body weight, tail width, and food intake were similar in each group. After caloric restriction, body weight ( P < 0.001) and tail width ( P < 0.001) decreased. On return to ad libitum feeding in the PBS-treated animals, body weight and tail width returned to baseline in the LabD-fed animals ( P < 0.001) and increased above baseline in the MW-fed animals ( P < 0.001). In the LabD groups, tail width ( P < 0.001) and body weight ( P < 0.001) decreased after leptin compared with PBS. In the MW groups, the increase in tail width ( P < 0.001) and body weight ( P = 0.001) were attenuated after leptin compared with PBS. The expression of leptin mRNA in groups fed MW were greater in PBS than in leptin-treated animals ( P < 0.05). Therefore, after diet-induced weight loss, leptin prevents a gain in fat mass in S. crassicaudata; this has potential implications for the therapeutic use of leptin.

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Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

Journal of Endocrinology ◽

10.1530/joe-13-0526 ◽

2014 ◽

Vol 221 (3) ◽

pp. 381-390 ◽

Cited By ~ 21

Author(s):

Gustavo W Fernandes ◽

Cintia B Ueta ◽

Tatiane L Fonseca ◽

Cecilia H A Gouveia ◽

Carmen L Lancellotti ◽

...

Keyword(s):

Body Weight ◽

Energy Expenditure ◽

Glucose Homeostasis ◽

High Fat Diet ◽

Liver Steatosis ◽

Mrna Levels ◽

High Fat ◽

Adaptive Thermogenesis ◽

Brown Adipose ◽

Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

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Effect of selective expression of dominant-negative PPARγ in pro-opiomelanocortin neurons on the control of energy balance

Physiological Genomics ◽

10.1152/physiolgenomics.00032.2016 ◽

2016 ◽

Vol 48 (7) ◽

pp. 491-501 ◽

Cited By ~ 9

Author(s):

Madeliene Stump ◽

Deng-Fu Guo ◽

Ko-Ting Lu ◽

Masashi Mukohda ◽

Xuebo Liu ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Energy Balance ◽

High Fat Diet ◽

Control Diet ◽

Cre Recombinase ◽

Dominant Negative ◽

High Fat ◽

Pparγ Agonist ◽

The Brain

Peroxisome proliferator-activated receptor-γ (PPARγ), a master regulator of adipogenesis, was recently shown to affect energy homeostasis through its actions in the brain. Deletion of PPARγ in mouse brain, and specifically in the pro-opiomelanocortin (POMC) neurons, results in resistance to diet-induced obesity. To study the mechanisms by which PPARγ in POMC neurons controls energy balance, we constructed a Cre-recombinase-dependent conditionally activatable transgene expressing either wild-type (WT) or dominant-negative (P467L) PPARγ and the tdTomato reporter. Inducible expression of both forms of PPARγ was validated in cells in culture, in liver of mice infected with an adenovirus expressing Cre-recombinase (AdCre), and in the brain of mice expressing Cre-recombinase either in all neurons (NESCre/PPARγ-P467L) or selectively in POMC neurons (POMCCre/PPARγ-P467L). Whereas POMCCre/PPARγ-P467L mice exhibited a normal pattern of weight gain when fed 60% high-fat diet, they exhibited increased weight gain and fat mass accumulation in response to a 10% fat isocaloric-matched control diet. POMCCre/PPARγ-P467L mice were leptin sensitive on control diet but became leptin resistant when fed 60% high-fat diet. There was no difference in body weight between POMCCre/PPARγ-WT mice and controls in response to 60% high-fat diet. However, POMCCre/PPARγ-WT, but not POMCCre/PPARγ-P467L, mice increased body weight in response to rosiglitazone, a PPARγ agonist. These observations support the concept that alterations in PPARγ-driven mechanisms in POMC neurons can play a role in the regulation of metabolic homeostasis under certain dietary conditions.

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