Kappa-Carrageenan Inhibited the High-Fat-Diet-Induced Obesity Through Up-Regulating the Hepatic Sirt1 Gene Expression

Abstract Objectives Kappa-Carrageenan(CGN) is a widely used food additive in the meat industry and a highly viscous soluble dietary fiber which can hardly be fermented. It has been shown to be able to regulate the energy metabolism and inhibit diet-induced obesity. However, the mechanism is not well understood. The purpose of this study is to investigate the mechanisms of κ-carrageenan to inhibit the body weight gain. Methods A high-fat diet incorporated with lard, pork protein and CGN (2% or 4%, w/w) was given to C57BL/6J mice for 90 days. The energy intake and weight changes were measured every three days. After the dietary intervention, mice were sacrificed, liver and epididymal adipose tissues were taken for real-time polymerase chain reaction (RT-qPCR) analysis. Results The CGN in the high-fat diet restricted weight gain by decreasing liver and adipose mass without inhibiting energy intake. The genes involving energy expenditure such as Acox1, Acadl, CPT-1A and Sirt1 were upregulated in the mice fed with carrageenan. However, the genes responsible for lipid synthesis were not significantly different compared to the diet-induced obese model. Conclusions The anti-obesity effect of the CGN in high-fat diet could be highly related to the enhancement of energy expenditure through up-regulating the downstream genes which promote β-oxidation by increasing the Sirt1 gene expression in liver. Funding Sources Ministry of Science and Technology of the People's Republic of China (10000 Talent Project)

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Loss of Selenoprotein V Predisposes Mice to Body Fat Accumulation (OR11-02-19)

Current Developments in Nutrition ◽

10.1093/cdn/nzz044.or11-02-19 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

Author(s):

Lingli Chen ◽

Jiaqiang Huang ◽

Yuanyuan Wu ◽

Fazheng Ren ◽

Xin Gen Lei

Keyword(s):

Gene Expression ◽

Body Fat ◽

High Fat Diet ◽

The Body ◽

High Fat ◽

Fat Accumulation ◽

Diet Induced Obesity ◽

Body Weights ◽

Its Gene ◽

Selenoprotein V

Abstract Objectives Metabolic function of selenoprotein V (SELENOV) remains unknown, although we previously showed a strong correlation of its gene expression with the high-fat diet-induced obesity in pigs. This study was conducted to explore the role and mechanism of SELENOV in body fat metabolism. Methods We applied the CRISPR/Cas9 gene-targeting deletion to generate Selenovknockout (KO) mice (C57BL/6 J background). Male KO and their wild-type (WT) (8 weeks old, n = 10 per genotype by treatment group) were fed a normal diet (NF, 10% calories coming from fat) or a high-fat diet (HF, 60% calories coming from fat) for 27 weeks. At the end, body weights and composition of mice were recorded, and tissues were collected to assay for gene expression and protein production related to lipid metabolism. Results Body weights of the KO mice fed the NF or HF diet were 16–19% higher (P < 0.05) than those of the WT mice. Total fat mass of the KO mice was 54% higher (P < 0.05) than the WT mice fed either diet, whereas total lean mass of the KO mice was 5 and 35% lower (P < 0.05) than that of WT mice fed the NF and HF diets, respectively. Gene expression of key enzymes (Fasn, Acaca, Dgat1, and Lpl) involved in lipogenesis was elevated (P < 0.05) in the white adipose tissue of the KO mice compared with the WT mice. In contrast, differences in gene expression of enzymes related to lipolysis and fatty acid oxidation (Atgl, Hsl, Ces1d, and Cpt1a) between the two genotypes were exactly the opposite (P < 0.05). Consistently, levels of proteins related to lipid accumulation (pACC, ACC, FAS, and LPL) were upregulated (P < 0.05) and proteins related to lipolysis (ATGL, HSL, and pHSL) were down-regulated (P < 0.05) in the KO mice compared with the WT mice. Conclusions Knockout of Selenov predisposed the male mice to elevated lipogenesis and attenuated lipolyis, leading to the body fat accumulation. This illustrated role and mechanism of SELENOV helps explain our previously-reported correlation between its gene expression and the high-fat diet-induced obesity in pigs. Funding Sources This research was supported in part by a NSFC grant #31,320,103,920.

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Leanness and Low Plasma Leptin in GPR17 Knockout Mice Are Dependent on Strain and Associated With Increased Energy Intake That Is Not Suppressed by Exogenous Leptin

Frontiers in Endocrinology ◽

10.3389/fendo.2021.698115 ◽

2021 ◽

Vol 12 ◽

Author(s):

Edward T. Wargent ◽

Suhaib J. S. Ahmad ◽

Qing Richard Lu ◽

Evi Kostenis ◽

Jonathan R. S. Arch ◽

...

Keyword(s):

Body Weight ◽

Food Intake ◽

Energy Intake ◽

High Fat Diet ◽

Sympathetic Activity ◽

The Body ◽

Whole Body ◽

High Fat ◽

Diet Induced Obesity ◽

Plasma Leptin

Previous studies have shown that agonists of GPR17 stimulate, while antagonists inhibit feeding. However, whole body knockout of GPR17 in mice of the C57Bl/6 strain did not affect energy balance, whereas selective knockout in oligodendrocytes or pro-opiomelanocortin neurons provided protection from high fat diet-induced obesity and impaired glucose homeostasis. We reasoned that whole body knockout of GPR17 in mice of the 129 strain might elicit more marked effects because the 129 strain is more susceptible than the C57Bl/6 strain to increased sympathetic activity and less susceptible to high fat diet-induced obesity. Consistent with this hypothesis, compared to wild-type mice, and when fed on either a chow or a high fat diet, GPR17 -/- mice of the 129 strain displayed increased expression of uncoupling protein-1 in white adipose tissue, lower body weight and fat content, reduced plasma leptin, non-esterified fatty acids and triglycerides, and resistance to high fat diet-induced glucose intolerance. Not only energy expenditure, but also energy intake was raised. Administration of leptin did not suppress the increased food intake in GPR17 -/- mice of the 129 strain, whereas it did suppress food intake in GPR17 +/+ mice. The only difference between GPR17 +/- and GPR17 +/+ mice of the C57Bl/6 strain was that the body weight of the GPR17 -/- mice was lower than that of the GPR17 +/+ mice when the mice were fed on a standard chow diet. We propose that the absence of GPR17 raises sympathetic activity in mice of the 129 strain in response to a low plasma fuel supply, and that the consequent loss of body fat is partly mitigated by increased energy intake.

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Energy expenditure in obesity-prone and obesity-resistant rats before and after the introduction of a high-fat diet

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00549.2009 ◽

2010 ◽

Vol 299 (4) ◽

pp. R1097-R1105 ◽

Cited By ~ 33

Author(s):

Matthew R. Jackman ◽

Paul S. MacLean ◽

Daniel H. Bessesen

Keyword(s):

Physical Activity ◽

Weight Gain ◽

Energy Expenditure ◽

Energy Intake ◽

High Fat Diet ◽

Female Rats ◽

High Fat ◽

Male And Female ◽

Male And Female Rats ◽

Before And After

While most rats gain weight when placed on a high-fat diet (HFD), some strains resist HFD-induced weight gain. To maintain weight, obesity-resistant (OR) rats must either eat less than obesity-prone (OP) rats or increase total energy expenditure (TEE). To determine if changes in TEE predispose to or protect from weight gain, energy expenditure, energy intake, and weight gain were measured in male and female OP and OR rats consuming a low-fat diet (LFD) and for 5 days after switching to a HFD. After 5 days on a HFD, OP rats gained significantly more weight (male: 42.8 ± 6.9 g, female: 25.5 ± 3.0 g) than their OR counterparts (male: 24.0 ± 7.5 g, female: 13.7 ± 1.4 g). Both male and female rats significantly increased their energy intake when transitioned to the HFD, and TEE increased modestly in all groups. Compared with female OP rats, female OR rats had a significantly greater increase in TEE on the HFD. This was due to an increase in both resting and nonresting energy expenditure. In contrast, the effect of the HFD in males was minor. TEE was also measured in female rats consuming a HFD, pair fed to LFD calories. The increase in TEE of pair-fed female OR rats was substantially less than what was seen in the HFD ad libitum condition. Physical activity was also measured in female rats. There was no evidence that increases in physical activity were the cause of the increased TEE seen in female OR rats consuming a HFD. These results suggest that resistance to HFD-induced weight gain in female OR rats may be due in part to an increase in TEE and a greater reliance on lipid as an energy source. Changes in TEE appear to be triggered by overconsumption of the HFD and not simply the diet composition.

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Abstract 75: Chronic Treatment With At2 Receptor Agonist Rescues High Fat Diet-induced Obesity in Female Mice.

Hypertension ◽

10.1161/hyp.60.suppl_1.a75 ◽

2012 ◽

Vol 60 (suppl_1) ◽

Author(s):

Mohammed A Khan ◽

Preethi Samuel ◽

Sourashish Nag ◽

Tahir Hussain

Keyword(s):

Body Weight ◽

Weight Gain ◽

High Fat Diet ◽

Body Weight Gain ◽

The Body ◽

Calorie Intake ◽

Adipocyte Size ◽

High Fat ◽

Female Mice ◽

Diet Induced Obesity

Obesity in itself is a disease condition and a major risk factor in the development of hypertension, dyslipidemia, and hyperglycemia. Therefore, successful strategies for improving obesity and related metabolic risk factors are needed. Role of renin-angiotensin system (RAS) has been implicated in obesity and metabolic dysfunction. Recently, we have shown that AT2R knock-out in female mice caused a greater body weight gain and hyperinsulimia in response to high fat diet (HFD). In the present study, we hypothesize that AT2R activation rescues diet-induced obesity in females. To test this hypothesis, we injected AT2R non-peptide agonist C21 (0.3mg/kg/day i.p) in C57BL6 female mice on HFD for 12 weeks. C21-treatment did not affect the HFD calorie intake (HFD: 937±18 Kcal; C21HFD: 886±37 Kcal) but caused lesser body weight gain compared to control (HFD: 4.4± 0.4g; C21HFD: 3.06± 0.4g). Similar to the body weight gain pattern, gonadal fat weight and adipocyte size were decreased significantly in C21-treated mice on HFD compared to control HFD group (HFD: 4.4± 0.4 g; C21 HFD: 3.06± 0.4g) and (HFD: 6404±161.6μm2 ; C21HFD: 3874±103.2μm2 ) respectively. Moreover, the C21-treated females on HFD had lower levels of plasma insulin, improved glucose tolerance, and decreased plasma free fatty acids and hepatic triglycerides. Western blot revealed that phospho-Ser79-acetyl CoA carboxylase (p-Ser79-ACC-1) was reduced, an index of increased lipogenic activity and decreased β-oxidation process, in both adipose (Adi) and hepatic (Hep) tissues of HFD fed groups (Adi: 86% and Hep: 73% of 100% controls); C21-treatment revered the decrease in p-ser79-ACC-1 in Adi (104% of control) and caused an increase in Hep (122% of control) respectively. The HFD feeding lowered the estradiol level (ND: 38.8±2.6 vs HFD:11.3±1.2ng), which was modestly reversed by C21 treatment (C21HFD:17.4± 1.5ng) in HFD mice. Our results strongly suggest that stimulation of AT2R in female mice positively contribute, predominantly independent of estrogen, to rescue body weight gain and adipocyte size increase in response to HFD. We propose reduced lipogenesis and enhanced lipid β-oxidation as potential mechanisms linked to AT2R action in reducing obesity and its related metabolic disorders in females.

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SUN-LB118 Mice With Skeletal Muscle-Specific DRP1 Deficiency Are Resistant to Obesity and Diabetes Induced by a High Fat Diet

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.2320 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Renato Daniel Jensen ◽

Joshua Peterson ◽

Benjamin Allington ◽

Alayna Dieter ◽

Linhai Cheng ◽

...

Keyword(s):

Gene Expression ◽

Skeletal Muscle ◽

Endoplasmic Reticulum ◽

Energy Expenditure ◽

Er Stress ◽

High Fat Diet ◽

High Fat ◽

Diet Induced Obesity ◽

Expression Of Genes ◽

Obesity And Diabetes

Abstract The skeletal muscle of type 2 diabetics exhibits mitochondrial dysfunction associated with increased mitochondrial fission. Dynamin-related protein 1 (DRP1) is responsible for mitochondrial division, whereas mitochondrial-endoplasmic reticulum contacts (MERCs) mark mitochondrial sites where fission occurs. Here, we have shown that skeletal muscle-specific DRP1 knock out (KO) mice are partly protected from high fat diet-induced obesity and diabetes, and exhibit increased insulin and glucose tolerance along with lower insulinemia. We also found that KO mice exhibit increased energy expenditure per unit of lean mass. Isolated DRP1-deficient skeletal muscle fibers from KO mice fed high fat diet have reduced respiratory capacity when exposed to ADP and palmitoyl-carnitine, but not when exposed to ADP, pyruvate, and malate. Additionally, the skeletal muscle of KO mice fed normal chow exhibited altered expression of genes associated with MERCs and increased expression of genes linked to ER stress. We observed substantial increases in gene expression of FGF21, a downstream signal of the ER stress response, in KO mice. However, FGF21 plasma concentration in KO mice was not elevated. Additionally, changes in MERC gene expression could potentially alter calcium signaling between the mitochondria and endoplasmic reticulum, changing insulin sensitivity in KO mice. In conclusion, we have shown that skeletal muscle-specific DRP1 KO mice are resistant to high fat diet-induced obesity and diabetes, perhaps due to elevated energy expenditure and differential mitochondrial respiratory adaptations to different substrates. Although FGF21 does not appear to contribute to this effect, it is possible that other ER-stress signals might help explain the observed phenotype in KO mice.

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Glial cell line-derived neurotrophic factor protects against high-fat diet-induced obesity

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00364.2013 ◽

2014 ◽

Vol 306 (6) ◽

pp. G515-G525 ◽

Cited By ~ 16

Author(s):

Simon Musyoka Mwangi ◽

Behtash Ghazi Nezami ◽

Blessing Obukwelu ◽

Mallappa Anitha ◽

Smitha Marri ◽

...

Keyword(s):

Weight Gain ◽

Energy Expenditure ◽

Cell Line ◽

Glial Cell ◽

Neurotrophic Factor ◽

High Fat Diet ◽

High Fat ◽

Brown Adipocytes ◽

Diet Induced Obesity

Obesity is a growing epidemic with limited effective treatments. The neurotrophic factor glial cell line-derived neurotrophic factor (GDNF) was recently shown to enhance β-cell mass and improve glucose control in rodents. Its role in obesity is, however, not well characterized. In this study, we investigated the ability of GDNF to protect against high-fat diet (HFD)-induced obesity. GDNF transgenic (Tg) mice that overexpress GDNF under the control of the glial fibrillary acidic protein promoter and wild-type (WT) littermates were maintained on a HFD or regular rodent diet for 11 wk, and weight gain, energy expenditure, and insulin sensitivity were monitored. Differentiated mouse brown adipocytes and 3T3-L1 white adipocytes were used to study the effects of GDNF in vitro. Tg mice resisted the HFD-induced weight gain, insulin resistance, dyslipidemia, hyperleptinemia, and hepatic steatosis seen in WT mice despite similar food intake and activity levels. They exhibited significantly ( P < 0.001) higher energy expenditure than WT mice and increased expression in skeletal muscle and brown adipose tissue of peroxisome proliferator activated receptor-α and β1- and β3-adrenergic receptor genes, which are associated with increased lipolysis and enhanced lipid β-oxidation. In vitro, GDNF enhanced β-adrenergic-mediated cAMP release in brown adipocytes and suppressed lipid accumulation in differentiated 3T3L-1 cells through a p38MAPK signaling pathway. Our studies demonstrate a novel role for GDNF in the regulation of high-fat diet-induced obesity through increased energy expenditure. They show that GDNF and its receptor agonists may be potential targets for the treatment or prevention of obesity.

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Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats

Advances in Biology ◽

10.1155/2014/162914 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 31

Author(s):

Souravh Bais ◽

Guru Sewak Singh ◽

Ramica Sharma

Keyword(s):

Body Weight ◽

Body Temperature ◽

Total Cholesterol ◽

High Fat Diet ◽

Moringa Oleifera ◽

Chronic Administration ◽

The Body ◽

Atherogenic Index ◽

High Fat ◽

Diet Induced Obesity

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.

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Dietary Isoliquiritigenin at a Low Dose Ameliorates Insulin Resistance and NAFLD in Diet-Induced Obesity in C57BL/6J Mice

International Journal of Molecular Sciences ◽

10.3390/ijms19103281 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3281 ◽

Cited By ~ 4

Author(s):

Youngmi Lee ◽

Eun-Young Kwon ◽

Myung-Sook Choi

Keyword(s):

Insulin Resistance ◽

Energy Expenditure ◽

Body Fat ◽

Fat Mass ◽

High Fat Diet ◽

Plasma Cholesterol ◽

Cellular Respiration ◽

Body Fat Mass ◽

High Fat ◽

Diet Induced Obesity

Isoliquiritigenin (ILG) is a flavonoid constituent of Glycyrrhizae plants. The current study investigated the effects of ILG on diet-induced obesity and metabolic diseases. C57BL/6J mice were fed a normal diet (AIN-76 purified diet), high-fat diet (40 kcal% fat), and high-fat diet +0.02% (w/w) ILG for 16 weeks. Supplementation of ILG resulted in decreased body fat mass and plasma cholesterol level. ILG ameliorated hepatic steatosis by suppressing the expression of hepatic lipogenesis genes and hepatic triglyceride and fatty acid contents, while enhancing β-oxidation in the liver. ILG improved insulin resistance by lowering plasma glucose and insulin levels. This was also demonstrated by the intraperitoneal glucose tolerance test (IPGTT). Additionally, ILG upregulated the expression of insulin signaling-related genes in the liver and muscle. Interestingly, ILG elevated energy expenditure by increasing the expression of thermogenesis genes, which is linked to stimulated mitochondrial biogenesis and uncoupled cellular respiration in brown adipose tissue. ILG also suppressed proinflammatory cytokine levels in the plasma. These results suggest that ILG supplemented at 0.02% in the diet can ameliorate body fat mass, plasma cholesterol, non-alcoholic fatty liver disease, and insulin resistance; these effects were partly mediated by increasing energy expenditure in high-fat fed mice.

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Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000783 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000783 ◽

Cited By ~ 7

Author(s):

Liang Xu ◽

Naoto Nagata ◽

Guanliang Chen ◽

Mayumi Nagashimada ◽

Fen Zhuge ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Energy Expenditure ◽

Chronic Inflammation ◽

Plasma Levels ◽

High Fat Diet ◽

Macrophage Activation ◽

Low Grade ◽

Obese Mice ◽

High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

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