scholarly journals Emodin Improves Glucose and Lipid Metabolism Disorders in Obese Mice via Activating Brown Adipose Tissue and Inducing Browning of White Adipose Tissue

2020 ◽  
Author(s):  
Long Cheng ◽  
Shuofeng Zhang ◽  
Fei Shang ◽  
Jianning Sun ◽  
Shifen Dong
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Fasting Blood Glucose ◽  
Lipid Levels ◽  
High Fat ◽  
Brown Adipose ◽  
Lipid Metabolites ◽  
O 18

Abstract Background: Obesity has become a worldwide health threat related to type 2 diabetes, hypertension, cardiovascular disease, etc. Activating brown adipocytes and inducing browning of white adipocytes has been proposed as a potential molecular target for obesity treatment. In the present study, we investigated the effects of emodin on browning in mice with high-fat diet (HFD) and explore its underlying pharmacological mechanisms. Methods: The positive effects of emodin (40, 80 mg/kg/day, i.g. for 6 weeks) on lipid metabolism were evaluated in mice model of hyperlipidemia. Hyperlipidemia mice were induced by high-fat diet (60% of kilocalories from fat, 5.24 Kcal/kg) for 8 weeks. Body weight and food intake were monitored every week. After 6 weeks of treatment, fasting blood glucose, oral glucose tolerance, Lee's index, the ratio of fat weight to body weight, blood lipids, and adipose tissues morphology were assayed. Then uncoupling protein 1 (UCP1), CD36, fatty acid transporter 4 (FATP4), peroxisome proliferator activated receptor α (PPARα) and prohibitin (PHB) protein of subcutaneous white adipose tissue (scWAT) and brown adipose tissue (BAT) were analyzed. In addition, the lipid metabolites in adipose tissues were analyzed by ultra-high- performance liquid chromatography with electrospray ionization tandem mass spectrometry.Results: Emodin treatment decreased body weight gain, fasting blood glucose, Lee's index, the ratio of scWAT weight to body weight, and the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-c) and Leptin in serum, and increased serum adiponectin content and improved glucose tolerance. Furthermore, emodin enhanced the expression of UCP1, CD36, FATP4, PPARα and PHB protein in scWAT and BAT. Meanwhile, emodin can significantly up-regulated lipid levels in scWAT of mice fed with HFD such as PC(O-18:2/22:5), PE(O-18:1/18:2), PE(O-18:2/20:4), PE(O-20:1/20:5), Cer(d14:1/20:0) and SM(d18:0/23:0), and reduced the lipid levels such as PC(O-18:0/20:0), PE(O-18:2/22:2), PE(O-18:0/22:5). In addition, emodin significantly up-regulate lipid levels in BAT of mice fed with HFD such as PC(14:0/16:0), PC(16:0/16:1), PC(16:1/16:1), PC(15:1/18:3), PC(18:0/20:0), LysoPC(20:0), LysoPC(22:0) and LysoPC(22:1), and reduced the lipid levels PC(12:0/20:4) and PC(17:0/22:5). Conclusions: These results indicated that hyperlipidemia could be alleviated by treatment of emodin via promoting browning of white adipose tissue. In addition, the disturbance of some small lipid metabolites in adipose also could be reversed by emodin.

scholarly journals Anti-Obesity Effects of Grateloupia elliptica, a Red Seaweed, in Mice with High-Fat Diet-Induced Obesity via Suppression of Adipogenic Factors in White Adipose Tissue and Increased Thermogenic Factors in Brown Adipose Tissue

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 308 ◽  
Author(s):  
Hyo-Geun Lee ◽  
Yu An Lu ◽  
Xining Li ◽  
Ji-Min Hyun ◽  
Hyun-Soo Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Red Seaweed ◽  
High Fat ◽  
Adipose Tissues ◽  
Ppar Γ ◽  
Brown Adipose ◽  
Treatment Of Obesity

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.

Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

2005 ◽  
Vol 288 (6) ◽  
pp. E1236-E1243 ◽  
Author(s):  
Elena Velkoska ◽  
Timothy J. Cole ◽  
Margaret J. Morris
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Neuropeptide Y ◽  
Litter Size ◽  
High Fat Diet ◽  
Dietary Intervention ◽  
High Fat ◽  
Brown Adipose

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.

Ventromedial hypothalamic knife-cut lesions in rats resistant to dietary obesity

1984 ◽  
Vol 246 (6) ◽  
pp. R943-R948 ◽  
Author(s):  
J. Oku ◽  
G. A. Bray ◽  
J. S. Fisler ◽  
R. Schemmel
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
High Fat Diet ◽  
Corn Oil ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Dietary Obesity

The effects of ventromedial hypothalamic (VMH) knife-cut lesions on food intake and body weight of S 5B/Pl rats, which are normally resistant to obesity when eating a high-fat diet, were examined in two experiments. In the first experiment body weight increased only slightly after VMH knife-cut lesions when animals were fed pelleted laboratory chow or a 10% corn oil diet. When eating the 30% corn oil diet, however, body weight increased in the VMH knife-cut rats. In the second experiment VMH knife-cut lesions produced a small weight gain in rats fed the 10% fat diet; this manipulation also increased food intake and disrupted the normal diurnal feeding pattern. Changes in the weight of the liver, interscapular brown adipose tissue, and white adipose tissue paralleled the changes in body weight. Plasma insulin increased in the rats eating the 30% corn oil diet ad libitum but not in the VMH-lesioned animals pair fed to the sham-operated rats. Incorporation of 3H from 3H2O into lipid was significantly increased in white fat of animals with VMH knife cuts. Similar results were obtained from incubation of adipose tissue in vitro with insulin and radioactively labeled glucose. These studies show that hypothalamic knife-cut lesions can remove the resistance of the S 5B/Pl rats to obesity when they are fed a high-fat diet.

scholarly journals Differential Protein Expression in White Adipose Tissue from Obesity-Prone and Obesity-Resistant Mice in Response to High Fat Diet and Anti-Obesity Herbal Medicines

2015 ◽  
Vol 35 (4) ◽  
pp. 1482-1498 ◽  
Author(s):  
Sang Woo Kim ◽  
Tae-Jun Park ◽  
Jae Heon Choi ◽  
Kanikkai Raja Aseer ◽  
Ji-Young Choi ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Proteomic Analysis ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Herbal Medicines ◽  
High Fat ◽  
Body Weight Reduction ◽  
Peptide Mass

Background: One of the most interesting issues in obesity research is why certain humans are obesity-prone (OP) while others are obesity-resistant (OR) upon exposure to a high-calorie diet. However, the pathways responsible for these phenotypic differences are still largely unknown. Methods: In order to discover marker molecules determining susceptibility and/or resistance to obesity in response to high fat diet (HFD) or anti-obesity herbal medicine (TH), we conducted comparative proteomic analysis of white adipose tissue (WAT) from OP, OR, as well as TH-treated mice. Results: OP mice fed HFD gained approximately 33% more body weight than OR mice, and TH significantly reduced body weight gain in HFD-fed mice by 30%. These mice were further subjected to proteomic analysis using two-dimensional electrophoresis (2-DE) combined with matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF-MS). Proteomic data revealed 59 spots that were differentially regulated from a total of 1,045 matched spots, and 57 spots of these were identified as altered WAT proteins between OP and OR mice by peptide mass finger printing. Interestingly, 45 proteins were similarly regulated in OR mice in response to TH treatment. Of these, 10 proteins have already been recognized in the context of obesity; however, other proteins involved in obesity susceptibility or resistance were identified for the first time in the present study. Conclusion: Our results suggest that TH actively contributed to body weight reduction in HFD-fed obese mice by altering protein regulation in WAT, and it was also found that TH-responsive proteins can be used as potent molecules for obesity treatment.

scholarly journals Anti-Obesity and Anti-Diabetic Effects of Acacia Polyphenol in Obese Diabetic KKAy Mice Fed High-Fat Diet

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Nobutomo Ikarashi ◽  
Takahiro Toda ◽  
Takehiro Okaniwa ◽  
Kiyomi Ito ◽  
Wataru Ochiai ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Acid Synthesis ◽  
Diet Group ◽  
High Fat ◽  
Kkay Mice

Acacia polyphenol (AP) extracted from the bark of the black wattle tree (Acacia meansii) is rich in unique catechin-like flavan-3-ols, such as robinetinidol and fisetinidol. The present study investigated the anti-obesity/anti-diabetic effects of AP using obese diabetic KKAy mice. KKAy mice received either normal diet, high-fat diet or high-fat diet with additional AP for 7 weeks. After the end of administration, body weight, plasma glucose and insulin were measured. Furthermore, mRNA and protein expression of obesity/diabetic suppression-related genes were measured in skeletal muscle, liver and white adipose tissue. As a result, compared to the high-fat diet group, increases in body weight, plasma glucose and insulin were significantly suppressed for AP groups. Furthermore, compared to the high-fat diet group, mRNA expression of energy expenditure-related genes (PPARα, PPARδ, CPT1, ACO and UCP3) was significantly higher for AP groups in skeletal muscle. Protein expressions of CPT1, ACO and UCP3 for AP groups were also significantly higher when compared to the high-fat diet group. Moreover, AP lowered the expression of fat acid synthesis-related genes (SREBP-1c, ACC and FAS) in the liver. AP also increased mRNA expression of adiponectin and decreased expression of TNF-αin white adipose tissue. In conclusion, the anti-obesity actions of AP are considered attributable to increased expression of energy expenditure-related genes in skeletal muscle, and decreased fatty acid synthesis and fat intake in the liver. These results suggest that AP is expected to be a useful plant extract for alleviating metabolic syndrome.

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

Metabolites ◽  
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.

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

2014 ◽  
Vol 306 (10) ◽  
pp. E1176-E1187 ◽  
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.

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

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 411-418 ◽  
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.

Sign in / Sign up

Export Citation Format

Share Document