scholarly journals Constitutive Activation of IKKβ in Adipose Tissue Prevents Diet-Induced Obesity in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (1) ◽  
pp. 154-165 ◽  
Author(s):  
Ping Jiao ◽  
Bin Feng ◽  
Jie Ma ◽  
Yaohui Nie ◽  
Erin Paul ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Fatty Acid Binding ◽  
Iκb Kinase ◽  
Age Related

The IκB kinase β (IKKβ) is a master kinase involved in obesity-related inflammation and insulin resistance through nuclear factor κB dependent and independent pathways. However, the effect of IKKβ activation in adipose tissue, the organ critical for storage of excessive energy and initiation of inflammatory responses in the context of obesity, on systemic insulin sensitivity and metabolism, has not been investigated. In our study, we found that mice overexpressing the constitutively active IKKβ in adipose tissue under the control of murine adipocyte fatty acid binding protein (aP2) promoter were protected from age-related and diet-induced body weight gains, despite increased food intake. The aP2-IKKβ SE mice have significantly reduced weights in all white adipose tissue depots and reduced triglyceride contents in adipose tissue, liver, and muscle. Despite increased systemic and tissue inflammation, aP2-IKKβ SE mice displayed decreased blood glucose levels, improved glucose, and insulin tolerance. This may be at least partially attributable to increased energy expenditure. Histological analysis revealed presence of many small adipocytes in white adipose tissue of aP2-IKKβ SE mice fed on high-fat diet. Furthermore, transgenic expression of IKKβ in adipose tissue improved high-fat diet-induced hepatosteatosis. Collectively, increased energy expenditure and reduced plasma free fatty acid levels may contribute to enhanced systemic insulin sensitivity in aP2-IKKβ SE mice. Our study demonstrates that presence of inflammation in adipose tissue before the development of obesity has beneficial effect on metabolism.

scholarly journals Antiobesity activity of Acer tegmentosum Maxim on 3T3-L1 preadipocyte and high-fat diet-induced obese rats

2020 ◽  
Author(s):  
Hang-Hee Cho ◽  
Soo-Jung Lee ◽  
Sung-Ho Kim ◽  
Sun-Hee Jang ◽  
Chungkil Won ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Binding Protein ◽  
High Fat ◽  
Tissue Mass ◽  
Fatty Acid Binding ◽  
Obese Rats

Abstract Background: The aim of this study was to investigate the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 adipocyte-derived cells and anti-obesity properties in high fat diet (HFD)-induced obese rats. Methods: 3T3-L1 adipocytes and HFD-induced obese rats were treated with ATM, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Results: Cellular lipid contents in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ) expressions in 3T3-L1 cells. Moreover, treatment with ATM caused a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), compared with DMI-stimulated adipocytes. In addition, phosphorylation levels of protein kinase B (Akt) and its downstream substrate, glycogen synthase kinase 3β (GSK3β), were significantly decreased by ATM treatment of 3T3-L1 adipocytes. Together, these results indicated that ATM caused inhibition of both adipocyte differentiation via suppression of the C/EBP family and PPARγ expressions and the Akt signaling pathway in 3T3-L1 adipocytes. In the present study, we further investigated anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with HFD demonstrated elevations in body weight gain, while the administration of ATM significantly reversed BW gains and adipose tissue weights in rats fed HFD. ATM supplementation also caused a decrease in the circulating triglyceride levels and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obesity in rats. Furthermore, epididymal fat exhibited larger adipocytes in the HFD group, whereas the ATM-treated group was significantly smaller than that of HFD group. These results strongly demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size. Conclusion: These finding demonstrated that ATM exerted anti-obesity effects through inhibition of adipocyte differentiation and adipogenesis, leading to a decrease in BW and fat tissue mass in HFD-induced obesity in rats.

Sex differences in the effect of high-fat diet feeding on rat white adipose tissue mitochondrial function and insulin sensitivity

Metabolism ◽  
2012 ◽  
Vol 61 (8) ◽  
pp. 1108-1117 ◽  
Author(s):  
Emilia Amengual-Cladera ◽  
Isabel Lladó ◽  
Magdalena Gianotti ◽  
Ana M. Proenza
Keyword(s):  
Sex Differences ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
White Adipose Tissue ◽  
Mitochondrial Function ◽  
High Fat Diet ◽  
High Fat

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.

Improved glucose control and reduced body fat mass in free fatty acid receptor 2-deficient mice fed a high-fat diet

2011 ◽  
Vol 300 (1) ◽  
pp. E211-E220 ◽  
Author(s):  
Mikael Bjursell ◽  
Therése Admyre ◽  
Melker Göransson ◽  
Anna E. Marley ◽  
David M. Smith ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Energy Expenditure ◽  
Body Fat ◽  
High Fat Diet ◽  
Body Fat Mass ◽  
High Fat ◽  
Free Fatty Acid Receptor ◽  
Deficient Mice

Free fatty acid receptor 2 (Ffar2), also known as GPR43, is activated by short-chain fatty acids (SCFA) and expressed in intestine, adipocytes, and immune cells, suggesting involvement in lipid and immune regulation. In the present study, Ffar2-deficient mice ( Ffar2-KO) were given a high-fat diet (HFD) or chow diet and studied with respect to lipid and energy metabolism. On a HFD, Ffar2-KO mice had lower body fat mass and increased lean body mass. The changed body composition was accompanied by improved glucose control and lower HOMA index, indicating improved insulin sensitivity in Ffar2-KO mice. Moreover, the Ffar2-KO mice had higher energy expenditure accompanied by higher core body temperature and increased food intake. The liver weight and content of triglycerides as well as plasma levels of cholesterol were lower in the Ffar2-KO mice fed a HFD. A histological examination unveiled decreased lipid interspersed in brown adipose tissue of the Ffar2-KO mice. Interestingly, no significant differences in white adipose tissue (WAT) cell size were observed, but significantly lower macrophage content was detected in WAT from HFD-fed Ffar2-KO compared with wild-type mice. In conclusion, Ffar2 deficiency protects from HFD-induced obesity and dyslipidemia at least partly via increased energy expenditure.

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 Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity

2018 ◽  
Vol 314 (1) ◽  
pp. E53-E65 ◽  
Author(s):  
Ivan Torre-Villalvazo ◽  
Luz Graciela Cervantes-Pérez ◽  
Lilia G. Noriega ◽  
Jose V. Jiménez ◽  
Norma Uribe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
The Metabolic Syndrome ◽  
Brown Adipose

The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl−]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.

scholarly journals No Additive Effects of Polyphenol Supplementation and Exercise Training on White Adiposity Determinants of High-Fat Diet-Induced Obese Insulin-Resistant Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Karen Lambert ◽  
Marie Hokayem ◽  
Claire Thomas ◽  
Odile Fabre ◽  
Cécile Cassan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
High Fat ◽  
Insulin Resistant ◽  
Polyphenol Intake ◽  
Tissue Alterations

One of the major insulin resistance instigators is excessive adiposity and visceral fat depots. Individually, exercise training and polyphenol intake are known to exert health benefits as improving insulin sensitivity. However, their combined curative effects on established obesity and insulin resistance need further investigation particularly on white adipose tissue alterations. Therefore, we compared the effects on different white adipose tissue depot alterations of a combination of exercise and grape polyphenol supplementation in obese insulin-resistant rats fed a high-fat diet to the effects of a high-fat diet alone or a nutritional supplementation of grape polyphenols (50 mg/kg/day) or exercise training (1 hr/day to 5 days/wk consisting of treadmill running at 32 m/min for a 10% slope), for a total duration of 8 weeks. Separately, polyphenol supplementation and exercise decreased the quantity of all adipose tissue depots and mesenteric inflammation. Exercise reduced adipocytes’ size in all fat stores. Interestingly, combining exercise to polyphenol intake presents no more cumulative benefit on adipose tissue alterations than exercise alone. Insulin sensitivity was improved at systemic, epididymal, and inguinal adipose tissues levels in trained rats thus indicating that despite their effects on adipocyte morphological/metabolic changes, polyphenols at nutritional doses remain less effective than exercise in fighting insulin resistance.

scholarly journals The Correlation between MicroRNA-199a and White Adipose Tissue in C57/BL6J Mice with High-Fat Diet

2017 ◽  
Author(s):  
Dan Liu ◽  
Xia Wang ◽  
Xinying Lin ◽  
Baihui Zhang ◽  
Shue Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Therapeutic Potential ◽  
Binding Protein ◽  
Regulatory Element ◽  
Control Group ◽  
Model Group ◽  
High Fat ◽  
Fatty Acid Binding

AbstractUnderstanding is emerging about microRNAs as mediators in the regulation of white adipose tissue (WAT) and obesity. The expression level of miR-199a in mice was investigated to test our hypothesis: miR-199a might be related to fat accumulation and try to find its target mRNA, which perhaps could propose strategies with a therapeutic potential affecting the fat storage. C57/BL6J mice were randomly assigned to either a control group or an obesity model group (n=10 in both groups). Control mice were fed a normal diet (fat: 10 kcal %) ad libitum for 12 weeks, and model mice were fed a high-fat diet (fat: 30 kcal %) ad libitum for 12 weeks to induce obesity. At the end of the experiment, body fat mass and the free fatty acids (FFAs) and triglycerides (TGs) in WAT were tested. Fat cell size was measured by hematoxylin-eosin (H&E) staining method. The fat mass of the model group was higher than that of the control group (P<0.05). In addition, the concentrations of the FFAs and TGs were higher (P<0.05) and the adipocyte count was lower (P<0.05) in the model group. We tested the expression levels of miR-199a and key adipogenic transcription factors, including peroxisome proliferator activated receptor gamma2 (PPARγ2), CCAAT/enhancer binding proteins alpha (C/EBPα), adipocyte fatty acid-binding protein (aP2), and sterol regulatory element binding protein-1c (SREBP-1c). Up-regulated expression of miR-199a was observed in model group. Increased levels of miR-199a was accompanied by high expression levels of SREBP-1c. We found that the 3’-UTR of SREBP-1c mRNA has a predicted binding site for miR-199a. Based on the current discoveries, we suggest that miR-199a may exert its action by binding to its target mRNA and cooperate with SREBP-1c to induce obesity. Therefore, if the predicted binding site is confirmed by further research, miR-199a may have therapeutic potential for obesity.AbbreviationsWAT, white adipose tissue; PPARγ2, peroxisome proliferator, activated receptor γ2; C/EBP αCCAAT/enhancer binding proteins α; aP2, adipocyte fatty acid-binding protein; SREBP-1c, sterol regulatory element binding protein-1c; HFD, high-fat diet.

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