scholarly journals TRPM2 Ca2+ channel regulates energy balance and glucose metabolism

2012 ◽  
Vol 302 (7) ◽  
pp. E807-E816 ◽  
Author(s):  
Zhiyou Zhang ◽  
Wenyi Zhang ◽  
Dae Young Jung ◽  
Hwi Jin Ko ◽  
Yongjin Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Gsk 3Β ◽  
Fat Feeding

TRPM2 Ca2+-permeable cation channel is widely expressed and activated by markers of cellular stress. Since inflammation and stress play a major role in insulin resistance, we examined the role of TRPM2 Ca2+ channel in glucose metabolism. A 2-h hyperinsulinemic euglycemic clamp was performed in TRPM2-deficient (KO) and wild-type mice to assess insulin sensitivity. To examine the effects of diet-induced obesity, mice were fed a high-fat diet for 4–10 mo, and metabolic cage and clamp studies were conducted in conscious mice. TRPM2-KO mice were more insulin sensitive partly because of increased glucose metabolism in peripheral organs. After 4 mo of high-fat feeding, TRPM2-KO mice were resistant to diet-induced obesity, and this was associated with increased energy expenditure and elevated expressions of PGC-1α, PGC-1β, PPARα, ERRα, TFAM, and MCAD in white adipose tissue. Hyperinsulinemic euglycemic clamps showed that TRPM2-KO mice were more insulin sensitive, with increased Akt and GSK-3β phosphorylation in heart. Obesity-mediated inflammation in adipose tissue and liver was attenuated in TRPM2-KO mice. Overall, TRPM2 deletion protected mice from developing diet-induced obesity and insulin resistance. Our findings identify a novel role of TRPM2 Ca2+ channel in the regulation of energy expenditure, inflammation, and insulin resistance.

scholarly journals Urtica dioica Whole Vegetable as a Functional Food Targeting Fat Accumulation and Insulin Resistance-a Preliminary Study in a Mouse Pre-Diabetic Model

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1059
Author(s):  
Si Fan ◽  
Samnhita Raychaudhuri ◽  
Olivia Kraus ◽  
Md Shahinozzaman ◽  
Leila Lofti ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Urtica Dioica ◽  
Whole Body ◽  
High Fat ◽  
Fat Accumulation ◽  
Diet Induced Obesity

The shoot of Urtica dioica is used in several cultures as a vegetable or herb. However, not much has been studied about the potential of this plant when consumed as a whole food/vegetable rather than an extract for dietary supplements. In a 12-week dietary intervention study, we tested the effect of U. dioica vegetable on high fat diet induced obesity and insulin resistance in C57BL/6J mice. Mice were fed ad libitum with isocaloric diets containing 10% fat or 45% fat with or without U. dioica. The diet supplemented with U. dioica attenuated high fat diet induced weight gain (p < 0.005; n = 9), fat accumulation in adipose tissue (p < 0.005; n = 9), and whole-body insulin resistance (HOMA-IR index) (p < 0.001; n = 9). Analysis of gene expression in skeletal muscle showed no effect on the constituents of the insulin signaling pathway (AKT, IRS proteins, PI3K, GLUT4, and insulin receptor). Notable genes that impact lipid or glucose metabolism and whose expression was changed by U. dioica include fasting induced adipocyte factor (FIAF) in adipose and skeletal muscle, peroxisome proliferator-activated receptor-α (Ppar-α) and forkhead box protein (FOXO1) in muscle and liver, and Carnitine palmitoyltransferase I (Cpt1) in liver (p < 0.01). We conclude that U. dioica vegetable protects against diet induced obesity through mechanisms involving lipid accumulation and glucose metabolism in skeletal muscle, liver, and adipose tissue.

scholarly journals Role of Muscle c-Jun NH2-Terminal Kinase 1 in Obesity-Induced Insulin Resistance

2009 ◽  
Vol 30 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Guadalupe Sabio ◽  
Norman J. Kennedy ◽  
Julie Cavanagh-Kyros ◽  
Dae Young Jung ◽  
Hwi Jin Ko ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Akt Activation ◽  
Peripheral Insulin Resistance ◽  
Diet Induced Obesity

ABSTRACT Obesity caused by feeding of a high-fat diet (HFD) is associated with an increased activation of c-Jun NH2-terminal kinase 1 (JNK1). Activated JNK1 is implicated in the mechanism of obesity-induced insulin resistance and the development of metabolic syndrome and type 2 diabetes. Significantly, Jnk1 − / − mice are protected against HFD-induced obesity and insulin resistance. Here we show that an ablation of the Jnk1 gene in skeletal muscle does not influence HFD-induced obesity. However, muscle-specific JNK1-deficient (MKO) mice exhibit improved insulin sensitivity compared with control wild-type (MWT) mice. Thus, insulin-stimulated AKT activation is suppressed in muscle, liver, and adipose tissue of HFD-fed MWT mice but is suppressed only in the liver and adipose tissue of MKO mice. These data demonstrate that JNK1 in muscle contributes to peripheral insulin resistance in response to diet-induced obesity.

scholarly journals RGC32 deficiency protects against high-fat diet-induced obesity and insulin resistance in mice

2014 ◽  
Vol 224 (2) ◽  
pp. 127-137 ◽  
Author(s):  
Xiao-Bing Cui ◽  
Jun-Na Luan ◽  
Jianping Ye ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Tolerance Test ◽  
High Fat ◽  
Diet Induced Obesity

Obesity is an important independent risk factor for type 2 diabetes, cardiovascular diseases and many other chronic diseases. Adipose tissue inflammation is a critical link between obesity and insulin resistance and type 2 diabetes and a contributor to disease susceptibility and progression. The objective of this study was to determine the role of response gene to complement 32 (RGC32) in the development of obesity and insulin resistance. WT and RGC32 knockout (Rgc32−/− (Rgcc)) mice were fed normal chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical, and histologic analyses were performed. 3T3-L1 preadipocytes were used to study the role of RGC32 in adipocytes in vitro. Rgc32−/− mice fed with HFD exhibited a lean phenotype with reduced epididymal fat weight compared with WT controls. Blood biochemical analysis and insulin tolerance test showed that RGC32 deficiency improved HFD-induced dyslipidemia and insulin resistance. Although it had no effect on adipocyte differentiation, RGC32 deficiency ameliorated adipose tissue and systemic inflammation. Moreover, Rgc32−/− induced browning of adipose tissues and increased energy expenditure. Our data indicated that RGC32 plays an important role in diet-induced obesity and insulin resistance, and thus it may serve as a potential novel drug target for developing therapeutics to treat obesity and metabolic disorders.

Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice

2007 ◽  
Vol 292 (4) ◽  
pp. E1079-E1086 ◽  
Author(s):  
John W. Bullen ◽  
Susann Bluher ◽  
Theodoros Kelesidis ◽  
Christos S. Mantzoros
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Adiponectin Mrna ◽  
Obesity In Mice ◽  
Fat Feeding

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.

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

2018 ◽  
Vol 19 (10) ◽  
pp. 3281 ◽  
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.

scholarly journals Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Bingxin Lu ◽  
Jianing Zhong ◽  
Jianfei Pan ◽  
Xiaopeng Yuan ◽  
Mingzhi Ren ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Balance ◽  
Glucose Metabolism ◽  
Gene Transfer ◽  
White Adipose Tissue ◽  
High Fat Diet ◽  
Diabetic Mice ◽  
Metabolic Homeostasis ◽  
High Fat

Abstract Background The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance. Methods Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models. Results Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-β/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue. Conclusions These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

Role of brown adipose tissue in modulating adipose tissue inflammation and insulin resistance in high-fat diet fed mice

2019 ◽  
Vol 854 ◽  
pp. 354-364 ◽  
Author(s):  
Kripa Shankar ◽  
Durgesh Kumar ◽  
Sanchita Gupta ◽  
Salil Varshney ◽  
Sujith Rajan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation ◽  
Brown Adipose

Abstract 537: Dock2 Deficiency Mitigates High-Fat Diet-Induced Obesity by Reducing Adipose Tissue Inflammation While Increasing Energy Expenditure

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Xia Guo ◽  
Feifei Li ◽  
Zaiyan Xu ◽  
Shi-You Chen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Inflammatory Diseases ◽  
Body Weight Gain ◽  
Public Health Problem ◽  
Adipose Tissue Inflammation ◽  
High Fat ◽  
Tissue Inflammation

Obesity is a public health problem as its association with type 2 diabetes, cardiovascular disorders and many other diseases. Adipose tissue inflammation is frequently observed and plays a vital role in obesity and insulin resistance. Dedicator of cytokinesis 2 (DOCK2) has shown proinflammatory effect in several inflammatory diseases, but its role in obesity remain unknown. To explore the function of DOCK2 in obesity and insulin resistance, wild-type (WT) and DOCK2 knockout (DOCK2-/-) mice were fed with chow or high-fat diet (HFD) for 12 weeks. Metabolic, biochemical and histologic analyses were performed. DOCK2 expression was robustly up-regulated in adipose tissue in WT mice given HFD. DOCK2-/- mice were protected against HFD-enhanced body weight gain with an improved metabolic homeostasis and insulin resistance. In addition, DOCK2 deficiency attenuated adipose tissue and systemic inflammation accompanied by a reduced macrophage infiltration. Moreover, DOCK2 deficiency induced the adipose tissue browning and increased energy expenditure as shown by the up-regulation of metabolic genes in DOCK2-/- mice. Our data indicated that DOCK2 deficiency can protect mice from HFD-induced obesity, metabolic disorders, and insulin resistance. Therefore, targeting DOCK2 may be a potential therapeutic strategy for treating obesity-associated diseases.

scholarly journals Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 26 ◽  
Author(s):  
Jin Choi ◽  
No-Joon Song ◽  
A Lee ◽  
Dong Lee ◽  
Min-Ju Seo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Obese Mice ◽  
High Fat ◽  
White Adipocyte

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.

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