Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1

Wang, Songbo; Liang, Xingwei; Yang, Qiyuan; Fu, Xing; Rogers, Carl J.; Zhu, Mei‐Jun; Rodgers, Buel D.; Jiang, Qingyan; Dodson, Michael V.; Du, Min

doi:10.1038/ijo.2015.23

Cited by 244 publications

(217 citation statements)

References 60 publications

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“…Metformin administration enhanced the expression of UCP1 and Cidea in WT BAT but not in KO BAT. Our findings are consistent with accumulating evidences showing the promotional effects of AMPK activation on brown and beige adipogenesis [17, 31–34]. On the other side, the expression of fibrogenic markers was higher in transplanted BAT with AMPK deficiency.…”

Section: Discussionsupporting

confidence: 92%

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AMPKα1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development

Zhao

Yang

Zhang

et al. 2017

Biochemical and Biophysical Research Communications

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Brown adipose tissue (BAT) dissipates energy for thermogenesis which reduces or prevents obesity and metabolic dysfunction. AMP-activated protein kinase (AMPK) is a master regulator of energy metabolism and its activity is inhibited in the developing BAT due to obesity. We previously found that AMPK is required for brown fat development and thermogenic function, but the non-brown adipogenic differentiation of progenitor cells due to AMPKα1 deficiency has not been defined. We found that, in vivo, the thermogenic capacity and morphology of BAT were compromised due to AMPK deficiency, which was correlated with decreased progenitor density in BAT. In addition, the expression of fibrogenic markers was higher in AMPK deficient compared to wild-type mice. Furthermore, we transplanted AMPKα1 wild-type (WT) and floxed BAT into the same recipient mice; following tamoxifen induced AMPKα1 knockout in floxed BAT, the fibrogenesis was enhanced compared to WT mice. Taken together, our data demonstrated that AMPKα1 deficiency suppressed brown adipogenesis in favor of fibrogenesis during BAT development.

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Section: Discussionsupporting

confidence: 92%

“…Oxygen consumption was measured using an Orion Dissolved Oxygen platform (Thermo Scientific, Waltham, MA, US) for approximately 25 min [17]. …”

Section: Methodsmentioning

confidence: 99%

AMPKα1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development

Zhao

Yang

Zhang

et al. 2017

Biochemical and Biophysical Research Communications

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“…Lasa, et al 29) reported that resveratrol increased fatty acid consumption via enhancement of CPT1 and PGC1α expressions in differentiated 3T3-L1 adipocytes. Furthermore, Wang, et al 30) reported that resveratrol induced brown-like adipocyte formation in white fat tissue. These findings suggest that the observed weight loss induced by resveratrol supplementation in this study may reflect reduction of body adiposity, but the mechanism remains to be studied.…”

Section: Discussionmentioning

confidence: 99%

Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus

et al. 2017

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SummaryResveratrol has been reported to have potent anti-atherosclerotic effects in animal studies. However, there are few interventional studies in human patients with atherosclerogenic diseases. The cardio-ankle vascular index (CAVI) reflects arterial stiffness and is a clinical surrogate marker of atherosclerosis. The aim of the present study was to investigate the effect of resveratrol on arterial stiffness assessed by CAVI in patients with type 2 diabetes mellitus (T2DM).In this double-blind, randomized, placebo-controlled study, 50 patients with T2DM received supplement of a 100-mg resveratrol tablet (total resveratrol: oligo-stilbene 27.97 mg/100 mg/day) or placebo daily for 12 weeks. CAVI was assessed at baseline and the end of study. Body weight (BW), blood pressure (BP), glucose and lipid metabolic parameters, and diacron-reactive oxygen metabolites (d-ROMs; an oxidative stress marker) were also measured.Resveratrol supplementation decreased systolic BP (-5.5 ± 13.0 mmHg), d-ROMs (-25.6 ± 41.8 U.CARR), and CAVI (-0.4 ± 0.7) significantly (P < 0.05) and decreased BW (-0.8 ± 2.1 kg, P = 0.083) and body mass index (-0.5 ± 0.8 kg/m 2 , P = 0.092) slightly compared to baseline, while there were no significant changes in the placebo group. Decreases in CAVI and d-ROMs were significantly greater in the resveratrol group than in the placebo group. Multivariate logistic regression analysis identified resveratrol supplementation as an independent predictor for a CAVI decrease of more than 0.5.In conclusion, 12-week resveratrol supplementation may improve arterial stiffness and reduce oxidative stress in patients with T2DM. Resveratrol may be beneficial in preventing the development of atherosclerosis induced by diabetes. However, a large-scale cohort study is required to validate the present findings. (Int Heart J 2017; 58: 577-583)

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“…The paraffin-embedded iWAT sections were stained with H&E as previously described [23]. Adipocyte diameter and adipocyte number analysis was performed as previously described [5].…”

Section: Hande Staining Adipocyte Diameter and Adipocyte Number Analysismentioning

confidence: 99%

“…Lipid accumulation and TG contents in the differentiated pBMSCs were determined by Oil Red O staining and a TG assay kit (Applygen Technologies Inc, China) as previously described [5,23].…”

Section: Oil Red-o Staining and Triglyceride (Tg) Assaymentioning

confidence: 99%

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

Zhang

Meng

et al. 2018

Cell Physiol Biochem

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Background/Aims: It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, we investigated the effects of calcium supplementation on adipogenesis and glucose homeostasis in porcine bone marrow mesenchymal stem cells (pBMSCs) and high fat diet (HFD)-fed mice and explored the involved signaling pathways. Methods: In vitro, pBMSCs were treated with 4 mM extracellular calcium ([Ca²⁺]_o) and/or 1 μM nifedipine, 0.1 μM BAPTA-AM, 1 μM KN-93, 50 nM wortmannin for 10 days. The intracellular calcium ([Ca²⁺]_i) levels were measured using Fluo 3-AM by flow cytometry. The adipogenic differentiation of pBMSCs was determined by Oil Red-O staining and triglyceride assay. The expression of marker genes involved in adipogenesis (peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)) and glucose uptake (glucose transporter 4 (GLUT4)), as well as the activation of Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1/AS160 signaling pathways were determined by Western blotting. Glucose uptake and utilization were examined using 2-NBDG assay and glucose content assay, respectively. In vivo, C57BL/6J male mice were fed a HFD (containing 1.2% calcium) without or with 0.6% (w/w) calcium chloride in drinking water for 13 weeks. The adipogenesis, glucose homeostasis and the involvement of CaMKII and PI3K/Akt signaling pathway were also assessed. Results: In vitro, [Ca²⁺]_o stimulated pBMSCs adipogenesis by increasing [Ca²⁺]_i level and activating CaMKII and PI3K/Akt-FoxO1 pathways. In addition, [Ca²⁺]_o promoted glucose uptake/utilization by enhancing AS160 phosphorylation, GLUT4 expression and translocation. However, the stimulating effects of [Ca²⁺]_o on pBMSCs adipogenesis and glucose uptake/utilization were abolished by L-VGCC blocker Nifedipine, [Ca²⁺]_i chelator BAPTA-AM, CaMKII inhibitor KN-93, or PI3K inhibitor Wortmannin. In vivo, calcium supplementation decreased body weight and fat content, increased adipocyte number, and improved glucose homeostasis, with elevated PPARγ and GLUT4 expression and PI3K/Akt activation in iWAT. Conclusion: calcium supplementation enhanced adipogenesis and glucose uptake in pBMSCs, which was coincident with the increased adipocyte number and improved glucose homeostasis in HFD-fed mice, and was associated with activation of CaMKII and PI3K/Akt-FoxO1/AS160 pathways. These data provided a broader understanding of the mechanisms underlying calcium-induced body weight/fat loss and glycemic control.

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Resveratrol induces brown-like adipocyte formation in white fat through activation of AMP-activated protein kinase (AMPK) α1

Cited by 244 publications

References 60 publications

AMPKα1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development

AMPKα1 deficiency suppresses brown adipogenesis in favor of fibrogenesis during brown adipose tissue development

Resveratrol Ameliorates Arterial Stiffness Assessed by Cardio-Ankle Vascular Index in Patients With Type 2 Diabetes Mellitus

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD)

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