Resveratrol Suppresses T0901317-Induced Hepatic Fat Accumulation in Mice

Gao, Mingming; Liu, Dexi

doi:10.1208/s12248-013-9473-7

Cited by 28 publications

(17 citation statements)

References 36 publications

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“…The procedure for quantitative determination of liver triglyceride has been previously described [20]. Liver samples (200-400 mg) were homogenized in a mixture of chloroform and methanol (2:1, volume ratio), and thereafter incubated overnight at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice fed a high-fat diet

Gao

Cui

et al. 2014

Journal of Controlled Release

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FGF21 is a secreted protein that plays critical roles in regulating glucose and lipid metabolism. In this study, we evaluated the effects of FGF21 gene transfer on C57BL/6 mice fed a high fat diet (HFD). We demonstrate that transfer of the FGF21 gene using a hydrodynamics-based procedure increased mRNA levels of FGF21 exclusively in the liver, consequently generating a sustained high level of FGF21 protein in blood that peaked at 500 ng/ml one day after injection, leading to a variety of beneficial effects including blockade of HFD-induced obesity, alleviation of fatty liver and improvement in glucose homeostasis. These effects were associated with altered expression of Ucp1, Dio2, Pgc1α, Pparγ2, Mgat1, F4/80, Mcp1 and Tnfα, which are involved in thermogenesis, lipogensis and chronic inflammation in the liver and adipose tissues. Transfer of the FGF21 gene in HFD-induced obese mice greatly increased expression of thermogenic genes in adipose tissue, resulting in similar improvements in systemic metabolism including reduction of adiposity, alleviation of fatty liver and attenuation of insulin resistance. Mechanistic studies on the effects of FGF21 gene transfer in lean mice revealed that mice transferred with FGF21 gene displayed suppressed lipogenesis in the liver and enhanced thermogenesis in brown adipose tissue which was coincident with a significant improvement in glucose tolerance. Collectively, our results suggest transfer of the FGF21 gene could be considered a promising approach for treating obesity and its complications.

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Section: Methodsmentioning

confidence: 99%

Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice fed a high-fat diet

Gao

Cui

et al. 2014

Journal of Controlled Release

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“…490 Baur et al [19] investigated resveratrol supplementation at a dose terol accumulation [35,[69][70][71][72][73][74], hepatic triglycerides [35,47,66,69,70,72,527 75-79] and liver weight [19,48,70,73,76,77]. Also, several other im-528 provements in liver fat content and anatomy were reported in rodents 529 after resveratrol supplementation [19,[48][49][50]67,[69][70][71][72]74,[76][77][78][79][80][81][82]. For To date, only four clinical trials have been performed investigating 536 effects of resveratrol on liver fat accumulation.…”

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confidence: 99%

Resveratrol and obesity: Can resveratrol relieve metabolic disturbances?

Ligt

Timmers

Schrauwen

2015

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

116

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There is an increasing need for novel preventive and therapeutic strategies to combat obesity and related metabolic disorders. In this respect, the natural polyphenol resveratrol has attracted significant interest. Animal studies indicate that resveratrol mimics the effects of calorie restriction via activation of sirtuin 1 (SIRT1). SIRT1 is an important player in the regulation of cellular energy homeostasis and mitochondrial biogenesis. Rodent studies have shown beneficial effects of resveratrol supplementation on mitochondrial function, glucose metabolism, body composition and liver fat accumulation. However, confirmation of these beneficial effects in humans by placebo-controlled clinical trials remains relatively limited. This review will give an overview of pre-clinical and clinical studies examining the effects of resveratrol on obesity-induced negative health outcomes. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.

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“…32 The agents inhibiting LXR-α and LXR-α-dependent lipogenesis do not enhance RCT. 33,34 A few studies have reported that activation of LXR can regulate RCT or atherosclerosis in an ABCA1-or macrophageindependent manner. T0901317 increases RCT to a similar degree in wild-type mice injected with radiolabeled wild-type macrophages or LXR-deleted macrophages, whereas it had little effect on LXR-deficient mice injected with wild-type macrophages.…”

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confidence: 99%

Inhibition of ERK1/2 and Activation of LXR Synergistically Reduce Atherosclerotic Lesions in ApoE-Deficient Mice

Chen

Duan

Yang

et al. 2015

ATVB

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Objective-Activation of liver X receptor (LXR) inhibits atherosclerosis but induces hypertriglyceridemia. In vitro, it has been shown that mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor synergizes LXR ligand-induced macrophage ABCA1 expression and cholesterol efflux. In this study, we determined whether MEK1/2 (U0126) and LXR ligand (T0901317) can have a synergistic effect on the reduction of atherosclerosis while eliminating LXR ligandinduced fatty livers and hypertriglyceridemia. We also set out to identify the cellular mechanisms of the actions. Approach and Results-Wild-type mice were used to determine the effect of U0126 on a high-fat diet or high-fat diet plus T0901317-induced transient dyslipidemia and liver injury. ApoE deficient (apoE −/− ) mice or mice with advanced lesions were used to determine the effect of the combination of T0901317 and U0126 on atherosclerosis and hypertriglyceridemia. We found that U0126 protected animals against T0901317-induced transient or long-term hepatic lipid accumulation, liver injury, and hypertriglyceridemia. Meanwhile, the combination of T0901317 and U0126 inhibited the development of atherosclerosis in a synergistic manner and reduced advanced lesions. Mechanistically, in addition to synergistic induction of macrophage ABCA1 expression, the combination of U0126 and T0901317 maintained arterial wall integrity, inhibited macrophage accumulation in aortas and formation of macrophages/foam cells, and activated reverse cholesterol transport. The inhibition of T0901317-induced lipid accumulation by the combined U0126 might be attributed to inactivation of lipogenesis and activation of lipolysis/fatty acid oxidation pathways. Conclusions-Our study suggests that the combination of mitogen-activated protein kinase kinase 1/2 inhibitor and LXR ligand can function as a novel therapy to synergistically reduce atherosclerosis while eliminating LXR-induced deleterious effects. (Arterioscler Thromb Vasc Biol. 2015;35:948-959.

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Resveratrol Suppresses T0901317-Induced Hepatic Fat Accumulation in Mice

Cited by 28 publications

References 36 publications

Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice fed a high-fat diet

Hydrodynamic delivery of FGF21 gene alleviates obesity and fatty liver in mice fed a high-fat diet

Resveratrol and obesity: Can resveratrol relieve metabolic disturbances?

Inhibition of ERK1/2 and Activation of LXR Synergistically Reduce Atherosclerotic Lesions in ApoE-Deficient Mice

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