Resveratrol exerts anti-obesity effects in high-fat diet obese mice and displays differential dosage effects on cytotoxicity, differentiation, and lipolysis in 3T3-L1 cells
Resveratrol exerts anti-obesity effects in high-fat diet obese mice and displays differential dosage effects on cytotoxicity, differentiation, and lipolysis in 3T3-L1 cells
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DOI：
10.1507/endocrj.ej15-0545
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发表时间：
2016-02-20
影响因子：
2
通讯作者：
Hung, Li-Man
中科院分区：
文献类型：
--
作者：
Chang, Chih-Chun;Lin, Keng-Yang;Hung, Li-Man
白藜芦醇在肥胖小鼠和脂肪细胞上的广泛浓度的研究是必要的，以了解其多样和矛盾的影响范围。在这项研究中，我们研究了白藜芦醇对高脂饮食（HFD）诱导的肥胖小鼠的抗肥胖作用，剂量范围为1至30 mg/kg，治疗10周。我们还评估了白藜芦醇在0.03至100 μ M浓度范围内对3 T3-L1细胞的细胞毒性、增殖、成脂分化和脂解的影响。在HFD肥胖小鼠中，白藜芦醇治疗10周而不减少热量摄入以剂量依赖性方式显著减弱HFD诱导的体重增加。白藜芦醇治疗还防止HFD诱导的脂肪组织和肝脏中的脂质沉积。在培养的3 T3-L1前脂肪细胞中，高剂量（10至100 μ M）白藜芦醇处理产生细胞毒性的前脂肪细胞和成熟的脂肪细胞。相反，低浓度白藜芦醇处理（1至10 μ M）显着抑制3 T3-L1细胞分化为成熟脂肪细胞的能力。低剂量白藜芦醇治疗也下调过氧化物酶体增殖物激活受体γ（过氧化物酶体增殖物激活受体γ）和周脂蛋白在分化的脂肪细胞中的表达。此外，低浓度白藜芦醇处理成熟脂肪细胞可抑制肿瘤坏死因子α（TNF α）诱导的脂解作用。在10-100 μ M的浓度下，白藜芦醇产生细胞毒性。相反，在1-10 μ M的浓度下，白藜芦醇抑制前脂肪细胞的成脂分化，并抑制成熟脂肪细胞的脂解。我们的研究结果表明，白藜芦醇具有抗肥胖作用的诱导细胞毒性在高剂量和低浓度的影响前脂肪细胞分化和成熟脂肪细胞的脂解。
Studies on resveratrol in a wide range of concentrations on obese mice and adipose cells are necessary to comprehend its range of diverse and contradictory effects. In this study, we examined the anti-obesity effects of resveratrol on high-fat diet (HFD)-induced obese mice at dosages ranging from 1 to 30 mg/kg treatment for 10 wk. We also evaluated the effects of resveratrol on cytotoxicity, proliferation, adipogenic differentiation, and lipolysis of 3T3-L1 cells at concentrations ranging from 0.03 to 100 mu M. In HFD obese mice, resveratrol treatment for 10 wk without decreased calories intake significantly attenuated HFD-induced weight gain in a dose-dependent manner. Resveratrol treatment also protected against HFD-induced lipid deposition in adipose tissues and liver. In cultured 3T3-L1 preadipocytes, high dosage (10 to 100 mu M) resveratrol treatment produced cytotoxicity in both preadipocytes and mature adipocytes. In contrast, low concentration resveratrol treatment (1 to 10 mu M) significantly inhibited the capacity of 3T3-L1 cells differentiated into mature adipocytes. Low dose resveratrol treatment also downregulated peroxisome proliferator-activated receptor gamma (PPAR gamma) and perilipin protein expressions in differentiated adipocytes. Additionally, tumor necrosis factor alpha (TNF alpha)-induced lipolysis was inhibited by low concentration resveratrol treatment in mature adipocytes. At concentrations of 10-100 mu M, resveratrol exerted cytotoxicity. In contrast, at concentrations of 1-10 mu M resveratrol inhibited adipogenic differentiation in preadipocytes and suppressed lipolysis in mature adipocytes. Our results suggest that resveratrol possessed anti-obesity effects by induction of cytotoxicity at high dosage and that it influences preadipocyte differentiation and mature adipocyte lipolysis at low concentration.