Laboratório de Endocrinologia Molecular, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, sl G0-16, Cidade Universitária, Rio de Janeiro, RJ, 21941-902, Brazil.
Laboratório de Fisiologia Endócrina, Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcântara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
Eur J Nutr. 2016 Mar;55(2):601-610. doi: 10.1007/s00394-015-0880-7. Epub 2015 Mar 24.
Perinatal high-fat diet is associated with obesity and metabolic diseases in adult offspring. Resveratrol has been shown to exert antioxidant and anti-obesity actions. However, the effects of resveratrol on leptinemia and leptin signaling are still unknown as well as whether resveratrol treatment can improve metabolic outcomes programmed by maternal high-fat diet. We hypothesize that resveratrol treatment in male rats programmed by high-fat diet would decrease body weight and food intake, and leptinemia with changes in central leptin signaling.
Female Wistar rats were divided into two groups: control group (C), which received a standard diet containing 9 % of the calories as fat, and high-fat group (HF), which received a diet containing 28 % of the calories as fat. Dams were fed in C or HF diet during 8 weeks before mating and throughout gestation and lactation. C and HF male offspring received standard diet throughout life. From 150 until 180 days of age, offspring received resveratrol (30 mg/Kg body weight/day) or vehicle (carboxymethylcellulose).
HF offspring had increased body weight, hyperphagia and increased subcutaneous and visceral fat mass compared to controls, and resveratrol treatment decreased adiposity. HF offspring had increased leptinemia as well as increased SOCS3 in the arcuate nucleus of the hypothalamus, which suggest central leptin resistance. Resveratrol treatment rescued leptinemia and increased p-STAT3 content in the hypothalamus with no changes in SOCS3, suggesting improvement in leptin signaling.
Collectively, our data suggest that resveratrol could reverse hyperleptinemia and improve central leptin action in adult offspring from HF mothers attenuating obesity.
围产期高脂肪饮食会导致成年后代肥胖和代谢疾病。白藜芦醇已被证明具有抗氧化和抗肥胖作用。然而，白藜芦醇对瘦素血症和瘦素信号的影响尚不清楚，以及白藜芦醇治疗是否可以改善由高脂肪饮食引起的母代代谢结果。我们假设高脂肪饮食编程的雄性大鼠的白藜芦醇治疗会降低体重和食物摄入量，并降低瘦素血症，同时改变中枢瘦素信号。
雌性 Wistar 大鼠分为两组：对照组（C），给予含有 9%卡路里的标准饮食；高脂肪组（HF），给予含有 28%卡路里的高脂肪饮食。在交配前、妊娠和哺乳期，母鼠分别接受 C 或 HF 饮食。C 和 HF 雄性后代在整个生命过程中均给予标准饮食。从 150 天到 180 天，后代接受白藜芦醇（30mg/Kg 体重/天）或载体（羧甲基纤维素）治疗。
HF 后代的体重、多食症以及皮下和内脏脂肪量均高于对照组，而白藜芦醇治疗降低了肥胖度。HF 后代的瘦素血症增加，下丘脑弓状核中的 SOCS3 增加，提示中枢性瘦素抵抗。白藜芦醇治疗可恢复瘦素血症，并增加下丘脑 p-STAT3 含量，而 SOCS3 无变化，提示改善了瘦素信号。
总的来说，我们的数据表明，白藜芦醇可能逆转高脂肪饮食母代后代的高瘦素血症，并改善中枢性瘦素作用，从而减轻肥胖。
