Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans
Genetic variation in PNPLA3 (adiponutrin) confers sensitivity to weight loss-induced decrease in liver fat in humans
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DOI：
10.3945/ajcn.111.012369
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发表时间：
2011-07-01
影响因子：
7.1
通讯作者：
Yki-Jarvinen, Hannele
中科院分区：
文献类型：
--
作者：
Sevastianova, Ksenia;Kotronen, Anna;Yki-Jarvinen, Hannele
背景：含PNPLA3(脂联素)的PNPLA3基因rs738409C-gt；G单核苷酸多态导致错义突变(I148M)，该突变与肝脏脂肪增加有关，但与胰岛素抵抗无关。目的：探讨rs738409 PNPLA3 G等位基因是否影响减肥或改变胰岛素敏感性的能力。设计：纳入8例rs738409 PNPLA3 G纯合子(PNPLA3-148 mm)和10例rs738409 PNPLA3 C纯合子(PNPLA3-148II)受试者。为了能够比较肝脏脂肪的变化，两组在基线年龄、性别、体重指数和肝脏脂肪方面进行了匹配。受试者接受低热量低碳水化合物饮食6d，测定饮食前后肝脏脂肪含量(质子磁共振波谱)、全身胰岛素对糖代谢的敏感性(正糖钳夹技术)和脂肪分解([H-2(5)]甘油输注)。结果：在基线时，PNPLA3-148 mM组的空腹血清胰岛素和C-肽浓度显著低于PNPLA3-148II组，按照研究设计的预测。两组间体重下降无显著差异(PNPLA3-148 mm：-3.1+/-0.5 kg；PNPLA3-148II：-3.1+/-0.4 kg)。PNPLA3-148 mM组和PNPLA3-148II组分别降低了45%和18%(P<；0.001)。结论：rs738409 PNPLA3 G或C等位基因纯合子受试者的减肥效果显著。这项试验在www.Hus.fi上注册为233775。AM J Clin Nutr 2011；94：104-11
Background: The rs738409 C -> G single nucleotide polymorphism in the patatin-like phospholipase domain-containing 3 (PNPLA3; adiponutrin) leads to a missense mutation (I148M), which is associated with increased liver fat but not insulin resistance. The I148M mutation impedes triglyceride hydrolysis in vitro, and its carriers have an increased risk of developing severe liver disease.Objective: We explored whether the rs738409 PNPLA3 G allele influences the ability of weight loss to decrease liver fat or change insulin sensitivity.Design: We recruited 8 subjects who were homozygous for the rs738409 PNPLA3 G allele (PNPLA3-148MM) and 10 who were homozygous for the rs738409 PNPLA3 C allele (PNPLA3-148II). To allow comparison of changes in liver fat, the groups were matched with respect to baseline age, sex, body mass index, and liver fat. The subjects were placed on a hypocaloric low-carbohydrate diet for 6 d. Liver fat content (proton magnetic resonance spectroscopy), whole-body insulin sensitivity of glucose metabolism (euglycemic clamp technique), and lipolysis ([H-2(5)] glycerol infusion) were measured before and after the diet.Results: At baseline, fasting serum insulin and C-peptide concentrations were significantly lower in the PNPLA3-148MM group than in the PNPLA3-148II group, as predicted by study design. Weight loss was not significantly different between groups (PNPLA3-148MM: -3.1 +/- 0.5 kg; PNPLA3-148II: -3.1 +/- 0.4 kg). Liver fat decreased by 45% in the PNPLA3-148MM group (P < 0.001) and by 18% in the PNPLA3-148II group (P < 0.01).Conclusion: Weight loss is effective in decreasing liver fat in subjects who are homozygous for the rs738409 PNPLA3 G or C allele. This trial was registered at www.hus.fi as 233775. Am J Clin Nutr 2011;94:104-11.