Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene.
Dissociation between fatty liver and insulin resistance in humans carrying a variant of the patatin-like phospholipase 3 gene.
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携带 patatin 样磷脂酶 3 基因变体的人类脂肪肝与胰岛素抵抗之间的关联。
作者：
Kantartzis K;Peter A;Machicao F;Machann J;Wagner S;Königsrainer I;Königsrainer A;Schick F;Fritsche A;Häring HU;Stefan N
在全基因组关联扫描中，Patatin样磷脂酶3基因(PNPLA3)中的rs738409C>；G单核苷酸多态(SNP)与肝脏脂肪增加密切相关，但与从空腹估测的胰岛素抵抗无关。我们调查了SNP是否独立于内脏脂肪决定肝脏脂肪，以及它是否甚至可能在预防胰岛素抵抗方面发挥作用。用~1H磁共振波谱测定330例受试者的肝脏脂肪，用磁共振断层扫描测定总脂肪和内脏脂肪。在口服葡萄糖耐量试验和正常血糖-高胰岛素钳夹试验(n=222)中评估胰岛素敏感性。检测16例受试者肝活检组织中PNPLA3、肿瘤坏死因子-α基因和甘油三酯的含量。肝脏脂肪与胰岛素敏感性显著相关(P<；0.0001)，与年龄、性别、总脂肪和内脏脂肪无关。携带G等位基因的Rs738409与C等位基因纯合子相比，肝脏脂肪含量更高(P<；0.0001)，患脂肪肝的优势比为2.38(95%可信区间1.37~4.20)。有趣的是，胰岛素敏感性(口服葡萄糖耐量试验：P=0.99；钳夹试验：P=0.32)、血清C反应蛋白水平、血脂或肝酶(均为P>；0.14)在不同的基因型之间没有差异。对肝脏脂肪的额外调整实际上表明，在更肥胖的G等位基因携带者中，胰岛素敏感性增加(P=0.01)。肝活检组织中甘油三酯含量与促炎基因肿瘤坏死因子-α在C等位基因纯合子中的表达呈正相关(n=6，P=0.027)，而在G等位基因携带者中无相关性(n=10，P=0.149)。PNPLA3可能是了解脂肪肝伴和不伴代谢后果的机制的重要关键。
In a genome-wide association scan, the rs738409 C>G single nucleotide polymorphism (SNP) in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with increased liver fat but not with insulin resistance estimated from fasting values. We investigated whether the SNP determines liver fat independently of visceral adiposity and whether it may even play a role in protecting from insulin resistance. Liver fat was measured by 1H magnetic resonance spectroscopy and total and visceral fat by magnetic resonance tomography in 330 subjects. Insulin sensitivity was estimated during an oral glucose tolerance test and the euglycemic-hyperinsulinemic clamp (n = 222). PNPLA3 and tumor necrosis factor-α mRNA and triglyceride content were measured in liver biopsies from 16 subjects. Liver fat correlated strongly with insulin sensitivity (P < 0.0001) independently of age, sex, total fat, and visceral fat. G allele carriers of the SNP rs738409 had higher liver fat (P < 0.0001) and an odds ratio of 2.38 (95% CI 1.37–4.20) for having fatty liver compared to C allele homozygotes. Interestingly, insulin sensitivity (oral glucose tolerance test: P = 0.99; clamp: P = 0.32), serum C-reactive protein levels, lipids, or liver enzymes (all P > 0.14) were not different among the genotypes. Additional adjustment for liver fat actually revealed increased insulin sensitivity in more obese carriers of the G allele (P = 0.01). In liver biopsies triglyceride content correlated positively with expression of the proinflammatory gene tumor necrosis factor-α in C allele homozygotes (n = 6, P = 0.027) but not in G allele carriers (n = 10, P = 0.149). PNPLA3 may be an important key to understand the mechanisms discriminating fatty liver with and without metabolic consequences.
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影响因子：
7.7
作者：
Johansson, LE;Hoffstedt, J;Ridderstråle, M
通讯作者：
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