Diraison Frédérique, Dusserre Eric, Vidal Hubert, Sothier Monique, Beylot Michel
Institut National de la Santé et de la Recherche Médicale Unité 499, Faculté RTH Laennec, 69008 Lyon, France.
Am J Physiol Endocrinol Metab. 2002 Jan;282(1):E46-51. doi: 10.1152/ajpendo.2002.282.1.E46.
To determine whether increased lipogenesis contributes to human obesity, we measured (postabsorptive state), in lean and obese subjects, lipid synthesis (deuterated water method) and the mRNA concentration (RT-competitive PCR) in subcutaneous adipose tissue of fatty acid synthase (FAS) and sterol regulatory element-binding protein (SREBP)-1c. Before energy restriction, obese subjects had an increased contribution of hepatic lipogenesis to the circulating triglyceride pool (14.5 +/- 1.3 vs. 7.5 +/- 1.9%, P < 0.01) without enhancement of cholesterol synthesis. This increased hepatic lipogenesis represented an excess of 2-5 g/day of triglycerides, which would represent 0.7-1.8 kg on a yearly basis. The lipogenic capacity of adipose tissue appeared, on the contrary, decreased with lower FAS mRNA levels (P < 0.01) and a trend for decreased SREBP-1c mRNA (P = 0.06). Energy restriction in obese patients decreased plasma insulin (P < 0.05) and leptin (P < 0.05) and normalized hepatic lipogenesis. FAS mRNA levels were unchanged, whereas SREBP-1c increased. In conclusion, subjects with established obesity have an increased hepatic lipogenesis that could contribute to their excessive fat mass but no evidence for an increased lipogenic capacity of adipose tissue.
为了确定脂肪生成增加是否会导致人类肥胖，我们在空腹状态下，对瘦人和肥胖受试者的脂肪酸合酶（FAS）和固醇调节元件结合蛋白（SREBP）-1c的脂质合成（氘水法）以及皮下脂肪组织中的mRNA浓度（RT竞争PCR）进行了测量。在能量限制之前，肥胖受试者肝脏脂肪生成对循环甘油三酯池的贡献增加（14.5±1.3%对7.5±1.9%，P<0.01），而胆固醇合成没有增强。这种肝脏脂肪生成增加相当于每天甘油三酯过量2-5克，按年计算相当于0.7-1.8千克。相反，脂肪组织的脂肪生成能力似乎随着FAS mRNA水平降低（P<0.01）以及SREBP-1c mRNA有降低趋势（P=0.06）而下降。肥胖患者的能量限制降低了血浆胰岛素（P<0.05）和瘦素（P<0.05），并使肝脏脂肪生成正常化。FAS mRNA水平未改变，而SREBP-1c增加。总之，已确诊肥胖的受试者肝脏脂肪生成增加，这可能导致其脂肪量过多，但没有证据表明脂肪组织的脂肪生成能力增加。
