Cettour-Rose Philippe, Samec Sonia, Russell Aaron P, Summermatter Serge, Mainieri Davide, Carrillo-Theander Claudia, Montani Jean-Pierre, Seydoux Josiane, Rohner-Jeanrenaud Françoise, Dulloo Abdul G
Department of Internal Medicine, Faculty of Medicine, University of Geneva, Switzerland.
Diabetes. 2005 Mar;54(3):751-6. doi: 10.2337/diabetes.54.3.751.
Catch-up growth, a risk factor for later obesity, type 2 diabetes, and cardiovascular diseases, is characterized by hyperinsulinemia and an accelerated rate for recovering fat mass, i.e., catch-up fat. To identify potential mechanisms in the link between hyperinsulinemia and catch-up fat during catch-up growth, we studied the in vivo action of insulin on glucose utilization in skeletal muscle and adipose tissue in a previously described rat model of weight recovery exhibiting catch-up fat caused by suppressed thermogenesis per se. To do this, we used euglycemic-hyperinsulinemic clamps associated with the labeled 2-deoxy-glucose technique. After 1 week of isocaloric refeeding, when body fat, circulating free fatty acids, or intramyocellular lipids in refed animals had not yet exceeded those of controls, insulin-stimulated glucose utilization in refed animals was lower in skeletal muscles (by 20-43%) but higher in white adipose tissues (by two- to threefold). Furthermore, fatty acid synthase activity was higher in adipose tissues from refed animals than from fed controls. These results suggest that suppressed thermogenesis for the purpose of sparing glucose for catch-up fat, via the coordinated induction of skeletal muscle insulin resistance and adipose tissue insulin hyperresponsiveness, might be a central event in the link between catch-up growth, hyperinsulinemia and risks for later metabolic syndrome.
追赶生长是日后肥胖、2型糖尿病和心血管疾病的一个风险因素，其特征为高胰岛素血症以及脂肪量恢复速率加快，即追赶性肥胖。为了确定追赶生长期间高胰岛素血症与追赶性肥胖之间联系的潜在机制，我们在先前描述的一种体重恢复大鼠模型中研究了胰岛素对骨骼肌和脂肪组织中葡萄糖利用的体内作用，该模型因本身产热受抑制而出现追赶性肥胖。为此，我们使用了与标记的2-脱氧葡萄糖技术相关的正常血糖-高胰岛素钳夹技术。在等热量再喂养1周后，当再喂养动物的体脂、循环游离脂肪酸或肌细胞内脂质尚未超过对照组时，再喂养动物中胰岛素刺激的葡萄糖利用在骨骼肌中较低（降低20%-43%），但在白色脂肪组织中较高（高出两到三倍）。此外，再喂养动物脂肪组织中的脂肪酸合酶活性高于喂食对照动物。这些结果表明，为了节省葡萄糖用于追赶性肥胖而抑制产热，通过协同诱导骨骼肌胰岛素抵抗和脂肪组织胰岛素高反应性，可能是追赶生长、高胰岛素血症与日后代谢综合征风险之间联系的核心事件。
