Aging per se Increases the Susceptibility to Free Fatty Acid-Induced Insulin Resistance
Aging per se Increases the Susceptibility to Free Fatty Acid-Induced Insulin Resistance
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DOI：
10.1093/gerona/glq078
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发表时间：
2010-08-01
影响因子：
5.1
通讯作者：
Muzumdar, Radhika H.
中科院分区：
文献类型：
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作者：
Einstein, Francine H.;Huffman, Derek M.;Muzumdar, Radhika H.
全身性游离脂肪酸(FFA)升高导致胰岛素抵抗。为了确定FFA的急性升高对胰岛素随年龄增长的影响，我们在高胰岛素-正常血糖钳夹期间向三组大鼠注入生理盐水或脂肪(IL)：青年自由采食组(YAL)、老年自由采食组(OAL)和老年终身热量限制组(OCR)。包括OCR组是为了区分衰老本身和与年龄相关的体脂分布变化。IL在YAL和OCR均可引起显著的胰岛素抵抗，但OCR的胰岛素抵抗发生速度约为YAL的两到三倍。注射IL后，OAL动物皮下脂肪中纤溶酶原激活抑制物-1(PAI-1)的表达增加。在内脏脂肪中，IL治疗后，OAL和OCR大鼠的PAI-1和IL-6的表达显著增加，而YAL则没有。因此，随着年龄的增长，衰老本身会增加对过量营养的炎症反应，并容易受到FFA诱导的胰岛素抵抗的影响。
Elevations in systemic free fatty acids (FFA) contribute to insulin resistance. To determine the effects of an acute elevation in FFA on insulin action with aging, we infused saline or intralipid (IL) during a hyperinsulinemic-euglycemic clamp in three groups of rats: young ad libitum-fed (YAL), old ad libitum-fed (OAL), and old on lifelong calorie restriction (OCR). The OCR group was included to distinguish between aging per se and age-related changes in body fat distribution. IL induced marked insulin resistance in both YAL and OCR, but the onset of insulin resistance was approximately two to three times more rapid in OCR as compared with YAL. In response to IL infusion, plasminogen-activating inhibitor-1 (PAI-1) expression was increased in subcutaneous fat from OAL animals. In visceral fat, a marked increase in PAI-1 and interleukin-6 expression was observed in OAL and OCR rats, but not YAL, in response to IL treatment. Thus, aging per se increases the inflammatory response to excess nutrients and vulnerability to FFA-induced insulin resistance with aging.