Aging per se Increases the Susceptibility to Free Fatty Acid-Induced Insulin Resistance

作者：Einstein Francine H; Huffman Derek M; Fishman Sigal; Jerschow Elina; Heo Hye J; Atzmon Gil; Schechter Clyde; Barzilai Nir^*; Muzumdar Radhika H

来源：Journals of Gerontology Series A-Biological Sciences and Medical Sciences, 2010, 65(8): 800-808.

DOI：10.1093/gerona/glq078

• Aging
• Calorie restriction
• Lipids
• Insulin resistance
• Adipokines

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.

• 出版日期2010-8