title: Aging per se increases the susceptibility to free fatty acid-induced insulin resistance.
abstract: 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.
authors.affiliation: Department of Obstetrics & Gynecology and Women's Health at Montefiore Medical Center, Bronx, New York, USA.
authors.forename: Francine H
authors.initials: FH
authors.lastname: Einstein
authors.forename: Derek M
authors.initials: DM
authors.lastname: Huffman
authors.forename: Sigal
authors.initials: S
authors.lastname: Fishman
authors.forename: Elina
authors.initials: E
authors.lastname: Jerschow
authors.forename: Hye J
authors.initials: HJ
authors.lastname: Heo
authors.forename: Gil
authors.initials: G
authors.lastname: Atzmon
authors.forename: Clyde
authors.initials: C
authors.lastname: Schechter
authors.forename: Nir
authors.initials: N
authors.lastname: Barzilai
authors.forename: Radhika H
authors.initials: RH
authors.lastname: Muzumdar
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D031204:Caloric Restriction; D005217:Fat Emulsions, Intravenous / Q000633:toxicity; D005230:Fatty Acids, Nonesterified / Q000633:toxicity*; D005947:Glucose / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000235:genetics; D008264:Macrophages / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D017395:Plasminogen Activator Inhibitor 1; D005947:Glucose