Aging per se increases the susceptibility to free fatty acid-induced insulin resistance

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

doi:10.1093/gerona/glq078

Aging per se increases the susceptibility to free fatty acid-induced insulin resistance

Francine H. Einstein, Derek M. Huffman, Sigal Fishman, Elina Jerschow, Hye J. Heo, Gil Atzmon, Clyde Schechter, Nir Barzilai, Radhika H. Muzumdar

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

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.

Original language	English (US)
Pages (from-to)	800-808
Number of pages	9
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	65 A
Issue number	8
DOIs	https://doi.org/10.1093/gerona/glq078
State	Published - Aug 2010

Keywords

Adipokines
Aging
Calorie restriction
Insulin resistance
Lipids

ASJC Scopus subject areas

General Medicine

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10.1093/gerona/glq078

Cite this

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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.",

keywords = "Adipokines, Aging, Calorie restriction, Insulin resistance, Lipids",

author = "Einstein, {Francine H.} and Huffman, {Derek M.} and Sigal Fishman and Elina Jerschow and Heo, {Hye J.} and Gil Atzmon and Clyde Schechter and Nir Barzilai and Muzumdar, {Radhika H.}",

note = "Funding Information: This work was supported by grants from the National Institutes of Health (AG21654 and AG18381 to N.B. and K08 AG027462 to R.H.M.), the Core laboratories of the Albert Einstein Diabetes Research and Training Center (DK20541), and the American Association of Obstetricians and Gynecologists Foundation with the Society of Maternal-Fetal Medicine (to F.H.E). D.M.H. is supported by a T32 Training Grant (T32AG23475).",

year = "2010",

month = aug,

doi = "10.1093/gerona/glq078",

language = "English (US)",

volume = "65 A",

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AU - Einstein, Francine H.

AU - Huffman, Derek M.

AU - Fishman, Sigal

AU - Jerschow, Elina

AU - Heo, Hye J.

AU - Atzmon, Gil

AU - Schechter, Clyde

AU - Barzilai, Nir

AU - Muzumdar, Radhika H.

N1 - Funding Information: This work was supported by grants from the National Institutes of Health (AG21654 and AG18381 to N.B. and K08 AG027462 to R.H.M.), the Core laboratories of the Albert Einstein Diabetes Research and Training Center (DK20541), and the American Association of Obstetricians and Gynecologists Foundation with the Society of Maternal-Fetal Medicine (to F.H.E). D.M.H. is supported by a T32 Training Grant (T32AG23475).

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Adipokines

KW - Aging

KW - Calorie restriction

KW - Insulin resistance

KW - Lipids

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ER -

Aging per se increases the susceptibility to free fatty acid-induced insulin resistance

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