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 B. Schechter, Nir Barzilai, Radhika H. Muzumdar

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)800-808
Number of pages9
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume65 A
Issue number8
DOIs
StatePublished - Aug 2010

Fingerprint

Nonesterified Fatty Acids
Insulin Resistance
Plasminogen
Body Fat Distribution
Glucose Clamp Technique
Intra-Abdominal Fat
Subcutaneous Fat
Interleukin-6
Insulin
Food
phospholipid emulsion soybean oil

Keywords

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

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Aging per se increases the susceptibility to free fatty acid-induced insulin resistance. / Einstein, Francine H.; Huffman, Derek M.; Fishman, Sigal; Jerschow, Elina; Heo, Hye J.; Atzmon, Gil; Schechter, Clyde B.; Barzilai, Nir; Muzumdar, Radhika H.

In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 65 A, No. 8, 08.2010, p. 800-808.

Research output: Contribution to journalArticle

@article{5e102acee5854136802c19eb6b0fe77e,
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 Schechter, {Clyde B.} and Nir Barzilai and Muzumdar, {Radhika H.}",
year = "2010",
month = "8",
doi = "10.1093/gerona/glq078",
language = "English (US)",
volume = "65 A",
pages = "800--808",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "8",

}

TY - JOUR

T1 - Aging per se increases the susceptibility to free fatty acid-induced insulin resistance

AU - Einstein, Francine H.

AU - Huffman, Derek M.

AU - Fishman, Sigal

AU - Jerschow, Elina

AU - Heo, Hye J.

AU - Atzmon, Gil

AU - Schechter, Clyde B.

AU - Barzilai, Nir

AU - Muzumdar, Radhika H.

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

UR - http://www.scopus.com/inward/record.url?scp=77954844474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954844474&partnerID=8YFLogxK

U2 - 10.1093/gerona/glq078

DO - 10.1093/gerona/glq078

M3 - Article

VL - 65 A

SP - 800

EP - 808

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

SN - 1079-5006

IS - 8

ER -