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J Gerontol A Biol Sci Med Sci. 2012 Dec;67(12):1321-8. doi: 10.1093/gerona/gls200. Epub 2012 Oct 22.

Fatty acid-induced production of plasminogen activator inhibitor-1 by adipose macrophages is greater in middle-aged versus younger adult participants.

Author information

1
Diabetes Research and Training Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Belfer 709, Bronx, NY 10461, USA.

Abstract

BACKGROUND:

Human aging is associated with heightened risk of diabetes and cardiovascular disease. Increased fat mass may contribute to age-related diseases by harboring inflammatory macrophages that produce metabolically important proteins such as plasminogen activator inhibitor-1 (PAI-1). Elevated PAI-1 concentrations have been implicated in the pathogenesis of such aging-related conditions as insulin resistance, obesity, and atherosclerosis. We have previously reported that increased plasma free fatty acid (FFA) concentrations augment both circulating PAI-1 concentrations and PAI-1 production by adipose tissue macrophages (ATMs).

METHODS:

Because increasing age is associated with increased infiltration and reactivity of adipose macrophages, we performed euglycemic-hyperinsulinemic clamp studies and adipose tissue biopsies with and without elevated FFA concentrations in 31 nondiabetic participants stratified by age, to determine whether middle-aged individuals manifest heightened insulin resistance and PAI-1 production by ATMs in response to elevated nutrient signals relative to their young adult peers.

RESULTS:

We observed that elevating FFA concentrations under euglycemic-hyperinsulinemic clamp conditions induced the same degree of insulin resistance in both middle-aged and younger body mass index-matched adults, whereas systemic PAI-1 concentrations were significantly increased in the middle-aged group. Likewise, elevated FFA and insulin concentrations induced larger increases in PAI-1 gene expression in the whole fat and ATMs of middle-aged compared with younger adult participants.

CONCLUSIONS:

These studies reveal a heightened adipose inflammatory response to increased FFA and insulin availability in middle-aged individuals relative to younger adults, suggesting that increased susceptibility to the effects of fatty acid excess may contribute to the pathogenesis of age-related diseases.

PMID:
23089338
PMCID:
PMC3670154
DOI:
10.1093/gerona/gls200
[Indexed for MEDLINE]
Free PMC Article
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