Abstract
Visceral fat accretion is a hallmark of aging and is associated with aging-induced metabolic dysfunction. PPARγ agonist was reported to improve insulin sensitivity by redistributing fat from visceral fat to subcutaneous fat. The purpose of this study was to investigate the underlying mechanisms by which aging affects adipose tissue remodeling in a type 2 diabetic animal model and through which PPARγ activation modulates aging-related fat tissue distribution. At the ages of 21, 31 and 43 weeks, OLETF rats as an animal model of type 2 diabetes were evaluated for aging-related effects on adipose tissue metabolism in subcutaneous and visceral fat depots. During aging, the ratio of visceral fat weight to subcutaneous fat weight (V/S ratio) increased. Aging significantly increased the mRNA expression of genes involved in lipogenesis such as lipoprotein lipase, fatty acid binding protein aP2, lipin 1, and diacylglycerol acyltransferase 1, which were more prominent in visceral fat than subcutaneous fat. The mRNA expression of adipose triglyceride lipase, which is involved in basal lipolysis and fatty acid recycling, was also increased, more in visceral fat compared to subcutaneous fat during aging. The mRNA levels of the genes associated with lipid oxidation were increased, whereas the mRNA levels of genes associated with energy expenditure showed no significant change during aging. PPARγ agonist treatment in OLETF rats resulted in fat redistribution with a decreasing V/S ratio and improved glucose intolerance. The genes involved in lipogenesis decreased in visceral fat of the PPARγ agonist-treated rats. During aging, fat distribution was changed by stimulating lipid uptake and esterification in visceral fat rather than subcutaneous fat, and by altering the lipid oxidation.
Highlights
Fat tissue is at the nexus of mechanisms and pathways involved in longevity, genesis of agerelated disease, inflammation and metabolic dysfunction
Aging led to changes in fat distribution by increasing lipid uptake and esterification and altering energy expenditure in visceral fat compared to subcutaneous fat
The PPARγ agonist rosiglitazone may affect adipose tissue distribution to subcutaneous deposits by changing several pathways of adipose lipid metabolism. These results suggests that the deleterious effects of fat distribution with aging might be partially modulated by PPARγ agonists such as rosiglitazone
Summary
Fat tissue is at the nexus of mechanisms and pathways involved in longevity, genesis of agerelated disease, inflammation and metabolic dysfunction. Fat mass and fat tissue distribution change dramatically throughout life [1,2]. While the total amount of fat tissue tends to decline or remain stable, fat distribution changes dramatically. Fat is redistributed from subcutaneous to intra-abdominal visceral deposits and to ectopic sites, including muscle, liver and bone marrow [3,4,5]. These changes are associated with diabetes, hypertension, cancer, cognitive dysfunction and atherosclerosis [1,2]. Several studies suggest that insulin resistance and altered glucose homeostasis are more closely related to regional adipose tissue distribution than total fat mass [6,7]
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