The role of leptin resistance in the lipid abnormalities of aging

Z. W. Wang, Wentong Pan, Y. Lee, T. Kakuma, Y. T. Zhou, R. H. Unger

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Leptin resistance has been implicated in the pathogenesis of obesity-related complications involving abnormalities of lipid metabolism that resemble those of old age. To determine whether development of leptin resistance in advancing age might account for such abnormalities, we compared the effects of hyperleptinemia (>40 ng/ml) induced in 2-month-old and 18-month-old lean wild-type (+/+) Zucker diabetic fatty rats by adenovirus gene transfer. The decline in food intake, body weight, and body fat in old rats was only 25%, 50%, and 16%, respectively, of the young rats. Whereas in young rats plasma free fatty acids fell 44% and triacylglycerol (TG) 94%, neither changed in the rats. In hyperleptinemic young rats, adipocyte expression of preadipocyte factor 1 increased dramatically and leptin mRNA virtually disappeared; there was increased expression of acyl CoA oxidase, carnitine palmitoyl transferase 1, and their transcription factor peroxisome proliferator-activated receptor α, accounting for the reduction in body fat. These hyperleptinemia-induced changes were profoundly reduced in the old rats. On a high-fat diet, old rats consumed 28% more calories than the young and gained 1.5× as much fat, despite greater endogenous hyperleptinemia. Expression of a candidate leptin resistance factor, suppressor of cytokine signaling 3 (SOCS-3), was compared in the hypothalamus and white adipocytes of young and old rats before and after induction of hyperleptinemia; hypothalamic SOCS-3 mRNA was ∼3× higher in old rats before, whereas it was 3× higher in WAT after, hyperleptinemia. We conclude that the anorexic and antilipopenic actions of leptin decline with age, possibly through increased SOCS-3 expression, and that this could account for the associated abnormalities in lipid metabolism of the elderly.

Original languageEnglish (US)
Pages (from-to)108-114
Number of pages7
JournalFASEB Journal
Volume15
Issue number1
DOIs
StatePublished - Jan 31 2001
Externally publishedYes

Fingerprint

Leptin
leptin
Rats
Aging of materials
Lipids
rats
lipids
Fats
cytokines
Cytokines
adipocytes
Lipid Metabolism
lipid metabolism
body fat
Adipose Tissue
White Adipocytes
Acyl-CoA Oxidase
Gene transfer
carnitine palmitoyltransferase
Messenger RNA

Keywords

  • Fatty acids
  • High-fat diet
  • Hyperleptinemia
  • Hypothalamus
  • Lipotoxicity
  • SOCS-3

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Wang, Z. W., Pan, W., Lee, Y., Kakuma, T., Zhou, Y. T., & Unger, R. H. (2001). The role of leptin resistance in the lipid abnormalities of aging. FASEB Journal, 15(1), 108-114. https://doi.org/10.1096/fj.00-0310com

The role of leptin resistance in the lipid abnormalities of aging. / Wang, Z. W.; Pan, Wentong; Lee, Y.; Kakuma, T.; Zhou, Y. T.; Unger, R. H.

In: FASEB Journal, Vol. 15, No. 1, 31.01.2001, p. 108-114.

Research output: Contribution to journalArticle

Wang, ZW, Pan, W, Lee, Y, Kakuma, T, Zhou, YT & Unger, RH 2001, 'The role of leptin resistance in the lipid abnormalities of aging', FASEB Journal, vol. 15, no. 1, pp. 108-114. https://doi.org/10.1096/fj.00-0310com
Wang, Z. W. ; Pan, Wentong ; Lee, Y. ; Kakuma, T. ; Zhou, Y. T. ; Unger, R. H. / The role of leptin resistance in the lipid abnormalities of aging. In: FASEB Journal. 2001 ; Vol. 15, No. 1. pp. 108-114.
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