Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice

N. Tsuboyama-Kasaoka, M. Takahashi, K. Tanemura, H. J. Kim, T. Tange, H. Okuyama, M. Kasai, S. Ikemoto, O. Ezaki

Research output: Contribution to journalArticlepeer-review

472 Citations (Scopus)

Abstract

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic derivatives of linoleic acid found in beef and dairy products. CLA has been reported to reduce body fat. To examine the mechanism(s) of CLA reduction of fat mass, female C57BL/6J mice were fed standard semipurified diets (10% fat of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and DNA fragmentation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-α and uncoupling protein (UCP)-2 mRNA levels increased 12-and 6-fold, respectively, in isolated adipocytes from CLA-fed mice compared with control mice. Because it is known that TNF-α induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked increase of TNF-α mRNA with an increase of UCP2 in adipocytes caused CLA-induced apoptosis. However, with a decrease of fat mass, CLA supplementation resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatomegaly, and marked insulin resistance. CLA supplementation decreased blood leptin levels, but continuous leptin infusion reversed hyperinsulinemia, indicating that leptin depletion contributes to the development of insulin resistance. These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results in lipodystrophy, but hyperinsulinemia by CLA can be normalized by leptin administration.

Original languageEnglish
Pages (from-to)1534-1542
Number of pages9
JournalDiabetes
Volume49
Issue number9
DOIs
Publication statusPublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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