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

Conjugated linoleic acid (CLA) is a naturally occurring group of dienoic de rivatives of linoleic acid found in beef and dairy products. CLA has been r eported 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% f at of total energy) with or without CLA (1% wt/wt). Terminal deoxynucleotid yl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) and DNA fragm entation analysis revealed that fat-mass decrease by CLA was mainly due to apoptosis. Tumor necrosis factor (TNF)-alpha 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- alpha induces apoptosis of adipocytes and upregulates UCP2 mRNA, a marked i ncrease of TNF-alpha mRNA with an increase of UCP2 in adipocytes caused CLA -induced apoptosis. However, with a decrease of fat mass, CLA supplementati on resulted in a state resembling lipoatrophic diabetes: ablation of brown adipose tissue, a marked reduction of white adipose tissue, marked hepatome galy, and marked insulin resistance. CLA supplementation decreased blood le ptin levels, but continuous leptin infusion reversed hyperinsulinemia, indi cating that leptin depletion contributes to the development of insulin resi stance, These results demonstrate that intake of CLA reduces adipose tissue by apoptosis and results: in Lipodystrophy, but hyperinsulinemia by CLA ca n be normalized by leptin administration.