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ENDOCRINE PHYSIOLOGY AND METABOLISM

Tissue-specific postprandial clearance is the major determinant of PPAR-induced triglyceride lowering in the rat

¹Laval Hospital Research Center and Department of Anatomy and Physiology, Faculty of Medicine, Laval University, Québec, Canada; ²Department of Metabolic Disorders, Merck Research Laboratories, Rahway, New Jersey; and ³Department of Medical Biosciences, Umeå University, Umeå, Sweden

Submitted 30 June 2008 ; accepted in final form 24 October 2008

Peroxisome proliferator-activated receptor- (PPAR) agonism potently reduces circulating triglycerides (TG) in rodents and more modestly so in humans. This study aimed to quantify in vivo the relative contribution of hepatic VLDL-TG secretion and tissue-specific TG clearance to such action. Rats were fed an obesogenic diet, treated with the PPAR full agonist COOH (30 mg·kg^–1·day^–1) for 3 wk, and studied in both the fasted and refed (fat-free) states. Hepatic VLDL-TG secretion rate was not affected by chronic COOH in the fasted state and was only modestly decreased (–30%) in refed rats. In contrast, postprandial VLDL-TG clearance was increased 2.6-fold by COOH, which concomitantly stimulated adipose tissue TG-derived lipid uptake and one of its major determinants, lipoprotein lipase (LPL) activity, in a highly depot-specific manner. TG-derived lipid uptake and LPL were indeed strongly increased in subcutaneous inguinal white adipose tissue and in brown adipose tissue, independently of the nutritional state, whereas of the three visceral fat depots examined (epididymal, retroperitoneal, mesenteric) only the latter responded consistently to COOH. Robust correlations (0.5 < r < 0.9) were observed between TG-derived lipid uptake and LPL in adipose tissues. The agonist did not increase LPL in muscle, and its enhancing action on postprandial muscle lipid uptake appeared to be mediated by post-LPL processes involving increased expression of fatty acid binding/transport proteins (aP2, likely in infiltrated adipocytes, FAT/CD36, and FATP-1). The study establishes in a diet-induced obesity model the major contribution of lipid uptake by specific, metabolically safe adipose depots to the postprandial hypotriglyceridemic action of PPAR agonism, and suggests a key role for LPL therein.

PPAR agonist; white adipose tissue; brown adipose tissue; triglyceride secretion; triglyceride clearance

This article has been cited by other articles:

				W. T. Festuccia, P.-G. Blanchard, V. Turcotte, M. Laplante, M. Sariahmetoglu, D. N. Brindley, D. Richard, and Y. Deshaies The PPAR{gamma} agonist rosiglitazone enhances rat brown adipose tissue lipogenesis from glucose without altering glucose uptake Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2009; 296(5): R1327 - R1335. [Abstract] [Full Text] [PDF]