Effects of IL-15 on rat brown adipose tissue:: Uncoupling proteins and PPARs

Objectives: Interleukin-15 (IL-15) plays an important role in lipid metabolism as its administration to rats causes a marked depletion of white adipose tissue (WAT). This reduction in fat mass seems to be caused by and related to hipotriglyceridemia as a result of a lower hepatic lipogenesis and an increased fatty acid oxidation. We have previously observed that IL-15 treatment induces the expression of uncoupling proteins (UCPs) in muscle. The aim of this study was to investigate the effects of IL-15 on brown adipose tissue (BAT), and in particular on genes related to lipid metabolism in this tissue. Methods and Procedures: Male Wistar rats were treated daily with IL-15 for 7 days. Adipose tissues were collected and the mRNA content of UCPs, peroxisome proliferator-activated receptors (PPARs) and several genes implicated in fatty acid transport and oxidation were evaluated on BAT. Results: IL-15 treatment in rats causes a decrease in the mass of both WAT and BAT (35 and 24%, respectively). In BAT, an important upregulation of the mRNA content of thermogenic proteins (UCP1 and UCP3), lipid-related transcription factors (PPAR delta and PPAR alpha) and other proteins implicated in membrane transport (fatty acid translocase (FAT) and fatty acid transport protein (FATP)), mitochondrial transport (carnitine palmitoyl transferase-I (CPT-I) and CPT-II) and consumption (acyl-CoA synthetase 4 (ACS4)) of fatty acids was observed as a consequence of the treatment. Discussion: The changes observed in BAT suggest that IL-15 could be implicated in lipid consumption in this tissue by regulating lipid oxidation and probably thermogenesis, processes mediated by UCPs and PPARs.