Program in Molecular Medicine; Department of Biochemistry and Molecular Pharmacology
3T3-L1 Cells; Adipocytes; Adipose Tissue; Animals; Blood Glucose; Blotting, Northern; Blotting, Western; Chaperonin 60; Fatty Acids; Insulin; Mass Spectrometry; Mice; Mice, Inbred C57BL; Mice, Obese; Mice, Transgenic; Microscopy, Fluorescence; Mitochondria; Obesity; Oligonucleotide Array Sequence Analysis; Oxygen; PPAR gamma; Palmitic Acid; RNA, Complementary; RNA, Messenger; Thiazolidinediones; Time Factors; Vasodilator Agents
Biochemistry | Cell Biology | Pharmacology
Adipose tissue plays a central role in the control of energy homeostasis through the storage and turnover of triglycerides and through the secretion of factors that affect satiety and fuel utilization. Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear. Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone. The levels of approximately 50% of gene transcripts encoding mitochondrial proteins were decreased with the onset of obesity. About half of those genes were upregulated after treatment with rosiglitazone, and this was accompanied by an increase in mitochondrial mass and changes in mitochondrial structure. Functionally, adipocytes from rosiglitazone-treated mice displayed markedly enhanced oxygen consumption and significantly increased palmitate oxidation. These data reveal mitochondrial remodeling and increased energy expenditure in white fat in response to rosiglitazone treatment in vivo and suggest that enhanced lipid utilization in this tissue may affect whole-body energy homeostasis and insulin sensitivity.
DOI of Published Version
J Clin Invest. 2004 Nov;114(9):1281-9. Link to article on publisher's site
The Journal of clinical investigation
Wilson-Fritch, Leanne; Nicoloro, Sarah M.; Chouinard, My T.; Lazar, Mitchell A.; Chui, Patricia C.; Leszyk, John D.; Straubhaar, Juerg R.; Czech, Michael P.; and Corvera, Silvia, "Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone" (2004). Open Access Articles. 995.