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Journal of Lipid Research, Vol. 48, 826-836, April 2007
Copyright © 2007 by American Society for Biochemistry and Molecular Biology

Effects of forced uncoupling protein 1 expression in 3T3-L1 cells on mitochondrial function and lipid metabolism

Yaguang Si^*, Santhosh Palani, Arul Jayaraman and Kyongbum Lee^1,

^* Department of Biology, Tufts University, Medford, MA 02155
Department of Chemical and Biological Engineering, Tufts University, Medford, MA 02155
Department of Chemical Engineering, Texas A&M University, College Station, TX 77843

Published, LR Papers in Press, January 3, 2007.

¹ To whom correspondence should be addressed. e-mail: kyongbum.lee{at}tufts.edu

Obesity-related increase in body fat mass is a risk factor for many diseases, including type 2 diabetes. Controlling adiposity by targeted modulation of adipocyte enzymes could offer an attractive alternative to current dietary approaches. Brown adipose tissue, which is present in rodents but not in adult humans, expresses the mitochondrial uncoupling protein 1 (UCP1) that promotes cellular energy dissipation as heat. Here, we report on the direct metabolic effects of forced UCP1 expression in white adipocytes derived from a murine (3T3-L1) preadipocyte cell line. After stable integration, the ucp1 gene product was continuously expressed during differentiation and reduced the total lipid accumulation by 30% without affecting other adipocyte markers, such as cytosolic glycerol-3-phosphate dehydrogenase activity and leptin production. The expression of UCP1 also decreased glycerol output and increased glucose uptake, lactate output, and the sensitivity of cellular ATP content to nutrient removal. However, oxygen consumption and ß-oxidation were minimally affected. Together, our results suggest that the reduction in intracellular lipid by constitutive expression of UCP1 reflects a downregulation of fat synthesis rather than an upregulation of fatty acid oxidation.

Supplementary key words adipocyte metabolic profile • glucose starvation • cellular ATP content

Abbreviations: BAT, brown adipose tissue; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; GPDH, glycerol-3-phosphate dehydrogenase; KRH, Krebs-Ringer buffer/HEPES; MMP, mitochondrial membrane potential; OUR, oxygen uptake rate; TG, triglyceride; TMRM, trimethylrhodamine; UCP1, uncoupling protein 1; WAT, white adipose tissue

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