Submitted on July 26, 2006
Revised on January 2, 2007
Accepted on January 3, 2007
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
Chemical and Biological Engineering, Tufts University, Medford, MA 02155
Corresponding Author: 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 (BAT), 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 ca. 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. Taken together, our results suggest that the reduction in intracellular lipid by constitutive expression of UCP1 reflects a down-regulation of fat synthesis, rather than an up-regulation of fatty acid oxidation.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
