the metabolism in (pre)adipocytes

Mitochondrial dysfunction has consequences on the glucose and fatty acid metabolisms of (pre)adipocytes.

In the 3T3-L1 murine preadipocytes, we have shown that a mitochondrial dysfunction induces the formation of triglyceride (TG) vesicles, and studied the metabolic modifications (Vankooningsloo et al, J Lipid Res 2005) as well as the associated transcription factors involved in this process (Vankooningsloo et al, J. Cell Sci 2006). Beside, adipocytes challenged with a mild mitochondrial uncoupling (using FCCP) undergo a partial « dedifferentiation » process, marked by a decreased TG content. This one is independent of PPARg and could be linked to a reduced lipid synthesis rather than an increase in fatty acid oxidation (Tejerina et al, J. Cell Sci 2009; De Pauw et al, Am. J. Pathol. 2009). In parallel, a subproteomic analysis of the mitochondrial protein content highlighted modifications in the protein composition of mitochondria in response to the mild uncoupling of 3T3-L1 adipocytes. Among others, the pyruvate carboxylase was shown to be significantly reduced in mitochondria of FCCP-treated adipocytes and to play a role in the TG content reduction after exposure to the uncoupling agent (De Pauw et al, Am. J. Pathol. 2009). In addition, obesity is characterized by lipid accumulation in white adipocytes and the tight regulation of triacylglycerol storage and mobilization by lipid droplet-associated proteins and lipolytic enzymes is emerging. As increase in energy expenditure resulting from mitochondrial uncoupling stimulates lipolysis, it represents a new anti-obesity strategy reducing adipose tissue triacylglycerol content. We investigated the molecular mechanisms involved in lipolysis induced by sub-lethal mitochondrial uncoupling event in white 3T3-L1 adipocytes.