Peroxisome proliferator-activated receptor α deficiency modifies glucose handling by isolated mouse adipocytes

Peroxisome proliferator-activated receptor alpha (PPAR alpha) is a transcription factor that regulates enzymes involved in fatty acid (FA) utilisation. PPARa null mice have recently been demonstrated to have increased whole-body glucose turnover in vivo. This has been attributed to increased glucose uptake by adipose tissue, but the impact of PPARa deficiency on the characteristics of glucose handling by isolated adipocytes ex vivo is unknown. To determine directly the impact of PPAR alpha deficiency on adipocyte glucose handling, thereby excluding any influence of humoral/neuronal factors, we examined total glucose metabolism as well as glucose disposition towards alternative fares in epididymal adipocytes isolated from wildtype and PPAR alpha null mice. Total glucose metabolism (oxidation, incorporation into FA and glycerol moieties of triglyceride (TAG) and conversion to lactate) was measured under basal conditions (low glucose) and 'stimulated lipogenic' conditions (high glucose + insulin). Adipocytes from PPAR alpha null mice had higher rates of glucose metabolism under both basal and stimulated lipogenic conditions, with increased glucose utilisation both for oxidation and entry into the synthesis of the FA and glycerol components of lipid. In particular, the capacity of adipocytes from PPAR alpha-deficient mice to utilise glucose for synthesis of the glycerol backbone of TAG was greatly enhanced under stimulated (high glucose + insulin) conditions. The increased use of glucose for the glycerol moiety of adipocyte TAG may therefore contribute to, and provide explanation for, enhanced glucose turnover in PPAR alpha null mice.