Attainment of brown adipocyte features in white adipocytes of hormone-sensitive lipase null mice

Abstract

Background: Hormone sensitive lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolysis cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. Methodology/Principal Findings: Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissu of HSL null mice wise characterized by reduced mass and reduced protein expression of PPARγ, a key transciption factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the diferentiation state of adipocyte. The protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7 fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The MRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. Conclusions: These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation. The exact mechanis(s) underlying this novel of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal espression levels of pRb and RIP 140, which both promote differentiation into the white, rather than the brown, adipocyte lineage. © 2008 Ström et al.