title: 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 hydrolyzes 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.
  
  
  RESULTS
  Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARgamma, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the 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 mechanism(s) underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown, adipocyte lineage.
authors.affiliation: Department of Experimental Medical Science, Lund University, Lund, Sweden. kristoffer.strom@med.lu.se
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Ström
authors.forename: Ola
authors.initials: O
authors.lastname: Hansson
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Lucas
authors.forename: Pernilla
authors.initials: P
authors.lastname: Nevsten
authors.forename: Céline
authors.initials: C
authors.lastname: Fernandez
authors.forename: Cecilia
authors.initials: C
authors.lastname: Klint
authors.forename: Sofia
authors.initials: S
authors.lastname: Movérare-Skrtic
authors.forename: Frank
authors.initials: F
authors.lastname: Sundler
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Cecilia
authors.initials: C
authors.lastname: Holm
mesh_terms: D017667:Adipocytes / Q000166:cytology*; D002001:Adipose Tissue, Brown / Q000166:cytology*; D000818:Animals; D002454:Cell Differentiation; D004032:Diet; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D009765:Obesity / Q000235:genetics; D002787:Sterol Esterase / Q000235:genetics / Q000502:physiology*
chemical_list: D002787:Sterol Esterase