Influence of RORalpha on lipid metabolism in adipose tissue — ASN Events
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  3. Influence of RORalpha on lipid metabolism in adipose tissue

Influence of RORalpha on lipid metabolism in adipose tissue (#223)

Patrick Lau 1 , Rebecca L Fitzsimmons 1 , Michael A Pearen 1 , Gethin Thomas 2 , George E.O. Muscat 1
  1. Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD, Australia
  2. Diamantina Institute, University of Queensland, Woolloongaba, QLD, Australia

Staggerer (sg) is a natural mutation of the nuclear receptor,retinoic acid receptor-related orphan receptor alpha (Rorα). The mice displayed a lean and dyslipidaemic phenotype. Previously we have shown that sg/sg mice were also resistant to (high fat) diet-induced obesity 1 and increased insulin sensitivity through AKT signalling pathway2 . 

To further understand  this phenotype we explored the metabolic role of Rorα in mice in the adipose tissue. 14-week old homozygous staggerer (sg/sg) mice were compared with wild type mice. Sg/sg mice showed reduced adiposity with decreased serum TG, total and HDL cholesterol. DXA and histology showed reduced fat content and lower lipid accumulation in adipocytes. Microarray and Ingenuity analysis of adipose tissue indicated that gene expression in the prostaglandin pathway is affected.  Furthermore total Hormone Sensitive Lipase (HSL) and phosphorylated HSL are induced in sg/sg mice, suggesting that lipolysis is enhanced in the adipose tissue.

  1. Lau P, Fitzsimmons RL, Raichur S, Wang SC, Lechtken A, Muscat GE. 2008 The orphan nuclear receptor, RORalpha, regulates gene expression that controls lipid metabolism: staggerer (SG/SG) mice are resistant to diet-induced obesity. J Biol Chem. 283(26):184
  2. Lau P, Fitzsimmons RL, Pearen MA, Watt MJ, Muscat GE. 2011 Homozygous staggerer (sg/sg) mice display improved insulin sensitivity and enhanced glucose uptake in skeletal muscle. Diabetologia. 54(5):1169-80.