Endocrine Abstracts (2006) 11 P394

Orexin receptor expression in human adipose tissue: differential effects of orexins

JE Digby, J Chen & HS Randeva

Biological Sciences, University of Warwick, Coventry, United Kingdom.

Besides playing a role in energy homeostasis, orexins have been reported to have divergent effects on physiological behaviour, cardiovascular regulation, glucocorticoid release, as well as playing a key role in the aetiopathogenesis of narcolepsy. Recent studies using rodent models suggest orexins may also be involved in the regulation of thermogenesis. For example, mice lacking the prepro-orexin gene are significantly hypophagic but have normal body weight suggesting differences in energy homeostasis and metabolic rate. Furthermore, orexins may regulate both brown adipose tissue energy expenditure and thermogenesis through stimulation of sympathetic nerve activity. There are no data as yet on the expression of orexin system components in adipose tissue. We therefore analyzed the expression and localization of orexin receptor-1 (OX1R) and orexin receptor 2 (OX2R) in intra-abdominal omental (Ome) and subcutaneous (Sc) adipose tissue. In addition the effects of orexin A and orexin B on the expression of key genes involved in adipose tissue metabolism and on glycerol release were measured. The study was approved by the Local Research Ethics Committee and all patients involved gave their informed consent

Using RT-PCR analysis we demonstrated expression of OX1R and OX2R mRNA in Sc and Ome human adipose tissue, as well as in pre-adipocytes and differentiated adipocytes in vitro. Immunohistochemical analysis revealed intense membrane staining for both OX1R and OX2R protein in human Sc adipocytes. Furthermore, treatment of human adipose tissue explants with OR-A, resulted in a significant decrease in glycerol release from Ome adipose tissue only (P<0.05). In OR-A and OR-B-treated adipose tissue explants (100 nM, 24 h), hormone sensitive lipase mRNA expression was significantly reduced in ome adipose tissue only. Interestingly, orexin B but not orexin A treatment resulted in an increase in PPAR-gamma mRNA expression in Sc but not ome. These findings indicate a direct role for orexins on adipose tissue metabolism and proliferation through PPAR-gamma activation.

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