Adipose tissue traditionally exists as two types of stores: white and brown. White adipose is predominately used to store excess energy and brown is used for thermogenesis. White adipose, particularly inguinal white adipose (iWAT) in rodents, has been shown to have plasticity under cold stress and β-adrenergic stimulation that allows it to take on brown-like adipose characteristics. The increase of this intermediate “beige” or “brown-in white” (brite) adipose profile in white adipose has been correlated with decreased body fat and resistance to diet induced obesity.
Growth hormone (GH) is an important regulator of metabolism. It is thought to regulate whole body adiposity by acting to increase lipolysis and suppress lipogenesis. Obesity is often associated with lower circulating GH or deficiency in GH action (as in hypopituitary patients or GH receptor mutations). GHR mutant knockin mouse models indicate that the transcription factor STAT5 is the likely mediator of the anti-obesity action of GH. This is because ghr-391 mice, with a truncation at the cytoplasmic residue 391, have lost the ability to activate STAT5 by GH, and these mice develop obesity by 16 weeks of age.
The transcript profile of the iWAT has revealed a number of brown or “beige” adipose markers down-regulated in the ghr-391 mutant mice and protein analysis shows a striking decrease in the levels of oxidative phosphorylation subunits in ghr-391 iWAT, indicating that GH-activated STAT5 has an important role in the “browning” of white adipose tissue. The inability to induce beige adipose profile in iWAT results in an ability to utilise fat reserves and therefore contributes to the accumulation of WAT and obesity, providing a novel aspect ot the anti-obesity effects of GH.
This work is supported by an NHMRC grant to Professor Michael Waters.