STAT5 as an anti-obesity agent

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An obesity epidemic is evident in first world countries including Australia. Twenty seven percent of men aged 55-64 in this country are obese. Obesity results in increased mortality and morbidity from type 2 diabetes, cardiovascular disease, renal disease and endometrial cancer, among others. Given our flaccid lifestyles, it is imperative that the metabolic processes underlying obesity be fully understood, to allow development of suitable treatment modalities. This proposal seeks to establish an important new element in our understanding of the development of obesity, the transcription factor STAT5. With previous NHMRC support, we developed sophisticated genetically modified mice which lack defined signalling processes initiated by growth hormone, an anti-obesity agent. These studies showed a strong correlation between ability to activate STAT5 and resistance to obesity. There is fragmentary literature evidence to support our hypothesis, which could also explain some of leptins anti-obesity actions. Using mice which lack STAT5, we shall establish a role for STAT5 as an antiobesity agent. The actions of STAT5 are normally blocked by feedback inhibitors referred to as SOCS, discovered by Australians. We shall define which SOCS is the feedback regulator for obesity control, allowing us to develop specific anti-SOCS agents which will act as novel anti-obesity agents.