Body weight and adiposity are determined by the balance between energy intake and energy expenditure. The latter is comprised of three major components including metabolic rate, physical activity and thermogenesis. Thermogenesis is defined as cellular dissipation of energy via heat production. This process has been extensively characterised in brown adipose tissue, wherein uncoupling protein 1 (UCP1) creates a proton leak across the inner mitochondrial membrane, diverting protons away from ATP synthesis and resulting in heat dissipation. Unlike rodents, sheep do not contain a defined or circumscribed brown fat depot but have dispersed brown adipocytes within defined white fat depots. In lambs, UCP1 is abundant in sternal and retroperitoneal fat beds [1]. Our work focuses on adult sheep, in which we use tissue-specific temperature recordings to characterise thermogenesis. Temperature probes (dataloggers: SubCue Calgary, Canada) are implanted into discrete tissue beds. For every surgery animals are anaesthetised via i.v. injection of thiopentane (20mg/kg body weight) and maintained through inhalation of halothane (3-5% in oxygen). All animal experimentation has been approved by the Monash Animal Research Platform ethics committee. We show that in sheep sternal and retroperitoneal adipose tissue and skeletal muscle are the primary sites of thermogenesis. In skeletal muscle thermogenesis occurs through mitochondrial uncoupling via UCP3 and futile calcium cycling [2]. We have utilised a number of physiological models to characterise the differential contribution of skeletal muscle and adipose thermogenesis in the regulation of body weight. Sheep are grazing animals and do not typically display meal-associated rhythms. Nonetheless, we show that temporal food restriction, whereby feeding is restricted to set meal times is able to entrain a number of meal-associated changes. This includes post-prandial thermogenesis which occurs in various tissue beds, albeit to varying degrees (sternal adipose tissue>skeletal muscle/ retroperitoneal adipose tissue> subcutaneous gluteal adipose tissue). Thus, different tissues exhibit inherent differences in thermogenic potential, which may be controlled in different ways. In line with the differences in thermogenic potential, our work highlights that innate differences in thermogenesis contribute to both the propensity to weight gain and obesity and the ability to lose weight in response to dietary restriction. Importantly, these differences occur in a tissue-specific manner. Chronic and severe food restriction (500g/ day Lucerne chaff for 1 year) leads to significant weight loss and causes severe compensatory changes in thermogenesis, being reduced in skeletal muscle as well as sternal and retroperitoneal adipose tissue. On the other hand, moderate food restriction (70% of ad lib) for 4 weeks reduces thermogenesis in adipose tissues only. Furthermore, this decrease in thermogenesis specifically occurs during the night time. Thus, adaptive changes in thermogenesis in response to under-nutrition occur primarily in adipose beds and presumably constitute a homeostatic mechanism that defends against weight loss in response to food restriction. Similarly, inherent differences in skeletal muscle thermogenesis precede weight gain in sheep. Selection for high cortisol responses to stress and adrenocorticotropin (ACTH) identifies individuals that have increased propensity to gain adipose tissue and obesity. In this model, increased predilection to obesity is associated with a number of metabolic, behavioural and neuroendocrine differences that ultimately lead to increased propensity to obesity [3-5]. A key metabolic feature of high cortisol responders is an inherent reduction in post-prandial thermogenesis in skeletal muscle [4]. In contrast to this, genetic selection for differences in adiposity are associated with differences in post-prandial thermogenesis in adipose tissue and not skeletal muscle. Thus, we demonstrate that skeletal muscle and adipose thermogenesis can be differentially regulated. Metabolic adaption to under-nutrition and/or altered propensity to obesity do not lead to global differences in thermogenesis, but in fact can lead to site and tissue specific changes.