Seasonal energy intake of Tibetan sheep on the harsh Qinghai-Tibetan Plateau (QTP) fluctuates greatly and is often well below maintenance requirements. The aim of this study was to gain insight into how the hypothalamus regulates energy homoeostasis in Tibetan sheep. We compared Tibetan and Small-tailed Han sheep (n 24 of each breed), which were each allocated randomly into four groups and offered one of four diets that differed in digestible energy densities: 8·21, 9·33, 10·45 and 11·57 MJ/kg DM. Sheep were weighed every 2 weeks, and it was assumed that the change in body weight (BW) reflected the change in energy balance. The arcuate nucleus of the hypothalamus in Tibetan sheep had greater protein expressions of neuropeptide Y (NPY) and agouti-related peptide (AgRP) when in negative energy balance, but lesser protein expressions of proopiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) when in positive energy balance than Small-tailed Han sheep. As a result, Tibetan sheep had a lesser BW loss when in negative energy balance and stored more energy and gained more BW when in positive energy balance than Small-tailed Han sheep with the same dietary intake. Moreover, in the hypothalamic adenosine monophosphate-activated protein kinase (AMPK) regulation pathway, Tibetan sheep had greater adenosine monophosphate-activated protein kinase-α 2 protein expression than Small-tailed Han sheep, which supported the premise of a better ability to regulate energy homoeostasis and better growth performance. These differences in the hypothalamic NPY/AgRP, POMC/CART and AMPK pathways between breeds conferred an advantage to the Tibetan over Small-tailed Han sheep to cope with low energy intake on the harsh QTP.

Rodent models of diet-induced obesity (DIO) mimic common human obesity more accurately than obese single-gene mutation lines, such as the ob/ob mouse. Sprague-Dawley rats sourced in the UK develop obesity when fed a high-energy diet, but susceptibility to DIO is normally distributed, as might be anticipated for a polygenic trait in an outbred population, in contrast to reports in the literature using ostensibly the same strain of rats sourced in the USA. Nevertheless, the responses of these rats to solid and liquid obesogenic diets are very similar to those reported elsewhere, and this model of DIO has much to commend it as a vehicle for the mechanistic study of susceptibility to DIO, development and reversal of obesity on solid and liquid diets and the response of peripheral and central energy balance systems to the development of obesity and to the obesogenic diets themselves. In general, hypothalamic energy-balance-related systems respond to obesogenic diets and developing obesity with activity changes that appear designed to counter the further development of the obese state. However, these hypothalamic changes are apparently unable to maintain body weight and composition within normal limits, suggesting that attributes of the obesogenic diets either evade the normal regulatory systems and/or engage with reward pathways that override the homeostatic systems. Since diets are a risk factor in the development of obesity, it will be important to establish how obesogenic diets interact with energy-balance pathways and whether there is potential for diets to be manipulated with therapeutic benefit.