Arcuate Nucleus Homeostatic Systems Reflect Blood Leptin Concentration but not Feeding Behaviour during Scheduled Feeding on a High Fat Diet in Mice

Abstract

Hypothalamic homeostatic and forebrain reward-related genes were examined in the context of scheduled meal feeding without caloric restriction in C57BL/6 mice. Mice fed ad libitum but allowed access to a palatable high fat diet for 2 h a day rapidly adapted their feeding behaviour and consumed approximately 80% of their daily caloric intake during this 2 h scheduled feed. Gene expression levels were examined during either the first or second hour of scheduled feeding vs. 24 h ad libitum feeding on the same high fat diet. Gene expression of neuropeptide Y, agouti-related peptide, cocaine- and amphetamine-regulated transcript, proopiomelanocortin, long-form leptin receptor and suppressor of cytokine signalling-3 in the hypothalamic arcuate nucleus (ARC), and enkephalin, dynorphin, dopamine-2-receptor and dopamine-3-receptor in the nucleus accumbens (NAcc) in the forebrain were measured by in situ hybridisation. Mice fed ad libitum on high fat diet had the highest total caloric intake, body weight gain, fat mass and serum leptin, whereas schedule-fed mice had a mild obese phenotype with intermediate total caloric intake, body weight gain, fat mass and serum leptin. The effects of feeding regime on ARC gene expression were emphasised by significant positive or negative correlations with body weight gain, fat mass and blood leptin, but did not appear to be related to feeding behaviour in the schedule-fed groups, i.e. the large, binge-type meals, and did not reveal any potential candidates for the regulation of these meals. Mechanisms underlying large meal/binge-type eating may be regulated by non-homeostatic hedonic processes. However, assessment of opioid and dopamine receptor gene expression in the NAcc did not reveal evidence of involvement of these genes in regulating the large meals. This complements our previous characterisation of ARC and NAcc genes in schedule-fed mice and rats, but still leaves open the fundamental question about the underlying mechanisms of meal feeding.

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