A test of the lipostat theory in a seasonal (ovine) model under natural conditions reveals a close relationship between adiposity and melanin concentrating hormone expression

A study was undertaken in Corriedale ewes to test the lipostat theory using data obtained from a model of seasonal change in food intake and body composition. The theory predicts adipose-derived factors signal to the brain and vice versa, to maintain homeostasis. It is held that leptin acts on cells in the brain to regulate food intake and energy expenditure, through “first order” neurons in the arcuate nucleus (ARC). These cells are thought to receive information that is relayed to “second order” neurons, to regulate food intake and other functions. In this study, groups (n = 4–5) of ovariectomized ewes were maintained under natural conditions and sampled at various points across the year. Food intake, body composition and indices of metabolic function were measured prior to collection of brains for in situ hybridization analysis. Expression of genes encoding for neuropeptide Y (NPY), pro-opiomelanocortin (POMC), orexin (ORX), melanin concentrating hormone (MCH) and leptin receptor (ObRb) was quantified. NPY gene expression was high when food intake was also high but, across the year, changes in NPY and POMC gene expression did not correspond predictably to plasma leptin levels or leptin receptor gene expression. Negative correlation was found between adiposity (omental and whole body fat) and gene expression of MCH and ORX, suggesting that changes in expression of genes for “second order” orexigenic peptides are closely linked to changes of metabolic state, even when similar relationships cannot be shown for expression of genes in “first order” neurons. These data provide support for the lipostat theory.