Resistin is a newly-described hormone whose expression in adipose tissue is regulated by fasting, insulin and obesity. We recently reported that resistin mRNA is also expressed in mouse hypothalamus and pituitary (FEBS Letts. 526, p26 (2002)). In the present study we hypothesized that adiposity would influence hypothalamic resistin immunoreactivity (ir). Two different, polyclonal antisera ( raised against aa 51-108, human ; aa 83-91, mouse ) revealed resistin ir in coronal sections from male mouse brain. Cell bodies in the arcuate nucleus (ARC) and median eminence were darkly stained with both antisera. The mouse peptide antibody also revealed a complex pattern of varicose processes that extended rostrally from the ARC to the preoptic area (POA) . Fibre density was heaviest in dorsal periventricular regions, the dorsomedial hypothalamus (DMH) and the POA. The ventromedial nucleus (VMH) was largely unstained. A few scattered cell bodies were noted in the cerebral cortex. Resistin ir was absent following removal of the primary antibodies from the staining procedure. We next examined three models of mouse obesity. Resistin-positive fibres were severely reduced in brain from male ob/ob mice, especially in the POA/DMH, though ARC staining remained essentially normal. Brain sections from mice lesioned with gold thioglucose or monosodium glutamate, treatments known to induce obesity ,also showed a deficit in fibre density in POA/DMH, together with a marked reduction in ARC resistin ir. This loss of resistin positive cell bodies in the ARC/VMH is consistent with the known effects of these neurotoxins. We conclude that the density of hypothalamic resistin ir is sensitive to peripheral adipose levels. The cellular phenotype of the resistin positive cells ( neuronal or glial ) may provide clues to the putative role of brain-derived resistin. Supported by NSHRF and IWK Health Centre.
24 - 26 Mar 2003
British Endocrine Societies