Endocrine Abstracts

The hypothalamus regulates multiple homeostatic systems, and is essential for the regulation of appetite and energy balance. Neuropeptide Y, a 36 amino acid peptide and member of the PP-fold family, is a key hypothalamic neuropeptide involved in the regulation of energy balance, potently stimulating food intake following central administration. NPY is expressed in the arcuate nucleus (ARC) and NPYergic neurones project to multiple hypothalamic nuclei and extra-hypothalamic sites. NPY is also expressed in the hypothalamic dorsomedial nucleus (DMN) and there is data to suggest that NPY is differentially regulated in the DMN compared to the ARC. In diet-induced obesity and a number of genetic models of obesity NPY mRNA levels are reduced in the ARC but increased in the DMN.

In order to study the role of NPY in the DMN in the regulation of energy balance, the gene transfer vector recombinant adeno-associated virus (rAAV) expressing NPY was administered with stereotactic microinjection to over-express NPY in the DMN of male Wistar rats. Body weight and food intake were monitored for 94 days.

Over-expression of NPY within the DMN resulted in a reduction in food intake and body weight gain in rats compared with controls injected with rAAV encoding enhanced green fluorescent protein (EGFP). This effect was accentuated in animals fed on a high fat diet. Plasma leptin was reduced in NPY injected rats compared to controls, reflecting a decrease in adiposity. Measurement of circulating thyroid hormone levels, brown adipose tissue (BAT) weight and BAT uncoupling protein-1 mRNA expression indicated that the reduction in body weight gain was not due to an increase in energy expenditure.

These results suggest that NPY may have a different role in the DMN compared to the ARC adding further complexity to the neuronal circulatory involved in the regulation of food intake.