Exaggerated anorexigenic response to restraint stress in Ay mice is associated with elevated CRFR2 mRNA expression in the hypothalamus

Abstract

The “lethal yellow” mutation at the mouse agouti locus (Ay) results in hyperphagia, obesity, and type 2 diabetes at rest, but helps to reduce food intake under stress. The aim of this work was to investigate mechanisms of exaggerated anorectic response to stress in Ay mice. All parameters were measured in C57BL/6J male mice of a/a (control) and Ay/a genotypes before, 0, 1, and 3h after a 1-h restraint. Baseline food intake and plasma insulin concentrations were higher in Ay/a mice compared to a/a mice. Restraint reduced food intake and plasma insulin concentrations only in Ay/a mice. Stress-induced anorexia in Ay/a mice was independent of pathways involving hypothalamic–pituitary–adrenal axis activity and hypothalamic orexigenic neuropeptide (agouti-related peptide and neuropeptide Y) gene expressions and corticotrophin-releasing factor type 1 receptor (CRFR1). Gene expression of CRFR2 was elevated in Ay/a mice with genotype differences particularly manifested immediately after the restraint. Hypothalamic CRFR2 is known to mediate anorectic signals from CRF-related peptides. Thus, our data suggest that stress-induced anorexia in Ay/a mice may be associated with increased anorectic signals mediated by CRFR2 in the hypothalamus.