the Arcuate Nucleus by High-Fat Feeding: A Novel Constraint to Hyperphagia?

11-Hydroxysteroid dehydrogenase type 1 (11-HSD1) cata-lyzes regeneration of active intracellular glucocorticoids in fat, liver, anddiscretebrain regions.Althoughoverexpression of 11-HSD1 in adipose tissue causes hyperphagia and the metabolic syndrome, male 11-HSD1 null (11-HSD1/) mice resist metabolic disease on high-fat (HF) diet, but also show hyperphagia. This suggests 11-HSD1 may influence the cen-tral actions of glucocorticoids onappetite andperhaps energy balance. We show that 11-HSD1/ mice express lower hy-pothalamic mRNA levels of the anorexigenic cocaine and am-phetamine-regulated transcript andmelanocortin-4 receptor, but higher levels of the orexigenic melanin-concentrating hormone mRNAs than controls (C57BL/6J) on a low-fat diet (11 % fat). HF (58 % fat) diet promoted transient (8 wk) hy-perphagia and decreased food efficiency in 11-HSD1/mic