Purpose: Agouti-related protein (AgRP) is known as an orexigenic neuropeptide which is expressed in the hypothalamic arcuate nucleus. Its possible AgRP is an important molecule in glucocorticoid (GC) induced obesity (e.g. Cushing syndrome), because GC positively regulate hypothalamic AgRP. To clarify the role of AgRP in GC-induced obesity, we investigate here the effect of GC on AgRP deficient mice.
Methods: Male wild-type littermates (n=20) and AgRP deficient mice (AgRP-KO, n=20) were randomly divided into two groups, and were implanted subcutaneously with either placebo or corticosterone (CORT) pellet. Their body weight and food consumption were measured every day. They were decapitated on day 14, and trunk blood, hypothalamus and fat tissue were collected for further examination.
Results: There were no differences in body weight between WT and AgRP-KO before treatment (WT 21.5±0.3, AgRP-KO 21.9±0.5 g), and CORT treatment increased circulating CORT levels compared with placebo in both groups. In WT group, CORT administration increased epididymal fat weight compared with placebo (Placebo 271±22, CORT 486±42 mg, P<0.05), but not their body weight (Placebo 25.2±0.7, CORT 24.9±0.6 g). In AgRP-KO group, CORT administration increased epididymal fat weight (Placebo 310±20, CORT 727±63 mg, P<0.05) and body weight (Placebo 25.2±0.4, CORT 29.4±0.5 g, P<0.05) compared with placebo.
Conclusion: These results suggest that AgRP is not necessary in GC-induced obesity. On the other hand, accumulated evidences support GC clearly increase AgRP, and its reported GR (GC receptor) deficient in AgRP neuron shows obesity resistant phenotype. Therefore, the role of AgRP in GC-induced obesity should be further examined.
18 - 21 May 2019
European Society of Endocrinology