The role of relaxin-3 and its receptor RXFP3 in defense of elevated body weight in diet-induced obesity

Abstract

Incidence of overweight and obesity has dramatically increased during the past three decades. Treatment of this serious clinical problem is hindered by the fact that once obesity has developed, the elevated body weight is defended against weight-decreasing treatment strategies by mechanisms that are not yet fully understood. This review focuses on the neuronal mechanisms that contribute to the maintenance of obesity after it develops in the DIO rat model. Among the neuronal factors regulating energy intake, orexigenic neuropeptide relaxin-3 and its cognate receptor RXFP3 may play an important role in the defense of elevated body weight in DIO. The levels of expression of relaxin-3 mRNA in the brainstem nucleus incertus (NI) were significantly increased in the ad libitum feeding state in DIO rats compared to DR rats. However, the effects of relaxin-3 in the DIO ad libitum-fed rats may be compensated by a significant decrease in the levels of expression of RXFP3 mRNA in the food intake-regulating brain regions of DIO rats including the paraventricular hypothalamic nucleus (PVN), central amygdala (CeA), NI, and nucleus of the solitary tract (NTS). Remarkably, the DIO rats showed an immediate rebound in food intake at refeeding and regained all body weight lost during starvation. This significant increase in food intake during refeeding was accompanied by an increase in the levels of expression of RXFP3 in the parvocellular PVN, CeA, NI, and NTS in the DIO rats to the levels of the DR rats. Moreover, the expression of RXFP3 in the paraventricular thalamic nucleus was significantly higher in the refed DIO rats compared to the DR counterparts. A constitutive increase in the expression of relaxin-3 accompanied by a relative increase in the expression of RXFP3 in food intake-regulating brain regions during refeeding after food deprivation may contribute to the mechanisms of defense of elevated body weight in the DIO phenotype.