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

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

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

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

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

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

Involvement of orexin in the sex-specific effect of relaxin-3 on food intake in rats

Involvement of orexin in the sex-specific effect of relaxin-3 on food intake in rats. 24. Annual Meeting of the International Behavioral Neuroscience Society (IBNS

Differential effects of central administration of relaxin-3 on food intake and hypothalamic neuropeptides in male and female rats

Relaxin-3 (RLN3) is an orexigenic neuropeptide that produces sex-specific effects on food intake by stronger stimulation of feeding in female compared with male rats. This study determined which hypothalamic nuclei and associated neuropeptides may be involved in the sex-specific orexigenic effects of RLN3. Relaxin-3 (800 pmol) or vehicle was injected into the lateral ventricle of female and male rats. Food and water intake were measured after the first injection, and rats were euthanized after the second injection to determine the mRNA expression of the hypothalamic neuropeptides. Food but not water intake showed sex-specific effects of RLN3. Stimulation of food intake by RLN3 was significantly higher in female than in male rats. No effect of RLN3 injection was found on c-fos mRNA expression in the arcuate, dorsomedial and ventromedial hypothalamic nuclei. Increased c-fos mRNA expression was observed in the paraventricular hypothalamic nucleus (PVN) in both sexes and in the lateral hypothalamic area (LHA) in female rats. Relaxin-3 injections led to a sex-nonspecific increase in the expression of oxytocin mRNA in the magnocellular PVN. Conversely, RLN3-induced expression of anorexigenic neuropeptide arginine vasopressin (AVP) was significantly higher in the parvocellular PVN in male compared with female rats. Finally, RLN3 administration significantly increased the expression of orexin (ORX) mRNA in the LHA in female but not in male rats. Stronger expression of anorexigenic AVP in the PVN in male rats and increased expression of ORX in the LHA in female rats may contribute to stronger orexigenic effects of RLN3 in female rats compared with male rats