Impact of acute anorexia nervosa and of short-/long-term recovery after refeeding on the hormonal profiles of activin A, GDF-15 and follistatins

Anorexia Nervosa (AN) is a severe eating disorder characterized by endocrine and metabolic abnormalities. In this study, we evaluated how the concentrations of proteins recently linked with energy homeostasis might be altered in acute AN (acAN), whether their levels are associated with reproductive hormones and whether they are restored after weight recovery. Our results show that activin A, follistatin, LH and estradiol concentrations are decreased while growth/differentiation factor-15 (GDF-15) concentrations are increased in 79 females with acAN before weight restoration (acAN_T1) compared to 79 healthy control females not receiving oral contraception (HC_OCP). The concentrations of all hormones were partially or completely restored after weight restoration by short-term refeeding (acAN_T2) and in 35 females after long-term ( >6 months) recovery from AN not receiving OCPs (recAN_OCP). Low activin A and high GDF-15 concentrations, as in acAN_T1, were also observed in 45 healthy control females under OCP (HC_OCP) compared to HC_OCP. Follistatin levels were ~3-fold higher in HC_OCP and recAN_OCP (45 female recAN under OCP) compared to HC_OCP or recAN_OCP respectively. LH, FSH and estradiol concentrations were positively associated with activin A and negatively with GDF-15 and follistatin. In conclusion, we report profound alterations in GDF-15, activin A and follistatin concentrations in acAN, which are associated with the concentrations of reproductive hormones and they are regulated by OCP and weight recovery by refeeding. Our findings support the evaluation of strategies targeting these hormones (e.g. GDF-15 inhibition) in AN to potentially increase body weight and thereby facilitate the resumption of reproductive function.