Mechanisms of sustained long-term weight loss after RYGB: α-MSH is a key factor

•Leptin, α-MSH and PYY has an intrinsic action stimulating the anorexigenic pathways in a post RYGB.•Anorexigenic pathways may play a prominent role in the effectiveness of the RYGB.•The central melanocortin system may be a key role in sustained long-term weight loss.•α-MSH contributes to weight loss by stimulate lipolysis and adipose tissue browning.•Compensatory hormonal adaptation leads to increased appetite favoring weight regain.