Changes in leptin and melanocortin peptides in cerebrospinal fluid after diet versus bariatric surgery

Peripheral metabolic signals elicit a host of neuronal responses that maintain energy balance and make it difficult to maintain diet-induced weight loss (WL). Why WL is sustained after bariatric surgery remains unclear but brain mechanisms have been implicated. The objective was to compare changes in leptin and the hypothalamic melanocortin system, consisting of proopiomelanocortin (POMC) and AgRP neurons, after WL from diet versus surgery to determine if diet-induced changes in melanocortin activity might be circumvented after surgery. Fourteen subjects (BMI 41.3) were studied before and 3.2-months after diet (WL 12.5%). Eighteen subjects (BMI 44.4) were studied before and 2.4-months after surgery (12-sleeve gastrectomy; 6-Roux-en-Y gastric bypass) (WL 15.0%); 11 were studied again 1-year after surgery (WL 29%). CSF measurements of POMC and POMC-derived ß-MSH were used as a surrogate of brain melanocortin activity. AgRP and leptin were measured in CSF and plasma. Leptin decreased in plasma and CSF at similar magnitudes after diet and surgery and there was a similar increase in the ratio of CSF/plasma leptin. Nonsignificant declines in CSF POMC but highly significant declines in CSF ß-MSH and ß-MSH/POMC ratio occurred after diet and surgery indicating a greater fall in processed peptide versus prohormone levels. CSF ß-MSH and ß-MSH/POMC remained suppressed by 31% and 29% 1-year after surgery (p < .0001). Plasma AgRP increased after diet (p < .001) and initially after surgery (p = .08) but not at 1-year. CSF AgRP was initially unchanged but increased 1-year after surgery (p < .05); the ratio of ß-MSH/AgRP in plasma and CSF decreased by 29% and 40% reflecting an overall fall in melanocortin activity. In conclusion WL is maintained after bariatric surgery despite counterregulatory changes in leptin and melanocortin activity similar to diet that would be expected to stimulate weight regain.