Weight loss from caloric restriction vs Roux-en-Y gastric bypass surgery differentially regulates systemic and portal vein GDF15 levels in obese Zucker fatty rats

Abstract

Weight loss from caloric restriction (i.e. dieting) tends to be modest and short-lived, whereas from bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) is pronounced and generally sustained. The reasons behind these opposing outcomes between interventions remain unclear, but likely involve differential effects on gut-brain communication. Growth differentiation factor 15 (GDF15) is a ubiquitously-induced, centrally-acting, anorexigenic cytokine whose systemic levels are elevated under a variety of conditions associated with a negative energy balance, including in patients following RYGB. We therefore asked whether systemic and portal vein GDF15 levels differ between obese Zucker fatty rats that experienced similar weight loss from RYGB or from forced caloric restriction (CR). Compared with ad libitum fed (ALF) controls, body weight, visceral adiposity and food intake of RYGB and CR rats were markedly lower during the postoperative observation period. Both systemic and portal vein GDF15 levels in RYGB rats at postoperative day 28 were higher compared with ALF rats and particularly compared with CR rats. Further, systemic and portal vein GDF15 levels negatively correlated with body weight and food intake specifically in RYGB rats. These findings provide evidence that, unlike dieting, RYGB might achieve sustained weight loss and appetite suppression partly through increased GDF15 release from epithelial cells of the gastrointestinal tract.