Gut-brain crosstalk regulates craving for fatty food

Abstract

Patients undergoing Roux-en-Y gastric bypass (RYGB) surgery elicit striking loss of body weight. Anatomical re-structuring of the gastrointestinal (GI) tract, leading to reduced caloric intake and changes in food preference, are thought to be the primary drivers of weight loss in bariatric surgery patients. However, the mechanisms by which RYGB surgery causes a reduced preference for fatty foods remain elusive. In a recent report, Hankir et al described how RYGB surgery modulated lipid nutrient signals in the intestine of rats to blunt their craving for fatty food. The authors reported that RYGB surgery restored an endogenous fat-satiety signaling pathway, mediated via oleoylethanolamide (OEA), that was greatly blunted in obese animals. In RYGB rats, high fat diet (HFD) led to increased production of OEA that activated the intestinal peroxisome proliferation activator receptors-α (PPARα). In RYGB rats, activation of PPARα by OEA was accompanied by enhanced dopamine neurotransmission in the dorsal striatum and reduced preference for HFD. The authors showed that OEA-mediated signals to the midbrain were transmitted via the vagus nerve. Interfering with either the production of OEA in enterocytes, or blocking of vagal and striatal D1 receptors signals eliminated the decreased craving for fat in RYGB rats. These studies demonstrated that bariatric surgery led to alterations in the reward circuitry of the brain in RYGB rats and reduced their preference for HFD.

Keywords: Roux-en-Y gastric bypass surgery; Dietary lipids; Dopamine D1 receptors; Peroxisome proliferator activated receptor-alpha; Oleoylethanolamide

Core tip: The mechanisms underlying a massive and sustained body weight loss after gastric bypass surgery remain poorly understood. Hankir et al describe how a fat-satiety signaling pathway that was greatly blunted in obese rats could be restored by Roux-en-Y gastric bypass (RYGB) surgery. The authors have demonstrated that RYGB rats on high fat diet (HFD) elicited an increased production of oleoylethanolamide (OEA) and activation of PPARα that led to a surge in dopamine release and activation of D1 in the dorsal striatum. The enhanced dopamine neurotransmission evoked by OEA was obligatorily dependent on intact vagus nerve that had no effect on the production of OEA in the small intestine. The heightened dopamine neurotransmission in the midbrain of RYGB rats was linked to their decreased preference for HFD. These elegant studies have provided a compelling mechanism by which RYGB surgery led to altered gut-brain communication to modify the reward circuitry involved in food preference and obesity. These observations have important clinical implications for the amelioration obesity and its pathological consequences.