Enterocyte fatty acid oxidation may influence eating through vagal afferent signals

Abstract

Mercaptoacetate (MA) and other fatty acid oxidation (FAO) inhibitors supposedly stimulate eating by inhibiting hepatic FAO, thus activating a hepatic vagal afferent signal to eat. This concept has been challenged because hepatic parenchymal vagal afferent innervation is scarce and because experimentally induced changes in hepatic FAO often fail to affect eating. Nevertheless, IP MA must act in the abdomen to stimulate eating because its effect was blocked by subdiaphragmatic vagal deafferentation (SDA) (Brandt et al, Neurosci Letters 411:104, 2007). This suggests a role of the small intestine in the effects of IP MA on eating. To examine this idea, we equipped adult male rats with jejunal catheters and tested the effects on eating of intrajejunal infusions (30 sec, 1 ml/kg, start at 3 h into the light phase) of MA (100, 200, and 400 μmol/kg BW). MA (200 and 400 μmol/kg) increased (P < 0.05) 30 and 60 min food intake vs. control, this effect was absent in rats after SDA, and MA infused into the superior mesenteric artery (SMA) increased (within 10 min) the activity of 34 (out of 37) serotonin‐sensitive single units isolated from celiac vagal fascicles originating in the proximal small intestine. Because the SMA supplies most of the small intestine, these data support the hypothesis that small intestinal enterocytes may serve as FAO sensors and influence eating through changes in intestinal vagal afferent activity.