HIGH FAT DIET ALTERS SPLANCHNIC SYMPATHOINHIBITORY RESPONSES TO GASTRIC HORMONES

Abstract

Gastric leptin and cholecystokinin (CCK) act on vagal afferents to induce reflex inhibition of splanchnic sympathetic nerve discharge (SSND), and may act co‐operatively in this response. We sought to determine whether this response is altered in animals exposed to a medium high fat diet (MHFD). Male Sprague‐Dawley rats were placed on a low‐fat diet (LFD; n=8) or a MHFD (n=24) for 13 weeks, after which animals were anesthetised and artificially ventilated. Baseline arterial pressure (AP) was measured and blood was collected for determination of plasma leptin and CCK. SSND responses to leptin (15 μg/kg) and CCK (2 μg/kg) administered close to the celiac artery were evaluated. Animals on the MHFD were grouped as obesity prone (OP; n=8) or obesity resistant (OR; n=8); the effects of diet alone were also examined. OP rats had significantly higher AP, fat pad mass and plasma leptin but lower plasma CCK, compared to LFD rats (P < 0.05 for all). Collectively, MHFD animals had elevated leptin but lower CCK levels than LFD rats (P < 0.05 for both) and this corresponded with attenuated/reversed SSND responses to CCK (LFD: −21 ± 2 Units vs MHFD −10 ± 2 Units; P < 0.05) and leptin (LFD: −6 ± 2 Units vs MHFD: 4 ± 1 Units; P < 0.001). High fat diets may induce leptin resistance that reduces the sensitivity of vagal afferents to gastrointestinal hormones. Increased gastrointestinal vascular resistance may contribute to hypertension in obesity.