Acyl ghrelin acts in the brain to control liver function and peripheral glucose homeostasis in male mice

Recent evidence suggests that peripheral ghrelin regulates glucose metabolism. Here, we designed experiments to examine how central acyl ghrelin infusion affects peripheral glucose metabolism under pairfed or ad libitum feeding conditions. Mice received ICV infusion of artificial cerebrospinal fluid (aCSF), ghrelin and allowed to eat ad libitum (icv ghrelin ad-lib) or ghrelin and pairfed to the aCSF group (icv ghrelin pf). Mini pumps delivered acyl ghrelin at a dose of 0.25 mug/hour at 0.5 mul/hour for 7 days. There was no difference in daily blood glucose, insulin, glucagon, triglycerides or non-esterified fatty acids. Body weight gain and food intake was significantly higher in icv ghrelin ad-lib mice, however, both icv ghrelin ad-lib and icv ghrelin pf groups exhibited heavier white adipose mass. Icv ghrelin pf mice exhibited better glucose tolerance than aCSF or icv ghrelin ad-lib mice during a GTT, although both icv ghrelin ad-lib and icv ghrelin pf increased insulin release during the GTT. Central acyl ghrelin infusion and pair feeding also increased breakdown of liver glycogen and triglyceride, and regulated genes involved in hepatic lipid and glucose metabolism. Icv ghrelin pf mice had an increase in plasma blood glucose during a pyruvate tolerance test relative to icv ghrelin ad-lib or aCSF mice. Our results suggest that under conditions of negative energy (icv ghrelin pf) central acyl ghrelin engages a neural circuit that influences hepatic glucose function. Metabolic status affects the ability of central acyl ghrelin to regulate peripheral glucose homeostasis.