High-Fat Diet Induces Resistance to Ghrelin and LEAP2 Peptide Analogs in Mice

Recent data suggest that the orexigenic peptide ghrelin and liverexpressed antimicrobial peptide 2 (LEAP2) have opposing effects on food intake regulation. Although circulating ghrelin is decreased in obesity, peripheral ghrelin administration does not induce food intake in obese mice. Limited information is available on ghrelin resistance in relation to LEAP2. In this study, the interplay between ghrelin and LEAP2 in obesity induced by a high-fat (HF) diet in mice was studied. First, the progression of obesity and intolerance to glucose together with plasma levels of active and total ghrelin, leptin, as well as liver LEAP2 mRNA expression at different time points of HF diet feeding was examined. In addition, the impact of switch from a HF diet to [Dpr3]Ghrelin or our novel LEAP2 analogue palm-LEAP2(1-14) on obesity-related ghrelin resistance.