An effect of dietary phloretin supplementation on feed intake in mice

Abstract

Phloretin, abundantly present in apples, pears and other fruits, has been found to have antioxidant, immunosuppressive and anti-inflammatory activities. It has been reported that oral administration of phloretin dose-dependently increased feed intake in mice, but the mechanism is unclear yet. The aim of this study was to investigate the effect of dietary phloretin supplementation on the feed intake in C57BL/6J mice and to identify its mechanism. Here, sixty C57BL/6J mice (28-day age) were randomly chosen for four dietary treatments and fed a basal diet or a basal diet supplemented with 0.1%, 0.2%, and 0.3% phloretin, respectively, in a 6-week trial. We showed that mice in the 0.1%, 0.2%, and 0.3% phloretin-supplemented groups had increased accumulative feed intake compared with the control group. Furthermore, dietary phloretin supplementation significantly increased the ghrelin mRNA level in the stomach and hypothalamus, and decreased the cholecystokinin (CCK) mRNA level in the duodenum in a dose-dependent manner. The mRNA levels of neuropeptide Y (NPY), agouti-related protein (AgRP), pro-opiomelanocortin and melanocortin receptors 4 (MC4R), and pro-opiomelanocortin (POMC) in the hypothalamus were altered in response to dietary phloretin supplementation. Moreover, we confirmed that dietary phloretin supplementation reduced the expressions of miR-488 and miR-103, two feed intake-related miRNAs. Our present study provides evidence that dietary phloretin supplementation could increase feed intake in mice, which might be attributed to the stimulation of the hypothalamic feeding center via ghrelin, miRNAs (miR-103 and miR-488) and feeding signal factor-related genes (NPY, AgRP, MC4R and POMC), and to the inhibition of CCK to increase gastric emptying.