POSTWEANING EXPOSURE TO A HIGH FAT DIET IS ASSOCIATED WITH ALTERATIONS TO THE HEPATIC HISTONE CODE IN JAPANESE MACAQUES

BACKGROUND: Expression of the circadian gene, Npas2, is altered in fetal life with maternal high fat diet exposure by virtue of alterations in the fetal histone code. We postulated that these disruptions would persist postnatally. METHODS: Pregnant macaques were fed a control (CTR) or high fat (HF) diet and delivered at term. When offspring were weaned, they were placed on either CTR or HF diet for a period of 5 months to yield four exposure models (in utero diet/postweaning diet: CTR/CTR n = 5; CTR/HF n = 4; HF/CTR n = 4; HF/HF n = 5). Liver specimens were obtained at necropsy at one year of age. RESULTS: Hepatic trimethylation of lysine 4 of histone H3 is decreased, (CTR/HF 0.87-fold, P = 0.038; HF/CTR 0.84-fold, P = 0.038) while hepatic methyltransferase activity increased by virtue of diet exposure (HF/HF 1.3-fold, P = 0.019). Using chromatin immunoprecipitation to determine Npas2 promoter occupancy, we found alterations of both repressive and permissive histone modifications specifically with postweaning high fat diet exposure. CONCLUSION: We find altered Npas2 expression corresponds with a change in the histone code within the Npas2 promoter.