Chronic Maternal Overnutrition and Nutritional Challenge in Adult Life Disrupt Metabolic Diurnal Rhythmicity and Clock Gene Expression in Central and Peripheral Circadian Oscillators.

Abstract

In mammals, the core molecular clock genes and the overall circadian system are established during early development; during this critical period of development, maternal metabolic condition plays a major role in programming temporal metabolic regulation. Therefore, this study aimed to evaluate the effects of the chronic maternal intake of a high-fat and high-carbohydrate diet (HFCD) before and during pregnancy, in addition to a challenge with HFCD during adulthood, on offspring diurnal metabolic profile and on clock gene expression in central and peripheral circadian oscillators. The HFCD offspring and/or those exposed to the metabolic challenge exhibited alterations in the temporal profiles of analytes associated with both the carbohydrate and lipid metabolisms, as well as markers associated with liver and kidney damage, ranging from phase changes in rhythmicity or, in some cases, to the complete loss of 24 h variations. At the molecular level, the expression of clock genes (Per1, Cry1, Bmal1, and Clock) in the central and peripheral oscillators showed differential susceptibility to undergoing changes in their abundance. Our data indicate that maternal HFCD during pregnancy, a second exposure in adulthood, or both result in the long-term misalignment of the diurnal rhythm's metabolic and damage markers; these changes are possibly associated with alterations in the core molecular circadian clockwork.