Time-of-Day-Dependent Dietary Fat Consumption Influences Multiple Cardiometabolic Syndrome Parameters in Mice

BACKGROUND: Excess caloric intake is strongly associated with the development of increased adiposity, glucose intolerance, insulin resistance, dyslipidemia, and hyperleptinemia (i.e., the cardiometabolic syndrome). Research efforts have focused attention primarily on the quality (i.e., nutritional content) and/or quantity of ingested calories as potential causes for diet-induced pathology. Despite growing acceptance that biological rhythms profoundly influence energy homeostasis, little is known regarding how the timing of nutrient ingestion influences development of common metabolic diseases. OBJECTIVE: To test the hypothesis that the time of day at which dietary fat is consumed significantly influences multiple cardiometabolic syndrome parameters. RESULTS: We report that mice fed either low or high fat diets in a contiguous fashion during the 12 hour awake/active period adjust both food intake and energy expenditure appropriately, such that metabolic parameters are maintained within a normal physiologic range. In contrast, fluctuation in dietary composition during the active period (as occurs in humans) markedly influences whole body metabolic homeostasis. Mice fed a high fat meal at the beginning of the active period retain metabolic flexibility in response to dietary challenges later in the active period (as revealed by indirect calorimetry). Conversely, consumption of high fat meal at the end of the active phase leads to increased weight gain, adiposity, glucose intolerance, hyperinsulinemia, hypertriglyceridemia, and hyperleptinemia (i.e., cardiometabolic syndrome) in mice. The latter perturbations in energy/metabolic homeostasis are independent of daily total or fat-derived calories. CONCLUSIONS: The time-of-day at which carbohydrate versus fat is consumed markedly influences multiple cardiometabolic syndrome parameters.