Metabolomic and transcriptomic changes induced by overnight (16 h) fasting in male and female XXXX .

@entity844 @entity1735 @entity6741 @entity35 @entity3645 @entity1718 @entity165
The overnight (16-h) fast is one of the most common experimental manipulations performed in rodent studies. Despite its ubiquitous employment, a comprehensive evaluation of metabolomic and transcriptomic sequelae of fasting in conjunction with routine clinical pathology evaluation has not been undertaken. This study assessed the impact of a 16-h fast on urine and serum metabolic profiles, transcript profiles of liver, psoas muscle, and jejunum as well as on routine laboratory clinical pathology parameters. Fasting @entity35 had an approximate 12% relative weight decrease compared to ad libitum fed animals, and urine volume was significantly increased. Fasting had no effect on hematology parameters, though several changes were evident in serum and urine clinical chemistry data. In general, metabolic changes in biofluids were modest in magnitude but broad in extent, with a majority of measured urinary metabolites and from 1/3 to 1/2 of monitored serum metabolites significantly affected. Increases in @entity1718 and @entity3645 dominated the upregulated metabolites. Downregulated serum metabolites were dominated by diet-derived and/or gut-microflora derived metabolites. Major transcriptional changes included genes with roles in @entity844 , @entity1735 , @entity165 , and @entity6741 metabolism indicating decreased activity in glycolytic pathways and a shift toward increased utilization of @entity1718 . Typically, several genes within these metabolic pathways, including key rate limiting genes, changed simultaneously, and those changes were frequently correlative to changes in clinical pathology parameters or metabolomic data. Importantly, up- or down-regulation of a variety of cytochrome P450s, transporters, and transferases was evident. Taken together, these data indicate profound consequences of fasting on systemic biochemistry and raise the potential for unanticipated interactions, particularly when metabolomic or transcriptomic data are primary end points.
