Metabolic Adaptation of the Small Intestine to Short- and Medium-Term High-Fat Diet Exposure

The small intestine is the main organ involved in the digestion and absorption of nutrients. It is in an ideal position to sense the availability of energy in the lumen in addition to its absorptive function. Consumption of a high-fat diet (HFD) influences the metabolic characteristics of the small intestine. Therefore, to better understand the metabolic features of the small intestine and their changes in response to dietary fat, we characterized the metabolism of duodenal, jejunal, and hepatic cell lines and assessed the metabolic changes in the enterocytes and the liver after short-term (3 days) or medium-term (14 days) HFD feeding in mice. Experiments with immortalized enterocytes indicated a higher glycolytic capacity in the duodenal cell line compared to the other two cell lines, whereas the jejunal cell line exhibited a high oxidative metabolism. Short-term HFD feeding induced changes in the expression of glucose and lipid metabolism-related genes in the duodenum and the jejunum of mice, but not in the liver. When focusing on fatty acid oxidation both, short- and medium-term HFD feeding induced an upregulation of 3-hydroxy-3-methylglutaryl-coenzyme A, the key enzyme of ketogenesis, at the protein level in the intestinal epithelial cells, but not in the liver. These results suggest that HFD feeding induces an early adaptation of the small intestine rather than the liver in response to a substantial fat load. This highlights the importance of the small intestine in the adaptation of the body to the metabolic changes induced by HFD exposure. J. Cell. Physiol. 232: 167–175, 2017. © 2016 Wiley Periodicals, Inc.