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

Abstract

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.

Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet

“…It is probably the high fat-content of breast milk that induces mHMGCS. Small intestinal expression of mHMGCS can also be reactivated by high-fat diet in adult rodents 21 22. Thus, intestinal ketogenesis could represent a fat-sensory mechanism of the small intestinal mucosa.…”

Brain Control of Plasma Cholesterol Involves Polysialic Acid Molecules in the Hypothalamus

“…Indeed, 1-week HFD is sufficient to change postprandial release, composition and size of chylomicrons by modulating intestinal lipid metabolism (Hernández Vallejo et al, 2009). Early transcriptional regulation of fatty acid metabolism-related enzymes has been observed in jejunum and duodenum upon 3-day HFD, indicating that the intestine is highly reactive to dietary fat (Clara et al, 2016). In the skeletal muscle, HFD suppresses lipogenic genes within a week and increases oxidative metabolism and markers of type I fiber, showing the metabolic adaptability of this tissue too (de Fourmestraux et al, 2004; Wilson et al, 2007; de Wilde et al, 2008).…”

Glucose stimulates intestinal epithelial crypt proliferation by modulating cellular energy metabolism

“…For glucose‐induced mitochondrial respiration measurement, the base XF assay medium was supplemented with 17.5 mM glucose, 2 mM Glutamax, 1 mM sodium pyruvate, and 100 U/ml Penicillin–Streptomycin (Fan et al, ). Mitochondrial respiration was determined by measuring OCR in response to modulators of mitochondrial respiration (i.e., ATP synthase inhibitor oligomycin [4 µg/ml, Sigma–Aldrich], mitochondrial uncoupler carbonyl cyanide‐4‐(trifluoromethoxy)phenylhydrazone [FCCP; 500 nM], complex I inhibitor rotenone [5 µM, Sigma–Aldrich], complex III inhibitor antimycin A [5 µg/ml, Sigma–Aldrich]) (Clara et al, , ).…”

“…Mitochondrial respiration was determined by measuring OCR in response to modulators of mitochondrial respiration (i.e., ATP synthase inhibitor oligomycin [4 µg/ml, Sigma-Aldrich], mitochondrial uncoupler carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone [FCCP; 500 nM], complex I inhibitor rotenone [5 µM, Sigma-Aldrich], complex III inhibitor antimycin A [5 µg/ml, Sigma-Aldrich])(Clara et al, 2016(Clara et al, , 2017.…”