Disturbed intestinal nitrogen homeostasis in a mouse model of high-fat diet-induced obesity and glucose intolerance

Abstract

Previous studies demonstrated that PEPT1 expression and function in jejunum are reduced in diabetes and obesity, suggesting a nitrogen malabsorption from the diet. Surprisingly, we reported here a decrease in gut nitrogen excretion in high-fat diet (HFD)-fed mice and further investigated the mechanisms that could explain this apparent contradiction. Upon HFD, mice exhibited an increased concentration of free amino acids (AAs) in the portal vein (60%) along with a selective increase in the expression of two AA transporters (Slc6a20a, Slc36a1), pointing to a specific and adaptive absorption of some AAs. A delayed transit time (ϩ40%) and an increased intestinal permeability (ϩ80%) also contribute to the increase in nitrogen absorption. Besides, HFD mice exhibited a 2.2-fold decrease in fecal DNA resulting from a reduction in nitrogen catabolism from cell desquamation and/or in the intestinal microbiota. Indeed, major quantitative (2.5-fold reduction) and qualitative alterations of intestinal microbiota were observed in feces of HFD mice. Collectively, our results strongly suggest that both increased AA transporters, intestinal permeability and transit time, and changes in gut microbiota are involved in the increased circulating AA levels. Modifications in nitrogen homeostasis provide a new insight in HFD-induced obesity and glucose intolerance; however, whether these modifications are beneficial or detrimental for the HFD-associated metabolic complications remains an open issue.

Beneficial metabolic effects of selected probiotics on diet‐induced obesity and insulin resistance in mice are associated with improvement of dysbiotic gut microbiota

“…Results also confirmed earlier observations that bifidobacteria were low or absent in lean, LFD‐fed mice, but present in obese mice (Do et al ., ). This could be due to the higher level of maltodextrin in the HFD (http://onlinelibrary.wiley.com/doi/10.1111/1462-2920.13181/suppinfo), known to exhibit bifidogenic activity (Probert and Gibson, ).…”

The Role of Microbial Amino Acid Metabolism in Host Metabolism

“…In line with this hypothesis, modulation of the gut microbiota by antibiotics has been shown to increase plasma amino acid concentrations in piglets compared with controls [ 84 ]. Furthermore, there is a marked increase in the portal concentrations of several essential amino acids during high-fat diet induced obesity and glucose intolerance [ 85 ]. It could also be speculated that chronic elevations in systemic BCAA levels, as seen in obesity [ 86 ], impair transport of these amino acids from the intestinal lumen into the systemic circulation, thereby contributing to persistent increased amino acid catabolism in the lumen and more SCFA formation.…”

Blood Transcriptomic Markers in Patients with Late-Onset Major Depressive Disorder

“…Furthermore, a selective serotonin reuptake inhibitor, sertraline, inhibits SLC36A1 activity [ 58 ]. In addition, the SLC36A1 mRNA level is increased in the jejunum of high fat diet-fed mice [ 59 ], and the transcriptional activity of SLC36A1 is up-regulated by insulin in skeletal muscle cells [ 60 ].…”