Effect of a High-Fat Diet on the Small-Intestinal Environment and Mucosal Integrity in the Gut-Liver Axis

Abstract

Although high-fat diet (HFD)-related dysbiosis is involved in the development of steatohepatitis, its pathophysiology especially in the small intestine remains unclear. We comprehensively investigated not only the liver pathology but also the microbiome profile, mucosal integrity and luminal environment in the small intestine of mice with HFD-induced obesity. C57BL/6J mice were fed either a normal diet or an HFD, and their small-intestinal contents were subjected to microbial 16S rDNA analysis. Intestinal mucosal permeability was evaluated by FITC-dextran assay. The levels of bile acids in the small-intestinal contents were measured by liquid chromatography/mass spectrometry. The expression of tight junction molecules, antimicrobial peptides, lipopolysaccharide and macrophage marker F4/80 in the small intestine and/or liver was examined by real-time RT-PCR and immunohistochemistry. The abundance of Lactobacillus was markedly increased and that of Clostridium was drastically decreased in the small intestine of mice fed the HFD. The level of conjugated taurocholic acid was significantly increased and those of deconjugated cholic acid/secondary bile acids were conversely decreased in the small-intestinal contents. The expression of occludin, antimicrobial Reg IIIβ/γ and IL-22 was significantly decreased in the small intestine of HFD-fed mice, and the intestinal permeability was significantly accelerated. Infiltration of lipopolysaccharide was significantly increased in not only the small-intestinal mucosa but also the liver of HFD-fed mice, and fat drops were apparently accumulated in the liver. Pathophysiological alteration of the luminal environment in the small intestine resulting from a HFD is closely associated with minimal inflammation involving the gut-liver axis through disturbance of small-intestinal mucosal integrity.

Dietary Choline Mitigates High-Fat Diet-Impaired Chylomicrons Assembly via UPRer Modulated by perk DNA Methylation

“…The present study Indicated that HFD caused intestinal structural damage, as evidenced by the incremental villi height and muscular layer thickness, which is in agreement with other studies [ 1 , 45 ]. Then, not surprisingly, our present study also found that HFD caused excessive TG accumulation and intestinal lipid dysregulation, which was also confirmed by our previous studies [ 19 ].…”

Ameliorating Effects of TRIM67 against Intestinal Inflammation and Barrier Dysfunction Induced by High Fat Diet in Obese Mice

“…Moreover, this study revealed that TRIM67 knockout mice showed pathological damage in the ileum and colon and a decline in goblet cell count, and that a HFD exacerbated this condition. Previous studies confirmed that a HFD causes intestinal injury [25,31], and an increase in goblet cell count [32]. The current study is in line with these studies, as we found intestinal injury due to a HFD; the effect is worsened in KO mice.…”

Weight cycling based on altered immune microenvironment as a result of metaflammation

“…In addition, recent research has linked specific microbial strains to weight loss. For instance, the abundance of Bifidobacterium in the gastrointestinal tract and eosinophilic Bifidobacterium in the mucous membrane is inversely associated with weight loss [ 47 ]. In addition, Firmicutes and actinomycetes produce conjugated linoleic acid, which promotes weight loss by increasing energy expenditure and metabolism, decreasing adipogenesis, promoting lipolysis, and inhibiting adipocyte death [ 48 ].…”