Abstract
Type 2 diabetes (T2D) and Non-Alcoholic Fatty Liver Disease (NAFLD) are pathologies
whose prevalence continues to increase worldwide. Both diseases are precipitated by
an excessive caloric intake, which promotes insulin resistance and fatty liver. The
role of the intestine and its crosstalk with the liver in the development of these
metabolic diseases is receiving increasing attention. Alterations in diet-intestinal
microbiota interactions lead to the dysregulation of intestinal functions, resulting
in altered metabolite and energy substrate production and increased intestinal permeability.
Connected through the portal circulation, these changes in intestinal functions impact
the liver and other metabolic organs, such as visceral adipose tissue, hence participating
in the development of insulin resistance, and worsening T2D and NAFLD. Thus, targeting
the intestine may be an efficient therapeutic approach to cure T2D and NAFLD.
In this review, we will first introduce the signaling pathways linking T2D and NAFLD.
Next, we will address the role of the gut-liver crosstalk in the development of T2D
and NAFLD, with a particular focus on the gut microbiota and the molecular pathways
behind the increased intestinal permeability and inflammation. Finally, we will summarize
the therapeutic strategies which target the gut and its functions and are currently
used or under development to treat T2D and NAFLD.
Abbreviations:
ALT (alanine aminotransferase), BA (bile acids), CYP7A1 (cholesterol 7 alpha-hydroxylase), DDP-4 (dipeptidyl peptidase-4), FGF (fibroblast growth factor), FMT (fecal microbiota transplantation), FXR (farnesoid X receptor), GLP-1 (glucagon-like peptide-1), GLP-1R (glucagon-like peptide-1 receptor), HFD (high fat diet), HOMA-IR (homeostatic model assessment of insulin resistance), IgA (immunoglobulin A), IR (insulin resistance), JAM-A (junctional adhesion molecule A), LPS (lipopolysaccharide), MRI (magnetic resonance imaging), NAFL/NAFLD (non-alcoholic fatty liver/disease), NAS (non-alcoholic fatty liver disease activity score), NASH (non-alcoholic steatohepatitis), OCA (obeticholic acid), SCFA (short chain fatty acid), T2D (type 2 diabetes), TG (triglycerides), TGR5 (takeda g-protein-coupled receptor 5)Keywords
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Article info
Publication history
Published online: August 02, 2021
Accepted:
July 29,
2021
Received in revised form:
July 28,
2021
Received:
April 19,
2021
Identification
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© 2021 Elsevier Inc. All rights reserved.
