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Review
. 2021 May;53(5):809-822.
doi: 10.1038/s12276-021-00614-x. Epub 2021 May 20.

The interaction between the gut microbiota and dietary carbohydrates in nonalcoholic fatty liver disease

Grace Park  1 , Sunhee Jung  1 , Kathryn E Wellen  2 , Cholsoon Jang  3
Affiliations
Review

The interaction between the gut microbiota and dietary carbohydrates in nonalcoholic fatty liver disease

Grace Park et al. Exp Mol Med. 2021 May.

Abstract

Imbalance between fat production and consumption causes various metabolic disorders. Nonalcoholic fatty liver disease (NAFLD), one such pathology, is characterized by abnormally increased fat synthesis and subsequent fat accumulation in hepatocytes1,2. While often comorbid with obesity and insulin resistance, this disease can also be found in lean individuals, suggesting specific metabolic dysfunction2. NAFLD has become one of the most prevalent liver diseases in adults worldwide, but its incidence in both children and adolescents has also markedly increased in developed nations3,4. Progression of this disease into nonalcoholic steatohepatitis (NASH), cirrhosis, liver failure, and hepatocellular carcinoma in combination with its widespread incidence thus makes NAFLD and its related pathologies a significant public health concern. Here, we review our understanding of the roles of dietary carbohydrates (glucose, fructose, and fibers) and the gut microbiota, which provides essential carbon sources for hepatic fat synthesis during the development of NAFLD.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1. ACLY- and ACSS2-mediated production of lipogenic acetyl-CoA for DNL.
Dietary carbohydrates, such as glucose and fructose, are absorbed by the small intestine and delivered to the liver via the portal circulation. Alternatively, fructose or fibers reach the colon and are catabolized by the gut microbiota, producing short-chain fatty acids, including acetate. In hepatocytes, glycolysis/fructolysis provides carbon sources for ACLY-mediated generation of cytosolic acetyl-CoA from cytosolic citrate. On the other hand, acetate provides carbon for ACSS2-mediated synthesis of cytosolic acetyl-CoA, especially in low-energy environments. Acetyl-CoA can also be used for histone acetylation in the nucleus. Cytosolic acetyl-CoA is used for DNL. Metabolites of glucose or fructose also act in a signaling capacity to turn on lipogenic transcription factors, such as SREBP-1c and ChREBP, a process that is further augmented by insulin signaling.
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