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Review
. 2021 Feb 1;17(1):29-32.
doi: 10.1002/cld.1062. eCollection 2021 Jan.

Insights Into Metabolic Mechanisms and Their Application in the Treatment of NASH

Phillip J White  1 , Manal F Abdelmalek  2
Affiliations
Review

Insights Into Metabolic Mechanisms and Their Application in the Treatment of NASH

Phillip J White et al. Clin Liver Dis (Hoboken). .

Abstract

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Figures

FIG 1
FIG 1
Hepatic lipid metabolism in NAFLD. Storage of fat in hepatic lipid vesicles is determined by balance of acyl‐CoA generated by DNL, undergoing β‐oxidation in the mitochondria, exported as TGs in VLDL, and arriving from adipose tissue TG hydrolysis. Inhibition of ACC enhances fatty acid β‐oxidation and reduces DNL but increases VLDL excretion by activating SREBP1c. Fibrate drugs decrease TGs by enhancing fatty acid oxidation in the liver. Insulin‐sensitizing agents lower lipid release from adipose tissue.
FIG 2
FIG 2
Schematic depicting novel mechanisms regulating NAFLD. Activation of hepatic ChREBP by glucose or fructose induces the expression of the lipogenic program and BDK, which results in activating phosphorylation of ACL, which enhances DNL. Expression of the common variant I148M form of PNPLA3 competitively inhibits ATGL activation by ABHD5 on the lipid droplet leading to lipid droplet expansion. Inhibition of PNPLA3 permits ATGL activation by ABHD5 and promotes TG hydrolysis and fatty acid oxidation.
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