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Review
. 2022 Jan 7:8:824776.
doi: 10.3389/fmolb.2021.824776. eCollection 2021.

HSD17B13: A Potential Therapeutic Target for NAFLD

Hai-Bo Zhang  1 , Wen Su  2 , Hu Xu  1 , Xiao-Yan Zhang  3 , You-Fei Guan  1
Affiliations
Review

HSD17B13: A Potential Therapeutic Target for NAFLD

Hai-Bo Zhang et al. Front Mol Biosci. .

Abstract

Nonalcoholic fatty liver disease (NAFLD), especially in its inflammatory form (steatohepatitis, NASH), is closely related to the pathogenesis of chronic liver disease. Despite substantial advances in the management of NAFLD/NASH in recent years, there are currently no efficacious therapies for its treatment. The biogenesis and expansion of lipid droplets (LDs) are critical pathophysiological processes in the development of NAFLD/NASH. In the past decade, increasing evidence has demonstrated that lipid droplet-associated proteins may represent potential therapeutic targets for the treatment of NAFLD/NASH given the critical role they play in regulating the biogenesis and metabolism of lipid droplets. Recently, HSD17B13, a newly identified liver-enriched, hepatocyte-specific, lipid droplet-associated protein, has been reported to be strongly associated with the development and progression of NAFLD/NASH in both mice and humans. Notably, human genetic studies have repeatedly reported a robust association of HSD17B13 single nucleotide polymorphisms (SNPs) with the occurrence and severity of NAFLD/NASH and other chronic liver diseases (CLDs). Here we briefly overview the discovery, tissue distribution, and subcellular localization of HSD17B13 and highlight its important role in promoting the pathogenesis of NAFLD/NASH in both experimental animal models and patients. We also discuss the potential of HSD17B13 as a promising target for the development of novel therapeutic agents for NAFLD/NASH.

Keywords: 17β-HSD13; NASH; SNPs; hepatocarcinoma; lipid droplet.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram of human HSD17B13 splice variants. Human hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) is located at chromosome 4q22.1 with 8 exons and encodes 9 different protein isoforms (HSD17B13 isoform A-H). The exons were boxed and the introns were shown as broken black lines. The newly identified exon 4 was boxed in blue. In isoform F, the C-terminal 52 amino acids (aa233-284) were encoded by the exon 7 and a part of intron 7 sequence (nt12665-13502). The asterisks indicated the position of A insertion from rs72613567 in human HSD17B13 gene. The genetic variant rs72613567 T/T gives rise to a wild type protein, while the variant rs72613567:TA results in a truncated loss-of-function of HSD17B13 protein.
FIGURE 2
FIGURE 2
Distribution of human and mouse HSD17B13 protein in liver cells. (A) Single cell RNA-sequencing (scRNA-seq) analysis showing that human HSD17B13 is mainly expressed in the hepatocytes. (B) Liver cell scRNA-seq analysis demonstrating that mouse HSD17B13 mRNA is highly abundant in the hepatocyte. (C) Two protein isoforms of mouse HSD17B13 (A8Y5N4, Q8VCR2) is abundantly expressed in the zone 1 of the liver.
See this image and copyright information in PMC

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