Evidence map›Paper›PMID 40016916›Full record

ArticleExperimental physiology2025

Hydroxysteroid 17β-dehydrogenase 13 (Hsd17b13) knockdown attenuates liver steatosis in high-fat diet obese mice.

Shehroz Mahmood, Nicola Morrice, Dawn Thompson, Sara Milanizadeh, Sophie Wilson, Philip D Whitfield, George D Mcilroy, Justin J Rochford, Nimesh Mody

Abstract read
In one paragraph

Article in Experimental physiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

7 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shehroz MahmoodAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Nicola MorriceAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Dawn ThompsonAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Sara MilanizadehAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Sophie WilsonAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Philip D WhitfieldGlasgow Polyomics, University of Glasgow, Glasgow, UK.
George D McilroyAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Justin J RochfordAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.
Nimesh ModyAberdeen Cardiovascular & Diabetes Centre, School of Medicine, Medical Sciences & Nutrition , University of Aberdeen, Aberdeen, UK.

Funding

British Heart Foundation PG16/90/32518James Mearns Trust PhD studentshipUniversity of Aberdeen CGEBM PhD studentshipWellcome TrustWellcome Trust ISSF international partnership awardWellcome Trust ISSF small project
6 · The paper itself

Abstract

Hydroxysteroid 17β-dehydrogenase 13 (HSD17B13) loss-of-function gene variants are associated with a decreased risk of metabolic dysfunction-associated steatotic liver disease (MASLD). Our RNA-seq analysis of steatotic liver from obese mice ± fenretinide treatment identified major beneficial effects of fenretinide on expression of hepatic genes including Hsd17b13. We sought to determine the relationship between Hsd17b13 expression and MASLD and to validate it as a therapeutic target by liver-specific knockdown. Hsd17b13 expression, which is unique to hepatocytes and associated with the lipid droplet, was elevated in multiple models of MASLD and normalised with the prevention of obesity and steatotic liver. Direct, liver-specific, shRNA-mediated knockdown of Hsd17b13 (shHsd17b13) in high-fat diet (HFD)-obese mice, markedly improved hepatic steatosis with no effect on body weight, adiposity or glycaemia. shHsd17b13 decreased elevated serum alanine aminotransferase (ALT), serum fibroblast growth factor 21 (FGF21) levels, and markers of liver fibrosis, for example, expression of Timp2. shHsd17b13 knockdown in HFD-obese mice and Hsd17b13 overexpression in cells reciprocally regulated expression of lipid metabolism genes, for example, Cd36. Global lipidomic analysis of liver tissue revealed a major decrease in diacylglycerols (e.g. DAG 34:3) with shHsd17b13 expression and an increase in phosphatidylcholines containing polyunsaturated fatty acids (PUFA) for example, phosphatidylcholine (PC) 34:3 and PC 42:10. Expression of key genes involved in phospholipid and PUFA metabolism, for example, Cept1, was also reciprocally regulated suggesting a potential mechanism of Hsd17b13 biological function and role in MASLD. In conclusion, Hsd17b13 knockdown in HFD-obese adult mice was able to alleviate MASLD via regulation of fatty acid and phospholipid metabolism, thereby confirming HSD17B13 as a genuine therapeutic target for MASLD and the development of liver fibrosis.

Indexed as

17-Hydroxysteroid DehydrogenasesFatty LiverAlanine TransaminaseAnimalsDiet, High-FatFatty AcidsFibroblast Growth FactorsGene Knockdown TechniquesLiverLoss of Function MutationMaleMiceMice, Inbred C57BLMice, ObesePhosphatidylcholinesPhospholipids17beta-hydroxysteroid dehydrogenase type 13, mouse17-Hydroxysteroid DehydrogenasesAlanine TransaminaseFatty Acidsfibroblast growth factor 21Fibroblast Growth FactorsPhosphatidylcholinesPhospholipidsfenretinidefibrosishydroxysteroid 17β‐dehydrogenase 13 (Hsd17b13)metabolic dysfunction‐associated steatotic liver disease (MASLD)phospholipids

Identifiers

PMID40016916
PMCPMC12314643

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.