Evidence map›Paper›PMID 42508572›Full record

ArticleJournal of lipid research2026

Intestinal lipase inhibition uncouples diet-induced obesity from MASH by remodeling the hepatic lipidome in mice.

Alvin P Chan, Tomasz J Czernuszewicz, Rochelle W Lai, Kelsey E Jarrett, Andrew Lau, Anisa Warshan, Angela S Cheng, Michelle E Steel, Heidi M Schmidt, Jakeline Larios and 14 more

Abstract read
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In one paragraph

Article in Journal of lipid research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

24 authors.

Alvin P ChanDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Division of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, Mattel Children's Hospital, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Tomasz J CzernuszewiczRevvity, Inc., Waltham, MA, USA.
Rochelle W LaiDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Kelsey E JarrettDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Andrew LauDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Anisa WarshanDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Angela S ChengDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Michelle E SteelDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Heidi M SchmidtDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Jakeline LariosDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Isaiah LittleDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Gabriella E RubertDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Madelaine C Brearley-SholtoDepartment of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Zeinab MamoueiRevvity, Inc., Waltham, MA, USA.
Jessica K PesnerRevvity, Inc., Waltham, MA, USA.
Christopher D HamadDepartment of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Kevin P FrancisDepartment of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Nicholas M BernthalDepartment of Orthopedic Surgery, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Elizabeth F RedenteDepartment of Pediatrics, National Jewish Health, Denver, CO, USA.
Clara E MagyarTranslational Pathology Core Laboratory, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Samual W FrenchTranslational Pathology Core Laboratory, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Kevin J WilliamsUCLA Lipidomics Core Laboratory, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Elizabeth J TarlingDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles (UCLA), Los Angeles, CA, USA.
Thomas Q de Aguiar VallimDivision of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Molecular Biology Institute, University of California, Los Angeles (UCLA), Los Angeles, CA, USA; Jonsson Comprehensive Cancer Center (JCCC), University of California, Los Angeles (UCLA), Los Angeles, CA, USA. Electronic address: tvallim@mednet.ucla.edu.

Funding

UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
GASTROENTEROLOGYT32DK007180 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI JENSEN, DENNIS MICHAEL · 1986 to 2025
$10.0M
Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
The impact of estrogen receptor alpha on cardiomyocellular metabolism and healthU54HL170326 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Karen Reue · 2023 to 2026
$7.5M
Vascular Biology Training GrantT32HL069766 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LUSIS, ALDONS JAKE · 2002 to 2022
$7.4M
Regenerative Musculoskeletal Medicine Training ProgramT32AR059033 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI John S Adams, Nicholas M. Bernthal · 2011 to 2026
$4.8M
Targeting the gut-liver axis in cardiovascular diseaseR01HL163908 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Elizabeth Joanna Tarling, Thomas A Vallim · 2023 to 2026
$2.9M
Post-transcriptional regulation of LDLRR01HL174008 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Elizabeth Joanna Tarling, Thomas A Vallim · 2024 to 2026
$2.5M
ATP Binding Cassette Transporters in Health and DiseaseR01DK128952 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TARLING, ELIZABETH JOANNA, VALLIM, THOMAS A · 2021 to 2024
$2.4M
Bile acid-mediated control of lipid absorption and fatty liver diseaseR01DK138340 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Thomas A Vallim · 2024 to 2026
$1.9M
UCLA Child Health Research Career Development AwardK12HD111040 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Sherin U Devaskar, Shafali Spurling Jeste · 2023 to 2026
$1.2M
Role of Bile Acids in Time-Restricted FeedingK08DK146180 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Alvin P Chan · 2026 to 2026
$171k
NCATS NIH HHS UL1 TR001881NHGRI NIH HHS T32 HG002536NHLBI NIH HHS R01 HL163908NHLBI NIH HHS R01 HL174008NHLBI NIH HHS T32 HL069766NHLBI NIH HHS U54 HL170326NIAMS NIH HHS T32 AR059033NICHD NIH HHS K12 HD111040NIDDK NIH HHS K08 DK146180NIDDK NIH HHS R01 DK128952NIDDK NIH HHS R01 DK138340NIDDK NIH HHS T32 DK007180
6 · The paper itself

Abstract

Dietary fatty acids exert distinct effects on hepatic metabolism. Intestinal lipase inhibition, used clinically for obesity, promotes weight loss by reducing dietary fat absorption, yet its impact on hepatic lipid metabolism in metabolic dysfunction-associated steatohepatitis (MASH) remains poorly defined. Here, we examined the metabolic consequences of lipase inhibition on fatty acid absorption in MASH. To induce MASH, C57BL/6J mice were fed the high-fat Gubra-Amylin NASH diet with or without the lipase inhibitor orlistat for 32 weeks. Orlistat protected against diet-induced obesity by promoting fat malabsorption, but failed to prevent the progression of hepatomegaly, steatosis, and fibrosis across longitudinal ultrasound imaging, biochemical assessments, and endpoint histology. Despite limiting weight gain, orlistat unexpectedly exacerbated hepatic inflammation. Lipidomic analyses revealed that the indiscriminate inhibition of fatty acid absorption by orlistat depleted the liver of essential PUFAs while increasing saturated fatty acids. This shift was associated with increased hepatic lipogenesis and proinflammatory signaling, preventing protection from MASH. In summary, lipase inhibition of intestinal fat absorption uncouples obesity from liver disease progression by reshaping the hepatic lipidome. These findings underscore the importance of dietary fat and hepatic lipid composition as key drivers of MASH pathogenesis.

Indexed as

Diet, High-FatFatty LiverIntestinesLipaseLipid MetabolismLiverObesityAnimalsLipidomicsMaleMiceMice, Inbred C57BLOrlistatLipaseOrlistatabsorptioncholesteroldietary fatdigestivelipaselipidomicsliverpolyunsaturated fatty acidshear wave elastographyultrasound

Identifiers

PMID42508572
PMCPMC13521235

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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.