Evidence map›Paper›PMID 28867301›Full record

ReviewCell metabolism2018

Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases.

Varman T Samuel, Gerald I Shulman

Registry-linked trialOpen access · bronzeAbstract readReview
In one paragraph

Review in Cell metabolism, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04898621 (The Effect of Dietary Fructose on Gut Microbiota and Hepatosteatosis in Healthy Men), which is not on this map. Cited by 409 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
409citing papers in PubMed, 2 pooled it
36.1field-weighted citation impact, top 1% of its field
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.

NCT04898621 nacompletednot on this mapstarted 2021, after this paper: background citation

The Effect of Dietary Fructose on Gut Microbiota and Hepatosteatosis in Healthy Men

TypeinterventionalSponsorShanghai Zhongshan HospitalRan2021 to 2022Enrolled58ConditionsHepatic Steatosis, Dietary Fructose ExposureArms75g fructose solution, 150g fructose solution
3 · Its place in the literature

Who cites it

409 citing papers in PubMed, 2 syntheses or guidelines pooled it, 708 citations in OpenAlex.

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349 more citing papers are in PubMed but not listed here.

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

2 authors at 2 institutions in 1 country.

Varman T SamuelDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Veterans Affairs Medical Center, West Haven, CT 06516, USA. Electronic address: varman.samuel@yale.edu.
Gerald I ShulmanDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510, USA; Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA; Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA. Electronic address: gerald.shulman@yale.edu.
Veterans Health Administration · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Diabetes Research CenterP30DK045735 · NIDDK · YALE UNIVERSITY · PI Richard A Flavell · 1993 to 2026
$44.0M
Mechanisms of Lipid-Induced Hepatic Insulin ResistanceR01DK040936 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 1989 to 2015
$5.1M
Effects of Hepatic Acetyl-CoA Carboxylase Inhibition on NAFLD and Hepatic Insulin ResistanceR01DK113984 · NIDDK · YALE UNIVERSITY · PI SHULMAN, GERALD I · 2017 to 2021
$3.7M
Cellular mechanisms for increased gluconeogenesis in type 2 diabetes mellitus: the role of lipid induced pyruvate carboxylase acetylation in increasing hepatic gluconeogenic capacity.I01BX000901 · VA · VA CONNECTICUT HEALTHCARE SYSTEM · PI SAMUEL, VARMAN T · 2012 to 2020
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BLRD VA I01 BX000901NCATS NIH HHS UL1 TR001863NIDDK NIH HHS P30 DK045735NIDDK NIH HHS R01 DK040936NIDDK NIH HHS R01 DK113984
6 · The paper itself

Abstract

NAFLD is closely linked with hepatic insulin resistance. Accumulation of hepatic diacylglycerol activates PKC-ε, impairing insulin receptor activation and insulin-stimulated glycogen synthesis. Peripheral insulin resistance indirectly influences hepatic glucose and lipid metabolism by increasing flux of substrates that promote lipogenesis (glucose and fatty acids) and gluconeogenesis (glycerol and fatty acid-derived acetyl-CoA, an allosteric activator of pyruvate carboxylase). Weight loss with diet or bariatric surgery effectively treats NAFLD, but drugs specifically approved for NAFLD are not available. Some new pharmacological strategies act broadly to alter energy balance or influence pathways that contribute to NAFLD (e.g., agonists for PPAR γ, PPAR α/δ, FXR and analogs for FGF-21, and GLP-1). Others specifically inhibit key enzymes involved in lipid synthesis (e.g., mitochondrial pyruvate carrier, acetyl-CoA carboxylase, stearoyl-CoA desaturase, and monoacyl- and diacyl-glycerol transferases). Finally, a novel class of liver-targeted mitochondrial uncoupling agents increases hepatocellular energy expenditure, reversing the metabolic and hepatic complications of NAFLD.

Indexed as

AnimalsGlucoseHumansInsulinInsulin ResistanceLipid MetabolismMetabolic DiseasesNon-alcoholic Fatty Liver DiseaseGlucoseInsulindiacylglycerolinsulin resistanceliver metabolismmitochondrianon-alcoholic fatty liver diseasenon-alcoholic steatohepatitistype 2 diabetes

Identifiers

PMID28867301
PMCPMC5762395
OpenAlexW2752428556

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

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.