Evidence map›Paper›PMID 34219361›Full record

Trial reportLiver international : official journal of the International Association for the Study of the Liver2021

PPAR-γ-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH.

Amalia Gastaldelli, Silvia Sabatini, Fabrizia Carli, Melania Gaggini, Fernando Bril, Renata Belfort-DeAguiar, Vincenzo Positano, Diana Barb, Sushma Kadiyala, Stephen Harrison and 1 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Liver international : official journal of the International Association for the Study of the Liver, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 4 pooled it
11.0field-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.

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

60 citing papers in PubMed, 4 syntheses or guidelines pooled it, 91 citations in OpenAlex.

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  6. PPAR-γ-induced changes in visceral fat and adiponectin levels are associated with improvement of steatohepatitis in patients with NASH.Liver international : official journal of the International Association for the Study of the Liver · 2021
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  19. MASH: the nexus of metabolism, inflammation, and fibrosis.The Journal of clinical investigation · 2025
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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

11 authors at 7 institutions in 2 countries.

Amalia GastaldelliDiabetes Division, The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.ORCID 0000-0003-2594-1651
Silvia SabatiniInstitute of Clinical Physiology, National Research Council, CNR, Pisa, Italy.ORCID 0000-0003-3251-4412
Fabrizia CarliInstitute of Clinical Physiology, National Research Council, CNR, Pisa, Italy.ORCID 0000-0003-2540-1110
Melania GagginiInstitute of Clinical Physiology, National Research Council, CNR, Pisa, Italy.ORCID 0000-0002-6311-502X
Fernando BrilDivision of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.ORCID 0000-0001-5570-4396
Renata Belfort-DeAguiarDepartment of Internal Medicine and Endocrinology, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-4357-0447
Vincenzo PositanoFondazione Toscana Gabriele Monasterio, Pisa, Italy.ORCID 0000-0001-6955-9572
Diana BarbDivision of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.ORCID 0000-0001-5208-6828
Sushma KadiyalaDivision of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.
Stephen HarrisonPinnacle Clinical Research Group, San Antonio, TX, USA.ORCID 0000-0001-8285-2204
Kenneth CusiDivision of Endocrinology, Diabetes and Metabolism, University of Florida, Gainesville, FL, USA.ORCID 0000-0002-8629-418X
University of Florida · USIstituto di Fisiologia Clinica · ITFondazione Toscana Gabriele Monasterio · ITPinnacle Clinical Research · USThe University of Texas Health Science Center at San Antonio · USUniversity of Siena · ITYale University · US

Funding

ZOLEDRONATE VS AREDIA IN MULTIPLE MYELOMA/BREAST CANCER W /BONE DISORDERSM01RR001346 · NCRR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI ESCAMILLA, MICHAEL A · 1985 to 2008
$23.1M
6 · The paper itself

Abstract

BACKGROUND AND

aimsPeroxisome proliferator-activated receptor (PPAR)-γ agonists decrease hepatic/visceral fat (VF) and improve necroinflammation despite subcutaneous (SC) fat weight-gain. Understanding the impact of changes in VF, VF-to-SC fat distribution (VF/SC) and adiponectin (ADPN) levels in relation to histological improvement after weight-loss or pioglitazone is relevant as novel PPAR-γ agonists are being developed for treating non-alcoholic steatohepatitis (NASH).

methodsFifty-five patients with NASH received a -500 kcal/d hypocaloric diet and were randomized (double-blind) to pioglitazone (45 mg/d) or placebo for 6-months. Before and after treatment patients underwent a liver biopsy and measurement of hepatic/peripheral glucose fluxes, hepatic/adipose tissue-IR and, in 35 patients, hepatic and VF/SC-fat was measured by magnetic resonance spectroscopy/imaging. Data were examined by multivariable statistical analyses combined with machine-learning techniques (partial least square discriminant analysis [PLS-DA]).

resultsBoth pioglitazone (despite weight-gain) and placebo (if weight-loss) reduced steatosis but only pioglitazone ameliorated necroinflammation. Using machine-learning PLS-DA showed that the treatment differences induced by a PPAR-γ agonist vs placebo on metabolic variables and liver histology could be best explained by the increase in ADPN and a decrease in VF/SC, and to a lesser degree, improvement in oral glucose tolerance test-glucose concentrations and ALT. Decrease in steatosis and disease activity score (ballooning plus lobular inflammation) kept a close relationship with an increase in ADPN (r = -.71 and r = -.44, P < .007, respectively) and reduction in VF/SC fat (r = .41 and r = .37, P < .03 respectively).

conclusionsReduction in VF and improved VF/SC-distribution, combined with an increase in ADPN, mediate the histological benefits of PPAR-γ action, highlighting the central role of fat metabolism and its distribution on steatohepatitis disease activity in patients with NASH.

Indexed as

Insulin ResistanceNon-alcoholic Fatty Liver DiseaseThiazolidinedionesAdiponectinDiet, ReducingHumansHypoglycemic AgentsIntra-Abdominal FatLiverObesityPPAR gammaAdiponectinHypoglycemic AgentsPPAR gammaThiazolidinedionesadiponectinfatty liverinsulin resistanceNASHpioglitazonePPAR-ytype 2 diabetes mellitusvisceral fat

Identifiers

PMID34219361
PMCPMC9290929
OpenAlexW3181783841

What OpenQuestion holds

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Registered trials

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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.