Evidence mapPaperPMID 34925073Full record

ArticleFrontiers in physiology2021

The Insulin-Sensitizer Pioglitazone Remodels Adipose Tissue Phospholipids in Humans.

Juan P Palavicini, Alberto Chavez-Velazquez, Marcel Fourcaudot, Devjit Tripathy, Meixia Pan, Luke Norton, Ralph A DeFronzo, Christopher E Shannon

Open access · goldAbstract read
In one paragraph

Article in Frontiers in physiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
3.3field-weighted citation impact, top 7% 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

21 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
  5. Article
  6. Evaluation of exploratory fluid biomarkers from a phase 1 senolytic trial in mild Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
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  15. Review
  16. Weight loss to disrupt type 2 diabetes.Diabetology international · 2023
    Review
  17. From an Apple to a Pear: Moving Fat around for Reversing Insulin Resistance.International journal of environmental research and public health · 2022
    Review
  18. Effects of Sustained Hyperglycemia on Skeletal Muscle Lipids in Healthy Subjects.The Journal of clinical endocrinology and metabolism · 2022
    Article
  19. Review
  20. Review
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

8 authors at 1 institution in 1 country.

Juan P PalaviciniDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Alberto Chavez-VelazquezDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Marcel FourcaudotDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Devjit TripathyDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Meixia PanDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Luke NortonDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Ralph A DeFronzoDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
Christopher E ShannonDivision of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States.
The University of Texas Health Science Center at San Antonio · US

Funding

TRANSGENIC COREP30AG013319 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 1995 to 2025
$7.5M
San Antonio OAIC - Research Education Component (REC)P30AG044271 · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2025 to 2025
$1.3M
NIA NIH HHS P30 AG013319NIA NIH HHS P30 AG044271
6 · The paper itself

Abstract

The insulin-sensitizer pioglitazone exerts its cardiometabolic benefits in type 2 diabetes (T2D) through a redistribution of body fat, from ectopic and visceral areas to subcutaneous adipose depots. Whereas excessive weight gain and lipid storage in obesity promotes insulin resistance and chronic inflammation, the expansion of subcutaneous adipose by pioglitazone is associated with a reversal of these immunometabolic deficits. The precise events driving this beneficial remodeling of adipose tissue with pioglitazone remain unclear, and whether insulin-sensitizers alter the lipidomic composition of human adipose has not previously been investigated. Using shotgun lipidomics, we explored the molecular lipid responses in subcutaneous adipose tissue following 6months of pioglitazone treatment (45mg/day) in obese humans with T2D. Despite an expected increase in body weight following pioglitazone treatment, no robust effects were observed on the composition of storage lipids (i.e., triglycerides) or the content of lipotoxic lipid species (e.g., ceramides and diacylglycerides) in adipose tissue. Instead, pioglitazone caused a selective remodeling of the glycerophospholipid pool, characterized by a decrease in lipids enriched for arachidonic acid, such as plasmanylethanolamines and phosphatidylinositols. This contributed to a greater overall saturation and shortened chain length of fatty acyl groups within cell membrane lipids, changes that are consistent with the purported induction of adipogenesis by pioglitazone. The mechanism through which pioglitazone lowered adipose tissue arachidonic acid, a major modulator of inflammatory pathways, did not involve alterations in phospholipase gene expression but was associated with a reduction in its precursor linoleic acid, an effect that was also observed in skeletal muscle samples from the same subjects. These findings offer important insights into the biological mechanisms through which pioglitazone protects the immunometabolic health of adipocytes in the face of increased lipid storage.

Indexed as

adiposelipidomicsobesitypioglitazonetype 2 diabetes

Identifiers

PMID34925073
PMCPMC8674727
OpenAlexW3217600654

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.