ArticleFrontiers in physiology2021
The Insulin-Sensitizer Pioglitazone Remodels Adipose Tissue Phospholipids in Humans.
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.
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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.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Clinical efficacy of liraglutide combined with pioglitazone in obese polycystic ovary syndrome and its effects on the serum chemerin/visfatin ratio.American journal of translational research · 2026Article
- Convergent Metabolic Pathways in MASH Therapeutics: An AMPK-Centric Analysis.Journal of cellular and molecular medicine · 2026Review
- Targeting adipose remodeling: Synergistic mechanisms of drugs and adipose-derived stem cells in obese type 2 diabetes mellitus.World journal of stem cells · 2025Review
- Changes in Apolipoprotein A1-Associated Proteomic Composition After Pioglitazone Treatment Versus Weight Loss.International journal of molecular sciences · 2025Article
- Preclinical Evaluation of 2-Aminobenzothiazole Derivatives: In Silico, In Vitro, and Preliminary In Vivo Studies as Diabetic Treatments and Their Complications.Molecules (Basel, Switzerland) · 2025Article
- 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 · 2025Article
- The Many Facets of PPAR-γ Agonism in Obesity and Associated Comorbidities: Benefits, Risks, Challenges, and Future Directions.Current obesity reports · 2025Review
- Zhuriheng pills improve adipose tissue dysfunction and inflammation by modulating PPARγ to stabilize atherosclerotic plaques.Frontiers in pharmacology · 2025Article
- Pioglitazone with SGLT2 inhibitors or GLP-1 receptor agonists in patients with type 2 diabetes and non-alcoholic fatty liver disease: could the combinations of an old friend with new players yield better outcomes?Archives of medical sciences. Atherosclerotic diseases · 2025Article
- Efficacy and Safety of Pioglitazone/Metformin Fixed-Dose Combination Versus Uptitrated Metformin in Patients with Type 2 Diabetes without Adequate Glycemic Control: A Randomized Clinical Trial.Diabetes therapy : research, treatment and education of diabetes and related disorders · 2024Article
- Sex-dependent adipose glucose partitioning by the mitochondrial pyruvate carrier.bioRxiv : the preprint server for biology · 2024Article
- Mechanisms of body fat distribution and gluteal-femoral fat protection against metabolic disorders.Frontiers in nutrition · 2024Review
- Therapeutic implications for sphingolipid metabolism in metabolic dysfunction-associated steatohepatitis.Frontiers in endocrinology · 2024Review
- Precision nutrition for targeting pathophysiology of cardiometabolic phenotypes.Reviews in endocrine & metabolic disorders · 2023Review
- Lipid remodeling of adipose tissue in metabolic health and disease.Experimental & molecular medicine · 2023Review
- Weight loss to disrupt type 2 diabetes.Diabetology international · 2023Review
- From an Apple to a Pear: Moving Fat around for Reversing Insulin Resistance.International journal of environmental research and public health · 2022Review
- Effects of Sustained Hyperglycemia on Skeletal Muscle Lipids in Healthy Subjects.The Journal of clinical endocrinology and metabolism · 2022Article
- Neuroprotective and Anti-inflammatory Effects of Pioglitazone on Traumatic Brain Injury.Mediators of inflammation · 2022Review
- Immunometabolic factors contributing to obesity-linked hepatocellular carcinoma.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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.
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What Socratic holds
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 Socratic graph.