ArticleRedox biology2017
Combined metformin and insulin treatment reverses metabolically impaired omental adipogenesis and accumulation of 4-hydroxynonenal in obese diabetic patients.
Article in Redox biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 47 citations in OpenAlex.
- Impact of Lipid Oxidation Products on Inflammation and Insulin Resistance: A Focus on Mechanisms of Action.Cell biochemistry and biophysics · 2025Review
- New Perspectives on the Molecular Action of Metformin in the Context of Cellular Transduction and Adipogenesis.International journal of molecular sciences · 2025Review
- Scars of oxidative stress: protein carbonylation and beta cell dysfunction in diabetes.Frontiers in endocrinology · 2025Review
- Understanding the link between ALDH2 genotypes and diabetes.Frontiers in endocrinology · 2025Article
- Regional primary preadipocyte characteristics in humans with obesity and type 2 diabetes mellitus.Heliyon · 2024Review
- Accumulation of 4-Hydroxynonenal Characterizes Diabetic Fat and Modulates Adipogenic Differentiation of Adipose Precursor Cells.International journal of molecular sciences · 2023Article
- The 4-Hydroxynonenal-Protein Adducts and Their Biological Relevance: Are Some Proteins Preferred Targets?Antioxidants (Basel, Switzerland) · 2023Review
- Relationship between 4-Hydroxynonenal (4-HNE) as Systemic Biomarker of Lipid Peroxidation and Metabolomic Profiling of Patients with Prostate Cancer.Biomolecules · 2023Article
- Regulatory network of metformin on adipogenesis determined by combining high-throughput sequencing and GEO database.Adipocyte · 2022Article
- Influence of Protein Carbonylation on Human Adipose Tissue Dysfunction in Obesity and Insulin Resistance.Biomedicines · 2022Article
- Lipid Peroxidation in Obesity: Can Bariatric Surgery Help?Antioxidants (Basel, Switzerland) · 2022Review
- Adipose Tissue Plasticity in Response to Pathophysiological Cues: A Connecting Link between Obesity and Its Associated Comorbidities.International journal of molecular sciences · 2022Review
- Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity.Life (Basel, Switzerland) · 2022Article
- Evaluating Possible Mechanisms Linking Obesity to COVID-19: a Narrative Review.Obesity surgery · 2022Review
- Role of Inflammatory Cytokines, Growth Factors and Adipokines in Adipogenesis and Insulin Resistance.Inflammation · 2022Review
- Article
- Association of Lipid Peroxidation Product 4-Hydroxynonenal with Post-Traumatic Stress Disorder.Biomolecules · 2021Article
- Preliminary Findings on the Association of the Lipid Peroxidation Product 4-Hydroxynonenal with the Lethal Outcome of Aggressive COVID-19.Antioxidants (Basel, Switzerland) · 2021Article
- 4-Hydroxy-2-nonenal, a lipid peroxidation product, as a biomarker in diabetes and its complications: challenges and opportunities.Free radical research · 2021Review
- Proteomic Analysis of Cardiac Adaptation to Exercise by High Resolution Mass Spectrometry.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveObesity-associated impaired fat accumulation in the visceral adipose tissue can lead to ectopic fat deposition and increased risk of insulin resistance and type 2 diabetes mellitus (T2DM). This study investigated whether impaired adipogenesis of omental (OM) adipose tissues and elevated 4-hydroxynonenal (4-HNE) accumulation contribute to this process, and if combined metformin and insulin treatment in T2DM patients could rescue this phenotype.
methodsOM adipose tissues were obtained from forty clinically well characterized obese individuals during weight reduction surgery. Levels of 4-HNE protein adducts, adipocyte size and number of macrophages were determined within these tissues by immunohistochemistry. Adipogenic capacity and gene expression profiles were assessed in preadipocytes derived from these tissues in relation to insulin resistance and in response to 4-HNE, metformin or combined metformin and insulin treatment.
resultsPreadipocytes isolated from insulin resistant (IR) and T2DM individuals exhibited lower adipogenesis, marked by upregulation of anti-adipogenic genes, compared to preadipocytes derived from insulin sensitive (IS) individuals. Impaired adipogenesis was also associated with increased 4-HNE levels, smaller adipocytes and greater macrophage presence in the adipose tissues. Within the T2DM group, preadipocytes from combined metformin and insulin treated subset showed better in vitro adipogenesis compared to metformin alone, which was associated with less presence of macrophages and 4-HNE in the adipose tissues. Treatment of preadipocytes in vitro with 4-HNE reduced their adipogenesis and increased proliferation, even in the presence of metformin, which was partially rescued by the presence of insulin.
conclusionThis study reveals involvement of 4-HNE in the impaired OM adipogenesis-associated with insulin resistance and T2DM and provides a proof of concept that this impairment can be reversed by the synergistic action of insulin and metformin. Further studies are needed to evaluate involvement of 4-HNE in metabolically impaired abdominal adipogenesis and to confirm benefits of combined metformin-insulin therapy in T2DM patients.
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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.