ArticleMolecular metabolism2015
Adipocyte SIRT1 knockout promotes PPARγ activity, adipogenesis and insulin sensitivity in chronic-HFD and obesity.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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Who cites it
97 citing papers in PubMed, 161 citations in OpenAlex.
- Vitamin D supplementation improves SIRT1, Irisin, and glucose indices in overweight or obese type 2 diabetic patients: a double-blind randomized placebo-controlled clinical trial.BMC family practice · 2020Trial
- Interplay of Ser273 Phosphorylation and K268 and K293 Acetylation in PPARγ: Implications for PPARγ Activation.Proteins · 2026Article
- The Ageing Adipose Paradox: Implications for Metabolic Health.Diabetes, obesity & metabolism · 2026Review
- SIRT1 Exon 2-Encoded IDR Gates CREB-Dependent Transcriptional Timing During Fasting.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- The Sirtuin Network: Linking NADDiabetes/metabolism research and reviews · 2026Review
- CD38 expression by neonatal human naive CD4+ T cells shapes their distinct metabolic and tolerogenic properties.The Journal of clinical investigation · 2026Article
- Dapagliflozin-intermittent fasting combination maximizes weight and metabolic regulation through AMPK/sirtuins/clock genes and gut microbiota signaling in high-fat diet-induced obesity: a novel anti-obesity approach.Cell & bioscience · 2026Article
- Obesity and Natural Products: Mechanisms, Therapeutic Potential, and Future Directions.Food science & nutrition · 2026Review
- Modulation of immune cells and metabolic reprogramming in efferocytosis.Cell death & disease · 2026Review
- RNA-based approaches in the diagnosis and treatment of obesity.Frontiers in pharmacology · 2026Review
- Lipin-1 Drives Browning of White Adipocytes via Promotion of Brown Phenotype Markers.Biomedicines · 2025Article
- Anti-Obesity Mechanisms of Plant and Fungal Polysaccharides: The Impact of Structural Diversity.Biomolecules · 2025Review
- Anti-Obesity Effects of Calcium Fructoborate by Inhibiting Adipogenesis and Increasing SIRT's Expression in 3T3-L1 Cells.Biological trace element research · 2025Article
- A novel deacetylase inhibitor KLX suppresses liver fibrosis by deacetylating PPARγ through promoting ubiquitination-mediated HDAC1 degradation.Science China. Life sciences · 2025Article
- Role of sirtuins in obesity and osteoporosis: molecular mechanisms and therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Unraveling the AMPK-SIRT1-FOXO Pathway: The In-Depth Analysis and Breakthrough Prospects of Oxidative Stress-Induced Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- Processed silkworm powder (Hongjam) ameliorates metabolic dysfunction-associated steatotic liver disease via GPR35/PKA and SIRT1/AMPK pathways.Frontiers in nutrition · 2025Article
- Therapeutic Targeting of PPARγ in Nonalcoholic Fatty Liver Disease: Efficacy, Safety, and Drug Development.Drug design, development and therapy · 2025Review
- Protein posttranslational modifications in metabolic diseases: basic concepts and targeted therapies.MedComm · 2024Review
- Sirt1: An Increasingly Interesting Molecule with a Potential Role in Bone Metabolism and Osteoporosis.Biomolecules · 2024Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
objectiveAdipose tissue is the primary site for lipid deposition that protects the organisms in cases of nutrient excess during obesogenic diets. The histone deacetylase Sirtuin 1 (SIRT1) inhibits adipocyte differentiation by targeting the transcription factor peroxisome proliferator activated-receptor gamma (PPARγ).
methodsTo assess the specific role of SIRT1 in adipocytes, we generated Sirt1 adipocyte-specific knockout mice (ATKO) driven by aP2 promoter onto C57BL/6 background. Sirt1 (flx/flx) aP2Cre (+) (ATKO) and Sirt1 (flx/flx) aP2Cre (-) (WT) mice were fed high-fat diet for 5 weeks (short-term) or 15 weeks (chronic-term). Metabolic studies were combined with gene expression analysis and phosphorylation/acetylation patterns in adipose tissue.
resultsOn standard chow, ATKO mice exhibit low-grade chronic inflammation in adipose tissue, along with glucose intolerance and insulin resistance compared with control fed mice. On short-term HFD, ATKO mice become more glucose intolerant, hyperinsulinemic, insulin resistant and display increased inflammation. During chronic HFD, WT mice developed a metabolic dysfunction, higher than ATKO mice, and thereby, knockout mice are more glucose tolerant, insulin sensitive and less inflamed relative to control mice. SIRT1 attenuates adipogenesis through PPARγ repressive acetylation and, in the ATKO mice adipocyte PPARγ was hyperacetylated. This high acetylation was associated with a decrease in Ser273-PPARγ phosphorylation. Dephosphorylated PPARγ is constitutively active and results in higher expression of genes associated with increased insulin sensitivity.
conclusionTogether, these data establish that SIRT1 downregulation in adipose tissue plays a previously unknown role in long-term inflammation resolution mediated by PPARγ activation. Therefore, in the context of obesity, the development of new therapeutics that activate PPARγ by targeting SIRT1 may provide novel approaches to the treatment of T2DM.
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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.