ArticleMolecular metabolism2022
SERPINA3C ameliorates adipose tissue inflammation through the Cathepsin G/Integrin/AKT pathway.
Article in Molecular metabolism, 2022. 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, 42 citations in OpenAlex.
- Article
- Hepatic Sirt2-PARP1-HMGB1 axis promotes exercise-mediated amelioration of MASH in mice.Science China. Life sciences · 2026Article
- The Serpin Superfamily in Adipose Tissue Remodeling: Molecular Drivers of Immune-Metabolic Crosstalk and Insulin Sensitivity.Biology · 2026Review
- Cathepsins as Core Players in Obesity Pathogenesis: Emerging Therapeutic Targets.Biomolecules · 2026Review
- N6-methyladenosine (m6A) methylation in adipose tissue: role, regulation, and therapeutic potential.Cellular and molecular life sciences : CMLS · 2026Review
- Serpina3c protects against metabolic dysfunction-associated steatotic liver disease in offspring induced by prenatal prednisone exposure.Signal transduction and targeted therapy · 2026Article
- Proteomic Profiles of Seminal Plasma in Individuals with Secondary Infertility: Insights into the Involvement of Oxidative Stress.Journal of clinical medicine · 2026Article
- Serpina3c Mitigates Adipose Tissue Inflammation by Inhibiting the HIF1α-Mediated Endoplasmic Reticulum Overoxidation in Adipocytes.Diabetes & metabolism journal · 2026Article
- Exercise-regulated lipolysis: Its role and mechanism in health and diseases.Journal of advanced research · 2025Review
- Serpina3c deficiency promotes obesity-related hypertriglyceridemia and inflammation through activation of the Hif1α-glycolysis axis in adipose tissue.Clinical science (London, England : 1979) · 2025Article
- The TWIK2-mtDNA-NLRP3 inflammasome signaling in hepatic macrophages facilitates exercise-induced attenuation of hepatic inflammation and insulin resistance in db/db mice.Journal of physiology and biochemistry · 2025Article
- Exercise-induced anti-obesity effects in male mice generated by a FOXO1-KLF10 reinforcing loop promoting adipose lipolysis.Nature communications · 2025Article
- Chronic binge alcohol dysregulates omental adipose tissue extracellular matrix in simian immunodeficiency virus-infected macaques.Alcohol, clinical & experimental research · 2025Article
- SERPINA3: A Novel Therapeutic Target for Diabetes-Related Cognitive Impairment Identified Through Integrated Machine Learning and Molecular Docking Analysis.International journal of molecular sciences · 2025Article
- Exercise in Diabetic Cardiomyopathy: Its Protective Effects and Molecular Mechanism.International journal of molecular sciences · 2025Review
- SERPINA3C as a mediator of metabolic health in offspring.Nature metabolism · 2025Article
- Maternal exercise prevents metabolic disorders in offspring mice through SERPINA3C.Nature metabolism · 2025Article
- Exercise in atherosclerosis: its beneficial effects and underlying mechanism.Frontiers in cell and developmental biology · 2025Review
- Salusin‑α alleviates lipid metabolism disorders via regulation of the downstream lipogenesis genes through the LKB1/AMPK pathway.International journal of molecular medicine · 2024Article
- Proteomics and metabolomics analyses of urine for investigation of gallstone disease in a high-altitude area.Metabolomics : Official journal of the Metabolomic Society · 2024Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveDue to the increasing prevalence of obesity and insulin resistance, there is an urgent need for better treatment of obesity and its related metabolic disorders. This study aimed to elucidate the role of SERPINA3C, an adipocyte secreted protein, in obesity and related metabolic disorders.
methodsMale wild type (WT) and knockout (KO) mice were fed with high-fat diet (HFD) for 16 weeks, adiposity, insulin resistance, and inflammation were assessed. AAV-mediated overexpression of SERPINA3C was injected locally in inguinal white adipose tissue (iWAT) to examine the effect of SERPINA3C. In vitro analyses were conducted in 3T3-L1 adipocytes to explore the molecular pathways underlying the function of SERPINA3C.
resultsFunctional exploration of the SERPINA3C knockout mice revealed that SERPINA3C deficiency led to an impaired metabolic phenotype (more severe obesity, lower metabolic rates, worse glucose intolerance and insulin insensitivity), which was associated with anabatic inflammation and apoptosis of white adipose tissues. Consistent with these results, overexpression of SERPINA3C in inguinal adipose tissue protected mice against diet-induced obesity and metabolic disorders with less inflammation and apoptosis in adipose tissue. Mechanistically, SERPINA3C inhibited Cathepsin G activity, acting as a serine protease inhibitor, which blocked Cathepsin G-mediated turnover of α5/β1 Integrin protein. Then, the preserved integrity (increase) of α5/β1 Integrin signaling activated AKT to decrease JNK phosphorylation, thereby inhibiting inflammation and promoting insulin sensitivity in adipocytes. CONCLUSIONS/
interpretationThese findings demonstrate a previously unknown SERPINA3C/Cathepsin G/Integrin/AKT pathway in regulating adipose tissue inflammation, and suggest the therapeutic potential of targeting SERPINA3C/Cathepsin G axis in adipose tissue for the treatment of obesity and metabolic diseases.
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