Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity
Open accessAbstract
Aim/hypothesis Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice. In humans, potential links with obesity comorbidities are poorly defined. Here, we investigated adipose tissue senescent status and relationships with metabolic complications in human obesity.Methods The study includes a prospective cohort of 227 individuals with severe obesity. A photometric method was used to quantify senescence-associated β-galactosidase (SA-β-gal) activity in paired subcutaneous and omental adipose tissue biopsies obtained during gastric surgery. Gene and secretory profiling was performed in adipose tissue biopsies and in human primary pre-adipocytes in the presence or absence of senolytic drugs targeting senescent cells. Participants were phenotyped for anthropometric and bioclinical variables, metabolic complications and gastric surgery-induced improvement to address relationships with adipose tissue SA-β-gal.Results SA-β-gal activity was sevenfold higher in subcutaneous than in omental adipose tissue and not associated with BMI or chronological age. Several factors, including insulin-like growth factor binding protein 3 (IGFBP3), plasminogen activator inhibitor 1 (PAI1), C-C motif chemokine ligand 2 (CCL2) and IL-6, were upregulated in subcutaneous adipose tissue in relation with SA-β-gal (p for linear trend across tertiles <0.05) and in pre-adipocytes cultured with inflammatory macrophage conditioned media. Senolytic treatment reduced SA-β-gal staining and normalised these alterations. In the whole population, subcutaneous adipose tissue SA-β-gal activity was positively associated with serum leptin, markers of insulin resistance and increased trunk fat mass. Metabolic complications, including type 2 diabetes and dyslipidaemia, were more prevalent in patients with high levels of SA-β-gal, but improved with bariatric surgery whatever the initial adipose tissue senescent status.Conclusions/interpretation This study highlights a phenotype of senescence in adipose tissue of severely obese individuals, which characterises prominently subcutaneous fat depots. Subcutaneous adipose tissue senescence is significantly linked to altered glucose metabolism and body fat distribution. Elimination of senescent cells through senolytic treatment could alleviate metabolic complications in severely obese people. Graphical abstract.
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Treatment of human adipose tissue biopsies with dasatinib (1 μmol/L) and quercetin (20 μmol/L) decreased senescence-associated β-galactosidase activity in subcutaneous tissue and omental adipose tissue.
“A subset of human adipose tissue biopsies was then treated with a cocktail of dasatinib (1 µmol/L) and quercetin (20 µmol/L), which decreased senescenceassociated β-galactosidase activity in subcutaneous tissue and omental adipose tissue.45”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [45]
In a prospective cohort of 227 individuals with severe obesity, senescence-associated β-galactosidase activity was seven times higher in subcutaneous tissue than in omental adipose tissue and was correlated with altered glycaemic status; however, this activity was not associated with body-mass index or chronological age.
“Senescence-associated β-galactosidase activity was seven times higher in subcutaneous tissue than in omental adipose tissue and was correlated with altered glycaemic status; however, this activity was not associated with body-mass index or chronological age.”
From The costs and benefits of senotherapeutics for human health (2022) · cites this paper as [45]
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- Authors
- Rouault, C., Marcelin, G., Adriouch, S., Rose, C., Genser, L., Ambrosini, M., Bichet, J.-C., Zhang, Y., Marquet, F., Aron-Wisnewsky, J., Poitou, C., André, S., Dérumeaux, G., Guerre-Millo, M., & Clément, K.
- Affiliations
- Inserm (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- Corresponding author
- Clément, Karine
- ORCID
- Venue
- Diabetologia
- Published
- 2020-10-30
- Volume
- 64
- Issue
- 1
- Pages
- 240-254
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- OpenAlex
- W3096400192
- Cited by
- 95
- References
- 52
- Citations by year
- 2026: 18 · 2025: 13 · 2024: 17 · 2023: 25 · 2022: 13 · 2021: 9
- FWCI
- 8.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-15-RHUS-0003, ANR-17-CE14-0009, ANR-10, ANR-10-IAHU-05)
- Fondation pour la Recherche Médicale (DEQ20120323701)
- Conseil Régional, Île-de-France
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- adipose tissue senescence, morbid obesity, subcutaneous adipose tissue, omental adipose tissue, senolytics, insulin resistance, type 2 diabetes, truncal fat, glycemic status, leptin, adipose tissue secretome, bariatric surgery, dyslipidemia
- MeSH terms
- beta-Galactosidase, Biopsy, Blood Glucose, Body Composition, Female, Humans, Insulin Resistance, Male, Obesity, Morbid, Prospective Studies, Cohort Studies, Treatment Outcome, Cellular Senescence, Adipocytes, Bariatric Surgery, Subcutaneous Fat
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