Higher Mast Cell Accumulation in Human Adipose Tissues Defines Clinically Favorable Obesity Sub-Phenotypes

Nir Goldstein, Yarden Kezerle, Yftach Gepner, Yulia Haim, Tal Pecht, Roi Gazit, Vera Polischuk, Idit F. Liberty, Boris Kirshtein, Ruthy Shaco-Levy, Matthias Blüher, Assaf Rudich

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The identification of human obesity sub-types may improve the clinical management of patients with obesity and uncover previously unrecognized obesity mechanisms. Here, we hypothesized that adipose tissue (AT) mast cells (MC) estimation could be a mark for human obesity sub-phenotyping beyond current clinical-based stratifications, both cross-sectionally and prospectively. We estimated MC accumulation using immunohistochemistry and gene expression in abdominal visceral AT (VAT) and subcutaneous (SAT) in a human cohort of 65 persons with obesity who underwent elective abdominal (mainly bariatric) surgery, and we validated key results in two clinically similar, independent cohorts (n = 33, n = 56). AT-MC were readily detectable by immunostaining for either c-kit or tryptase and by assessing the gene expression of KIT (KIT Proto-Oncogene, Receptor Tyrosine Kinase), TPSB2 (tryptase beta 2), and CMA1 (chymase 1). Participants were characterized as VAT-MClow if the expression of both CMA1 and TPSB2 was below the median. Higher expressers of MC genes (MChigh) were metabolically healthier (lower fasting glucose and glycated hemoglobin, with higher pancreatic beta cell reserve (HOMA-β), and lower triglycerides and alkaline-phosphatase) than people with low expression (MClow). Prospectively, higher MC accumulation in VAT or SAT obtained during surgery predicted greater postoperative weight-loss response to bariatric surgery. Jointly, high AT-MC accumulation may be used to clinically define obesity sub-phenotypes, which are associated with a "healthier" cardiometabolic risk profile and a better weight-loss response to bariatric surgery.

Original languageEnglish
Article number1497
JournalCells
Volume9
Issue number6
DOIs
StatePublished - 20 Jun 2020

Funding

FundersFunder number
Deutsche Forschungsgemeinschaft209933838 - SFB 1052

    Keywords

    • adipose tissue
    • bariatric surgery
    • mast cells
    • obesity
    • type 2 diabetes

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