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
Affiliations
Nir Goldstein
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Yarden Kezerle
Institute of Pathology, Soroka University Medical Center Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
Yftach Gepner
Department of Epidemiology and Preventive Medicine, School of Public Health, Sackler Faculty of Medicine and Sylvan Adams Sports Institute Tel Aviv University, Tel-Aviv 6997801, Israel
Yulia Haim
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Tal Pecht
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Roi Gazit
The Shraga Segal Department of Microbiology Immunology and Genetics Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
Vera Polischuk
Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
Idit F. Liberty
Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
Boris Kirshtein
Soroka University Medical Center and Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
Ruthy Shaco-Levy
Institute of Pathology, Soroka University Medical Center Ben-Gurion University of the Negev, Beer-Sheva 84101, Israel
Matthias Blüher
Department of Medicine, University of Leipzig, 04103 Leipzig, Germany
Assaf Rudich
Department of Clinical Biochemistry and Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel
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.
