Mast cells promote seasonal white adipose beiging in humans

Brian S. Finlin, Beibei Zhu, Amy L. Confides, Philip M. Westgate, Brianna D. Harfmann, Esther E. Dupont-Versteegden, Philip A. Kern

Research output: Contribution to journalArticlepeer-review

49 Scopus citations

Abstract

Human subcutaneous (SC) white adipose tissue (WAT) increases the expression of beige adipocyte genes in the winter. Studies in rodents suggest that a number of immune mediators are important in the beiging response. We studied the seasonal beiging response in SC WAT from lean humans. We measured the gene expression of various immune cell markers and performed multivariate analysis of the gene expression data to identify genes that predict UCP1. Interleukin (IL)-4 and, unexpectedly, the mast cell marker CPA3 predicted UCP1 gene expression. Therefore, we investigated the effects of mast cells on UCP1 induction by adipocytes. TIB64 mast cells responded to cold by releasing histamine and IL-4, and this medium stimulated UCP1 expression and lipolysis by 3T3-L1 adipocytes. Pharmacological block of mast cell degranulation potently inhibited histamine release by mast cells and inhibited adipocyte UCP1 mRNA induction by conditioned medium (CM). Consistently, the histamine receptor antagonist chlorpheniramine potently inhibited adipocyte UCP1 mRNA induction by mast cell CM. Together, these data show that mast cells sense colder temperatures, release factors that promote UCP1 expression, and are an important immune cell type in the beiging response of WAT.

Original languageEnglish
Pages (from-to)1237-1246
Number of pages10
JournalDiabetes
Volume66
Issue number5
DOIs
StatePublished - May 1 2017

Bibliographical note

Funding Information:
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (R01-DK-107646), National Center for Advancing Translational Sciences (UL1-TR-001998), National Institute of General Medical Sciences (P20-GM-103527-06), and National Center for Research Resources (P20-RR-021954).

Publisher Copyright:
© 2017 by the American Diabetes Association.

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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