Human subcutaneous white adipose tissue (SC 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. Here 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. IL4 and, unexpectedly, the mast cell marker CPA3 predicted UCP1 gene expression. We therefore investigated the effects of mast cells on UCP1 induction by adipocytes. TIB64 mast cells responded to cold by releasing histamine and IL4, 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. Consistent with this, the histamine receptor antagonist chlorpheniramine potently inhibited adipocyte UCP1 mRNA induction by mast cell conditioned medium. 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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1057/-/DC1.
- Received August 30, 2016.
- Accepted February 23, 2017.
- © 2017 by the American Diabetes Association.