Sleeve gastrectomy alters adipose tissue B cell biology through weight independent and dependent mechanisms
Renuka Subramaniam BVSc, PhD, James Luo MD, Tammy Lo MD, Brian Hou BS, Ali Tavakkoli MD, Eric G Sheu MD, PhD
Brigham and Women’s Hospital, Harvard Medical School, Boston, MA
Sleeve gastrectomy (SG) improves glucose homeostasis independent of weight loss. We have shown this improved glucose tolerance is characterized by increased glucose uptake in the visceral adipose tissue (VAT) and upregulation in adipose B lymphocyte chemotaxis and function. We hypothesize that SG induces changes in B cell function that mediate adipose tissue metabolic remodeling. This study characterizes weight dependent and independent impacts of SG on adipose B cell phenotype and function.
C57BL/6J mice fed normal chow (lean) or high fat diet (HFD) (n-7-8/group) underwent SG or sham surgery. B cell subsets in VAT were quantified by flow cytometry. Adipose total immune cells were stimulated with LPS, and IgM, IgG, IgE, IL-10, IL-6 and TNFα levels measured by ELISA. P<0.05 considered significant.
SG induced weight loss and improved glucose tolerance in HFD mice. In lean mice, glucose tolerance improved without changes in weight. Total adipose B cells significantly increased in lean and HFD mice following SG. SG significantly increased B2 cells in HFD mice but no effect on B cell subsets in lean mice. SG significantly increased natural IgM antibody secretion >8 fold in both mice. SG also significantly reduced IL-10 and TNF? secretion, and did not affect IL-6, IgG and IgE secretion in HFD mice.
SG increases adipose B cells and secretion of natural IgM independent of weight loss. Natural IgMs and anti-inflammatory B cells are known to improve insulin resistance. Therefore, changes in adipose B cell function likely contribute to diabetes resolution after SG.
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