Abstract
It has recently been found that B cell activating factor (BAFF) plays an important role in the regulation of energy homeostasis. We also have previously reported that BAFF deficiency reverses high-fat (HF) diet-induced glucose intolerance by potentiating adipose tissue function. In the present study, we found that BAFF deficient (BAFF-/-) mice exhibit gender-specific differences in protection against diet-induced glucose intolerance, and aimed to characterize the gender-dependent molecular alterations in energy metabolism. Under HF feeding conditions, serum BAFF level of female wild-type (WT) mice was considerably higher than that of male mice. Despite increased body weight gain, both male and female BAFF-/- mice showed significantly improved glucose tolerance compared to their WT counterparts. Expressions of genes involved in glucose transport, thermogenesis and lipid oxidation were up-regulated in brown adipose tissues of both male and female BAFF-/- mice. Interestingly, the expression of thermogenic genes in subcutaneous adipose tissue was significantly enhanced in female BAFF-/- compared to WT mice, but the difference was not observed between male BAFF-/- and WT mice. The enhanced thermogenic program was confirmed by higher protein levels of UCP1 and irisin in female BAFF-/- than in WT mice. Additionally, adiponectin production in white adipose tissues and AMPK phosphorylation in subcutaneous adipose tissue were also significantly elevated in female BAFF-/- compared to WT mice, but not in male BAFF-/- mice. Our findings define a comprehensive scenario for the enhancing effect of BAFF depletion on glucose tolerance wherein the underlying mechanism is, at least in part, gender-specific, and suggest that gender difference should be considered as an important factor in the use of BAFF blockade as a therapeutic approach for the prevention and treatment of type 2 diabetes.
Highlights
B-cell-activating factor (BAFF) is a tumor necrosis factor ligand family protein which promotes B-cell survival and development, which is a ligand for receptors including BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI) [1]
We reported that insulin resistance in BAFF knockout (BAFF-/-) male mice was significantly improved in spite of diet-induced weight gain, which was found to be due to up-regulated metabolic functions of brown and white adipose tissues mediated by fibroblast growth factor 21 (FGF21) and leptin [6]
Since BAFF is known to be expressed by immune cells as well as adipocytes, BAFF mRNA expression level was measured in various tissues including the spleen, liver, skeletal muscle, and several adipose tissues
Summary
B-cell-activating factor (BAFF) is a tumor necrosis factor ligand family protein which promotes B-cell survival and development, which is a ligand for receptors including BAFF receptor (BAFF-R), B-cell maturation antigen (BCMA), and transmembrane activator and CAML interactor (TACI) [1]. It has been reported that BAFF and its receptors act as trophic factors in lymphocyte malignancies and immune-related disorders, such as systemic lupus erythematosus (SLE), Sjögren’s syndrome, and rheumatoid arthritis (RA), which are characterized by the production of pathogenic autoantibodies against certain nuclear antigens and DNA [7,8,9]. These autoimmune diseases exhibit a strong sex bias in patients and mouse models in common: SLE develops at a female-to-male ratio of 9:1, Sjögren’s syndrome at a ratio of 9–15:1, and RA at a ratio of 3:1 [10,11]. Based on these findings of recent studies, we hypothesized that BAFF expression could be associated with a gender-specific insulin sensitization in BAFF depleted mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
