B-cell activating factor (BAFF) — a new factor linking immunity to diet?

2016

PLoS ONE

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.

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Section: Discussionmentioning

confidence: 99%

Gender-Specific Mechanisms Underlying the Amelioration of High-Fat Diet-Induced Glucose Intolerance in B-Cell-Activating Factor Deficient Mice

2016

PLoS ONE

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“…Recent studies have shown that mature adipocytes produce BAFF, which has been identified as an adipokine with metabolic effects [3][4][5]. The aim of this study was to elucidate the role of BAFF deficiency in metabolic regulation through exploring the molecular mechanism underlying the effect of BAFF depletion on improved glucose tolerance in HFD-fed BAFF -/-mice.…”

Section: Discussionmentioning

confidence: 99%

“…They also found that treatment with recombinant BAFF protein impaired insulin-mediated glucose uptake in 3T3-L1 adipocytes. BAFF plasma levels were significantly correlated with body fat and dietary composition in obese CentralEuropean Caucasian individuals [5], and the levels were also observed to be significantly higher in Japanese patients with nonalcoholic fatty liver disease [6].…”

Section: Introductionmentioning

confidence: 94%

B-cell-activating factor deficiency attenuates high-fat diet-induced glucose intolerance by potentiating adipose tissue function

Biochemical and Biophysical Research Communications

2015

“…Several studies have reported positive correlations between plasma BAFF level and metabolic diseases, such as insulin resistance and non-alcoholic fatty liver disease [ 3 , 4 , 5 , 6 , 7 ]. We also previously reported a protective effect of BAFF depletion against high-fat diet-induced glucose intolerance using BAFF −/− mice on a high-fat diet, which exhibited improved insulin sensitivity and potentiated adipose tissue function [ 18 ].…”

Section: Discussionmentioning

confidence: 99%

“…Although BAFF was originally identified as a secretory protein in immunocytes, recent studies have described that mature adipocytes also produce BAFF and its receptors, suggesting a role of BAFF in the regulation of energy metabolism [ 2 ]. It has recently been reported that a circulating BAFF level is positively correlated with body mass index in individuals with obesity [ 3 ], and patients with non-alcoholic fatty liver disease have increased levels of serum BAFF [ 4 ]. Several studies using mouse models also have shown a positive correlation between BAFF and energy metabolism dysregulation.…”

Section: Introductionmentioning

confidence: 99%

B-Cell-Activating Factor Depletion Ameliorates Aging-Dependent Insulin Resistance via Enhancement of Thermogenesis in Adipose Tissues

2020

IJMS