B Cell‐Activating Factor Controls the Production of Adipokines and Induces Insulin Resistance

Abstract

Visceral adipose tissue (VAT) inflammation has been linked to the pathogenesis of insulin resistance and metabolic syndrome. VAT has recently been established as a new component of the immune system and is involved in the production of various adipokines and cytokines. These molecules contribute to inducing and accelerating systemic insulin resistance. In this report, we investigated the role of B cell‐activating factor (BAFF) in the induction of insulin resistance. We investigated BAFF levels in the sera and VAT of obese mice. In obese mice, the BAFF levels were preferentially increased in VAT and sera compared to these levels in normal control mice. Next, we treated mice with BAFF to analyze its influence on insulin sensitivity. BAFF impaired insulin sensitivity in normal mice. Finally, we investigated the mechanisms underlying insulin resistance induced by BAFF in adipocytes. BAFF also induced alterations in the expression levels of genes related to insulin resistance in adipocytes. In addition, BAFF directly affected the glucose uptake and phosphorylation of insulin receptor substrate‐1 in adipocytes. We propose that autocrine or paracrine BAFF and BAFF‐receptor (BAFF‐R) interaction in VAT leads to impaired insulin sensitivity via inhibition of insulin signaling pathways and alterations in adipokine production.

Blockade of B-cell-activating factor signaling enhances hepatic steatosis induced by a high-fat diet and improves insulin sensitivity

“…11VATs in high-fat diet (HFD)-fed mice. 13 We also found that in these mice, BAFF-R was preferentially expressed in the VATs and liver, 13 in addition to B cells and plasma cells. Furthermore, we found that NASH patients have higher serum BAFF levels than simple steatosis patients.…”

“…The HFD group was fed an HFD (60% fat, 20% protein, and 20% carbohydrates; 520 kcal/100 g; D12492; Research Diets, New Brunswick, NJ, USA), as described previously. 13 All animals received humane care, and the study protocols complied with the guidelines of Ehime University.…”

“…13 Whole-cell lysates were sonicated, boiled at 95 1C for 5 min, and chilled on ice for 10 min. The protein concentration of the lysates was measured using the DC protein assay kit (Bio-Rad, Hercules, CA, USA).…”

The Answer to Why Some Are Obese but Healthy?!

“…WAT has a role in the regulation of whole-body energy metabolism and its endocrine function has a critical role in the development of obesity and its metabolic and cardiovascular complications by secreting cytokines/adipokines in distorted proportions. In obese individuals, monocyte and B and T lymphocyte infiltration into the adipose tissue results in low-grade inflammatory state associated with a rise in circulating C-reactive protein (CRP) which could be used as a marker for the development of type 2 diabetes mellitus (T2DM) and insulin resistance (IR) [2][3][4]. However, it should be noted that obesity itself will not lead to the development of IR but, the adipose tissue inflammatory condition is the culprit in metabolic disorders of humans [2].…”

“…In obese individuals, monocyte and B and T lymphocyte infiltration into the adipose tissue results in low-grade inflammatory state associated with a rise in circulating C-reactive protein (CRP) which could be used as a marker for the development of type 2 diabetes mellitus (T2DM) and insulin resistance (IR) [2][3][4]. However, it should be noted that obesity itself will not lead to the development of IR but, the adipose tissue inflammatory condition is the culprit in metabolic disorders of humans [2]. This fact is further supported by a study on metabolically normal obese postmenopausal women who had exhibited lower CRP and alpha-1 antitrypsin levels suggesting a protective role of these inflammatory markers against cardiometabolic risks [5].…”