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.
The prevalence of thyroid dysfunction in relation to iodine intake was studied in adults (n = 1061) in five coastal areas of Japan that produce iodine-rich seaweed (kelp). The prevalence of hyperthyroidism (TSH < 0.15 mU/L) was similar in these areas, whereas that of hypothyroidism (TSH > 5.0 mU/L) varied from 0-9.7%. The relative frequency of above normal iodide concentration in the morning urine (> or = 75 mumol/L) [high urinary iodide (UI)] varied from 3.7%-30.3%. Together with previously reported results of a noncoastal city, the frequency of high UI correlated significantly with that of hypothyroidism with negative thyroid autoantibody (r = 0.829, n = 6, P < 0.05) but not with positive thyroid autoantibody (r = 0.278, NS) or with that of hyperthyroidism (r = 0.038, NS). Hypothyroidism was more prevalent in thyroid autoantibody-negative subjects with high UI (group II, 12.1%) than with normal UI (group I, 2.3%) (P < 0.001). The TSH [21.9(6.5-73.7)mU/L] (mean +/- SD) and thyroglobulin [288 (182-456) micrograms/L] levels in group II were significantly higher than the respective levels in group I [9.6(3.7-25.3)mU/L and 123 (38-399) micrograms/L] (P < 0.05). Free T4 of group II (9.9 +/- 3.9 pmol/L) was significantly lower than in group I (14.2 +/- 3.9 pmol/L) (P < 0.05). These results indicate that 1) the prevalence of hypothyroidism in iodine sufficient areas may be associated with the amount of iodine ingested; 2) hypothyroidism is more prevalent and marked in subjects consuming further excessive amounts of iodine; and 3) excessive intake of iodine should be considered an etiology of hypothyroidism in addition to chronic thyroiditis in these areas.
This study demonstrates an association between sleep duration and NAFLD onset. Short sleep duration reduced the risk of NAFLD onset in men. Correct recognition is important to prevent disease progression and further complications.
À mice fed a high-fat diet (HFD). Furthermore, the effect of BAFF on lipid metabolism in hepatocytes was analyzed in vitro. BAFF-R À / À mice showed improvements in HFD-induced obesity and insulin resistance. In addition, the number of B cells, levels of serum IgG, and inflammation of visceral fat were reduced in these mice. However, the expression of steatogenic genes and fatty acid deposition in the liver was higher in these mice than in control mice. BAFF was also found to downregulate the expression of steatogenesis genes and enhance steatosis in hepatocytes through BAFF-R. Collectively, these data indicated that, in addition to its known functions in inflammation and glucose metabolism, BAFF has a protective role in hepatic steatosis by regulating lipid metabolism in the liver.
Nonalcoholic steatohepatitis patients had higher levels of serum BAFF than patients with SS, and higher levels were associated with the presence of hepatocyte ballooning and advanced fibrosis. The serum BAFF level may be a useful tool for distinguishing NASH from SS.
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