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Gastric banding-associated weight loss diminishes hepatic Tsukushi expression
Cytokine ( IF 3.7 ) Pub Date : 2020-09-01 , DOI: 10.1016/j.cyto.2020.155114
Christoph Grander 1 , Nikolai Jaschke 1 , Barbara Enrich 1 , Felix Grabherr 1 , Lisa Mayr 1 , Julian Schwärzler 1 , Maria Effenberger 1 , Timon E Adolph 1 , Herbert Tilg 1
Affiliation  

Obesity has emerged as a substantial global healthcare issue that is frequently associated with insulin resistance and non-alcoholic fatty liver disease (NAFLD). Tsukushi (TSK), a liver-derived molecule, was recently identified as a major driver of NAFLD. Laparoscopic adjustable gastric banding (LAGB) has proven effective in reducing body weight and improving NAFLD. We therefore aimed to investigate the relation between LAGB-induced weight loss and TSK expression. Twenty-six obese patients undergoing LAGB were included in the study and metabolic parameters were assessed before (t0) and six months after LAGB (t6). The expression of TSK in liver and subcutaneous adipose tissue (AT) specimens was determined at both time points. To unravel regulatory mechanisms of TSK expression, human peripheral blood mononuclear cells (PBMCs) were stimulated with pro-inflammatory cytokines and TSK mRNA levels were analyzed by quantitative polymerase chain reaction. LAGB induced pronounced weight loss which was paralleled by amelioration of metabolic disturbances and histologically defined NAFLD. While hepatic TSK expression was markedly decreased after LAGB, adipose tissue TSK expression remained comparable to baseline. The decline in hepatic TSK expression after LAGB positively correlated with weight loss and the reduction in BMI, and negatively correlated with NAFLD activity score (NAS). In human PBMCs, pro-inflammatory cytokines such as IL-1β and TNFα induced the expression of TSK. In conclusion, LAGB-induced weight loss reduces hepatic TSK expression. Inhibiting TSK might represent a promising target for treating NAFLD in the future.

中文翻译:

胃束带相关的体重减轻减少了肝脏 Tsukushi 的表达

肥胖已成为一个重大的全球医疗保健问题,经常与胰岛素抵抗和非酒精性脂肪肝 (NAFLD) 相关。Tsukushi (TSK) 是一种肝脏衍生的分子,最近被确定为 NAFLD 的主要驱动因素。腹腔镜可调节胃束带 (LAGB) 已被证明可有效减轻体重和改善 NAFLD。因此,我们旨在研究 LAGB 诱导的体重减轻与 TSK 表达之间的关系。26 名接受 LAGB 的肥胖患者被纳入研究,并在 LAGB 之前(t0)和 6 个月后(t6)评估代谢参数。在两个时间点测定肝脏和皮下脂肪组织 (AT) 标本中 TSK 的表达。为了解开 TSK 表达的调控机制,用促炎细胞因子刺激人外周血单核细胞 (PBMC),并通过定量聚合酶链反应分析 TSK mRNA 水平。LAGB 诱导明显的体重减轻,同时代谢紊乱和组织学定义的 NAFLD 的改善。虽然 LAGB 后肝脏 TSK 表达显着降低,但脂肪组织 TSK 表达仍与基线相当。LAGB 后肝脏 TSK 表达的下降与体重减轻和 BMI 降低呈正相关,与 NAFLD 活动评分(NAS)呈负相关。在人 PBMC 中,促炎细胞因子如 IL-1β 和 TNFα 诱导 TSK 的表达。总之,LAGB 诱导的体重减轻降低了肝脏 TSK 的表达。抑制 TSK 可能是未来治疗 NAFLD 的一个有希望的目标。
更新日期:2020-09-01
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