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减肥手术引起的体重减轻对肝脏脂肪细胞因子表达的影响。

Effects of weight loss induced by bariatric surgery on hepatic adipocytokine expression.

作者信息

Moschen Alexander R, Molnar Clemens, Wolf Anna Maria, Weiss Helmut, Graziadei Ivo, Kaser Susanne, Ebenbichler Christoph F, Stadlmann Sylvia, Moser Patrizia L, Tilg Herbert

机构信息

Christian Doppler Research Laboratory for Gut Inflammation, Innsbruck Medical University, Anichstrasse 35, 6020 Innsbruck, Austria.

出版信息

J Hepatol. 2009 Oct;51(4):765-77. doi: 10.1016/j.jhep.2009.06.016. Epub 2009 Jul 5.

Abstract

BACKGROUND/AIMS: Adipocytokines play a key role in the pathophysiology of non-alcoholic fatty liver diseases (NAFLD). Whereas adiponectin has mainly anti-inflammatory functions, leptin, resistin and pre-B cell enhancing factor (PBEF)/Nampt/visfatin are considered as mainly pro-inflammatory mediators regulating metabolic and immune processes.

METHODS

We prospectively examined the effect of weight loss on systemic levels and/or hepatic expression of adiponectin/adiponectin receptors, leptin/leptin receptors, resistin and PBEF/Nampt/visfatin. Severely obese patients underwent laparoscopic adjustable gastric banding (LABG) and serum samples (n=30) were collected before, and after 6 and 12 months. Paired liver biopsies (before and 6 months after LABG) were obtained from 18 patients.

RESULTS

Bariatric surgery improved insulin resistance, abnormal liver function tests and liver histology. Pronounced weight loss after 6 and 12 months was accompanied by a significant increase in serum adiponectin levels whereas both leptin and PBEF/Nampt/visfatin levels decreased. Resistin serum levels increased after 6 months but fell below baseline values after 12 months. Liver mRNA expression of adiponectin increased slightly after 6 months whereas leptin mRNA expression did not change. Interestingly, weight loss resulted in a significant decrease of hepatic mRNA expression of resistin, PBEF/Nampt/visfatin and both leptin receptor isoforms while expression of type 1 and 2 adiponectin receptor was not affected. Liver immunohistochemistry performed on index and follow-up liver biopsies revealed an increase in adiponectin staining, showed no effect on resistin/leptin positivity, and demonstrated a decrease in PBEF/Nampt/visfatin immunoreactivity.

CONCLUSIONS

Weight loss after LABG surgery drives the adipocytokine milieu towards a more anti-inflammatory direction both systemically and in the liver.

摘要

背景/目的:脂肪细胞因子在非酒精性脂肪性肝病(NAFLD)的病理生理学中起关键作用。脂联素主要具有抗炎功能,而瘦素、抵抗素和前B细胞增强因子(PBEF)/烟酰胺磷酸核糖转移酶(Nampt)/内脂素则被视为主要的促炎介质,调节代谢和免疫过程。

方法

我们前瞻性地研究了体重减轻对脂联素/脂联素受体、瘦素/瘦素受体、抵抗素和PBEF/Nampt/内脂素的全身水平和/或肝脏表达的影响。重度肥胖患者接受腹腔镜可调节胃束带术(LABG),并在术前、术后6个月和12个月采集血清样本(n = 30)。从18例患者中获取配对的肝脏活检组织(LABG术前和术后6个月)。

结果

减肥手术改善了胰岛素抵抗、肝功能检查异常和肝脏组织学。6个月和12个月后显著的体重减轻伴随着血清脂联素水平的显著升高,而瘦素和PBEF/Nampt/内脂素水平降低。抵抗素血清水平在6个月后升高,但在12个月后降至基线值以下。脂联素的肝脏mRNA表达在6个月后略有增加,而瘦素mRNA表达没有变化。有趣的是,体重减轻导致抵抗素、PBEF/Nampt/内脂素和两种瘦素受体亚型的肝脏mRNA表达显著降低,而1型和2型脂联素受体的表达未受影响。对索引肝脏活检组织和随访肝脏活检组织进行的肝脏免疫组织化学显示脂联素染色增加,对抵抗素/瘦素阳性无影响,并显示PBEF/Nampt/内脂素免疫反应性降低。

结论

LABG手术后的体重减轻使脂肪细胞因子环境在全身和肝脏中朝着更具抗炎性的方向发展。

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