高脂饮食小鼠肝脏脂肪变性的发生取决于肝脏中是否存在支配肝脏的副交感神经胆碱能神经元。

IF 9.8 1区 生物学 Q1 Agricultural and Biological Sciences PLoS Biology Pub Date : 2024-10-22 eCollection Date: 2024-10-01 DOI:10.1371/journal.pbio.3002865
Jiyeon Hwang, Junichi Okada, Li Liu, Jeffrey E Pessin, Gary J Schwartz, Young-Hwan Jo
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引用次数: 0

摘要

肝脏脂质代谢受肝脏自主神经系统的调节,其中交感神经支配已被广泛研究,而副交感神经传出神经支配尽管具有潜在的重要性,但人们对其了解较少。在这项研究中,我们研究了在肥胖条件下,大脑与肝脏之间的交流中断对小鼠肝脏脂质代谢的影响。我们发现,一部分肝细胞和胆管细胞受到源自迷走神经背运动核的副交感神经终端的支配。通过删除支配肝脏的副交感神经胆碱能神经元来消除脑-肝轴,可防止肝脏脂肪变性,并促进腹股沟白色脂肪组织(ingWAT)褐变。失去支配肝脏的胆碱能神经元会增加肝脏 Cyp7b1 的表达和空腹血清胆汁酸水平。此外,敲除ingWAT中的G蛋白偶联胆汁酸受体1基因可逆转失去肝脏支配胆碱能神经元的有益影响,从而导致肝脏脂肪变性的再次出现。删除支配肝脏的胆碱能神经元对体重的影响很小,但却很显著,同时还增加了能量消耗。总之,这些数据表明,针对肝脏的副交感神经胆碱能神经支配是一种潜在的治疗方法,可促进肥胖症和糖尿病患者的肝脏脂质代谢。
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The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.

Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.

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来源期刊
PLoS Biology
PLoS Biology BIOCHEMISTRY & MOLECULAR BIOLOGY-BIOLOGY
CiteScore
15.40
自引率
2.00%
发文量
359
审稿时长
3-8 weeks
期刊介绍: PLOS Biology is the flagship journal of the Public Library of Science (PLOS) and focuses on publishing groundbreaking and relevant research in all areas of biological science. The journal features works at various scales, ranging from molecules to ecosystems, and also encourages interdisciplinary studies. PLOS Biology publishes articles that demonstrate exceptional significance, originality, and relevance, with a high standard of scientific rigor in methodology, reporting, and conclusions. The journal aims to advance science and serve the research community by transforming research communication to align with the research process. It offers evolving article types and policies that empower authors to share the complete story behind their scientific findings with a diverse global audience of researchers, educators, policymakers, patient advocacy groups, and the general public. PLOS Biology, along with other PLOS journals, is widely indexed by major services such as Crossref, Dimensions, DOAJ, Google Scholar, PubMed, PubMed Central, Scopus, and Web of Science. Additionally, PLOS Biology is indexed by various other services including AGRICOLA, Biological Abstracts, BIOSYS Previews, CABI CAB Abstracts, CABI Global Health, CAPES, CAS, CNKI, Embase, Journal Guide, MEDLINE, and Zoological Record, ensuring that the research content is easily accessible and discoverable by a wide range of audiences.
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