Dataset Information

Bone Morphogenetic Protein-8B Expression is Induced in Steatotic Hepatocytes and Promotes Hepatic Steatosis and Inflammation In Vitro.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome. The bone morphogenetic protein-8B (BMP8B) has been shown to be expressed in brown adipose tissues and the hypothalamus and to affect thermogenesis and susceptibility to diet-induced obesity. Here, we aimed to analyze BMP8B expression in NAFLD and to gain insight into BMP8B effects on pathophysiological steps of NAFLD progression. BMP8B mRNA and protein expression were dose-dependently induced in primary human hepatocytes in vitro upon incubation with fatty acids. Furthermore, hepatic BMP8B expression was significantly increased in a murine NAFLD model and in NAFLD patients compared with controls. Incubation with recombinant BMP8B further enhanced the fatty acid-induced cellular lipid accumulation as well as NF?B activation and pro-inflammatory gene expression in hepatocytes, while siRNA-mediated BMP8B depletion ameliorated these fatty acid-induced effects. Analysis of the expression of key factors of hepatocellular lipid transport and metabolisms indicated that BMP8B effects on fatty acid uptake as well as de novo lipogenesis contributed to hepatocellular accumulation of fatty acids leading to increased storage in the form of triglycerides and enhanced combustion by beta oxidation. In conclusion, our data indicate that BMP8B enhances different pathophysiological steps of NAFLD progression and suggest BMP8B as a promising prognostic marker and therapeutic target for NAFLD and, potentially, also for other chronic liver diseases.

SUBMITTER: Mahli A

PROVIDER: S-EPMC6562647 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Bone Morphogenetic Protein-8B Expression is Induced in Steatotic Hepatocytes and Promotes Hepatic Steatosis and Inflammation In Vitro.

Mahli Abdo A Seitz Tatjana T Beckröge Tobias T Freese Kim K Thasler Wolfgang Erwin WE Benkert Matthias M Dietrich Peter P Weiskirchen Ralf R Bosserhoff Anja A Hellerbrand Claus C

Cells 20190515 5

Non-alcoholic fatty liver disease (NAFLD) is considered to be the hepatic manifestation of the metabolic syndrome. The bone morphogenetic protein-8B (BMP8B) has been shown to be expressed in brown adipose tissues and the hypothalamus and to affect thermogenesis and susceptibility to diet-induced obesity. Here, we aimed to analyze BMP8B expression in NAFLD and to gain insight into BMP8B effects on pathophysiological steps of NAFLD progression. BMP8B mRNA and protein expression were dose-dependent ...[more]

PMID: 31096638

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Project description:Fatty liver hemorrhagic syndrome (FLHS) in laying hens, a nutritional metabolic disorder disease, can lead to the decline of laying rate, shortening of laying peak period and increase of mortality, which seriously constrain the sustainable development of layer industry. Until now, there is no effective strategies can prevent and control the occurrence of fatty liver hemorrhagic syndrome in laying hens. The AMP-activated protein kinase (AMPK), a major sensor of cellular energy status, acts a crucial role in regulating lipid metabolism, oxidative stress and inflammatory responses in body. However, the potential molecular mechanisms about AMP-activated protein kinase signal in controlling the occurrence of fatty liver hemorrhagic syndrome are remain unclear. In present study, we found that the phosphorylated AMP-activated protein kinase (Thr172) protein level was markedly reduced in palmitic acid plus oleic acid (PO)-induced primary chicken hepatocytes. Moreover, blocked AMP-activated protein kinase signal by AMP-activated protein kinase inhibitor compound C obviously exacerbated lipid metabolism disorders, oxidative stress and inflammatory response triggered by palmitic acid plus oleic acid in primary chicken hepatocytes. Nevertheless, the lipid metabolism disorders, oxidative stress and inflammatory response challenged by palmitic acid plus oleic acid were obviously alleviated through activation of AMP-activated protein kinase signal with AMP-activated protein kinase activator AICAR in hepatocytes. In addition, we found that the beneficial effects of AMP-activated protein kinase signal in relieving lipid metabolism disorders, oxidative stress and inflammatory response are achieved by activating the nuclear factor erythroid 2-related factor 2 (NRF-2)/kelch-like ECH-associated protein 1 (KEAP1) pathway and inhibiting the NF-κB pathway in PO-stimulated primary chicken hepatocytes. Collectively, our data demonstrated that AMP-activated protein kinase acts as a potential target for the prevention of fatty liver hemorrhagic syndrome occurrence in laying hens.

Dataset Information

Bone Morphogenetic Protein-8B Expression is Induced in Steatotic Hepatocytes and Promotes Hepatic Steatosis and Inflammation In Vitro.

Publications

Bone Morphogenetic Protein-8B Expression is Induced in Steatotic Hepatocytes and Promotes Hepatic Steatosis and Inflammation In Vitro.

Similar Datasets

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