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Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling.

ABSTRACT: Fatty liver disease (FLD) is characterized by accumulation of excess fat in the liver. The underlying molecular mechanism associated with the progression of the disease has been in elusive. Hepatocellular demise due to increased oxidative stress resulting in an inflammatory response may be a key feature in FLD. Recent advances in molecular biology have led to an improved understanding of the molecular pathogenesis, suggesting a critical association between the PI3K/AKT/PTEN signaling pathway and FLD. In particular, PTEN has been associated with regulating the pathogenesis of hepatocyte degeneration. Given the function of mitochondria in reactive oxygen species (ROS) generation and the initiation of oxidative stress, the mitochondrial antioxidant network is of interest. It is vital to balance the activity of intracellular key molecules to maintain a healthy liver. Consequently, onset of FLD may be delayed using dietary protective agents that alter PTEN signaling and reduce ROS levels. The advancement of research on dietary regulation with a focus on modulatory roles in ROS generation and PTEN associated signaling is summarized in the current study, supporting further preventive and therapeutic exploration.

SUBMITTER: Ikeda Y

PROVIDER: S-EPMC7201141 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling.

Ikeda Yuka Y Murakami Mutsumi M Nakagawa Yukie Y Tsuji Ai A Kitagishi Yasuko Y Matsuda Satoru S

Biomedical reports 20200422 6

Fatty liver disease (FLD) is characterized by accumulation of excess fat in the liver. The underlying molecular mechanism associated with the progression of the disease has been in elusive. Hepatocellular demise due to increased oxidative stress resulting in an inflammatory response may be a key feature in FLD. Recent advances in molecular biology have led to an improved understanding of the molecular pathogenesis, suggesting a critical association between the PI3K/AKT/PTEN signaling pathway and ...[more]

PMID: 32382414

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Project description:We previously reported the effects of the total flavonoids (TFs) from Rosa laevigata Michx fruit against carbon tetrachloride-induced liver damage, non-alcoholic fatty liver disease, and liver ischemia-reperfusion injury. However, there have been no papers reporting the role of R. laevigata TFs against lipopolysaccharide (LPS)-induced liver injury. In this paper, liver injury in mice was induced by LPS, and R. Laevigata extract was intragastrically administered to the mice for 7 days. Biochemical parameters in serum and liver tissue were examined, and pathological changes were observed by transmission electron microscopy, hematoxylin and eosin (H&E) and Oil Red O staining. The results showed that the TFs markedly reduced serum ALT (alanine transferase), AST (aspartate transaminase), TG (total triglyceride), and TC (total cholesterol) levels and relative liver weights and improved liver pathological changes. In addition, the TFs markedly decreased tissue MDA (malondialdehyde) level and increased the levels of SOD (superoxide dismutase) and GSH-Px (glutathione peroxidase). A mechanistic study showed that the TFs significantly increased the expression levels of Nrf2 (nuclear erythroid factor2-related factor 2), HO-1 (heme oxygenase-1), NQO1 (NAD(P)H dehydrogenase (quinone 1), GCLC (glutamate-cysteine ligase catalytic subunit), and GCLM (glutamate-cysteine ligase regulatory subunit) and decreased Keap1 (Kelch-like ECH-associated protein 1) level by activating FXR (farnesoid X receptor) against oxidative stress. Furthermore, the TFs markedly suppressed the nuclear translocation of NF-κB (nuclear factor-kappa B) and subsequently decreased the expression levels of IL (interleukin)-1β, IL-6, HMGB-1 (high -mobility group box 1), and COX-2 (cyclooxygenase-2) by activating FXR and FOXO3a (forkhead box O3) against inflammation. Besides, the TFs obviously reduced the expression levels of SREBP-1c (sterol regulatory element-binding proteins-1c), ACC1 (acetyl-CoA carboxylase-1), FASN (fatty acid synthase), and SCD1 (stearoyl-coenzyme A desaturase 1), and improved CPT1 (carnitine palmitoyltransferase 1) level by activating FXR to regulate lipid metabolism. Our results suggest that TFs exhibited protective effect against LPS-induced liver injury by altering FXR-mediated oxidative stress, inflammation, and lipid metabolism, and should be developed as an effective food and healthcare product for the therapy of liver injury in the future.

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Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling.

Publications

Diet induces hepatocyte protection in fatty liver disease via modulation of PTEN signaling.

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