Imbalanced insulin substrate-1 and insulin substrate-2 signaling trigger hepatic steatosis in vitamin D deficient rats: 8-methoxypsoralen, a vitamin D receptor ligand with a promising anti-steatotic action

Elhafiz, Muhanad; Zhao, Guolin; Ismail, Mohammed; Xu, Dengqiu; Das, Debanjan; Fan, Sisi; Cheng, Nong; Yousef, Bashir A.; Jiang, Zhenzhou; Zhang, Luyong

doi:10.1016/j.bbalip.2020.158657

Cited by 6 publications

(9 citation statements)

References 59 publications

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“…Compared with the NFD group, the abundance of g_Ileibacterium , g_Lachnospiraceae_UCG-006 , g __Ruminococcus_UCG_004 , and g_Lachnoclostridium ( Figure 7(d) ) in feces of HFD-fed mice was increased, which has been reported to be associated with liver and colon inflammation and relevant mouse or human diseases, including metabolic syndrome, gastrointestinal injury, and immune system disinfection [ 25 , 26 ]. The same result was obtained in the abundance of g_Desulfovibrio , which is a key producer of endotoxins in animal models of obesity ( Figure 7(l) ) [ 27 ]. The FV supplementation significantly reduced these genera ( Figure 7(e) ).…”

Section: Resultssupporting

confidence: 72%

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Quan

Zhou

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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Nonalcoholic fatty liver disease (NAFLD) has gradually become one of the most serious liver diseases threatening human health in the world. Currently, Chinese herbal medicine is a potentially important treatment option for NAFLD, and the development of effective Chinese herbal medicine has a good prospect. Previous studies have suggested that Ficus hirta Vahl. (FV) has various protective effects on the liver. In this study, we investigated the therapeutic outcomes of FV treatment for the liver disease and its underlying mechanism using HepG2 cell lines induced by palmitate (PA) and mouse model fed with high-fat diet (HFD). FV mainly exerts pharmacological effects by mediating lipid metabolism and inflammation. During the lipid metabolism regulation process, CD36, SREBP-1, SCD1, PPAR γ, ACOX1, and CPT1α are the key factors related to the healing effects of FV on NAFLD. During the inflammation process, the downregulation of IL-6, IL-1β, and TNF-α is involved in alleviation of NAFLD. Furthermore, CD36 overexpression promotes lipid abnormal metabolism and inflammation in PA-induced HepG2 cells, while CD36 knockdown and FV supplementation reverse these responses. In addition, FV also modulates gut microbiota composition, such as Allobaculum, Faecalibaculum, and Butyricicoccus in HFD-fed mice. In summary, our findings demonstrated that FV exerted a beneficial preventive and therapeutic effect on NAFLD by improving lipid metabolism and inflammation as well as regulating the structure of gut microbiota, and therefore, FV may be a candidate for the treatment of NAFLD.

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Section: Resultssupporting

confidence: 72%

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Quan

Zhou

Chen

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Furthermore, the attenuating effects related to the expression of hepatic lipid metabolizing molecules and concentrations of adipokines were stronger in the OM group compared with VD group, suggesting that VD 3 monotherapy is a less effective strategy for repressing MAFLD. An explanation for the lower efficacy of VD 3 against MAFLD could be related to an abnormal expression of its nuclear receptor (VDR), 53,54 which mediates many of the hormone protective actions 55 . In this context, VDR activation modulated several hepatocyte lipid metabolizing molecules in vitro, 55,56 while liver‐specific deletion of VDR gene aggravated insulin resistance and steatosis and blocked the VD 3 protective effects against MAFLD in mice 27 .…”

Section: Discussionmentioning

confidence: 99%

“…An explanation for the lower efficacy of VD 3 against MAFLD could be related to an abnormal expression of its nuclear receptor (VDR), 53,54 which mediates many of the hormone protective actions 55 . In this context, VDR activation modulated several hepatocyte lipid metabolizing molecules in vitro, 55,56 while liver‐specific deletion of VDR gene aggravated insulin resistance and steatosis and blocked the VD 3 protective effects against MAFLD in mice 27 . Moreover, MAFLD impedes the renal production of calcitriol, the active form of VD, which could consequently avert VDR activation 57 .…”

Section: Discussionmentioning

confidence: 99%

Vitamin D₃ enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat

et al. 2021

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This study investigated the effects of omega-3 oils (OM) and/or vitamin D 3 (VD) against metabolic dysfunction-associated fatty liver disease (MAFLD). Forty rats were divided into negative (NC) and positive (PC) controls, OM, VD, and OM + VD groups, and MAFLD was induced by high-fat/high-fructose diet (12 weeks). Oral OM (415 mg/kg/day) and/or intramuscular VD (290 IU/kg/ day) were given for 4 weeks (5 times/week). The PC animals were markedly obese and had hyperglycemia, insulin resistance, dyslipidemia, elevated liver enzymes, abnormal hepatic histology, and increased caspase-3 with apoptosis than the NC group. The expression of hepatic peroxisome proliferator-activated receptor-α (PPAR-α; 5.3-fold), insulin induced gene-1 (INSIG1; 7.8-fold), adiponectin receptor-1 (AdipoR1; 4.4-fold), and leptin receptor (LEPR; 6-fold) declined, while PPAR-γ (3.7-fold) and sterol regulatory element-binding protein-1 (SREBP1; 2.4-fold) increased, in the PC than the NC group. Leptin (2.2-fold), malondialdehyde (2.1-fold), protein carbonyl groups (17.3-fold), IL-1β (4.4-fold), IL-6 (2.1-fold), TNF-α (1.8-fold) also increased, whereas adiponectin (2.8-fold) glutathione (2.1-fold), glutathione peroxidase-1 (2.4-fold), glutathione reductase (2.2-fold), catalase (1.4-fold), and IL-10 (2.8-fold) decreased, in the PC livers. Both monotherapies attenuated obesity, metabolic profiles, and PPAR-γ/SREBP1/leptin/Caspase-3/apoptosis, while

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“…NAFLD patients are characterized by an increased load of free fatty acids (FFAs) in the liver, which can be due both to increased lipolysis from adipose tissue but also to de novo lipogenesis in hepatocytes [24][25][26][27][28][29][30]. Insulin resistance has a prominent role in these processes by favoring an increased lipolytic response to the meal, and by inducing the expression of lipogenic pathways in the liver [24,25,27,31,32]. In the liver, FFAs are metabolized by beta-oxidation in mitochondria, or esterified as triglycerides (TGs), and either secreted within very-low-density lipoproteins (VLDL) or stored in lipid droplets leading to hepatic steatosis [25].…”

Section: Lipotoxicity In Hepatocytesmentioning

confidence: 99%

Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis

Overi

Carpino

Franchitto

et al. 2020

Cells

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Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by lipid accumulation in hepatocytes in the absence of excessive alcohol consumption. The global prevalence of NAFLD is constantly increasing. NAFLD is a disease spectrum comprising distinct stages with different prognoses. Non-alcoholic steatohepatitis (NASH) is a progressive condition, characterized by liver inflammation and hepatocyte ballooning, with or without fibrosis. The natural history of NAFLD is negatively influenced by NASH onset and by the progression towards advanced fibrosis. Pathogenetic mechanisms and cellular interactions leading to NASH and fibrosis involve hepatocytes, liver macrophages, myofibroblast cell subpopulations, and the resident progenitor cell niche. These cells are implied in the regenerative trajectories following liver injury, and impairment or perturbation of these mechanisms could lead to NASH and fibrosis. Recent evidence underlines the contribution of extra-hepatic organs/tissues (e.g., gut, adipose tissue) in influencing NASH development by interacting with hepatic cells through various molecular pathways. The present review aims to summarize the role of hepatic parenchymal and non-parenchymal cells, their mutual influence, and the possible interactions with extra-hepatic tissues and organs in the pathogenesis of NAFLD.

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Imbalanced insulin substrate-1 and insulin substrate-2 signaling trigger hepatic steatosis in vitamin D deficient rats: 8-methoxypsoralen, a vitamin D receptor ligand with a promising anti-steatotic action

Cited by 6 publications

References 59 publications

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Vitamin D₃ enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat

Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis

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Imbalanced insulin substrate-1 and insulin substrate-2 signaling trigger hepatic steatosis in vitamin D deficient rats: 8-methoxypsoralen, a vitamin D receptor ligand with a promising anti-steatotic action

Cited by 6 publications

References 59 publications

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Ficus hirta Vahl. Ameliorates Nonalcoholic Fatty Liver Disease through Regulating Lipid Metabolism and Gut Microbiota

Vitamin D3 enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat

Hepatocyte Injury and Hepatic Stem Cell Niche in the Progression of Non-Alcoholic Steatohepatitis

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Vitamin D₃ enhances the effects of omega‐3 oils against metabolic dysfunction‐associated fatty liver disease in rat