Relevance between lipid metabolism‐associated genes and rat liver regeneration

Xu, Chi; Lin, Fang; Qin, Shaowei

doi:10.1111/j.1872-034x.2008.00345.x

Cited by 18 publications

(17 citation statements)

References 49 publications

(77 reference statements)

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“…S4 A). In agreement with previous studies [39][40][41], which suggested that the pre-existing cholesterol storage or the delivered lipoprotein cholesterol may be insufficient to meet the cellular required demand soon after the start of cell division in the regenerating liver (2-3 days after PH) while higher expression of HMGCR and its activity and strong new cholesterol synthesis are required. Interestingly, in the present study, we found that precursors of SREBP-2 were increased after PH (Fig.…”

Section: Discussionsupporting

confidence: 78%

Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability

Peng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Transient lipid accumulation within hepatocytes preceding the peak proliferative process is a characteristic feature of liver regeneration. However, molecular mediators responsible for this lipid accumulation and their functions are not well defined. Sterol regulatory element-binding proteins-1c (SREBP-1c) are critical transcriptional factors that regulate lipid homeostasis in the liver. We hypothesized that SREBP-1c deficiency induced alterations of lipid metabolism may influence hepatocyte proliferation and liver regeneration. Methods: 2/3 partial hepatectomy (PH) was performed in wild type C57BL/6J (WT) and Srebp-1c-/- mice. The lipid contents in serum and liver were measured by enzymatic colorimetric methods. Hepatic lipid droplets were detected by Oil Red O staining and immunohistological staining. Hepatic expression of genes involved in lipid metabolism and cellular proliferation was determined by real-time PCR and/or immunoblot. Hepatocyte proliferation and liver regeneration were assessed by BrdU staining and the weight of remanent liver lobes in Srebp-1c-/- mice, respectively. Results: Srebp-1c-/- mice displayed reduced triglyceride and fatty acids but increased cholesterol in the liver before PH. In response to PH, hepatocellular DNA synthesis was elevated and cell cycle progression was prolonged in Srebp-1c-/- mice, which was associated with enhanced liver regeneration. However, Srebp-1c-/- mice had comparable triglyceride and fatty acid contents and expressions of related genes compared with WT mice during the liver regeneration. In contrast, SREBP-1c-deficiency-induced alteration of cholesterol metabolism was retained during the liver regeneration after PH. Srebp-1c-/- mice exhibited higher cholesterol contents and enhanced expression of SREBP-2 and 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in the liver than WT mice after PH. Moreover, downregulation of genes involved in cholesterol elimination was observed after PH in Srebp-1c-/- mice. Conclusion: SREBP-1c deficiency in mice did not interfere with triglyceride and fatty acid metabolism but was associated with significant changes in cholesterol profiles during liver regeneration after PH. These results suggest that increased hepatocellular cholesterol storage and cholesterol availability with the enhanced liver regeneration are identified in Srebp-1c-/- mice. This study also shows that providing requisite cholesterol levels to proliferating hepatocytes and keeping appropriate cholesterol metabolism are required for normal liver regeneration.

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Section: Discussionsupporting

confidence: 78%

Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability

Peng

et al. 2018

Cell Physiol Biochem

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“…Liver regeneration (LR) represents a good model of synchronized proliferation in vivo that is very useful for studying events correlated with various phases of the cell cycle. The hepatocytes have low mitotic activity in adult rats and acquire the ability to divide during LR following partial hepatectomy (PH) re-entering rapidly in the cell cycle from the G0-phase [2,3]. G0/G1 phase transition occurs 4–6 h after PH, whereas cell proliferation 6–66 h after PH, characterized by G1/S phase transition at 6–12 h, DNA synthesis (S phase) at 18 h, S/G2 phase transition at 18–24 h and first cell division at 24 h after PH [2,3].…”

Section: Introductionmentioning

confidence: 99%

“…The hepatocytes have low mitotic activity in adult rats and acquire the ability to divide during LR following partial hepatectomy (PH) re-entering rapidly in the cell cycle from the G0-phase [2,3]. G0/G1 phase transition occurs 4–6 h after PH, whereas cell proliferation 6–66 h after PH, characterized by G1/S phase transition at 6–12 h, DNA synthesis (S phase) at 18 h, S/G2 phase transition at 18–24 h and first cell division at 24 h after PH [2,3]. For cell differentiation and liver tissue structure, functional rebuilding occurs 72–168 h after PH [2].…”

Section: Introductionmentioning

confidence: 99%

“…G0/G1 phase transition occurs 4–6 h after PH, whereas cell proliferation 6–66 h after PH, characterized by G1/S phase transition at 6–12 h, DNA synthesis (S phase) at 18 h, S/G2 phase transition at 18–24 h and first cell division at 24 h after PH [2,3]. For cell differentiation and liver tissue structure, functional rebuilding occurs 72–168 h after PH [2]. The process of LR has been widely studied since the 1960s, demonstrating the importance of different regulatory proteins, growth factors and hormones [4,5].…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration

Albi¹,

Lazzarini

Lazzarini³

et al. 2013

IJMS

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Nuclear sphingomyelin is a key molecule for cell proliferation. This molecule is organized with cholesterol and proteins to form specific lipid microdomains bound to the inner nuclear membrane where RNA is synthesized. Here, we have reported the ability of the sphingomyelin present in the nuclear microdomain to bind DNA and regulate its synthesis, and to highlight its role in cell proliferation induced by partial hepatectomy. During G1/S transition of the cell cycle, sphingomyelin and DNA content is very high and it is strongly reduced after exogenous sphingomyelinase treatment. During the S-phase of the cell cycle, the stimulation of sphingomyelinase and inhibition of sphingomyelin–synthase are accompanied by the DNA synthesis start. To assess the specificity of the results, experiments were repeated with trifluoperazine, a drug known to affect the synthesis of lipids and DNA and to stimulate sphingomyelinase activity. The activity of sphingomyelinase is stimulated in the first hour after hepatectomy and sphingomyelin–DNA synthesis is strongly attenuated. It may be hypothesized that the nuclear microdomain represents a specific area of the inner nuclear membrane that acts as an active site of chromatin anchorage thanks to the stabilizing action of sphingomyelin. Thus, sphingomyelin metabolism in nuclear lipid microdomains is suggested to regulate cell proliferation.

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“…These have looked at expression of: lipid metabolism-associated genes 88 ; genes associated with cellular immune response 89 and blood coagulation 90 ; cell junction-associated genes 91 ; and genes associated with the metabolism and transport of amino acids. 92 Each study identified a large number of genes which are up-or down-regulated during liver regeneration but unfortunately the studies did not determine whether the genes altered protein expression nor did they assess for polymorphisms of the genes concerned.…”

Section: Future Developmentsmentioning

confidence: 99%

Quantitative Assessment of Hepatic Function and its Relevance to the Liver Surgeon

Morris‐Stiff

Gomez

Prasad

2009

Journal of Gastrointestinal Surgery

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The review has identified a number of different methods of dynamically assessing hepatic function, the most frequently performed being through the use of indocyanine green clearance. With the recent and further anticipated developments in hepatic resectional surgery, it is likely that quantitative assessment will become more widely practiced in order to reduce post-operative hepatic failure and improve outcome.

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Relevance between lipid metabolism‐associated genes and rat liver regeneration

Cited by 18 publications

References 49 publications

Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability

Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability

Nuclear Lipid Microdomain as Place of Interaction between Sphingomyelin and DNA during Liver Regeneration

Quantitative Assessment of Hepatic Function and its Relevance to the Liver Surgeon

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