Metabolic functions of the liver

Mitra, Vikramjit; Metcalf, Jane

doi:10.1016/j.mpaic.2011.11.006

Cited by 55 publications

(38 citation statements)

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“…The liver is subjected to regulation by insulin that maintains normal liver function. The loss of insulin signalling in hepatocytes leads to progressive hepatic dysfunction ( 37 , 38 ) , resulting in inflammation, morphological and histopathological changes, necrosis and fibrosis ( 5 ) , and ultimately causing acute liver failure ( 6 ) . The observed increased levels of liver enzymes, ALT and AST, at 4 weeks after STZ administration described herein revealed hepatocellular damage and changes in liver function, with the increase in the liver weight:body weight ratio, suggesting the onset of liver hypertrophy ( 39 ) .…”

Section: Discussionmentioning

confidence: 99%

DecreasedO-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a novel mechanism of the beneficial effect of α-lipoic acid in diabetic liver

et al. 2013

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The present study aimed to investigate the effects of the treatment with a-lipoic acid (LA), a naturally occurring compound possessing antioxidant activity, on liver oxidant stress in a rat model of streptozotocin (STZ)-induced diabetes by examining potential mechanistic points that influence changes in the expression of antioxidant enzymes such as catalase (CAT) and CuZn/Mn superoxide dismutase(s) (SOD). LA was administered for 4 weeks by daily intraperitoneal injections (10 mg/kg) to STZ-induced diabetic rats, starting from the last STZ treatment. LA administration practically normalised the activities of the indicators of hepatocellular injury, alanine and aspartate aminotransferases, and lowered oxidative stress, as observed by the thiobarbituric acid-reactive substance assay, restored the reduced glutathione:glutathione disulphide ratio and increased the protein sulfhydryl group content. The lower level of DNA damage detected by the comet assay revealed that LA reduced cytotoxic signalling, exerting a hepatoprotective effect. The LA-treated diabetic rats displayed restored specific enzymatic activities of CAT, CuZnSOD and MnSOD. Quantitative real-time PCR analysis showed that LA restored CAT gene expression to its physiological level and increased CuZnSOD gene expression, but the gene expression of MnSOD remained at the diabetic level. Although the amounts of CAT and CuZnSOD protein expression returned to the control levels, the protein expression of MnSOD was elevated. These results suggested that LA administration affected CAT and CuZnSOD expression mainly at the transcriptional level, and MnSOD expression at the post-transcriptional level. The observed LA-promoted decrease in the O-GlcNAcylation of extracellular signal-regulated kinase, protein 38 kinase, NF-kB, CCAAT/enhancer-binding protein and the antioxidative enzymes themselves in diabetic rats suggests that the regulatory mechanisms that supported the changes in antioxidative enzyme expression were also influenced by post-translational mechanisms.

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Section: Discussionmentioning

confidence: 99%

DecreasedO-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a novel mechanism of the beneficial effect of α-lipoic acid in diabetic liver

et al. 2013

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“…The main essential functions of the liver are related to protein synthesis and metabolism, including amino acids, carbohydrate, lipid and vitamin metabolism. Also, the degradation of toxins, xenobiotics and waste products are essential functions performed by the liver (Mitra and Metcalf, 2009). Leishmania infantum , a protozoan parasite, and the agent of zoonotic visceral leishmaniasis (ZVL) and canine leishmaniasis (CanL) is able to target the liver, establishing inside the Kupffer cells (KC), the liver resident macrophages (Kaye and Beattie, 2016).…”

Section: Introductionmentioning

confidence: 99%

Dog hepatocytes are key effector cells in the liver innate immune response toLeishmania infantum

et al. 2018

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Hepatocytes constitute the majority of hepatic cells, and play a key role in controlling systemic innate immunity, via pattern-recognition receptors (PRRs) and by synthesizing complement and acute phase proteins. Leishmania infantum, a protozoan parasite that causes human and canine leishmaniasis, infects liver by establishing inside the Kupffer cells. The current study proposes the elucidation of the immune response generated by dog hepatocytes when exposed to L. infantum. Additionally, the impact of adding leishmanicidal compound, meglumine antimoniate (MgA), to parasite-exposed hepatocytes was also addressed. L. infantum presents a high tropism to hepatocytes, establishing strong membrane interactions. The possibility of L. infantum internalization by hepatocytes was raised, but not confirmed. Hepatocytes were able to recognize parasite presence, inducing PRRs [nucleotide oligomerization domain (NOD)1, NOD2 and Toll-like receptor (TLR)2] gene expression and generating a mix pro- and anti-inflammatory cytokine response. Reduction of cytochrome P 450s enzyme activity was also observed concomitant with the inflammatory response. Addition of MgA increased NOD2, TLR4 and interleukin 10 gene expression, indicating an immunomodulatory role for MgA. Hepatocytes seem to have a major role in coordinating liver's innate immune response against L. infantum infection, activating inflammatory mechanisms, but always balancing the inflammatory response in order to avoid cell damage.

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“…The DE analysis revealed 25 enriched pathways, most of which contained upregulated genes (in the liver as compared to gut) such as “Ribosome, Oxidative phosphorylation, Carbon metabolism, Glycolysis/Gluconeogenesis, Fatty acid degradation and Complement & coagulation cascades” pathways, highlighting that the liver is an extremely active organ that conducts a wide variety of functions including vascular functions (under normal physiological conditions, the liver comprises 10-15% of the total body blood volume, it functions as a supply center when the peripheral circulation is encumbered and releases blood into the circulation when a blood loss occurs, and synthesizes approximately 50% of all circulating lymph), immunological functions (the Kupffer cells act as macrophages and establish a component of the body’s phagocytic system), metabolic functions (carbohydrate metabolism such as glycogenesis/glycogenolysis/ gluconeogenesis, protein metabolism including transamination/deamination/urea synthesis, lipid metabolism such as lipogenesis/fatty acid oxidation/lipoprotein synthesis/phos- pholipid/cholesterol synthesis), secretory functions (the liver secretes bile acids required for the digestion and absorption of fat and fat-soluble vitamins from the small intestine) and excretory & detoxification functions [18, 73]. In fact, after the skin, the liver is the largest organ in the body, comprising up to 2.5% of lean body mass [73].…”

Section: Discussionmentioning

confidence: 99%

Interplay Between MicroRNAs and Targeted Genes in Cellular Homeostasis of Adult Zebrafish (Danio rerio)

Renaud

Silveira

Glen

et al. 2018

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Background:Cellular homeostasis is regulated by the intricate interplay between a plethora of signaling pathways and “energetic sensors” in organs. In order to maintain energy balance, induction or repression of metabolic pathways must be regulated and act in concert with the energetic demands of the cell at a given point in time. A new class of small noncoding RNAs, the microRNAs (miRNAs), has added yet further complexity to the control of metabolic homeostasis.Objective: Understanding the damages induced by toxins in the liver and the intestine as well as the interplay between the miRNome and transcriptome first requires baseline characterization in these tissues in healthy animals under cellular homeostasis.Methods: The liver (main site for detoxification) and the gut (primary exposure routes for contaminant exposure) were dissected out (wildtype fish), total and small RNA extracted, mRNA and miRNA libraries constructed and subjected to high throughput sequencing. Differential Expression (DE) analysis was performed comparing liver with gut and an “miRNA matrix” that integrates the miRNA-seq and mRNA-seq data was constructed.Results:Both the miRNome and transcriptome of the liver and gut tissues were characterized and putative novel miRNAs were identified. Exploration of the “miRNA matrix” regulatory network revealed that miRNAs uniquely expressed in the liver or gut tissue regulated fundamental cellular processes important for both organs, and that commonly expressed miRNAs in both tissues regulated biological processes that were specific to either the liver or the gut.Conclusion: The result of our analyses revealed new insights into microRNA function in these tissues.

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Metabolic functions of the liver

Cited by 55 publications

References 0 publications

DecreasedO-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a novel mechanism of the beneficial effect of α-lipoic acid in diabetic liver

DecreasedO-GlcNAcylation of the key proteins in kinase and redox signalling pathways is a novel mechanism of the beneficial effect of α-lipoic acid in diabetic liver

Dog hepatocytes are key effector cells in the liver innate immune response toLeishmania infantum

Interplay Between MicroRNAs and Targeted Genes in Cellular Homeostasis of Adult Zebrafish (Danio rerio)

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