Osmosensing and osmosignaling in the liver

Häussinger, Dieter

doi:10.1007/s10354-008-0593-0

Cited by 14 publications

(24 citation statements)

References 22 publications

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“…Betaine is an intracellular osmolyte involved in cell volume regulation and osmosignaling that also serves as a methyl donor for the conversion of homocysteine to methionine (11,20,36,54). Betaine, being a long-term osmolyte, could influence macromolecular crowding in maintaining intracytoplasmic normal osmotic pressure (13,19).…”

Section: Discussionmentioning

confidence: 99%

Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine

Kathirvel

Morgan

Nandgiri

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

160

145

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Nonalcoholic fatty liver (NAFL) is a common liver disease, associated with insulin resistance. Betaine has been tested as a treatment for NAFL in animal models and in small clinical trials, with mixed results. The present study aims to determine whether betaine treatment would prevent or treat NAFL in mice and to understand how betaine reverses hepatic insulin resistance. Male mice were fed a moderate high-fat diet (mHF) containing 20% of calories from fat for 7 (mHF) or 8 (mHF8) mo without betaine, with betaine (mHFB), or with betaine for the last 6 wk (mHF8B). Control mice were fed standard chow containing 9% of calories from fat for 7 mo (SF) or 8 mo (SF8). HepG2 cells were made insulin resistant and then studied with or without betaine. mHF mice had higher body weight, fasting glucose, insulin, and triglycerides and greater hepatic fat than SF mice. Betaine reduced fasting glucose, insulin, triglycerides, and hepatic fat. In the mHF8B group, betaine treatment significantly improved insulin resistance and hepatic steatosis. Hepatic betaine content significantly decreased in mHF and increased significantly in mHFB. Betaine treatment reversed the inhibition of hepatic insulin signaling in mHF and in insulin-resistant HepG2 cells, including normalization of insulin receptor substrate 1 (IRS1) phosphorylation and of downstream signaling pathways for gluconeogenesis and glycogen synthesis. Betaine treatment prevents and treats fatty liver in a moderate high-dietary-fat model of NAFL in mice. Betaine also reverses hepatic insulin resistance in part by increasing the activation of IRS1, with resultant improvement in downstream signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine

Kathirvel

Morgan

Nandgiri

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

160

145

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“…It is not unreasonable that these two apparently completely different functions of taurine might be mechanistically related because of the way by which cellular osmolyte content and volume now has been reported to regulate processes of cellular protein synthesis and apoptosis, at least in liver cells (678–681). The nature of these phenomena, even though it may be possible that they have been well studied only in hepatocytes, suggest that one might be dealing with very fundamental regulatory mechanisms, which presumably also could be very phylogenetically ancient.…”

Section: Functions Of Taurine As An Osmolyte and As A Growth Factor Tmentioning

confidence: 99%

“…It has been found that when alterations of hepatocyte volume are induced either by anisoosmotic environments or under the influence of hormones, concentrative amino acid uptake and oxidative stress function as independent signals which contribute to the regulation of liver cell function and gene expression (681). Several long-known but mechanistically poorly understood effects of amino acids, which could not be related to their metabolism, such as the stimulation of glycogen synthesis or the inhibition of proteolysis, can now be explained as due to their effects on hepatocyte hydration, because they are quantitatively mimicked by swelling the cells in hypoosmotic media to the extent as the amino acids do (681).…”

Section: Functions Of Taurine As An Osmolyte and As A Growth Factor Tmentioning

confidence: 99%

“…Several long-known but mechanistically poorly understood effects of amino acids, which could not be related to their metabolism, such as the stimulation of glycogen synthesis or the inhibition of proteolysis, can now be explained as due to their effects on hepatocyte hydration, because they are quantitatively mimicked by swelling the cells in hypoosmotic media to the extent as the amino acids do (681). Likewise, transmembrane ion movements under the influence of hormones have been found to be an integral part of hormonal signal transduction mechanisms with alterations of cellular hydration acting as some kind of "second messenger" of hormone action (681). Integrins act as osmosensors for hepatocyte swelling and trigger activation of mitogen-activated protein kinase systems that function as osmosignaling cascades towards choleresis and autophagy inhibition (681).…”

Section: Functions Of Taurine As An Osmolyte and As A Growth Factor Tmentioning

confidence: 99%

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Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

Christophersen¹

2012

Microbial Ecology in Health & Disease

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There are several animal experiments showing that high doses of ionizing radiation lead to strongly enhanced leakage of taurine from damaged cells into the extracellular fluid, followed by enhanced urinary excretion. This radiation-induced taurine depletion can itself have various harmful effects (as will also be the case when taurine depletion is due to other causes, such as alcohol abuse or cancer therapy with cytotoxic drugs), but taurine supplementation has been shown to have radioprotective effects apparently going beyond what might be expected just as a consequence of correcting the harmful consequences of taurine deficiency per se. The mechanisms accounting for the radioprotective effects of taurine are, however, very incompletely understood. In this article an attempt is made to survey various mechanisms that potentially might be involved as parts of the explanation for the overall beneficial effect of high levels of taurine that has been found in experiments with animals or isolated cells exposed to high doses of ionizing radiation. It is proposed that taurine may have radioprotective effects by a combination of several mechanisms: (1) during the exposure to ionizing radiation by functioning as an antioxidant, but perhaps more because it counteracts the prooxidant catalytic effect of iron rather than functioning as an important scavenger of harmful molecules itself, (2) after the ionizing radiation exposure by helping to reduce the intensity of the post-traumatic inflammatory response, and thus reducing the extent of tissue damage that develops because of severe inflammation rather than as a direct effect of the ionizing radiation per se, (3) by functioning as a growth factor helping to enhance the growth rate of leukocytes and leukocyte progenitor cells and perhaps also of other rapidly proliferating cell types, such as enterocyte progenitor cells, which may be important for immunological recovery and perhaps also for rapid repair of various damaged tissues, especially in the intestines, and (4) by functioning as an antifibrogenic agent. A detailed discussion is given of possible mechanisms involved both in the antioxidant effects of taurine, in its anti-inflammatory effects and in its role as a growth factor for leukocytes and nerve cells, which might be closely related to its role as an osmolyte important for cellular volume regulation because of the close connection between cell volume regulation and the regulation of protein synthesis as well as cellular protein degradation. While taurine supplementation alone would be expected to exert a therapeutic effect far better than negligible in patients that have been exposed to high doses of ionizing radiation, it may on theoretical grounds be expected that much better results may be obtained by using taurine as part of a multifactorial treatment strategy, where it may interact synergistically with several other nutrients, hormones or other drugs for optimizing antioxidant protection and minimizing harmful posttraumatic inflammatory reactions, while using ...

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“…As a result, following cell swelling, the intracellular amino acids and glucose are incorporated into and upon cell shrinkage they are released from the osmotically less active macromolecules [26]. Cell volume further influences glycolysis, flux through the pentose phosphate pathway, lipogenesis from glucose, gluconeogenesis, oxidation of glycine and alanine, degradation of glutamine, degradation of amino acids to NH 4 + and urea, ketoisocaproate oxidation, acetyl CoA carboxylase, lipogenesis, carnitine palmitoyltransferase I activity, cytosolic ATP and phosphocreatine concentrations, respiration as well as RNA and DNA synthesis [26,29,32]. Whether or not pendrin indeed participates in cell volume regulatory transport, remains, however, to be tested.…”

mentioning

confidence: 99%

Impact of Bicarbonate, Ammonium Chloride, and Acetazolamide on Hepatic and Renal SLC26A4 Expression

Alesutan¹,

Daryadel²,

Mohebbi³

et al. 2011

Cell Physiol Biochem

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SLC26A4 encodes pendrin, a transporter exchanging anions such as chloride, bicarbonate, and iodide. Loss of function mutations of SLC26A4 cause Pendred syndrome characterized by hearing loss and enlarged vestibular aqueducts as well as variable hypothyroidism and goiter. In the kidney, pendrin is expressed in the distal nephron and accomplishes HCO(3)(-) secretion and Cl(-) reabsorption. Renal pendrin expression is regulated by acid-base balance. The liver contributes to acid-base regulation by producing or consuming glutamine, which is utilized by the kidney for generation and excretion of NH(4)(+), paralleled by HCO(3)(-) formation. Little is known about the regulation of pendrin in liver. The present study thus examined the expression of Slc26a4 in liver and kidney of mice drinking tap water without or with NaHCO(3) (150 mM), NH(4)Cl (280 mM) or acetazolamide (3.6 mM) for seven days. As compared to Gapdh transcript levels, Slc26a4 transcript levels were moderately lower in liver than in renal tissue. Slc26a4 transcript levels were not significantly affected by NaHCO(3) in liver, but significantly increased by NaHCO(3) in kidney. Pendrin protein expression was significantly enhanced in kidney and reduced in liver by NaHCO(3). Slc26a4 transcript levels were significantly increased by NH(4)Cl and acetazolamide in liver, and significantly decreased by NH(4)Cl and by acetazolamide in kidney. NH(4)Cl and acetazolamide reduced pendrin protein expression significantly in kidney, but did not significantly modify pendrin protein expression in liver. The observations point to expression of pendrin in the liver and to opposite effects of acidosis on pendrin transcription in liver and kidney. Little is known about the regulation of pendrin in liver. The present study thus examined the expression of Slc26a4 in liver and kidney of mice drinking tap water without or with NaHCO 3 (150 mM), NH 4 Cl (280 mM) or acetazolamide (3.6 mM) for seven days. As compared to Gapdh transcript levels, Slc26a4 transcript levels were moderately lower in liver than in renal tissue. Slc26a4 transcript levels were not significantly affected by NaHCO 3 in liver, but significantly increased by NaHCO 3 in kidney. Pendrin protein expression was significantly enhanced in kidney and reduced in liver by NaHCO 3 . Slc26a4 transcript levels were significantly increased by NH 4 Cl and acetazolamide in liver, and significantly decreased by NH 4 Cl and by acetazolamide in kidney. NH 4 Cl and acetazolamide reduced pendrin protein expression significantly in kidney, but did not significantly modify pendrin protein expression in liver. The observations point to expression of pendrin in the liver and to opposite effects of acidosis on pendrin transcription in liver and kidney.

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Osmosensing and osmosignaling in the liver

Cited by 14 publications

References 22 publications

Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine

Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine

Radiation protection following nuclear power accidents: a survey of putative mechanisms involved in the radioprotective actions of taurine during and after radiation exposure.

Impact of Bicarbonate, Ammonium Chloride, and Acetazolamide on Hepatic and Renal SLC26A4 Expression

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