Oral Glutamine Supplementation Protects Female Mice from Nonalcoholic Steatohepatitis

Sellmann, Cathrin; Wei, Huangzhao; Degen, Christian; Bandt, Jean‐Pascal De; Bergheim, Ina

doi:10.3945/jn.115.215517

Cited by 31 publications

(28 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Two studies in experimental cirrhosis and HE described that ammonia lowering improved sarcopenia in cirrhotic Sprague–Dawley rats by stabilizing amino acid metabolism [22], and that LOLA treatment resulted in a significant increase of plasma glutamine, which probably derived from l -ornithine via GS [23]. Glutamine has been shown to be protective in preclinical models of NAFLD and NASH, possibly by reducing oxidative stress [24, 25]. Indirect evidence suggests that LOLA could diminish liver injury in NAFLD by reducing ammonia and oxidative stress.…”

Section: Rationale For Lola As Possible Treatment For Nafldmentioning

confidence: 99%

l-Ornithine l-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease

Canbay

Sowa

2019

Drugs

View full text Add to dashboard Cite

l-ornithine l-aspartate (LOLA) has been known as an effective ammonia-lowering agent for more than 50 years with good evidence in hepatic encephalopathy. Administration of LOLA removes ammonia via two distinct mechanisms: by synthesis of urea and by the synthesis of glutamine via the enzyme glutamine synthetase. While LOLA has been used in cirrhosis and acute liver injury settings, it is less clear if LOLA could be used in non-alcoholic fatty liver disease (NAFLD). NAFLD and the progressive form non-alcoholic steatohepatitis (NASH) are currently the leading causes of chronic liver disease worldwide, with roughly 25% of the world population affected by NAFLD. Consequences of NASH are end-stage liver disease and cardiovascular morbidity and mortality. As the basis for NAFLD is excess calorie uptake and excess adipose tissue mass, the conservative therapeutic approach is weight loss by intense lifestyle change. However, no pharmacological treatment options are currently approved. LOLA is being investigated as a pharmacological tool to ameliorate liver injury in NAFLD on the basis that it lowers liver ammonia concentrations and supplies anti-oxidative glutamine and glutathione. Indirect hepatoprotective effects currently under investigation could also be beneficial.

show abstract

Section: Rationale For Lola As Possible Treatment For Nafldmentioning

confidence: 99%

l-Ornithine l-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease

Canbay

Sowa

2019

Drugs

View full text Add to dashboard Cite

show abstract

“…Restoration of the synthesis of glutamine in liver may represent an important step implicated in the hepatoprotective properties of LOLA in NAFLD/ NASH in view of the observations that administration of glutamine results in improvement of hepatic injury caused by a range of insults including ischemia/reperfusion injury and that resulting from chronic alcohol ingestion [15,16]. More recently, reports from 2 studies in experimental NAFLD/NASH demonstrate significant hepatoprotective effects of glutamine [17,18]. In the first of these studies, NAFLD was induced by a high fat diet and oral treatment with glutamine resulted in reduced expression of hepatic markers of oxidative stress and inhibition of NFkB p65 accompanied by improvement in hepatic steatosis.…”

Section: Glutaminementioning

confidence: 99%

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Butterworth

Canbay

2018

Dig Dis

View full text Add to dashboard Cite

Background: Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited. Summary: L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with non-alcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties. Key Messages: (1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.

show abstract

“…Восстанов-ление синтеза глутамина в печени может представлять собой важный этап, относящийся к гепатопротекторным свойствам L-орнитина-L-аспартата при неалкогольной жировой болезни печении / неалкогольном стеатогепатите, исходя из данных о том, что применение глутамина приводит к улучшению состояния печени, чье поражение вызвано рядом факторов, включая травму, ишемию/реперфузию, а также факторами, обусловленными хроническим употреблением алкоголя [15,16]. Позднее отчеты о двух исследованиях экспериментальной неалкогольной жировой болезни печени / неалкогольного стеатогепатита продемонстрировали значительные гепатопротекторные эффекты глутамина [17,18]. В ходе первого из этих исследований неалкогольная жировая болезнь печени была индуцирована рационом с высоким содержанием жиров, а прием внутрь глутамина привел к снижению экспрессии печеночных маркеров оксидативного стресса и ингибированию транскрипционного фактора NFkB p65, что сопровождалось снижением выраженности стеатоза печени.…”

Section: глутаминunclassified

“…Gln -глутамин; WSD -диета по западному образцу; C -контроль; DE -эффект диеты; GE -эффект глутамина; DEXGE -взаимодействие между диетой и глутамином; NAS -оценка активности неалкогольной жировой болезни печени. По материалам Sellmann et al [18] и с их разрешения. Fig.…”

Section: заключениеunclassified

“…Gln -glutamine; WSD -Western-style diet; C -control; DE -diet effect; GE -glutamine effect; DEXGE -interaction between diet and glutamine; NAS -non-alcoholic fatty liver disease activity score. From Sellmann et al [18] with permission. Было предположено, что применение нового морфологического метода обнаружения повышения концентраций аммиака в печени, которое, как доказано, коррелирует с тяжестью хронического заболевания печени, может быть полезным для прогнозирования результатов лечения пациентов с жировой дистрофией печени [3].…”

Section: заключениеunclassified

See 1 more Smart Citation

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Баттерворт

Канбэй

2019

Rossijskij žurnal gastroènterologii, gepatologii, koloproktolog

View full text Add to dashboard Cite

Background.Non-alcoholic fatty liver disease (NAFLD) is the leading chronic hepatic condition worldwide and new approaches to management and treatment are limited.Summary.L-ornithine L-aspartate (LOLA) has hepatoprotective properties in patients with fatty liver of diverse etiology and results of a multicenter randomized clinical trial reveal that 12 weeks treatment with oral LOLA (6–9 g/d) results in a dose-related reduction in activities of liver enzymes and triglycerides together with significant improvements of liver/spleen CT ratios. A preliminary report described improvements of hepatic microcirculation in patients with nonalcoholic steatohepatitis (NASH) following treatment with LOLA. Mechanisms responsible for the beneficial effects of LOLA in NAFLD/NASH involve, in addition to its established ammonia-lowering effect, metabolic transformations of the LOLA-constituent amino acids L-ornithine and L-aspartate into L-glutamine, L-arginine, and glutathione. These metabolites have well-established actions implicated in the prevention of lipid peroxidation, improvement of hepatic microcirculation in addition to anti-inflammatory, and anti-oxidant properties.Key messages.(1) LOLA is effective for the treatment of key indices in NAFLD/NASH. (2) Mechanisms other than LOLA’s ammonia-lowering action have been postulated. (3) Further assessments in the clinical setting are now required.

show abstract

Oral Glutamine Supplementation Protects Female Mice from Nonalcoholic Steatohepatitis

Abstract: Our data suggest that the protective effects of oral Gln supplementation on the development of WSD-induced NASH in mice are associated with protection against the induction of iNOS and lipid peroxidation in the liver.

Cited by 31 publications

References 40 publications

l-Ornithine l-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease

l-Ornithine l-Aspartate (LOLA) as a Novel Approach for Therapy of Non-alcoholic Fatty Liver Disease

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Hepatoprotection by L-Ornithine L-Aspartate in Non-Alcoholic Fatty Liver Disease

Contact Info

Product

Resources

About