Long-term Branched-chain Amino Acid Supplementation Improves Glucose Tolerance in Patients with Nonalcoholic Steatohepatitis-related Cirrhosis

Miyake, Teruki; Abe, Masanori; Furukawa, Shinya; Terada, Yoshio; Toshimitsu, Kumiko; Ueda, T.; Yamamoto, Shin; Hirooka, Masashi; Kumagi, Teru; Hiasa, Yoichi; Matsuura, Bunzo; Onji, Morikazu

doi:10.2169/internalmedicine.51.7578

Cited by 34 publications

(25 citation statements)

References 17 publications

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“…Importantly, systemic amino acid increases are reported to function as adaptive responses against disease (Adams 2011; Kalhan et al 2011; Newgard et al 2009; She et al 2007). In light of recent discoveries demonstrating the clinical effectiveness of BCAA supplementation in liver disease and cancer prevention (Hagiwara et al 2012; Hayaishi et al 2011; Miyake et al 2012), the present study provides important information for NASH researchers and clinicians.…”

Section: Discussionmentioning

confidence: 96%

“…These roles range from cancer stem cell suppression to inhibition of reactive oxygen species (ROS). BCAA supplementation is also reported to improve insulin resistance and can promote liver regeneration (Miyake et al 2012; Nagao et al 2012; Tajiri and Shimizu 2013; Yoshida et al 2012). Determining the alterations in hepatic profiles of BCAA composition, with metabolism and signaling genes will provide important mechanistic information on the biochemical changes occurring in response to progression of this disease.…”

Section: Introductionmentioning

confidence: 99%

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Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease

et al. 2014

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Nonalcoholic fatty liver disease (NAFLD) is a globally widespread disease of increasing clinical significance. The pathological progression of the disease from simple steatosis to nonalcoholic steatohepatitis (NASH) has been well defined, however, the contribution of altered branched chain amino acid metabolomic profiles to the progression of NAFLD is not known. The three BCAAs: leucine, isoleucine and valine are known to mediate activation of several important hepatic metabolic signaling pathways ranging from insulin signaling to glucose regulation. The purpose of this study is to profile changes in hepatic BCAA metabolite levels with transcriptomic changes in the progression of human NAFLD to discover novel mechanisms of disease progression. Metabolomic and transcriptomic data sets representing the spectrum of human NAFLD (normal, steatosis, NASH fatty, and NASH not fatty livers) were utilized for this study. During the transition from steatosis to NASH, increases in the levels of leucine (127 % of normal), isoleucine (139 %), and valine (147 %) were observed. Carnitine metabolites also exhibited significantly elevated profiles in NASH fatty and NASH not fatty samples and included propionyl, hexanoyl, lauryl, acetyl and butyryl carnitine. Amino acid and BCAA metabolism gene sets were significantly enriched among downregulated genes during NASH. These cumulative alterations in BCAA metabolite and amino acid metabolism gene profiles represent adaptive physiological responses to disease-induced hepatic stress in NASH patients.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease

et al. 2014

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“…BCAA infusion was reported to decrease plasma glucose concentrations in patients with advanced liver cirrhosis [102] , and oral BCAA administration was recently shown to reduce both blood glucose concentrations [103,104] and insulin resistance in patients with chronic liver diseases, especially in men [19,105] . More recently, long-term BCAA supplementation was shown to improve glucose tolerance in patients with nonalcoholic steatohepatitis (NASH)-related cirrhosis, and may be an alternative treatment for NASH [106] .…”

Section: Liver Transplantationmentioning

confidence: 99%

Branched-chain amino acids in liver diseases

Tajiri¹,

Shimizu²

2018

Transl. Gastroenterol. Hepatol.

100

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Branched chain amino acids (BCAAs) have been shown to affect gene expression, protein metabolism, apoptosis and regeneration of hepatocytes, and insulin resistance. They have also been shown to inhibit the proliferation of liver cancer cells in vitro , and are essential for lymphocyte proliferation and dendritic cell maturation. In patients with advanced chronic liver disease, BCAA concentrations are low, whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high, conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients. Based on these basic observations, patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines, with positive effects.© 2013 Baishideng Publishing Group Co., Limited. All rights reserved.Key words: Liver disease; Branched chain amino acids; Gene expression; Hepatocyte apoptosis; Hepatocyte regeneration; Immunity; Treatment Core tip: Advanced liver diseases are commonly accompanied by nutritional disturbances, which worsen the prognosis of the patients. Serum levels of branchedchain amino acids (BCAAs) are decreased in patients with liver cirrhosis, and the amino acids imbalance could affect the clinical picture of the disease and the prognosis of the patients. However, there are few comprehensive reviews on the biological activities of BCAAs. In this review, we summarize the biological activities of BCAAs, and discuss possible applications of BCAAs for the management of patients with advanced liver diseases with a list of clinical trials of BCAA administration.Tajiri K, Shimizu Y. Branched-chain amino acids in liver diseases. World

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“…This observation may be related to increased expression and autophosphorylation of the IR, as observed in experimental and clinical T2DM [148]. In line with this observation, BCAA supplementation has been linked to reduced insulin resistance in patients with chronic viral liver disease [149,150] and in patients with nonalcoholic steatohepatitis-related liver cirrhosis [151]. Interestingly, beneficial effects of BCAA supplementation have been also observed in animal models of insulin-dependent diabetes mellitus, such as the streptozotocin rat model [152][153][154], suggesting a possible metabolic amelioration in the presence of normal insulin sensitivity and loss of insulin activation.…”

Section: Amino Acids and The Preservation Or Augmentation Of Lean Bodmentioning

confidence: 61%

Essential Amino Acid Supplementation for the Prevention and Treatment of Obesity

D’Antona

2014

Nutrition in the Prevention and Treatment of Abdominal Obesity

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Long-term Branched-chain Amino Acid Supplementation Improves Glucose Tolerance in Patients with Nonalcoholic Steatohepatitis-related Cirrhosis

Cited by 34 publications

References 17 publications

Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease

Branched chain amino acid metabolism profiles in progressive human nonalcoholic fatty liver disease

Branched-chain amino acids in liver diseases

Essential Amino Acid Supplementation for the Prevention and Treatment of Obesity

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