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Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model.
Metabolism. 2011 Jun; 60(6):805-14.M

Abstract

Nonalcoholic steatohepatitis (NASH) is one of the most frequent causes of abnormal liver dysfunction associated with synthesis and oxidation of fatty acids. Adiponectin receptors (AdipoR1/R2) and insulin receptor substrates (IRS-1/-2) are known as modulators of these fatty acid metabolisms in the liver; however, the regulatory roles of these receptors in the synthesis and oxidation of fatty acids are unclear in the liver of NASH. In this study, we examined the roles of hepatic AdipoR1/R2 and IRS-1/-2 in NASH using an animal model. After feeding a high-fat and high-cholesterol diet to obese fa/fa Zucker rats for 8 weeks, rats showed fatty liver spontaneously with inflammation and fibrosis that are characteristic of NASH. The expression levels of AdipoR1/R2 and IRS-2 were significantly decreased, whereas IRS-1 was significantly increased, in NASH. As a result of the decrease of AdipoR1/R2 expression, the messenger RNA expression levels of genes located downstream of AdipoR1/R2, adenosine monophosphate-activated protein kinase α1/α2, which inhibits fatty acid synthesis, and peroxisome proliferator-activated receptor α, which activates fatty acid oxidation, also decreased. Expression level of sterol regulatory element binding protein-1c was found to be elevated, suggesting the up-regulation of IRS-1, and resulted in increased fatty acid synthesis. Furthermore, increase of forkhead box protein A2 expression was observed, which might be associated with the down-regulation of IRS-2, facilitating fatty acid oxidation. Taken together, increased synthesis and oxidation of fatty acids by up- or down-regulation of AdipoR or IRS may contribute to the progression of NASH. Thus, AdipoR and IRS might be crucially important regulators for the synthesis and oxidation of fatty acids in the liver of NASH.

Authors+Show Affiliations

Laboratory of Biomedical Science, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, Fujisawa 252-0880, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20846698

Citation

Matsunami, Tokio, et al. "Regulation of Synthesis and Oxidation of Fatty Acids By Adiponectin Receptors (AdipoR1/R2) and Insulin Receptor Substrate Isoforms (IRS-1/-2) of the Liver in a Nonalcoholic Steatohepatitis Animal Model." Metabolism: Clinical and Experimental, vol. 60, no. 6, 2011, pp. 805-14.
Matsunami T, Sato Y, Ariga S, et al. Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism. 2011;60(6):805-14.
Matsunami, T., Sato, Y., Ariga, S., Sato, T., Shimomura, T., Kashimura, H., Hasegawa, Y., & Yukawa, M. (2011). Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism: Clinical and Experimental, 60(6), 805-14. https://doi.org/10.1016/j.metabol.2010.07.032
Matsunami T, et al. Regulation of Synthesis and Oxidation of Fatty Acids By Adiponectin Receptors (AdipoR1/R2) and Insulin Receptor Substrate Isoforms (IRS-1/-2) of the Liver in a Nonalcoholic Steatohepatitis Animal Model. Metabolism. 2011;60(6):805-14. PubMed PMID: 20846698.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. AU - Matsunami,Tokio, AU - Sato,Yukita, AU - Ariga,Satomi, AU - Sato,Takuya, AU - Shimomura,Toshiko, AU - Kashimura,Haruka, AU - Hasegawa,Yuki, AU - Yukawa,Masayoshi, Y1 - 2010/09/16/ PY - 2010/03/15/received PY - 2010/07/21/revised PY - 2010/07/26/accepted PY - 2010/9/18/entrez PY - 2010/9/18/pubmed PY - 2011/7/20/medline SP - 805 EP - 14 JF - Metabolism: clinical and experimental JO - Metabolism VL - 60 IS - 6 N2 - Nonalcoholic steatohepatitis (NASH) is one of the most frequent causes of abnormal liver dysfunction associated with synthesis and oxidation of fatty acids. Adiponectin receptors (AdipoR1/R2) and insulin receptor substrates (IRS-1/-2) are known as modulators of these fatty acid metabolisms in the liver; however, the regulatory roles of these receptors in the synthesis and oxidation of fatty acids are unclear in the liver of NASH. In this study, we examined the roles of hepatic AdipoR1/R2 and IRS-1/-2 in NASH using an animal model. After feeding a high-fat and high-cholesterol diet to obese fa/fa Zucker rats for 8 weeks, rats showed fatty liver spontaneously with inflammation and fibrosis that are characteristic of NASH. The expression levels of AdipoR1/R2 and IRS-2 were significantly decreased, whereas IRS-1 was significantly increased, in NASH. As a result of the decrease of AdipoR1/R2 expression, the messenger RNA expression levels of genes located downstream of AdipoR1/R2, adenosine monophosphate-activated protein kinase α1/α2, which inhibits fatty acid synthesis, and peroxisome proliferator-activated receptor α, which activates fatty acid oxidation, also decreased. Expression level of sterol regulatory element binding protein-1c was found to be elevated, suggesting the up-regulation of IRS-1, and resulted in increased fatty acid synthesis. Furthermore, increase of forkhead box protein A2 expression was observed, which might be associated with the down-regulation of IRS-2, facilitating fatty acid oxidation. Taken together, increased synthesis and oxidation of fatty acids by up- or down-regulation of AdipoR or IRS may contribute to the progression of NASH. Thus, AdipoR and IRS might be crucially important regulators for the synthesis and oxidation of fatty acids in the liver of NASH. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/20846698/Regulation_of_synthesis_and_oxidation_of_fatty_acids_by_adiponectin_receptors__AdipoR1/R2__and_insulin_receptor_substrate_isoforms__IRS_1/_2__of_the_liver_in_a_nonalcoholic_steatohepatitis_animal_model_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(10)00260-X DB - PRIME DP - Unbound Medicine ER -