title: Abnormalities in the Metabolism of Fatty Acids and Triacylglycerols in the Liver of the Goto-Kakizaki Rat: A Model for Non-Obese Type 2 Diabetes.
abstract: The Goto-Kakizaki (GK) rat is widely used as an animal model for spontaneous-onset type 2 diabetes without obesity; nevertheless, little information is available on the metabolism of fatty acids and triacylglycerols (TAG) in their livers. We investigated the mechanisms underlying the alterations in the metabolism of fatty acids and TAG in their livers, in comparison with Zucker (fa/fa) rats, which are obese and insulin resistant. Lipid profiles, the expression of genes for enzymes and proteins related to the metabolism of fatty acid and TAG, de novo synthesis of fatty acids and TAG in vivo, fatty acid synthase activity in vitro, fatty acid oxidation in liver slices, and very-low-density-lipoprotein (VLDL)-TAG secretion in vivo were estimated. Our results revealed that (1) the TAG accumulation was moderate, (2) the de novo fatty acid synthesis was increased by upregulation of fatty acid synthase in a post-transcriptional manner, (3) fatty acid oxidation was also augmented through the induction of carnitine palmitoyltransferase 1a, and (4) the secretion rate of VLDL-TAG remained unchanged in the livers of GK rats. These results suggest that, despite the fact that GK rats exhibit non-obese type 2 diabetes, the upregulation of de novo lipogenesis is largely compensated by the upregulation of fatty acid oxidation, resulting in only moderate increase in TAG accumulation in the liver.
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Minako
authors.initials: M
authors.lastname: Karahashi
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hirata-Hanta
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Kawabata
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsutsumi
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Kametani
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Nanako
authors.initials: N
authors.lastname: Takamatsu
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Sakamoto
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Yamazaki
authors.affiliation: Department of Pharmaceutical Sciences, International University of Health and Welfare, 2600-1 Kitakanemaru, Ohtawara, Tochigi, 324-8501, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Asano
authors.affiliation: Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba, 283-8555, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Mitsumoto
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Kawashima
authors.affiliation: School of Pharmaceutical Sciences, Josai University, 1-1 Keyakidai, Sakado, Saitama, 350-0295, Japan. naokudo@josai.ac.jp.
authors.forename: Naomi
authors.initials: N
authors.lastname: Kudo
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D005227:Fatty Acids / Q000378:metabolism*; D005786:Gene Expression Regulation; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D009765:Obesity / Q000378:metabolism; D051381:Rats; D011924:Rats, Zucker; D014280:Triglycerides / Q000378:metabolism
chemical_list: D005227:Fatty Acids; D014280:Triglycerides
keywords: Fatty acid synthesis; Fatty acid β-oxidation; Goto-Kakizaki rat; Liver; Non-obese diabetes; Triacylglycerol metabolism