title: Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle.
abstract: BACKGROUND
  Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain.
  
  
  METHODS
  C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro.
  
  
  RESULTS
  Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle.
  
  
  CONCLUSIONS
  Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders.
authors.affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Tsutsumi
authors.affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoshida
authors.affiliation: Tokushima Prefectural Industrial Technology Center, Tokushima, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Nii
authors.affiliation: Tokushima Prefectural Industrial Technology Center, Tokushima, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Okahisa
authors.affiliation: Tokushima Prefectural Industrial Technology Center, Tokushima, Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Iwata
authors.affiliation: Tokushima Prefectural Industrial Technology Center, Tokushima, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Tsukayama
authors.affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Rei
authors.initials: R
authors.lastname: Hashimoto
authors.affiliation: Department of Metabolism and Nutrition, Institute of Health Bioscience, University of Tokushima, Tokushima, Japan.
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Taniguchi
authors.affiliation: Department of Metabolism and Nutrition, Institute of Health Bioscience, University of Tokushima, Tokushima, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakaue
authors.affiliation: Department of Endocrinology and Diabetes, Department of General Internal Medicine, School of Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Emi
authors.initials: E
authors.lastname: Shuto
authors.affiliation: Department of Public Health and Applied and Nutrition, Institute of Health Bioscience, University of Tokushima, 3-18-15 Kuramoto, Tokushima 770-8503, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Sakai
keywords: Glucose metabolism; Lipid metabolism; Mitochondria; Sudachitin
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