title: Licochalcone F alleviates glucose tolerance and chronic inflammation in diet-induced obese mice through Akt and p38 MAPK.
abstract: OBJECTIVE
  Licochalcone (lico) F is a novel synthetic retrochalcone. In this study, we investigated the anti-inflammatory effects of lico F in vitro, and its effects on obesity-induced chronic inflammation, glucose intolerance, and fatty liver in vivo.
  
  
  METHODS
  The inhibitory effects of lico F on TNFα-induced inflammation were investigated using NF-κB luciferase reporter assay and RT-PCR. Diet-induced obese mice were treated orally, once per day, with vehicle or lico F (10 mg/kg/day), for 3 weeks, and blood, liver, and adipose tissues were analyzed.
  
  
  RESULTS
  Lico F inhibited TNFα-induced NF-κB activation and mRNA expression of TNFα, COX-2, IL-6, IL-1β, and NOS2. In obese mice, lico F administration significantly alleviated glucose tolerance without changes in body weight gain and food intake. Lico F reduced adipocyte size and macrophage infiltration into white adipose tissue and improved hepatic lesions, by decreasing fat droplets and glycogen deposition. The mRNA expression levels of TNFα, MCP-1, and CD68 in white adipose tissue also decreased markedly. Moreover, lico F enhanced Akt signaling, but reduced p38 MAPK signaling in white adipose tissue.
  
  
  CONCLUSIONS
  Lico F had anti-inflammatory effects and showed beneficial effects on glucose metabolism, which could be partially caused by activation of the Akt signal pathway and obesity-induced chronic inflammation, probably by downregulating p38 signal pathway. Moreover, lico F could be used as a potential novel therapeutic compound against type 2 diabetes and obesity-induced chronic inflammation without the deleterious effects of body weight gain and fatty liver.
authors.affiliation: Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Bak
authors.affiliation: Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul, South Korea.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
authors.affiliation: BK21 PLUS Project, Yonsei University College of Dentistry, South Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea.
authors.forename: Sungil
authors.initials: S
authors.lastname: Jang
authors.affiliation: Department of Clinical Laboratory Science, Semyung University, Jecheon, South Korea.
authors.forename: Gye-Hyeong
authors.initials: GH
authors.lastname: Woo
authors.affiliation: Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, College of Medicine, Yonsei University, Seoul, South Korea.
authors.forename: Ho-Geun
authors.initials: HG
authors.lastname: Yoon
authors.affiliation: College of Pharmacy, CHA University, Seoul, South Korea.
authors.forename: Younghwa
authors.initials: Y
authors.lastname: Na
authors.affiliation: Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea.
authors.forename: Yun-Jung
authors.initials: YJ
authors.lastname: Yoo
authors.affiliation: Department of Bio and Fermentation Convergence Technology, Kookmin University, Seoul, South Korea.
authors.forename: Youngseok
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Yonsei University Wonju College of Medicine, Wonju, South Korea. Electronic address: yjeong@yonsei.ac.kr.
authors.forename: Yangsik
authors.initials: Y
authors.lastname: Jeong
authors.affiliation: Oral Cancer Research Institute, Yonsei University College of Dentistry, Seoul, South Korea; BK21 PLUS Project, Yonsei University College of Dentistry, South Korea; Department of Oral Biology, Yonsei University College of Dentistry, Seoul, South Korea; Department of Applied Life Science, The Graduate School, Yonsei University, Seoul, South Korea. Electronic address: Jcha@yuhs.ac.
authors.forename: Jeong-Heon
authors.initials: JH
authors.lastname: Cha
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D047188:Chalcones / Q000494:pharmacology*; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D015536:Down-Regulation; D018149:Glucose Intolerance / Q000188:drug therapy*; D007249:Inflammation / Q000188:drug therapy*; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D001786:Blood Glucose; C491768:Ccl2 protein, mouse; D047188:Chalcones; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C541672:licochalcone F; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Anti-inflammatory effect; Diet-induced obese mice; Licochalcone F; Obesity-induced chronic inflammation