title: Artemisia scoparia extract attenuates non-alcoholic fatty liver disease in diet-induced obesity mice by enhancing hepatic insulin and AMPK signaling independently of FGF21 pathway.
abstract: OBJECTIVE
  Nonalcoholic fatty liver disease (NAFLD) is a common liver disease which has no standard treatment. In this regard, we sought to evaluate the effects of extracts of Artemisia santolinaefolia (SANT) and Artemisia scoparia (SCO) on hepatic lipid deposition and cellular signaling in a diet-induced obesity (DIO) animal model.
  
  
  METHODS
  DIO C57/B6J mice were randomly divided into three groups, i.e. HFD, SANT and SCO. Both extracts were incorporated into HFD at a concentration of 0.5% (w/w). Fasting plasma glucose, insulin, adiponectin, and FGF21 concentrations were measured.
  
  
  RESULTS
  At the end of the 4-week intervention, liver tissues were collected for analysis of insulin, AMPK, and FGF21 signaling. SANT and SCO supplementation significantly increased plasma adiponectin levels when compared with the HFD mice (P<0.001). Fasting insulin levels were significantly lower in the SCO than HFD mice, but not in SANT group. Hepatic H&E staining showed fewer lipid droplets in the SCO group than in the other two groups. Cellular signaling data demonstrated that SCO significantly increased liver IRS-2 content, phosphorylation of IRS-1, IR β, Akt1 and Akt2, AMPK α1 and AMPK activity and significantly reduced PTP 1B abundance when compared with the HFD group. SCO also significantly decreased fatty acid synthase (FAS), HMG-CoA Reductase (HMGR), and Sterol regulatory element-binding protein 1c (SREBP1c), but not Carnitine palmitoyltransferase I (CPT-1) when compared with HFD group. Neither SANT nor SCO significantly altered plasma FGF21 concentrations and liver FGF21 signaling.
  
  
  CONCLUSIONS
  This study suggests that SCO may attenuate liver lipid accumulation in DIO mice. Contributing mechanisms were postulated to include promotion of adiponectin expression, inhibition of hepatic lipogenesis, and/or enhanced insulin and AMPK signaling independent of FGF21 pathway.
authors.affiliation: Nutrition and Diabetes Research Laboratory, Pennington Biomedical Research Center, LSU System, Baton Rouge, LA 70808, USA.
authors.forename: Zhong Q
authors.initials: ZQ
authors.lastname: Wang
authors.forename: Xian H
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Yu
authors.forename: Russell C
authors.initials: RC
authors.lastname: Tipton
authors.forename: Ilya
authors.initials: I
authors.lastname: Raskin
authors.forename: David
authors.initials: D
authors.lastname: Ribnicky
authors.forename: William
authors.initials: W
authors.lastname: Johnson
authors.forename: William T
authors.initials: WT
authors.lastname: Cefalu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D019306:Artemisia; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000188:drug therapy* / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000097:blood / Q000502:physiology*; D007328:Insulin / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000378:metabolism*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D007328:Insulin; D010936:Plant Extracts; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D055372:AMP-Activated Protein Kinases
keywords: AMPK; FGF21; FGFR; Fibroblast growth factor 21; Fibroblast growth factor receptor, NAFLD, nonalcoholic fatty liver disease; IPGTT; Insulin resistance; NAFLD; Obesity; intraperitoneal glucose tolerance test. AMPK, AMP-activated protein kinase