title: Impact of gut hormone FGF-19 on type-2 diabetes and mitochondrial recovery in a prospective study of obese diabetic women undergoing bariatric surgery.
abstract: The ileal-derived hormone, fibroblast growth factor 19 (FGF-19), may promote weight loss and facilitate type-2 diabetes mellitus remission in bariatric surgical patients. We investigated the effect of different bariatric procedures on circulating FGF-19 levels and the resulting impact on mitochondrial health in white adipose tissue (AT).
  
  
  
  Obese and type-2 diabetic women (n = 39, BMI > 35 kg/m2) undergoing either biliopancreatic diversion (BPD), laparoscopic greater curvature plication (LGCP), or laparoscopic adjustable gastric banding (LAGB) participated in this ethics approved study. Anthropometry, biochemical, clinical data, serum, and AT biopsies were collected before and 6 months after surgery. Mitochondrial gene expression in adipose biopsies and serum FGF-19 levels were then assessed.
  
  
  
  All surgeries led to metabolic improvements with BPD producing the greatest benefits on weight loss (↓30%), HbA1c (↓28%), and cholesterol (↓25%) reduction, whilst LGCP resulted in similar HbA1c improvements (adjusted for BMI). Circulating FGF-19 increased in both BPD and LGCP (χ2(2) = 8.088; P = 0.018), whilst, in LAGB, FGF-19 serum levels decreased (P = 0.028). Interestingly, circulating FGF-19 was inversely correlated with mitochondrial number in AT across all surgeries (n = 39). In contrast to LGCP and LAGB, mitochondrial number in BPD patients corresponded directly with changes in 12 of 14 mitochondrial genes assayed (P < 0.01).
  
  
  
  Elevated serum FGF-19 levels post-surgery were associated with improved mitochondrial health in AT and overall diabetic remission. Changes in circulating FGF-19 levels were surgery-specific, with BPD producing the best metabolic outcomes among the study procedures (BPD > LGCP > LAGB), and highlighting mitochondria in AT as a potential target of FGF-19 during diabetes remission.
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.|Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire (UHCW) NHS Trust, Coventry, UK.
authors.forename: Lucia
authors.initials: L
authors.lastname: Martinez de la Escalera
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.|Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire (UHCW) NHS Trust, Coventry, UK.|Aston Medical Research Institute, Aston Medical School, Aston University, Birmingham, UK.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kyrou
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Vrbikova
authors.affiliation: Institute of Endocrinology, Prague, Czech Republic.
authors.forename: Voitech
authors.initials: V
authors.lastname: Hainer
authors.affiliation: OB Clinic, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Sramkova
authors.affiliation: OB Clinic, Prague, Czech Republic.
authors.forename: Martin
authors.initials: M
authors.lastname: Fried
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.|Derby Teaching Hospitals NHS Foundation Trust, Derby, UK.
authors.forename: Milan K
authors.initials: MK
authors.lastname: Piya
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK.|Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire (UHCW) NHS Trust, Coventry, UK.
authors.forename: Sudhesh
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK. g.tripathi@westminster.ac.uk.|Department of Biomedical Sciences, University of Westminster, London, W1W 6UW, UK. g.tripathi@westminster.ac.uk.
authors.forename: Gyanendra
authors.initials: G
authors.lastname: Tripathi
authors.affiliation: Warwick Medical School, University of Warwick, Coventry, UK. p.g.mcternan@warwick.ac.uk.|Warwickshire Institute for the Study of Diabetes, Endocrinology and Metabolism (WISDEM), University Hospitals of Coventry and Warwickshire (UHCW) NHS Trust, Coventry, UK. p.g.mcternan@warwick.ac.uk.|School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS, UK. p.g.mcternan@warwick.ac.uk.
authors.forename: Philip G
authors.initials: PG
authors.lastname: McTernan
mesh_terms: D000328:Adult; D050110:Bariatric Surgery / Q000379:methods*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D011446:Prospective Studies
chemical_list: C117476:FGF19 protein, human; D005346:Fibroblast Growth Factors
keywords: Bariatric surgery; FGF-19; Gut hormone; Mitochondria; Obesity; Type-2 diabetes recovery