title: Cellular mechanisms underlying the protective effects of preoperative feeding: a randomized study investigating muscle and liver glycogen content, mitochondrial function, gene and protein expression.
abstract: OBJECTIVE
  To investigate the effects of preoperative feeding with a carbohydrate-based drink that also contained glutamine and antioxidants (oral nutritional supplement [ONS], Fresenuis Kabi, Germany) on glycogen reserves, mitochondrial function, and the expression of key metabolic genes and proteins.
  
  
  BACKGROUND
  Preoperative carbohydrate loading attenuates the decline in postoperative insulin sensitivity but the cellular mechanisms underlying this remain unclear.
  
  
  METHODS
  Two groups of 20 patients undergoing laparoscopic cholecystectomy participated in this randomized placebo-controlled double-blind study. Patients received either 600 mL of ONS or placebo the evening before surgery, and again 300 mL 3 to 4 hours before anesthesia. A 300-mL aliquot of ONS contained 50 g of carbohydrate, 15 g of glutamine and antioxidants. Blood was sampled before ingestion of the evening drink, after induction of anesthesia, and on postoperative day 1 for measurement of concentrations of glucose, glutamine, and antioxidants. Rectus abdominis muscle and liver biopsies were performed intraoperatively to determine glycogen and glutamine concentrations, mitochondrial function, pyruvate dehydrogenase kinase (PDK4), forkhead transcription factor 1 (FOXO1), and metallothionein 1A (Mt1A) expression.
  
  
  RESULTS
  There were no drink-related complications. ONS ingestion led to increased intraoperative liver glycogen reserves (44%, P < 0.001) and plasma glutamine and antioxidant concentrations, the latter 2 remaining elevated up to the first postoperative day. Muscle PDK4 mRNA, PDK4 protein expression, and Mt1A mRNA expression were 4-fold (P < 0.001), 44% (P < 0.05), and 1.5-fold (P < 0.001), respectively, lower in the ONS group. There were no differences in FOXO1 mRNA and protein expression.
  
  
  CONCLUSIONS
  The changes in muscle PDK4 may explain the mechanism by which preoperative feeding with carbohydrate-based drinks attenuates the development of postoperative insulin resistance.
authors.affiliation: Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre NIHR Biomedical Research Unit, Nottingham University Hospitals, Queen's Medical Centre, Nottingham, United Kingdom.
authors.forename: Sherif
authors.initials: S
authors.lastname: Awad
authors.forename: Dumitru
authors.initials: D
authors.lastname: Constantin-Teodosiu
authors.forename: Despina
authors.initials: D
authors.lastname: Constantin
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Rowlands
authors.forename: Kenneth C H
authors.initials: KC
authors.lastname: Fearon
authors.forename: Ian A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: Dileep N
authors.initials: DN
authors.lastname: Lobo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000975:Antioxidants / Q000008:administration & dosage; D016009:Chi-Square Distribution; D017081:Cholecystectomy, Laparoscopic; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology*; D005947:Glucose / Q000008:administration & dosage; D005973:Glutamine / Q000008:administration & dosage; D006801:Humans; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D008668:Metallothionein / Q000378:metabolism; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010919:Placebos; D011300:Preoperative Care; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric
chemical_list: D000975:Antioxidants; D004040:Dietary Carbohydrates; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D008112:Liver Glycogen; C530099:MT1A protein, human; C000631432:PDK4 protein, human; D010919:Placebos; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D005973:Glutamine; D008668:Metallothionein; D017346:Protein Serine-Threonine Kinases; D005947:Glucose