title: Effects of visceral adiposity on glycerol pathways in gluconeogenesis.
abstract: OBJECTIVE
  To determine the feasibility of using oral13C labeled glycerol to assess effects of visceral adiposity on gluconeogenic pathways in obese humans.
  
  
  METHODS
  Obese (BMI ≥30kg/m2) participants without type 2 diabetes underwent visceral adipose tissue (VAT) assessment and stratification by median VAT into high VAT-fasting (n=3), low VAT-fasting (n=4), and high VAT-refed (n=2) groups. Participants ingested [U-13C3] glycerol and blood samples were subsequently analyzed at multiple time points over 3h by NMR spectroscopy. The fractions of plasma glucose (enrichment) derived from [U-13C3] glycerol via hepatic gluconeogenesis, pentose phosphate pathway (PPP), and tricarboxylic acid (TCA) cycle were assessed using13C NMR analysis of glucose. Mixed linear models were used to compare13C enrichment in glucose between groups.
  
  
  RESULTS
  Mean age, BMI, and baseline glucose were 49years, 40.1kg/m2, and 98mg/dl, respectively. Up to 20% of glycerol was metabolized in the TCA cycle prior to gluconeogenesis and PPP activity was minor (<1% of total glucose) in all participants. There was a 21% decrease in13C enrichment in plasma glucose in the high VAT-fasting compared with low VAT-fasting group (p=0.03), suggesting dilution by endogenous glycerol. High VAT-refed participants had 37% less13C enrichment in glucose compared with high VAT-fasting (p=0.02). There was a trend toward lower [1,2-13C2] (via PPP) and [5,6-13C2]/[4,5,6-13C3] (via TCA cycle) glucose in high VAT versus low VAT groups.
  
  
  CONCLUSIONS
  We applied a simple method to detect gluconeogenesis from glycerol in obese humans. Our findings provide preliminary evidence that excess visceral fat disrupts multiple pathways in hepatic gluconeogenesis from glycerol.
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA. Electronic address: ian.neeland@utsouthwestern.edu.
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Neeland
authors.affiliation: Department of Internal Medicine, Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Connor
authors.initials: C
authors.lastname: Hughes
authors.affiliation: Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Colby R
authors.initials: CR
authors.lastname: Ayers
authors.affiliation: Advanced Imaging Research Center and Departments of Internal Medicine and Radiology, University of Texas Southwestern Medical Center and VA North Texas Healthcare System, Dallas, TX, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
authors.affiliation: Advanced Imaging Research Center and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Eunsook S
authors.initials: ES
authors.lastname: Jin
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology*; D050154:Adiposity; D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D002952:Citric Acid Cycle; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D004435:Eating; D005215:Fasting / Q000378:metabolism; D005260:Female; D005943:Gluconeogenesis; D005990:Glycerol / Q000378:metabolism*; D006801:Humans; D050152:Intra-Abdominal Fat / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010427:Pentose Phosphate Pathway
chemical_list: D001786:Blood Glucose; D005990:Glycerol
keywords: Gluconeogenesis; Glycerol; Pentose phosphate pathway; Tricarboxylic acid cycle; Visceral fat