A simple method to monitor hepatic gluconeogenesis and triglyceride synthesis following oral sugar tolerance test in obese adolescents

Anne Marie Carreau, Eunsook S Jin, Yesenia Garcia-Reyes, Haseeb Rahat, Kristen J. Nadeau, Craig R Malloy, Melanie Cree-Green

Research output: Contribution to journalArticle

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Abstract

Hepatic energy metabolism is a key element in many metabolic diseases. Hepatic anaplerosis provides carbons for gluconeogenesis (GNG) and triglyceride (TG) synthesis. We aimed to optimize a protocol that measures hepatic anaplerotic contribution for GNG, TG synthesis, and hepatic pentose phosphate pathway (PPP) activity using a single dose of oral [U-13C3]glycerol paired with an oral sugar tolerance test (OSTT) in a population with significant insulin resistance. The OSTT (75 g glucose + 25 g fructose) was administered to eight obese adolescents with polycystic ovarian syndrome (PCOS) followed by ingestion of [U-13C3]glycerol at t = 180 or t = 210 min. 13C-labeling patterns of serum glucose and TG-glycerol were determined by nuclear magnetic resonance. 13C enrichment in plasma TG-glycerol was detectable and stable from 240 to 390 min with the [U-13C3]glycerol drink at t = 180 min(3.65 ± 2.3 to 4.47 ± 1.4%; P > 0.4), but the enrichment was undetectable at 240 min with the glycerol drink at t = 210 min. The relative contribution from anaplerosis was determined at the end of the OSTT [18.5 ±3.4% (t = 180 min) vs. 16.0 ± 3.5% (t = 210 min); P = 0.27]. [U-13C3]glycerol was incorporated into GNG 390 min after the OSTT with an enrichment of 7.5-12.5%. Glucose derived from TCA cycle activity was 0.3-1%, and the PPP activity was 2.8-4.7%. In conclusion, it is possible to obtain relative measurements of hepatic anaplerotic contribution to both GNG and TG esterification following an OSTT in a highly insulin-resistant population using a minimally invasive technique. Tracer administration should be timed to allow enough de novo TG esterification and endogenous glucose release after the sugar drink.

Original languageEnglish (US)
Pages (from-to)R134-R142
JournalAmerican journal of physiology. Regulatory, integrative and comparative physiology
Volume317
Issue number1
DOIs
StatePublished - Jul 1 2019

Fingerprint

Gluconeogenesis
Glycerol
Triglycerides
Liver
Glucose
Pentose Phosphate Pathway
Esterification
Activity Cycles
Polycystic Ovary Syndrome
Metabolic Diseases
Fructose
Energy Metabolism
Population
Insulin Resistance
Magnetic Resonance Spectroscopy
Carbon
Eating
Insulin
Serum

Keywords

  • anaplerosis
  • gluconeogenesis
  • insulin resistance
  • liver metabolism
  • mitochondria
  • pentose phosphate pathway
  • polycystic ovarian syndrome

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

A simple method to monitor hepatic gluconeogenesis and triglyceride synthesis following oral sugar tolerance test in obese adolescents. / Carreau, Anne Marie; Jin, Eunsook S; Garcia-Reyes, Yesenia; Rahat, Haseeb; Nadeau, Kristen J.; Malloy, Craig R; Cree-Green, Melanie.

In: American journal of physiology. Regulatory, integrative and comparative physiology, Vol. 317, No. 1, 01.07.2019, p. R134-R142.

Research output: Contribution to journalArticle

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abstract = "Hepatic energy metabolism is a key element in many metabolic diseases. Hepatic anaplerosis provides carbons for gluconeogenesis (GNG) and triglyceride (TG) synthesis. We aimed to optimize a protocol that measures hepatic anaplerotic contribution for GNG, TG synthesis, and hepatic pentose phosphate pathway (PPP) activity using a single dose of oral [U-13C3]glycerol paired with an oral sugar tolerance test (OSTT) in a population with significant insulin resistance. The OSTT (75 g glucose + 25 g fructose) was administered to eight obese adolescents with polycystic ovarian syndrome (PCOS) followed by ingestion of [U-13C3]glycerol at t = 180 or t = 210 min. 13C-labeling patterns of serum glucose and TG-glycerol were determined by nuclear magnetic resonance. 13C enrichment in plasma TG-glycerol was detectable and stable from 240 to 390 min with the [U-13C3]glycerol drink at t = 180 min(3.65 ± 2.3 to 4.47 ± 1.4{\%}; P > 0.4), but the enrichment was undetectable at 240 min with the glycerol drink at t = 210 min. The relative contribution from anaplerosis was determined at the end of the OSTT [18.5 ±3.4{\%} (t = 180 min) vs. 16.0 ± 3.5{\%} (t = 210 min); P = 0.27]. [U-13C3]glycerol was incorporated into GNG 390 min after the OSTT with an enrichment of 7.5-12.5{\%}. Glucose derived from TCA cycle activity was 0.3-1{\%}, and the PPP activity was 2.8-4.7{\%}. In conclusion, it is possible to obtain relative measurements of hepatic anaplerotic contribution to both GNG and TG esterification following an OSTT in a highly insulin-resistant population using a minimally invasive technique. Tracer administration should be timed to allow enough de novo TG esterification and endogenous glucose release after the sugar drink.",
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