Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease

Nishanth E. Sunny, Elizabeth J. Parks, Jeffrey D. Browning, Shawn C. Burgess

Research output: Contribution to journalArticle

245 Citations (Scopus)

Abstract

Approximately one-third of the U.S. population has nonalcoholic fatty liver disease (NAFLD), a condition closely associated with insulin resistance and increased risk of liver injury. Dysregulated mitochondrial metabolism is central in these disorders, but the manner and degree of dysregulation are disputed. This study tested whether humans with NAFLD have abnormal in vivo hepatic mitochondrial metabolism. Subjects with low (3.0%) and high (17%) intrahepatic triglyceride (IHTG) were studied using 2H and 13C tracers to evaluate systemic lipolysis, hepatic glucose production, and mitochondrial pathways (TCA cycle, anaplerosis, and ketogenesis). Individuals with NAFLD had 50% higher rates of lipolysis and 30% higher rates of gluconeogenesis. There was a positive correlation between IHTG content and both mitochondrial oxidative and anaplerotic fluxes. These data indicate that mitochondrial oxidative metabolism is ∼2-fold greater in those with NAFLD, providing a potential link between IHTG content, oxidative stress, and liver damage.

Original languageEnglish (US)
Pages (from-to)804-810
Number of pages7
JournalCell Metabolism
Volume14
Issue number6
DOIs
StatePublished - Dec 7 2011

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Gluconeogenesis
Triglycerides
Lipolysis
Liver
Insulin Resistance
Oxidative Stress
Glucose
Non-alcoholic Fatty Liver Disease
Wounds and Injuries
Population

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Physiology

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Excessive hepatic mitochondrial TCA cycle and gluconeogenesis in humans with nonalcoholic fatty liver disease. / Sunny, Nishanth E.; Parks, Elizabeth J.; Browning, Jeffrey D.; Burgess, Shawn C.

In: Cell Metabolism, Vol. 14, No. 6, 07.12.2011, p. 804-810.

Research output: Contribution to journalArticle

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