Excessive Hepatic Mitochondrial TCA Cycle and Gluconeogenesis in Humans with Nonalcoholic Fatty Liver Disease

By N. Sunny, E. Parks, J. Browning, Shawn C. Burgess. Cell Metabolism, 2011

617 citations recorded by the source corpus.

Summary 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.

Subfields: Endocrinology, Diabetes and Metabolism, Epidemiology, Physiology

View Paper: https://www.semanticscholar.org/paper/9ca6a585f12a17d4331106820f21c2dd11d482e1

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Citations in the corpus

Integrating Mechanisms for Insulin Resistance: Common Threads and Missing Links (2012, positive): “, 2011) and others reporting increased hepatic mitochondrial metabolism (Sunny et al., 2011).”
Adaptation of hepatic mitochondrial function in humans with non-alcoholic fatty liver is lost in steatohepatitis. (2015, positive): “reported increased hepatic mitochondrial function in obese humans with NAFLD using stable isotope techniques (Sunny et al., 2011).”
Energy Metabolism in the Liver (2014, neutral): “associated with increased gluconeogenesis in humans (258).”
Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics (2017, background): “There is general consensus (Felig et al., 1974; Iozzo et al., 2010; Koliaki et al., 2015; Satapati et al., 2012, 2015; Sunny et al., 2011), but not uniform consensus (Koliaki and Roden, 2013; Perry et al., 2016; Rector et al., 2010), that before the development of bona fide NASH, hepatic…”
Non Alcoholic Fatty Liver Disease, Hepatic Insulin Resistance and Type 2 Diabetes (2014, background): “The relationship raises the question of why excess calories are not exclusively stored in adipose tissue, the primary storage site of TAG.(44) Fig.”
Endoplasmic reticulum stress signalling and the pathogenesis of non-alcoholic fatty liver disease. (2018, background): “suggesting that mitochondrial remodelling is present in NAFLD (94, 95).”
Non-Alcoholic Fatty Liver Disease (NAFLD) and Its Connection with Insulin Resistance, Dyslipidemia, Atherosclerosis and Coronary Heart Disease (2013, neutral): “[45] it ranged from 0% to 21% and this could explain at least in part the different results.”