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Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance
Theresia Sarabhai, … , John Griffith Jones, Michael Roden
Theresia Sarabhai, … , John Griffith Jones, Michael Roden
Published May 21, 2020
Citation Information: JCI Insight. 2020;5(10):e134520. https://doi.org/10.1172/jci.insight.134520.
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Clinical Medicine Endocrinology Metabolism

Monounsaturated fat rapidly induces hepatic gluconeogenesis and whole-body insulin resistance

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Abstract

BACKGROUND While saturated fat intake leads to insulin resistance and nonalcoholic fatty liver, Mediterranean-like diets enriched in monounsaturated fatty acids (MUFA) may have beneficial effects. This study examined effects of MUFA on tissue-specific insulin sensitivity and energy metabolism.METHODS A randomized placebo-controlled cross-over study enrolled 16 glucose-tolerant volunteers to receive either oil (OIL, ~1.18 g/kg), rich in MUFA, or vehicle (VCL, water) on 2 occasions. Insulin sensitivity was assessed during preclamp and hyperinsulinemic-euglycemic clamp conditions. Ingestion of 2H2O/acetaminophen was combined with [6,6-2H2]glucose infusion and in vivo 13C/31P/1H/ex vivo 2H-magnet resonance spectroscopy to quantify hepatic glucose and energy fluxes.RESULTS OIL increased plasma triglycerides and oleic acid concentrations by 44% and 66% compared with VCL. Upon OIL intervention, preclamp hepatic and whole-body insulin sensitivity markedly decreased by 28% and 27%, respectively, along with 61% higher rates of hepatic gluconeogenesis and 32% lower rates of net glycogenolysis, while hepatic triglyceride and ATP concentrations did not differ from VCL. During insulin stimulation hepatic and whole-body insulin sensitivity were reduced by 21% and 25%, respectively, after OIL ingestion compared with that in controls.CONCLUSION A single MUFA-load suffices to induce insulin resistance but affects neither hepatic triglycerides nor energy-rich phosphates. These data indicate that amount of ingested fat, rather than its composition, primarily determines the development of acute insulin resistance.TRIAL REGISTRATION ClinicalTrials.gov NCT01736202.FUNDING German Diabetes Center, German Federal Ministry of Health, Ministry of Culture and Science of the state of North Rhine-Westphalia, German Federal Ministry of Education and Research, German Diabetes Association, German Center for Diabetes Research, Portugal Foundation for Science and Technology, European Regional Development Fund, and Rede Nacional de Ressonancia Magnética Nuclear.

Authors

Theresia Sarabhai, Sabine Kahl, Julia Szendroedi, Daniel F. Markgraf, Oana-Patricia Zaharia, Cristina Barosa, Christian Herder, Frithjof Wickrath, Pavel Bobrov, Jong-Hee Hwang, John Griffith Jones, Michael Roden

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Figure 1

Study design.

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Study design.
Participants randomly received either an oral dose of cano...
Participants randomly received either an oral dose of canola oil (OIL, blue) or an identical volume of water (vehicle [VCL]) on 2 occasions spaced by an 8-week period. Hepatic glucose and energy metabolism was measured by in vivo 13C/31P/1H and ex vivo 2H-magnetic resonance spectroscopy (MRS) combined with 2H2O and acetaminophen ingestion before and during hyperinsulinemic-euglycemic clamps, for which a “hot” glucose infusion (hot-GINF) protocol with [6,6-2H2]glucose was used.

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