Abstract
BACKGROUNDWhile 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.METHODSA 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.RESULTSOIL 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.CONCLUSIONA 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 REGISTRATIONClinicalTrials.gov NCT01736202.FUNDINGGerman 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.
Highlights
There is an ongoing debate as to whether nutrient quality or quantity is mainly responsible for the effects on health or disease [1]
Mediterranean diet, which is rich in monounsaturated fatty acids (MUFA), may lower the risk of type 2 diabetes mellitus (T2D), nonalcoholic fatty liver disease (NAFLD) [2] and cardiovascular disease [3]
Fatty acid composition appears to play an important role for lipid-induced metabolic alterations, which is supported by the finding of higher liver TG content and insulin resistance with diets enriched in SAFA compared with those with MUFA, polyunsaturated fatty acids (PUFA), or simple sugars [4]
Summary
There is an ongoing debate as to whether nutrient quality or quantity is mainly responsible for the effects on health or disease [1]. We recently demonstrated that a single oral SAFA-rich lipid load initiates hepatic insulin resistance (HEP-IR) and fat accumulation in healthy lean men [5], likely resulting from lipid-mediated inhibition of insulin signaling [6]. This lipid load raised hepatic gluconeogenesis (GNG), which is possibly due to lipid-induced allosteric stimulation of hepatic mitochondrial activity, as reported in rodent models [6]. 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
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