Abstract
Aims/hypothesisEnergy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling.MethodsIn a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic–euglycaemic clamps with d-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals.ResultsSAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05).Conclusions/interpretationLipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling.Trial registrationClinicalTrials.gov.NCT01736202.FundingGerman Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.Graphical abstract
Highlights
Western-style diets, as defined by high intake of energy and fat, have been related to the rising prevalence of insulinresistant states such as obesity and type 2 diabetes [1, 2]
palm oil (PAL) led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs safflower oil (SAF))
SAF and PAL both decreased insulin-stimulated rate of glucose disposal (Rd) (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05)
Summary
Western-style diets, as defined by high intake of energy and fat, have been related to the rising prevalence of insulinresistant states such as obesity and type 2 diabetes [1, 2]. Current guidelines recommend diets low in saturated fatty acid (FA) for type 2 diabetes and CVD, the evidence remains limited [3, 4]. We have demonstrated that the skeletal muscle insulin resistance in obesity and type 2 diabetes associates with activation of the myocellular diacylglycerol (DAG)– novel protein kinase C (nPKC) isoform θ pathway, an inhibitory cascade of proximal insulin signalling [5, 6]. In line with results from preclinical models [7], we showed that this pathway is operative in glucose-tolerant humans upon i.v. infusion of lipid emulsions containing predominately monounsaturated FA, as well as in obese individuals and those with type 2 diabetes without any infusion [6]. The temporal sequence of the molecular events in human skeletal muscle upon ingestion of differently composed lipid meals remains unknown
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