Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle

Diabetologia. 2022 Feb;65(2):301-314. doi: 10.1007/s00125-021-05596-z. Epub 2021 Oct 26.

Abstract

Aims/hypothesis: Energy-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.

Methods: In 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.

Results: SAF 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/interpretation: Lipid-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 registration: ClinicalTrials.gov .NCT01736202.

Funding: German 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.

Keywords: Glucose metabolism; Insulin signalling; Lipotoxicity; Monounsaturated fatty acids; Saturated fat; Skeletal muscle.

Publication types

  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • Calorimetry
  • Cross-Over Studies
  • Dietary Fats / administration & dosage*
  • Diglycerides / blood
  • Fatty Acids / blood
  • Female
  • Glucose Clamp Technique
  • Healthy Volunteers
  • Humans
  • Insulin Resistance / physiology*
  • Male
  • Muscle, Skeletal / metabolism*
  • Oleic Acid / administration & dosage*
  • Palm Oil / administration & dosage
  • Palmitates / administration & dosage*
  • Protein Kinase C / blood
  • Safflower Oil / administration & dosage
  • Young Adult

Substances

  • Blood Glucose
  • Dietary Fats
  • Diglycerides
  • Fatty Acids
  • Palmitates
  • Oleic Acid
  • Palm Oil
  • Safflower Oil
  • Protein Kinase C

Associated data

  • ClinicalTrials.gov/NCT01736202