Reduction of AMPK activity and altered MAPKs signalling in peripheral blood mononuclear cells in response to acute glucose ingestion following a short-term high fat diet in young healthy men

Abstract

BackgroundPeripheral blood mononuclear cells (PBMCs) are known to respond to systematic changes in nutrient availability. The impact of a short-term high fat diet (HFD), with and without acute glucose ingestion, on the energy-sensing enzyme 5’ AMP-activated protein kinase (AMPK) as well as mitochondrial oxidative phosphorylation (OXPHOS) proteins in PBMCs is currently unknown. MethodsNine healthy, lean young males participated in a 7day HFD intervention, designed to induce transient glucose intolerance. The phosphorylation status and total protein content of AMPK and inflammatory mitogen-activated protein kinases (MAPKs), and total OXPHOS protein in PBMCs, along with circulating cytokines, were assessed in the fasted state and following an oral glucose tolerance test (OGTT) before and after the HFD. ResultsOne week of HFD resulted in relative glucose intolerance. The HFD resulted in a reduction of AMPK phosphorylation under fasting basal conditions and following the OGTT (both P<0.05), while there were no differences in OXPHOS protein expression. Although the short-term HFD had no effect on basal phosphorylation of p38, JNK or ERK1/2, the activation of MAPKs signalling in response to glucose ingestion was attenuated post-HFD as compared to pre-HFD (P<0.05 for all). Circulating cytokines were not significantly affected by the HFD. ConclusionsWe conclude that impaired glucose tolerance in response to 7day HFD resulted in decreased AMPK activity and impaired glucose-stimulated MAPK activation following glucose ingestion in vivo in PBMCs from young, lean subjects. Further studies are warranted to explore how dietary manipulations impact interplay between AMPK and inflammatory signalling, along with immune function, in PBMCs.