title: 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: BACKGROUND
  Peripheral 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.
  
  
  METHODS
  Nine healthy, lean young males participated in a 7 day 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.
  
  
  RESULTS
  One 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.
  
  
  CONCLUSIONS
  We conclude that impaired glucose tolerance in response to 7 day 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.
authors.affiliation: School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
authors.forename: Zhongxiao
authors.initials: Z
authors.lastname: Wan
authors.affiliation: School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
authors.forename: Cody
authors.initials: C
authors.lastname: Durrer
authors.affiliation: School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
authors.forename: Dorrian
authors.initials: D
authors.lastname: Mah
authors.affiliation: School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Simtchouk
authors.affiliation: School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
authors.forename: Emily
authors.initials: E
authors.lastname: Robinson
authors.affiliation: School of Health and Exercise Sciences, University of British Columbia Okanagan, Kelowna, British Columbia, Canada.
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Little
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D016207:Cytokines / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D015536:Down-Regulation; D005947:Glucose / Q000378:metabolism*; D018149:Glucose Intolerance / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D008297:Male; D010085:Oxidative Phosphorylation; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012720:Severity of Illness Index; D013997:Time Factors; D055815:Young Adult
chemical_list: D016207:Cytokines; D055372:AMP-Activated Protein Kinases; D005947:Glucose
keywords: 5’ AMP-activated protein kinase; Inflammation; Mitogen-activated protein kinase; Monocytes; Postprandial hyperglycemia