Inactivity-mediated insulin resistance is associated with upregulated pro-inflammatory fatty acids in human cell membranes.
OBJECTIVE
Low-grade systemic inflammation and pro-inflammatory pattern of cell membrane fatty acid composition characterize patients affected by type 2 diabetes and metabolic syndrome. We hypothesize that inactivity-induced insulin resistance could affect levels of pro-inflammatory fatty acids in cell membranes.


METHODS
Thirty healthy, male, young volunteers were investigated before and after 35-day experimental bed rest. Diet composition was adapted to previous dietary habits. Fatty acid composition of erythrocyte membranes was analyzed by gas-chromatography using flame ionization detector.


RESULTS
Following bed rest, the HOMA index of insulin resistance significantly increased by +51+/-11% (P<0.01). Bed rest was associated with increased n-6 polyunsaturated (+4.7+/-2.2%; P<0.01) and decreased monounsaturated (-4.8+/-1.5%; P<0.01) fatty acid content in erythrocyte membranes. Fractional content of arachidonic acid increased by +14+/-12% (P=0.01) following inactivity. Delta5 and Delta9 desaturase indexes, as estimated from product-to-precursor ratios, significantly diminished following bed rest from 9.6+/-0.4 to 8.4+/-0.3 (P<0.001) and from 0.72+/-0.02 to 0.69+/-0.01 (P<0.05), respectively. The n-3 fatty acids, alpha-linolenic and eicosapentaenoic, were decreased (P=0.05) following inactivity by 4.7+/-13.2% and 3.8+/-5.2%, respectively.


CONCLUSIONS
Inactivity-mediated insulin resistance was associated with altered Delta5 and Delta9 desaturase indexes and with pro-inflammatory fatty acid pattern in erythrocyte membranes. These abnormalities could contribute to the low-grade inflammation associated to inactivity.
Mazzucco
Sara
S
Department of Medical, Technological and Translational Sciences, University of Trieste, Clinica Medica, Strada di Fiume 447, Ospedale di Cattinara, Trieste, Italy.
Agostini
Francesco
F
Biolo
Gianni
G
D016718:Arachidonic Acid / Q000097:blood; D001510:Bed Rest / Q000009:adverse effects; D001823:Body Composition / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism*; D000090943:Delta-5 Fatty Acid Desaturase; D004032:Diet; D004910:Erythrocyte Membrane / Q000378:metabolism; D044943:Fatty Acid Desaturases / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000097:blood; D043371:Fatty Acids, Omega-6 / Q000097:blood; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D057185:Sedentary Behavior; D013230:Stearoyl-CoA Desaturase; D015854:Up-Regulation / Q000502:physiology*; D055815:Young Adult
D000090943:Delta-5 Fatty Acid Desaturase; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D043371:Fatty Acids, Omega-6; D018836:Inflammation Mediators; D007328:Insulin; D016718:Arachidonic Acid; D044943:Fatty Acid Desaturases; D013230:Stearoyl-CoA Desaturase; C029627:delta-9 fatty acid desaturase