Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes.
We recently reported that lowering the high, habitual palmitic acid (PA) intake in ovulating women improved insulin sensitivity and both inflammatory and oxidative stress. In vitro studies indicate that PA can activate both cell membrane toll-like receptor-4 and the intracellular nucleotide oligomerization domain-like receptor protein (NLRP3). To gain further insight into the relevance to human metabolic disease of dietary PA, we studied healthy, lean and obese adults enrolled in a randomized, crossover trial comparing 3-week, high-PA (HPA) and low-PA/high-oleic-acid (HOA) diets. After each diet, both hepatic and peripheral insulin sensitivities were measured, and we assessed cytokine concentrations in plasma and in supernatants derived from lipopolysaccharide-stimulated peripheral blood mononuclear cells (PBMCs) as well as proinflammatory gene expression in skeletal muscle. Insulin sensitivity was unaffected by diet. Plasma concentration of tumor necrosis factor-α was higher during the HPA diet. Lowering the habitually high PA intake by feeding the HOA diet resulted in lower secretion of interleukin (IL)-1β, IL-18, IL-10, and tumor necrosis factor-α by PBMCs, as well as lower relative mRNA expression of cJun and NLRP3 in muscle. Principal components analysis of 156 total variables coupled to analysis of covariance indicated that the mechanistic pathway for the differential dietary effects on PBMCs involved changes in the PA/OA ratio of tissue lipids. Our results indicate that lowering the dietary and tissue lipid PA/OA ratio resulted in lower leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes, but the relevance to diabetes risk is uncertain.
Department of Pediatrics, University of Vermont, Burlington, VT; Department of Medicine, University of Vermont, Burlington, VT. Electronic address: cl.kien@uvm.edu.
C Lawrence
CL
Kien
Department of Medical Biostatistics, University of Vermont, Burlington, VT.
Janice Y
JY
Bunn
Department of Medicine, University of Vermont, Burlington, VT.
Naomi K
NK
Fukagawa
Department of Pathology and Laboratory Medicine, University of Vermont, Burlington, VT.
Vikas
V
Anathy
Department of Medicine, University of Vermont, Burlington, VT; Department of Chemistry, University of Vermont, Burlington, VT.
Dwight E
DE
Matthews
Department of Medicine, University of Vermont, Burlington, VT.
Karen I
KI
Crain
Department of Medicine, University of Vermont, Burlington, VT.
David B
DB
Ebenstein
College of Medicine Clinical Research Center, University of Vermont, Burlington, VT.
Emily K
EK
Tarleton
Translational Research Institute for Metabolism and Diabetes, Sanford-Burnham Medical Research Institute, Orlando, FL.
Richard E
RE
Pratley
Department of Medicine, University of Vermont, Burlington, VT.
Matthew E
ME
Poynter
D000293:Adolescent; D000328:Adult; D001823:Body Composition; D018592:Cross-Over Studies; D016207:Cytokines / Q000097:blood; D004032:Diet; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D007249:Inflammation; D007333:Insulin Resistance; D016753:Interleukin-10 / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D008055:Lipids / Q000097:blood / Q000737:chemistry*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D019301:Oleic Acid / Q000737:chemistry*; D018384:Oxidative Stress; D019308:Palmitic Acid / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D016207:Cytokines; C508609:IL10 protein, human; C508585:IL1B protein, human; D020382:Interleukin-18; D053583:Interleukin-1beta; D008055:Lipids; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019301:Oleic Acid; D019308:Palmitic Acid
Cytokines; Fatty acids; Inflammation; Innate immunity; Oleic acid; Palmitic acid