A saturated fatty acid-rich diet induces an obesity-linked proinflammatory gene expression profile in adipose tissue of subjects at risk of metabolic syndrome.

BACKGROUND Changes in dietary fat composition could lower the risk of developing metabolic syndrome. Adipose tissue is an interesting tissue in this respect because of its role in lipid metabolism and inflammation. OBJECTIVE Our objective was to investigate the effect of a saturated fatty acid (SFA)- and a monounsaturated fatty acid (MUFA)-rich diet on insulin sensitivity, serum lipids, and gene expression profiles of adipose tissue in subjects at risk of metabolic syndrome. DESIGN A parallel controlled-feeding trial was conducted in 20 abdominally overweight subjects. Subjects received an SFA diet or a MUFA diet for 8 wk. Plasma and subcutaneous adipose tissue samples were obtained, and insulin sensitivity was measured by using a hyperinsulinemic-euglycemic clamp. Adipose tissue samples underwent whole-genome microarray and histologic analysis. Plasma and adipose tissue fatty acid composition and concentrations of serum cholesterol and plasma cytokine were determined. RESULTS Consumption of the SFA diet resulted in increased expression of genes involved in inflammation processes in adipose tissue, without changes in morphology or insulin sensitivity. The MUFA diet led to a more antiinflammatory gene expression profile, which was accompanied by a decrease in serum LDL-cholesterol concentrations and an increase in plasma and adipose tissue oleic acid content. CONCLUSIONS Consumption of an SFA diet resulted in a proinflammatory "obesity-linked" gene expression profile, whereas consumption of a MUFA diet caused a more antiinflammatory profile. This suggests that replacement of dietary SFA with MUFA could prevent adipose tissue inflammation and may reduce the risk of inflammation-related diseases such as metabolic syndrome. This trial was registered at clinicaltrials.gov as NCT00405197.

[1]  D. B. Allison,et al.  Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes , 2005, Diabetologia.

[2]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[3]  L. Afman,et al.  Activation of peroxisome proliferator-activated receptor alpha in human peripheral blood mononuclear cells reveals an individual gene expression profile response , 2008, BMC Genomics.

[4]  David A Fields,et al.  Body-composition assessment via air-displacement plethysmography in adults and children: a review. , 2002, The American journal of clinical nutrition.

[5]  R. Mensink,et al.  Effects of monounsaturated fatty acids v complex carbohydrates on serum lipoproteins and apoproteins in healthy men and women. , 1989, Metabolism: clinical and experimental.

[6]  B. M. Rasmussen,et al.  Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study , 2001, Diabetologia.

[7]  A. Kennedy,et al.  Saturated fatty acid-mediated inflammation and insulin resistance in adipose tissue: mechanisms of action and implications. , 2009, The Journal of nutrition.

[8]  B. Nicklas,et al.  Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors. , 2005, American journal of physiology. Endocrinology and metabolism.

[9]  K. Clément,et al.  Adipose tissue transcriptomic signature highlights the pathological relevance of extracellular matrix in human obesity , 2008, Genome Biology.

[10]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[11]  Terence P. Speed,et al.  A comparison of normalization methods for high density oligonucleotide array data based on variance and bias , 2003, Bioinform..

[12]  Shupei Wang,et al.  Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans Published, JLR Papers in Press, September 8, 2005. DOI 10.1194/jlr.M500294-JLR200 , 2005, Journal of Lipid Research.

[13]  C. Bogardus,et al.  Increased expression of inflammation-related genes in cultured preadipocytes/stromal vascular cells from obese compared with non-obese Pima Indians , 2005, Diabetologia.

[14]  Jean-Daniel Zucker,et al.  Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. , 2005, Diabetes.

[15]  Arya M. Sharma,et al.  Peroxisome Proliferator-Activated Receptor γ and Adipose Tissue—Understanding Obesity-Related Changes in Regulation of Lipid and Glucose Metabolism , 2007 .

[16]  S. Devaraj,et al.  ATVB In Focus Nutrition and Atherosclerosis , 2006 .

[17]  E. Feskens,et al.  Effect of a high monounsaturated fatty acids diet and a Mediterranean diet on serum lipids and insulin sensitivity in adults with mild abdominal obesity. , 2010, Nutrition, metabolism, and cardiovascular diseases : NMCD.

[18]  J. Deslypere,et al.  Stability of n-3 fatty acids in human fat tissue aspirates during storage. , 1993, The American journal of clinical nutrition.

[19]  J. Lehmann,et al.  Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. , 2000, Molecular cell.

[20]  U. Smith,et al.  Culprit Underlying the Metabolic Syndrome and Atherosclerosis , 2007 .

[21]  J. López-Miranda,et al.  A Mediterranean and a high-carbohydrate diet improve glucose metabolism in healthy young persons , 2001, Diabetologia.

[22]  S. Haffner,et al.  The metabolic syndrome as predictor of type 2 diabetes: the San Antonio heart study. , 2003, Diabetes care.

[23]  Michael Müller,et al.  Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increases in fatty acid beta-oxidation: functional role of peroxisome proliferator activated receptor alpha in human peripheral blood mononuclear cells. , 2007, The American journal of clinical nutrition.

[24]  J. Drai,et al.  Plasma fatty acid composition is associated with the metabolic syndrome and low-grade inflammation in overweight adolescents. , 2005, The American journal of clinical nutrition.

[25]  L. Sanderson,et al.  Effect of Synthetic Dietary Triglycerides: A Novel Research Paradigm for Nutrigenomics , 2008, PloS one.

[26]  Leif E. Peterson,et al.  T-Cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity , 2007, Circulation.

[27]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[28]  D. Giugliano,et al.  Are there specific treatments for the metabolic syndrome? , 2008, The American journal of clinical nutrition.

[29]  G. Beunen,et al.  Clustering of metabolic risk factors in young adults: genes and environment. , 2008, Atherosclerosis.

[30]  V. Hombach,et al.  T-lymphocyte Infiltration in Visceral Adipose Tissue: A Primary Event in Adipose Tissue Inflammation and the Development of Obesity-Mediated Insulin Resistance , 2008, Arteriosclerosis, thrombosis, and vascular biology.

[31]  P. Zimmet,et al.  Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[32]  Gordon K Smyth,et al.  Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray Experiments , 2004, Statistical applications in genetics and molecular biology.

[33]  M. Czech,et al.  Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes , 2008, Nature Reviews Molecular Cell Biology.

[34]  Katherine Esposito,et al.  Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. , 2004 .

[35]  D. Baer,et al.  Dietary fatty acids affect plasma markers of inflammation in healthy men fed controlled diets: a randomized crossover study. , 2004, The American journal of clinical nutrition.

[36]  I. S. Wood,et al.  Adipokines: inflammation and the pleiotropic role of white adipose tissue , 2004, British Journal of Nutrition.

[37]  B. Egan,et al.  Relation of dietary fat and fiber to elevation of C-reactive protein. , 2003, The American journal of cardiology.

[38]  T. Speed,et al.  Summaries of Affymetrix GeneChip probe level data. , 2003, Nucleic acids research.

[39]  Victor M Montori,et al.  Metabolic syndrome and risk of incident cardiovascular events and death: a systematic review and meta-analysis of longitudinal studies. , 2007, Journal of the American College of Cardiology.

[40]  D. Hwang,et al.  The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors. , 2006, Molecules and cells.

[41]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[42]  R. Myers,et al.  Evolving gene/transcript definitions significantly alter the interpretation of GeneChip data , 2005, Nucleic acids research.

[43]  S. Haffner,et al.  The relation of body fat mass and distribution to markers of chronic inflammation , 2001, International Journal of Obesity.

[44]  K. Clément,et al.  The FASEB Journal • Research Communication Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects , 2022 .

[45]  S. Kihara,et al.  Adiponectin and Metabolic Syndrome , 2004, Arteriosclerosis, thrombosis, and vascular biology.