Differential gene expression in adipose tissue from obese human subjects during weight loss and weight maintenance.

BACKGROUND Differential gene expression in adipose tissue during diet-induced weight loss followed by a weight stability period is poorly characterized. Markers of these processes may provide a deeper understanding of underlying mechanisms. OBJECTIVE We aimed to identify differentially expressed genes in human adipose tissue during weight loss and weight maintenance after weight loss. DESIGN RNA from subcutaneous abdominal adipose tissue from 9 obese subjects was analyzed by using a complementary DNA microarray at baseline after weight loss on a low-calorie diet and after weight maintenance. RESULTS Subjects lost 18.8 ± 1.8% of weight and maintained this loss during weight maintenance (1.1 ± 2.1%; range: -9.3 to 10.6%). Most differentially expressed genes exhibited a reciprocal regulation and returned to baseline after weight loss (2163 genes) and weight maintenance (3175 genes). CETP and ABCG1, both of which participate in the HDL-mediated reverse cholesterol transport (RCT), were among the most upregulated of the 750 genes that were differentially expressed after both processes. Several genes involved in inflammation were downregulated. The use of real-time polymerase chain reaction confirmed or partially confirmed the previously implicated genes TNMD and MMP9 (both downregulated), PNPLA3 (upregulated), and CIDEA and SCD (both reciprocally regulated). CONCLUSIONS The beneficial effects of weight loss should be investigated after long-term weight maintenance. The processes of weight loss and weight maintenance should be viewed as biologically distinct. CETP and ABCG1 may be important mediators of these effects through HDL-mediated RCT.

[1]  G. Hotamisligil,et al.  Inflammation and metabolic disorders , 2006, Nature.

[2]  P. Toth CETP Inhibition: Does the Future Look Promising? , 2011, Current cardiology reports.

[3]  Yudi Pawitan,et al.  False discovery rate, sensitivity and sample size for microarray studies , 2005, Bioinform..

[4]  P. Arner,et al.  A human-specific role of cell death-inducing DFFA (DNA fragmentation factor-alpha)-like effector A (CIDEA) in adipocyte lipolysis and obesity. , 2005, Diabetes.

[5]  M. Ridderstråle,et al.  A common variant in PNPLA3, which encodes adiponutrin, is associated with liver fat content in humans , 2009, Diabetologia.

[6]  Udo Hoffmann,et al.  Genome-Wide Association Analysis Identifies Variants Associated with Nonalcoholic Fatty Liver Disease That Have Distinct Effects on Metabolic Traits , 2011, PLoS genetics.

[7]  W. Saris,et al.  Role of stearoyl-CoA desaturases in obesity and the metabolic syndrome , 2008, International Journal of Obesity.

[8]  Bing Zhang,et al.  WebGestalt: an integrated system for exploring gene sets in various biological contexts , 2005, Nucleic Acids Res..

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

[10]  K. Clément,et al.  Effect of bariatric surgery-induced weight loss on SR-BI-, ABCG1-, and ABCA1-mediated cellular cholesterol efflux in obese women. , 2011, The Journal of clinical endocrinology and metabolism.

[11]  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.

[12]  S. Kahn,et al.  Mechanisms linking obesity to insulin resistance and type 2 diabetes , 2006, Nature.

[13]  A. Attie,et al.  Physiological insights gained from gene expression analysis in obesity and diabetes. , 2010, Annual review of nutrition.

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

[15]  J. Miyazaki,et al.  Expression and localization of tenomodulin, a transmembrane type chondromodulin-I-related angiogenesis inhibitor, in mouse eyes. , 2003, Investigative ophthalmology & visual science.

[16]  M. Ridderstråle,et al.  Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. , 2008, European journal of endocrinology.

[17]  J. Tuomilehto,et al.  Tenomodulin is Associated with Obesity and Diabetes Risk: The Finnish Diabetes Prevention Study , 2007, Obesity.

[18]  K. Clément,et al.  Adipose tissue transcriptome reflects variations between subjects with continued weight loss and subjects regaining weight 6 mo after caloric restriction independent of energy intake. , 2010, The American journal of clinical nutrition.

[19]  E. Carlsson,et al.  Variation in the adiponutrin gene influences its expression and associates with obesity. , 2006, Diabetes.

[20]  Z. Kováčová,et al.  Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women , 2011, International Journal of Obesity.

[21]  P. Arner,et al.  Changes in Adipose Tissue Gene Expression with Energy-restricted Diets in Obese Women , 2022 .

[22]  E. Van Obberghen,et al.  Matrix Metalloproteinases Are Differentially Expressed in Adipose Tissue during Obesity and Modulate Adipocyte Differentiation* , 2003, The Journal of Biological Chemistry.

[23]  J. Miyazaki,et al.  Anti-angiogenic action of the C-terminal domain of tenomodulin that shares homology with chondromodulin-I , 2004, Journal of Cell Science.

[24]  John Okyere,et al.  How to decide? Different methods of calculating gene expression from short oligonucleotide array data will give different results , 2006, BMC Bioinformatics.

[25]  Bart Lammers,et al.  ATP-binding cassette transporters A1 and G1, HDL metabolism, cholesterol efflux, and inflammation: important targets for the treatment of atherosclerosis. , 2011, Current drug targets.

[26]  A. Hamsten,et al.  Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance , 2008, Diabetologia.

[27]  Leena Peltonen,et al.  Global Transcript Profiles of Fat in Monozygotic Twins Discordant for BMI: Pathways behind Acquired Obesity , 2008, PLoS medicine.

[28]  Gang Qu,et al.  AffyProbeMiner: a web resource for computing or retrieving accurately redefined Affymetrix probe sets , 2007, Bioinform..

[29]  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.

[30]  G. Sweeney,et al.  Implications of myocardial matrix remodeling by adipokines in obesity-related heart failure. , 2008, Trends in cardiovascular medicine.

[31]  Gregory R. Grant,et al.  A practical false discovery rate approach to identifying patterns of differential expression in microarray data , 2005, Bioinform..

[32]  Rafael A. Irizarry,et al.  Stochastic Models Inspired by Hybridization Theory for Short Oligonucleotide Arrays , 2005, J. Comput. Biol..

[33]  A. Dobrzyń,et al.  Stearoyl‐CoA desaturase: A novel control point of lipid metabolism and insulin sensitivity , 2008 .

[34]  Howard J. Edenberg,et al.  Effects of filtering by Present call on analysis of microarray experiments , 2006, BMC Bioinformatics.

[35]  L. Niskanen,et al.  Weight reduction modulates expression of genes involved in extracellular matrix and cell death: the GENOBIN study , 2008, International Journal of Obesity.

[36]  José M Mato,et al.  Gene Expression Profile of Omental Adipose Tissue in Human Obesity , 2022 .

[37]  Z. Werb,et al.  How matrix metalloproteinases regulate cell behavior. , 2001, Annual review of cell and developmental biology.

[38]  J. Mill,et al.  Differential epigenomic and transcriptomic responses in subcutaneous adipose tissue between low and high responders to caloric restriction. , 2010, The American journal of clinical nutrition.

[39]  M. Uusitupa,et al.  Tenomodulin gene and obesity-related phenotypes , 2010, Annals of medicine.

[40]  W. Pories,et al.  Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult‐Onset Diabetes Mellitus , 1995, Annals of surgery.

[41]  Robert L Wilensky,et al.  Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. , 2011, The New England journal of medicine.

[42]  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.

[43]  D. Williamson,et al.  Intentional Weight Loss and Death in Overweight and Obese U.S. Adults 35 Years of Age and Older , 2003, Annals of Internal Medicine.

[44]  H. Stefánsson,et al.  Genetics of gene expression and its effect on disease , 2008, Nature.

[45]  Jaakko Tuomilehto,et al.  The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity. , 2003, Diabetes care.

[46]  H. Lijnen,et al.  Matrix Metalloproteinase Inhibition Impairs Adipose Tissue Development in Mice , 2002, Arteriosclerosis, thrombosis, and vascular biology.

[47]  S. Fowler,et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. , 2002 .

[48]  T. Pers,et al.  Macrophages and Adipocytes in Human Obesity , 2009, Diabetes.

[49]  J. Gregg,et al.  Fatty acid desaturase regulation in adipose tissue by dietary composition is independent of weight loss and is correlated with the plasma triacylglycerol response. , 2007, The American journal of clinical nutrition.

[50]  Sheng-Cai Lin,et al.  Cidea-deficient mice have lean phenotype and are resistant to obesity , 2003, Nature Genetics.

[51]  K. Clément,et al.  A distinct adipose tissue gene expression response to caloric restriction predicts 6-mo weight maintenance in obese subjects. , 2011, The American journal of clinical nutrition.

[52]  L. Kaplan Body weight regulation and obesity , 2003, Journal of Gastrointestinal Surgery.

[53]  P. Froguel,et al.  Tenomodulin is highly expressed in adipose tissue, increased in obesity, and down-regulated during diet-induced weight loss. , 2009, The Journal of clinical endocrinology and metabolism.

[54]  B. Fagerberg,et al.  Relations of adipose tissue CIDEA gene expression to basal metabolic rate, energy restriction, and obesity: population-based and dietary intervention studies. , 2007, The Journal of clinical endocrinology and metabolism.