Background: The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. Aim: This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Methods: Q-PCR was utilized to assess the mRNA expression levels of target genes. Results: In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. Conclusion: However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel

Keywords:
Free fatty acids, Obesity, PBMC, PPARα
1.
Bünger M, Hooiveld GJ, Kersten S, Müller M: Exploration of PPAR functions by microarray technology - a paradigm for nutrigenomics. Biochim Biophys Acta 2007;1771:1046-1064.
2.
Muller M, Kersten S: Nutrigenomics: goals and strategies. Nat Rev Genet 2003;4:315-322.
3.
Ordovas JM, Mooser V: Nutrigenomics and nutrigenetics. Curr Opin Lipidol 2004;15:101-108.
4.
Afman L, Muller M: Nutrigenomics: from molecular nutrition to prevention of disease. J Am Diet Assoc 2006;106:569-576.
5.
Patsouris D, Mandard S, Voshol PJ, Escher P, et al: PPARα governs glycerol metabolism. J Clin Invest 2004;114:94-103.
6.
Consitt LA, Bell JA, Houmard JA: Intramuscular lipid metabolism, insulin action, and obesity. IUBMB Life 2009;61:47-55.
7.
Instituto Brasileiro de Geografia e Estatística (IBGE), Consumer Expenditure Survey (POF 2008-2009): Anthropometry and nutritional status of children, teenagers and adult in Brazil, 2011. http://www.ibge.gov.br/english/xml/pof_2008_2009.shtm.
8.
La Vecchia C, Giordano SH, Hortobagyi GN, Chabner B: Overweight, obesity, diabetes, and risk of breast cancer: interlocking pieces of the puzzle. Oncologist 2011;16:726-729.
9.
Phillips CM: Nutrigenetics and metabolic disease: current status and implications for personalised nutrition. Nutrients 2013;5:32-57.
10.
Houmard JA: Intramuscular lipid oxidation and obesity. Am J Physiol Regul Integr Comp Physiol 2008;294:R1111-R1116.
11.
Boden G, Shulman GI: Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and β-cell disfunction. Eur J Clin Invest 2002;32:14-23.
12.
Dagenais GR, Tancredi RG, Zierler KL: Free fatty acid oxidation by forearm muscle at rest, and evidence for an intramuscular lipid pool in the human forearm. J Clin Invest 1976;58:421-431.
13.
Kim JY, Hickner RC, Cortright RL, Dohm GL, Houmard JA: Lipid oxidation is reduced in obese human skeletal muscle. Am J Physiol Endocrinol Metab 2000;279:E1039-E1044.
14.
Napal L, Marrero PF, Haro D: An intronic peroxisome proliferator-activated receptor-binding sequence mediates fatty acid induction of the human carnitine palmitoyltransferase 1A. J Mol Biol 2005;354:751-759.
15.
Carlson MG, Snead WL, Campbell PJ: Fuel and energy metabolism in fasting humans. Am J Clin Nutr 1994;60:29-36.
16.
Finn PF, Dice JF: Proteolytic and lipolytic responses to starvation. Nutrition 2006;22:830-844.
17.
Rakhshandehroo M, Hooiveld G, Müller M, Kersten S: Comparative analysis of gene regulation by the transcription factor PPARα between mouse and human. PLoS One 2009;4:e6796.
18.
Kersten S, Desvergne B, Wahli W: Roles of PPARs in health and disease. Nature 2000;405:421-424.
19.
Ren B, Thelen A, Jump DB: Peroxisome proliferator-activated receptor alpha inhibits hepatic S14 gene transcription. Evidence against the peroxisome proliferator-activated receptor alpha as the mediator of polyunsaturated fatty acid regulation of S14 gene transcription. J Biol Chem 1996;271:17167-17173.
20.
Bouwens M, Grootte Bromhaar M, Jansen J, Müller M, Afman LA: Postprandial dietary lipid-specific effects on human peripheral blood mononuclear cell gene expression profiles. Am J Clin Nutr 2010;91:208-217.
21.
Stoll G, Bendszus M: Inflammation and atherosclerosis: novel insights into plaque formation and destabilization. Stroke 2006;37:1923-1932.
22.
Lefebvre P, Chinetti G, Fruchart JC, Staels B: Sorting out the roles of PPARα in energy metabolism and vascular homeostasis. J Clin Invest 2006;116:571-580.
23.
Kersten S, Mandard S, Escher P, Gonzalez FJ, et al: The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism. FASEB J 2001;15:1971-1978.
24.
Kostadinova R, Wahli W, Michalik L: PPARs in diseases: control mechanisms of inflammation. Curr Med Chem 2005;12:2995-3009.
25.
Stienstra R, Duval C, Müller M, Kersten S: PPARs, obesity, and inflammation. PPAR Res 2007;2007:95974.
26.
Liew CC, Ma J, Tang HC, Zheng R, Dempsey AA: The peripheral blood transcriptome dynamically reflects system wide biology: a potential diagnostic tool. J Lab Clin Med 2006;147:126-132.
27.
Crujeiras AB, Parra D, Milagro FI, Goyenechea E, et al: Differential expression of oxidative stress and inflammation related genes in peripheral blood mononuclear cells in response to a low-calorie diet: a nutrigenomics study. OMICS 2008;12:251-261.
28.
Bouwens M, Afman LA, Müller M: Fasting induces changes in peripheral blood mononuclear cell gene expression profiles related to increase in fatty acid β-oxidation: functional role of peroxisome proliferator activated receptor α in human peripheral blood mononuclear cells. Am J Clin Nutr 2007;86:1515-1523.
29.
WHO: World Health Organization: Global Database on Body Mass Index - Body Mass Index (BMI) classification. http://apps.who.int/bmi/index.jsp?introPage=intro_3.html.
30.
American Diabetes Association: http://www.diabtes.org.
31.
Datasus: Ordinance no 788: 25 October 2002. http://pnass.datasus.gov.br/documentos/normas/54.pdf.
32.
Verma RS, Babu A (eds): Lymphocyte isolation; in Human Chromosomes: principles and techniques, ed 2. McGraw-Hill, 1995, p 9.
33.
Chege D, Chai Y, Huibner S, Mckinnon L, et al: Evaluation of a quantitative real-time PCR assay to measure HIV-specific mucosal CD8+ T cell responses in the cervix. PLoS One 2010;5:e13077.
34.
Sugaya S, Nakanishi H, Tanzawa H, Sugita K, et al: Down-regulation of SMT3A gene expression in association with DNA synthesis induction after X-ray irradiation in nevoid basal cell carcinoma syndrome (NBCCS) cells. Mutat Res 2005;578:327-332.
35.
Leone TC, Weinheimer CJ, Kelly DP: A critical role for the peroxisome proliferator-activated receptor alpha (PPARα) in the cellular fasting response: the PPARα-null mouse as a model of fatty acid oxidation disorders. Proc Natl Acad Sci U S A 1999;96:7473-7478.
36.
Sugden MC, Zariwala MG, Holness MJ: PPARs and the orchestration of metabolic fuel selection. Pharmacol Res 2009;60:141-150.
37.
Brandt JM, Djouadi F, Kelly DP: Fatty acids activate transcription of the muscle carnitine palmitoyltransferase I gene in cardiac myocytes via the peroxisome proliferator-activated receptor α. J Biol Chem 1998;273:23786-23792.
38.
Mascaró C, Acosta E, Ortiz JA, Marrero PF, et al: Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. J Biol Chem 1998;273:8560-8563.
39.
Barrero MJ, Camarero N, Marrero PF, Haro D: Control of human carnitine palmitoyltransferase II gene transcription by peroxisome proliferator-activated receptor through a partially conserved peroxisome proliferator-responsive element. Biochem J 2003;369:721-729.
40.
Lemay DG, Hwang DH: Genome-wide identification of peroxisome proliferator response elements using integrated computational genomics. J Lipid Res 2006;47:1583-1587.
41.
Houten SM, Chegary M, Te Brinke H, Wijnen WJ, et al: Pyruvate dehydrogenase kinase 4 expression is synergistically induced by AMP-activated protein kinase and fatty acids. Cell Mol Life Sci 2009;66:1283-1294.
42.
Kelley DE, Goodpaster B, Wing RR, Simoneau JA: Skeletal muscle fatty acid metabolism in association with insulin resistance, obesity, and weight loss. Am J Physiol 1999;277:E1130-E1141.
43.
Hulver MW, Berggren JR, Cortright RN, Dudek RW, et al: Skeletal muscle lipid metabolism with obesity. Am J Physiol Endocrinol Metab 2003;284:E741-E747.
44.
Steinberg GR, Parolin ML, Heigenhauser GJ, Dyck DJ: Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance. Am J Physiol Endocrinol Metab 2002;283:E187-E192.
45.
Palou M, Sánchez J, Priego T, Rodríguez AM, et al: Regional differences in the expression of genes involved in lipid metabolism in adipose tissue in response to short- and médium-term fasting and refeeding. J Nutr Biochem 2010;21:23-33.
46.
Fruchart JC: Peroxisome proliferator-activated receptor-alpha (PPARα): at the crossroads of obesity, diabetes and cardiovascular disease. Atherosclerosis 2009;205:1-8.
47.
Indiveri C, Tonazzi A, Palmieri F: Identification and purification of the carnitine carrier from rat liver mitochondria. Biochim Biophys Acta 1990;1020:81-86.
48.
Leslie ND, Tinkle BT, Strauss AW, et al: Very Long-Chain Acyl-Coenzyme A Dehydrogenase Deficiency, 2009; in Pagon RA, Bird TD, Dolan CR, et al (eds): GeneReviews™. Seattle: University of Washington, Seattle, 1993-2014. http://www.ncbi.nlm.nih.gov/books/NBK6816/.
49.
McAndrew RP, Wang Y, Mohsen AW, He M, et al: Structural basis for substrate fatty acyl chain specificity: crystal structure of human very-long-chain acyl-CoA dehydrogenase. J Biol Chem 2008;283:9435-9443.
© 2014 S. Karger AG, Basel
2014
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