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Licensed Unlicensed Requires Authentication Published by De Gruyter July 5, 2017

Browning formation markers of subcutaneous adipose tissue in relation to resting energy expenditure, physical activity and diet in humans

  • Petros C. Dinas EMAIL logo , Angelica Valente , Marnie Granzotto , Marco Rossato , Roberto Vettor , Aikaterini Zacharopoulou , Andres E. Carrillo , Natalie A. Davies , Paraskevi Gkiata , Athanasios Z. Jamurtas , Yiannis Koutedakis , George S. Metsios and Andreas D. Flouris ORCID logo

Abstract

Background

Regular exercise and diet may contribute to white adipose tissue (WAT) conversion into a brown adipose-like phenotype that may increase resting energy expenditure (REE), leading to weight loss. We examined the relationship between REE, physical activity (PA) participation and diet with browning formation markers of subcutaneous WAT in healthy men.

Materials and methods

We assessed REE, diet and body composition of 32 healthy men [age (years): 36.06 ± 7.36, body mass index (BMI): 27.06 ± 4.62 (kg/m2)]. Participants also underwent measurements of PA [metabolic equivalent (MET)-min/week] using the International Physical Activity Questionnaire (IPAQ), while they undertook a subcutaneous fat biopsy from the abdominal region to assess the mRNA expressions of uncoupling protein 1 (UCP1), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor gamma (PPARγ).

Results

We found no associations between the UCP1, PGC-1α, PPARα and PPARγ mRNAs with REE, PA levels and diet (p > 0.05). However, the PGC-1α, PPARα and PPARγ mRNAs were more expressed in individuals displaying moderate rather than low PA levels (p < 0.05). Furthermore, PGC-1α, PPARα and PPARγ mRNAs were negatively correlated with fat mass percentage (p < 0.05). PGC-1α and PPARα mRNAs were also negatively correlated with BMI, while PGC-1α mRNA was inversely associated with waist-to-hip ratio (p < 0.05).

Conclusion

REE, PA levels and diet are not associated with browning formation indices of subcutaneous adipose tissue in healthy adult men.

Author Statement

  1. Research funding: This study was supported by funding from the European Union 7th Framework Program (FP7-PEOPLE-2012-IRSES grant 319010; FP7-PEOPLE-2013-IRSES grant 612547). A.V. was supported by funding from the Education and Lifelong Learning Programme of the Greek Ministry of Education, Co-financed by Greece and the European Union (NSRF 2007–2013, IRAKLITOS II, grant 162).

  2. Conflict of interest: Authors state no conflict of interest.

  3. Informed consent: Informed consent has been obtained from all individuals included in the study.

  4. Ethical approval: The research related to human use complied with all the relevant national regulations and institutional policies, was performed in accordance with the tenets of the Helsinki declaration and has been approved by the authors’ institutional review board or equivalent committee.

[1] Mattson MP. Perspective: does brown fat protect against diseases of aging?. Ageing Res Rev. 2010;9:69–76.Search in Google Scholar

[2] van Marken Lichtenbelt WD, Schrauwen P. Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol. 2011;301:R285–96.Search in Google Scholar

[3] Kopecky J, Clarke G, Enerback S, Spiegelman B, Kozak LP. Expression of the mitochondrial uncoupling protein gene from the aP2 gene promoter prevents genetic obesity. J Clin Invest. 1995;96:2914–23.Search in Google Scholar

[4] Kopecky J, Rossmeisl M, Hodny Z, Syrovy I, Horakova M, Kolarova P. Reduction of dietary obesity in aP2-Ucp transgenic mice: mechanism and adipose tissue morphology. Am J Physiol. 1996;270(5 Pt 1):E776–86.Search in Google Scholar

[5] Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, Enerback S. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell. 2001;106:563–73.Search in Google Scholar

[6] Tsukiyama-Kohara K, Poulin F, Kohara M, DeMaria CT, Cheng A, Wu Z, et al. Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Nat Med. 2001;7:1128–132.Search in Google Scholar

[7] Seale P, Kajimura S, Spiegelman BM. Transcriptional control of brown adipocyte development and physiological function – of mice and men. Genes Dev. 2009;23:788–97.Search in Google Scholar

[8] Yamashita H, Yamamoto M, Sato Y, Izawa T, Komabayashi T, Saito D, et al. Effect of running training on uncoupling protein mRNA expression in rat brown adipose tissue. Int J Biometeorol. 1993;37:61–4.Search in Google Scholar

[9] Ozden H, Ozbag D, Akyuz F, Sunal E, Gurer F, Inal M. The effect of melathonin on changes in brown and white adipose tissue ratios induced by exercise. The significance of age in this effect. Saudi Med J. 2004;25:1753–4.Search in Google Scholar

[10] Schroeder M, Shbiro L, Gelber V, Weller A. Post-weaning voluntary exercise exerts long-term moderation of adiposity in males but not in females in an animal model of early-onset obesity. Horm Behav. 2010;57:496–505.Search in Google Scholar

[11] Oh KS, Kim EY, Yoon M, Lee CM. Swim training improves leptin receptor deficiency-induced obesity and lipid disorder by activating uncoupling proteins. Exp Mol Med. 2007;39:385–94.Search in Google Scholar

[12] Xu X, Ying Z, Cai M, Xu Z, Li Y, Jiang SY, et al. Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol. 2011;300:R1115–25.Search in Google Scholar

[13] Dinas PC, Nikaki A, Jamurtas AZ, Prassopoulos V, Efthymiadou R, Koutedakis Y, et al. Association between habitual physical activity and brown adipose tissue activity in individuals undergoing PET-CT scan. Clin Endocrinol (Oxf). 2015;82:147–54.Search in Google Scholar

[14] Rothwell NJ, Stock MJ, Tyzbir RS. Energy balance and mitochondrial function in liver and brown fat of rats fed “cafeteria” diets of varying protein content. J Nutr. 1982;112:1663–72.Search in Google Scholar

[15] Rothwell NJ, Stock MJ, Tyzbir RS. Mechanisms of thermogenesis induced by low protein diets. Metabolism. 1983;32:257–61.Search in Google Scholar

[16] Leblanc J. Prefeeding of high fat diet and resistance of rats to intense cold. Can J Biochem Physiol. 1957;35:25–30.Search in Google Scholar

[17] Yoshimura M, Hori S, Yoshimura H. Effect of high-fat diet on thermal acclimation with special reference to thyroid activity. Jpn J Physiol. 1972;22:517–531.Search in Google Scholar

[18] Kuroshima A, Doi K, Yahata T, Ohno T. Improved cold tolerance and its mechanism in cold-acclimated rats by high fat diet feeding. Can J Physiol Pharmacol. 1977;55:943–50.Search in Google Scholar

[19] Mercer SW, Trayhurn P. Effect of high fat diets on the thermogenic activity of brown adipose tissue in cold-acclimated mice. J Nutr. 1984;114:1151–8.Search in Google Scholar

[20] Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009;9:203–9.Search in Google Scholar

[21] Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, et al. PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008;454:961–7.Search in Google Scholar

[22] Stanford KI, Middelbeek RJ, Townsend KL, Lee MY, Takahashi H, So K, et al. A novel role for subcutaneous adipose tissue in exercise-induced improvements in glucose homeostasis. Diabetes. 2015;64:2002–14.Search in Google Scholar

[23] Sutherland LN, Bomhof MR, Capozzi LC, Basaraba SA, Wright DC. Exercise and adrenaline increase PGC-1{alpha} mRNA expression in rat adipose tissue. J Physiol. 2009;587(Pt 7):1607–17.Search in Google Scholar

[24] Trevellin E, Scorzeto M, Olivieri M, Granzotto M, Valerio A, Tedesco L, et al. Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms. Diabetes. 2014;63:2800–11.Search in Google Scholar

[25] Cao L, Choi EY, Liu X, Martin A, Wang C, Xu X, et al. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 2011;14:324–38.Search in Google Scholar

[26] Dillon LM, Rebelo AP, Moraes CT. The role of PGC-1 coactivators in aging skeletal muscle and heart. IUBMB Life. 2012;64:231–41.Search in Google Scholar

[27] Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM. A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell. 1998;92:829–39.Search in Google Scholar

[28] Puigserver P, Spiegelman B. Peroxisome proliferator-activated receptorgamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev. 2003;24:78–90.Search in Google Scholar

[29] Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta. 2001;1504:82–106.Search in Google Scholar

[30] Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285:7153–64.Search in Google Scholar

[31] Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481:463–8.Search in Google Scholar

[32] Rachid TL, Penna-de-Carvalho A, Bringhenti I, Aguila MB, Mandarim-de-Lacerda CA, Souza-Mello V. Fenofibrate (PPARalpha agonist) induces beige cell formation in subcutaneous white adipose tissue from diet-induced male obese mice. Mol Cell Endocrinol. 2015;402:86–94.Search in Google Scholar

[33] Li M, Bai Y, Chen C, Cui J, Xu X, Dai Y. Effects of exercise and conjugated linoleic acid on PPARgamma in adolescent obese rats. Wei Sheng Yan Jiu. 2015;44:179–84.Search in Google Scholar

[34] Tanaka G, Kato H, Izawa T. Endurance exercise training induces fat depot-specific differences in basal autophagic activity. Biochem Biophys Res Commun. 2015;466:512–7.Search in Google Scholar

[35] Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, et al. The effects of acute and chronic exercise on PGC-1alpha, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014;281:739–49.Search in Google Scholar

[36] Enerback S. Human brown adipose tissue. Cell Metab. 2010;11:248–52.Search in Google Scholar

[37] Wu J, Cohen P, Spiegelman BM. Adaptive thermogenesis in adipocytes: is beige the new brown?. Genes Dev. 2013;27:234–50.Search in Google Scholar

[38] Srivastava S, Kashiwaya Y, King MT, Baxa U, Tam J, Niu G, et al. Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet. FASEB J. 2012;26:2351–62.Search in Google Scholar

[39] Papathanasiou G, Georgoudis G, Papandreou M, Spyropoulos P, Georgakopoulos D, Kalfakakou V, et al. Reliability measures of the short International Physical Activity Questionnaire (IPAQ) in Greek young adults. Hellenic J Cardiol. 2009;50:283–94.Search in Google Scholar

[40] Jamurtas AZ, Koutedakis Y, Paschalis V, Tofas T, Yfanti C, Tsiokanos A, et al. The effects of a single bout of exercise on resting energy expenditure and respiratory exchange ratio. Eur J Appl Physiol. 2004;92:393–8.Search in Google Scholar

[41] Adriaens MP, Schoffelen PF, Westerterp KR. Intra-individual variation of basal metabolic rate and the influence of daily habitual physical activity before testing. Br J Nutr. 2003;90:419–23.Search in Google Scholar

[42] Weir JB. New methods for calculating metabolic rate with special reference to protein metabolism. J Physiol. 1949;109:1–9.Search in Google Scholar

[43] International Physical Activity Questionnaire. [http://www.ipaq.ki.se/] Accessed: May 20, 2013.Search in Google Scholar

[44] Mutch DM, Tordjman J, Pelloux V, Hanczar B, Henegar C, Poitou C, et al. Needle and surgical biopsy techniques differentially affect adipose tissue gene expression profiles. Am J Clin Nutr. 2009;89:51–7.Search in Google Scholar

[45] Campbell KL, Makar KW, Kratz M, Foster-Schubert KE, McTiernan A, Ulrich CM. A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk. Cancer Prev Res (Phila). 2009;2:37–42.Search in Google Scholar

[46] Nedergaard J, Cannon B. UCP1 mRNA does not produce heat. Biochim Biophys Acta. 2013;1831:943–9.Search in Google Scholar

[47] Stuempfle KJ, Hoffman MD, Hew-Butler T. Association of gastrointestinal distress in ultramarathoners with race diet. Int J Sport Nutr Exerc Metab. 2013;23:103–9.Search in Google Scholar

[48] Michaliszyn SF, Shaibi GQ, Quinn L, Fritschi C, Faulkner MS. Physical fitness, dietary intake, and metabolic control in adolescents with type 1 diabetes. Pediatr Diabetes. 2009;10:389–4.Search in Google Scholar

[49] Ratcliff R. Methods for dealing with reaction time outliers. Psychol Bull. 1993;114:510–32.Search in Google Scholar

[50] Nakhuda A, Josse AR, Gburcik V, Crossland H, Raymond F, Metairon S, et al. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss. Am J Clin Nutr. 2016;104:557–65.Search in Google Scholar

[51] Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19:1252–63.Search in Google Scholar

[52] Rosenwald M, Perdikari A, Rulicke T, Wolfrum C. Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol. 2013;15:659–67.Search in Google Scholar

[53] Wu MV, Bikopoulos G, Hung S, Ceddia RB. Thermogenic capacity is antagonistically regulated in classical brown and white subcutaneous fat depots by high fat diet and endurance training in rats: impact on whole-body energy expenditure. J Biolo Chem. 2014;289:34129–40.Search in Google Scholar

[54] Koppen A, Kalkhoven E. Brown vs. white adipocytes: the PPARgamma coregulator story. FEBS Lett. 2010;584:3250–9.Search in Google Scholar

[55] Castillo-Quan JI. From white to brown fat through the PGC-1alpha-dependent myokine irisin: implications for diabetes and obesity. Dis Model Mech. 2012;5:293–5.Search in Google Scholar

[56] Rachid TL, Penna-de-Carvalho A, Bringhenti I, Aguila MB, Mandarim-de-Lacerda CA, Souza-Mello V. PPAR-α agonist elicits metabolically active brown adipocytes and weight loss in diet-induced obese mice. Cell Biochem Funct. 2015;33:249–56.Search in Google Scholar

[57] Rocha-Rodrigues S, Rodriguez A, Gouveia AM, Goncalves IO, Becerril S, Ramirez B, et al. Effects of physical exercise on myokines expression and brown adipose-like phenotype modulation in rats fed a high-fat diet. Life Sci. 2016165;100–8.Search in Google Scholar

[58] Alvehus M, Boman N, Soderlund K, Svensson MB, Buren J. Metabolic adaptations in skeletal muscle, adipose tissue, and whole-body oxidative capacity in response to resistance training. Eur J Appl Physiol. 2014;114:1463–71.Search in Google Scholar

[59] Petridou A, Tsalouhidou S, Tsalis G, Schulz T, Michna H, Mougios V. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue. Metabolism. 2007;56:1029–36.Search in Google Scholar

[60] Fukui Y, Masui S, Osada S, Umesono K, Motojima K. A new thiazolidinedione, NC-2100, which is a weak PPAR-gamma activator, exhibits potent antidiabetic effects and induces uncoupling protein 1 in white adipose tissue of KKAy obese mice. Diabetes. 2000;49:759–67.Search in Google Scholar

[61] WHO. Physical activity Fact sheet N°385, January 2015 edn. Geneva, 2015.Search in Google Scholar

[62] Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature. 2001;413:179–83.Search in Google Scholar

[63] Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature. 2001;413:131–8.Search in Google Scholar

[64] Kersten S, Seydoux J, Peters JM, Gonzalez FJ, Desvergne B, Wahli W. Peroxisome proliferator-activated receptor alpha mediates the adaptive response to fasting. J Clin Invest. 1999;103:1489–98.Search in Google Scholar

[65] Kersten S. Integrated physiology and systems biology of PPARalpha. Mol Metab. 2014;3:354–71.Search in Google Scholar

[66] Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–56.Search in Google Scholar

[67] Ahmadian M, Duncan RE, Sul HS. The skinny on fat: lipolysis and fatty acid utilization in adipocytes. Trends Endocrinol Metab. 2009;20:424–8.Search in Google Scholar

[68] Ahmadian M, Suh JM, Hah N, Liddle C, Atkins AR, Downes M, et al. PPARgamma signaling and metabolism: the good, the bad and the future. Nat Med. 2013;19:557–66.Search in Google Scholar

[69] Frohnert BI, Jacobs DR, Steinberger J, Moran A, Steffen LM, Sinaiko AR. Relation between serum free fatty acids and adiposity, insulin resistance, and cardiovascular risk factors from adolescence to adulthood. Diabetes. 2013;62:3163–9.Search in Google Scholar

[70] Cooper S, Shedden K. Microarrays and the relationship of mRNA variation to protein variation during the cell cycle. J Theor Biol. 2007;249:574–81.Search in Google Scholar

[71] Greenbaum D, Colangelo C, Williams K, Gerstein M. Comparing protein abundance and mRNA expression levels on a genomic scale. Genome Biol. 2003;4:117.Search in Google Scholar

[72] Maier T, Guell M, Serrano L. Correlation of mRNA and protein in complex biological samples. FEBS Lett. 2009;583:3966–73.Search in Google Scholar

[73] Martinez de Mena R, Scanlan TS, Obregon MJ. The T3 receptor beta1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes. Endocrinology. 2010;151:5074–83.Search in Google Scholar

[74] Garber JR, Cobin RH, Gharib H, Hennessey JV, Klein I, Mechanick JI, et al. Clinical practice guidelines for hypothyroidism in adults: cosponsored by the American Association of Clinical Endocrinologists and the American Thyroid Association. Thyroid. 2012;22:1200–35.Search in Google Scholar

[75] Ma Y, Olendzki BC, Pagoto SL, Hurley TG, Magner RP, Ockene IS, et al. Number of 24-hour diet recalls needed to estimate energy intake. Ann Epidemiol. 2009;19:553–9.Search in Google Scholar

[76] Program IoMUCoDRAitW: Dietary Risk Assessment in the WIC Program. Washington (DC): National Academies Press (US). 5 Food-Based Assessment of Dietary Intake 2002.Search in Google Scholar

Received: 2017-03-15
Accepted: 2017-04-09
Published Online: 2017-07-05

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