The effect of continuous aerobic exercise on the expression of UCP1 and PGC1a genes in brown adipose tissue in obese male rats.

Subject Areas : Physical Activity and Health

Sarvenaz Ali Askari ¹ , محمد علی آذربایجانی ² , سیروان آتشک ³ , maghsoud peeri ⁴ , Saleh Rahmati ⁵

1 - دانشگاه آزاد واحد تهران مرکز
2 - استاد گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی، دانشگاه آزاد اسلامی واحد تهران مرکز، تهران، ایران
3 - گروه تربیت بدنی و علوم ورزشی، دانشگاه آزاد اسلامی، واحد مهاباد مهاباد، ایران.
4 - Department of Exercise Physiology, Islamic Azad University, Central Tehran Branch, Tehran, Iran
5 - Department of Physical Education, Pardis Branch, Islamic Azad University, Pardis, Iran.

Received: 2024-04-19 Accepted : 2024-08-21 Published : 2024-08-28

Keywords: Mitochondrial biogenesis, thermogenesis, aerobic exercise,

Abstract :

Brown adipose tissue plays a very important role in the pathogenesis of obesity. However, the effect of aerobic exercises on this tissue has received less attention. Based on this, the aim of the present study was to determine the effect of continuous aerobic exercise on the expression of UCP1 and PGC1a genes in brown adipose tissue in obese male rats. In an experimental study, 18 male rats were selected as subjects and randomly divided into three groups: control-fed with normal food, control-fed with high-fat food, and fed with high-fat diet and continuous aerobic exercise. The groups fed with high-fat diet received high-fat diet for eight weeks. Continuous aerobic exercise also included four weeks of running on a rodent treadmill. The expression of UCP1 and PGC1a genes in brown adipose tissue was measured by Real Time PCR method. The results showed that feeding with high-fat diet caused a significant decrease in the expression of UCP1 (P=0.002) and PGC1a (P=0.001) genes in brown adipose tissue. Continuous aerobic exercise increased the expression of UCP1 (P=0.040) and PGC1a (P=0.040) genes in brown fat tissue. Based on the findings of this study, it can be concluded that continuous aerobic exercise reduces the metabolic side effects of eating high-fat diet by increasing the expression of mitochondrial biogenesis and thermogenesis of brown adipose tissue. Therefore, it is recommended to perform these exercises while eating high-fat diet.

References:

1-Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity and severe obesity among adults: United States, 2017-2018. NCHS Data Brief. 2020;(360):1-8.
2-Kotsis V, Jordan J, Micic D, et al.. Obesity and cardiovascular risk: a call for action from the European Society of Hypertension Working Group of Obesity, Diabetes and the High-risk Patient and European Association for the Study of Obesity: part A: mechanisms of obesity induced hypertension, diabetes and dyslipidemia and practice guidelines for treatment. J Hypertens. 2018;36(7):1427-1440.
3- Liu X, Zhang Z, Song Y, Xie H, Dong M. An update on brown adipose tissue and obesity intervention: Function, regulation and therapeutic implications. Front Endocrinol (Lausanne). 2023 Jan 11;13:1065263.
4-Bartelt A, Bruns OT, Reimer R, Hohenberg H, Ittrich H, Peldschus K, Kaul MG, Tromsdorf UI, Weller H, Waurisch C, Eychmüller A, Gordts PL, Rinninger F, Bruegelmann K, Freund B, Nielsen P, Merkel M, Heeren J. Brown adipose tissue activity controls triglyceride clearance. Nat Med. 2011 Feb;17(2):200-5.
5-Mory G. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360(15):1518–25.
6-Joo JI, Yun JW. Gene expression profiling of adipose tissues in obesity susceptible and resistant rats under a high fat diet. Cell Physiol Biochem. 2011;27(3–4):327–40.
7-Rothwell NJ, Stock MJ, Effects of age on diet-induced thermogenesis and brown adipose tissue metabolism in the rat, Int. J. Obes 7 (6) (1983) 583–589.
8-Saugen E, Vøllestad NK, Nonlinear relationship between heat production and force during voluntary contractions in humans, J. Appl. Physiol. 79 (6) (1995) 2043–2049.
9- van Marken Lichtenbelt W, Brown adipose tissue and the regulation of nonshivering thermogenesis, Curr. Opin. Clin. Nutr. Metab. Care 15 (6) (2012) 547–552.
10- Lee JH, Park A, Oh KJ, Lee SC, Kim WK, Bae KH. The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases. Int J Mol Sci. 2019 Oct 4;20(19):4924.
11-Shen SH, Singh SP, Raffaele M, Waldman M, Hochhauser E, Ospino J, Arad M, Peterson SJ. Adipocyte-Specific Expression of PGC1α Promotes Adipocyte Browning and Alleviates Obesity-Induced Metabolic Dysfunction in an HO-1-Dependent Fashion. Antioxidants (Basel). 2022 Jun 10;11(6):1147.
12- Zouhal H, et al., Catecholamines and the effects of exercise, training and gender, Sports Med 38 (5) (2008) 401–423.
13- Sanchez-Delgado G, et al., Role of exercise in the activation of brown adipose tissue, Ann. Nutr. Metab 67 (1) (2015) 21–32.
14- e Las Heras N, Klett-Mingo M, Ballesteros S, Martín-Fernández B, Escribano Ó, Blanco-Rivero J, Balfagón G, Hribal ML, Benito M, Lahera V, Gómez-Hernández A. Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue. Front Physiol. 2018 Aug 17;9:1122.
15- Od-Ek P, Deenin W, Malakul W, Phoungpetchara I, Tunsophon S. Anti-obesity effect of Carica papaya in high-fat diet fed rats. Biomed Rep. 2020 Oct;13(4):30.
16- Nikbin S, Tajik A, Allahyari P, Matin G, Hoseini Roote SS, Barati E, Ayazi M, Karimi L, Dayani Yazdi F, Javadinejad N, Azarbayjani MA. Aerobic exercise and eugenol supplementation ameliorated liver injury induced by chlorpyrifos via modulation acetylcholinesterase activation and antioxidant defense. Environmental toxicology. 2020 Jul;35(7):783-93.

17- Aldiss P, Lewis JE, Boocock DJ, Miles AK, Bloor I, Ebling FJ, Budge H, Symonds ME. Interscapular and perivascular brown adipose tissue respond differently to a short-term high-fat diet. Nutrients. 2019 May 13;11(5):1065.
18- Shin S, Ajuwon KM. Effects of Diets Differing in Composition of 18-C Fatty Acids on Adipose Tissue Thermogenic Gene Expression in Mice Fed High-Fat Diets. Nutrients. 2018 Feb 23;10(2):256.
19-Chouchani E.T., Kazak L., Spiegelman B.M. Mitochondrial reactive oxygen species and adipose tissue thermogenesis: Bridging physiology and mechanisms. J. Biol. Chem. 2017;292:16810–16816.
20- Chouchani E.T., Kazak L., Spiegelman B.M. Mitochondrial reactive oxygen species and adipose tissue thermogenesis: Bridging physiology and mechanisms. J. Biol. Chem. 2017;292:16810–16816.
21- Kleiner S., Mepani R.J., Laznik D., Ye L., Jurczak M.J., Jornayvaz F.R., Estall J.L., Chatterjee B.D., Shulman G.I., Spiegelman B.M. Development of insulin resistance in mice lacking PGC-1alpha in adipose tissues. Proc. Natl. Acad. Sci. USA. 2012;109:9635–9640.
22- Kong X., Banks A., Liu T., Kazak L., Rao R.R., Cohen P., Wang X., Yu S., Lo J.C., Tseng Y.H., et al. IRF4 is a key thermogenic transcriptional partner of PGC-1alpha. Cell. 2014;158:69–83.
23- Mouton A.J., Li X., Hall M.E., Hall J.E. Obesity, Hypertension, and Cardiac Dysfunction: Novel Roles of Immunometabolism in Macrophage Activation and Inflammation. Circ. Res. 2020;126:789–806.
24- Collins S., Daniel K.W., Petro A.E., Surwit R.S. Strain-specific response to β 3-adrenergic receptor agonist treatment of diet-induced obesity in mice. Endocrinology. 1997;138:405–413.
25- Lopez-Vicchi F, De Winne C, Ornstein AM, Sorianello E, Toneatto J, Becu-Villalobos D. Severe Hyperprolactinemia Promotes Brown Adipose Tissue Whitening and Aggravates High Fat Diet Induced Metabolic Imbalance. Front Endocrinol (Lausanne). 2022 Jun 10;13:883092.
26- Sakamoto T, Nitta T, Maruno K, Yeh YS, Kuwata H, Tomita K, Goto T, Takahashi N, Kawada T. Macrophage infiltration into obese adipose tissues suppresses the induction of UCP1 level in mice. Am J Physiol Endocrinol Metab. 2016 Apr 15;310(8):E676-E687.
27- Masaki T, Yoshimatsu H, Chiba S, Hidaka S, Tajima D, Kakuma T, Kurokawa M, Sakata T. Tumor necrosis factor-alpha regulates in vivo expression of the rat UCP family differentially. Biochim Biophys Acta 1436: 585–592, 1999.
28- Nisoli E, Briscini L, Giordano A, Tonello C, Wiesbrock SM, Uysal KT, Cinti S, Carruba MO, Hotamisligil GS. Tumor necrosis factor alpha mediates apoptosis of brown adipocytes and defective brown adipocyte function in obesity. Proc Natl Acad Sci USA 97: 8033–8038, 2000.

29- Porras A, Valladares A, Alvarez AM, Roncero C, Benito M. Differential role of PPAR gamma in the regulation of UCP-1 and adipogenesis by TNF-alpha in brown adipocytes. FEBS Lett 520: 58–62, 2002.
30- Romanatto T, Roman EA, Arruda AP, Denis RG, Solon C, Milanski M, Moraes JC, Bonfleur ML, Degasperi GR, Picardi PK, Hirabara S, Boschero AC, Curi R, Velloso LA. Deletion of tumor necrosis factor-alpha receptor 1 (TNFR1) protects against diet-induced obesity by means of increased thermogenesis. J Biol Chem 284: 36213–36222, 2009.

31- Sakamoto T, Takahashi N, Sawaragi Y, Naknukool S, Yu R, Goto T, Kawada T. Inflammation induced by RAW macrophages suppresses UCP1 mRNA induction via ERK activation in 10T1/2 adipocytes. Am J Physiol Cell Physiol 304: C729–C738, 2013.
32- Morton TL, Galior K, McGrath C, Wu X, Uzer G, Uzer GB, Sen B, Xie Z, Tyson D, Rubin J, Styner M. Exercise Increases and Browns Muscle Lipid in High-Fat Diet-Fed Mice. Front Endocrinol (Lausanne). 2016 Jun 30;7:80.
33- Bartelt A, Heeren J. Adipose tissue browning and metabolic health. Nat Rev Endocrinol. (2014) 10:24–36.
34- De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, Cinti S, Cuppini R. Exercise as a new physiological stimulus for brown adipose tissue activity. Nutr Metab Cardiovasc Dis. 2013 Jun;23(6):582-90.
35- de Las Heras N, Klett-Mingo M, Ballesteros S, Martín-Fernández B, Escribano Ó, Blanco-Rivero J, Balfagón G, Hribal ML, Benito M, Lahera V, Gómez-Hernández A. Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue. Front Physiol. 2018 Aug 17;9:1122.
36- Dominy J. E., Jr., Lee Y., Gerhart-Hines Z., Puigserver P. (2010). Nutrient-dependent regulation of PGC-1alpha’s acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. Biochim. Biophys. Acta 1804 1676–1683.
37- Zhu Y, Qi Z, Ding S. Exercise-Induced Adipose Tissue Thermogenesis and Browning: How to Explain the Conflicting Findings? Int J Mol Sci. 2022 Oct 28;23(21):13142.
38- Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK, Gulseth HL, Birkeland KI, Jensen J, Drevon CA. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J. 2014 Feb;281(3):739-49.
39- Ricquier D. (2006). Fundamental mechanisms of thermogenesis. C. R. Biol. 329 578–586.
40- Félix-Soriano E, Sáinz N, Gil-Iturbe E, Castilla-Madrigal R, Celay J, Fernández-Galilea M, Pejenaute Á, Lostao MP, Martínez-Climent JA, Moreno-Aliaga MJ. Differential remodeling of subcutaneous white and interscapular brown adipose tissue by long-term exercise training in aged obese female mice. J Physiol Biochem. 2023 May;79(2):451-465.
41- Puigserver P., Spiegelman B. M. (2003). Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr. Rev. 24 78–90.
42- Farshbaf M.J., Garasia S., Moussoki D.P.K., Mondal A.K., Cherkowsky D., Manal N., Alvina K. Hippocampal Injection of the Exercise-Induced Myokine Irisin Suppresses Acute Stress-Induced Neurobehavioral Impairment in a Sex-Dependent Manner. Behav. Neurosci. 2020;134:233–247.
43- Sleiman S.F., Henry J., Al-Haddad R., El H.L., Abou H.E., Stringer T., Ulja D., Karuppagounder S.S., Holson E.B., Ratan R.R., et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body beta-hydroxybutyrate. Elife. 2016;5:e15092.