Advertisement

Activation of brown adipose tissue in diet-induced thermogenesis is GC-C dependent

  • Nikola Habek
  • Marina Dobrivojević Radmilović
  • Milan Kordić
  • Katarina Ilić
  • Sandra Grgić
  • Vladimir Farkaš
  • Robert Bagarić
  • Siniša Škokić
  • Alfred Švarc
  • Aleksandra DugandžićEmail author
Signaling and cell physiology
Part of the following topical collections:
  1. Signaling and cell physiology
  2. Signaling and cell physiology

Abstract

Uroguanylin (UGN) is released from the intestine after a meal. When applied in brain ventricles, UGN increases expression of markers of thermogenesis in brown adipose tissue (BAT). Therefore, we determine the effects of its receptor, guanylate cyclase C (GC-C), on mouse interscapular BAT (iBAT) activity during diet-induced thermogenesis (DIT). The activation of iBAT after a meal is diminished in GC-C KO mice, decreased in female wild type (WT) mice, and abolished in old WT animals. The activation of iBAT after a meal is the highest in male WT animals which leads to an increase in GC-C expression in the hypothalamus, an increase in iBAT volume by aging, and induction of iBAT markers of thermogenesis. In contrast to iBAT activation after a meal, iBAT activation after a cold exposure could still exist in GC-C KO mice and it is significantly higher in female WT mice. The expression of GC-C in the proopiomelanocortin neurons of the arcuate nucleus of the hypothalamus but not in iBAT suggests central regulation of iBAT function. The iBAT activity during DIT has significantly reduced in old mice but an intranasal application of UGN leads to an increase in iBAT activity in a dose-dependent manner which is in strong negative correlation to glucose concentration in blood. This activation was not present in GC-C KO mice. Our results suggest the physiological role of GC-C on the BAT regulation and its importance in the regulation of glucose homeostasis and the development of new therapy for obesity and insulin resistance.

Keywords

Uroguanylin Hypothalamus Male vs female PET-CT MRI Infrared thermography 

Notes

Acknowledgments

We would like to thank Petar Škavić, MD, Department of Forensic Medicine and Criminology, University of Zagreb, School of Medicine, Zagreb, Croatia for obtaining written consent from the families and collecting human samples, Danica Budinščak for technical support, Josip Dugandžić for expertise in graphic presentation and figure preparation, and Dr. Kris A. Steinbrecher, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio, USA for a donation of GC-C KO animals.

Authors’ contributions

Nikola Habek designed research; performed oxygen consumption, locomotor activity, RT-PCR, qPCR, intranasal application of UGN, and immunohistochemistry; analyzed data; performed statistical analysis; and contributed to the writing of the manuscript.

Marina Dobrivojević Radmilović designed and performed MRI experiments and analyzed data.

Milan Kordić designed and performed infrared thermography experiments and analyzed data.

Katarina Ilić designed and performed western blot analysis.

Sandra Grgić performed genotyping of WT and GC-C KO littermates.

Vladimir Farkaš, Robert Bagarić, and Alfred Švarc designed and performed PET-CT experiments and analyzed data.

Siniša Škokić designed and performed MRI experiments and analyzed data.

Aleksandra Dugandžić designed research, analyzed data, and wrote and revised the manuscript.

All authors read and approved the final manuscript.

Funding information

This study was funded by a grant from the Croatian Science Foundation (FURNACE: 2018-01-7416).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. The experiments were performed in accordance with the ARRIVE guidelines. All procedures performed in studies involving animals were in accordance with the ethical standards of the University of Zagreb, School of Medicine, approved by Ethics Committee (EP 185/2018), and in accordance with the Ethical Codex of Croatian Society for Laboratory Animal Science. All efforts were made to minimize animal suffering and to reduce the number of animals used.

Supplementary material

424_2020_2347_MOESM1_ESM.docx (3.5 mb)
ESM 1 (DOCX 3626 kb)

References

  1. 1.
    Al-Lawati JA, Mohammed AJ, Al-Hinai HQ, Jousilahti P (2003) Prevalence of the metabolic syndrome among Omani adults. Diabetes Care 26:1781–1785. doi:  https://doi.org/10.2337/diacare.26.6.1781
  2. 2.
    Ang QY, Goh HJ, Cao Y, Li Y, Chan SP, Swain JL, Henry CJ, Leow MK (2017) A new method of infrared thermography for quantification of brown adipose tissue activation in healthy adults (TACTICAL): a randomized trial. J Physiol Sci 67:395–406.  https://doi.org/10.1007/s12576-016-0472-1 CrossRefPubMedGoogle Scholar
  3. 3.
    Begg DP, Steinbrecher KA, Mul JD, Chambers AP, Kohil R, Haller A, Cohen MB, Woods SC, Seeley RJ (2014) Effect of guanylate cyclase-C activity on energy and glucose homeostasis. Diabetes 63:3798–3904.  https://doi.org/10.2337/db14-0160 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Benedict C, Brede S, Schiöth HB, Lehnert H, Schultes B, Born J, Hallschmid M (2011) Intranasal insulin enhances postprandial thermogenesis and lowers postprandial serum insulin levels in healthy men. Diabetes 60:114–118.  https://doi.org/10.2337/db10-0329 CrossRefPubMedGoogle Scholar
  5. 5.
    Branca RT, Zhang L, Warren WS, Auerbach E, Khanna A, Degan S, Ugurbil K, Maronpot R (2013) In vivo noninvasive detection of brown adipose tissue through intermolecular zero-quantum MRI. PLoS One 8:e74206.  https://doi.org/10.1371/journal.pone.0074206 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Carter EA, Bonab AA, Paul K, Yerxa J, Tompkins RG, Fischman AJ (2011) Association of heat production with FDG accumulation by murine brown adipose tissue (BAT) after stress. J Nucl Med 52:1616–1620.  https://doi.org/10.2967/jnumed.111.090175 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Crane JD, Mottillo EP, Farncombe TH, Morrison KM, Steinberg GR (2014) A standardized infrared imaging technique that specifically detects UCP1-mediated thermogenesis in vivo. Mol Metab 3:490–494.  https://doi.org/10.1016/j.molmet.2014.04.007 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Di Guglielmo MD, Perdue L, Adeyemi A, van Golen KL, Corao DU (2017) Immunohistochemical staining for uroguanylin, a satiety hormone, is decreased in intestinal tissue specimens from female adolescents with obesity. Pediatr Dev Pathol 21:285–295.  https://doi.org/10.1177/1093526617722912 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Di Guglielmo MD, Tonb D, He Z, Adeyemi A, van Golen KL (2017) A pilot study measuring the novel satiety hormone, pro-uroguanylin, in adolescents with and without obesity. J Pediatr Gastroenterol Nutr 66:489–495.  https://doi.org/10.1097/MPG.0000000000001796 CrossRefGoogle Scholar
  10. 10.
    Dodd GT, Decherf S, Loh K, Simonds SE, Wiede F, Balland E, Merry TL, Münzberg H, Zhang ZY, Kahn BB, Neel BG, Bence KK, Andrews ZB, Cowley MA, Tiganis T (2015) Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell 160:8–104.  https://doi.org/10.1016/j.cell.2014.12.022 CrossRefGoogle Scholar
  11. 11.
    Egawa M, Yoshimatsu H, Bray GA (1991) Neuropeptide Y suppresses sympathetic activity to interscapular brown adipose tissue in rats. Am J Phys 260:R328–R334Google Scholar
  12. 12.
    Folgueira C, Sanchez-Rebordelo E, Barja-Fernandez S, Leis R, Tovar S, Casanueva FF, Dieguez C, Nogueiras R, Seoane LM (2016) Uroguanylin levels in intestine and plasma are regulated by nutritional status in a leptin-dependent manner. Eur J Nutr 55:529–536.  https://doi.org/10.1007/s00394-015-0869-2 CrossRefPubMedGoogle Scholar
  13. 13.
    Folgueira C, Beiroa D, Callon A, Al-Massadi O, Barja-Fernandez S, Senra A, Fernø J, López M, Dieguez C, Casanueva FF, Rohner-Jeanrenaud F, Seoane LM, Nogueiras R (2016) Uroguanylin action in the brain reduces weight gain in obese mice via different efferent autonomic pathways. Diabetes 65:421–432.  https://doi.org/10.2337/db15-0889 CrossRefPubMedGoogle Scholar
  14. 14.
    Glumer C, Jorgensen T, Borch-Johnsen K (2003) Prevalences of diabetes and impaired glucose regulation in a Danish population: the Inter99 study. Diabetes Care 26:2335–2340. doi:  https://doi.org/10.2337/diacare.26.8.2335
  15. 15.
    Gong R, Ding C, Hu J, Lu Y, Liu F, Mann E, Xu CMB, Luo M (2011) Role for the membrane receptor guanylyl cyclase-C in attention deficiency and hyperactive behavior. Science 333:1642–1646.  https://doi.org/10.1126/science.1207675 CrossRefPubMedGoogle Scholar
  16. 16.
    Gu D, Reynolds K, Wu X, Chen J, Duan X, Reynolds RF Whelton PK, He J (2005) Prevalence of the metabolic syndrome and overweight among adults in China. Lancet 365:1398–1405. doi:  https://doi.org/10.1016/S0140-6736(05)66375-1
  17. 17.
    Gupta R, Deedwania PC, Gupta A, Rastogi S, Panwar RB, Kothari K (2004) Prevalence of metabolic syndrome in an Indian urban population. Int J Cardiol 97:257–261. doi:  https://doi.org/10.1016/j.ijcard.2003.11.003
  18. 18.
    Habek N, Kordić M, Jurenec F, Dugandžić A (2018) Infrared thermography, a new method for detection brown adipose tissue activity after a meal in humans. Infrared Phys Technol 89:271-276. doi:  https://doi.org/10.1016/j.infrared.2018.01.020
  19. 19.
    Hallschmid M, Benedict C, Schultes B, Fehm HL, Born J, Kern W (2004) Intranasal insulin reduces body fat in men but not in women. Diabetes 53:3024–3029CrossRefGoogle Scholar
  20. 20.
    Hibi M, Oishi S, Matsushita M, Yoneshiro T, Yamaguchi T, Usui C, Yasunaga K, Katsuragi Y, Kubota K, Tanaka S, Saito M (2016) Brown adipose tissue is involved in diet-induced thermogenesis and whole-body fat utilization in healthy humans. Int J Obes 40:1655–1661.  https://doi.org/10.1038/ijo.2016.124 CrossRefGoogle Scholar
  21. 21.
    Kim GW, Lin JE, Snook AE, Aing AS, Merlino DJ, Li P, Waldman SA (2016) Calorie-induced ER stress suppresses uroguanylin satiety signaling in diet-induced obesity. Nutr Diabetes 6:e211.  https://doi.org/10.1038/nutd.2016.18 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Machin D, Campbell M, Fayers P, Pinol A (1997) Sample size tables for clinical studies, 2nd edn. Blackwell Science, Malden, MAGoogle Scholar
  23. 23.
    Mann EA, Jump ML, Wu J, Yee E, Giannella RA (1997) Mice lacking the guanylyl cyclase C receptor are resistant to STa-induced intestinal secretion. Biochem Biophys Res Commun 239:463–466CrossRefGoogle Scholar
  24. 24.
    Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, Richard D (2011) Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 96:192–199.  https://doi.org/10.1210/jc.2010-0989 CrossRefPubMedGoogle Scholar
  25. 25.
    Pfannenberg C, Werner MK, Ripkens S, Stef I, Deckert A, Schmadl M, Reimold M, Häring HU, Claussen CD, Stefan N (2010) Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes 59:1789–1793.  https://doi.org/10.2337/db10-0004 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Rasmussen JM, Entringer S, Nguyen A, van Erp TG, Burns J, Guijarro A, Oveisi F, Swanson JM, Piomelli D, Wadhwa PD, Buss C, Potkin SG (2013) Brown adipose tissue quantification in human neonates using water-fat separated MRI. PLoS One B:e77907. doi:  https://doi.org/10.1371/journal.pone.0077907 CrossRefGoogle Scholar
  27. 27.
    Rodríguez A, Gómez-Ambrosi J, Catalán V, Ezquerro S, Méndez-Giménez L, Becerril S. Ibáñez P, Vila N, Margall MA, Moncada R, Valentí V, Silva C, Salvador J, Frühbeck G (2016) Guanylin and uroguanylin stimulate lipolysis in human visceral adipocytes. Int J Obes 40:1405–1415. doi:  https://doi.org/10.1038/ijo.2016.66 CrossRefGoogle Scholar
  28. 28.
    Roldan PS, Chereul E, Dietzel O, Magnier L, Pautrot C, Rbah-Vidal L, Sappey-Marinier D, Wagner A, Zimmer L, Janier MF, Tarazona V, Dietzel G (2007) Raytest ClearPET™, a new generation small animal PET scanner. Nucl Instr Meth Phys Res A 571:498–501CrossRefGoogle Scholar
  29. 29.
    Scheving LA, Russell WE, Chong KM (1996) Structure, glycosilation and localisation of rat intestinal guanylyl cyclase C: modulation by fasting. Am J Physiology 271:G959–G968Google Scholar
  30. 30.
    Schwarz JM, Schutz Y, Froidevaux F, Acheson KJ, Jeanprêtre N, Schneider H, Felber JP, Jéquier E (1989) Thermogenesis in men and women induced by fructose vs glucose added to a meal. Am J Clin Nutr 49, 667–674 (1989)CrossRefGoogle Scholar
  31. 31.
    Shi H, Strader AD, Woods SC, Seeley RJ (2007) Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy. Am J Physiol Endocrinol Metab 293:E316–E326.  https://doi.org/10.1152/ajpendo.00710.2006 CrossRefPubMedGoogle Scholar
  32. 32.
    Sicree RA, Zimmet PZ, Dunstan DW, Cameron AJ, Welborn TA, Shaw JE (2008) Differences in height explain gender differences in the response to the oral glucose tolerance test—the AusDiab study. Diabet Med 25:296–302.  https://doi.org/10.1111/j.1464-5491.2007.02362.x CrossRefPubMedGoogle Scholar
  33. 33.
    Simões-Silva L, Moreira-Rodrigues M, Quelhas-Santos J, Fernandes-Cerqueira C, Pestana M, Soares-Silva I, Sampaio-Maia B (2013) Intestinal and renal guanylin peptides system in hypertensive obese mice. Exp Biol Med (Maywood) 238:90–97.  https://doi.org/10.1258/ebm.2012.012232 CrossRefGoogle Scholar
  34. 34.
    Sinđić A, Velic A, Başoglu C, Hirsch JR, Edemir B, Kuhn M, Schlatter E (2005) Uroguanylin and guanylin regulate transport of mouse cortical collecting duct independent of guanylate cyclase C. Kidney Int 68:1008–1017CrossRefGoogle Scholar
  35. 35.
    Steculorum SM, Ruud J, Karakasilioti I, Backes H, Engström Ruud L, Timper K. Hess ME, Tsaousidou E, Mauer J, Vogt MC, Paeger L, Bremser S, Klein AC, Morgan DA, Frommolt P, Brinkkötter PT, Hammerschmidt P, Benzing T, Rahmouni K, Wunderlich FT, Kloppenburg P, Brüning JC (2016) AgRP neurons control systemic insulin sensitivity via myostatin expression in brown adipose tissue. Cell 165:125–138. doi:  https://doi.org/10.1016/j.cell.2016.02.044 CrossRefGoogle Scholar
  36. 36.
    Thielemans K, Tsoumpas C, Mustafovic S, Beisel T, Aguiar P, Dikaios N, Jacobson M (2012) STIR: software for tomographic image reconstruction release 2. Phys Med Biol 57:867–883.  https://doi.org/10.1088/0031-9155/57/4/867 CrossRefPubMedGoogle Scholar
  37. 37.
    Valentino MA, Lin JE, Snook AE, Li P, Kim GW, Marszalowicz G, Magee MS, Hyslop T, Schulz S, Waldman SA (2011) A uroguanylin-GUCY2C endocrine axis regulates feeding in mice. J Clin Invest 121:3578–3588.  https://doi.org/10.1172/JCI57925 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    van Genugten RE, Utzschneider KM, Tong J, Gerchman F, Zraika S, Udayasankar, J, Boyko EJ, Fujimoto WY, Kahn SE (2006) Effects of sex and hormone replacement therapy use on the prevalence of isolated impaired fasting glucose and isolated impaired glucose tolerance in subjects with a family history of type 2 diabetes. Diabetes 55:3529–3535. doi:  https://doi.org/10.2337/db06-0577
  39. 39.
    Vosselman MJ, Brans B, van der Lans AA, Wierts R, van Baak MA, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD (2013) Brown adipose tissue activity after a high-calorie meal in humans. Am J Clin Nutr 98:57–64.  https://doi.org/10.3945/ajcn.113.059022 CrossRefPubMedGoogle Scholar
  40. 40.
    Wang X, Minze LJ, Shi Z (2012) Functional imaging of brown fat in mice with 18F-FDG micro-PET/CT. J Vis Exp 69:4060.  https://doi.org/10.3791/4060 CrossRefGoogle Scholar
  41. 41.
    Weber S, Morel C, Simon L, Krieguer M, Rey M, Gundlich B, Khodaverdi M (2006) Image reconstruction for the ClearPET™. Neuro Nucl Instr Meth Phys Res A 569:381–385CrossRefGoogle Scholar
  42. 42.
    Williams JW, Zimmet PZ, Shaw JE, de Courten MP, Cameron AJ, Chitson P, Tuomilehto J, Alberti KG (2003) Gender differences in the prevalence of impaired fasting glycaemia and impaired glucose tolerance in Mauritius. Does sex matter? Diabet Med 20:915–920.  https://doi.org/10.1046/j.1464-5491.2003.01059.x CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2020

Authors and Affiliations

  • Nikola Habek
    • 1
    • 2
    • 3
  • Marina Dobrivojević Radmilović
    • 1
    • 4
  • Milan Kordić
    • 5
  • Katarina Ilić
    • 1
    • 2
  • Sandra Grgić
    • 1
  • Vladimir Farkaš
    • 6
  • Robert Bagarić
    • 6
  • Siniša Škokić
    • 1
    • 2
  • Alfred Švarc
    • 6
  • Aleksandra Dugandžić
    • 1
    • 2
    • 3
    Email author
  1. 1.School of Medicine, Croatian Institute for Brain ResearchUniversity of ZagrebZagrebCroatia
  2. 2.School of Medicine, Centre of Excellence for Basic, Clinical and Translational NeuroscienceUniversity of ZagrebZagrebCroatia
  3. 3.Department of Physiology and Immunology, School of MedicineUniversity of ZagrebZagrebCroatia
  4. 4.Department of Histology and Embryology, School of MedicineUniversity of ZagrebZagrebCroatia
  5. 5.MKP Ltd. ZagrebZagrebCroatia
  6. 6.Division of Experimental PhysicsRuđer Bošković InstituteZagrebCroatia

Personalised recommendations