The Journal of Physiological Sciences

, Volume 69, Issue 1, pp 23–30 | Cite as

Effect of ambient temperature on the proliferation of brown adipocyte progenitors and endothelial cells during postnatal BAT development in Syrian hamsters

  • Kazuki Nagaya
  • Yuko Okamatsu-OguraEmail author
  • Junko Nio-Kobayashi
  • Shohei Nakagiri
  • Ayumi Tsubota
  • Kazuhiro Kimura
Original Paper


In Syrian hamsters, brown adipose tissue (BAT) develops postnatally through the proliferation and differentiation of brown adipocyte progenitors. In the study reported here, we investigated how ambient temperature influenced BAT formation in neonatal hamsters. In both hamsters raised at 23 or 30 °C, the interscapular fat changed from white to brown coloration in an age-dependent manner and acquired the typical morphological features of BAT by day 16. However, the expression of uncoupling protein 1, a brown adipocyte marker, and of vascular endothelial growth factor α were lower in the group raised at 30 °C than in that raised at 23 °C. Immunofluorescent staining revealed that the proportion of Ki67-expressing progenitors and endothelial cells was lower in the 30 °C group than in the 23 °C group. These results indicate that warm ambient temperature suppresses the proliferation of brown adipocyte progenitors and endothelial cells and negatively affects the postnatal development of BAT in Syrian hamsters.


Adipocyte Brown adipose tissue Uncoupling protein 1 Syrian hamster Proliferation Ambient temperature 


Author contributions

KN, YOO, JNK, SN, and AT conducted the experiments; YOO and KK designed the experiments; KN and YOO wrote the manuscript.


This study was supported by JSPS KAKENHI Grant Numbers 17K0811807 and 15H04545, Grants-in-Aid for the Naito Foundation, and for the Akiyama Life Science Foundation.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving animals were performed in accordance with the guidelines of Hokkaido University Manual for Implementing Animal Experimentation, in the animal facility approved by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International. The experimental procedures and care of animals were approved by the Animal Care and Use Committee of Hokkaido University (Hokkaido, Japan). This article does not contain any studies with human participants performed by any of the authors.


  1. 1.
    Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359CrossRefGoogle Scholar
  2. 2.
    Cinti S (2005) The adipose organ. Prostaglandins Leukot Essent Fat Acids 73:9–15CrossRefGoogle Scholar
  3. 3.
    Kajimura S, Saito M (2014) A new era in brown adipose tissue biology: molecular control of brown fat development and energy homeostasis. Annu Rev Physiol 76:225–249CrossRefGoogle Scholar
  4. 4.
    Xue Y, Petrovic N, Cao R (2009) Hypoxia-independent angiogenesis in adipose tissues during cold acclimation. Cell Metab 9:99–109CrossRefGoogle Scholar
  5. 5.
    Enerbäck S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, Kozak LP (1997) Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387:90–94CrossRefGoogle Scholar
  6. 6.
    Jimenez M, Léger B, Canola K, Lehr L, Arboit P, Seydoux J, Russell A, Giacobino J, Muzzin P, Preitner F (2002) β1/β 2/β 3-Adrenoceptor knockout mice are obese and cold-sensitive but have normal lipolytic responses to fasting. FEBS Lett 530:37–40CrossRefGoogle Scholar
  7. 7.
    Houstĕk J, Janíková D, Bednár J, Kopecký J, Sebestián J, Soukup T (1990) Postnatal appearance of uncoupling protein and formation of thermogenic mitochondria in hamster brown adipose tissue. Biochim Biophys Acta 1015:441–449CrossRefGoogle Scholar
  8. 8.
    Smalley RL, Smalley KN (1967) Brown and White fats; development in the hamster. Science 157:1449–1551CrossRefGoogle Scholar
  9. 9.
    Okamatsu-Ogura Y, Nio-Kobayashi J, Nagaya K, Tsubota A, Kimura K (2018) Brown adipocytes postnatally arise through both differentiation from progenitors and conversion from white adipocytes in Syrian hamster. J Appl Physiol 124(1):99–108Google Scholar
  10. 10.
    Hissa R (1968) Postnatal development of thermoregulation in the norwegian lemming and the golden hamster. Ann Zool Fennici 5:345–383Google Scholar
  11. 11.
    Xue B, Rim JS, Hogan JC, Coulter AA, Koza RA, Kozak LP (2007) Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J Lipid Res 48:41–51CrossRefGoogle Scholar
  12. 12.
    Mouroux I, Bertin R, Portet R (1990) Thermogenic capacity of the brown adipose tissue of developing rats; effects of rearing temperature. J Dev Physiol 14:337–342Google Scholar
  13. 13.
    Holloway BR, Davidson RG, Freeman S, Wheeler H, Stribling D (1984) Post-natal development of interscapular (brown) adipose tissue in the guina pig- effect of environmental temperature. Obesity 8:295–303Google Scholar
  14. 14.
    Peng XR, Gennemark P, O’Mahony G, Bartesaghi S (2015) Unlock the thermogenic potential of adipose tissue: pharmacological modulation and implications for treatment of diabetes and obesity. Front Endocrinol (Lausanne) 6:174CrossRefGoogle Scholar
  15. 15.
    Xiao C, Goldgof M, Gavrilova O, Reitman ML (2015) Anti-obesity and metabolic efficacy of the β3-adrenergic agonist, CL316243, in mice at thermoneutrality compared to 22 °C. Obesity 23:1450–1459CrossRefGoogle Scholar
  16. 16.
    Sakurai Y, Okamatsu-Ogura Y, Nakao R, Ohnuma A, Saito M, Kobayashi M, Kimura K (2015) Brown adipose tissue expressed uncoupling protein 1 in newborn harbor seals (Phoca vitulina). Mar Mamm Sci 31(2):818–827CrossRefGoogle Scholar
  17. 17.
    Sellayah D, Sikder D (2014) Orexin restores aging-related brown adipose tissue dysfunction in male mice. Endocrinology 155:485–501CrossRefGoogle Scholar
  18. 18.
    Teramura Y, Terao A, Okada Y, Tomida J, Okamatsu-Ogura Y, Kimura K (2014) Organ-specific changes in norepinephrine turnover against various stress conditions in thermoneutral mice. Jpn J Vet Res 62:117–127Google Scholar
  19. 19.
    Beauvallet M, Portet R, Blancher G, Solier M (1978) Post-natal development of brown adipose tissue in the rat bred at 23 or 28 °C. Arch Int Physiol Biochim 86:145–152Google Scholar
  20. 20.
    Fukano K, Okamatsu-Ogura Y, Tsubota A, Nio-Kobayashi J, Kimura K (2016) Cold exposure induces proliferation of mature brown adipocyte in a β3-adrenergic receptor-mediated pathway. PLoS One 11:1–13Google Scholar
  21. 21.
    Asano A, Morimatsu M, Nikami H, Yoshida T, Saito M (1997) Adrenergic activation of vascular endothelial growth factor mRNA expression in rat brown adipose tissue: implication in cold-induced angiogenesis. Biochem J 328:179–183CrossRefGoogle Scholar
  22. 22.
    Asano A, Kimura K, Saito M (1999) Cold-induced mRNA expression of angiogenic factors in rat brown adipose tissue. J Vet Med Sci 61:403–409CrossRefGoogle Scholar
  23. 23.
    Duchamp C, Burton KA, Geloen A, Dauncey MJ (1997) Transient upregulation of IGF-I gene expression in brown adipose tissue of cold-exposed rats. Am J Physiol 272:E453–E460Google Scholar
  24. 24.
    Garcia B, Obregon MJ (1997) Norepinephrine potentiates the mitogenic effect of growth factors in quiescent peadipocytes:relationship with uncoupling protein messenger ribonucleic acid expression. Endocrinology 138:4227–4233CrossRefGoogle Scholar
  25. 25.
    Geloen A, Collet AJ, Bukowiecki LJ (1992) Role of sympathetic innervation in brown adipocyte proliferation. Am J Physiol 263:1176–1181Google Scholar
  26. 26.
    Bagchi M, Kim LA, Boucher J, Walshe TE, Kahn CR, D’Amore PA (2013) Vascular endothelial growth factor is important for brown adipose tissue development and maintenance. FASEB J 27:3257–3271CrossRefGoogle Scholar
  27. 27.
    Sung HK, Doh K, Son J, Park J, Bae Y, Choi S, Nelson S, Mary L, Cowling R, Nagy K, Michael I, Koh G, Adamson S, Pawson T, Nagy A (2013) Adipose vascular endothelial growth factor regulates metabolic homeostasis through angiogenesis. Cell Metab 17:61–72CrossRefGoogle Scholar
  28. 28.
    Himms-Hagen J, Gwilliam C (1980) Abnormal brown adipose tissue in hamsters with muscular dystrophy. Am J Physiol 239:18–22CrossRefGoogle Scholar
  29. 29.
    Himms-Hagen J (1984) Nonshivering thermogenesis. Brain Res Bull 12:151–160CrossRefGoogle Scholar
  30. 30.
    Matos-Cruz V, Schneider ER, Mastrotto M, Merriman DK, Bagriantsev SN, Gracheva EO (2017) Molecular prerequisites for diminished cold sensitivity in ground squirrels and hamsters. Cell Rep 21:3329–3337CrossRefGoogle Scholar

Copyright information

© The Physiological Society of Japan and Springer Japan KK, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Laboratory of Biochemistry, Division of Veterinary Medicine, Graduate School of Veterinary MedicineHokkaido UniversitySapporoJapan
  2. 2.Laboratory of Histology and Cytology, Faculty of Medicine and Graduate School of MedicineHokkaido UniversitySapporoJapan

Personalised recommendations