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Relationships between expression levels of genes related to adipogenesis and adipocyte function in dogs

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Abstract

There are three kinds of adipocytes; white adipocytes accumulate excess energy as fat, whereas brown/beige adipocytes dissipate energy through expression of uncoupling protein 1 (UCP1). Obesity, a feature of excess accumulation of white adipocytes in a body, is one of the risk factors for onset of various diseases in dogs. As the first step to explore adipose genes related to dog obesity, we examined relationships among mRNA levels of putative molecules related to adipogenesis and function of adipocytes in fat of hospitalized dogs. Gonadal adipose tissues were collected from a total of 29 dogs, and the gene expression levels were examined by quantitative RT-PCR analysis. The multicollinearity analysis revealed that body condition score (BCS), which reflects adiposity, did not correlate with expression levels of any genes but correlated with age of dog. Bone morphogenetic protein (BMP) pathway stimulates not only commitment of mesenchymal stem cells to white adipocyte-lineage cells but also brown/beige adipogenesis. Some relationships between expression levels of BMP receptors were significant; especially, expression levels of activin receptor-like kinase (Alk) 3 (a BMP type I receptor) positively related to those of Alk2 (another BMP type I receptor), activin receptor type II (ActRII) A (a type II receptor to transmit BMP signal), ActRIIB (another type II receptor to transmit BMP signal) and BMP receptor type 2 (Bmpr2). PR domain containing 16 (Prdm16) expression levels strongly correlated with expression levels of ActRIIB. Although PRDM16 is known to stimulate brown/beige adipogenesis, expression levels of Ucp1 did not correlate with those of Prdm16. On the other hand, expression levels of Ucp1 correlated with those of Alk6. The present study suggests close relationships among adipose expressions of BMP signal components, and the relationships of expression levels of BMP receptor and those of Prdm16 or Ucp1 in dogs. Further studies using more dogs with various BCS potentially lead to identification of adipose factors to relate with adiposity in dogs.

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References

  1. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359

    Article  CAS  PubMed  Google Scholar 

  2. Kajimura S, Spiegelman BM, Seale P (2015) Brown and beige fat: physiological roles beyond heat generation. Cell Metab 2:546–559

    Article  Google Scholar 

  3. Lavie CJ, Milani RV, Ventura HO (2009) Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol 53:1925–1932

    Article  PubMed  Google Scholar 

  4. van der Klaauw AA, Farooqi IS (2015) The hunger genes: pathways to obesity. Cell 161:119–132

    Article  PubMed  Google Scholar 

  5. Chandler M, Cunningham S, Lund EM, Khanna C, Naramore R, Patel A, Day MJ (2017) Obesity and associated comorbidities in people and companion animals: a one health perspective. J Comp Pathol 156:296–309

    Article  CAS  PubMed  Google Scholar 

  6. Klimentidis YC, Beasley TM, Lin HY, Murati G, Glass GE, Guyton M, Newton W, Jorgensen M, Heymsfield SB, Kemnitz J, Fairbanks L, Allison DB (2011) Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics. Proc Biol Sci 278:1626–1632

    Article  PubMed  Google Scholar 

  7. Loftus JP, Wakshlag JJ (2014) Canine and feline obesity: a review of pathophysiology, epidemiology, and clinical management. Vet Med (Auckl) 6:49–60

    Google Scholar 

  8. Tang QQ, Lane MD (2012) Adipogenesis: from stem cell to adipocyte. Annu Rev Biochem 81:715–736

    Article  CAS  PubMed  Google Scholar 

  9. Ahima RS, Lazar MA (2008) Adipokines and the peripheral and neural control of energy balance. Mol Endocrinol 22:1023–1031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang W, Seale P (2016) Control of brown and beige fat development. Nat Rev Mol Cell Biol 17:691–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR (2008) Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454:961–967

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Seale P, Conroe HM, Estall J, Kajimura S, Frontini A, Ishibashi J, Cohen P, Cinti S, Spiegelman BM (2011) Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice. J Clin Invest 121:96–105

    Article  CAS  PubMed  Google Scholar 

  13. Tang QQ, Otto TC, Lane MD (2004) Commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage. Proc Natl Acad Sci USA 101:9607–9611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454:1000–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Xue R, Wan Y, Zhang S, Zhang Q, Ye H, Li Y (2014) Role of bone morphogenetic protein 4 in the differentiation of brown fat-like adipocytes. Am J Physiol Endocrinol Metab 306:E363–E372

    Article  CAS  PubMed  Google Scholar 

  16. Jimenez AG, Winward J, Beattie U, Cipolli W (2018) Cellular metabolism and oxidative stress as a possible determinant for longevity in small breed and large breed dogs. PLoS ONE 13:e0195832

    Article  PubMed  PubMed Central  Google Scholar 

  17. Salt C, Morris PJ, German AJ, Wilson D, Lund EM, Cole TJ, Butterwick RF (2017) Growth standard charts for monitoring bodyweight in dogs of different sizes. PLoS ONE 12:e0182064

    Article  PubMed  PubMed Central  Google Scholar 

  18. Weber MP, Biourge VC, Nguyen PG (2017) Digestive sensitivity varies according to size of dogs: a review. J Anim Physiol Anim Nutr 101:1–9

    Article  CAS  Google Scholar 

  19. Kida R, Noguchi T, Murakami M, Hashimoto O, Kawada T, Matsui T, Funaba M (2018) Supra-pharmacological concentration of capsaicin stimulates brown adipogenesis through induction of endoplasmic reticulum stress. Sci Rep 8:845

    Article  PubMed  PubMed Central  Google Scholar 

  20. SAS Institute (2001) SAS User’s Guide: Statistics, Ver. 9.2. SAS Institute, Cary, NC

  21. Bastien BC, Patil A, Satyaraj E (2015) The impact of weight loss on circulating cytokines in Beagle dogs. Vet Immunol Immunopathol 163:174–182

    Article  CAS  PubMed  Google Scholar 

  22. German AJ, Hervera M, Hunter L, Holden SL, Morris PJ, Biourge V, Trayhurn P (2009) Improvement in insulin resistance and reduction in plasma inflammatory adipokines after weight loss in obese dogs. Domest Anim Endocrinol 37:214–226

    Article  CAS  PubMed  Google Scholar 

  23. Ishioka K, Hosoya K, Kitagawa H, Shibata H, Honjoh T, Kimura K, Saito M (2007) Plasma leptin concentration in dogs: effects of body condition score, age, gender and breeds. Res Vet Sci 82:11–15

    Article  CAS  PubMed  Google Scholar 

  24. Verkest KR, Fleeman LM, Morton JM, Ishioka K, Rand JS (2011) Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis. Domest Anim Endocrinol 41:24–34

    Article  CAS  PubMed  Google Scholar 

  25. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432

    Article  CAS  PubMed  Google Scholar 

  26. Kawasumi K, Kashiwado N, Okada Y, Sawamura M, Sasaki Y, Iwazaki E, Mori N, Yamamoto I, Arai T (2014) Age effects on plasma cholesterol and triglyceride profiles and metabolite concentrations in dogs. BMC Vet Res 10:57

    Article  PubMed  PubMed Central  Google Scholar 

  27. Streeter RM, Struble AM, Mann S, Nydam DV, Bauer JE, Castelhano MG, Todhunter RJ, Cummings BP, Wakshlag JJ (2015) The associations between serum adiponectin, leptin, C-reactive protein, insulin, and serum long-chain omega-3 fatty acids in Labrador Retrievers. Vet Med 6:103–110

    Google Scholar 

  28. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746–26749

    Article  CAS  PubMed  Google Scholar 

  29. Leray V, Serisier S, Khosniat S, Martin L, Dumon H, Nguyen P (2008) Adipose tissue gene expression in obese dogs after weight loss. J Anim Physiol Anim Nutr (Berl) 92:390–398

    Article  CAS  Google Scholar 

  30. Wajchenberg BL (2000) Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21:697–738

    Article  CAS  PubMed  Google Scholar 

  31. Miyazono K (2000) Positive and negative regulation of TGF-β signaling. J Cell Sci 113:1101–1109

    CAS  PubMed  Google Scholar 

  32. Schulz TJ, Tseng YH (2009) Emerging role of bone morphogenetic proteins in adipogenesis and energy metabolism. Cytokine Growth Factor Rev 20:523–531

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Kajimura S (2015) Promoting brown and beige adipocyte biogenesis through the PRDM16 pathway. Int J Obes Suppl 5:S11–S14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Chen HJ, Ihara T, Yoshioka H, Itoyama E, Kitamura S, Nagase H, Murakami H, Hoshino Y, Murakami M, Tomonaga S, Matsui T, Funaba M (2018) Expression levels of brown/beige adipocyte-related genes in fat depots of vitamin A-restricted fattening cattle. J Anim Sci 96:3884–3896

    Article  PubMed Central  PubMed  Google Scholar 

  35. Donadelli M, Dando I, Fiorini C, Palmieri M (2014) UCP2, a mitochondrial protein regulated at multiple levels. Cell Mol Life Sci 71:1171–1190

    Article  CAS  PubMed  Google Scholar 

  36. Lanni A, Moreno M, Lombardi A, Goglia F (2003) Thyroid hormone and uncoupling proteins. FEBS Lett 543:5–10

    Article  CAS  PubMed  Google Scholar 

  37. Shigematsu M, Wong Yamada T, Yi Yun, Kanamori Y, Murakami M, Fujimoto Y, Suzuki M, Kida K, Qiao Y, Tomonaga S, Matsui T, Funaba M (2016) Dietary regulation of Ucp2 and Ucp3 expression in white adipose tissues of beef cattle. Can J Anim Sci 96:457–460

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by the JSPS KAKENHI (26450442 to M.F.) and MEXT-Supported Program for the Private University Research Branding Project (2016–2020 to M. Murakami).

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Author notes

  1. Mikako Motomura and Fumie Shimokawa authors equally contributed to this study.

Authors and Affiliations

  1. Division of Applied Biosciences, Kyoto University Graduate School of Agriculture, Kyoto, 606-8502, Japan

    Mikako Motomura, Itoyo Shimizu, Tohru Matsui & Masayuki Funaba

  2. Laboratory of Molecular Biology, Azabu University School of Veterinary Medicine, Sagamihara, 252-5201, Japan

    Fumie Shimokawa, Takashi Kobayashi & Masaru Murakami

  3. Kobayashi Animal Hospital, Nagano, 380-0816, Japan

    Takashi Kobayashi

  4. Aoi Animal Hospital, Shizuoka, 420-0076, Japan

    Yusuke Yamashita

  5. Mizoguchi Animal Hospital, Amagasaki, 660-0881, Japan

    Itsune Mizoguchi

  6. Sato Animal Hospital, Kyoto, 605-0971, Japan

    Yutaka Sato

  7. Animale Animal Hospital, Amagasaki, 661-0984, Japan

    Yoshihisa Murakami

Authors
  1. Mikako Motomura
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  2. Fumie Shimokawa
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Correspondence to Masaru Murakami or Masayuki Funaba.

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Motomura, M., Shimokawa, F., Kobayashi, T. et al. Relationships between expression levels of genes related to adipogenesis and adipocyte function in dogs. Mol Biol Rep 46, 4771–4777 (2019). https://doi.org/10.1007/s11033-019-04923-3

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  • DOI: https://doi.org/10.1007/s11033-019-04923-3

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