Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Adipocyte and Cell Biology

Asprosin contributes to pathogenesis of obesity by adipocyte mitophagy induction to inhibit white adipose browning in mice

International Journal of Obesity (2024)Cite this article

Subjects

Abstract

Background

Asprosin (ASP) is a newly discovered adipokine secreted by white adipose tissue (WAT), which can regulate the homeostasis of glucose and lipid metabolism. However, it is not clear whether it can regulate the browning of WAT and mitophagy during the browning process. Accordingly, this study aims to investigate the effects and possible mechanisms of ASP on the browning of WAT and mitophagy in vivo and in vitro.

Methods

In in vivo experiments, some mouse models were used including adipose tissue ASP-specific deficiency (ASP–/–), high fat diet (HFD)-induced obesity and white adipose browning; in in vitro experiments, some cell models were also established and used, including ASP-deficient 3T3-L1 preadipocyte (ASP–/–) and CL-316243 (CL, 1 µM)-induced browning. Based on these models, the browning of WAT and mitophagy were evaluated by morphology, functionality and molecular markers.

Results

Our in vivo data show that adipose tissue-specific deletion of ASP contributes to weight loss in mice; supplementation of ASP inhibits the expressions of browning-related proteins including UCP1, PRDM16 and PGC1ɑ during the cold exposure-induced browning, and promotes the expressions of mitophagy-related proteins including PINK1 and Parkin under the conditions of whether normal diet (ND) or HFD. Similarly, our in vitro data also show that the deletion of ASP in 3T3-L1 cells significantly increases the expressions of the browning-related proteins and decreases the expressions of the mitophagy-related proteins.

Conclusions

These data demonstrate that ASP deletion can facilitate the browning and inhibit mitophagy in WAT. The findings will lay an experimental foundation for the development of new drugs targeting ASP and the clinical treatment of metabolic diseases related to obesity.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: ASP-deficiency contributes to the weight loss in mice.
Fig. 2: ASP-deficiency promotes the expressions of browning- specific thermogenic genes in mouse adipose tissue.
Fig. 3: ASP-deficiency promotes the expressions of browning- specific thermogenic genes in 3T3-L1 cells.
Fig. 4: ASP-deficiency inhibits the over-mitophagy induced by HFD during the cold exposure-induced browning of white fat in mice.
Fig. 5: ASP-deficiency inhibits adipocyte mitophagy during CL-induced browning in 3T3-L1 cells.

Similar content being viewed by others

Data availability

All the data supporting the findings of the study were shown in this paper and are available upon reasonable request.

References

  1. Okunogbe A, Nugent R, Spencer G, Powis J, Ralston J, Wilding J. Economic impacts of overweight and obesity: current and future estimates for 161 countries. BMJ Glob Health. 2022;7:e009773.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Rabiee A. Beige fat maintenance; toward a sustained metabolic health. Front Endocrinol (Lausanne). 2020;11:634.

    Article  PubMed  Google Scholar 

  3. Cohen P, Kajimura S. The cellular and functional complexity of thermogenic fat. Nat Rev Mol Cell Biol. 2021;22:393–409.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Zhu T, Chen X, Jiang SL. Progress and obstacles in transplantation of brown adipose tissue or engineered cells with thermogenic potential for metabolic benefits. Front Endocrinol (Lausanne). 2023;14:1191278.

    Article  PubMed  Google Scholar 

  5. Kurylowicz A, Puzianowska-Kuznicka M. Induction of adipose tissue browning as a strategy to combat obesity. Int J Mol Sci. 2020;21:6241

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Xue SW, Lee D, Berry DC. Thermogenic adipose tissue in energy regulation and metabolic health. Front Endocrinol (Lausanne). 2023;14:1150059.

    Article  PubMed  Google Scholar 

  7. Saito M, Okamatsu-Ogura Y. Thermogenic brown fat in humans: implications in energy homeostasis, obesity and metabolic disorders. World J Mens Health. 2023;41:489–507.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Ferhat M, Funai K, Boudina S. Autophagy in adipose tissue physiology and pathophysiology. Antioxid Redox Signal. 2019;31:487–501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Cho YK, Son Y, Saha A, Kim D, Choi C, Kim M, et al. STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure. Nat Metab. 2021;3:428–41.

    Article  CAS  PubMed  Google Scholar 

  10. Goodall EA, Kraus F, Harper JW. Mechanisms underlying ubiquitin-driven selective mitochondrial and bacterial autophagy. Mol Cell. 2022;82:1501–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ro SH, Jang Y, Bae J, Kim IM, Schaecher C, Shomo ZD. Autophagy in adipocyte browning: emerging drug target for intervention in obesity. Front Physiol. 2019;10:22.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, et al. Asprosin, a fasting-induced glucogenic protein hormone. Cell. 2016;165:566–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Farrag M, Ait Eldjoudi D, Gonzalez-Rodriguez M, Cordero-Barreal A, Ruiz-Fernandez C, Capuozzo M, et al. Asprosin in health and disease, a new glucose sensor with central and peripheral metabolic effects. Front Endocrinol (Lausanne). 2022;13:1101091.

    Article  PubMed  Google Scholar 

  14. Shabir K, Brown JE, Afzal I, Gharanei S, Weickert MO, Barber TM, et al. Asprosin, a novel pleiotropic adipokine implicated in fasting and obesity-related cardio-metabolic disease: Comprehensive review of preclinical and clinical evidence. Cytokine Growth Factor Rev. 2021;60:120–32.

    Article  CAS  PubMed  Google Scholar 

  15. Yin TT, Chen S, Zeng GH, Yuan WW, Lu YL, Zhang YN, et al. Angiogenesis-browning interplay mediated by asprosin-knockout contributes to weight loss in mice with obesity. Int J Mol Sci. 2022;23:16166

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lu YL, Yuan WW, Xiong XW, Huang QQ, Chen S, Yin TT, et al. Asprosin aggravates vascular endothelial dysfunction via disturbing mitochondrial dynamics in obesity models. Obesity (Silver Spring). 2023;31:732–43.

    Article  CAS  PubMed  Google Scholar 

  17. Huang QQ, Chen S, Xiong XW, Yin TT, Zhang YN, Zeng GH, et al. Asprosin exacerbates endothelium inflammation induced by hyperlipidemia through activating IKKbeta-NF-kappaBp65 pathway. Inflammation. 2023;46:623–38.

    Article  CAS  PubMed  Google Scholar 

  18. Zhang YN, Huang QQ, Xiong XW, Yin TT, Chen S, Yuan WW, et al. Acacetin alleviates energy metabolism disorder through promoting white fat browning mediated by AC-cAMP pathway. J Physiol Biochem. 2023;79:529–41.

    Article  CAS  PubMed  Google Scholar 

  19. Vamos A, Shaw A, Varga K, Csomos I, Mocsar G, Balajthy Z, et al. Mitophagy mediates the beige to white transition of human primary subcutaneous adipocytes ex vivo. Pharmaceuticals (Basel). 2022;15:363.

    Article  PubMed  Google Scholar 

  20. Lu XD, Altshuler-Keylin S, Wang Q, Chen Y, Henrique Sponton C, Ikeda K., et al. Mitophagy controls beige adipocyte maintenance through a Parkin-dependent and UCP1-independent mechanism. Sci Signal. 2018;11:eaap8526.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Lu XD. Maintaining mitochondria in beige adipose tissue. Adipocyte. 2019;8:77–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Camilleri M, Acosta A. Combination therapies for obesity. Metab Syndr Relat Disord. 2018;16:390–4.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Cheng L, Wang JK, Dai HY, Duan YH, An YC, Shi L, et al. Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus. Adipocyte. 2021;10:48–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Dodd GT, Decherf S, Loh K, Simonds SE, Wiede F, Balland E, et al. Leptin and insulin act on POMC neurons to promote the browning of white fat. Cell. 2015;160:88–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Kita S, Maeda N, Shimomura I. Interorgan communication by exosomes, adipose tissue, and adiponectin in metabolic syndrome. J Clin Invest. 2019;129:4041–9.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Ke F, Xue GH, Jiang XL, Li FF, Lai XY, Zhang MY, et al. Combination of asprosin and adiponectin as a novel marker for diagnosing non-alcoholic fatty liver disease. Cytokine. 2020;134:155184.

    Article  CAS  PubMed  Google Scholar 

  27. Zhang L, Chen C, Zhou N, Fu YM, Cheng XB. Circulating asprosin concentrations are increased in type 2 diabetes mellitus and independently associated with fasting glucose and triglyceride. Clin Chim Acta. 2019;489:183–8.

    Article  CAS  PubMed  Google Scholar 

  28. Alan M, Gurlek B, Yilmaz A, Aksit M, Aslanipour B, Gulhan I, et al. Asprosin: a novel peptide hormone related to insulin resistance in women with polycystic ovary syndrome. Gynecol Endocrinol. 2019;35:220–3.

    Article  CAS  PubMed  Google Scholar 

  29. Wang M, Yin CY, Wang L, Liu YS, Li HG, Li M, et al. Serum asprosin concentrations are increased and associated with insulin resistance in children with obesity. Ann Nutr Metab. 2019;75:205–12.

    Article  CAS  PubMed  Google Scholar 

  30. Wang CY, Lin TA, Liu KH, Liao CH, Liu YY, Wu VC, et al. Serum asprosin levels and bariatric surgery outcomes in obese adults. Int J Obes (Lond). 2019;43:1019–25.

    Article  CAS  PubMed  Google Scholar 

  31. Sunnetci Silistre E, Hatipogl HU. Increased serum circulating asprosin levels in children with obesity. Pediatr Int. 2020;62:467–76.

    Article  PubMed  Google Scholar 

  32. Duerrschmid C, He YL, Wang CM, Li C, Bournat JC, Romere C, et al. Asprosin is a centrally acting orexigenic hormone. Nat Med. 2017;23:1444–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150:366–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Park A, Kim WK, Bae KH. Distinction of white, beige and brown adipocytes derived from mesenchymal stem cells. World J Stem Cells. 2014;6:33–42.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Kajimura S. Adipose tissue in 2016: Advances in the understanding of adipose tissue biology. Nat Rev Endocrinol. 2017;13:69–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wiecek M, Szymura J, Sproull J, Szygula Z. Decreased blood asprosin in hyperglycemic menopausal women as a result of whole-body cryotherapy regardless of metabolic syndrome. J Clin Med. 2019;8:1428.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Miao YL, Qin HJ, Zhong Y, Huang K, Rao C. Novel adipokine asprosin modulates browning and adipogenesis in white adipose tissue. J Endocrinol. 2021;249:83–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Rui LY. Brown and beige adipose tissues in health and disease. Compr Physiol. 2017;7:1281–306.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We acknowledge the support from the National Natural Science Foundation of China (81960153 and 82260726), the Natural Science Foundation of Jiangxi Province (20232ACB206061 and 20192BCD40003), the Graduate Innovation Project of Nanchang University (YC2020-B026) and the Undergraduate Innovation Plan Project of China (202110403096).

Author information

Authors and Affiliations

  1. Provincial Key Laboratory of Basic Pharmacology, Nanchang University, Nanchang, Jiangxi, 330006, P.R. China

    Sheng Chen, Wanwan Yuan, Qianqian Huang, Xiaowei Xiong, Chaowen Wang, Wenjing Zeng, Li Wang & Qiren Huang

  2. Department of Pharmacology, School of Pharmacy, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, P.R. China

    Sheng Chen, Wanwan Yuan, Qianqian Huang, Xiaowei Xiong, Chaowen Wang, Wenjing Zeng, Li Wang, Yijun Huang, Yeyi Liu, Yan Wang & Qiren Huang

Authors
  1. Sheng Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wanwan Yuan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Qianqian Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xiaowei Xiong
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chaowen Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wenjing Zeng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Li Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Yijun Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yeyi Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yan Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Qiren Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Sheng Chen was responsible for conceptualization, formal analysis, investigation, data curation, writing-original draft, writing-review & editing. Wanwan Yuan was responsible for investigation and validation. Qianqian Huang and Xiaowei Xiong was responsible for conceptualization. Chaowen Wang, Wenjing Zeng and Li Wang was responsible for methodology. Yijun Huang, Yeyi Liu and Yan Wang were responsible for validation. Qiren Huang was responsible for conceptualization, writing-review & editing, supervision and funding acquisition. All authors have read and agreed to the published version for the manuscript.

Corresponding author

Correspondence to Qiren Huang.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chen, S., Yuan, W., Huang, Q. et al. Asprosin contributes to pathogenesis of obesity by adipocyte mitophagy induction to inhibit white adipose browning in mice. Int J Obes (2024). https://doi.org/10.1038/s41366-024-01495-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1038/s41366-024-01495-6

Search

Advanced search

Quick links