Nucleophosmin3 carried by small extracellular vesicles contribute to white adipose tissue browning

  • J Nanobiotechnology. 2022 Mar 28;20(1):165. doi: 10.1186/s12951-022-01381-1.
Yan Zhang   #  1  2  3 Mei Yu   #  4  5  6 Jia Dong  7  1  2  8 Yue Wu  7  1  2  8 Weidong Tian  9  10  11  12
Affiliations
  • 1. National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, China.
  • 2. Engineering Research Center of Oral Translational Medicine, Ministry of Education, Sichuan University, Chengdu, China.
  • 3. Department of Oral and Maxillofacial Surgery, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China.
  • 4. State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 5. National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 6. Engineering Research Center of Oral Translational Medicine, Ministry of Education, Sichuan University, Chengdu, China. [email protected].
  • 7. State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China.
  • 8. Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
  • 9. State Key Laboratory of Oral Disease & National Clinical Research Center for Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 10. National Engineering Laboratory for Oral Regenerative Medicine, West China School of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • 11. Engineering Research Center of Oral Translational Medicine, Ministry of Education, Sichuan University, Chengdu, China. [email protected].
  • 12. Department of Oral and Maxillofacial Surgery, West China Hospital of Stomatology, Sichuan University, Chengdu, China. [email protected].
  • # Contributed equally.
Abstract

Background: Browning of white adipose tissue (WAT) is a particularly appealing target for therapeutics in the treatment of obesity and related metabolic diseases. Although small extracellular vesicles (sEVs) released from adipose tissue (sEVs-AT) have emerged as novel player that regulate systemic metabolism by connecting different organs, the role of specific contents in sEVs-AT played in WAT browning has not been clarified.

Results: We revealed Nucleophosmin3 (NPM3), which was mainly transferred by sEVs derived from brown adipose tissue (sEVs-BAT), was served as a batokine that could induce WAT browning by regulating the stability of PRDM16 mRNA. sEVs-BAT enhanced the expressions of browning related genes in 3T3-L1 preadipocytes and WAT while knocking down of NPM3 in BAT impaired sEVs-BAT mediated WAT browning and weight loss in obesity.

Conclusion: These data provided new insight into the role of NPM3 in regulating the browning of WAT. Our study indicated that a supplement of sEVs-BAT might represent a promising therapeutic strategy to promote thermogenesis and energy expenditure in the future.

Keywords
Batokine; NPM3; Obesity; Small extracellular vesicles; White adipose tissue browning.
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