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PTIP Deficiency in B Lymphocytes Reduces Subcutaneous Fat Deposition in Mice

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Abstract

Recent studies have predominantly focused on the role of B cells in metabolic diseases, yet the function of B cells in adipose homeostasis remains unclear. Pax transactivation domain-interacting protein (PTIP), a licensing factor for humoral immunity, is necessary for B cell development and activation. Here, using mice that lack PTIP in B cells (PTIP−/− mice), we explored the role of B cells in adipose homeostasis under physiological conditions. Fat deposition in 8-week-old mice was measured by micro-CT, and PTIP−/− mice presented a marked decrease in the deposition of subcutaneous adipose tissue (SAT). Untargeted lipidomics revealed that the triglyceride composition in SAT was altered in PTIP−/− mice. In addition, there was no difference in the number of adipocyte progenitor cells in the SAT of wild-type (WT) and PTIP−/− mice as measured by flow cytometry. To study the effects of steady-state IgM and IgG antibody levels on fat deposition, PTIP−/− mice were injected intraperitoneally with serum from WT mice once every 3-4 days for 4 weeks. The iSAT mass of the recipient mice showed no significant increase in comparison to the controls after 4 weeks of injections. Our findings reveal that PTIP plays an essential role in regulating subcutaneous adipocyte size, triglyceride composition, and fat deposition under physiological conditions by controlling B cells. The decreased subcutaneous fat deposition in PTIP−/− mice does not appear to be related to the number of adipocyte progenitor cells. The steady-state levels of IgM and IgG antibodies in vivo are not associated with the subcutaneous fat deposition.

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Abbreviations

ACN:

acetonitrile

BAT:

brown adipose tissue

H&E:

hematoxylin and eosin

IPA:

isopropanol alcohol

iSAT:

inguinal subcutaneous adipose tissue

AP:

adipocyte progenitor

PTIP:

pax transactivation domain-interacting protein

SAT:

subcutaneous adipose tissue

SVF:

stromal vascular fraction

TAG:

triacylglyceride

TC:

total cholesterol

VAT:

visceral adipose tissue

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Funding

This research was supported by the National Natural Science Foundation of China (grant no. 31872794), Natural Science Foundation of Jiangsu Province (No. BK20181346), the National Key Research and Development Program of China (2017YFD0400200), and the National Natural Science Foundation of China (grant no. 31771539).

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Correspondence to Yong Q. Chen.

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The authors declare no conflicts of interest in financial or any other sphere. All experiments carried out on animals in this study were approved by the Experimental Animal Ethics Committee of Jiangnan University (permission JN. No20200710c0440930[167]). All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Xu, Y., Zhu, D., Yang, Q. et al. PTIP Deficiency in B Lymphocytes Reduces Subcutaneous Fat Deposition in Mice. Biochemistry Moscow 86, 568–576 (2021). https://doi.org/10.1134/S0006297921050060

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