Metformin abrogates pathological TNF- α-producing B cells through mTORdependent metabolic reprogramming in polycystic ovary syndrome
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Release time:2022-12-20
Journal:eLife
Funded by:国家自然科学基金
Abstract:B cells contribute to the pathogenesis of polycystic ovary syndrome (PCOS). Clinically,
metformin is used to treat PCOS, but it is unclear whether metformin exerts its therapeutic effect
by regulating B cells. Here, we showed that the expression level of TNF-α in peripheral blood B
cells from PCOS patient was increased. Metformin used in vitro and in vivo was able to reduce the
production of TNF-α in B cells from PCOS patient. Administration of metformin improved mouse
PCOS phenotypes induced by dehydroepiandrosterone (DHEA) and also inhibited TNF-α expression
in splenic B cells. Further, metformin induced metabolic reprogramming of B cells in PCOS patients,
including the alteration in mitochondrial morphology, the decrease in mitochondrial membrane
potential, ROS production and glucose uptake. In DHEA-induced mouse PCOS model, metformin
altered metabolic intermediates in splenic B cells. Moreover, the inhibition of TNF-α expression
and metabolic reprogramming in B cells of PCOS patients and mouse model by metformin were
associated with decreased mTOR phosphorylation. Together, TNF-α-producing B cells are involved
in the pathogenesis of PCOS, and metformin inhibits mTOR phosphorylation and affects metabolic
reprogramming, thereby inhibiting TNF-α expression in B cells, which may be a new mechanism of
metformin in the treatment of PCOS.
Indexed by:Unit Twenty Basic Research
Volume:2022;11:e7
Translation or Not:no
Date of Publication:2022-06-24
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