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Publication : Opposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity.

First Author  Cuesta N Year  2022
Journal  Int J Mol Sci Volume  23
Issue  24 PubMed ID  36555322
Mgi Jnum  J:332819 Mgi Id  MGI:7412026
Doi  10.3390/ijms232415682 Citation  Cuesta N, et al. (2022) Opposing Actions of TLR2 and TLR4 in Adipocyte Differentiation and Mature-Onset Obesity. Int J Mol Sci 23(24)
abstractText  Understanding the signaling cascades that govern adipocyte metabolism and differentiation is necessary for the development of therapies for obesity. Toll-like receptors (TLRs) are key mediators in adipogenesis, but their specific role is not completely understood. In this study, siRNA knockdown of Tlr2 in 3T3-L1 cells allowed them to differentiate more efficiently into adipocytes, whereas the opposite was observed for the knockdown of Tlr4. At the same time, we show that TLR2 knock-out mice spontaneously developed mature-onset obesity and insulin resistance. Besides a higher incidence of hyperplasia and hypertrophy in white adipose tissue (WAT), we found a significantly increased number of adipocyte precursor cells in TLR2(-/-) mice compared to TLR4(-/-) mice. Interestingly, genetic inactivation of Tlr4 in TLR2(-/-) mice reverted their increased adiposity, insulin resistance, and restored normal levels of adipocyte precursor cells. These findings provide evidence that TLR2 and TLR4 play opposing roles in WAT homeostasis and point to the existence of cross-regulation among TLR2 and TLR4 during adipocyte differentiation both in vitro and in vivo.
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