Chronic low-grade inflammation present in hypertrophic obesity has the ability to cause remodeling of the adipose tissue due to the increased presence of macrophages and pro-inflammatory cytokines. Transforming Growth Factor-β (TGF- β) is a cytokine released from macrophages that is increased in obesity and plays a major role in extracellular matrix (ECM) remodeling of tissues. Lipocalin 2 (Lcn2), a cytokine expressed in adipose tissue, is related to inflammation and ECM remodeling. Due to the qualities that both adipokines possess the role in extracellular matrix remodeling and inflammation, we looked into the TGF- β effect on the regulation of ECM and inflammatory cytokines in Lcn2 deficient adipocytes to acquire more information about the function of Lcn2 under inflammatory stimuli and the association with metabolic diseases. Therefore, we performed experiments to address how Lcn2 knock out (KO) influences the response of adipocytes to TGF- β in the production of proinflammatory and anti-inflammatory cytokines and ECM proteins. Our results demonstrate that TGF- β down-regulates Lcn2 expression at both the mRNA and protein levels in inguinal adipocytes. Lcn2 KO adipocytes have lower levels of TGF- β expression, but normal levels of p70S6K phosphorylation and normal response to TGF- β stimulation in mammalian target of rapamycin complex 1 (mTORC1) signaling activation. However, the inhibitory effect of rapamycin on TGF- β expression is attenuated in Lcn2 KO adipocytes. Moreover, Lcn2 KO impairs the rapamycin potentiation of TGF- β effect on the expression of ECM proteins, but shows little effect on dysregulation of cytokines.
University of Minnesota M.S. thesis. September 2015. Major: Nutrition. Advisors: Xiaoli Chen, Linda Brady. 1 computer file (PDF); iv, 64 pages.
Lipocalin 2 Deficiency Influences Transforming Growth Factor-Beta Effect On Inflammation And Extracellular Matrix Remodeling In Inguinal Adipocytes.
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