Lipopolysaccharides Reduce Adipogenesis in 3T3-L1 Adipocytes Through Activation of NF-κB Pathway and Downregulation of AMPK Expression

Abstract

Lipopolysaccharides (LPS) from the outer membrane of Gram-negative bacteria serve as endotoxin to exert potent immune responses. However, the effect of LPS on adipogenesis has not been elucidated. The present study was designed to examine the effect of LPS on adipogenesis in 3T3-L1 preadipocytes and possible mechanism(s) of action involved. Our results revealed that LPS challenge significantly suppressed adipogenesis in 3T3-L1 preadipocytes mainly through downregulated expression of the late adipogenic markers PPARγ and aP2 as well as AMP-activated protein kinase (AMPK) expression and activity. As an inflammatory factor, LPS was found to lead to an overt reduction in IκBα levels compared with the time-matched controls, consolidating its pro-inflammatory property in 3T3-L1 preadipocytes. Our data also revealed that LPS retarded adipogenesis, the effect of which was partially reversed by the selective inhibitor of IKKβ. IκBα was found to be involved in the anti-adipogenic effect of LPS. In conclusion, LPS is capable of inhibiting adipogenesis in 3T3-L1 adipocytes possibly through activation of NF-κB and inhibition of AMPK. With the activation of NF-κB pathway and inhibition of AMPK, LPS suppresses C/EBP α DNA-binding activity and the expression of late adipogenic markers PPARγ and aP2.

Metformin exerts glucose-lowering action in high-fat fed mice via attenuating endotoxemia and enhancing insulin signaling

“…This work provides an additional pathway by which metformin activates AMPK through reducing endotoxemia-mediated inhibition in HFDfed mice. In agreement with these finding, other studies have indicated that LPS can lead to an inhibition of AMPK activity [29,30] . Furthermore, we revealed that in cultured hepatic HepG2 cells, LPS reduced AMPK activation through LKB inhibition.…”

Effect of lipopolysaccharides on adipogenic potential and premature senescence of adipocyte progenitors

“…Most of the previous studies conducted in adipose cell lines were focused on the inhibitory effect of inflammation on adipogenesis by examining the effect of adding inflammatory factors to the adipocyte cultures during either the entire period of differentiation process or the short-term effect on mature adipocytes (11,40,55). The present study attempted to more precisely understand the target points where LPS does its inhibitory effect on adipocyte differentiation in inguinal SV cell cultures.…”

“…The inhibitory effects of inflammatory inducers such as LPS, TNF␣, and macrophage-conditioned medium on adipocyte differentiation when they are added during the adipocyte differentiation process have been studied extensively (11,40,55). The mechanism for the effect of proinflammatory factors on adipogenesis is speculated to be largely through the direct activation of NF-B pathway, which in turn reduces PPAR␥ activity during adipocyte differentiation process (11,40,55). Therefore, we determined the role of the NF-B signaling pathway in the LPS-induced intrinsic inhibition of adipogenesis.…”

“…With regard to the regulation of adipogenesis, studies from in vitro cultures of 3T3-L1 cells and human adipocyte progenitor cells have consistently demonstrated that LPS treatment during adipocyte differentiation led to the inhibition of adipocyte differentiation (19,55). Previous reports have also shown that LPS induces cellular senescence in multiple types of cells (18,36,57).…”

“…It is possible that LPS may have a differential impact on adipogenesis and metabolism in different depots. However, most of the previous in vitro studies were conducted in 3T3-L1 cells, focusing on the effect of LPS on inflammation, lipid metabolism, and adipogenesis (13,17,20,27,43,55). The effect of LPS on the intrinsic differentiation potential of adipocyte progenitors using primary inguinal SV cell cultures that better reflect the physiological conditions has not been reported previously.…”