Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression

Abstract

The proliferation and adipogenesis of preadipocytes played important roles in the development of adipose tissue and contributed much to the processes of obesity. On the other hand, lipopolysaccharide (LPS), also known as endotoxin, is a key outer membrane component of gram-negative bacteria in the gut microbiota, and has a dominant role in linking inflammation to high-fat diet-induced metabolic syndrome. Studies suggested the potential roles of LPS in hepatic steatosis and in obese mice models. However, the molecular mechanisms underlying LPS-regulated obesity remained largely unknown. Here we reported that LPS stimulated expression of cyosolic phospholipase A2 (cPLA2), one of inflammation regulators of obesity, in the preadipocytes. Pretreatment the inhibitors of JAK2, STAT3, STAT5 or AMPK significantly reduced LPS-increased mRNA and protein expression of cPLA2 together with phosphorylation of JAK2, STAT3, STAT5 and AMPK, separately. Similarly, transfection of siRNA against JAK2 or AMPK abolished expression of cPLA2 and phosphorylation of JAK2 or AMPK together with downregulated expression of JAK2 and AMPK protein. LPS enhanced activation of STAT3 and STAT5 via JAK2-dependent manner in the preadipocytes. Transfection of JAK2 or AMPK siRNA further proofed the independence of JAK2 and AMPK in LPS-treated preadipocytes. In addition, LPS-increased DNA synthesis, cell numbers and cell viability of preadipocytes were attenuated by AACOCF3, AG490, BML-275, cPLA2 siRNA, JAK2 siRNA or AMPK siRNA. Attenuation JAK2/STAT or AMPK-dependent cPLA2 expression reduced LPS-mediated adipogenesis of preadipocytes. Stimulation of arachidonic acid or AMPK activator, A-769662, increased cell numbers and cell viability and promoted differentiation of preadipocytes. Collectively, these results indicated that LPS increased preadipocytes proliferation and adipogenesis via JAK/STAT and AMPK-dependent cPLA2 expression. The mechanisms of LPS-stimulated cPLA2 expression may be a link between bacteria and obesity and provides the molecular basis for preventing metabolic syndrome or hyperplasic obesity.

HIV and antiretroviral therapy-related fat alterations

“…LPS stimulates the proliferation of pre-adipocytes through a CD14-dependent mechanism 205 , possibly through activation of JAK/ STAT and AMPK via cytosolic phospholipase A2 (reF. 206 ).…”

Effects of LPS on the accumulation of lipid droplets, proliferation, and steroidogenesis in goat luteinized granulosa cells

“…Previous studies indicated that LPS could promote the proliferation in several cell types . However, whether LPS stimulate or inhibit and /or did not affect the proliferation of the cells may depend on the cell type and LPS itself, as well as concentrations of LPS.…”

“…However, whether LPS stimulate or inhibit and /or did not affect the proliferation of the cells may depend on the cell type and LPS itself, as well as concentrations of LPS. Recent study showed that LPS (1 μg/mL) had no impact on the viability of ovarian granulosa cells in buffalo, while LPS (20 μg/mL) enhanced the proliferation of preadipocytes, and LPS increased the number of sertoli cells in a dose‐dependent way (0.1‐100 μg/mL) . Studies also have showed that LPS from Porphyromonas gingivalis at 10 μg/mL increased periodontal ligament cells proliferation, but LPS from E. coli reduced the proliferation in this cell type .…”

“…Previous study has confirmed that LPS can shift LDs size and distribution, and lead LDs accumulation in microglia . Besides, LPS can stimulate the proliferation in pulmonary microvascular endothelial cells, vascular smooth muscle cells and preadipocytes . However, little is known about the effects of LPS on LDs, cell proliferation and steroidogenesis in goat luteinized granulosa cells (LGCs).…”

Latest advances in STAT signaling and function in adipocytes

“…This effect was abrogated by inhibition of either EGF receptor (EGFR) or STAT3 expression, revealing a role for EGF-mediated STAT activation both in delaying senescence of ASCs, and in enhancing their adipogenic potential [20]. Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα), two mediators known to contribute to obesity-related inflammation, both induce the expression of cytosolic phospholipase A2 (cPLA2) through activation of JAK2/STAT3/STAT5 signaling in various cell types [21][22][23]. It has also been shown that cPLA2 induces adipogenesis [24].…”