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Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression
- Source :
- International Journal of Medical Sciences. 16:167-179
- Publication Year :
- 2019
- Publisher :
- Ivyspring International Publisher, 2019.
-
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.
- Subjects :
- Lipopolysaccharides
STAT3 Transcription Factor
Cell Survival
Phospholipases A2, Cytosolic
Adipose tissue
AMP-Activated Protein Kinases
Mice
03 medical and health sciences
0302 clinical medicine
3T3-L1 Cells
hemic and lymphatic diseases
Adipocytes
STAT5 Transcription Factor
Animals
Viability assay
STAT3
STAT5
Cell Proliferation
Adipogenesis
biology
Chemistry
JAK-STAT signaling pathway
AMPK
General Medicine
Transfection
Janus Kinase 2
Cell biology
Endotoxins
biology.protein
030211 gastroenterology & hepatology
Subjects
Details
- ISSN :
- 14491907
- Volume :
- 16
- Database :
- OpenAIRE
- Journal :
- International Journal of Medical Sciences
- Accession number :
- edsair.doi.dedup.....ac0dd578a8c60eb206ec5acfa7590739