Int J Med Sci 2019; 16(1):167-179. doi:10.7150/ijms.24068 This issue Cite

Research Paper

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

Chao-Chien Chang1,2,3,4, Kee-Chin Sia5, Jia-Feng Chang5,6,7, Chia-Mo Lin5,8,9, Chuen-Mao Yang10,11,12, Kuo-Yang Huang13, Wei-Ning Lin5✉

1. Division of Cardiology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan;
2. Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan;
3. Department of Pharmacology, School of medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;
4. School of Medicine, College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan;
5. Graduate Institute of Biomedical and Pharmaceutical Science, Fu Jen Catholic University, New Taipei City, Taiwan;
6. PhD Program in Nutrition and Food Science, Fu Jen Catholic University, New Taipei City, Taiwan;
7. Department of Internal Medicine, En-Chu-Kong Hospital, New Taipei City, Taiwan;
8. Department of Chemistry, Fu-Jen Catholic University, New Taipei, Taiwan;
9. Division of Chest Medicine, Shin Kong Hospital, Taipei, Taiwan;
10. Department of Physiology and Pharmacology and Health Ageing Research Center, College of Medicine, Chang Gung University, Kwei-San, Tao-Yuan, Taiwan;
11. Department of Anesthetics, Chang Gung Memorial Hospital at Linkuo and Chang Gung University, Kwei-San, Tao-Yuan, Taiwan:
12. Research Center for Chinese Herbal Medicine and Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Tao-Yuan, Taiwan;
13. Graduate Institute of Pathology and Parasitology, National Defense Medical Center, Taipei, Taiwan

Citation:
Chang CC, Sia KC, Chang JF, Lin CM, Yang CM, Huang KY, Lin WN. Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. Int J Med Sci 2019; 16(1):167-179. doi:10.7150/ijms.24068. https://www.medsci.org/v16p0167.htm
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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.

Keywords: cPLA2, Lipopolysaccharide, Adipocyte, Proliteration, Adipogenesis


Citation styles

APA
Chang, C.C., Sia, K.C., Chang, J.F., Lin, C.M., Yang, C.M., Huang, K.Y., Lin, W.N. (2019). Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. International Journal of Medical Sciences, 16(1), 167-179. https://doi.org/10.7150/ijms.24068.

ACS
Chang, C.C.; Sia, K.C.; Chang, J.F.; Lin, C.M.; Yang, C.M.; Huang, K.Y.; Lin, W.N. Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. Int. J. Med. Sci. 2019, 16 (1), 167-179. DOI: 10.7150/ijms.24068.

NLM
Chang CC, Sia KC, Chang JF, Lin CM, Yang CM, Huang KY, Lin WN. Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. Int J Med Sci 2019; 16(1):167-179. doi:10.7150/ijms.24068. https://www.medsci.org/v16p0167.htm

CSE
Chang CC, Sia KC, Chang JF, Lin CM, Yang CM, Huang KY, Lin WN. 2019. Lipopolysaccharide promoted proliferation and adipogenesis of preadipocytes through JAK/STAT and AMPK-regulated cPLA2 expression. Int J Med Sci. 16(1):167-179.

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