2. Academic Validation
  3. Adipocyte-derived Lysophosphatidylcholine Activates Adipocyte and Adipose Tissue Macrophage Nod-Like Receptor Protein 3 Inflammasomes Mediating Homocysteine-Induced Insulin Resistance

Adipocyte-derived Lysophosphatidylcholine Activates Adipocyte and Adipose Tissue Macrophage Nod-Like Receptor Protein 3 Inflammasomes Mediating Homocysteine-Induced Insulin Resistance

  • EBioMedicine. 2018 May;31:202-216. doi: 10.1016/j.ebiom.2018.04.022.
Song-Yang Zhang 1,  Yong-Qiang Dong 1,  Pengcheng Wang 1,  Xingzhong Zhang 1,  Yu Yan 1,  Lulu Sun 1,  Bo Liu 1,  Dafang Zhang 2,  Heng Zhang 3,  Huiying Liu 1,  Wei Kong 1,  Gang Hu 4,  Yatrik M Shah 5,  Frank J Gonzalez 6,  Xian Wang 7,  Changtao Jiang 8
Affiliations

Affiliations

  • 1 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China.
  • 2 Department of Hepatobiliary Surgery, Peking University People's Hospital, Peking University, Beijing 100044, People's Republic of China.
  • 3 Department of Endocrinology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, People's Republic of China.
  • 4 Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Jiangsu Key Laboratory of Neurodegeneration, Nanjing 210029, Jiangsu, People's Republic of China; Department of Pharmacology, School of Basic Medical Sciences, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu, People's Republic of China.
  • 5 Department of Molecular & Integrative Physiology, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, MI, USA.
  • 6 Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
  • 7 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. Electronic address: [email protected].
  • 8 Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, People's Republic of China. Electronic address: [email protected].
PMID: 29735414 DOI: 10.1016/j.ebiom.2018.04.022
Abstract

The adipose Nod-like receptor protein 3 (NLRP3) inflammasome senses danger-associated molecular patterns (DAMPs) and initiates Insulin resistance, but the mechanisms of adipose inflammasome activation remains elusive. In this study, Homocysteine (Hcy) is revealed to be a DAMP that activates adipocyte NLRP3 inflammasomes, participating in Insulin resistance. Hcy-induced activation of NLRP3 inflammasomes were observed in both adipocytes and adipose tissue macrophages (ATMs) and mediated Insulin resistance. Lysophosphatidylcholine (lyso-PC) acted as a second signal activator, mediating Hcy-induced adipocyte NLRP3 inflammasome activation. Hcy elevated adipocyte lyso-PC generation in a hypoxia-inducible factor 1 (HIF1)-phospholipase A2 group 16 (PLA2G16) axis-dependent manner. Lyso-PC derived from the Hcy-induced adipocyte also activated ATM NLRP3 inflammasomes in a paracrine manner. This study demonstrated that Hcy activates adipose NLRP3 inflammasomes in an adipocyte lyso-PC-dependent manner and highlights the importance of the adipocyte NLRP3 inflammasome in Insulin resistance.

Keywords

Adipocyte; Adipose tissue macrophage; Homocysteine; Insulin resistance; NLRP3 inflammasome.

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