Pro-atherogenic and pro-oxidant crosstalk between adipocytes and macrophages
Obesity, which is characterized by triglyceride accumulation mainly in adipocytes but also in arterial wall cells such as macrophages, is a major risk factor for developing atherosclerosis. We aimed to identify the crosstalk related to lipid metabolism and oxidation status between adipocytes and macrophages.
We used a co-culture model system with J477A.1 cultured macrophages and 3T3L1 cultured adipocytes. For an in-vivo co-culture system, we used C57BL/6 mouse peritoneal macrophages and visceral or subcutaneous adipose tissue.
Adipocytes significantly increased reactive oxygen species generation, up to twofold, and decreased cholesterol content by 22% in the co-cultured macrophages. Macrophages significantly increased triglyceride-biosynthesis rate by twofold and decreased triglyceride-degradation rate by 30%, resulting in increased triglyceride accumulation in the co-cultured adipocytes by up to 72%. In the in-vivo mouse model, visceral adipose tissue crosstalk with macrophages resulted in a significant pro-atherogenic phenotype with respect to cellular cholesterol metabolism. In contrast, the interaction between subcutaneous adipose tissue and macrophages mostly affected cellular triglyceride metabolism. There were no significant effects on mitochondrial respiration capacity in the macrophages. Upon oxidative-stress reduction in the co-cultured cells using the polyphenol-rich antioxidant, pomegranate juice, the expression of genes related to cellular lipid accumulation was significantly reduced.
We reveal, for the first time, that paracrine interactions between adipocytes and macrophages result in oxidative stress and lipids metabolic alterations in both cells, toward increased atherogenicity which can be reversed by phenolic antioxidants.
KeywordsAdipocyte Macrophage Atherogenicity Co-culture Crosstalk
The current work was supported by the Israel Medical Association and the Society for Research, Prevention and Treatment of Atherosclerosis, the Fund for Research Projects and Fellowships on Food and Nutrition with Implications on Public Health of the Israeli Ministry of Health (3-00000-12135), and the University of Michigan–Israel Partnership for Research and Education. We thank Dr. Niroz Abu Saleh and Dr. Mahmoud Najjar, for their most valuable scientific advice and technical assistance.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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