1. Cyclooxygenase-2 in adipose tissue macrophages limits adipose tissue dysfunction in obese mice
- Author
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Pan, Yu, Cao, Shirong, Tang, Jiaqi, Arroyo, Juan P., Terker, Andrew S., Wang, Yinqiu, Niu, Aolei, Fan, Xiaofeng, Wang, Suwan, Zhang, Yahua, Jiang, Ming, Wasserman, David H., Zhang, Ming-Zhi, and Harris, Raymond C.
- Subjects
Obesity -- Complications and side effects ,Adipose tissues -- Health aspects -- Physiological aspects ,Inflammation -- Development and progression ,Cyclooxygenases -- Health aspects -- Physiological aspects ,Macrophages -- Health aspects -- Physiological aspects ,Health care industry - Abstract
Obesity-associated complications are causing increasing morbidity and mortality worldwide. Expansion of adipose tissue in obesity leads to a state of low-grade chronic inflammation and dysregulated metabolism, resulting in insulin resistance and metabolic syndrome. Adipose tissue macrophages (ATMs) accumulate in obesity and are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. Macrophages are rich sources of cyclooxygenase (COX), the rate limiting enzyme for prostaglandin E2 (PGE2) production. When mice were fed a high-fat diet (HFD), ATMs increased expression of COX-2. Selective myeloid cell COX-2 deletion resulted in increased monocyte recruitment and proliferation of ATMs, leading to increased proinflammatory ATMs with decreased phagocytic ability. There were increased weight gain and adiposity, decreased peripheral insulin sensitivity and glucose utilization, increased adipose tissue inflammation and fibrosis, and abnormal adipose tissue angiogenesis. HFD pair-feeding led to similar increases in body weight, but mice with selective myeloid cell COX-2 still exhibited decreased peripheral insulin sensitivity and glucose utilization. Selective myeloid deletion of the macrophage PGE2 receptor subtype, EP4, produced a similar phenotype, and a selective EP4 agonist ameliorated the metabolic abnormalities seen with ATM COX-2 deletion. Therefore, these studies demonstrated that an ATM COX-2/PGE2/ EP4 axis plays an important role in inhibiting adipose tissue dysfunction., Introduction There are currently about 2 billion people globally who are obese or overweight, leading to health complications, type 2 diabetes, cardiovascular disease, and liver disease. The expansion of adipose [...]
- Published
- 2022
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