EGFR-mediated activation of adipose tissue macrophages promotes obesity and insulin resistance.
Shirong CaoYu PanJiaqi TangAndrew S TerkerJuan Pablo Arroyo OrnelasGuan-Nan JinYinqiu WangAolei NiuXiaofeng FanSuwan WangRaymond C HarrisMing-Zhi ZhangPublished in: Nature communications (2022)
Obesity and obesity-related health complications are increasing in prevalence. Adipose tissue from obese subjects has low-grade, chronic inflammation, leading to insulin resistance. Adipose tissue macrophages (ATMs) are a source of proinflammatory cytokines that further aggravate adipocyte dysfunction. In response to a high fat diet (HFD), ATM numbers initially increase by proliferation of resident macrophages, but subsequent increases also result from infiltration in response to chemotactic signals from inflamed adipose tissue. To elucidate the underlying mechanisms regulating the increases in ATMs and their proinflammatory phenotype, we investigated the role of activation of ATM epidermal growth factor receptor (EGFR). A high fat diet increased expression of EGFR and its ligand amphiregulin in ATMs. Selective deletion of EGFR in ATMs inhibited both resident ATM proliferation and monocyte infiltration into adipose tissue and decreased obesity and development of insulin resistance. Therefore, ATM EGFR activation plays an important role in adipose tissue dysfunction.
Keyphrases
- insulin resistance
- adipose tissue
- high fat diet
- epidermal growth factor receptor
- tyrosine kinase
- high fat diet induced
- small cell lung cancer
- advanced non small cell lung cancer
- polycystic ovary syndrome
- low grade
- metabolic syndrome
- dna damage
- dna repair
- oxidative stress
- dna damage response
- type diabetes
- signaling pathway
- skeletal muscle
- high grade
- healthcare
- glycemic control
- public health
- weight loss
- patient safety
- body mass index
- poor prognosis
- physical activity
- risk assessment
- mass spectrometry
- high resolution
- peripheral blood
- drug induced