Abstract
The prevalence of obesity is escalating and has become a worldwide health challenge coinciding with the development of metabolic diseases. Emerging evidence has shown that obesity is accompanied by the infiltration of macrophages into adipose tissue, contributing to a state of low-grade chronic inflammation and dysregulated metabolism. Moreover, in the state of obesity, the phenotype of adipose tissue macrophages switches from the M2 polarized state to the M1 state, thereby contributing to chronic inflammation. Notably, multiple metabolic organs (adipose tissue, gut, skeletal muscle, and the liver) communicate with adipose tissue macrophages via secreting organokines or exosomes. In this review, we systematically summarize how the organokines (adipokines, gut microbiota and its metabolites, gut cytokines, myokines, and hepatokines) and exosomes (adipocyte-, skeletal muscle-, and hepatocyte-derived exosomes) act as important triggers for macrophage recruitment in adipose tissue and adipose tissue macrophage polarization, thus providing further insight into obesity treatment. In addition, we also highlight the complex interaction of organokines with organokines and organokines with exosomes, revealing new paths in understanding adipose tissue macrophage recruitment and polarization.
Highlights
As per the World Health Organization, since the mid-1970s, the global prevalence of obesity has tripled, with an estimated 1 billion adults being overweight, as well as 650 million adults and 124 million children and adolescents being obese
It has been suggested that glucagon-like peptide-1 (GLP-1)/GLP-1 receptors (GLP-1R) signaling dampens M1 activation and triggers M2 activation by cyclic adenosine monophosphate/protein kinase A (PKA) mediated c-Jun N-terminal kinase (JNK) downregulation in RAW264.7 cells [73]
They found that Fibronectin type III domain-containing protein 5 (FNDC5) overexpression attenuates adipose tissue inflammation in obesity by inhibiting macrophage recruitment and M1 phenotype polarization via AMPKa signaling in high-fat diet (HFD)-induced obese mice [90]
Summary
As per the World Health Organization, since the mid-1970s, the global prevalence of obesity has tripled, with an estimated 1 billion adults being overweight, as well as 650 million adults and 124 million children and adolescents being obese. ATMs originated from obese mice express elevated levels of genes for instance tumor necrosis factor alpha (TNF-a) and inducible nitric oxide synthase (iNOS), which are characteristic of ‘classically activated’ or M1-like macrophages [9] Both ATM populations can be distinguished based on the expression of surface markers, where most ATMs express CD206 in lean mice, whereas in obese conditions, CD11c is upregulated [9]. Gut, skeletal muscle, and the liver act as endocrine organs by secreting organokines (adipokines, gut microbiota-derived metabolites, gut hormones, myokines, and hepatokines) and exoxomes (adipocyte-, skeletal muscle-, and hepatocyte-derived exosomes), which are increased or decreased in obesity, affecting the phenotype of ATMs switch from the anti-infammatory (M2) state to the pro-infammatory (M1) state. With increasing understanding of organokines and exosomes in regulating ATM recruitment and polarization, novel insights, as well as treatment strategies should emerge in the prevention of obesity
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