Adipose tissue macrophages as potential targets for obesity and metabolic diseases

Abstract

Macrophage infiltration into adipose tissue is a key pathological factor inducing adipose tissue dysfunction and contributing to obesity-induced inflammation and metabolic disorders. In this review, we aim to present the most recent research on macrophage heterogeneity in adipose tissue, with a focus on the molecular targets applied to macrophages as potential therapeutics for metabolic diseases. We begin by discussing the recruitment of macrophages and their roles in adipose tissue. While resident adipose tissue macrophages display an anti-inflammatory phenotype and promote the development of metabolically favorable beige adipose tissue, an increase in pro-inflammatory macrophages in adipose tissue has negative effects on adipose tissue function, including inhibition of adipogenesis, promotion of inflammation, insulin resistance, and fibrosis. Then, we presented the identities of the newly discovered adipose tissue macrophage subtypes (e.g. metabolically activated macrophages, CD9+ macrophages, lipid-associated macrophages, DARC+ macrophages, and MFehi macrophages), the majority of which are located in crown-like structures within adipose tissue during obesity. Finally, we discussed macrophage-targeting strategies to ameliorate obesity-related inflammation and metabolic abnormalities, with a focus on transcriptional factors such as PPARγ, KLF4, NFATc3, and HoxA5, which promote macrophage anti-inflammatory M2 polarization, as well as TLR4/NF-κB-mediated inflammatory pathways that activate pro-inflammatory M1 macrophages. In addition, a number of intracellular metabolic pathways closely associated with glucose metabolism, oxidative stress, nutrient sensing, and circadian clock regulation were examined. Understanding the complexities of macrophage plasticity and functionality may open up new avenues for the development of macrophage-based treatments for obesity and other metabolic diseases.

Extract mixture of plants (OXYLIA) inhibits fat accumulation by blocking FAS-related factors and promoting lipolysis via cAMP-dependent PKA activation

“…Adipogenesis refers to the formation and development of adipocytes (fat cells), while lipogenesis involves the synthesis of TGs within adipocytes, leading to fat accumulation. On the other hand, lipolysis is the breakdown of stored TGs into free fatty acids (FFAs) and glycerol (15)(16)(17).…”

Targeting Metabolic Diseases: The Role of Nutraceuticals in Modulating Oxidative Stress and Inflammation

“…Recent research emphasizes macrophage infiltration into adipose tissue as a critical factor in obesity-related inflammation and metabolic disorders. This infiltration occurs in response to various signals, including chemokines and cytokines, secreted by adipocytes and other immune cells within the adipose tissue microenvironment [ 32 ]. This intricate interplay between oxidative stress and inflammation forms a self-sustaining loop, magnifying cellular damage and hastening the progression of metabolic diseases.…”

Clinical Classification of Obesity and Implications for Metabolic Dysfunction-Associated Fatty Liver Disease and Treatment

“…134 Obesity-related inflammation and metabolic problems are exacerbated by macrophage infiltration into adipose tissue, which is a significant pathogenic component. 135,136 Alanine aminotransferase (ALT) is a metabolic syndrome-related biomarker that can be significantly increased. The pro-inflammatory cytokines IL-6, IL-8, Monocyte chemoattractant protein-1 (MCP-1), regulated upon activation normal T cell expressed and presumably secreted(RANTES), Mps1 interacting protein-1 (MIP1), and plasminogen activator inhibitor-1 (PAI-1) are more incidents of heterogeneous expression seen in VAT, whereas leptin and interferon-gamma (IFN-gamma)-induced protein 10 (IP-10) are mostly expressed in SAT.…”