Adipocyte

Obesity and diabetes are associated with the metabolic remodeling of the extracellular matrix (ECM), which can contribute to insulin resistance and obesity- and diabetes-associated complications. In obesity, the adipose tissue remodels its ECM components and structure to accommodate excess fat. Moreover, obesity increases ectopic fat deposition and ECM remodeling in skeletal muscles, impairing insulin sensitivity and muscle contraction. In addition, cancer-associated adipose tissue (CAAT) remodeling develops a unique microenvironment that promotes tumor growth and metastasis.

Unbalanced ECM remodeling, characterized by the accumulation of collagen fibers and other ECM components, leads to metabolic tissue fibrosis and dysfunction. Metabolic tissue fibrosis is often associated with chronic inflammation, characterized by increased infiltration of lymphocytes and macrophages. Inflammatory cytokines released by these immune cells in the metabolic tissues can stimulate ECM production by fibroblasts, adipocytes, fibro-adipogenic progenitors (FAPs), and cancer-associated fibroblasts (CAFs).

Recent advances in single cell/nucleus RNA sequencing allow us to better understand the cellular mechanisms of adipose and skeletal muscle remodeling in obesity and diabetes. Fibrosis promoted by stromal cells coupled with inflammation negatively impacts the function of adipose tissues and skeletal muscles. Adipose tissue fibrosis may limit the physiological regulation of adipocyte size and number, impairing the storage and release of free fatty acids. In addition, excess fibrosis may restrict blood flow and oxygen delivery to the tissue, contributing to insulin resistance and inflammation. Skeletal muscle fibrosis may impair contractile function and insulin-dependent and -independent glucose uptake of skeletal muscles.

In this Article Collection, we aim to address the cellular and molecular aspects of metabolic tissue remodeling and dysfunction in obesity, diabetes, and cancer, focusing on the fibrotic and inflammatory remodeling of adipose tissues, skeletal muscles, and cancer-associated stroma.

Disclosure Statement: Dr. Chun declares no conflict of interest regarding this work.

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