Inflammation‐induced macrophage lysyl oxidase in adipose stiffening and dysfunction in obesity

To test whether obesity upregulated LOX in macrophages, we isolated peritoneal macrophages from WT and ob/ob mice and found that mRNA and protein levels and enzymatic activity of LOX were significantly augmented in ob/ob peritoneal macrophages (Figure 2C–E). [...]ob/ob peritoneal macrophages showed the ability to stiffen type I collagen gel, a mimicry of AT environment with its predominant extracellular matrix protein (Figure 2F). Collectively, these results implied increased LOX levels in macrophages caused by inflammatory stimuli resulted in AT stiffening. [...]we hypothesized that obesity-associated inflammatory responses upregulate LOX and collagen crosslinking, leading to AT stiffening and dysfunction. [...]we identified inflamed macrophages as key players in substratum stiffening by upregulating and releasing LOX, which further stiffened the environment where the cells were cultivated, leading to dysfunctional adipocytes.