Indexed on: 13 Feb '16Published on: 13 Feb '16Published in: Diabetes
Adipose tissue macrophages (ATMs) contribute to obesity-induced inflammation and metabolic dysfunction, but also play critical roles in maintaining tissue homeostasis. ATMs catabolize lipid in a lysosomal dependent manner required for maintenance of adipose tissue (AT); deficiency in Lysosomal Acid Lipase (Lipa), the enzyme required for lysosome lipid catabolism, leads to AT atrophy and severe hepatic steatosis, phenotypes rescued by macrophage-specific expression of Lipa. Autophagy delivers cellular products including lipid droplets to lysosomes. Given that obesity increases autophagy in AT and contributes to lipid catabolism in other cells, it was proposed that autophagy delivers lipid to lysosomes in ATMs and is required for AT homeostasis. We found that obesity does increase autophagy in ATMs. However, genetic or pharmacologic inhibition of autophagy does not alter lipid balance of ATMs in vitro or in vivo. In contrast to deficiency of lysosomal lipid hydrolysis, the ablation of autophagy in macrophages does not lead to AT atrophy or alter metabolic phenotypes in lean or obese animals. Although the lysosomal catabolism of lipid is necessary for normal ATM function and AT homeostasis, delivery of lipid to lysosomes is not autophagy dependent and strongly suggests the existence of another lipid delivery pathway critical to lysosomes triglyceride hydrolysis in ATMs.