title: Autophagy Is Dispensable for Macrophage-Mediated Lipid Homeostasis in Adipose Tissue.
abstract: Adipose tissue (AT) 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 the maintenance of 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 pharmacological inhibition of autophagy does not alter the lipid balance of ATMs in vitro or in vivo. In contrast to the 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 lysosome triglyceride hydrolysis in ATMs.
authors: Department of Medicine, The Naomi Berrie Diabetes Center, Columbia University, New York, NY.
authors: Ambar
authors: A
authors: Grijalva
authors: Department of Medicine, The Naomi Berrie Diabetes Center, Columbia University, New York, NY.
authors: Xiaoyuan
authors: X
authors: Xu
authors: Department of Medicine, The Naomi Berrie Diabetes Center, Columbia University, New York, NY awf7@columbia.edu.
authors: Anthony W
authors: AW
authors: Ferrante
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D001343:Autophagy / Q000235:genetics / Q000502:physiology*; D000071193:Autophagy-Related Protein 7 / Q000235:genetics; D002478:Cells, Cultured; D006706:Homeostasis / Q000502:physiology; D020738:Leptin / Q000172:deficiency / Q000235:genetics; D050356:Lipid Metabolism / Q000235:genetics; D008066:Lipolysis / Q000235:genetics; D008247:Lysosomes / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism
chemical_list: C502661:Atg7 protein, mouse; D020738:Leptin; D002787:Sterol Esterase; D000071193:Autophagy-Related Protein 7