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However, the importance of polyunsaturated fatty acids (PUFA) in sulfated lysosomal substrate metabolism and its related disorders is currently unknown. We investigated the effects of deficiency or supplementation of PUFA on the metabolism of sulfatides and sulfated glycosaminoglycans (sGAGs) in sulfatide\u2010rich organs (brain and kidney) of mice. A PUFA\u2010deficient diet for over 5\u00a0weeks significantly reduced the sulfatide expression by increasing the sulfatide degradative enzymes arylsulfatase A and galactosylceramidase in brain and kidney. This sulfatide degradation was clearly associated with the activation of autophagy and lysosomal hyperfunction, the former of which was induced by suppression of the Erk\/mTOR pathway. A PUFA\u2010deficient diet also activated the degradation of sGAGs in the brain and kidney and that of amyloid precursor proteins in the brain, indicating an involvement in general lysosomal function and the early developmental process of AD. PUFA supplementation prevented all of the above abnormalities. Taken together, a PUFA deficiency might lead to sulfatide and sGAG degradation associated with autophagy activation and general lysosomal hyperfunction and play a role in many types of disease development, suggesting a possible benefit of prophylactic PUFA supplementation.<\/jats:p>","DOI":"10.1096\/fj.202000030rr","type":"journal-article","created":{"date-parts":[[2020,7,27]],"date-time":"2020-07-27T10:37:08Z","timestamp":1595846228000},"page":"9594-9614","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Polyunsaturated fatty acid deficiency affects sulfatides and other sulfated glycans in lysosomes through autophagy\u2010mediated degradation"],"prefix":"10.1096","volume":"34","author":[{"given":"Yaping","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Metabolic Regulation Shinshu University School of Medicine Matsumoto 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