Neuronal ceroid lipofuscinoses (NCL), known as Batten disease, are the most common of the rare neurodegenerative disorders in children. To date, defects in thirteen different genes have been identified in NCL patients. Despite the genetic heterogeneity, Batten diseases are grouped together based on clinical similarities and broadly uniform neuropathological features, including accumulation of lipofuscin in lysosomes, as well as profound neurodegeneration and widespread gliosis. Amongst these, the incidence of Cln7 disease, caused by mutation in MFSD8 gene, is the highest in southern and Mediterranean Europe. CLN7/MFSD8 encodes a lysosomal membrane glycoprotein with unknown function. Lysosomes are the only organelles able to hydrolyze triacylglycerols, which fuels the mitochondria for energy generation. The autophagic machinery provides TGs to the lysosomes through a process known as lipophagy. Although defective autophagy has been related with Cln7 disease, Cln7 role in lipid metabolism is unknown, particularly in lipophagy. Here, we hypothesized that impaired brain autophagy disrupts peripheric lipophagy, which can cause some of the disease symptoms. To address this, we have studied lipophagy in Cln7 knockout (Cln7-KO) mice and investigated whether Cln7 loss in the hypothalamus disrupts liver lipophagy. We have obtained experimental data from different techniques in Cln7-KO mice fibroblasts, liver, brown fat and brain, to stablish a connection between the brain and the metabolism of the peripheral tissues. Thus, our data show that Cln7 deficiency in the hypothalamus damages liver lipophagy resulting in fat accumulation. Ongoing work is being developed to validate these observations using robust metabolic and in vivo uncoupling approaches. As a conclusion we can agree that Cln7 deficiency causes neuronal damages which seem to produce lipophagy impairment in the periphery tissues.

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• https://produccioncientifica.usal.es/investigadores/446343/detalle