An altered lipid metabolism characterizes Charcot-Marie-Tooth type 2B peripheral neuropathy

Anna Maria Giudetti, Flora Guerra, Serena Longo, Raffaella Beli, Roberta Romano, Fiore Manganelli, Maria Nolano, Vincenzo Mangini, Lucio Santoro, Cecilia Bucci

Research output: Contribution to journalArticlepeer-review


Charcot-Marie Tooth type 2B (CMT2B) is a rare inherited peripheral neuropathy caused by five missense mutations in the RAB7A gene, which encodes a small GTPase of the RAB family. Currently, no cure is available for this disease. In this study, we approached the disease by comparing the lipid metabolism of CMT2B-derived fibroblasts to that of healthy controls. We found that CMT2B cells showed increased monounsaturated fatty acid level and increased expression of key enzymes of monounsaturated and polyunsaturated fatty acid synthesis. Moreover, in CMT2B cells a higher expression of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS), key enzymes of de novo fatty acid synthesis, with a concomitantly increased [1-14C]acetate incorporation into fatty acids, was observed. The expression of diacylglycerol acyltransferase 2, a rate-limiting enzyme in triacylglycerol synthesis, as well as triacylglycerol levels were increased in CMT2B compared to control cells. In addition, as RAB7A controls lipid droplet breakdown and lipid droplet dynamics have been linked to diseases, we analyzed these organelles and showed that in CMT2B cells there is a strong accumulation of lipid droplets compared to control cells, thus reinforcing our data on abnormal lipid metabolism in CMT2B. Furthermore, we demonstrated that ACC and FAS expression levels changed upon RAB7 silencing or overexpression in HeLa cells, thus suggesting that metabolic modifications observed in CMT2B-derived fibroblasts can be, at least in part, related to RAB7 mutations.

Original languageEnglish
Article number158805
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Issue number12
Publication statusPublished - Dec 2020


  • de novo lipogenesis
  • Fibroblast
  • Lipid droplet
  • Lipid metabolism
  • Neurodegenerative disease
  • RAB7A

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology


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