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

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

doi:10.1016/j.bbalip.2020.158805

Cited by 15 publications

(25 citation statements)

References 91 publications

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“…On the other hand, while several mitochondrial fission proteins linked to peripheral neuropathy are also involved in mediating peroxisomal fission (e.g., DRP1, MFF, GDAP1), the fact that some pathogenic variants in DRP1 and GDAP1 do not appear to inhibit peroxisomal fission suggests that impaired peroxisomal fission is not relevant to peripheral neuropathy. Finally, while altered lipid droplets have been described in parallel with impaired mitochondrial dynamics (e.g., MFN2, DNM2), and lipid droplet impairment is also associated with peripheral neuropathy [ 61 , 62 , 63 ], there is not a good appreciation of whether lipid droplet alterations are upstream or downstream of mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…For example, impaired interactions between mitochondria and the endoplasmic reticulum (ER), which regulate calcium signaling and lipid metabolism, have also been linked to peripheral neuropathy [ 55 , 56 , 57 , 58 , 59 ]. Similarly, mitochondria can regulate the formation and utilization of lipid droplets [ 60 ], the impairment of which is associated with peripheral neuropathy [ 61 , 62 , 63 ]. Here, we will review the dynamic processes of mitochondrial fission, fusion and movement, focusing on specific pathogenic variants in key proteins mediating these functions that are linked to peripheral neuropathy.…”

Section: Introductionmentioning

confidence: 99%

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Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Sharma

Pfeffer

Shutt

2021

Biology

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Mitochondria are dynamic organelles capable of fusing, dividing, and moving about the cell. These properties are especially important in neurons, which in addition to high energy demand, have unique morphological properties with long axons. Notably, mitochondrial dysfunction causes a variety of neurological disorders including peripheral neuropathy, which is linked to impaired mitochondrial dynamics. Nonetheless, exactly why peripheral neurons are especially sensitive to impaired mitochondrial dynamics remains somewhat enigmatic. Although the prevailing view is that longer peripheral nerves are more sensitive to the loss of mitochondrial motility, this explanation is insufficient. Here, we review pathogenic variants in proteins mediating mitochondrial fusion, fission and transport that cause peripheral neuropathy. In addition to highlighting other dynamic processes that are impacted in peripheral neuropathies, we focus on impaired mitochondrial quality control as a potential unifying theme for why mitochondrial dysfunction and impairments in mitochondrial dynamics in particular cause peripheral neuropathy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Sharma

Pfeffer

Shutt

2021

Biology

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“…On the day of the experiment, liver sections were fixed in 4% paraformaldehyde in PBS pH 7.4 for 5 min at room temperature; after several washes in distilled water sections were stained with Oil Red-O solution at 5% in isopropyl alcohol for 1 h. Sections were then rinsed with distilled water, washed with 10% isopropanol, and counterstained with hematoxylin for 30 s. Sections were then visualized and photographed by EVOS FL Auto Cell Imaging System (Thermo Fisher Scientific, Waltham, MA, USA) with PlanApo N 60 X/1.42 oil (Olympus, Shinjuku, Tokyo, Japan) at ×40 magnification. Lipid droplet average size was determined as reported in [ 39 ] through ImageJ Software (Version 1.5Oi, NIH, Bethesda, MD, USA). Measures were obtained by analyzing at least 50 sections for each group in three independent experiments.…”

Section: Methodsmentioning

confidence: 99%

Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats

et al. 2021

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Long-term high-fat diet (HFD) consumption can cause weight gain and obesity, two conditions often associated with hepatic non-alcoholic fatty liver and oxidative stress. Oleoylethanolamide (OEA), a lipid compound produced by the intestine from oleic acid, has been associated with different beneficial effects in diet-induced obesity and hepatic steatosis. However, the role of OEA on hepatic oxidative stress has not been fully elucidated. In this study, we used a model of diet-induced obesity to study the possible antioxidant effect of OEA in the liver. In this model rats with free access to an HFD for 77 days developed obesity, steatosis, and hepatic oxidative stress, as compared to rats consuming a low-fat diet for the same period. Several parameters associated with oxidative stress were then measured after two weeks of OEA administration to diet-induced obese rats. We showed that OEA reduced, compared to HFD-fed rats, obesity, steatosis, and the plasma level of triacylglycerols and transaminases. Moreover, OEA decreased the amount of malondialdehyde and carbonylated proteins and restored the activity of antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase, which decreased in the liver of HFD-fed rats. OEA had also an improving effect on parameters linked to endoplasmic reticulum stress, thus demonstrating a role in the homeostatic control of protein folding. Finally, we reported that OEA differently regulated the expression of two transcription factors involved in the control of lipid metabolism and antioxidant genes, namely nuclear factor erythroid-derived 2-related factor 1 (Nrf1) and Nrf2, thus suggesting, for the first time, new targets of the protective effect of OEA in the liver.

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“…Ceramide and sphingomyelin were identified by comparison with specific standards (C18 ceramide and sphingomyelin (d18:1/12:0) from Avanti Polar). After separation, plates were sprayed uniformly with 8% cupric sulfate in 8% aqueous phosphoric acid, allowed to dry 10 min at room temperature, and then placed into a 145 • C oven for 10 min as reported in [41]. Band intensities were quantified using Image LabTM Version 6.0.1 2017 (Bio-Rad Laboratories, Inc., Segrate (MI)-Italy) software.…”

Section: Tissue Collection and Lipid Analysismentioning

confidence: 99%

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

et al. 2021

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Oleoylethanolamide (OEA) is a naturally occurring bioactive lipid belonging to the family of N-acylethanolamides. A variety of beneficial effects have been attributed to OEA, although the greater interest is due to its potential role in the treatment of obesity, fatty liver, and eating-related disorders. To better clarify the mechanism of the antiadipogenic effect of OEA in the liver, using a lipidomic study performed by 1H-NMR, LC-MS/MS and thin-layer chromatography analyses we evaluated the whole lipid composition of rat liver, following a two-week daily treatment of OEA (10 mg kg−1 i.p.). We found that OEA induced a significant reduction in hepatic triacylglycerol (TAG) content and significant changes in sphingolipid composition and ceramidase activity. We associated the antiadipogenic effect of OEA to decreased activity and expression of key enzymes involved in fatty acid and TAG syntheses, such as acetyl-CoA carboxylase, fatty acid synthase, diacylglycerol acyltransferase, and stearoyl-CoA desaturase 1. Moreover, we found that both SREBP-1 and PPARγ protein expression were significantly reduced in the liver of OEA-treated rats. Our findings add significant and important insights into the molecular mechanism of OEA on hepatic adipogenesis, and suggest a possible link between the OEA-induced changes in sphingolipid metabolism and suppression of hepatic TAG level.

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

Cited by 15 publications

References 91 publications

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Genetic Neuropathy Due to Impairments in Mitochondrial Dynamics

Oleoylethanolamide Reduces Hepatic Oxidative Stress and Endoplasmic Reticulum Stress in High-Fat Diet-Fed Rats

Chronic Oleoylethanolamide Treatment Decreases Hepatic Triacylglycerol Level in Rat Liver by a PPARγ/SREBP-Mediated Suppression of Fatty Acid and Triacylglycerol Synthesis

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