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Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by significant metabolic disruptions, including weight loss and hypermetabolism in both patients and animal models. Leptin, an adipose-derived hormone, displays altered levels in ALS. Genetically reducing leptin levels (Lepob/+) to maintain body weight improved motor performance and extended survival in female SOD1G93A mice, although the exact molecular mechanisms behind these effects remain elusive. Here, we corroborated the sexual dimorphism in circulating leptin levels in ALS patients and in SOD1G93A mice. We reproduced a previous strategy to generate a genetically deficient leptin SOD1G93A mice (SOD1G93ALepob/+) and studied the transcriptomic profile in the subcutaneous adipose tissue and the spinal cord. We found that leptin deficiency reduced the inflammation pathways activated by the SOD1G93A mutation in the adipose tissue, but not in the spinal cord. These findings emphasize the importance of considering sex-specific approaches in metabolic therapies and highlight the role of leptin in the systemic modulation of ALS by regulating immune responses outside the central nervous system.

There is an increasing interest in the study of the relation between alterations in systemic lipid metabolism and neurodegenerative disorders, in particular in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD). In ALS these alterations are well described and evident not only with the progression of the disease but also years before diagnosis. Still, there are some discrepancies in findings relating to the causal nature of lipid metabolic alterations, partly due to the great clinical heterogeneity in ALS. ALS presentation is within a disorder spectrum with Frontotemporal Dementia (FTD), and many patients present mixed forms of ALS and FTD, thus increasing the variability. Lipid metabolic and other systemic metabolic alterations have not been well studied in FTD, or in ALS–FTD mixed forms, as has been in pure ALS. With the recent development in lipidomics and the integration with other -omics platforms, there is now emerging data that not only facilitates the identification of biomarkers but also enables understanding of the underlying pathological mechanisms. Here, we reviewed the recent literature to compile lipid metabolic alterations in ALS, FTD, and intermediate mixed forms, with a view to appraising key commonalities or differences within the spectrum.

Background. Nutritional deficiencies may aggravate the course of chronic hepatitis C (CHC). Our aim has been to perform a comprehensive analysis of body composition and nutritional deficiencies in CHC patients in non-cirrhotic and compensated cirrhotic stages to correlate the detected deficiencies with the fibrosis stage.Material and methods. Body multifrequency bioimpedance analysis (BIA) and a wide and simultaneous analytical profile were prospectively performed in 74 CHC patients (36 male) with known METAVIR fibrosis stage established with liver biopsy or transient elastography. Results were analyzed to identify deviations from the normal range and variations according to the fibrosis stage.Results. Body fat compartment was greater in women. Body composition did not change among the 4 stages of liver fibrosis. Low levels (< 30 μg/L) of vitamin D were detected in 74.3% of patients irrespective of the fibrosis stage. Most analytical results remained into the normal range with the exceptions of thrombocytopenia and vitamin A deficiency, that were limited to the stage 4 of fibrosis, and low Zn and LDL-cholesterol values, that were frequently found in patients with advanced (F3 and F4) fibrosis stage.Conclusion. Body composition and most biochemical parameters, including cyanocobalamin, folic acid and vitamin E, are well preserved in compensated patients with CHC, with the exception of generalized vitamin D insufficiency and of deficiencies of vitamin A and zinc that are restricted to the more advanced, although still compensated, stages of the disease.