Low fat diets increase survival of a mouse model of spinal muscular atrophy

Deguise, Marc-Olivier; Chehadé, Lucia; Tierney, Alexandra; Beauvais, Ariane; Kothary, Rashmi

doi:10.1002/acn3.50920

Cited by 12 publications

(17 citation statements)

References 26 publications

(35 reference statements)

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“…Fatty liver appears to be a common trait of ALS as well [ 126 , 127 ], although this is not seen in a commonly used mouse model of ALS [ 31 ]. Moreover, a low-fat diet nearly doubled the lifespan of Smn 2B/− mice [ 41 ] and may be beneficial for individuals living with SMA. In contrast to these findings, high caloric [ 120 , 135 ] and ketogenic diets [ 136 ] delayed disease onset and extended survival in mouse models of ALS, while caloric restriction shortened the lifespan of superoxide dismutase 1 (SOD1) mice [ 137 ].…”

Section: Intermediary Metabolism In Smamentioning

confidence: 99%

“…Early research focused on lipid disturbances in different forms of spinal muscular atrophies [ 36 , 37 , 38 , 39 ]. Several new studies have highlighted numerous metabolic alterations in SMA patients and animal models of the disease [ 30 , 31 , 40 , 41 ]. However, it should be noted that a clear mechanism linking SMN depletion and the various metabolic abnormalities is currently lacking.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Dysfunction in Spinal Muscular Atrophy

Deguise

Chehadé

Kothary

2021

IJMS

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Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder leading to paralysis, muscle atrophy, and death. Significant advances in antisense oligonucleotide treatment and gene therapy have made it possible for SMA patients to benefit from improvements in many aspects of the once devastating natural history of the disease. How the depletion of survival motor neuron (SMN) protein, the product of the gene implicated in the disease, leads to the consequent pathogenic changes remains unresolved. Over the past few years, evidence toward a potential contribution of gastrointestinal, metabolic, and endocrine defects to disease phenotype has surfaced. These findings ranged from disrupted body composition, gastrointestinal tract, fatty acid, glucose, amino acid, and hormonal regulation. Together, these changes could have a meaningful clinical impact on disease traits. However, it is currently unclear whether these findings are secondary to widespread denervation or unique to the SMA phenotype. This review provides an in-depth account of metabolism-related research available to date, with a discussion of unique features compared to other motor neuron and related disorders.

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Section: Intermediary Metabolism In Smamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Metabolic Dysfunction in Spinal Muscular Atrophy

Deguise

Chehadé

Kothary

2021

IJMS

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“…These findings suggested that higher fat content may confer protective benefits during motor neuron loss. However, an updated study reported that low-fat diets could nearly double survival in Smn 2B/− mice, independent of changes in SMN levels, liver steatosis, or enhanced hepatic functions [ 81 ]. Although both studies are in the preclinical phase, such controversies suggest a need to establish clinical nutrition guidance from evidence-based research to provide better care for SMA patients.…”

Section: Dietary Issues In Smamentioning

confidence: 99%

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

Chen

et al. 2020

Nutrients

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Spinal muscular atrophy (SMA), the main genetic cause of infant death, is a neurodegenerative disease characterized by the selective loss of motor neurons in the anterior horn of the spinal cord, accompanied by muscle wasting. Pathomechanically, SMA is caused by low levels of the survival motor neuron protein (SMN) resulting from the loss of the SMN1 gene. However, emerging research extends the pathogenic effect of SMN deficiency beyond motor neurons. A variety of metabolic abnormalities, especially altered fatty acid metabolism and impaired glucose tolerance, has been described in isolated cases of SMA; therefore, the impact of SMN deficiency in metabolic abnormalities has been speculated. Although the life expectancy of these patients has increased due to novel disease-modifying therapies and standardization of care, understanding of the involvement of metabolism and nutrition in SMA is still limited. Optimal nutrition support and metabolic monitoring are essential for patients with SMA, and a comprehensive nutritional assessment can guide personalized nutritional therapy for this vulnerable population. It has recently been suggested that metabolomics studies before and after the onset of SMA in patients can provide valuable information about the direct or indirect effects of SMN deficiency on metabolic abnormalities. Furthermore, identifying and quantifying the specific metabolites in SMA patients may serve as an authentic biomarker or therapeutic target for SMA. Here, we review the main epidemiological and mechanistic findings that link metabolic changes to SMA and further discuss the principles of metabolomics as a novel approach to seek biomarkers and therapeutic insights in SMA.

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“…The fast steatosis phenotype, paired with the fact that no special and expensive diet is required, make it a cost-effective option. In fact, introduction of high fat diet did not drastically worsen the overall metabolic phenotype of the Smn 2B/mice [38]. In addition, our study made use of both male and female mice, unlike other mouse models where males are predominantly used [39].…”

Section: Discussionmentioning

confidence: 85%

A mouse model for spinal muscular atrophy provides insights into non-alcoholic fatty liver disease pathogenesis

Deguise

Pileggi

Beauvais

et al. 2020

Preprint

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Charles Best CIHR Doctoral Research Award. contrast to typical NAFLD/NASH, the Smn 2B/mice lose weight due to their neurological condition, develop hypoglycemia and do not develop hepatic fibrosis. ConclusionThe Smn 2B/mice represent a good model of microvesicular steatohepatitis. Like other models, it is not representative of the complete NAFLD/NASH spectrum. Nevertheless, it offers a reliable, low-cost, early onset model that is not dependent on diet to identify molecular players in NAFLD pathogenesis and can serve as one of the very few models of microvesicular steatohepatitis for both adult and pediatric populations.

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Low fat diets increase survival of a mouse model of spinal muscular atrophy

Cited by 12 publications

References 26 publications

Metabolic Dysfunction in Spinal Muscular Atrophy

Metabolic Dysfunction in Spinal Muscular Atrophy

Metabolic and Nutritional Issues Associated with Spinal Muscular Atrophy

A mouse model for spinal muscular atrophy provides insights into non-alcoholic fatty liver disease pathogenesis

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