Paradox of amyotrophic lateral sclerosis and energy metabolism

Dupuis, Luc; Kiernan, Matthew C.

doi:10.1136/jnnp-2018-318428

Cited by 18 publications

(10 citation statements)

References 16 publications

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“…The primary aim of this study was to explore the potential mechanisms underpinning altered whole-body metabolic balance in ALS ( Ahmed et al , 2018 ; Steyn et al , 2018a ; Vandoorne et al , 2018 ). We show that an increase in whole-body energy expenditure in symptomatic SOD1 G93A mice is associated with a decline in both fat mass and fat free mass.…”

Section: Discussionmentioning

confidence: 99%

Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis

Steyn

Kirk

et al. 2020

Brain Communications

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Amyotrophic lateral sclerosis is characterized by the degeneration of upper and lower motor neurons, yet an increasing number of studies in both mouse models and patients with amyotrophic lateral sclerosis suggest that altered metabolic homeostasis is also a feature of disease. Pre-clinical and clinical studies have shown that modulation of energy balance can be beneficial in amyotrophic lateral sclerosis. However, the capacity to target specific metabolic pathways or mechanisms requires detailed understanding of metabolic dysregulation in amyotrophic lateral sclerosis. Here, using the SOD1G93A mouse model of amyotrophic lateral sclerosis, we demonstrate that an increase in whole-body metabolism occurs at a time when glycolytic muscle exhibits an increased dependence on fatty acid oxidation. Using myotubes derived from muscle of amyotrophic lateral sclerosis patients, we also show that increased dependence on fatty acid oxidation is associated with increased whole-body energy expenditure. In the present study, increased fatty acid oxidation was associated with slower disease progression. However, within the patient cohort there was considerable heterogeneity in whole-body metabolism and fuel oxidation profiles. Thus, future studies that decipher specific metabolic changes at an individual patient level are essential for the development of treatments that aim to target metabolic pathways in amyotrophic lateral sclerosis.

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Section: Discussionmentioning

confidence: 99%

Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis

Steyn

Kirk

et al. 2020

Brain Communications

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“…A breakdown of central processes of energy homeostasis could contribute to changes in appetite in ALS (43). Recent studies have reported gross changes in areas of the brain, including the hypothalamus, that control metabolism in ALS (44).…”

Section: Discussionmentioning

confidence: 99%

Loss of appetite is associated with a loss of weight and fat mass in patients with amyotrophic lateral sclerosis

Ngo

Eijk

Chachay

et al. 2019

Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration

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Objective: Weight loss in amyotrophic lateral sclerosis (ALS) is associated with faster disease progression and shorter survival. It has different possible causes, including loss of appetite. Our objective is to determine the prevalence and impact of loss of appetite on change in body weight and composition in patients with ALS. Methods: We conducted a prospective case-control study, comparing demographic, clinical, appetite and prognostic features between 62 patients with ALS and 45 healthy non-neurodegenerative disease (NND) controls. To determine the impact of loss of appetite on weight throughout disease course, we conducted serial assessments at $three to four-month intervals. Results: Loss of appetite is more prevalent in patients with ALS than NND controls (29 vs. 11.1%, odds ratio ¼ 3.27 (1.1-9.6); p < 0.01). In patients with ALS, loss of appetite is associated with greater weight loss and greater loss of fat mass. Appetite scores in patients with ALS worsens as disease progresses and are correlated with worsening ALS Functional Rating Scale-Revised scores. Conclusion: We confirm that loss of appetite is prevalent in patients with ALS and is significantly associated with weight loss and loss of fat mass. Appetite worsens with disease progression. Identification and early interventions to address loss of appetite in patients with ALS may prevent or slow weight loss; this could improve disease outcome.

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“…It is increasingly recognized that amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a spectrum of diseases with considerable overlap at genetic, pathological, and behavioral levels . Patients along this spectrum also have differing changes in eating and metabolism that may potentially effect disease progression and survival . It is widely accepted that ALS patients are hypermetabolic which is associated with worse prognosis.…”

Section: Introductionmentioning

confidence: 99%

Eating peptides: biomarkers of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia

Ahmed

Phan

Highton‐Williamson

et al. 2019

Ann Clin Transl Neurol

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Objective Physiological changes potentially influence disease progression and survival along the Amyotrophic Lateral Sclerosis (ALS)‐Frontotemporal dementia (FTD) spectrum. The peripheral peptides that regulate eating and metabolism may provide diagnostic, metabolic, and progression biomarkers. The current study aimed to examine the relationships and biomarker potential of hormonal peptides. Methods One hundred and twenty‐seven participants (36 ALS, 26 ALS‐ cognitive, patients with additional cognitive behavioral features, and 35 behavioral variant FTD (bvFTD) and 30 controls) underwent fasting blood analyses of leptin, ghrelin, neuropeptide Y (NPY), peptide YY (PYY), and insulin levels. Relationships between endocrine measures, cognition, eating behaviors, and body mass index (BMI) were investigated. Biomarker potential was evaluated using multinomial logistic regression for diagnosis and correlation to disease duration. Results Compared to controls, ALS and ALS‐cognitive had higher NPY levels and bvFTD had lower NPY levels, while leptin levels were increased in all patient groups. All groups had increased insulin levels and a state of insulin resistance compared to controls. Lower NPY levels correlated with increasing eating behavioral change and BMI, while leptin levels correlated with BMI. On multinomial logistic regression, NPY and leptin levels were found to differentiate between diagnosis. Reduced Neuropeptide Y levels correlated with increasing disease duration, suggesting it may be useful as a potential marker of disease progression. Interpretation ALS‐FTD is characterized by changes in NPY and leptin levels that may impact on the underlying regional neurodegeneration as they were predictive of diagnosis and disease duration, offering the potential as biomarkers and for the development of interventional treatments.

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Paradox of amyotrophic lateral sclerosis and energy metabolism

Cited by 18 publications

References 16 publications

Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis

Altered skeletal muscle glucose-fatty acid flux in amyotrophic lateral sclerosis

Loss of appetite is associated with a loss of weight and fat mass in patients with amyotrophic lateral sclerosis

Eating peptides: biomarkers of neurodegeneration in amyotrophic lateral sclerosis and frontotemporal dementia

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