Hypermetabolism associated with worse prognosis of amyotrophic lateral sclerosis

He, Ji; Fu, Jiayu; Zhao, Wei; Ren, Chuan; Liu, Ping; Chen, Lu; Li, Dan; Tang, Lu; Zhou, Lequn; Zhang, Yixuan; Ma, Xinran; Zhang, Gaoqi; Li, Nan

doi:10.1007/s00415-021-10716-1

Cited by 23 publications

(18 citation statements)

References 41 publications

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“…Hypermetabolism has recently been implicated in the poor prognosis of ALS 4 – 6 . In this study, patients with hypermetabolism along with high HDL exhibited significantly shorter survival than those with low HDL.…”

Section: Discussionmentioning

confidence: 99%

“…We defined hypermetabolism as mREE/LSTM ≥ 38, according to our previous report 8 . The ratio of mREE to calculated REE (cREE) obtained using the Harris-Benedict equation 26 is universally used to estimate metabolism 4 – 6 , 26 . However, cREE might be overestimated in Japanese people 27 , and thus, we used our own formula in order to exclude the effects caused by population-based differences.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies have shown that hypermetabolism is a feature of ALS and is a poor prognostic factor 4 – 6 . On the other hand, Steyn et al demonstrated that increased fatty acid oxidation enhances resting energy expenditure, which leads to slower progression in superoxide dismutase (SOD) mice 7 .…”

Section: Introductionmentioning

confidence: 99%

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Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism

Nakamura

Kurihara

Ogawa

et al. 2022

Sci Rep

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The prognostic predictive value of lipid profiling in amyotrophic lateral sclerosis (ALS) remains unclear. Here, we aimed to clarify the value of the levels of serum lipids, including high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and triglycerides (TG), for predicting the prognosis in ALS. This was a single-center retrospective study of 78 patients with ALS. The serum lipid profiles at the first hospital visit after symptom onset were analyzed to determine the correlations of lipids with survival and physical parameters, including nutritional, respiratory, and metabolic conditions. The cutoff level for high HDL was defined as the third quartile, while that of low LDL and TG, as the first quartile. Hypermetabolism was defined as the ratio of resting energy expenditure to lean soft tissue mass ≥ 38 kcal/kg. High HDL was an independent factor for poor prognosis in all patients (hazards ratio [HR]: 9.87, p < 0.001) in the Cox proportional hazard model, including %vital capacity and the monthly decline rate in body mass index and the Revised Amyotrophic Lateral Functional Rating Scale score from symptom onset to diagnosis. Low LDL was a factor for poor prognosis (HR: 6.59, p = 0.017) only in women. Moreover, subgroup analyses with log-rank tests revealed that the prognostic predictive value of high HDL was evident only in the presence of hypermetabolism (p = 0.005). High HDL predicts poor prognosis in all patients, whereas low LDL, only in women. Hypermetabolism and high HDL synergistically augment the negative effect on prognosis.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism

Nakamura

Kurihara

Ogawa

et al. 2022

Sci Rep

View full text Add to dashboard Cite

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“…The liver is a pivotal metabolic organ that acts as a hub that connects various organs, including skeletal muscle and adipose tissue [ 30 ]. Growing evidence suggests that dysregulated energy metabolism in patients with ALS and mouse models is closely correlated with metabolic abnormalities in disease progression and susceptibility [ 31 , 32 , 33 ]. It has been reported that the activity of Mdh is increased in the synaptosomes and homogenates from the spinal cord and motor cortex in hSOD1 G93A mice in the early stages of the disease [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Combined Treatment with Herbal Medicine and Drug Ameliorates Inflammation and Metabolic Abnormalities in the Liver of an Amyotrophic Lateral Sclerosis Mouse Model

Park

Yang

2022

Antioxidants

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To date, no effective drugs exist for amyotrophic lateral sclerosis (ALS), although riluzole (RZ) and edaravone have been approved for treatment. We previously reported that Bojungikgi-tang (BJIGT) improved motor activity through anti-inflammatory effects in the muscle and spinal cord of hSOD1G93A mice. Therefore, whether combined treatment with BJIGT and RZ synergistically affects liver function in hSOD1G93A mice was investigated. Two-month-old male hSOD1G93A mice were treated with BJIGT (1 mg/g) and RZ (8 μg/g) administered orally for 5 weeks. Drug metabolism and liver function tests of serum and liver homogenates were conducted. mRNA expression levels of cytochrome P450 (CYP) isozymes, inflammatory cytokines, metabolic factors, and mitochondrial oxidative phosphorylation (OXPHOS) subunits were examined using qPCR and Western blotting. Combined administration of BJIGT and RZ did not alter mRNA expression levels of drug-metabolism-related isozymes (CYP1A2 and CYP3A4) but significantly decreased the activity of liver-function-related enzymes (AST, ALT, ALP, and LDH). Increased expression of inflammatory cytokines (IL-1β, TNF-α, and IL-6) and of intracellular stress-related proteins (Bax, AMPKα, JNK, and p38) was reduced by the combined treatment in hSOD1G93A mice compared to that in control mice. Combined administration reduced the mRNA expression of metabolism-related factors and the expression of OXPHOS subunits. Elevated ATP levels and mitochondrial-fusion-associated protein were decreased after co-administration. Co-administration of BJIGT and RZ did not cause liver damage or toxicity but rather restored liver function in hSOD1G93A mice. This suggests that this combination can be considered a candidate therapeutic agent for ALS.

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“…This inconsistency is largely because most of this evidence came from observational studies, which are plagued by selection bias and unmeasured confounders. In addition, we previously found that most ALS patients showed a loss of appetite [ 18 ] and the presence of metabolic disorders [ 19 ], which may affect the absorption and consumption of dietary nutrients, making the true relationship between essential nutrients and ALS elusive. Randomized controlled trials (RCTs) are recognized to overcome the limitations of observational studies and provide the highest level of evidence [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study

et al. 2022

Self Cite

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Previous studies have suggested a close but inconsistent relationship between essential nutrients and the risk of amyotrophic lateral sclerosis (ALS), and whether this association is causal remains unknown. We aimed to investigate the potential causal relation between essential nutrients (essential amino acids, essential fatty acids, essential minerals, and essential vitamins) and the risk of ALS using Mendelian randomization (MR) analysis. Large-scale European-based genome-wide association studies’ (GWASs) summary data related to ALS (assembling 27,205 ALS patients and 110,881 controls) and essential nutrient concentrations were separately obtained. MR analysis was performed using the inverse variance–weighted (IVW) method, and sensitivity analysis was conducted by the weighted median method, simple median method, MR–Egger method and MR–PRESSO method. We found a causal association between genetically predicted linoleic acid (LA) and the risk of ALS (OR: 1.066; 95% CI: 1.011–1.125; p = 0.019). An inverse association with ALS risk was noted for vitamin D (OR: 0.899; 95% CI: 0.819–0.987; p = 0.025) and for vitamin E (OR: 0.461; 95% CI: 0.340–0.626; p = 6.25 × 10−7). The sensitivity analyses illustrated similar trends. No causal effect was observed between essential amino acids and minerals on ALS. Our study profiled the effects of diet-derived circulating nutrients on the risk of ALS and demonstrated that vitamin D and vitamin E are protective against the risk of ALS, and LA is a suggested risk factor for ALS.

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Hypermetabolism associated with worse prognosis of amyotrophic lateral sclerosis

Cited by 23 publications

References 41 publications

Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism

Investigation of the prognostic predictive value of serum lipid profiles in amyotrophic lateral sclerosis: roles of sex and hypermetabolism

Combined Treatment with Herbal Medicine and Drug Ameliorates Inflammation and Metabolic Abnormalities in the Liver of an Amyotrophic Lateral Sclerosis Mouse Model

Dietary-Derived Essential Nutrients and Amyotrophic Lateral Sclerosis: A Two-Sample Mendelian Randomization Study

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