Novel targets for ameliorating energy metabolism disorders in depression through stable isotope-resolved metabolomics

Linghu, Ting; Zhao, Yun-hao; Wu, Wen-ze; Gao, Yao; Tian, Jun-Sheng; Qin, Xuemei

doi:10.1016/j.bbabio.2022.148578

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…As for the associations between predicted pathways and genes, we would like to emphasize the linkage between CYP39A1 and PWY-5913. PWY-5913 was partial of the TCA cycle and commonly involved with energy utilization ( Anderson et al, 2018 ; Linghu et al, 2022 ). Our results have shown no significant correlation between PWY-5913 and significantly different microbes, which indicated that this different pathway uncovered a whole-level difference.…”

Section: Discussionmentioning

confidence: 99%

The host genetics affects gut microbiome diversity in Chinese depressed patients

Han

Ji²,

Wang³

et al. 2023

Front. Genet.

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The gut microbiome and host genetics are both associated with major depressive disorder (MDD); however, the molecular mechanisms among the associations are poorly understood, especially in the Asian, Chinese group. Our study applied linear discriminant analysis (LDA) effect size (LEfSe) and genome-wide association analysis in the cohort with both gut sequencing data and genomics data. We reported the different gut microbiota characteristics between MDD and control groups in the Chinese group and further constructed the association between host genetics and the gut microbiome. Actinobacteria and Pseudomonades were found more in the MDD group. We found significant differences in the ACE and Chao indexes of alpha diversity while no discrepancy in beta diversity. We found three associations between host genetics with microbiome features: beta diversity and rs6108 (p = 8.65 × 10–9), Actinobacteria and rs77379751 (p = 8.56 × 10–9), and PWY-5913 and rs1775633082 (p = 4.54 × 10–8). A species of the Romboutsia genus was co-associated with the species of Ruminococcus gnavus in an internetwork through four genes: METTL8, ITGB2, OTULIN, and PROSER3, with a strict threshold (p < 5 × 10–4). Furthermore, our findings suggested that the gut microbiome diversity might affect microRNA expression in the brain and influenced SERPINA5 and other spatially close genes afterward. These findings suggest new linkages between depression and gut microbiome in Asian, Chinese people, which might be mediated by genes and microRNA regulation in space distance.

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Section: Discussionmentioning

confidence: 99%

The host genetics affects gut microbiome diversity in Chinese depressed patients

Han

Ji²,

Wang³

et al. 2023

Front. Genet.

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“…Another alternative pathway explaining a decrease in pyruvate may be the promoted entry of oxaloacetate into the TCA by increased pyruvate carboxylase activity (PC). In summary, both, PDH and PC, may be the key metabolic enzymes relevant for overcoming energy shortage under MCT consumption ( 37 , 96 ).…”

Section: Discussionmentioning

confidence: 99%

Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil

Berk

Ottka²,

Law³

et al. 2022

Front. Vet. Sci.

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Consumption of medium-chain triglycerides (MCT) has been shown to improve seizure control, reduce behavioural comorbidities and improve cognitive function in epileptic dogs. However, the exact metabolic pathways affected by dietary MCT remain poorly understood. In this study, we aimed to identify changes in the metabolome and neurotransmitters levels relevant to epilepsy and behavioural comorbidities associated with the consuming of an MCT supplement (MCT-DS) in dogs with idiopathic epilepsy (IE). Metabolic alterations induced by a commercial MCT-DS in a population of 28 dogs with IE were evaluated in a 6-month multi-centre, prospective, randomised, double-blinded, controlled cross-over trial design. A metabolic energy requirement-based amount of 9% MCT or control oil was supplemented to the dogs' stable base diet for 3 months, followed by the alternative oil for another 3 months. A validated, quantitative nuclear magnetic resonance (NMR) spectroscopy platform was applied to pre- and postprandially collected serum samples to compare the metabolic profile between both DS and baseline. Furthermore, alterations in urinary neurotransmitter levels were explored. Five dogs (30%) had an overall reduction in seizure frequency of ≥50%, and were classified as MCT-responders, while 23 dogs showed a ≤50% reduction, and were defined as MCT non-responders. Amino-acid metabolism was significantly influenced by MCT consumption compared to the control oil. While the serum concentrations of total fatty acids appeared similar during both supplements, the relative concentrations of individual fatty acids differed. During MCT supplementation, the concentrations of polyunsaturated fatty acids and arachidonic acid were significantly higher than under the control oil. β-Hydroxybutyric acid levels were significantly higher under MCT supplementation. In total, four out of nine neurotransmitters were significantly altered: a significantly increased γ-aminobutyric acid (GABA) concentration was detected during the MCT-phase accompanied by a significant shift of the GABA-glutamate balance. MCT-Responders had significantly lowered urinary concentrations of histamine, glutamate, and serotonin under MCT consumption. In conclusion, these novel data highlight metabolic changes in lipid, amino-acid and ketone metabolism due to MCT supplementation. Understanding the metabolic response to MCT provides new avenues to develop better nutritional management with improved anti-seizure and neuroprotective effects for dogs with epilepsy, and other behavioural disorders.

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“…Recently, it has been shown that TCA cycle in aerobic glycolysis is also involved in the development of depression. Linghu et al 43 . revealed depressive rats caused by CUMS show significantly decreased TCA cycle and increased gluconeogenesis pathway, which may be related to the decrease of mitochondrial pyruvate carrier.…”

Section: Mitochondrial Energy Metabolism and Depressionmentioning

confidence: 99%

Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems

Jiang,

Wang,

Sheng

2024

CNS Neurosci Ther

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BackgroundDepression is the most disabling neuropsychiatric disorder, causing difficulties in daily life activities and social interactions. The exact mechanisms of depression remain largely unclear. However, some studies have shown that mitochondrial dysfunction would play a crucial role in the occurrence and development of depression.AimsTo summarize the known knowledge about the role of mitochondrial dysfunction in the pathogenesis of depression.MethodsWe review the recent literature， including 105 articles, to summarize the mitochondrial energy metabolism and quality control systems in the occurrence and development of depression. Some antidepressants which may exert their effects by improving mitochondrial function are also discussed.ResultsImpaired brain energy metabolism and (or) damaged mitochondrial quality control systems have been reported not only in depression patients but in animal models of depression. Although the classical antidepressants have not been specially designed to target mitochondria, the evidence suggests that many antidepressants may exert their effects by improving mitochondrial function.ConclusionsThis brief review focuses on the findings that implicate mitochondrial dysfunction and the quality control systems as important etiological factors in the context of depressive disorders. It will help us to understand the various concepts of mitochondrial dysfunction in the pathogenesis of depression, and to explore novel and more targeted therapeutic approaches for depression.

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Novel targets for ameliorating energy metabolism disorders in depression through stable isotope-resolved metabolomics

Cited by 9 publications

References 42 publications

The host genetics affects gut microbiome diversity in Chinese depressed patients

The host genetics affects gut microbiome diversity in Chinese depressed patients

Metabolic fingerprinting of dogs with idiopathic epilepsy receiving a ketogenic medium-chain triglyceride (MCT) oil

Mitochondria in depression: The dysfunction of mitochondrial energy metabolism and quality control systems

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