The Latest Articles on Metabolism and Neurodegenerative Diseases

Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.

This week, we would like to share several latest articles on Metabolism and Neurodegenerative Diseases.

Title: Mitochondrial and metabolic features of salugenesis and the healing cycle
Authors: Robert K. Naviaux
Type: Review
Abstract:
Pathogenesis and salugenesis are the first and second stages of the two-stage problem of disease production and health recovery. Salugenesis is the automatic, evolutionarily conserved, ontogenetic sequence of molecular, cellular, organ system, and behavioral changes that is used by living systems to heal. It is a whole-body process that begins with mitochondria and the cell. The stages of salugenesis define a circle that is energy- and resource-consuming, genetically programmed, and environmentally responsive. Energy and metabolic resources are provided by mitochondrial and metabolic transformations that drive the cell danger response (CDR) and create the three phases of the healing cycle: Phase 1—Inflammation, Phase 2—Proliferation, and Phase 3—Differentiation. Each phase requires a different mitochondrial phenotype. Without different mitochondria there can be no healing. The rise and fall of extracellular ATP (eATP) signaling is a key driver of the mitochondrial and metabolic reprogramming required to progress through the healing cycle.

Sphingolipid and cholesterol-enriched membrane lipid rafts act as rheostats for tuning cellular sensitivity to purinergic signaling. Abnormal persistence of any phase of the CDR inhibits the healing cycle, creates dysfunctional cellular mosaics, causes the symptoms of chronic disease, and accelerates the process of aging. New research reframes the rising tide of chronic disease around the world as a systems problem caused by the combined action of pathogenic triggers and anthropogenic factors that interfere with the mitochondrial functions needed for healing. Once chronic pain, disability, or disease is established, salugenesis-based therapies will start where pathogenesis-based therapies end.
Access this article: https://doi.org/10.1016/j.mito.2023.04.003

Title: Intermittent fasting alleviates type 1 diabetes-induced cognitive dysfunction by improving the frontal cortical metabolic disorder
Authors: Fen Xiong, Kaiyuan Jiang, Yali Wu, Cong Lou, Chengjie Ding, Wenli Zhang, Xi Zhang, Chen Li, Hong Zheng, Hongchang Gao
Type: Research Article
Abstract:
Sirtuin 3 (SIRT3), a mitochondrial deacetylase expressed preferentially in high-metabolic-demand tissues including the brain, requires NAD+ as a cofactor for catalytic activity. It regulates various processes such as energy homeostasis, redox balance, mitochondrial quality control, mitochondrial unfolded protein response, biogenesis, dynamics and mitophagy by altering protein acetylation status. Reduced SIRT3 expression or activity causes hyperacetylation of hundreds of mitochondrial proteins, which has been linked with neurological abnormalities, neuro-excitotoxicity and neuronal cell death. A body of evidence has suggested, SIRT3 activation as a potential therapeutic modality for age-related brain abnormalities and neurodegenerative disorders.
Access this article: https://doi.org/10.1016/j.bbadis.2023.166725

Title: Pharmacological and physiological roles of adipokines and myokines in metabolic-related dementia
Authors: Archana Arjunan, Juhyun Song
Type: Review
Abstract:
Dementia is a detrimental neuropathologic condition with considerable physical, mental, social, and financial impact on patients and society. Patients with metabolic syndrome (MetS), a group of diseases that occur in tandem and increase the risk of neurologic diseases, have a higher risk of dementia. The ratio between muscle and adipose tissue is crucial in MetS, as these contain many hormones, including myokines and adipokines, which are involved in crosstalk and local paracrine/autocrine interactions. Evidence suggests that abnormal adipokine and myokine synthesis and release may be implicated in various MetS, such as atherosclerosis, diabetic mellitus (DM), and dyslipidemia, but their precise role is unclear. Here we review the literature on adipokine and myokine involvement in MetS-induced dementia via glucose and insulin homeostasis regulation, neuroinflammation, vascular dysfunction, emotional changes, and cognitive function.
Access this article: https://doi.org/10.1016/j.biopha.2023.114847

Title: Using stable isotope tracing to unravel the metabolic components of neurodegeneration: Focus on neuron-glia metabolic interactions
Authors: Emil W. Westi, Jens V. Andersen, Blanca I. Aldana
Type: Research Article
Abstract:
Disrupted brain metabolism is a critical component of several neurodegenerative diseases. Energy metabolism of both neurons and astrocytes is closely connected to neurotransmitter recycling via the glutamate/GABA-glutamine cycle. Neurons and astrocytes hereby work in close metabolic collaboration which is essential to sustain neurotransmission. Elucidating the mechanistic involvement of altered brain metabolism in disease progression has been aided by the advance of techniques to monitor cellular metabolism, in particular by mapping metabolism of substrates containing stable isotopes, a technique known as isotope tracing. Here we review key aspects of isotope tracing including advantages, drawbacks and applications to different cerebral preparations. In addition, we narrate how isotope tracing has facilitated the discovery of central metabolic features in neurodegeneration with a focus on the metabolic cooperation between neurons and astrocytes.
Access this article: https://doi.org/10.1016/j.nbd.2023.106145

Title: Calorie restriction mitigates metabolic, behavioral and neurochemical effects of cafeteria diet in aged male rats
Authors: Jeferson Jantsch, Fernanda da Silva Rodrigues, Gabriel de Farias Fraga, Sarah Eller, Alexandre Kleber Silveira, José Cláudio Fonseca Moreira, Márcia Giovernardi, Renata Padilha Guedes
Type: Research Article
Abstract:
Besides metabolic dysfunctions, elderly individuals with obesity are at special risk of developing cognitive decline and psychiatric disturbances. Restricted calorie consumption could be an efficient strategy to improve metabolic function after obesity. However, its effects on anxiety-like behaviors in aged rats submitted to an obesogenic diet are unknown. For this purpose, 42 Wistar rats (18-months old) were divided into four groups: Control (CT), calorie restriction (CR), cafeteria diet (CAF), and CAF+CR (CAF/CR). CT, CR, and CAF groups received the diets for 8 weeks. CAF/CR group was submitted to the CAF menu for 7 weeks and then switched to a standard diet on a CR regimen, receiving 30% lower calories than consumed by the CT, for another 5 weeks. CAF's menu consisted of ultra-processed foods such as cookies, chocolate, sausage, and bologna. Body weight, visceral adiposity, and biochemical blood analysis were evaluated for obesity diagnosis. The profile of gut microbiota was investigated, along with circulating levels of LPS. Neurochemical parameters, such as neurotransmitter levels, were dosed. Anxiety-like behaviors were accessed using open field (OF) and elevated plus maze (EPM) tests. As expected, CR reduced weight gain and improved glucose homeostasis. Gut microbiome disturbance was found in CAF-fed animals accompanied by increased levels of LPS. However, CR after CAF mitigated several harmful responses. The obesogenic diet triggered anxiety-like manifestations in the OF and EPM tests that were not evidenced in the CAF/CR group. These findings indicate that CR can be a promising strategy for the neurological effects of obesity in aged rats.
Access this article: https://doi.org/10.1016/j.jnutbio.2023.109371