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Nature Metabolism Jul 2020For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that... (Review)
Review
For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that infectious diseases are complex, multisystem conditions, and a holistic understanding will be necessary to maximize survival. For COVID-19 and all other infectious diseases, metabolic processes are intimately connected to the mechanisms of disease pathogenesis and the resulting pathology and pathophysiology, as well as the host defence response to the infection. Here, I examine the relationship between metabolism and COVID-19. I discuss why preexisting metabolic abnormalities, such as type 2 diabetes and hypertension, may be important risk factors for severe and critical cases of infection, highlighting parallels between the pathophysiology of these metabolic abnormalities and the disease course of COVID-19. I also discuss how metabolism at the cellular, tissue and organ levels might be harnessed to promote defence against the infection, with a focus on disease-tolerance mechanisms, and speculate on the long-term metabolic consequences for survivors of COVID-19.
Topics: COVID-19; Coronavirus Infections; Diabetes Mellitus, Type 2; Humans; Hypertension; Metabolic Diseases; Pandemics; Pneumonia, Viral; Risk Factors
PubMed: 32694793
DOI: 10.1038/s42255-020-0237-2 -
Reviews in Endocrine & Metabolic... Jun 2022TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation,... (Review)
Review
TWEAK (tumor necrosis factor-like weak inducer of apoptosis) is a member of the TNF superfamily that controls a multitude of cellular events including proliferation, migration, differentiation, apoptosis, angiogenesis, and inflammation. TWEAK control of these events is via an expanding list of intracellular signalling pathways which include NF-κB, ERK/MAPK, Notch, EGFR and AP-1. Two receptors have been identified for TWEAK - Fn14, which targets the membrane bound form of TWEAK, and CD163, which scavenges the soluble form of TWEAK. TWEAK appears to elicit specific events based on the receptor to which it binds, tissue type in which it is expressed, specific extrinsic conditions, and the presence of other cytokines. TWEAK signalling is protective in healthy tissues, but in chronic inflammatory states become detrimental to the tissue. Consistent data show a role for the TWEAK/FN14/CD163 axis in metabolic disease, chronic autoimmune diseases, and acute ischaemic stroke. Low circulating concentrations of soluble TWEAK are predictive of poor cardiovascular outcomes in those with and without diabetes. This review details the current understanding of the TWEAK/Fn14/CD163 axis as one of the chief regulators of immune signalling and its cell-specific role in metabolic disease development and progression.
Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Brain Ischemia; Cytokine TWEAK; Humans; Inflammation; Metabolic Diseases; Receptors, Cell Surface; Receptors, Tumor Necrosis Factor; Stroke; TWEAK Receptor; Tumor Necrosis Factors
PubMed: 34542797
DOI: 10.1007/s11154-021-09688-4 -
Current Opinion in Clinical Nutrition... Mar 2023This review aims to discuss the most recent evidence identifying the presence of distinct white adipocyte subpopulations in white adipose tissue (WAT) and how these may... (Review)
Review
PURPOSE OF REVIEW
This review aims to discuss the most recent evidence identifying the presence of distinct white adipocyte subpopulations in white adipose tissue (WAT) and how these may be altered with increasing adiposity and/or metabolic disease. We conceptualize how changes in adipocyte subpopulations may contribute to alterations in WAT function and the development of metabolic diseases such as type 2 diabetes mellitus (T2DM), nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD).
RECENT FINDINGS
Studies utilizing novel analytical approaches support the existence of distinct white adipocyte subpopulations in both human and murine WAT. Adipocyte subtypes are potentially functionally distinct and may have different roles in WAT function and obesity-associated metabolic diseases.
SUMMARY
The exploration of white adipocyte heterogeneity using novel analytical technologies, has unveiled a new layer of complexity in the study of WAT biology. Interrogation of potential functional differences between adipocyte subpopulations and their role in the function of different WAT depots is now needed. Through understanding the mechanisms regulating white adipocyte subtype development and potential pathophysiological consequences of changes in the presence of adipocyte subpopulations, studies could provide novel therapeutic targets for the treatment of T2DM, NAFLD, and CVD.
Topics: Humans; Mice; Animals; Adipocytes, White; Diabetes Mellitus, Type 2; Non-alcoholic Fatty Liver Disease; Adipose Tissue, White; Metabolic Diseases; Cardiovascular Diseases
PubMed: 36728211
DOI: 10.1097/MCO.0000000000000885 -
Danish Medical Journal Dec 2022Recent studies show that incretin hormone analogues effectively control blood glucose while producing major weight losses and reducing the risk of all-cause mortality,...
Recent studies show that incretin hormone analogues effectively control blood glucose while producing major weight losses and reducing the risk of all-cause mortality, myocardial infarction, stroke and kidney function impairment. Furthermore, the risk of dementia and cognitive impairment is reduced. A monomolecular coagonist (tirzepatide) of receptors for both incretin hormones (glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide) produced HbA1c values below 5.7% in 50% of the treated patients and weight losses exceeding 20% in obese individuals. These new agents will radically change our approach to the treatment of T2DM and obesity alike.
Topics: Humans; Blood Glucose; Diabetes Mellitus, Type 2; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Incretins; Metabolic Diseases; Obesity; Weight Loss
PubMed: 36629298
DOI: No ID Found -
Metabolic Brain Disease Mar 2023Schizophrenia (SZ) is a devastating neurodevelopmental disease with an accelerated ageing feature. The criteria of metabolic disease firmly fit with those of... (Review)
Review
Schizophrenia (SZ) is a devastating neurodevelopmental disease with an accelerated ageing feature. The criteria of metabolic disease firmly fit with those of schizophrenia. Disturbances in energy and mitochondria are at the core of complex pathology. Genetic and environmental interaction creates changes in redox, inflammation, and apoptosis. All the factors behind schizophrenia interact in a cycle where it is difficult to discriminate between the cause and the effect. New technology and advances in the multi-dispensary fields could break this cycle in the future.
Topics: Humans; Schizophrenia; Oxidation-Reduction; Aging; Mitochondria; Metabolic Diseases
PubMed: 36656396
DOI: 10.1007/s11011-022-01147-6 -
Therapeutic Advances in Cardiovascular... 2023Cardio-metabolic diseases are the leading causes of premature death worldwide. The conditions are together some of the most prevalent and severe multimorbidities and... (Review)
Review
Cardio-metabolic diseases are the leading causes of premature death worldwide. The conditions are together some of the most prevalent and severe multimorbidities and include conditions such as diabetes, hypertension, coronary heart disease and stroke. People with these conditions are at a higher risk of all-cause death and have a reduction in life expectancy when compared to patients without cardio-metabolic disorders. As a result of the increasing prevalence and impact of cardio-metabolic multimorbidity on disability, no healthcare system can 'treat' its way out of this pandemic. 'Treating our way out' requires the use of multiple medications which can lead to improper prescribing, insufficient compliance, overdosing or underdosing, improper drug choice, insufficient monitoring, unfavourable drug effects, and drug interactions and inappropriate wastes and costs. Therefore, individuals living with these conditions should be empowered to adopt lifestyle changes that foster independent living with their conditions. Adopting these healthy lifestyles such as smoking cessation, improving dietary habits, sleep hygiene and physical activity is a suitable adjunctive measure if not an alternative to polypharmacy in cardio-metabolic multimorbidity.
Topics: Humans; Metabolic Diseases; Life Style; Heart; Healthy Lifestyle; Polypharmacy
PubMed: 37381922
DOI: 10.1177/17539447231177175 -
Biomolecules May 2023It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more... (Review)
Review
It is estimated that, at minimum, 500 million individuals suffer from cellular metabolic dysfunction, such as diabetes mellitus (DM), throughout the world. Even more concerning is the knowledge that metabolic disease is intimately tied to neurodegenerative disorders, affecting both the central and peripheral nervous systems as well as leading to dementia, the seventh leading cause of death. New and innovative therapeutic strategies that address cellular metabolism, apoptosis, autophagy, and pyroptosis, the mechanistic target of rapamycin (mTOR), AMP activated protein kinase (AMPK), growth factor signaling with erythropoietin (EPO), and risk factors such as the apolipoprotein E (APOE-ε4) gene and coronavirus disease 2019 (COVID-19) can offer valuable insights for the clinical care and treatment of neurodegenerative disorders impacted by cellular metabolic disease. Critical insight into and modulation of these complex pathways are required since mTOR signaling pathways, such as AMPK activation, can improve memory retention in Alzheimer's disease (AD) and DM, promote healthy aging, facilitate clearance of β-amyloid (Aß) and tau in the brain, and control inflammation, but also may lead to cognitive loss and long-COVID syndrome through mechanisms that can include oxidative stress, mitochondrial dysfunction, cytokine release, and APOE-ε4 if pathways such as autophagy and other mechanisms of programmed cell death are left unchecked.
Topics: Humans; AMP-Activated Protein Kinases; Post-Acute COVID-19 Syndrome; COVID-19; TOR Serine-Threonine Kinases; Diabetes Mellitus; Alzheimer Disease; Neurodegenerative Diseases; Metabolic Diseases; Brain
PubMed: 37238686
DOI: 10.3390/biom13050816 -
Seminars in Immunopathology Dec 2021We are currently experiencing an enduring global epidemic of obesity and diabetes. It is now understood that chronic low-grade tissue inflammation plays an important... (Review)
Review
We are currently experiencing an enduring global epidemic of obesity and diabetes. It is now understood that chronic low-grade tissue inflammation plays an important role in metabolic disease, brought upon by increased uptake of a so-called Western diet, and a more sedentary lifestyle. Many evolutionarily conserved links exist between metabolism and the immune system, and an imbalance in this system induced by chronic over-nutrition has been termed 'metaflammation'. The complement system is an important and evolutionarily ancient part of innate immunity, but recent work has revealed that complement not only is involved in the recognition of pathogens and induction of inflammation, but also plays important roles in cellular and tissue homeostasis. Complement can therefore contribute both positively and negatively to metabolic control, depending on the nature and anatomical site of its activity. This review will therefore focus on the interactions of complement with mechanisms and tissues relevant for metabolic control, obesity and diabetes.
Topics: Complement System Proteins; Humans; Immunity, Innate; Inflammation; Metabolic Diseases; Obesity
PubMed: 34159399
DOI: 10.1007/s00281-021-00873-w -
Frontiers in Endocrinology 2024The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The... (Review)
Review
The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.
Topics: Humans; Circadian Rhythm; Cardiovascular Diseases; Metabolic Diseases; Diabetes Mellitus, Type 2; Chronobiology Disorders
PubMed: 38742195
DOI: 10.3389/fendo.2024.1328139 -
Molecular Metabolism Sep 2019The prevalence of obesity and metabolic diseases continues to rise globally. The increased consumption of unhealthy energy-rich diets that are high in fat and sugars... (Review)
Review
BACKGROUND
The prevalence of obesity and metabolic diseases continues to rise globally. The increased consumption of unhealthy energy-rich diets that are high in fat and sugars results in oxidative stress and inflammation leading to hypothalamic dysfunction, which has been linked with these diseases. Conversely, diets rich in polyphenols, which are phytochemicals known for their antioxidant and anti-inflammatory properties, are associated with a reduced risk for developing metabolic diseases.
SCOPE OF REVIEW
This review provides an overview of the effects of polyphenols against diet-induced hypothalamic dysfunction with respect to neural inflammation and mitochondrial dysfunction. Results show that polyphenols ameliorate oxidative stress and inflammation within the hypothalamus, thereby improving leptin signaling and mitochondrial biogenesis. Furthermore, they protect against neurodegeneration by decreasing the production of reactive oxygen species and enhancing natural antioxidant defense systems.
MAJOR CONCLUSIONS
The potential of polyphenols as nutraceuticals against hypothalamic inflammation, mitochondrial dysfunction, and neurodegeneration could hold tremendous value. With hypothalamic inflammation increasing naturally with age, the potential to modulate these processes in order to extend longevity is exciting and warrants exploration. The continued escalation of mental health disorders, which are characterized by heightened neuronal inflammation, necessitates the furthered investigation into polyphenol therapeutic usage in this regard.
Topics: Animals; Diet; Dietary Supplements; Humans; Hypothalamus; Inflammation; Metabolic Diseases; Obesity; Polyphenols
PubMed: 31300352
DOI: 10.1016/j.molmet.2019.06.022