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World Journal of Gastroenterology Dec 2022Bile acids (BAs) serve as physiological detergents that enable the intestinal absorption and transportation of nutrients, lipids and vitamins. BAs are primarily produced... (Review)
Review
Bile acids (BAs) serve as physiological detergents that enable the intestinal absorption and transportation of nutrients, lipids and vitamins. BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism, microbiota habitat regulation and cell signaling. BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy, lipid, glucose, and drug metabolism. The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism. Therefore, altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes, such as diabetes mellitus, obesity/hypercholesterolemia, and cardiovascular diseases. BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases. This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases. Moreover, we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders. Finally, we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.
Topics: Humans; Bile Acids and Salts; Obesity; Signal Transduction; Metabolic Diseases; Glucose
PubMed: 36632317
DOI: 10.3748/wjg.v28.i48.6846 -
Cell Metabolism Oct 2017In anticipation of our upcoming Cell Symposium on Metabolic Disease Therapies in San Diego, CA, on October 15-17 (http://cell-symposia.com/metabolic-therapies-2017/),...
In anticipation of our upcoming Cell Symposium on Metabolic Disease Therapies in San Diego, CA, on October 15-17 (http://cell-symposia.com/metabolic-therapies-2017/), the speakers and organizers share their perspectives on why now, more than ever, cutting-edge research is needed to support effective therapies to combat metabolic disease.
Topics: Animals; Biomedical Research; Brain; Glucose; Hormones; Humans; Inflammation; Metabolic Diseases; Mitochondria; Mitochondrial Dynamics
PubMed: 28978419
DOI: 10.1016/j.cmet.2017.09.017 -
The FEBS Journal Jun 2021The word 'metabolism' is derived from the Greek word μεταβολή (metabolē), denoting 'change'. True to this definition, it is now appreciated that a cell or...
The word 'metabolism' is derived from the Greek word μεταβολή (metabolē), denoting 'change'. True to this definition, it is now appreciated that a cell or tissue cannot change its behaviour without altering its metabolism. Hence, most key cell decision-making processes are tightly coupled to metabolic change. Conversely, perturbations in metabolite abundance or flux can alter cellular (and whole-body) function profoundly, giving rise to disease. This Special Issue on Systemic and Cellular Metabolism and Disease provides an integrative perspective on the importance of metabolism for health and disease alike. Spanning several orders of scale (from metabolites, proteins, organelles, organs/tissues and whole-body physiology), these review articles cover a breadth of topics, including the importance of metabolites as signalling regulators, metabolic disease, immunity, organelle function/dysfunction, ageing and neurodegenerative disease. One of the emergent themes is that just as metabolism is the fulcrum of biology, metabolic perturbances underpin most forms of acute, chronic, infectious and non-infectious human disease; ageing and senescence could be similarly viewed. Arguably most diseases are metabolic diseases; hence, modulating metabolism may help to 'change' disease outcomes.
Topics: AMP-Activated Protein Kinases; Adipose Tissue, Brown; Aging; Animals; Gene Expression Regulation; Humans; Interferon Regulatory Factors; Metabolic Diseases; Metabolic Networks and Pathways; Mitochondria; Neoplasms; Neurodegenerative Diseases; RNA, Circular; Signal Transduction
PubMed: 34152675
DOI: 10.1111/febs.16033 -
Journal of Immunology (Baltimore, Md. :... Oct 2021Metabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the... (Review)
Review
Metabolic diseases are common worldwide and include diseases of overnutrition, such as obesity, or undernutrition, such as kwashiorkor. Both the immune system and the microbiota contribute to a variety of metabolic diseases; however, these two processes have largely been studied independently of one another in this context. The gastrointestinal system houses the greatest density of microbes but also houses one of the largest collections of immune molecules, especially Abs. The IgA isotype dominates the Ab landscape at mucosal sites, and a number of studies have demonstrated the importance of this Ab to the stability of the microbiota. In this article, we review the literature that demonstrates how homeostatic Ab responses control microbiota composition and function to influence metabolic disease. We propose that many metabolic diseases may arise from disruptions to homeostatic immune control of gut commensals and that further understanding this interaction can offer a novel opportunity for therapeutic interventions.
Topics: Animals; Dysbiosis; Host Microbial Interactions; Humans; Immunity, Mucosal; Immunoglobulin A; Immunomodulation; Metabolic Diseases; Microbiota; Mucous Membrane
PubMed: 34544814
DOI: 10.4049/jimmunol.2100419 -
Diabetologia Dec 2019Extracellular vesicles (EVs) are submicron-sized lipid envelopes that are produced and released from a parent cell and can be taken up by a recipient cell. EVs are... (Review)
Review
Extracellular vesicles (EVs) are submicron-sized lipid envelopes that are produced and released from a parent cell and can be taken up by a recipient cell. EVs are capable of mediating cellular signalling by carrying nucleic acids, proteins, lipids and cellular metabolites between cells and organs. Metabolic dysfunction is associated with changes in plasma concentrations of EVs as well as alterations in their EV cargo. Since EVs can act as messengers between parent and recipient cells, they could be involved in cell-to-cell and organ-to-organ communication in metabolic diseases. Recent literature has shown that EVs are produced by cells within metabolic tissues, such as adipose tissue, pancreas, muscle and liver. These vesicles have therefore been proposed as a novel intercellular communication mode in systemic metabolic regulation. In this review, we will describe and discuss the current literature that investigates the role of adipose-derived EVs in the regulation of obesity-associated metabolic disease. We will particularly focus on the EV-dependent communication between adipocytes, the vasculature and immune cells in type 2 diabetes.
Topics: Adipocytes; Cell Communication; Diabetes Mellitus, Type 2; Exosomes; Extracellular Vesicles; Humans; Macrophages; Metabolic Diseases
PubMed: 31690986
DOI: 10.1007/s00125-019-05014-5 -
Trends in Endocrinology and Metabolism:... May 2018Human stem cell-based models of thermogenic adipocytes provide an opportunity for the establishment of new therapeutics, modeling of disease mechanisms, and... (Review)
Review
Human stem cell-based models of thermogenic adipocytes provide an opportunity for the establishment of new therapeutics, modeling of disease mechanisms, and understanding of development. Pluripotent stem cells, adipose-derived stem cells/preadipocytes, and programming-reprogramming-based approaches have been used to develop cell-based platforms for drug screening and transplantable therapeutics in the metabolic disease arena. Here we provide a detailed overview of these approaches, the latest advances in this field, and the opportunities and shortcomings they present. Moreover, we comment on how stem-cell-based platforms can be best utilized in the future for the treatment and understanding of metabolic diseases, including type 2 diabetes and associated medical issues such as obesity.
Topics: Adipose Tissue, Beige; Adipose Tissue, Brown; Animals; Diabetes Mellitus, Type 2; Humans; Metabolic Diseases; Pluripotent Stem Cells
PubMed: 29606342
DOI: 10.1016/j.tem.2018.03.002 -
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 -
Biochemical Pharmacology Nov 2021Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular... (Review)
Review
Herein we trace links between biochemical pathways, pathogenesis, and metabolic diseases to set the stage for new therapeutic advances. Cellular and acellular microorganisms including bacteria and viruses are primary pathogenic drivers that cause disease. Missing from this statement are subcellular compartments, importantly mitochondria, which can be pathogenic by themselves, also serving as key metabolic disease intermediaries. The breakdown of food molecules provides chemical energy to power cellular processes, with mitochondria as powerhouses and ATP as the principal energy carrying molecule. Most animal cell ATP is produced by mitochondrial synthase; its central role in metabolism has been known for >80 years. Metabolic disorders involving many organ systems are prevalent in all age groups. Progressive pathogenic mitochondrial dysfunction is a hallmark of genetic mitochondrial diseases, the most common phenotypic expression of inherited metabolic disorders. Confluent genetic, metabolic, and mitochondrial axes surface in diabetes, heart failure, neurodegenerative disease, and even in the ongoing coronavirus pandemic.
Topics: Animals; COVID-19; Diet, Healthy; Energy Metabolism; Humans; Metabolic Diseases; Mitochondria; Mitochondrial Diseases; Neurodegenerative Diseases; Oxidative Stress
PubMed: 34673016
DOI: 10.1016/j.bcp.2021.114809 -
Molecular Metabolism Sep 2019Metabolic diseases represent a wide category of alterations affecting metabolism. These pathologies are notably marked by inflammation that implicates the immune system.... (Review)
Review
BACKGROUND
Metabolic diseases represent a wide category of alterations affecting metabolism. These pathologies are notably marked by inflammation that implicates the immune system. Mucosal Associated Invariant (MAI)T cells are immune cells expressing a semi-invariant TCR able to recognize bacterial and fungal vitamin B metabolites. MAIT cells can promote inflammation and are present in many organs central to metabolism, suggesting a role in the etiopathology of these diseases.
SCOPE OF THE REVIEW
Here, we will review what is known of the involvement of MAIT cells in metabolic pathologies in humans and mice.
MAJOR CONCLUSIONS
MAIT cells are severely affected, overactivated with a frequency reduction and a phenotype shift from protective to deleterious. Therefore, they might be a novel target to treat, in particular, pancreas and liver metabolic diseases.
Topics: Animals; Humans; Inflammation; Metabolic Diseases; Mucosal-Associated Invariant T Cells
PubMed: 31500822
DOI: 10.1016/j.molmet.2019.06.025 -
Open Biology Dec 2020Adipose, or fat, tissue (AT) was once considered an inert tissue that primarily existed to store lipids, and was not historically recognized as an important organ in the... (Review)
Review
Adipose, or fat, tissue (AT) was once considered an inert tissue that primarily existed to store lipids, and was not historically recognized as an important organ in the regulation and maintenance of health. With the rise of obesity and more rigorous research, AT is now recognized as a highly complex metabolic organ involved in a host of important physiological functions, including glucose homeostasis and a multitude of endocrine capabilities. AT dysfunction has been implicated in several disease states, most notably obesity, metabolic syndrome and type 2 diabetes. The study of AT has provided useful insight in developing strategies to combat these highly prevalent metabolic diseases. This review highlights the major functions of adipose tissue and the consequences that can occur when disruption of these functions leads to systemic metabolic dysfunction.
Topics: Adipocytes; Adipose Tissue; Animals; Biomarkers; Disease Susceptibility; Energy Metabolism; Exosomes; Extracellular Space; Homeostasis; Humans; Insulin Resistance; Lipolysis; Metabolic Diseases; Obesity; Organogenesis
PubMed: 33292104
DOI: 10.1098/rsob.200291