Interleukin 6 as an energy allocator in muscle tissue

Nature Metabolism, Journal Year: 2022, Volume and Issue: 4(2), P. 170 - 179

Published: Feb. 24, 2022

Language: Английский

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Adipose Tissue and Metabolic Health

Diabetes & Metabolism Journal, Journal Year: 2023, Volume and Issue: 47(5), P. 595 - 611

Published: Sept. 26, 2023

In this review, we provide a brief synopsis of the connections between adipose tissue and metabolic health highlight some recent developments in understanding exploiting adipocyte biology. Adipose plays critical roles regulation systemic glucose lipid metabolism secretes bioactive molecules possessing endocrine, paracrine, autocrine functions. Dysfunctional has detrimental impact on is intimately involved key aspects diseases such as insulin resistance, overload, inflammation, organelle stress. Differences distribution fat depots characteristics relate to divergent degrees dysfunction found metabolically healthy unhealthy obese individuals. Thermogenic adipocytes increase energy expenditure via mitochondrial uncoupling or adenosine triphosphate-consuming futile substrate cycles, while functioning sink participating crosstalk with other organs. Manipulation provides wealth opportunities intervene combat progression associated diseases. We discuss current treatment modalities for obesity including incretin hormone analogs touch upon emerging strategies therapeutic potential exosome-based therapy, pharmacological activation brown beige thermogenesis, administration inhibition adipocyte-derived factors.

Language: Английский

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The Metabolic Syndrome, a Human Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2251 - 2251

Published: Feb. 13, 2024

This review focuses on the question of metabolic syndrome (MS) being a complex, but essentially monophyletic, galaxy associated diseases/disorders, or just related rather independent pathologies. The human nature MS (its exceptionality in Nature and its close interdependence with action evolution) is presented discussed. text also describes components, special emphasis description their interrelations (including syndromic development recruitment), as well consequences upon energy handling partition. main theories MS’s origin are relation to hepatic steatosis, type 2 diabetes, obesity, encompass most components described so far. differential effects sex biological considered under light social needs evolution, which directly epidemiology, severity, relations senescence. triggering maintenance factors discussed, especial inflammation, complex process affecting different levels organization critical element for development. Inflammation operation connective tissue adipose organ) widely studied acknowledged influence diet. role diet composition, including transcendence anaplerotic Krebs cycle from dietary amino acid supply (and timing), developed context testosterone β-estradiol control insulin-glycaemia core system carbohydrate-triacylglycerol handling. high probability acting unique (essentially monophyletic) presented, together additional perspectives/considerations treatment this ‘very’ disease.

Language: Английский

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β-Adrenergic Receptors and Adipose Tissue Metabolism: Evolution of an Old Story

Annual Review of Physiology, Journal Year: 2022, Volume and Issue: 84(1), P. 1 - 16

Published: Feb. 10, 2022

The role of β-adrenergic receptors (βARs) in adipose tissue to promote lipolysis and the release fatty acids nonshivering thermogenesis brown fat has been studied for so many decades that one would think there is nothing left discover. With rediscovery humans renewed interest UCP1 uncoupled mitochondrial respiration, it seems a review as an organ, pivotal observations, investigators who made them be instructive understanding where field stands now. discovery β 3 -adrenergic receptor was important accurately defining pharmacology adipocyte, while clinical targeting this obesity metabolic disease had its highs lows. Many questions still remain about how βARs regulate adipocyte metabolism signaling molecules through which they do it.

Language: Английский

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Pharmacological Support for the Treatment of Obesity—Present and Future

Healthcare, Journal Year: 2023, Volume and Issue: 11(3), P. 433 - 433

Published: Feb. 2, 2023

Obesity is a growing civilization problem, associated with number of negative health consequences affecting almost all tissues and organs. Currently, obesity treatment includes lifestyle modifications (including diet exercise), pharmacologic therapies, in some clinical situations, bariatric surgery. These treatments seem to be the most effective method supporting obesity. However, they are many limitations options, both for practitioners patients. Often comorbidities, cost, age patient, even geographic locations may influence choices. The pharmacotherapy fast-growing market. we have at our disposal drugs various mechanisms action (directly reducing absorption calories-orlistat, acting centrally-bupropion naltrexone, phentermine topiramate, or multidirectional-liraglutide, dulaglutide, semaglutide). whose weight-reducing effect used course other diseases (e.g., glucose-sodium cotransporter inhibitors, exenatide) also worth mentioning. focusing on novel therapeutic agents improved safety efficacy profiles. trends include an assessment usefulness properties previously diseases. presented paper overview studies related currently those undergoing trials, taking into account individual approach patient.

Language: Английский

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Nitric Oxide Signaling and Regulation in the Cardiovascular System: Recent Advances

Pharmacological Reviews, Journal Year: 2024, Volume and Issue: 76(6), P. 1038 - 1062

Published: June 12, 2024

Nitric oxide (NO) from endothelial NO synthase (eNOS) importantly contributes to vascular homeostasis. Reduced production or increased scavenging during disease conditions with oxidative stress contribute dysfunction and deficiency. In addition the classical enzymatic NOS system, can also be generated via nitrate-nitrite-NO pathway. Dietary pharmacological approaches aimed at increasing bioactivity, especially in cardiovascular have been focus of much research since discovery this small gaseous signaling molecule. Despite wide appreciation biological role NOS/NO signaling, questions still remain about chemical nature NOS-derived bioactivity. Recent studies show that NO-like bioactivity efficiently transduced by mobile NO-ferroheme species which transfer between proteins, partition into a hydrophobic phase, directly activate sGC-cGMP-PKG pathway without intermediacy free NO. Moreover, interaction red blood cells endothelium regulation homeostasis gained attention, cardiometabolic disease. review we discuss both non-classical pathways for generation how these modulated therapeutic purposes. Significance Statement After four decades intensive research, persist transduction control Here health disease, highlighting new findings, such as important Non-classical modes, like pathway, opportunities related system are discussed. Existing potential treatments/strategies, well dietary components influencing covered.

Language: Английский

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Genetic evidence for involvement of β2-adrenergic receptor in brown adipose tissue thermogenesis in humans

International Journal of Obesity, Journal Year: 2024, Volume and Issue: 48(8), P. 1110 - 1117

Published: April 17, 2024

Sympathetic activation of brown adipose tissue (BAT) thermogenesis can ameliorate obesity and related metabolic abnormalities. However, crucial subtypes the β-adrenergic receptor (AR), as well effects its genetic variants on functions BAT, remains unclear in humans. We conducted association analyses genes encoding β-ARs BAT activity human adults.

Language: Английский

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Obesity‐induced tissue alterations resist weight loss: A mechanistic review

Diabetes Obesity and Metabolism, Journal Year: 2024, Volume and Issue: 26(8), P. 3045 - 3057

Published: May 8, 2024

Abstract Interventions aimed at weight control often have limited effectiveness in combating obesity. This review explores how obesity‐induced dysfunction white (WAT) and brown adipose tissue (BAT), skeletal muscle, the brain blunt loss, leading to retention of stored fat. In obesity, increased adrenergic stimulation inflammation downregulate β‐adrenoreceptors impair catecholaminergic signalling adipocytes. disrupts adrenergic‐mediated lipolysis, diminishing lipid oxidation both adipocytes, lowering thermogenesis blunting fat loss. Emerging evidence suggests that WAT fibrosis is associated with worse loss outcomes; indeed, limiting collagen laminin‐α4 deposition mitigates accumulation, enhances browning, protects against high‐fat‐diet‐induced Obesity compromises mitochondrial oxidative capacity impairing its ability switch between glucose metabolism response varying nutrient levels exercise. dysfunctional phenotype muscle exacerbated presence obesity‐associated sarcopenia. Additionally, obesity suppresses sarcolipin‐induced sarcoplasmic reticulum calcium ATPase (SERCA) activation, resulting reduced capacity, diminished energy expenditure, adiposity. hypothalamus, overnutrition insulin leptin signalling. blunts central satiety signals, favouring a shift balance toward conservation body retention. Moreover, obese animals humans demonstrate impaired dopaminergic responses intake striatum, which tend persist after may result enduring inclinations overeating sedentary lifestyle. Collectively, adaptations described pose significant challenges effectively achieving sustaining

Language: Английский

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Absence of MCJ/DnaJC15 promotes brown adipose tissue thermogenesis

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 13, 2025

Obesity poses a global health challenge, demanding deeper understanding of adipose tissue (AT) and its mitochondria. This study describes the role mitochondrial protein Methylation-controlled J (MCJ/DnaJC15) in orchestrating brown (BAT) thermogenesis. Here we show how MCJ expression decreases during obesity, as evident human mouse samples. MCJKO mice, even without UCP1, fundamental thermogenic protein, exhibit elevated BAT Electron microscopy unveils changes morphology resembling activation. Proteomic analysis confirms these findings suggests involvement eIF2α mediated stress response. The pivotal is scrutinized by vivo CRISPR deletion abrogating These uncover importance regulator thermogenesis, presenting it promising target for obesity therapy. How mitochondria activity fine-tuned response to an active area study. Here, authors that can block thermogenesis silencing this gene correct obesity-related comorbidities.

Language: Английский

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G-Protein-Coupled Receptor (GPCR) Signaling and Pharmacology in Metabolism: Physiology, Mechanisms, and Therapeutic Potential

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 291 - 291

Published: Feb. 15, 2025

G-protein coupled receptors (GPCRs), the largest family of integral membrane proteins, enable cells to sense and appropriately respond environment through mediating extracellular signaling intercellular messenger molecules. GPCRs' pairing with a diverse array G protein subunits related downstream secondary messengers, combined their ligand versatility-from conventional peptide hormone numerous bioactive metabolites, allow GPCRs comprehensively regulate metabolism physiology. Consequently, have garnered significant attention for therapeutic potential in metabolic diseases. This review focuses on six GPCRs, GPR40, GPR120, GLP-1R, ß-adrenergic (ADRB1, ADRB2, ADRB3), GLP-1R recognized as prominent regulator system-level metabolism, while roles GPR120 central carbon energy homeostasis are increasingly appreciated. Here, we discuss physiological functions current pharmacological landscape, intricacies pathways via ß-arrestin activation. Additionally, limitations existing GPCR-targeted strategies treating diseases offer insights into future perspectives advancing GPCR pharmacology.

Language: Английский

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