Metabolic dysfunction in polycystic ovary syndrome: Pathogenic role of androgen excess and potential therapeutic strategies

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 35, P. 100937 - 100937

Published: Feb. 5, 2020

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among reproductive age women. Although its cardinal manifestations include hyperandrogenism, oligo/anovulation, and/or polycystic ovarian morphology, PCOS women often display also notable metabolic comorbidities. An array of pathogenic mechanisms have been implicated in etiology this heterogeneous endocrine disorder; hyperandrogenism at various developmental periods proposed as a major driver and perturbations associated with PCOS. However, current understanding pathophysiology PCOS-associated disease incomplete, therapeutic strategies used to manage syndrome's complications remain limited.This study systematic review potential etiopathogenic dysfunction frequently PCOS, special emphasis on impact androgen excess different tissues brain. We briefly summarize approaches currently available linked highlighting weaknesses future directions.Androgen plays prominent role development disturbances discernible key peripheral tissues, including adipose, liver, pancreas, muscle, very prominently brain, contributing constellation from obesity insulin resistance. roles underlying largely incomplete. In addition, more efficient, even personalized for management patients persists an unmet need that will certainly benefit better comprehension molecular basis syndrome.

Language: Английский

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Adipokines and Obesity. Potential Link to Metabolic Disorders and Chronic Complications

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(10), P. 3570 - 3570

Published: May 18, 2020

The World Health Organization (WHO) has recognized obesity as one of the top ten threats to human health. It is estimated that number obese and overweight people worldwide exceeds those who are undernourished. Obesity not only a state abnormally increased adipose tissue in body, but also release biologically active adipokines. Adipokines released into circulating blood, due their specific receptors on surface target cells, act classic hormones affecting metabolism tissues organs. What more, adipokines cytokines may decrease insulin sensitivity induce inflammation development chronic complications. Certainly, it can be stated an era global pandemic, gain more importance regards use diagnostic evaluation treatment diseases. An extensive search for materials role white, brown perivascular fatty obesity-related metabolic complications was conducted online using PubMed, Cochrane database Embase.

Language: Английский

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Mechanisms of insulin resistance related to white, beige, and brown adipocytes

Molecular Metabolism, Journal Year: 2020, Volume and Issue: 34, P. 27 - 42

Published: Jan. 7, 2020

The diminished glucose lowering effect of insulin in obesity, called "insulin resistance," is associated with intolerance, type 2 diabetes, and other serious maladies. Many publications on this topic have suggested numerous hypotheses the molecular cellular disruptions that contribute to syndrome. However, significant uncertainty remains mechanisms its initiation long-term maintenance. To simplify resistance analysis, review focuses unifying concept adipose tissue a central regulator systemic homeostasis by controlling liver skeletal muscle metabolism. Key aspects function related reviewed are: 1) modes which specific tissues control hepatic output disposal, 2) recently acquired understanding underlying these regulation, 3) steps pathways adversely affected obesity cause resistance. Adipocyte heterogeneity required mediate multiple tolerance. White adipocytes specialize sequestering triglycerides away from liver, muscle, limit toxicity. In contrast, brown/beige are very active directly taking up response β adrenergic signaling enhancing energy expenditure. Nonetheless, white, beige, brown all share common feature secreting factors possibly exosomes act distant homeostasis. Obesity exerts deleterious effects each adipocyte functions

Language: Английский

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Molecular Mechanisms of Adipogenesis: The Anti-adipogenic Role of AMP-Activated Protein Kinase

Frontiers in Molecular Biosciences, Journal Year: 2020, Volume and Issue: 7

Published: May 8, 2020

Obesity is now a widespread disorder, and its prevalence has become critical concern worldwide, due to association with common co-morbidities like cancer, cardiovascular diseases diabetes.Adipose tissue an endocrine organ therefore plays role in the survival of individual, but dysfunction or excess directly linked obesity.The journey from multipotent mesenchymal stem cells formation mature adipocytes well-orchestrated program which requires expression several genes, their transcriptional factors, signaling intermediates numerous pathways.Understanding all intricacies adipogenesis vital if we are counter current epidemic obesity because limited understanding these main barrier development potent therapeutic strategies against obesity.In particular, AMP-Activated Protein Kinase (AMPK) crucial regulating -it arguably central cellular energy regulation protein body.Since AMPK promotes brown adipose over that white tissue, special attention been given recent years.In this review, describe molecular mechanisms involved adipogenesis, pathways substantial activated inhibition adiposity, concluding observations will support novel chemotherapies epidemics.

Language: Английский

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Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(17), P. 6241 - 6241

Published: Aug. 28, 2020

The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies restore the energy balance. Therefore, concept of activating brown adipose tissue (BAT) in order increase expenditure has been revived. In mammals, two developmentally distinct types adipocytes exist; classical or constitutive BAT that arises during embryogenesis, and beige is recruited postnatally within white (WAT) process called browning. Research recent years significantly increased our understanding mechanisms involved activation WAT They also allowed for identification critical molecules steps both processes and, therefore, many targets. Several non-pharmacological approaches, as well chemical compounds aiming at induction browning activation, have tested vitro animal models genetically determined and/or diet-induced obesity. potential some these humans. this review, we summarize present concepts regarding targets available them.

Language: Английский

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Exercise adaptations: molecular mechanisms and potential targets for therapeutic benefit

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 16(9), P. 495 - 505

Published: July 6, 2020

Language: Английский

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Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases

Nutrition & Metabolism, Journal Year: 2022, Volume and Issue: 19(1)

Published: Sept. 6, 2022

Abstract Adipose tissues are dynamic that play crucial physiological roles in maintaining health and homeostasis. Although white adipose tissue brown currently considered key endocrine organs, they differ functionally morphologically. The existence of the beige or brite adipocytes, cells displaying intermediary characteristics between illustrates plastic nature tissue. These generated through browning, a process associated with augmented non-shivering thermogenesis metabolic capacity. This involves upregulation uncoupling protein 1, molecule uncouples respiratory chain from Adenosine triphosphate synthesis, producing heat. β-3 adrenergic receptor system is one important mediator during cold exposure. Surprisingly, hyperthermia may also induce activation beiging. Physical exercising copes increased levels specific molecules, including Beta-Aminoisobutyric acid, irisin, Fibroblast growth factor 21 (FGF21), which browning. FGF21 stress-responsive hormone interacts beta-klotho. central played by hormones browning highlight relevance individual lifestyle, circadian rhythm diet. Circadian sleep–wake cycle regulated melatonin, UCP1 level upregulation. In contrast to pro-inflammatory disrupting effects western diet, food items, capsaicin n-3 polyunsaturated fatty acids, dietary interventions such as calorie restriction intermittent fasting, favor efficiency. intestinal microbiome has been pictured regulating it modulates bile acid levels, molecules for thermogenic program activation. During embryogenesis, formation affected Bone morphogenetic proteins regulate gene expression, stimuli herein discussed influence an orchestra expression regulators, plethora transcription factors, chromatin remodeling enzymes, non-coding RNAs. Considering detrimental disparities mice humans, further efforts will benefit better understanding plasticity biology its applicability managing overwhelming burden several chronic diseases.

Language: Английский

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Leptin in Leanness and Obesity

Journal of the American College of Cardiology, Journal Year: 2021, Volume and Issue: 77(6), P. 745 - 760

Published: Feb. 1, 2021

Language: Английский

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Hypothalamic control of energy expenditure and thermogenesis

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(4), P. 358 - 369

Published: March 17, 2022

Abstract Energy expenditure and energy intake need to be balanced maintain proper homeostasis. homeostasis is tightly regulated by the central nervous system, hypothalamus primary center for regulation of balance. The exerts its effect through both humoral neuronal mechanisms, each hypothalamic area has a distinct role in expenditure. Recent studies have advanced understanding molecular thermogenesis with targeted manipulation techniques mouse genome function. In this review, we elucidate recent progress mechanism how affects basal metabolism, modulates physical activity, adapts environmental temperature food changes.

Language: Английский

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The Action of Vitamin D in Adipose Tissue: Is There the Link between Vitamin D Deficiency and Adipose Tissue-Related Metabolic Disorders?

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(2), P. 956 - 956

Published: Jan. 16, 2022

Adipose tissue plays an important role in systemic metabolism via the secretion of adipocytokines and storing releasing energy. In obesity, adipose becomes dysfunctional characterized by hypertrophied adipocytes, increased inflammation, hypoxia, decreased angiogenesis. Although is one major stores vitamin D, its deficiency detective obese subjects. presented review, we show how D regulates numerous processes their dysregulation leads to metabolic disorders. The molecular response affects not only energy adipokine anti-inflammatory cytokine production regulation gene expression but also genes participating antioxidant defense, adipocytes differentiation, apoptosis. Thus, disturbs secretion, metabolism, lipid storage, adipogenesis, thermogenesis, oxidative stress balance. Restoring proper functionality overweight or subjects particular importance order reduce risk developing obesity-related complications, such as cardiovascular diseases diabetes. Taking into account results experimental studies, it seemed that may be a remedy for dysfunction, clinical trials are consistent, some them improvement others no effect this on insulin resistance parameters. Therefore, further studies required evaluate beneficial effects especially subjects, due presence volumetric dilution among them.

Language: Английский

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