White adipocyte dysfunction and obesity-associated pathologies in humans

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(4), P. 270 - 289

Published: Dec. 12, 2023

Language: Английский

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New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(11), P. 6218 - 6218

Published: June 5, 2024

Although good glycemic control in patients with type 2 diabetes (T2D) can prevent cardiovascular complications, many diabetic still have poor optimal control. A new class of antidiabetic drugs (e.g., glucagon-like peptide-1-GLP-1 receptor agonists, sodium-glucose co-transporters-SGLT2 inhibitors), addition to the low hypoglycemic effect, exert multiple beneficial effects at a metabolic and level, through mechanisms other than antihyperglycemic agents. This review aims discuss these drugs, highlighting benefits, description their action as well available data by preclinical clinical studies. Moreover, innovative tools T2D field will be described which may help advance towards better targeted personalized care future.

Language: Английский

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Lipid and glucose metabolism in senescence

Frontiers in Nutrition, Journal Year: 2023, Volume and Issue: 10

Published: Aug. 23, 2023

Senescence is an inevitable biological process. Disturbances in glucose and lipid metabolism are essential features of cellular senescence. Given the important roles these types metabolism, we review evidence for how key metabolic enzymes influence senescence senescence-related secretory phenotypes, autophagy, apoptosis, insulin signaling pathways, environmental factors modulate homeostasis. We also discuss alterations abnormal diseases anti-cancer therapies that target through interventions. Our work offers insights developing pharmacological strategies to combat cancer.

Language: Английский

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Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(14), P. 11676 - 11676

Published: July 19, 2023

The adipose organ is involved in many metabolic functions, ranging from the production of endocrine factors to regulation thermogenic processes. Aging a natural process that affects physiology organ, leading disorders, thus strongly impacting healthy aging. Cellular senescence modifies functional aspects tissue, alterations through defective adipogenesis, inflammation, and aberrant adipocytokine production, turn, it triggers systemic inflammation senescence, as well insulin resistance metabolically active tissues, premature declined physiological features. In various aging fat depots, involves multiplicity cell types, including mature adipocytes immune, endothelial, progenitor cells are aging, highlighting their involvement loss flexibility, one common features aging-related disorders. Since mitochondrial stress represents key trigger cellular leads accumulation abnormal mitochondria with impaired dynamics hindered homeostasis, this review focuses on beneficial potential targeting mitochondria, so strategies can be developed manage tissue for treatment age-related

Language: Английский

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Senescent adipocytes and type 2 diabetes – current knowledge and perspective concepts

BioMolecular Concepts, Journal Year: 2024, Volume and Issue: 15(1)

Published: Jan. 1, 2024

Abstract Among civilization diseases, the number of individuals suffering from type 2 diabetes (T2DM) is expected to increase more than a billion in less 20 years, which associated with, e.g., populational aging, poor diet, sedentary lifestyle, genetic predispositions, and immunological factors. T2DM affects many organs characterized by insulin resistance, high glucose levels, adipocyte dysfunction, are related senescence. Although this cellular aging has beneficial biological functions, it can also act unfavorable since senescent adipocytes resist apoptosis, enhance cytokine secretion, downregulate cell identity genes, acquire senescence-associated secretory phenotype that renders oxidative environment. Opposing possible via wide variety senotherapies, including senolytics senomorphics; nevertheless, further research advised expand therapeutic possibilities benefits. Consequences ought be deeply researched include phenotype, chronic inflammation, increasing as well impairment adipogenesis functioning cells. Herein, despite reviewing fat tissue senescence, we summarized latest adipocyte-related anti-diabetes solutions suggested directions.

Language: Английский

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Deep learning and genome-wide association meta-analyses of bone marrow adiposity in the UK Biobank

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

Published: Jan. 2, 2025

Abstract Bone marrow adipose tissue is a distinct subtype comprising more than 10% of fat mass in healthy humans. However, the functions and pathophysiological correlates this are unclear, its genetic determinants remain unknown. Here, we use deep learning to measure bone adiposity femoral head, total hip, diaphysis, spine from MRI scans approximately 47,000 UK Biobank participants, including over 41,000 white 6300 non-white participants. We then establish heritability genome-wide significant associations for at each site. Our meta-GWAS population finds 67, 147, 134, 174 independent single nucleotide polymorphisms, which map 54, 90, 43, 100 genes spine, respectively. Transcriptome-wide association studies, colocalization analyses, sex-stratified meta-GWASes participants further resolve functional sex-specific associated with Finally, perform multi-ancestry identify across different regions ancestry groups. findings provide insights into BMAT formation function basis study impact on human health disease.

Language: Английский

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Treating Metabolic Dysregulation and Senescence by Caloric Restriction: Killing Two Birds with One Stone?

Antioxidants, Journal Year: 2025, Volume and Issue: 14(1), P. 99 - 99

Published: Jan. 16, 2025

Cellular senescence is a state of permanent cell cycle arrest accompanied by metabolic activity and characteristic phenotypic changes. This process crucial for developing age-related diseases, where excessive calorie intake accelerates dysfunction aging. Overnutrition disturbs key pathways, including insulin/insulin-like growth factor signaling (IIS), the mammalian target rapamycin (mTOR), AMP-activated protein kinase. The dysregulation these pathways contributes to insulin resistance, impaired autophagy, exacerbated oxidative stress, mitochondrial dysfunction, further enhancing cellular systemic derangements. On other hand, dysfunctional endothelial cells adipocytes contribute inflammation, reduced nitric oxide production, altered lipid metabolism. Numerous factors, extracellular vesicles, mediate pathological communication between vascular system adipose tissue, amplifying imbalances. Meanwhile, caloric restriction (CR) emerges as potent intervention counteract overnutrition effects, improve function, reduce restore balance. CR modulates such IIS, mTOR, sirtuins, glucose metabolism, reducing promoting autophagy. can extend health span mitigate diseases delaying improving healthy endothelial-adipocyte interactions. review highlights crosstalk adipocytes, emphasizing potential in counteracting overnutrition-induced restoring homeostasis.

Language: Английский

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Molecular bases of adipose tissue aging

Published: Feb. 14, 2025

Aging impacts each and every living organism. In higher organisms, it is an asynchronous process with its onset pace varying among tissue types as well different cell within a tissue. Adipose the largest energy depot in body endocrine organ responsible for metabolic homeostasis. aging marked by fat redistribution, increased visceral reduced subcutaneous observed we age. At molecular level, adipose multifaceted driven diverse mechanisms, involving dysregulated adipogenic pathways, impaired thermogenesis, regeneration, of senescence, emergence inflammation. Dysregulated pathways introduce dysfunction compromising lipid metabolism, leading to complications such insulin resistance diabetes. addition, beige brown further aggravates scenario impacting thermogenesis. Moreover, decline regenerative potential due loss function APSCs limits adipogenesis. Onset senescence disrupts local homeostasis impairing cellular increasing stress. Chronic inflammation extends effects beyond disruption, contributing systemic imbalances. Here, discuss our current understanding mechanisms driving aging, highlighting their implications health. Interventions, as, senolytics, pharmacological modulators, tissue-specific approaches offer promising avenues mitigating aging-related Identifying therapeutic targets clinical translation preserving crucial associated aging.

Language: Английский

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Fasting Mimicking Diet for Metabolic Syndrome: A Narrative Review of Human Studies

Metabolites, Journal Year: 2025, Volume and Issue: 15(3), P. 150 - 150

Published: Feb. 23, 2025

Metabolic syndrome (MetS) is an association of risk factors that share insulin resistance (IR), exerting a super cumulative effect on the developing cardiometabolic diseases. Lifestyle optimization key element in prevention and non-pharmacological therapy MetS. Certain studies have concluded some dietary patterns could be more beneficial as adjunctive treatment for Fasting mimicking diet (FMD) form periodic fasting which caloric intake restricted 5 days each month. It has been studied its effects not only patients with neoplasia neurodegenerative diseases but also IR metabolism. In this narrative review, FMD MetS were analyzed, focusing impact metabolic components summarizing findings from human studies. demonstrated by reducing BMI waist circumference, preserving lean mass, improving profile. Moreover, individuals higher or greater number appear to derive benefits intervention. However, limitations such high dropout rates, small sample sizes, methodological constraints restrict generalizability current findings. Further large-scale are needed confirm these establish viable strategy managing

Language: Английский

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Pathological and Inflammatory Consequences of Aging

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 404 - 404

Published: March 12, 2025

Aging is a complex, progressive, and irreversible biological process that entails numerous structural functional changes in the organism. These affect all bodily systems, reducing their ability to respond adapt environment. Chronic inflammation one of key factors driving development age-related diseases, ultimately causing substantial decline abilities older individuals. This persistent inflammatory state (commonly known as “inflammaging”) characterized by elevated levels pro-inflammatory cytokines, an increase oxidative stress, perturbation immune homeostasis. Several factors, including cellular senescence, contribute this milieu, thereby amplifying conditions such cardiovascular disease, neurodegeneration, metabolic disorders. Exploring mechanisms chronic aging essential for developing targeted interventions aimed at promoting healthy aging. review explains strong connection between inflammation, highlighting potential therapeutic approaches like pharmacological treatments, dietary strategies, lifestyle changes.

Language: Английский

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