White adipocyte dysfunction and obesity-associated pathologies in humans

Nature Reviews Molecular Cell Biology, Год журнала: 2023, Номер 25(4), С. 270 - 289

Опубликована: Дек. 12, 2023

Язык: Английский

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Lipid and glucose metabolism in senescence

Frontiers in Nutrition, Год журнала: 2023, Номер 10

Опубликована: Авг. 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.

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 6218 - 6218

Опубликована: Июнь 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.

Язык: Английский

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Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(14), С. 11676 - 11676

Опубликована: Июль 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

Язык: Английский

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Beyond Inflammaging: The Impact of Immune System Aging on Age-Related Muscle Decline, Results From the InCHIANTI Study

The Journals of Gerontology Series A, Год журнала: 2023, Номер 79(2)

Опубликована: Окт. 5, 2023

Abstract Aging is characterized by chronic low-level inflammation and associated with geriatric syndromes such as sarcopenia frailty. Our aim was to evaluate the longitudinal variation of muscle area, quality, strength, relative leukocyte-derived markers, assess presence a pathway associations among derived leukocyte ratios, components health. The InCHIANTI cohort study aging that began in 1998 follow-up visits every 3 years. Out 1 453 participants enrolled at baseline, this includes 179 complete data. Muscle strength assessed hand grip test, whereas density fat area were considered indirect markers from peripheral quantitative computed tomography calf. neutrophil-to-lymphocyte ratio (NL-ratio), age, gender, comorbidities, body mass index (BMI). over time inversely BMI, while being positively monocyte-to-lymphocyte (ML-ratio) male gender. Fat interleukine-6 (IL-6), NL-ratio, ML-ratio, BMI. Handgrip decreased IL-6 levels, but increased male, having higher In path-analysis model, ML-ratio correlates mass, density, NL-ratio only density. are may be implicated age-related mechanisms affect composition strength. These ratios represent link between immune system decline health aging. However, further studies needed identify their usefulness for early detection sarcopenia, myosteatosis, frailty older adult.

Язык: Английский

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

BioMolecular Concepts, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 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.

Язык: Английский

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DNA damage, obesity and obesity-related health complications: what are new data telling us?

Current Opinion in Clinical Nutrition & Metabolic Care, Год журнала: 2024, Номер 27(4), С. 325 - 330

Опубликована: Апрель 19, 2024

Obesity is associated with increased DNA damage, which may in turn contribute to the development of obesity-related complications. damage can also affect adipocyte biology, resulting adiposity. Carefully managed weight loss programs reverse this process. This article surveys new data that support these contentions.

Язык: Английский

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Metabolic syndrome-associated murine aortic wall stiffening is associated with premature elastic fibers aging

AJP Cell Physiology, Год журнала: 2024, Номер 327(3), С. C698 - C715

Опубликована: Июль 1, 2024

Type 2 diabetes (T2D) constitutes a major public health problem, and despite prevention efforts, this pandemic disease is one of the deadliest diseases in world. In 2022, 6.7 million patients with T2D died prematurely from vascular complications. Indeed, increases risk myocardial infarction or stroke eightfold. The identification molecular factors involved occurrence cardiovascular complications their are therefore axes. Our hypothesis that brought into play during physiological aging appear progression. study focused on extracellular matrix (ECM), element maintenance homeostasis. We characterized morphological functional aspects aorta, focus collagen elastic fibers diabetic mice aged 6 mo to nondiabetic 20 mo. comparison two models (young old) highlighted an exacerbated activity proteases, which could explain disturbance accumulation excessive degradation fibers. Moreover, generation circulating elastin-derived peptides reflects premature ECM. These elements contribute appearance rigidity, often origin pathologies such as hypertension atherosclerosis. conclusion, we show present same characteristics ECM wear those observed This accelerated aortic wall remodeling then early onset and, therefore, death T2D.

Язык: Английский

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Cathelicidin: Insights into Its Impact on Metabolic Syndrome and Chronic Inflammation

Metabolites, Год журнала: 2024, Номер 14(12), С. 672 - 672

Опубликована: Дек. 2, 2024

Background/Objectives: LL-37 is associated with metabolic syndrome (MetS), a constellation of risk factors comprising obesity, insulin resistance (IR), dyslipidemia, and hypertension, which elevates the cardiovascular disease type 2 diabetes. Methods: In this narrative review, we analyzed literature focusing on recent developments in relationship between cathelicidin various components MetS to provide comprehensive overview. Results: Studies have shown that linked inflammation adipose tissue (AT) development IR obesity. Cathelicidin can enhance by activating pro-inflammatory genes, as well modulate inflammatory response. The mechanisms include activation complex signaling pathways induce reduce adipocytes. Toll-like receptors (TLRs) stimulates secretion cytokines, contributing disruption function cells. also influences lipid metabolism, research showing negative levels HDL cholesterol. Therefore, involved not only regulation but potentially aggravating complications MetS. Conclusions: plays crucial role regulating balance anti-inflammatory responses Understanding impact these may unveil novel approaches for addressing its complications.

Язык: Английский

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

Nature Communications, Год журнала: 2025, Номер 16(1)

Опубликована: Янв. 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.

Язык: Английский

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