Exercise Improves the Cytoskeletal and Metabolic Functions of Brown Adipocytes Through the ADRβ3/COX2-Ywhah Axis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 2978 - 2978

Published: March 25, 2025

Brown adipose tissue (BAT) is a critical target for obesity treatment, and exercise can enhance BAT function through the activation of ADRβ3. However, molecular mechanisms underlying metabolism following exercise-induced ADRβ3 remain unclear. This study utilized RNA sequencing, Western blotting, Oil Red O staining, weighted gene co-expression network analysis (WGCNA), machine learning to investigate role ADRβ3-COX2 pathway in lipid brown adipocytes. We identified Ywhah as key validated our findings using external datasets. Our results demonstrate that significantly enhances mice, with promoting metabolic activity In contrast, COX2 inhibition notably reduced lipolytic effect thermogenic expression induced by activation. WGCNA most important feature variable downstream signaling pathway. External microarray data further confirmed 8 weeks aerobic upregulated expression. Additionally, displayed strong binding affinity cytoskeletal proteins purification-mass spectrometry experiments, its was highly correlated GSVA scores. summary, this reveals potential ADRβ3-COX2-Ywhah-cytoskeleton axis regulating adipocyte metabolism, providing new insights into treatment mechanisms.

Language: Английский

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(+)-Terrein exerts anti-obesity and anti-diabcetic effects by regulating the differentiation and thermogenesis of brown adipocytes in mice fed a high-fat diet

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 186, P. 118030 - 118030

Published: April 8, 2025

Language: Английский

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Obesity: pathophysiology and therapeutic interventions

Molecular Biomedicine, Journal Year: 2025, Volume and Issue: 6(1)

Published: April 25, 2025

Abstract Over the past few decades, obesity has transitioned from a localized health concern to pressing global public crisis affecting over 650 million adults globally, as documented by WHO epidemiological surveys. As chronic metabolic disorder characterized pathological adipose tissue expansion, inflammation, and neuroendocrine dysregulation that disrupts systemic homeostasis impairs physiological functions, is rarely an isolated condition; rather, it frequently complicated severe comorbidities collectively elevate mortality risks. Despite advances in nutritional science initiatives, sustained weight management success rates prevention remain limited, underscoring its recognition multifactorial disease influenced genetic, environmental, behavioral determinants. Notably, escalating prevalence of earlier onset younger populations have intensified urgency develop novel therapeutic agents simultaneously ensure efficacy safety. This review aims elucidate pathophysiological mechanisms underlying obesity, analyze major complications—including type 2 diabetes mellitus (T2DM), cardiovascular diseases (CVD), non-alcoholic fatty liver (NAFLD), obesity-related respiratory disorders, nephropathy (ORN), musculoskeletal impairments, malignancies, psychological comorbidities—and critically evaluate current anti-obesity strategies. Particular emphasis placed on emerging pharmacological interventions, exemplified plant-derived natural compounds such berberine (BBR), with focus their molecular mechanisms, clinical efficacy, advantages. By integrating mechanistic insights evidence, this seeks provide innovative perspectives for developing safe, accessible, effective treatments.

Language: Английский

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Human miR-1 Stimulates Metabolic and Thermogenic-Related Genes in Adipocytes

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 276 - 276

Published: Dec. 31, 2024

MicroRNAs play a pivotal role in the regulation of adipose tissue function and have emerged as promising therapeutic candidates for management obesity associated comorbidities. Among them, miR-1 could be potential biomarker metabolic diseases contribute to homeostasis. However, thorough research is required fully elucidate impact on human adipocyte thermogenesis metabolism. This study aimed explore effect browning, process whose activation has been linked protection counteraction. Human multipotent adipose-derived stem cells, hMADS were differentiated into white brown-like adipocytes transfected with mimics gene expression western blotting analyses. inhibited its previously validated target PTK9/TWF1 modulated profile key genes involved browning (increased UCP1 at mRNA protein level, increased CPT1M, decreased HIF3A), differentiation metabolism (decreased PLIN1, FASN, RXRA, PPARG, FABP4, MAPKAPK2), well related cytoskeleton ACTB) extracellular matrix COL1A1). These findings suggest that can modulate metabolism, which hold value eventual obesity.

Language: Английский

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Effect of Diet on HDL in Obesity

Molecules, Journal Year: 2024, Volume and Issue: 29(24), P. 5955 - 5955

Published: Dec. 17, 2024

Alterations of plasma lipoprotein levels and oxidative stress are frequently observed in obese patients, including low high-density (HDL) cholesterol (HDL-C) alterations HDL composition. Dysfunctional with lower antioxidant anti-inflammatory properties have also been demonstrated obesity. There is increasing evidence that white adipose tissue (WAT) participates several metabolic activities modulates HDL-C function. In subjects, the changes morphology function lead to impaired regulatory associated a state low-grade chronic inflammation, increased release pro-inflammatory adipokines cytokines. These may affect metabolism functions; thus, considered potential target for prevention treatment A cornerstone obesity therapy lifestyle modification through dietary changes, which reflected modulation metabolism. Some components metabolites directly composition structure modulate its vasoprotective properties. The aims review summarize crosstalk between adipocytes dysfunction human highlight recent discoveries on beneficial patterns as well nutritional inflammation

Language: Английский

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Sexual dimorphism in the effects of maternal adipose tissue growth hormone receptor deficiency on offspring metabolic health

Biology of Sex Differences, Journal Year: 2024, Volume and Issue: 15(1)

Published: Dec. 2, 2024

Abstract Background The global incidence of obesity continues to rise, which increases the prevalence metabolic diseases. We previously demonstrated beneficial effect adipose-specific growth hormone receptor ( Ghr ) knockout (KO) on parameters in male mice exposed high fat diet. Although (GH) axis lipid metabolism has been well studied, sexual dimorphism not considered. Furthermore, effects GH intergenerational adipose development are understudied. present study aimed evaluate whether is associated with sex-specific differences health female offspring. Methods flox/flox (LL) were crossed Adipoq-Cre generate mice. Physiological phenotype and fertility LL KO measured. Body weight, organ glucose homeostasis, liver histology, hepatic triglycerides (TG) content, serum TG low-density lipoprotein cholesterol (LDL-C) levels offspring detected. Results found an increase adipocyte size mice, but no change tolerance or insulin sensitivity. Adipose-specific deficiency impairs Maternal had a considerable protected against diet-induced degree steatosis hyperlipidemia was reduced. did significantly despite decrease weight. phenotypes fostered by mothers differed from those remaining maternal nest. Conclusions findings our suggest that plays complex important role adipocytes manner. Future studies needed reveal mechanisms these sexually dimorphic feasibility providing new interventions for improving health.

Language: Английский

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Phytoreduced gold nanoparticles from vitalmelon promote white adipocyte browning in murine cells by targeting phospholipase D2

Journal of Photochemistry and Photobiology, Journal Year: 2024, Volume and Issue: 25, P. 100254 - 100254

Published: Dec. 10, 2024

Language: Английский

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A Comprehensive Atlas of Multi-Tissue Metabolome and Microbiome Shifts: Exploring Obesity and Insulin Resistance Induced by Perinatal Bisphenol S Exposure in High-Fat Diet-Fed Offspring

Journal of Hazardous Materials, Journal Year: 2024, Volume and Issue: 485, P. 136895 - 136895

Published: Dec. 15, 2024

Language: Английский

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