Search Results (6,366)

Background/Objectives: Lipedema is a chronic, progressive disorder of the adipo-fascial tissue characterized by abnormal subcutaneous fat accumulation, inflammation, fibrosis, pain, and edema. Despite its considerable impact on patients’ quality of life, it remains underdiagnosed. Recent studies have suggested a potential overlap between lipedema and hypermobility spectrum disorders (HSDs), both involving connective tissue dysfunction. This work explores the shared pathophysiological features of lipedema and HSD, highlighting clinical correlations, comorbidities, and the need for integrated diagnostic and therapeutic approaches. Methods: A cross-sectional observational study was conducted through an online survey targeting individuals with lipedema and a control group with lymphedema. The questionnaire assessed symptoms typically associated with HSD, including musculoskeletal, gastrointestinal, urogynecological, vascular, and neuropsychological manifestations. Descriptive statistics were used to evaluate clinical patterns in both groups. Results: Among the lipedema patients, 44% reported joint hypermobility and 60% recalled being hypermobile during childhood. High rates of pediatric overweight (50%), low muscle tone (55%), and exercise-induced fatigue (70%) were observed. Adult symptoms included joint pain (notably in the ankles, knees, cervical spine, sacrum, and feet), digestive issues (50%), and thyroid disorders (24.4%). Compared with the control group, patients with lipedema showed significantly more connective tissue-related motor deficits and systemic symptoms. Conclusions: Connective tissue laxity may play a critical role in the pathogenesis of lipedema, contributing to multisystemic manifestations through vascular, lymphatic, gastrointestinal, and musculoskeletal involvement. The high prevalence of HSD-like features calls for a paradigm shift in the understanding of lipedema as a systemic disorder. Early identification of connective tissue alterations, especially in children with familial predisposition, could enable timely interventions, potentially mitigating disease progression. A multidisciplinary, evidence-based approach is essential for accurate diagnosis and effective management. Full article

Decellularized extracellular matrix (dECM) scaffolds preserve native tissue structure and biochemical cues while minimizing immune responses, creating biomimetic templates that promote cell integration and tissue remodeling. This review examines the current state of dECM research, encompassing decellularization methods, scaffold quality evaluation assays, and tissue-specific applications across dermis, nerve, heart, lung, adipose, and placental ECMs. We analyze commercially available dECM products and ongoing clinical trials, while highlighting recent advances including 3D bioprinting and the integration of dECM with stem cells and growth factors. Despite these promising developments, several challenges continue to limit broader clinical translation: protocol standardization, residual immunogenicity, mechanical durability, and regulatory, manufacturing, and cost barriers. To address these limitations, we outline future directions focusing on patient-specific scaffolds, scalable bioprocessing, and integrated biofabrication strategies that will enable the development of safe and effective dECM-based therapies. Full article

Background/Objectives: Ketogenic diets (KDs), defined by very low carbohydrate and high fat content, are widely studied for obesity and metabolic disease. However, KD formulations vary from 60–95% fat, leading to inconsistent induction of ketogenesis and variable outcomes. The fat threshold required for sustained ketosis, and the tissue-specific programs that mediate KD efficacy, remain unclear. Methods: We evaluated multiple KD formulations (80–95% fat) in C57BL/6J wild-type (WT) and diet-induced obese (DIO) mice. Plasma, hepatic, and intestinal β-hydroxybutyrate (BHB) were measured together with expression of ketogenesis and fatty acid oxidation genes. Body weight, adipose distribution, and liver morphology were assessed under both direct feeding and therapeutic settings. Results: In WT mice, only diets exceeding 85% fat induced robust ketogenesis, reflected by elevated BHB and hepatic upregulation of Cd36, Cpt1a, Acat1, and Hmgcs2. Moderate KDs (80–85%) failed to trigger ketosis and resembled high-fat feeding. In obese mice, an 80% KD lowered fasting glucose without reducing body weight, whereas a 90% KD promoted systemic ketosis, weight loss, and adipose reduction. Interestingly, hepatic transcriptional programs for fatty acid oxidation and ketogenesis were suppressed under 90% KD despite elevated BHB, suggesting reliance on substrate availability and peripheral utilization. In contrast, intestinal Hmgcs2 was strongly induced in both WT and DIO mice, with Oxct1 upregulated only in obesity, indicating local ketone production and consumption. Conclusions: These findings identify > 85% dietary fat as a threshold for sustained ketosis and highlight distinct liver–intestine contributions, underscoring ketogenesis as the central driver of KD’s anti-obesity benefits. Full article

MicroRNA-22 (miR-22) is a negative regulator of mitochondrial biogenesis, as well as lipid and glucose metabolism, in metabolically active tissues. Silencing miR-22 holds promise as a potential treatment of obesity and metabolic syndrome, as it restores metabolic capacity—enhancing oxidative metabolism—and reduces ectopic fat accumulation in chronic obesity, a driver of impaired metabolic flexibility and muscle mass loss. Intramuscular adipose accumulation and defective mitochondrial function are features associated with obese-mediated muscle atrophy and hallmarks of neuromuscular disorders such as Duchenne muscular dystrophy. Therefore, miR-22 could represent a compelling molecular target to improve muscle health across various muscle-wasting conditions. This study describes a pharmacological strategy for the inhibition of miR-22 in skeletal muscle by employing a mixmer antisense oligonucleotide (ASO, anti-miR-22). Administration of the ASO in a mouse model of obesity positively modulated myogenesis while protecting dystrophic mice from muscle function decline, enhancing fatigue resistance, and limiting pathological fibrotic remodeling. Mechanistically, we show that anti-miR-22 treatment promotes derepression of genes involved in mitochondrial homeostasis, favoring oxidative fiber content regardless of the disease model, thus promoting a more resilient phenotype. Furthermore, we suggest that miR-22 inhibition increases autophagy by transcriptional activation of multiple negative regulators of mammalian target of rapamycin (mTOR) signaling to decrease immune infiltration and fibrosis. These findings position miR-22 as a promising therapeutic target for muscle atrophy and support its potential to restore muscle health. Full article

L-fucose is a monosaccharide derived from brown algae and has potential applications as a functional food ingredient. Previous studies have reported that L-fucose reduces lipid accumulation in murine adipose tissue. Adipose tissue not only regulates energy metabolism but also functions as an endocrine organ involved in inflammation through the production and secretion of various adipokines. L-fucose is expected to exert anti-inflammatory effects and modulate adipokine secretion in adipocytes. In the present study, we investigated the anti-inflammatory effects of L-fucose in adipocytes. L-fucose significantly suppressed the expression of pro-inflammatory mediators and reduced the production of reactive oxygen species induced by inflammatory stimulation with a combination of lipopolysaccharide (LPS), tumor necrosis factor-⍺ (TNF-⍺), and interferon-γ (IFN-γ). These effects are likely mediated through the inhibition of key signaling pathways, including mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) pathways. Additionally, we found that L-fucose promoted the multimerization and secretion of high molecular weight (HMW) adiponectin, even under inflammatory conditions. Our results suggest that although L-fucose downregulates adiponectin expression, it contributes to the formation and/or stabilization of HMW adiponectin, which is functionally more relevant in anti-inflammatory and metabolic regulation. L-fucose thus holds promise as a functional food ingredient for mitigating inflammation in adipocytes. Full article

Asthma is a chronic respiratory disease affecting over 262 million people worldwide, with obesity-associated asthma emerging as a distinct endotype of increasing prevalence characterized by metabolic inflammation and airway remodeling. Unlike allergic asthma, this phenotype is driven by chronic low-grade inflammation, originating from hypertrophic and hypoxic adipose tissue. This dysregulated state leads to the activation of pro-inflammatory pathways and the secretion of cytokines, contributing to airway dysfunction and remodeling. Recent evidence highlights non-coding RNAs (ncRNAs) as key regulators of these processes. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) influence inflammation and remodeling by modulating immune cell polarization, cytokine secretion, extracellular matrix composition, and airway smooth muscle cell (ASMC) proliferation. Notably, H19, MEG3, GAS5, miR-26a-1-3p, and miR-376a-3p have been implicated in both asthma and obesity, suggesting their role in linking metabolic dysfunction with airway pathology. Moreover, ncRNAs regulate Treg/Th17 balance, fibroblast activation, and autophagy-related pathways, further influencing airway remodeling. Our in silico analysis highlighted the IGF1R signaling pathway as a key enriched mechanism, linking selected ncRNAs with metabolic dysregulation and inflammation in obesity-related asthma. This paper reviews how ncRNAs regulate inflammation and airway remodeling in obesity-associated asthma, emphasizing their potential molecular links between metabolic dysfunction and airway pathology. Full article

The parallel global increase in obesity and Alzheimer’s disease (AD) underscores an urgent public health challenge, with converging evidence indicating that metabolic dysfunction strongly contributes to neurodegeneration. Obesity is now recognized not only as a systemic metabolic condition but also as a modifiable risk factor for AD, acting through mechanisms such as chronic low-grade inflammation, insulin resistance, and adipose tissue dysfunction. Among the molecular mediators at this interface, adipokines have emerged as pivotal regulators linking metabolic imbalance to cognitive decline. Adipokines are hormone-like proteins secreted by adipose tissue, including adiponectin, leptin, and resistin, that regulate metabolism, inflammation and can influence brain function. Resistin, frequently elevated in obesity, promotes neuroinflammation, disrupts insulin signaling, and accelerates β-amyloid (Aβ) deposition and tau pathology. Conversely, adiponectin enhances insulin sensitivity, suppresses oxidative stress, and supports mitochondrial and endothelial function, thereby exerting neuroprotective actions. The imbalance between resistin and adiponectin may shift the central nervous system toward a pro-inflammatory and metabolically compromised state that predisposes to neurodegeneration. Beyond their mechanistic relevance, adipokines hold translational promise as biomarkers for early risk stratification and therapeutic monitoring. Importantly, natural compounds, including polyphenols, alkaloids, and terpenoids, have shown the capacity to modulate adipokine signaling, restore metabolic homeostasis, and attenuate AD-related pathology in preclinical models. This positions adipokines not only as pathogenic mediators but also as therapeutic targets at the intersection of diabetes, obesity, and dementia. By integrating mechanistic, clinical, and pharmacological evidence, this review emphasizes adipokine signaling as a novel axis for intervention and highlights natural compound-based strategies as emerging therapeutic approaches in obesity-associated AD. Beyond nutraceuticals, antidiabetic agents also modulate adipokines and AD-relevant pathways. GLP-1 receptor agonists, metformin, and thiazolidinediones tend to increase adiponectin and reduce inflammatory tone, while SGLT2 and DPP-4 inhibitors exert systemic anti-inflammatory and hemodynamic benefits with emerging but still limited cognitive evidence. Together, these drug classes offer mechanistically grounded strategies to target the adipokine–inflammation–metabolism axis in obesity-associated AD. Full article

The original purpose of this study was to compare human and pig scRNA-seq data to determine why pigs do not have brown adipocytes. However, during the experiment, we identified brown adipocytes in pigs. Therefore, we aimed to confirm that these adipocytes were brown adipocytes via a comparative analysis using typical mouse brown adipose tissue sections. We found that swine brown adipocytes were distributed in an island-like pattern, with three typical characteristics: (1) numerous mitochondria and small lipid droplets, (2) a cellular volume smaller than that of white adipocytes, and (3) expression of specific marker genes (EBF2 and ATP2B4). The expression levels of the thermogenesis-related genes UCP2/3 were not significantly increased. Thus, we conducted ceRNA network analysis, revealing that high expression of the key microRNA miR-10383 increased the thermogenic efficiency of UCP3 in the cold exposure group. In addition, the epigenetic memory of UCP3 was disrupted. Chromatin accessibility and Whole-Transcriptome Sequencing of Groin Adiposesibility results revealed peaks in the promoter regions of the UCP2/3 genes. In our discussion of the study’s limitations, we explain how to repeat the experiment to significantly increase the UCP2/3 protein content. This study fills a research gap regarding brown fat in pigs and can provide a reference for future studies on fat metabolism. Full article

Obesity is considered a state of chronic low-grade inflammation that impacts the development of chronic degenerative diseases. Cellular immunity plays a crucial role in the onset and persistence of this inflammatory condition. As the degree of obesity increases, significant distinct immunometabolic alterations are observed compared to individuals with normal weight. Moreover, obese patients who undergo bariatric surgical procedures for weight loss exhibit changes in the proportion of immune cells. These alterations help to explain several molecular processes associated with inflammation in obesity, including protein activation and inactivation, precursor molecule synthesis, phosphorylation events, and the activation of signal transduction pathways, all of which are orchestrated by immune cells, primarily lymphocyte subpopulations. The study of the immunometabolic profile through lymphocyte subpopulations in obese patients can provide a more comprehensive and objective understanding of disease severity and the risk of developing obesity-related chronic degenerative conditions and thereby improve or propose therapeutic and novel approaches. Therefore, the objective of this narrative review is to offer an integrative perspective on the molecular and pathophysiological mechanisms through which lymphocyte populations contribute to obesity-related inflammation and how weight loss through bariatric surgical procedures may contribute to the therapeutic management of inflammation. Full article

The global rise in obesity continues to outpace advances in pharmacologic treatment. While incretin-based therapies have demonstrated significant efficacy in promoting weight loss, their widespread use remains limited by gastrointestinal side effects, long-term tolerability concerns, and access issues. Additionally, sustaining weight loss over time poses an ongoing clinical challenge. These limitations highlight the need for alternative or complementary pharmacologic strategies. One such approach involves stimulating thermogenesis, particularly through the activation of brown and beige adipose tissue. This narrative review focuses on β3 adrenergic receptors as key mediators of browning and thermogenic energy expenditure. We review preclinical and clinical data, address pharmacokinetic and delivery challenges, and assess the translational potential of targeting thermogenesis in the management of obesity. Future directions are proposed to guide the development of safe and effective therapies that utilize this underexplored pharmacologic pathway. Full article

Background/Objectives: Obesity, defined by the excessive accumulation of adipose tissue, is associated with an increased risk of type 2 diabetes and metabolic dysfunction-associated steatotic liver disease (MASLD). Obesity treatments based on natural products are receiving increasing attention as viable alternatives to conventional treatments. Methods: To investigate the anti-obesity effects of Paliurus ramosissimus leaf extract (PRLE) in vitro and in vivo, we conducted studies using 3T3-L1 pre-adipocytes. The in vivo studies used high-fat diet (HFD)-fed C57BL/6 mice. PRLE effects were assessed through Oil Red O staining, RT-qPCR, Western blot, and morphological analysis of adipose tissue. Results: PRLE significantly reduced lipid accumulation in 3T3-L1 cells without cytotoxicity. PRLE treatment decreased mRNA expression of adipogenic genes (PPARγ, C/EBPα, FABP4, and leptin) and protein levels of adipogenesis-related markers. In HFD-fed mice, PRLE administration significantly reduced body weight gain (p < 0.001), decreased adipose tissue mass, and diminished the weight and size of white adipose tissue. Conclusions: PRLE exhibits anti-obesity effects both in vitro and in vivo, suggesting its potential as a therapeutic agent for obesity prevention. Full article

Starvation in horses presents critical welfare, economic, and management challenges with underlying molecular mechanisms of metabolic modification and recovery left poorly defined. Prolonged caloric deprivation induces significant systemic shifts in carbohydrate, protein, and lipid metabolism, reflected in coordinated changes in tissue-specific gene expression. This review synthesizes current knowledge on equine metabolic responses to starvation, emphasizing pathways found through RNA sequencing (RNA-seq) and real-time quantitative polymerase chain reaction (RT-qPCR) studies. Molecular investigations using RNA-seq and RT-qPCR have provided insight into transcriptional reprogramming during starvation and subsequent refeeding. Shifts in gene expression reflect the metabolic transition from carbohydrate dependence to lipid use, suppression of anabolic signaling, and activation of proteolytic pathways. However, interpretation of these data requires caution, as factors such as post-mortem interval, tissue handling, and euthanasia methods particularly the use of sodium barbiturates can influence transcript stability and abundance, potentially confounding results. The literature shows that starvation-induced molecular changes are not uniform across tissues, with skeletal muscle, liver, and adipose tissue showing distinct transcriptional signatures and variable recovery patterns during refeeding. Cross-species comparisons with hibernation, caloric restriction, and cachexia models provide context for understanding these changes, though equine-specific studies remain limited. Identified gaps include the scarcity of longitudinal data, inconsistent tissue sampling protocols, and lack of standardized reference genes for transcriptomic analyses in horses. Addressing these limitations will improve the accuracy of molecular evaluations and enhance our ability to predict recovery trajectories. A more comprehensive understanding of systemic and tissue-specific responses to starvation will inform evidence-based rehabilitation strategies, reduce the risk of refeeding syndrome, and improve survival and welfare outcomes for affected horses. Full article

We engineer an enhanced three-dimensional (3D) adipose model by integrating mesoporous silica (mSiO₂) nanoparticles into human adipose-derived stem cell spheroids. The mSiO₂ is highly cytocompatible, enables stable dispersion, and yields spheroids that preserve structural integrity and roundness for at least 14 days, accompanied by higher metabolic activity and reduced hypoxic stress. Under adipogenic induction, the nanoparticles embedded spheroids exhibit deeper lipid accumulation and increased expression of PPARγ, adiponectin, and FABP4. As a proof of concept, we leveraged this 3D platform to examine phage uptake and tissue-level distribution in adipose spheroids in comparison with conventional 2D cultures. These experiments reveal that both the cellular differentiation state and the tissue architecture govern phage association and uptake. Together, our findings indicate that phages engage mammalian cells beyond their bacterial hosts, a consideration that should inform future phage therapy design with implications for innate immune responses and overall therapeutic efficacy. Full article

Background: Due to the continuous global rise in obesity prevalence, foods rich in bioactive compounds are increasingly recognised for the management of several diseases. Objective: The present study aims to investigate whether an Opuntia stricta var. dillenii fruit peel extract, rich in betalains and phenolic compounds, is able to prevent obesity induced by a high-fat high-fructose diet in rats, along with the potential mechanisms of action underlying this effect. Results: The supplementation with Opuntia stricta var. dillenii extract obtained from the peel fruit partially prevents obesity development by attenuating HFHF-induced fat accumulation. This effect was observed predominantly in visceral adipose tissue, rather than in the subcutaneous depot. The obesity prevention was accompanied by the improvement of serum lipid profile. The mechanisms underlying the extract anti-obesity effect which were analysed in epididymal adipose tissue, involve preventing the rise in the availability of triglyceride synthesis substrates induced by high-fat high-fructose feeding, the inhibition of triglyceride assembly, and in the case of the high dose, increased lipolysis. Conclusions: According to these results, the peel wastes of Opuntia stricta var. dillenii fruit represent a promising natural source of bioactive compounds for obesity prevention. Nevertheless, these preclinical effects should be replicated in further studies in human beings. Full article

The tumor microenvironment (TME) comprises neoplastic and stromal cells, and extracellular matrix elements, all engaging in a complex interplay that ultimately dictates tumorigenesis, cancer progression, and therapeutic response. While extensive research on the TME has been conducted in human oncology, data on its veterinary counterpart, particularly in feline mammary tumors (FMTs), are still scarce. In this review, we explore current understanding of feline mammary carcinoma (FMC) microenvironment, focusing on tumor necrosis, fibrosis, angiogenesis, adipose tissue tumor-associated inflammation, extracellular vesicles, and epithelial–mesenchymal transition (EMT) and their prognostic implications. In FMC, remodeling of collagen fibers, cancer-associated fibroblasts (CAFs), regulatory T cells (Tregs) and elevated serum leptin have been associated with poor prognosis, whereas stromal cytotoxic T cells correlate with more favorable outcomes. By contrast, findings on necrosis and pro-angiogenic factors remain inconsistent, and research on extracellular vesicles (EVs) is still in its early stages. This review presents insights from human breast cancer (HBC) that further support and elucidate the potential relevance of these TME components. As FMCs are highly aggressive tumors, a deeper understanding of their microenvironment could not only improve prognostic accuracy but also uncover novel therapeutic targets. Furthermore, due to their similarities, FMCs offer a potential valuable spontaneous model for HBC, particularly for the aggressive triple-negative phenotypes. Full article