Adipose Tissue Dysfunction Research Articles

The Role of Adipocytes Recruited as Part of Tumor Microenvironment in Promoting Colorectal Cancer Metastases.

Adipose tissue dysfunction, which is associated with an increased risk of colorectal cancer (CRC), is a significant factor in the pathophysiology of obesity. Obesity-related inflammation and extracellular matrix (ECM) remodeling promote colorectal cancer metastasis (CRCM) by shaping the tumor microenvironment (TME). When CRC occurs, the metabolic symbiosis of tumor cells recruits adjacent adipocytes into the TME to supply energy. Meanwhile, abundant immune cells, from adipose tissue and blood, are recruited into the TME, which is stimulated by pro-inflammatory factors and triggers a chronic local pro-inflammatory TME. Dysregulated ECM proteins and cell surface adhesion molecules enhance ECM remodeling and further increase contractibility between tumor and stromal cells, which promotes epithelial-mesenchymal transition (EMT). EMT increases tumor migration and invasion into surrounding tissues or vessels and accelerates CRCM. Colorectal symbiotic microbiota also plays an important role in the promotion of CRCM. In this review, we provide adipose tissue and its contributions to CRC, with a special emphasis on the role of adipocytes, macrophages, neutrophils, T cells, ECM, and symbiotic gut microbiota in the progression of CRC and their contributions to the CRC microenvironment. We highlight the interactions between adipocytes and tumor cells, and potential therapeutic approaches to target these interactions.

From fasting to fat reshaping: exploring the molecular pathways of intermittent fasting-induced adipose tissue remodeling.

Obesity, characterised by excessive fat accumulation, is a complex chronic condition that results from dysfunctional adipose tissue expansion due to prolonged calorie surplus. This leads to rapid adipocyte enlargement that exceeds the support capacity of the surrounding neurovascular network, resulting in increased hypoxia, inflammation, and insulin resistance. Intermittent fasting (IF), a dietary regimen that cycles between periods of fasting and eating, has emerged as an effective strategy to combat obesity and improve metabolic homeostasis by promoting healthy adipose tissue remodeling. However, the precise molecular and cellular mechanisms behind the metabolic improvements and remodeling of white adipose tissue (WAT) driven by IF remain elusive. This review aims to summarise and discuss the relationship between IF and adipose tissue remodeling and explore the potential mechanisms through which IF induces alterations in WAT. This includes several key structural changes, including angiogenesis and sympathetic innervation of WAT. We will also discuss the involvement of key signalling pathways, such as PI3K, SIRT, mTOR, and AMPK, which potentially play a crucial role in IF-mediated metabolic adaptations.

Adipose Tissue Dysfunction Related to Climate Change and Air Pollution: Understanding the Metabolic Consequences.

Obesity, a global pandemic, poses a major threat to healthcare systems worldwide. Adipose tissue, the energy-storing organ during excessive energy intake, functions as a thermoregulator, interacting with other tissues to regulate systemic metabolism. Specifically, brown adipose tissue (BAT) is positively associated with an increased resistance to obesity, due to its thermogenic function in the presence of uncoupled protein 1 (UCP1). Recently, studies on climate change and the influence of environmental pollutants on energy homeostasis and obesity have drawn increasing attention. The reciprocal relationship between increasing adiposity and increasing temperatures results in reduced adaptive thermogenesis, decreased physical activity, and increased carbon footprint production. In addition, the impact of climate change makes obese individuals more prone to developing type 2 diabetes mellitus (T2DM). An impaired response to heat stress, compromised vasodilation, and sweating increase the risk of diabetes-related comorbidities. This comprehensive review provides information about the effects of climate change on obesity and adipose tissue, the risk of T2DM development, and insights into the environmental pollutants causing adipose tissue dysfunction and obesity. The effects of altered dietary patterns on adiposity and adaptation strategies to mitigate the detrimental effects of climate change are also discussed.

Tissue-Level Effect of Andrographis and Ashwagandha Metabolites on Metabolic and Inflammatory Gene Expression in Skeletal Muscle and Adipose Tissue: An Ex Vivo/In Vitro Investigation.

Adipose tissue and skeletal muscle dysfunction play a central role in cardiometabolic morbidity. Ashwagandha and Andrographis are purported to have anti-inflammatory and antioxidant activity, but this is based on exposure of cells to the parent compounds ignoring phytochemical absorption and metabolism. We explored the anti-inflammatory/antioxidant effects of ashwagandha and Andrographis in ex vivo human models of skeletal muscle and adipose tissue. Healthy participants supplemented with 2000 mg/day Andrographis (n = 10) or 1100 mg/day ashwagandha (n = 10) for 28 days. Sera collected pre (D0) and post (D28) supplementation were pooled by timepoint and added to adipose explant (AT) and primary human myotube (SKMC) culture media (15% v/v) for treatment. A Taqman panel of 56 genes was used to quantify these. In AT, treatment with ashwagandha sera decreased the expression of genes involved in antioxidant defence and inflammatory response (CCL5, CD36, IL6, IL10, ADIPOQ, NFEL2, UCP2, GPX3, GPX4; geometric 95% CI for fold change > 1) and altered the expression of genes involved in fatty acid metabolism. In SKMC, ashwagandha sera altered FOXO1 and SREBF1 expression. Andrographis sera decreased IL18 and SERPINEA3 expression in AT. This physiologically relevant in vitro screening characterises the effects of ashwagandha in AT to guide future clinical trials.

Exercise Reduces Glucose Intolerance, Cardiac Inflammation and Adipose Tissue Dysfunction in Psammomys obesus Exposed to Short Photoperiod and High Energy Diet.

Circadian disruption causes glucose intolerance, cardiac fibrosis, and adipocyte dysfunction in sand rats (Psammomys obesus). Exercise intervention can improve glucose metabolism, insulin sensitivity, adipose tissue function and protect against inflammation. We investigated the influence of exercise on male P. obesus exposed to a short photoperiod (5 h light:19 h dark) and high-energy diet. Exercise reduced glucose intolerance. Exercise reduced cardiac expression of inflammatory marker Ccl2 and Bax:Bcl2 apoptosis ratio. Exercise increased heart:body weight ratio and hypertrophy marker Myh7:Myh6, yet reduced Gata4 expression. No phenotypic changes were observed in perivascular fibrosis and myocyte area. Exercise reduced visceral adipose expression of inflammatory transcription factor Rela, adipogenesis marker Ppard and browning marker Ppargc1a, but visceral adipocyte size was unaffected. Conversely, exercise reduced subcutaneous adipocyte size but did not affect any molecular mediators. Exercise increased ZT7 Bmal1 and Per2 in the suprachiasmatic nucleus and subcutaneous Per2. Our study provides new molecular insights and histological assessments on the effect of exercise on cardiac inflammation, adipose tissue dysfunction and circadian gene expression in P. obesus exposed to short photoperiod and high-energy diet. These findings have implications for the protective benefits of exercise for shift workers in order to reduce the risk of diabetes and cardiovascular disease.

Biodistribution and Biotoxicity Assessment of Fluorescent Conjugated Polymer Dots.

Conjugated polymer dots (Pdots) have shown potential in the biomedical fields due to their optical properties and customizable design. However, the limited research on the biotoxicity of Pdots hinders their further application and translation. Lipophilic Pdots are prone to adsorbing specific proteins, leading to targeted tissue accumulation. Therefore, lipophilic fluorescent Pdots (Bare-Pdots) are synthesized using the conjugated polymer poly[2-methoxy-5-(2'-ethylhexyloxy)-1,4-phenylenevinylene] (MEH-PPV) to systematically evaluate their biodistribution and biotoxicity in stem cells, zebrafish embryos, and mice. It is observed that Bare-Pdots are readily internalized by cells and adhered to the embryonic chorion. Additionally, Bare-Pdots exhibit a distinct distribution in brown adipose tissue and heart, closely associated with phagocytosis of capillary endothelial cells involved in lipid metabolism. Notably, injection of Bare-Pdots at 5mgkg-1results in dysfunction of brown adipose tissue and an increased risk of obesity 90days post-injection. Furthermore, hydrophilic COOH-Pdots and NH2-Pdots with reduced lipophilicity are synthesized using amphiphilic ligands. NH2-Pdots show similar distribution but lower biotoxicity compared to Bare-Pdots. Nevertheless, injection of COOH-Pdots at 5mgkg-1 causes a decrease in white blood cells and renal tubular damage. These findings provide valuable insights for optimizing dosage to ensure the safe use of Pdots in preclinical applications.

Association between Visceral Adipose Tissue Metabolism and Cerebral Glucose Metabolism in Patients with Cognitive Impairment.

Visceral adipose tissue (VAT) dysfunction has been recently recognized as a potential contributor to the development of Alzheimer's disease (AD). This study aimed to explore the relationship between VAT metabolism and cerebral glucose metabolism in patients with cognitive impairment. This cross-sectional prospective study included 54 patients who underwent 18F-fluorodeoxyglucose (18F-FDG) brain and torso positron emission tomography/computed tomography (PET/CT), and neuropsychological evaluations. VAT metabolism was measured by 18F-FDG torso PET/CT, and cerebral glucose metabolism was measured using 18F-FDG brain PET/CT. A voxel-based analysis revealed that the high-VAT-metabolism group exhibited a significantly lower cerebral glucose metabolism in AD-signature regions such as the parietal and temporal cortices. In the volume-of-interest analysis, multiple linear regression analyses with adjustment for age, sex, and white matter hyperintensity volume revealed that VAT metabolism was negatively associated with cerebral glucose metabolism in AD-signature regions. In addition, higher VAT metabolism was correlated with poorer outcomes on cognitive assessments, including the Korean Boston Naming Test, Rey Complex Figure Test immediate recall, and the Controlled Oral Word Association Test. In conclusion, our study revealed significant relationships among VAT metabolism, cerebral glucose metabolism, and cognitive function. This suggests that VAT dysfunction actively contributes to the neurodegenerative processes characteristic of AD, making VAT dysfunction targeting a novel AD therapy approach.

Fish Oil Supplementation Mitigates High-Fat Diet-Induced Obesity: Exploring Epigenetic Modulation and Genes Associated with Adipose Tissue Dysfunction in Mice.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were divided into two groups: control diet and HFD for 16 weeks. In the last 8 weeks, the HFD group was subdivided into HFD and HFD + FO (treated with FO). WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR, and Western Blot assays. Mice receiving an HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. This study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the obesity-rich leptin environment of WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

Female Psammomys obesus Are Protected from Circadian Disruption-Induced Glucose Intolerance, Cardiac Fibrosis and Adipocyte Dysfunction.

Circadian disruption increases the development of cardiovascular disease and diabetes. We found that circadian disruption causes glucose intolerance, cardiac fibrosis and adipocyte tissue dysfunction in male sand rats, Psammomys obesus. Whether these effects occur in female P. obesus is unknown. Male and female P. obesus were fed a high energy diet and exposed to a neutral (12 light:12 dark, control) or short (5 light:19 dark, circadian disruption) photoperiod for 20 weeks. Circadian disruption impaired glucose tolerance in males but not females. It also increased cardiac perivascular fibrosis and cardiac expression of inflammatory marker Ccl2 in males, with no effect in females. Females had reduced proapoptotic Bax mRNA and cardiac Myh7:Myh6 hypertrophy ratio. Cardiac protection in females occurred despite reductions in the clock gene Per2. Circadian disruption increased adipocyte hypertrophy in both males and females. This was concomitant with a reduction in adipocyte differentiation markers Pparg and Cebpa in males and females, respectively. Circadian disruption increased visceral adipose expression of inflammatory mediators Ccl2, Tgfb1 and Cd68 and reduced browning marker Ucp1 in males. However, these changes were not observed in females. Collectively, our study show that sex differentially influences the effects of circadian disruption on glucose tolerance, cardiac function and adipose tissue dysfunction.

Tangzhiping Decoction Improves Glucose and Lipid Metabolism and Exerts Protective Effects Against White Adipose Tissue Dysfunction in Prediabetic Mice.

Prediabetes, characterized by a series of metabolic abnormalities, increases the risk of diabetes and cardiovascular diseases. Tangzhiping (TZP), a clinically validated traditional Chinese medicine formula, is used to treat impaired glucose tolerance. However, the underlying mechanism of TZP in intervening prediabetes is not fully elucidated. The current study aimed to evaluate the protective effect of TZP against prediabetes mice and explore its potential mechanism. After establishing a prediabetic animal model through 12 weeks of high-fat diet (HFD) feeding, mice were subjected to TZP for 8 weeks. Various parameters related to body weight, glucose and lipid metabolism, and insulin sensitivity were measured. Histopathological examinations observed adipose cell size and liver lipid deposition. The Sable Promethion system assessed energy metabolism activity. Transcriptomic analysis of Epididymal white adipose tissue (EWAT) identified enriched pathways and genes. The key genes in the enriched pathways were identified through RT-PCR. Our data revealed that the administration of TZP reduced body weight and fat mass in a prediabetes mouse model. TZP normalized the glucose and insulin levels, improved insulin resistance, and decreased plasma TC and FFA. The alleviation of adipose tissue hypertrophy and lipid deposition by TZP was demonstrated through pathological examination. Indirect calorimetry measurements indicated a potential increase in VO2 and EE levels with TZP. The results of EWAT transcription showed that TZP reversed pathways and genes related to inflammation and catabolic metabolism. RT-PCR demonstrated that the mRNA expression of inflammation and lipolysis, including Tlr2, Ccr5, Ccl9, Itgb2, Lipe, Pnpla2, Cdo1, Ces1d, Echs1, and Acad11, were changed by TZP treatment. TZP effectively alleviates obesity, impaired glucose and lipid metabolism, and insulin resistance. The effect of TZP might be associated with the regulation of gene expression in dysfunctional adipose tissue.

The association between the size of adipocyte-derived extracellular vesicles and fasting serum triglyceride-glucose index as proxy measures of adipose tissue insulin resistance in a rat model of early-stage obesity.

Obesity is a complex disease that predisposes individuals to cardiometabolic alterations. It leads to adipose tissue (AT) dysfunction, which triggers insulin resistance (IR). This suggests that people with obesity develop local IR first and systemic IR later. AT secretes extracellular vesicles, which may be physiopathologically associated with the development of IR. Our aim was to evaluate the effect of a high-fat diet on different parameters of adiposity in a rat model of early-stage obesity and to determine if these parameters are associated with markers of systemic IR. In addition, we sought to explore the relationship between fasting blood measures of IR (Triglycerides/High Density Lipoprotein-cholesterol [TAG/HDL-c] and Triglycerides-Glucose Index [TyG Index]) with the size of adipocyte-derived extracellular vesicles (adEV). We used a model of diet-induced obesity for ten weeks in Wistar rats exposed to a high-fat diet. Final weight gain was analyzed by Dual X-ray absorptiometry. Visceral obesity was measured as epididymal AT weight. IR was evaluated with fasting TyG Index & TAG/HDL-c, and adEV were isolated from mature adipocytes on ceiling culture. In the high-fat diet group, glucose and triglyceride blood concentrations were higher in comparison to the control group (Log2FC, 0.5 and 1.5 times higher, respectively). The values for TyG Index and adEV size were different between the control animals and the high-fat diet group. Multiple linear regression analyses showed that adEV size can be significantly associated with the TyG Index value, when controlling for epididymal AT weight. Our results show that lipid and glucose metabolism, as well as the size and zeta potential of adEV are already altered in early-stage obesity and that adEV size can be significantly associated with liver and systemic IR, estimated by TyG Index.

Maternal High-Fat Diet-Induced Obesity in Offspring: Unraveling Adipose Tissue Dysfunction Mediated by Increased Heat Shock Proteins

Maternal High-Fat Diet-Induced Obesity in Offspring: Unraveling Adipose Tissue Dysfunction Mediated by Increased Heat Shock Proteins

The role of adipose tissue dysfunction in hepatic insulin resistance and T2D.

The root cause of type 2 diabetes (T2D) is insulin resistance (IR), defined by the failure of cells to respond to circulating insulin to maintain lipid and glucose homeostasis. While the causes of whole-body insulin resistance are multifactorial, a major contributing factor is dysregulation of liver and adipose tissue function. Adipose dysfunction, particularly adipose tissue-IR (adipo-IR), plays a crucial role in the development of hepatic insulin resistance and the progression of metabolic dysfunction-associated steatotic liver disease (MASLD) in the context of T2D. In this review, we will focus on molecular mechanisms of hepatic insulin resistance and its association with adipose tissue function. A deeper understanding of the pathophysiological mechanisms of the transition from a healthy state to insulin resistance, impaired glucose tolerance, and T2D may enable us to prevent and intervene in the progression to T2D.

Sodium-glucose cotransporter 2 inhibitors induce anti-inflammatory and anti-ferroptotic shift in epicardial adipose tissue of subjects with severe heart failure

BackgroundSodium-glucose cotransporter 2 inhibitors (SGLT-2i) are glucose-lowering agents used for the treatment of type 2 diabetes mellitus, which also improve heart failure and decrease the risk of cardiovascular complications. Epicardial adipose tissue (EAT) dysfunction was suggested to contribute to the development of heart failure. We aimed to elucidate a possible role of changes in EAT metabolic and inflammatory profile in the beneficial cardioprotective effects of SGLT-2i in subjects with severe heart failure.Methods26 subjects with severe heart failure, with reduced ejection fraction, treated with SGLT-2i versus 26 subjects without treatment, matched for age (54.0 ± 2.1 vs. 55.3 ± 2.1 years, n.s.), body mass index (27.8 ± 0.9 vs. 28.8 ± 1.0 kg/m2, n.s.) and left ventricular ejection fraction (20.7 ± 0.5 vs. 23.2 ± 1.7%, n.s.), who were scheduled for heart transplantation or mechanical support implantation, were included in the study. A complex metabolomic and gene expression analysis of EAT obtained during surgery was performed.ResultsSGLT-2i ameliorated inflammation, as evidenced by the improved gene expression profile of pro-inflammatory genes in adipose tissue and decreased infiltration of immune cells into EAT. Enrichment of ether lipids with oleic acid noted on metabolomic analysis suggests a reduced disposition to ferroptosis, potentially further contributing to decreased oxidative stress in EAT of SGLT-2i treated subjects.ConclusionsOur results show decreased inflammation in EAT of patients with severe heart failure treated by SGLT-2i, as compared to patients with heart failure without this therapy. Modulation of EAT inflammatory and metabolic status could represent a novel mechanism behind SGLT-2i-associated cardioprotective effects in patients with heart failure.

Adipose Tissue Dysfunction and the Role of Adipocyte-Derived Extracellular Vesicles in Obesity and Metabolic Syndrome.

Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.

Efficacy and safety of tesamorelin in people with HIV on integrase inhibitors.

Tesamorelin is the only FDA-approved therapy to treat abdominal fat accumulation in people with HIV (PWH). Phase III clinical trials were conducted prior to the introduction of integrase inhibitors (INSTIs), which are now a mainstay of HIV antiretroviral therapy. We leveraged a randomized double-blind trial of 61 PWH and metabolic dysfunction-associated steatotic liver disease to evaluate the efficacy and safety of tesamorelin 2 mg once daily vs. identical placebo among participants on INSTI-based regimens at baseline. In the parent clinical trial, visceral fat cross-sectional area, hepatic fat fraction, and trunk-to-appendicular fat ratio were quantified using magnetic resonance imaging, proton magnetic resonance spectroscopy, and dual-energy x-ray absorptiometry, respectively, at baseline and 12 months. Metabolic and safety outcomes were compared between treatment arms. Among 38 participants on INSTI-based regimens at baseline, 15 individuals on tesamorelin and 16 individuals on placebo completed the 12-month study. Tesamorelin led to significant declines in visceral fat (median [interquartile range]: -25 [-93, -2] vs. 14 [3, 41] cm 2 , P = 0.001), hepatic fat (-4.2% [-12.3%, -2.7%] vs. -0.5% [-3.9%, 2.7%], P = 0.01), and trunk-to-appendicular fat ratio (-0.1 [-0.3, 0.0] vs. 0.0 [-0.1, 0.1], P = 0.03). Tesamorelin was well tolerated with a similar frequency of adverse events, including hyperglycemia, between groups. The current analysis provides the first dedicated data on the efficacy and safety of tesamorelin among PWH on INSTI-based regimens. Despite the association of INSTI use with weight gain and adipose tissue dysfunction, tesamorelin had beneficial effects on body composition with no exacerbation of glycemic control.

2054-LB: Mitigating Adipose Tissue Dysfunction and Insulin Resistance in Obesity via SVEP1 Peptide-Mediated Suppression of Adipose Tissue Macrophage-Induced Inflammation

2054-LB: Mitigating Adipose Tissue Dysfunction and Insulin Resistance in Obesity via SVEP1 Peptide-Mediated Suppression of Adipose Tissue Macrophage-Induced Inflammation

Adipocyte-specific Nrf2 deletion negates nitro-oleic acid benefits on glucose tolerance in diet-induced obesity

Obesity is commonly linked with white adipose tissue (WAT) dysfunction, setting off inflammation and oxidative stress, both key contributors to the cardiometabolic complications associated with obesity. To improve metabolic and cardiovascular health, countering these inflammatory and oxidative signaling processes is crucial. Offering potential in this context, the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) by nitro-fatty acids (NO2-FA) promote diverse anti-inflammatory signaling and counteract oxidative stress. Additionally, we previously highlighted that nitro-oleic acid (NO2-OA) preferentially accumulates in WAT and provides protection against already established high fat diet (HFD)-mediated impaired glucose tolerance. The precise mechanism accounting for these protective effects remained largely unexplored until now. Herein, we reveal that protective effects of improved glucose tolerance by NO2-OA is absent when Nrf2 is specifically ablated in adipocytes (ANKO mice). NO2-OA treatment did not alter body weight between ANKO and littermate controls (Nrf2fl/fl) mice on both the HFD and low-fat diet (LFD). As expected, at day 76 (before NO2-OA treatment) and notably at day 125 (daily treatment of 15 mg/kg NO2-OA for 48 days), both HFD-fed Nrf2fl/fl and ANKO mice exhibited increased fat mass and reduced lean mass compared to LFD controls. However, throughout the NO2-OA treatment, no distinction was observed between Nrf2fl/fl and ANKO in the HFD-fed mice as well as in the Nrf2fl/fl mice fed a LFD. Glucose tolerance tests revealed impaired glucose tolerance in HFD-fed Nrf2fl/fl and ANKO compared to LFD-fed Nrf2fl/fl mice. Notably, NO2-OA treatment improved glucose tolerance in HFD-fed Nrf2fl/fl but did not yield the same improvement in ANKO mice at days 15, 30, and 55 of treatment. Unraveling the pathways linked to NO2-OA's protective effects in obesity-mediated impairment in glucose tolerance is pivotal within the realm of precision medicine, crucially propelling future applications and refining novel drug-based strategies.

Rethinking weight loss treatments as cardiovascular medicine in obesity, a comprehensive review.

The global escalation of obesity has made it a worldwide health concern, notably as a leading risk factor for cardiovascular disease (CVD). Extensive evidence corroborates its association with a range of cardiac complications, including coronary artery disease, heart failure, and heightened vulnerability to sudden cardiac events. Additionally, obesity contributes to the emergence of other cardiovascular risk factors including dyslipidaemia, type 2 diabetes, hypertension, and sleep disorders, further amplifying the predisposition to CVD. To adequately address CVD in patients with obesity, it is crucial to first understand the pathophysiology underlying this link. We herein explore these intricate mechanisms, including adipose tissue dysfunction, chronic inflammation, immune system dysregulation, and alterations in the gut microbiome.Recent guidelines from the European Society of Cardiology underscore the pivotal role of diagnosing and treating obesity to prevent CVD. However, the intricate relationship between obesity and CVD poses significant challenges in clinical practice: the presence of obesity can impede accurate CVD diagnosis while optimizing the effectiveness of pharmacological treatments or cardiac procedures requires meticulous adjustment, and it is crucial that cardiologists acknowledge the implications of excessive weight while striving to enhance outcomes for the vulnerable population affected by obesity. We, therefore, sought to overcome controversial aspects in the clinical management of heart disease in patients with overweight/obesity and present evidence on cardiometabolic outcomes associated with currently available weight management interventions, with the objective of equipping clinicians with an evidence-based approach to recognize and address CVD risks associated with obesity.

Exploring the Link Between Metabolic Syndrome and Cellulite.

Metabolic syndrome (MetS) encompasses a cluster of metabolic abnormalities, including insulin resistance, hypertension, abdominal obesity, and dyslipidemia, increasing cardiovascular disease and type 2 diabetes risks. Cellulite, a cosmetic condition marked by dimpled skin, predominantly affects women and shares risk factors with MetS, such as obesity and hormonal imbalances. This review examines the potential link between MetS and cellulite, focusing on shared pathophysiological pathways and implications for clinical practice and future research. Common factors such as inflammation, hormonal changes, and adipose tissue dysfunction are explored. The review highlights the importance of longitudinal studies to track cellulite progression in MetS patients, biomarker identification for early detection, intervention trials to assess therapeutic efficacy, mechanistic studies to elucidate underlying pathways and the impact of comorbidities on cellulite development. Understanding these relationships can enhance prevention, diagnosis, and treatment strategies for both MetS and cellulite, addressing significant public health and cosmetic concerns.