Excessive Accumulation Of Adipose Tissue Research Articles

Exploring the multifaceted role of obesity in breast cancer progression

Obesity is a multifaceted metabolic disorder characterized by excessive accumulation of adipose tissue. It is a well-established risk factor for the development and progression of breast cancer. Adipose tissue, which was once regarded solely as a passive energy storage depot, is now acknowledged as an active endocrine organ producing a plethora of bioactive molecules known as adipokines that contribute to the elevation of proinflammatory cytokines and estrogen production due to enhanced aromatase activity. In the context of breast cancer, the crosstalk between adipocytes and cancer cells within the adipose microenvironment exerts profound effects on tumor initiation, progression, and therapeutic resistance. Moreover, adipocytes can engage in direct interactions with breast cancer cells through physical contact and paracrine signaling, thereby facilitating cancer cell survival and invasion. This review endeavors to summarize the current understanding of the intricate interplay between adipocyte-associated factors and breast cancer progression. Furthermore, by discussing the different aspects of breast cancer that can be adversely affected by obesity, this review aims to shed light on potential avenues for new and novel therapeutic interventions.

Exploring the multifaceted role of obesity in breast cancer progression.

Obesity is a multifaceted metabolic disorder characterized by excessive accumulation of adipose tissue. It is a well-established risk factor for the development and progression of breast cancer. Adipose tissue, which was once regarded solely as a passive energy storage depot, is now acknowledged as an active endocrine organ producing a plethora of bioactive molecules known as adipokines that contribute to the elevation of proinflammatory cytokines and estrogen production due to enhanced aromatase activity. In the context of breast cancer, the crosstalk between adipocytes and cancer cells within the adipose microenvironment exerts profound effects on tumor initiation, progression, and therapeutic resistance. Moreover, adipocytes can engage in direct interactions with breast cancer cells through physical contact and paracrine signaling, thereby facilitating cancer cell survival and invasion. This review endeavors to summarize the current understanding of the intricate interplay between adipocyte-associated factors and breast cancer progression. Furthermore, by discussing the different aspects of breast cancer that can be adversely affected by obesity, this review aims to shed light on potential avenues for new and novel therapeutic interventions.

SGLT2 inhibitor canagliflozin reduces visceral adipose tissue in db/db mice by modulating AMPK/KLF4 signaling and regulating mitochondrial dynamics to induce browning

Obesity is characterized by excessive accumulation of adipose tissue (mainly visceral). The morphology and function of mitochondria are crucial for regulating adipose browning and weight loss. Research suggests that the SGLT2 inhibitor canagliflozin may induce weight loss through an unknown mechanism, particularly targeting visceral adipose tissue. While Krueppel-Like Factor 4 (KLF4) is known to be essential for energy metabolism and mitochondrial function, its specific impact on visceral adipose tissue remains unclear. We administered canagliflozin to db/db mice for 8 weeks, or exposed adipocytes to canagliflozin for 24 h. The expression levels of browning markers, mitochondrial dynamics, and KLF4 were assessed. Then we validated the function of KLF4 through overexpression in vivo and in vitro. Adenosine monophosphate-activated protein kinase (AMPK) agonists, inhibitors, and KLF4 si-RNA were employed to elucidate the relationship between AMPK and KLF4. The findings demonstrated that canagliflozin significantly decreased body weight in db/db mice and augmented cold-induced thermogenesis. Additionally, canagliflozin increased the expression of mitochondrial fusion-related factors while reducing the levels of fission markers in epididymal white adipose tissue. These consistent findings were mirrored in canagliflozin-treated adipocytes. Similarly, overexpression of KLF4 in both adipocytes and db/db mice yielded comparable results. In all, canagliflozin mitigates obesity in db/db mice by promoting the brown visceral adipocyte phenotype through enhanced mitochondrial fusion via AMPK/KLF4 signaling.

Efficacy of Probiotic Strains Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 in Management of Obesity: An In Vitro and In Vivo Analysis.

The prevalence of obesity, characterized by an excessive accumulation of adipose tissue and adipocyte hypertrophy, presents a major public health challenge. This study investigates the therapeutic potential of two probiotic strains, Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093, in the context of obesity. Utilizing 3T3-L1 cell-derived human adipocytes, we assessed Probio65's and Probio-093's capacity to mitigate triglyceride accumulation and influence adipocytokine production in vitro. Subsequently, an in vivo trial with male C57BL/6J mice examined the effects of both probiotic strains on adipose tissue characteristics, body weight, fat mass, and obesity-related gene expression. This study employed both live and ethanol-extracted bacterial cells. The results demonstrated significant reductions in the triglyceride deposition, body weight, and adipose tissue mass in the treated groups (p < 0.05). Furthermore, both strains modulated adipokine profiles by downregulating proinflammatory markers such as PAI-1, leptin, TNF-α, STAMP2, F4/80, resistin, and MCP-1, and upregulating the insulin-sensitive transporter GLUT4 and the anti-inflammatory adiponectin (p < 0.05). Our findings suggest that Lactobacillus sakei Probio65 and Lactobacillus plantarum Probio-093 are promising agents for microbiome-targeted anti-obesity therapies, offering the effective mitigation of obesity and improvement in adipocyte function in a murine model.

Comparative proteomic analysis of pathological characterization of adipose tissue remodeling induced by high-fat diet and high-carbohydrate diet in grass carp (Ctenopharyngodon idellus)

Our previous research found that excessive accumulation of adipose tissue is an important factor that reduces fish tolerance and utilization of high-energy feeds and limits the development of high-energy feeds in the aquaculture industry. However, the pathological characteristics and molecular mechanisms of fish adipose tissue remodeling caused by high-energy diet were still unclear. In this study, using histopathological observation, we found that restricted adipocyte hyperplasia, adipocyte hypertrophy, inflammation, and fibrosis are the main characteristics of pathological remodeling of fish adipose tissue induced by high-fat diet (HFD) and high-carbohydrate diet (HCD). Besides, this study further analyzed the molecular mechanisms and key marker proteins invovled in pathological remodeling of adipose tissue induced by HFD and HCD through comparative proteomics. The results found: (1) Inhibition of the differentiation of preadipocytes may be the main pathway through which both HCD and HFD inhibited adipocyte hyperplasia in grass carp; (2) Although both HFD and HCD induce adipocyte hypertrophy by increasing the de novo lipogenesis (DNL) pathway and promoting triglycerides (TG) synthesis. But the difference is that HFD increases fatty acid transport, while HCD increases glycolysis; (3) The inhibitory effect of HCD on glucose transporter type 4 (Glut4) may be an important cause of carbohydrate intolerance in fish; (4) Both HFD and HCD increase lactate production by promoting the expression of lactate dehydrogenase (Ldh), which may be the molecular mechanism of high-energy diet-induced adipose tissue hypoxia; (5) Interleukin-8 (Il-8) can be used as a pro-inflammatory marker for identifying HFD and HCD induced adipose tissue inflammation. This study aims to incestigate the reasons why HFD and HCD have negative effects on fish from the perspective of pathological remodeling of adipose tissue, and provide new underlying regulatory targets for improving the tolerance and utilization of HCD or HFD in farmed fish.

Plasticity of Adipose Tissues: Interconversion among White, Brown, and Beige Fat and Its Role in Energy Homeostasis.

Obesity, characterized by the excessive accumulation of adipose tissue, has emerged as a major public health concern worldwide. To develop effective strategies for treating obesity, it is essential to comprehend the biological properties of different adipose tissue types and their respective roles in maintaining energy balance. Adipose tissue serves as a crucial organ for energy storage and metabolism in the human body, with functions extending beyond simple fat storage to encompass the regulation of energy homeostasis and the secretion of endocrine factors. This review provides an overview of the key characteristics, functional differences, and interconversion processes among white adipose tissue (WAT), brown adipose tissue (BAT), and beige adipose tissue. Moreover, it delves into the molecular mechanisms and recent research advancements concerning the browning of WAT, activation of BAT, and whitening of BAT. Although targeting adipose tissue metabolism holds promise as a potential approach for obesity treatment, further investigations are necessary to unravel the intricate biological features of various adipose tissue types and elucidate the molecular pathways governing their interconversion. Such research endeavors will pave the way for the development of more efficient and targeted therapeutic interventions in the fight against obesity.

Retrospective investigation of the energy requirements for weight loss and weight maintenance after weight loss programme in obese dogs.

Obesity is a highly prevalent disease in dogs and is characterized by the excessive accumulation of adipose tissue that results in metabolic changes. Its treatment is based on a negative energy balance focusing on energy restriction. However, there are few studies in dogs that assessed the energy intake needed for adequate weight loss and to weight maintenance afterward. The aim of this study was to evaluate data about the treatment of canine obesity, with emphasis on energy restriction to induce weight loss and to maintain body weight (BW) and ideal body condition after weight loss. This was a retrospective study in which records of obese dogs from a veterinary teaching hospital were assessed between 2014 and 2020. Sixteen dogs were considered in the study according to inclusion and exclusion criteria and 10 of these participated in the maintenance phase after weight loss. The animals lost a mean of 23.2% their initial weight in a mean of 422 days. The mean weekly weight loss rate was 0.58% of BW, and the mean daily energy intake for weight loss was 59 kcal/kg current BW0.75. When the target BW was considered, which was defined as the current weight minus 10% for every point in the body condition score scale above 5, the mean energy for weight loss was 71 kcal/kg target BW0.75. In the maintenance phase, the animals were assessed for a mean of 134 days. The mean energy intake to maintenance BW was 70 kcal/kg BW0.75. The lower energy requirement of obese dogs during and after weight loss can work as an alert for the formulations of therapeutic weight loss diets to contain a high nutrient density focusing on the wellbeing, health, and quality of life of obese dogs, not just for the weight loss phase, but a diet for the weight maintenance phase.

Exploring the Interplay between Bone Marrow Stem Cells and Obesity.

Obesity, a complex disorder with rising global prevalence, is a chronic, inflammatory, and multifactorial disease and it is characterized by excessive adipose tissue accumulation and associated comorbidities. Adipose tissue (AT) is an extremely diverse organ. The composition, structure, and functionality of AT are significantly influenced by characteristics specific to everyone, in addition to the variability connected to various tissue types and its location-related heterogeneity. Recent investigation has shed light on the intricate relationship between bone marrow stem cells and obesity, revealing potential mechanisms that contribute to the development and consequences of this condition. Mesenchymal stem cells within the bone marrow, known for their multipotent differentiation capabilities, play a pivotal role in adipogenesis, the process of fat cell formation. In the context of obesity, alterations in the bone marrow microenvironment may influence the differentiation of mesenchymal stem cells towards adipocytes, impacting overall fat storage and metabolic balance. Moreover, bone marrow's role as a crucial component of the immune system adds another layer of complexity to the obesity-bone marrow interplay. This narrative review summarizes the current research findings on the connection between bone marrow stem cells and obesity, highlighting the multifaceted roles of bone marrow in adipogenesis and inflammation.

Metabolic Insights into Caffeine's Anti-Adipogenic Effects: An Exploration through Intestinal Microbiota Modulation in Obesity.

Obesity, a chronic condition marked by the excessive accumulation of adipose tissue, not only affects individual well-being but also significantly inflates healthcare costs. The physiological excess of fat manifests as triglyceride (TG) deposition within adipose tissue, with white adipose tissue (WAT) expansion via adipocyte hyperplasia being a key adipogenesis mechanism. As efforts intensify to address this global health crisis, understanding the complex interplay of contributing factors becomes critical for effective public health interventions and improved patient outcomes. In this context, gut microbiota-derived metabolites play an important role in orchestrating obesity modulation. Microbial lipopolysaccharides (LPS), secondary bile acids (BA), short-chain fatty acids (SCFAs), and trimethylamine (TMA) are the main intestinal metabolites in dyslipidemic states. Emerging evidence highlights the microbiota's substantial role in influencing host metabolism and subsequent health outcomes, presenting new avenues for therapeutic strategies, including polyphenol-based manipulations of these microbial populations. Among various agents, caffeine emerges as a potent modulator of metabolic pathways, exhibiting anti-inflammatory, antioxidant, and obesity-mitigating properties. Notably, caffeine's anti-adipogenic potential, attributed to the downregulation of key adipogenesis regulators, has been established. Recent findings further indicate that caffeine's influence on obesity may be mediated through alterations in the gut microbiota and its metabolic byproducts. Therefore, the present review summarizes the anti-adipogenic effect of caffeine in modulating obesity through the intestinal microbiota and its metabolites.

Gastro-esophageal diagnostic workup before bariatric surgery or endoscopic treatment for obesity: position statement of the International Society of Diseases of the Esophagus.

Obesity is a chronic and multifactorial condition characterized by abnormal weight gain due to excessive adipose tissue accumulation that represents a growing worldwide challenge for public health. In addition, obese patients have an increased risk of hiatal hernia, esophageal, and gastric dysfunction, as well as gastroesophageal reflux disease, which has a prevalence over 40% in those seeking endoscopic or surgical intervention. Surgery has been demonstrated to be the most effective treatment for severe obesity in terms of long-term weight loss, comorbidities, and quality of life improvements and overall mortality decrease. The recent emergence of bariatric endoscopic techniques promises less invasive, more cost-effective, and reproducible approaches to the treatment of obesity. With the endorsement of the International Society for Diseases of the Esophagus, we started a Delphi process to develop consensus statements on the most appropriate diagnostic workup to preoperatively assess gastroesophageal function before bariatric surgical or endoscopic interventions. The Consensus Working Group comprised 11 international experts from five countries. The group consisted of gastroenterologists and surgeons with a large expertise with regard to gastroesophageal reflux disease, bariatric surgery and endoscopy, and physiology. Ten statements were selected, on the basis of the agreement level and clinical relevance, which represent an evidence and experience-based consensus of the International Society for Diseases of the Esophagus.

Inhibition of Pancreatic Lipase by Flavonoid Derivatives: In Vitro and In Silico Investigations.

Obesity, characterized by excessive adipose tissue accumulation, has emerged as a crucial determinant for a wide range of chronic medical conditions. The identification of effective interventions for obesity is of utmost importance. Widely researched antiobesity agents focus on pancreatic lipase, a significant therapeutic target. This study presented the evaluation of ten flavonoid compounds in terms of their inhibitory activities against pancreatic lipase, utilizing both in vitro and in silico approaches. The results indicated that all tested compounds demonstrated modest and weaker inhibitory activities compared to the reference compound, orlistat. Among the compounds investigated, F01 exhibited the highest potency, with an IC50 value of 17.68 ± 1.43 µM. The enzymatic inhibition kinetic analysis revealed that F01 operated through a competitive inhibition mechanism with a determined Ki of 7.16 μM. This value suggested a moderate binding affinity for the pancreatic lipase enzyme. Furthermore, the associated Vmax value was quantified at 0.03272 ΔA·min-1. In silico studies revealed that F01 displayed a binding mode similar to that of orlistat, despite lacking an active functional group capable of forming a covalent bond with Ser152 of the catalytic triad. However, F01 formed a hydrogen bond with this crucial amino acid. Furthermore, F01 interacted with other significant residues at the enzyme's active site, particularly those within the lid domain. Based on these findings, F01 demonstrates substantial potential as a candidate for further investigations.

Effect of Guduchi Triphala Kwatha with Lohabhasma as Prakshepa Churna in the Management of Obesity

Obesity a complex metabolic disorder, involves the excessive accumulation of adipose tissue and it is recognised as a major global health challenge. Preclinical study conducted on obesity provides valuable insights into the revalidation of the treatment approach of Sthoulya. Methods: In this study the efficacy of Guduchi Triphala Kwatha added with Lohabhasma, as Prakshepa Churna evaluated in High fat diet (HFD) fed, obese Wistar albino rats. A Control group containing 6 rats were administered with distilled water (9.86ml/kg), another group received standard drug Orlistat (30mg/kg) and the trial group was given Kwatha (9.86ml/kg) added with Lohabhasma (25.65mg/kg). High fat diet was continued throughout the study period. All the drugs were administered orally once a day for 30 days. At the end of the experimental period various physical, biochemical and histopathological observations were made. Results: Data of in-vivo studies revealed that significant reduction in body weight, body mass index (BMI), waist circumference (WC), upon trial drug treatment. Elevated levels of, insulin, leptin, lipid profile, liver function, kidney function and antioxidant status were also showed significant results. Milder changes were observed in histopathological examination of Liver, Kidney and Adipose tissue even though HFD was continuing throughout the study period. Conclusion: The trial drug showed significant result in the assessment parameters after treatment.

Management of obesity: Going beyond eating less and moving more

Overweight and obesity are defined as abnormal or excessive adipose tissue accumulation that results in a risk to health. This is caused not simply by poor lifestyle, but rather a complex interplay of health inequalities, genetic inheritance, as well as social and environmental factors. Excess weight significantly increases the risk of chronic illnesses, including cardiovascular diseases, diabetes, musculoskeletal disorders, and various types of cancer. Individuals with a body mass index (BMI) of 30–35 kg/m2 experience an average reduction in life expectancy of 2–4 years and for those with a BMI of 40–50 kg/m2, the decrease in life expectancy ranges from 8–10 years. Experts predict that by 2030, the UK will see 11 000 000 more adults affected by obesity, resulting in a significant increase in the cost of treating obesity-related diseases. This article provides a contemporary overview of obesity understanding and management in adults, including brief interventions, motivational interviewing, as well as pharmacological and surgical options.

Diet quality is associated with adipose tissue and muscle mass: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

Aging is associated with changes in body composition, and preventing loss of muscle mass and accumulation of excess adipose tissue in middle-aged adults may reduce age-related conditions at older ages. Dietary intake is one lifestyle factor shown to improve or maintain body composition. However, few studies have examined the Healthy Eating Index2015 (HEI2015), a measure of diet quality, and the association with body composition in adult men and women. Participant data (n=3017) from the Coronary Artery Risk Development in Young Adults (CARDIA) study were used to examine the associations of the HEI2015 with body composition measures at Year 25 (Y25), including (1) 25year-change in weight, body mass index (BMI), and waist circumference and (2) a computed tomography (CT) scan at Y25 measured muscle mass, muscle quality (better quality=less lipid within the muscle), and adipose tissue depots visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), and adipose within skeletal muscle (intermuscular adipose tissue; IMAT). Dietary intake was assessed by a diet history three times over 20years, at years 0, 7, and 20. HEI2015, averaged over three exams, was created and categorized into quintiles. Multiple regression analysis evaluated the associations of body composition stratified across quintiles of HEI2015 adjusted for demographic characteristics, energy intake, lifestyle factors, and baseline anthropometric measures as appropriate. Race-sex interaction was tested (Pinteraction >0.30). Over 25years of follow-up, averaged HEI2015 was significantly and inversely associated with weight gain (Quintile 1 (Q1) 37.3lb vs. 32.9 in Q5; Ptrend =0.01), change in BMI (Q1 5.8kg/m2 vs. 5.0 in Q5; Ptrend =0.005), and change in waist circumference (Q1 17.5cm vs. 15.2cm in Q5; Ptrend <0.001). By Y25, HEI2015 was inversely associated with VAT Q1 136.8cm3 vs. 116.6 in Q5; Ptrend <0.001) and IMAT volumes (Q1 9.52 vs. 8.12cm3 in Q5; Ptrend <0.001). Although total muscle volume declined (Ptrend =0.03), lean muscle mass volume was similar across quintiles (Ptrend =0.55). The IMAT/total muscle mass ratio declined across HEI2015 quintiles (Ptrend <0.001). Finally, higher HEI2015 was associated with better muscle quality at Y25 (higher value=less lipid within the muscle; Q1 41.1 vs. 42.2 HU in Q5; Ptrend =0.002). HEI2015 was nonlinearly, but inversely, associated with SAT (nonlinear P=0.011). Improving diet quality in young to middle-aged adults is a recommended strategy to promote better measures of body composition. Our study findings suggest that healthier food choices may influence body composition.

Pharmacological methods for weight reduction and their connection with the human gut microbiota

In the beginning of the twenty-first century, obesity has become a concerning world-wide issue due to its high prevalence in modern society. It is a metabolic disorder, caused by excessive accumulation of adipose tissue in the human organism – the main reason for which is increased caloric intake and decreased caloric expenditure in combination with dysregulation of hunger. It is a chronic systematic disease that leads to the development of a large number of health complications, the most common of which are: diabetes mellitus type 2, arterial hypertension, atherosclerosis, sleep apnea, different types of cancer and more. During the last decade, significant advancements have been made in regard to treatment of many endocrine and metabolic conditions, using pharmacological means, and some of these novel medications have proven to be an effective therapy for obesity. There is emerging evidence that such drugs can exhibit an effect over the human gut microbiota – the complex system of commensal bacteria located in the gastrointestinal tract, which could affect appetite, mucosal integrity, nutrient absorption, and that interaction can be the key to understanding the pathogenesis of obesity and its treatment.

A single session of strength training changed plasma levels of resistin, but not leptin in overweight and obese men

Obesity has a complex multifactorial etiology and is characterized by excessive accumulation of adipose tissue. Visceral adipose tissue has deleterious effects on health because it secretes large amounts of inflammatory cytokines. Nutritional calorie restriction associated with strength training may be useful in managing chronic systemic inflammation. This study aimed to evaluate the acute effect of a single strength-training session on plasma adipokine levels in sedentary, overweight, and obese young men. This study included twelve men (Age: [34.95 ± 9.77] years; Height: [174.16 ± 3.66] centimeter [cm]; Weight: [97.83 ± 12.87] kilogram (kg); body mass index [BMI]: [32.30 ± 4.51] kg/m2), who performed a single strength training session. The strength training protocol consisted of 4 sets of 12 repetitions in the following six exercises, 45° leg press, bench press, leg extension, machine row, leg curl, and shoulder press. Blood samples were collected before, immediately after, and 1-h subsequent after strength training. The plasma levels of resistin and leptin were measured. A significant decrease in resistin levels were found 1 h after the strength training session if compared to levels before the training session (pre-[before] [2390 ± 1199] picograms per milliliter [pg/mL] vs post-1 h [1-h subsequent] [1523 ± 798],6 pg/mL, p = 0.002 8). The plasma leptin levels did not differ at any time point. In conclusion, a very well controlled single session of strength training significantly decreased the plasma levels of resistin without altering the concentration of leptin in overweight and obese individuals. This effect, at least in part, supports the benefits of exercise by reducing the low grade inflammation and insulin resistance in obesity.

High intensity interval exercise maintains irisin level and reduces body fat in overweight women

Abstract A body mass index of more than 23 kg/m2 refers to being overweight. When overweight is not treated well, it can lead to obesity which is the condition of accumulation of excess adipose tissue. Obesity increases the risk of metabolic disease and physical activity has been known to prevent it. Irisin has been established to have a positive correlation with body fat burning. The purpose of this study is to analyse the acute effect of high intensity interval exercise on irisin level and body fat percentage in overweight sedentary women. Subjects were divided into 2 groups, the experimental (EXP) group (n = 10) and the control (CON) group (n = 10). The EXP group was using an ergo cycle of 10 sets, consisting of 60 s at 80-90% HRmax (cycling ∼120 rpm) and 60 s of active resting (cycling ∼40 rpm), intermittently. Blood serum and body fat percentage were measured before treatment and after 60 min of treatment. The results showed the serum irisin level was insignificant differences between EXP and CON groups. However, there was a significant decrease of irisin level between pre- and post-data in both EXP and CON, and the significant decrease of it between pre and post was in control group (EXP 6.65 ± 0.767 vs 5.76 ± 0.825, ; CON 7.46 ± 1.659 vs 5.80 ± 0.935 ng/ml, ). The change in body fat percentage was significant lower in EXP compared to CON (0.30 ± 0.217; 0.23 ± 0.118%; ). The conclusion is that the acute effect of HIIE can maintain the irisin level, and may also maintain the burning of body fat, which will lead to the reduction of body fat.

Specific features of endocrine regulation of plastic processes in premature infants and children small for gestational age

Low-birthweight and preterm infants have high risk of obesity and obesity-related diseases in the future. This review article identifies risk factors and endocrine biomarkers with greatest predictive value to the metabolic diseases development. Low concentrations of IGF-1 in low-birthweight children are associated with adipogenesis. Low leptin levels may be considered as a biomarker of catch-up growth. Long term programming effects of in utero exposure to leptin extend beyond infancy into early childhood. Adiponectin levels are positively correlated with obesity in early life, but not at ages older than three years. Rapid postnatal growth rate is associated with metabolic syndrome. Conclusion. Specific features of endocrine regulation of growth and dynamics of plastic processes in premature infants and SGA children are associated with excessive accumulation of adipose tissue, which can function as a mechanism for metabolic programming of distant endocrine and cardiometabolic disorders.

Mineralocorticoid Receptor Antagonism Prevents Type 2 Familial Partial Lipodystrophy Brown Adipocyte Dysfunction.

Type-2 Familial Partial Lipodystrophy (FPLD2), a rare lipodystrophy caused by LMNA mutations, is characterized by a loss of subcutaneous fat from the trunk and limbs and excess accumulation of adipose tissue in the neck and face. Several studies have reported that the mineralocorticoid receptor (MR) plays an essential role in adipose tissue differentiation and functionality. We previously showed that brown preadipocytes isolated from a FPLD2 patient's neck aberrantly differentiate towards the white lineage. As this condition may be related to MR activation, we suspected altered MR dynamics in FPLD2. Despite cytoplasmic MR localization in control brown adipocytes, retention of MR was observed in FPLD2 brown adipocyte nuclei. Moreover, overexpression of wild-type or mutated prelamin A caused GFP-MR recruitment to the nuclear envelope in HEK293 cells, while drug-induced prelamin A co-localized with endogenous MR in human preadipocytes. Based on in silico analysis and in situ protein ligation assays, we could suggest an interaction between prelamin A and MR, which appears to be inhibited by mineralocorticoid receptor antagonism. Importantly, the MR antagonist spironolactone redirected FPLD2 preadipocyte differentiation towards the brown lineage, avoiding the formation of enlarged and dysmorphic lipid droplets. Finally, beneficial effects on brown adipose tissue activity were observed in an FPLD2 patient undergoing spironolactone treatment. These findings identify MR as a new lamin A interactor and a new player in lamin A-linked lipodystrophies.

9.D. Workshop: Obesity: the greatest burden of the 21st Century and the post-pandemic

Abstract Obesity, a complex multifactorial disorder, is defined as excess accumulation of adipose tissue that presents as a risk to health. There is an ongoing debate whether obesity should be labelled as a chronic disease or as a risk factor due to the associated economic, health, labour related implications among others. Although, some international organization such as the World Health Organization (WHO), has declared obesity as a disease. Another challenge is the mode of measurement utilized. The body mass index (BMI) is commonly used to define obesity, while others utilize the waist circumference or the waist-hip ratio. However, it is well established that these modes of measurement are not perfect, leaving room for discussion as to the best way forward. Amidst all this, obesity has been a global epidemic for decades with progressive increasing population rates. Country specific policies targeting obesity have been implemented across the years, yet the obesogenic environment is still dominating in most countries. Furthermore, the recent onset of COVID-19 pandemic brought with it the implementation of mitigations measures and restrictions which further increased the risk of obesity, even among children. This period saw unfavourable shifts in food consumption as well as distribution in physical activity patterns. As we enter the post-COVID era, we are faced with a multitude of challenges one being the “Obesity ever-growing epidemic”. This workshop aims to bring together expert presentations from a multidisciplinary field to discuss the direction that should be taken to halt this epidemic especially at the backdrop of COVID-19. The workshop will open with a debacle on the heterogeneity of obesity and how to define weight status correctly and accurately. This will set the scene as to the complexity of obesity, from its definition to appropriate management. The population's nutritional intake plays a role in this epidemic and is a valuable tool for obesity prevention, management, and treatment. Targeting the paediatric population is key, while highlighting the importance of following the Mediterranean Diet to tackle this epidemic. Additionally creating a healthy food system is also merited. One cannot forget the impact that the environment plays in development of obesity. Indeed, targeting the environment is crucial to ensure that the population is exposed to a “healthy environment” that promotes population wellbeing. Several obesity targeted policies and interventions have been implemented across countries, yet obesity epidemic is ever so growing. This sets forward the question as to whether behavioural aspects could be the leading contributor to this epidemic? The final presentation will provide insights on how the socio-behavioural aspects of a population effect the rampant obesity ecosystem we are living in. Key messages • Obesity is still a global epidemic requiring an urgent multidisciplinary approach. • Action targeting the nutrition, environment and socio-behavioural aspects are a must to deal with the obesity epidemic.