Excessive Fat Accumulation Research Articles

Lupeol Attenuates Palmitate-Induced Hypertrophy in 3T3-L1 Adipocytes

Obesity is characterized by the enlargement of adipose tissue due to an increased calorie intake exceeding the body’s energy expenditure. Changes in the size of adipose tissue can lead to harmful consequences, with excessive fat accumulation resulting in adipocyte hypertrophy and promoting metabolic dysfunction. These adiposity-associated pathologies can be influenced by dietary components and their potential health benefits. Lupeol, a pharmacologically active pentacyclic triterpenoid found in medicinal plants, vegetables, and fruits, has been shown to exhibit antioxidant and anti-inflammatory properties. This study investigated the role of lupeol on adipocyte hypertrophy by evaluating key adipogenic regulators in vitro. First, 3T3-L1 MBX mouse embryonic cells were differentiated into adipocytes and hypertrophy was induced using 500 µM palmitic acid. The treated adipocytes showed a significantly increased lipid droplet size, confirming adipocyte hypertrophy. Both adipocytes and hypertrophied adipocytes were then treated with or without 60 µM lupeol, following a dose-dependent study. Lipid droplet size was assessed and validated by Oil Red O staining. Western blot analysis was performed to measure the expression of adipogenic and inflammatory markers. Differentiated adipocytes showed increased fatty acid-binding protein 4 (FABP4) expression and Oil Red O staining, indicating an increased lipid content. Western blot analysis revealed that lupeol treatment reduced the expression of FABP4, peroxisome proliferator-activated receptor-γ (PPARγ), and adipokines. In conclusion, the results suggest that lupeol reverts the inflammatory and adipogenic markers that are enhanced in adipocyte hypertrophy. Through its anti-inflammatory effects, lupeol offers protective effects against adipocyte hypertrophy and contributes to reducing hypertrophic adiposity.

Myristoylated Eepd1 Enhances Lipolysis and Thermogenesis through PKA Activation to Combat Obesity

Middle-aged obesity, characterized by excessive fat accumulation and systemic energy imbalance, often precedes various health complications. Recent research has unveiled a surprising link between DNA damage response and energy metabolism. Here, we explore the role of Eepd1, a DNA repair enzyme, in regulating adipose tissue function and obesity onset. Eepd1 is primarily expressed in adipose tissue, where its downregulation or deletion accelerates obesity development. We show that Eepd1 ablation hinders PKA activation, thereby inhibiting lipolysis and thermogenesis in adipose tissue. Notably, cold exposure enhances Eepd1’s myristoylation, facilitating its anchorage to adipocyte membranes and subsequent activation of PKA, while a mutation at the myristoylation site of Eepd1 disrupts this process. Moreover, individuals with obesity exhibit reduced Eepd1 expression. Pharmacological restoration of Eepd1 with Retigabine dihydrochloride effectively mitigates obesity. This study reveals Eepd1’s unexpected role in promoting adipose lipolysis and thermogenesis, underscoring its potential as a promising therapeutic target to combat obesity.

Impact of Hypocaloric Diets on Weight Loss and Body Composition in Obese Dogs: A Meta-Analysis

Canine obesity is a complex, multifactorial condition marked by excessive body fat accumulation due to a sustained positive energy balance. Over the past decade, its global prevalence has risen significantly in most industrialized nations. Despite the availability of numerous commercial diets designed for obesity management in dogs, these products exhibit considerable variability in nutrient composition, and there is currently no standardized guideline on optimal macronutrient levels for effective weight loss. This study aimed to evaluate the effects of specific macronutrient levels on weight loss and body composition in obese dogs. A comprehensive literature search was conducted from 2022 to 2024 across PUBMED, Scielo, Web of Science, and Google Scholar. Out of an initial 1727 documents, 20 studies met the inclusion criteria and were incorporated into this meta-analysis. Diets with energy densities below 3.275 kcal, protein levels above 25%, total dietary fiber exceeding 12%, lower fat (<10%), and reduced non-nitrogenous extract (<40%) demonstrated beneficial effects on all evaluated parameters, including weight loss and body composition assessment. This meta-analysis provides evidence-based nutritional recommendations on optimal caloric, protein, fiber, fat, and carbohydrate levels for hypocaloric diet formulations, supporting healthy weight loss and lean mass preservation in obese dogs. These findings contribute to the development of effective dietary strategies that enhance canine quality of life and longevity.

An enhanced predictive modelling framework for highly accurate non-alcoholic fatty liver disease forecasting

Non-alcoholic fatty liver disease (NAFLD) is a chronic medical ailment characterized by accumulation of excessive fat in the liver of non-alcoholic patients. In absence of any early visible indications, application of machine learning based predictive techniques for early prediction of NAFLD are quite beneficial. The objective of this paper is to present a complete framework for guided development of varied predictive machine learning models and predict NAFLD disease with high accuracy. The framework employs step–by-step data quality enhancement to medical data such as cleaning, normalization, data upscaling using SMOTE (for handling class imbalances) and correlation analysis-based feature selection to predict NAFLD with high accuracy using only clinically recorded identifiers. Comprehensive comparative analysis of prediction results of seven machine learning predictive models is done using unprocessed as well as quality enhanced data. As per the observed results, XGBoost, random forest and neural network machine learning models reported significantly higher accuracies with improved ‘AUC’ and ‘ROC’ values using preprocessed data in contrast to unprocessed data. The prediction results are also assessed on various quality metrics such as ‘accuracy’, ‘f1-score’, ‘precision’, and ‘recall’ significantly support the need for presented methodologies for qualitative NAFLD prediction modelling.

Chitooligosaccharide-Epigallocatechin Gallate Conjugate Ameliorates Lipid Accumulation and Promotes Browning of White Adipose Tissue in High Fat Diet Fed Rats

The prevalence of obesity has increased progressively worldwide. Obesity is characterized by excessive accumulation of fat in adipose tissues, leading to metabolic impairment. The anti-obese effects of chitooligosaccharide (COS) and epigallocatechin-3-gallate (EGCG) have been extensively clarified. This study aimed to investigate the effects and potential mechanisms of the COS-EGCG conjugate (CE) on anti-obesity, specifically by alleviating lipid accumulation and promoting the browning of white adipose tissue (WAT) in obese rats. Obesity as a consequence of a high-fat diet (HFD) was induced in male Wistar rats. The HFD was given for 16 weeks and the rats were then randomly subdivided into five groups namely: vehicle (control group), HFD plus CE at 150 mg/kg/day, HFD plus CE at 600 mg/kg/day, HFD plus COS at 600 mg/kg/day, and HFD plus atorvastatin at 10 mg/kg/day for 4 weeks. CE could reduce body weight, improve serum lipid profiles, and promote lipid metabolism via activation of AMP-activated protein kinase (AMPK) in WAT and enhance the processes of WAT browning by activating sirtuin 1 (Sirt 1), peroxisome proliferator-activated receptor-gamma coactivator (PGC1-α), and uncoupling the protein 1 (UCP1) signaling pathway. CE reduced obesity and promoted WAT browning in HFD-fed rats. Therefore, CE might be a new therapy for metabolic syndrome and obesity.

Understanding Adipose Tissue Dysfunction.

Diseases affecting adipose tissue (AT) function include obesity, lipodystrophy, and lipedema, among others. Both a lack of and excess AT are associated with increased risk for developing diseases including type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and some types of cancer. However, individual risk of developing cardiometabolic and other 'obesity-related' diseases is not entirely determined by fat mass. Rather than excess fat accumulation, AT dysfunction may represent the mechanistic link between obesity and comorbid diseases. There are people who remain metabolically healthy despite obesity, whereas people with normal weight or very low subcutaneous AT mass may develop typically obesity-related diseases. AT dysfunction is characterized by adipocyte hypertrophy, impaired subcutaneous AT expandability (ectopic fat deposition), hypoxia, a variety of stress, inflammatory processes, and the release of proinflammatory, diabetogenic, and atherogenic signals. Genetic and environmental factors might contribute to AT heterogeneity either alone or via interaction with intrinsic biological factors. However, many questions remain regarding the mechanisms of AT dysfunction initiation and whether and how it could be reversed. Do AT signatures define clinically relevant subtypes of obesity? Is the cellular composition of AT associated with variation in obesity phenotypes? What roles do environmental compounds play in the manifestation of AT dysfunction? Answers to these and other questions may explain AT disease mechanisms and help to define strategies for improving AT health. This review focuses on recent advances in our understanding of AT biology.

Semaglutide, liraglutide and tirzepatide: Comparison of effectiveness in the treatment of obesity – a literature review

Introduction Obesity is a complex, multifactorial condition characterized by an excessive accumulation of body fat. It is widely recognized as a major public health issue due to its strong association with numerous chronic diseases. [1][2] The use of GLP-1 receptor agonists in obesity treatment began with the recognition that these drugs, initially developed for type 2 diabetes, could significantly reduce body weight due to their effects on appetite regulation and satiety. Liraglutide was the first to be approved specifically for obesity, followed by semaglutide, The development of tirzepatide, which targets both GLP-1 and GIP receptors, has further expanded the potential for obesity treatment. As clinical evidence continues to support their efficacy and safety, GLP-1 receptor agonists are becoming an important tool in the management of obesity, offering a promising option for individuals struggling with weight and related health conditions [3][4][5]. Aim of the study The aim of this study was to compare the effectiveness of semaglutide, liraglutide and tirzepatide in reducing body weight in obesity. Materials and methods The article was created based on the PubMed and Cochrane databases. The literature was analyzed using the fallow keywords: Obesity treatment, liraglutide, tirzepatide, semaglutide, glucagon-like peptide-1 (GLP-1) receptor agonists Results The research proved that tirzepatide is more effective in reducing body weight compared to semaglutide and liraglutide [6][7]. Conclusion Thanks to the comparison of results from multiple studies, we can assume that, at this point, tirzepatide is the most effective pharmacological treatment for obesity, which, when used in combination with lifestyle changes, provides a lasting effect on weight reduction and, consequently, helps treat obesity-related comorbidities[6][8].

The Role of Kinesiotherapy in Enhancing Physical Performance and Self-Esteem: A Prospective Observational Study in Obese Adolescents

Obesity is a multifactorial chronic condition characterized by excessive fat accumulation, which adversely affects health and quality of life. This prospective observational study aimed to evaluate the impact of a 9-month tailored kinesiotherapy program on physical performance, body composition, and self-esteem in overweight and obese adolescents. Participants were divided into a study group (SG, n=40) and a control group (CG, n=40). The SG engaged in individualized kinesiotherapy sessions, while the CG maintained their usual activities. Both groups received education on the 5-2-1-0 rule for obesity prevention and management. Results indicated significant improvements in the SG, including enhancements in the 6-minute walk distance (6MWD), Timed Up-and-Go test (TUG), and Rosenberg Self-Esteem Scale (all p < 0.001). Notably, BMI and body fat percentage decreased significantly in the SG compared to the CG. Regression analysis revealed strong correlations between body composition, physical performance, and self-esteem improvements, particularly in girls and rural participants, highlighting the intervention's adaptability and effectiveness. Although limited by a relatively small sample size, short duration, and variability in adherence tracking, the study highlights the essential role of individualized physical activity programs in improving health outcomes. In conclusion, the findings from our study emphasize the significant role of individualized kinesiotherapy programs in improving physical and psychological health outcomes in overweight/obese adolescents. By integrating instrumental assessments, such as the BTS system, with subjective evaluations like PAQ-A and the Rosenberg scale, our study high-lights the multifaceted impact of physical activity on this vulnerable population.

Antibiotic Exposure and Childhood Overweight/Obesity: Evidence From Epidemiological and Experimental Studies.

Childhood overweight and obesity are nutritional disorders in which children's energy intake exceeds energy consumption for a long period, resulting in the excessive accumulation of body fat and weight that exceeds a certain range. It is one of the most serious public health issues. In recent years, its prevalence has shown a significant upward trend, and 41-80% of childhood obesity can persist into adulthood.Scholars are now more interested in researching this further. Since antibiotics have been used extensively since their discovery, more focus has been paid to the possible risks these medications pose to children who are exposed to them. Recently, some studies have explored the possible link between antibiotic exposure and the prevalence of overweight and obesity in children. However, their findings are inconsistent. Therefore, this review aims to synthesize and summarize the studies related to the effects of antibiotics on childhood obesity, elucidate the possible associations between the two, and provide an in-depth discussion of the potential biological mechanisms by which antibiotics exposure may contribute to childhood obesity.

Yogurt Supplementation Can Ameliorate Fatty Liver Diseases and Metabolic Syndrome in High Fat-Induced Conditions in Mice.

Hepatic steatosis/non-alcoholic fatty liver disease is a major public health delinquent caused by the excess deposition of lipid into lipid droplets (LDs) as well as metabolic dysregulation. Hepatic cells buildup with more fat molecules when a person takes high fat diet that is excessive than the body can handle. At present, millions of people in the world are affected by this problem. So, it is very important to know the effects of factors responsible for the disease. Here, the role of lipid droplet (LD) biogenesis and metabolism was analyzed and intended to investigate if defects in biogenesis/metabolic enzymes are responsible for the accumulation of lipids other than LDs in fatty liver disease in high-fat-induced conditions in mice model. To explore it, high-fat diet (HFD), fast food (FF), and soft drinks (SD) were administered to wild-type Swiss albino mice for 14 weeks following yogurt supplementation. After experimental period, glucose tolerance, enzyme function, lipid profile, plasma biochemistry, and other analytical tests were analyzed by auto-analyzer including different oxidative stress markers. Lipids from hepatic tissues were extracted, and purified by Floatation Assay and subsequently analyzed by different biochemical and chromatographic techniques. Histological architecture of hepatocytes was performed using Zeiss microscope. Finally, increased amount of lipids biogenesis/accumulation was found in liver tissues that causes Fatty liver disease. Significantly, HFD, FF, and SD were identified as factors for the increased LD biogenesis and or lipid metabolic disorder. Nevertheless, yogurt supplementation can homeostasis those LD formation and metabolic syndrome as it increases the down regulation of lipid biogenesis as well as lipid metabolic rate. So, yogurt supplementation was considered as a novel agent for decreasing LD biogenesis as well as excessive accumulation of fat in hepatocytes which can be used as therapeutics for the treatment of NAFLD.

Inappropriate Diet Exacerbates Metabolic Dysfunction-Associated Steatotic Liver Disease via Abdominal Obesity.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a refined categorization of non-alcoholic fatty liver disease (NAFLD), highlighting the intricate relationship between hepatic steatosis and metabolic dysfunction. Abdominal obesity (AO), a key diagnostic criterion for metabolic dysfunction, predominantly results from inappropriate diet and unhealthy dietary habits. To comprehensively investigate which dietary factors contribute to MASLD through AO and to understand the underlying biological mechanisms, we initially conducted a systematic review of meta-analysis articles in the PubMed database from the past decade, summarizing dietary factors that affect AO. Subsequently, we conducted targeted searches in the PubMed database for these dietary factors and provided a narrative review of the mechanisms of how these dietary factors lead to AO and how AO exacerbates MASLD. A diet characterized by excessive intake of energy, carbohydrates, fructose, or ultra-processed foods (UPFs) is considered inappropriate. Inappropriate diet leads to the formation of MASLD and AO by enhancing pathways such as de novo lipid synthesis (DNL) in the liver, insulin resistance (IR), gut-liver dysfunction, and inflammation. Dietary interventions for inappropriate diets can effectively intervene in and improve MASLD and AO. The mechanism of inappropriate diet on abdominal fat deposition is through excessive energy or the activation of the enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1) to increase endocortisol secretion. Then, the excessive accumulation of visceral fat facilitates a rapid and augmented flux of free fatty acids (FFAs) to the liver and initiates a series of deleterious effects, including oxidative stress (OS), endoplasmic reticulum stress (ERS), activation of protein kinase C (PKC) pathways, and inflammation. Additionally, FFAs may mediate excessive lipid deposition and hepatocellular damage through the action of hormones. These pathways to liver damage exacerbate MASLD and progression to metabolic dysfunction-associated steatohepatitis (MASH) and fibrosis. Furthermore, investigating other potential mechanisms by which AO may influence MASLD could offer new recommendations for the treatment guidelines of MASLD.

The effect of oyster mushroom (Pleurotus ostreatus) beta-glucan extract on brain -derived neurotrophic factor and neuron in high-fat-high-fructose diet-induced male Sprague Dawley rats

Obesity is a condition where there is an accumulation of excess body fat, which can increase oxidative stress either in the blood or in tissues, such as brain tissue. This situation can trigger atrophy in neurons and reduce brain-derived neurotrophic factor (BDNF) levels, which can increase the risk of impaired cognitive function. This study aimed to ascertain the effect of oyster mushroom (Pleurotus ostreatus) β-glucan extract on the number of neurons and levels of BDNF in rats. The study design was a true experimental with a randomized control group post-test only with white male Sprague Dawley rats as the subjects. A total of twenty-four rats were divided into four groups, namely the normal diet group fed AIN-93M standard diet (KN), the high-fat-high-fructose (HFHF) diet group (KP), and the HFHF diet group with the addition of β-glucan extract dose of 125 mg/kg body weight (P1), and dose of 375 mg/kg body weight (P2). The BDNF was measured by ELISA, and the number of neurons was by histological staining approach. Although there was no significant difference in the number of neurons (p = 0.692), the data revealed a significant difference in BDNF levels (p = 0.005). There was no relationship between the number of neurons and BDNF levels (p = 0.874) and between the β-glucan dose and the number of neurons (p = 0.796). However, there was a relationship between β-glucan dose and BDNF levels (p = 0.001; r = 0.695). This study concludes that the dose of β-glucan from oyster mushroom extract positively affects BDNF levels but not the number of neurons. There was no relationship between the number of neurons with BDNF levels and β-glucan dose. It was presumable because the staining technique was less specific, so the possibility of other cells counted as neurons may occur

Erhong Jiangzhi Decoction Inhibits Lipid Accumulation and Alleviates Nonalcoholic Fatty Liver Disease with Nrf2 Restoration Under Obesity.

Nonalcoholic fatty liver disease (NAFLD) refers to the liver pathological changes caused by excessive fat accumulation in hepatocytes owing to various reasons, which has become an emerging health challenge. Erhong Jiangzhi Decoction (EHJD) is a traditional Chinese medicine decoction. This study aims to investigate the therapeutic effect of EHJD on NAFLD. NAFLD model was constructed by high-fat diet (HFD)-induced mice and oleic acid-induced HepG2 cells. Mice were intragastrically administered with EHJD and HepG2 cells were treated with EHJD drug-containing serum. The effects of EHJD on NAFLD were explored in vivo and in vitro. Histological assessment was performed by hematoxylin-eosin and oil red O staining. ELISA was exploited to detect the expression of lipid accumulation, liver function, inflammation, and oxidative stress related indicators. The expression of Nrf2/HO-1 pathway was detected by qRT-PCR and Western blot. In HFD-induced NAFLD mice, the body weight was increased, and liver/weight, inguinal fat/weight, and epididymal fat/weight were higher, while EHJD reduced them. Staining results exhibited that EHJD decreased inflammatory cell infiltration and oil red lipid droplets in HFD-induced mice. In addition, EHJD treatment suppressed TC, TG, ALT and AST levels; TNF-α, IL-1β, IL-6 and MDA levels were inhibited by EHJD, while GSH-Px, CAT and T-AOC levels were increased in NAFLD through the in vivo and in vitro experiments. The suppression of Nrf2 weakened the inhibitory effect of EHJD on lipid metabolism, liver injury, inflammation and oxidative stress. EHJD had a protective effect on NAFLD by alleviating lipid accumulation and liver injury, inhibiting inflammation, and oxidative stress, which was achieved by the restoration of Nrf2.

Intervention effects of Er Miao san on metabolic syndrome in Bama miniature pigs.

Metabolic syndrome (MS) refers to a cluster of metabolic disorders characterized by systemic chronic inflammation. Er Miao San (EMS) is a classic traditional Chinese medicine compound containing Phellodendron amurense and Atractylodis rhizome at a ratio of 1:1, proven to be effective against inflammatory diseases in clinical practice. Nevertheless, the precise functions of EMS in treating MS and its underlying mechanism have yet to be elucidated. This study focuses on the intervention effects of EMS on high humidity exposure and high sugar-fat diet (HHSF)-induced MS in pigs. Blood biochemical indices and metabolome analysis were employed to confirm the successful establishment of the MS model, and the preliminary evaluation of the intervention effect of EMS was conducted. Subsequently, a parallel microbiota analysis of the tongue and cecum was combined with metabolomic analysis, histopathologic examination, and other molecular biological detection to further assess the administration mechanism of EMS. The results demonstrated that EMS significantly reduced the excessive weight gain rate, fat accumulation, hyperlipidemia, hyperglycemia, and systemic inflammation while improving serum metabolic disorder in MS pigs. Moreover, microbiota analysis indicates that EMS restored the diversity and composition of oral-gut microbiota by increasing the proportions of Lactobacillus (gut), Roseburia (gut), Faecalibacterium (gut), CF231 (gut), Streptococcus (gut), Prevotella (gut), while decreasing those of Chryseobacterium (oral), Corynebacterium (oral), Clostridium (oral), Oscillospira (gut), and Turicibacter (oral, gut). Subsequently, EMS up-regulated the concentrations of acetic acid, butyric acid, propionic acid, while down-regulated isobutyric acid and isovaleric acid. This resulted in a suppression of HDAC3 expression and an increase of SCL16A1 expression in the colon. Notably, the changes in acetic acid and butyric acid showed a strong correlation with gut microbiota. Additionally, EMS reduced the serum level of lipopolysaccharide (LPS) and enhanced epithelial barrier integrity by inhibiting the LPS-TLR4/MyD88/NF-κB pathways. EMS was found to ameliorate MS by alleviating the dysbiosis of the oral-gut microbiota and serum metabolome, thereby improving gut barrier and reducing systemic inflammation. These findings suggest that EMS holds promise as a therapeutic agent for MS.

Content Analysis through TikTok Social Media Comments: Use of Herbal Medicine

Obesity is a condition where there is excessive accumulation of body fat so that a person's weight is far above normal, this is caused by an imbalance in energy intake and expenditure. The high number of Tiktok users in Indonesia makes Tiktok an effective social media application. This makes the content on Tiktok easily attract the attention of viewers in the field of health and healthy lifestyles in the comments column. This study wants to find out how the audience receives messages from health content creator Dr. Rianti Maharani with the account name @dr.riantiherbal through the comments column. This study uses a qualitative descriptive method with reception analysis theory. The subjects in this study were 17-45 years old, were viewers and provided comments on the @drriantiherbal account. The results of the study found that opposite comments appeared a lot in the comments column, namely 41 comment samples.

A Study of Body Composition as a Predictor of Muscle Quality and Endurance- A Cross-Sectional Study

Background: The alarming rise in sarcopenic obesity is compromising the quality of life for millions, underscoring the urgent need to unravel the factors contributing to muscle decline. Sarcopenic obesity, characterized by the concurrent loss of muscle mass and accumulation of excess fat, is a growing public health concern. This condition, often exacerbated by aging and poor lifestyle, negatively impacts muscle quality and contributes to a multitude of comorbidities. Previous research has demonstrated a significant association between obesity and reduced muscle strength compared to non-obese individuals, hindering activities of daily living such as stair climbing and walking. This study aims to investigate the predictive role of body composition on muscle quality and endurance. Methods: This cross-sectional study was carried out on 385 healthy male and female subjects aged between 18-67 years. The staff and students of JMMC and RI were selected for the study based on the inclusion and exclusion criteria, after obtaining the Institutional Ethical Clearance. Handgrip strength (HGS) and endurance (HE) was measured using handgrip dynamometer while body composition was assessed using Omron body fat analyser. Comparisons were done between age and gender. Statistical analysis was done using Independent T test, One-Way ANOVA and Mann Whitney test on SPSS version 20.Results: As age advances, there is statistically significant increase in BMI and BFP (body fat percentage) in both the genders. Increase in BMI and BFP is more pronounced in females with significant decrease in muscle mass percentage and HGS. Females had significant decline in endurance in all age groups (p<0.001).Conclusion: As the BMI and BFP increase with age, the muscle quality deteriorates. Females have more adiposity, poor muscle strength and endurance even though BMI remains same in both genders. To identify the early onset of decrease in muscle quality and endurance, a combination of parameters like BMI, BFP, HGS and HE should form a part of routine clinical screening.

A systematic review, ANCOVA meta-analysis, and meta-regression of clinical trials : Orlistat and body mass index of overweight and obese patients

Background: Obesity or overfat (i.e., excessive fat accumulation in the host) contributes to cerebrocardiovascular and other diseases. Orlistat is a good obesity medication, unlike other drugs that have higher cardiac toxicity. It reversibly inhibits pancreatic and gastric lipases, and improves oxysterol metabolism. This study summarizes and elaborates the impact of orlistat on BMI in overweight and obese adult patients. Methods: All authors systematically searched and retrieved 288 controlled trial articles on orlistat and BMI from three databases, two registries, and citation searches using specific keywords. The quality and bias risks were determined by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE), Risk of Bias in Non-Randomized Study (ROBINS-I), and modified Jadad scale. R version 4.2.2 software calculated the effect size and the analysis of covariance (ANCOVA) effect, and subsequently analyzed using metafor. Results: This novel meta-analysis included 114 studies with 24,600 overweight or obese participants. We showed that orlistat substantially reduced BMI (mean difference −0.78 [−0.94, −0.63], p < 0.0001; I2 = 90.19%, pheterogeneity < 0.0001). Similarly, meta-regression showed a significant impact of orlistat daily dose (ß = −0.0019), yet not for duration (ß = −0.0024) and location (ß = −0.8591, −0.0190). Conclusion: Orlistat has the capacity to reduce BMI in overweight and obese individuals. Medical practitioners shall prescribe orlistat as a BMI lowering agent to complement other intervention in those patients

Obesity impact on bones and joints health

Introduction and objective Obesity, characterized by excessive fat accumulation, poses significant health risks. The WHO classifies overweight as a BMI of 25 to <30 kg/m² and obesity as a BMI of ≥30 kg/m², divided into three classes. This study examines the relationship between obesity and bone health, focusing on osteoarthritis (OA), rheumatoid arthritis (RA), and fracture risks. Review methods A review of epidemiological and clinical studies was conducted, including WHO statistics, U.S. obesity trends, and recent findings on the mechanisms linking obesity with bone health and joint diseases. Studies were selected for their relevance to understanding obesity's impact on skeletal health. Abbreviated description of the state of knowledge Obesity is influenced by sociodemographic, behavioral, and genetic factors. While excess weight was once considered beneficial for bones due to increased mechanical loading, recent research shows its harmful effects. Obesity is linked to chronic inflammation, altered adipokine levels, and higher risk of atypical fractures. In OA, obesity accelerates joint degeneration through mechanical and metabolic pathways. In RA, obesity is associated with increased disease activity and cardiovascular complications. Summary Obesity significantly affects bone and joint health, increasing the risk of OA, RA, and fractures. The paradox of obesity providing mechanical benefits while causing metabolic and inflammatory issues is crucial. Understanding these mechanisms is vital for developing effective prevention and management strategies for obesity-related skeletal diseases. Further research is essential to clarify the complex interactions between adipose tissue and bone health, aiming to improve outcomes for obese individuals.

Unveiling the Anti-Obesity Potential of Thunder God Vine: Network Pharmacology and Computational Insights into Celastrol-like Molecules.

Obesity, characterized by abnormal or excessive fat accumulation, has become a chronic degenerative health condition that poses significant threats to overall well-being. Pharmacological intervention stands at the forefront of strategies to combat this issue. Recent studies, notably by Umut Ozcan's team, have uncovered the remarkable potential of Celastrol, a small-molecule compound derived from the traditional Chinese herb thunder god vine (Tripterygium wilfordii) as an anti-obesity agent. In this research, computational chemical analysis was employed, incorporating the "TriDimensional Hierarchical Fingerprint Clustering with Tanimoto Representative Selection (3DHFC-TRS)" algorithm to systematically explore 139 active small molecules from thunder god vine. These compounds were classified into six categories, with a particular focus on Category 1 molecules for their exceptional binding affinity to obesity-related targets, offering new avenues for therapeutic development. Using advanced molecular docking techniques and Cytoscape prediction models, six representative Celastrol-like molecules were identified, namely 3-Epikatonic Acid, Hederagenin, Triptonide, Triptotriterpenic Acid B, Triptotriterpenic Acid C, and Ursolic Acid. These compounds demonstrated superior binding affinity and specificity toward two key obesity targets, PPARG and PTGS2, suggesting their potential to regulate fat metabolism and mitigate inflammatory responses. To further substantiate these findings, molecular dynamics simulations and MM-PBSA free-energy calculations were applied to analyze the dynamic interactions between these small molecules and the enzymatic active sites of their targets. The results provide robust theoretical evidence that support the feasibility of these molecules as promising candidates for anti-obesity therapies. This study underscores the power of the 3DHFC-TRS algorithm in uncovering bioactive compounds from natural sources, such as thunder god vine, and highlights the therapeutic promise of PPARG and PTGS2 as novel obesity-related targets. Furthermore, it emphasizes the essential role of computational science in expediting drug discovery, paving the way for personalized and precision-based treatments for obesity and heralding a future of more effective healthcare solutions.

Contribution of glucose and glutamine to hypoxia-induced lipid synthesis decreases, while contribution of acetate increases, during 3T3-L1 differentiation

The molecular mechanisms linking obstructive sleep apnea syndrome (OSA) to obesity and the development of metabolic diseases are still poorly understood. The role of hypoxia (a characteristic feature of OSA) in excessive fat accumulation has been proposed. The present study investigated the possible effects of hypoxia (4% oxygen) on de novo lipogenesis by tracking the major carbon sources in differentiating 3T3-L1 adipocytes. Gas-permeable cultuware was employed to cultivate 3T3-L1 adipocytes in hypoxia (4%) for 7 or 14 days of differentiation. We investigated the contribution of glutamine, glucose or acetate using 13C or 14C labelled carbons to the newly synthesized lipid pool, changes in intracellular lipid content after inhibiting citrate- or acetate-dependent pathways and gene expression of involved key enzymes. The results demonstrate that, in differentiating adipocytes, hypoxia decreased the synthesis of lipids from glucose (44.1 ± 8.8 to 27.5 ± 3.0 pmol/mg of protein, p < 0.01) and partially decreased the contribution of glutamine metabolized through the reverse tricarboxylic acid cycle (4.6% ± 0.2–4.2% ± 0.1%, p < 0.01). Conversely, the contribution of acetate, a citrate- and mitochondria-independent source of carbons, increased upon hypoxia (356.5 ± 71.4 to 649.8 ± 117.5 pmol/mg of protein, p < 0.01). Further, inhibiting the citrate- or acetate-dependent pathways decreased the intracellular lipid content by 58% and 73%, respectively (p < 0.01) showing the importance of de novo lipogenesis in hypoxia-exposed adipocytes. Altogether, hypoxia modified the utilization of carbon sources, leading to alterations in de novo lipogenesis in differentiating adipocytes and increased intracellular lipid content.