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Adipocyte Dec 2024Adipose tissue plays a crucial role in metabolic syndrome, autoimmune diseases, and many cancers. Because of adipose's role in so many aspects of human health, there is...
Adipose tissue plays a crucial role in metabolic syndrome, autoimmune diseases, and many cancers. Because of adipose's role in so many aspects of human health, there is a critical need for in vitro models that replicate adipose architecture and function. Traditional monolayer models, despite their convenience, are limited, showing heterogeneity and functional differences compared to 3D models. While monolayer cultures struggle with detachment and inefficient differentiation, healthy adipocytes in 3D culture accumulate large lipid droplets, secrete adiponectin, and produce low levels of inflammatory cytokines. The shift from monolayer models to more complex 3D models aims to better replicate the physiology of healthy adipose tissue in culture. This study introduces a simple and accessible protocol for generating adipose organoids using a scaffold-free spheroid model. The method, utilizing either 96-well spheroid plates or agarose micromolds, demonstrates increased throughput, uniformity, and ease of handling compared to previous techniques. This protocol allows for diverse applications, including drug testing, toxin screening, tissue engineering, and co-culturing. The choice between the two methods depends on the experimental goals, with the 96-well plate providing individualized control and the micromold offering scale advantages. The outlined protocol covers isolation, expansion, and characterization of stromal vascular fraction cells, followed by detailed steps for spheroid formation and optional downstream analyses.
Topics: Spheroids, Cellular; Adipose Tissue; Humans; Adipocytes; Cell Culture Techniques; Animals; Tissue Engineering; Cells, Cultured; Cell Differentiation; Mice
PubMed: 38864486
DOI: 10.1080/21623945.2024.2347215 -
Surgery For Obesity and Related... May 2024The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk.
BACKGROUND
The stage of life at the onset of obesity is an important factor in assessing inflammatory state and cardiometabolic risk.
OBJECTIVES
This study aimed to evaluate the relationship between the obesity onset and the inflammatory profile in women with severe obesity.
SETTING
Public hospital, Brazil.
METHODS
Forty-eight women with severe obesity (20-59 yr old) were evaluated according to weight, height, neck circumference (NC), waist circumference (WC), and hip circumference, as well blood metabolic and inflammatory parameters. The participants were grouped according to obesity onset stage of life (early group: ≤19 yr; late group: >19 yr).
RESULTS
The demographic means of the participants were: age of 39.7 years, weight of 122.7 kg and body mass index (BMI) of 48.4 kg/m. The late group presented significantly higher values of leptin (lep)/adiponectin (adipo) ratio and homeostatic model assessment for insulin resistance (HOMA-IR) than the early group. The late group also had a lower adipo/lep ratio. Moreover, the late group showed correlations between the lep/adipo ratio and BMI (r = .460, P = .021), NC (r = .478, P = .016), and WC (r = .535, P = .006). Adipo was also correlated with NC (r = -.418, P = .038), WC (r = -.437, P = .029), and glycated hemoglobin (HbA1C) (r = -.485, P = .019). By contrast, in the early group, the lep/adipo ratio showed correlations with insulin (r = .647, P = .004) and HOMA-B (r = .564, P = .015).
CONCLUSIONS
The inflammatory profile is correlated with anthropometric values in women with late-onset obesity. Inflammatory markers seemed to correlate with the glycemic profile in women with early-onset obesity. Furthermore, inflammation was higher in women with late-onset obesity compared to those with early-onset obesity.
PubMed: 38862297
DOI: 10.1016/j.soard.2024.04.015 -
Clinical Nutrition (Edinburgh, Scotland) Jul 2024Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern. The disease is silent, and its diagnosis is often delayed.... (Randomized Controlled Trial)
Randomized Controlled Trial
Inflammatory markers as diagnostic and precision nutrition tools for metabolic dysfunction-associated steatotic liver disease: Results from the Fatty Liver in Obesity trial.
BACKGROUND & AIMS
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing public health concern. The disease is silent, and its diagnosis is often delayed. Inflammatory markers constitute an interesting tool to act as subrogate, non-invasive markers. This study aimed to evaluate the changes of inflammatory markers throughout a two-year dietary intervention in subjects presenting MASLD, to determine which of the markers are suitable to predict the disease, and act as a customizing tool for MASLD's dietary treatment.
METHODS
Ninety-eight subjects with MASLD and forty-five controls from the Fatty Liver in Obesity (FLiO) Study were analyzed. MASLD was diagnosed and graded by ultrasound. The MASLD subjects were randomly assigned to two different dietary strategies, the American Heart Association (AHA diet) or a dietary strategy based on the Mediterranean pattern, which was specially designed for the study (FLiO diet), and then followed for two years. Hepatic status was additionally assessed through Magnetic Resonance Imaging (MRI), elastography, and determination of transaminases.
RESULTS & DISCUSSION
Inflammatory markers improved throughout the intervention in the MASLD subjects and managed to reach similar levels to controls, especially at 6 and 12 months. Additionally, leptin, adiponectin, M30, and LECT2 managed to significantly diagnose the disease at all time marks of the intervention, making them candidates for subrogate non-invasive markers of the disease. Moreover, baseline chemerin, leptin, LECT2, and M65 were used to build a predictive score to achieve greater weight loss, and therefore, which strategy could be more useful for MASLD 's treatment. The predictive score was significantly able assign a specific diet to 55% of the study participants, meaning that the remaining 45% could achieve the same amount of weight loss following either diet equally.
CONCLUSION
Inflammatory markers constitute a potential non-invasive tool to be used in MASLD screening and could also constitute an interesting tool for MASLD's treatment customization, being able to predict the effectiveness of a dietary strategy based on the initial inflammatory state of each subject.
TRIAL REGISTRATION
www.
CLINICALTRIALS
gov (NCT03183193).
Topics: Humans; Male; Female; Biomarkers; Middle Aged; Obesity; Adult; Inflammation; Fatty Liver; Diet, Mediterranean; Liver; Non-alcoholic Fatty Liver Disease; Leptin
PubMed: 38861890
DOI: 10.1016/j.clnu.2024.05.042 -
Adiponectin rescues synaptic plasticity in the dentate gyrus of a mouse model of Fragile X Syndrome.Philosophical Transactions of the Royal... Jul 2024Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is the leading known single-gene cause of autism spectrum disorder. Patients...
Fragile X syndrome (FXS) is the most common inherited cause of intellectual disability and is the leading known single-gene cause of autism spectrum disorder. Patients with FXS display varied behavioural deficits that include mild to severe cognitive impairments in addition to mood disorders. Currently, there is no cure for this condition; however, there is an emerging focus on therapies that inhibit mechanistic target of rapamycin (mTOR)-dependent protein synthesis owing to the clinical effectiveness of metformin for alleviating some behavioural symptoms in FXS. Adiponectin (APN) is a neurohormone that is released by adipocytes and provides an alternative means to inhibit mTOR activation in the brain. In these studies, we show that knockout mice, like patients with FXS, show reduced levels of circulating APN and that both long-term potentiation (LTP) and long-term depression (LTD) in the dentate gyrus (DG) are impaired. Brief (20 min) incubation of hippocampal slices in APN (50 nM) was able to rescue both LTP and LTD in the DG and increased both the surface expression and phosphorylation of GluA1 receptors. These results provide evidence for reduced APN levels in FXS playing a role in decreasing bidirectional synaptic plasticity and show that therapies which enhance APN levels may have therapeutic potential for this and related conditions.This article is part of a discussion meeting issue 'Long-term potentiation: 50 years on'.
Topics: Animals; Fragile X Syndrome; Dentate Gyrus; Mice; Neuronal Plasticity; Mice, Knockout; Disease Models, Animal; Fragile X Mental Retardation Protein; Adiponectin; Long-Term Potentiation; Male; Receptors, AMPA
PubMed: 38853554
DOI: 10.1098/rstb.2023.0221 -
Food Chemistry Jun 2024Green tea polyphenols (GTP) have been shown to ameliorate lipid metabolic disorders by regulating intestinal bacteria. Given the significant role of intestinal...
Green tea polyphenols (GTP) have been shown to ameliorate lipid metabolic disorders by regulating intestinal bacteria. Given the significant role of intestinal bacteriophages in shaping the gut microbiota, this study investigates GTP's influence on gut bacteriophage-bacteria interactions and lipid metabolism using metagenomics and metabonomics. The research results indicated that GTP significantly reduced body weight, serum triglycerides, leptin, insulin resistance, interleukin-6, and TNF-α levels while increasing adiponectin in ob/ob mice fed high-fat diet, aiding intestinal repair. GTP improved gut health by decreasing Enterobacter, Siphoviridae and Enterobacteria_phage_sfv, increasing Bifidobacterium and intestinal metabolites SCFA and hippuric acid. Correlation analysis showed negative correlations between Enterobacter sp. 50,588,862 and Enterobacteria_phages, Shigella_phages with 4-hydroxyphenylpyruvate and hippuric acid. Bifidobacterium choerinum and Bifidobacterium sp. AGR2158 were positively correlated with fatty acids and bile acids. In conclusion, GTP reduced fat accumulation and inflammation, enhanced gut barrier function in obese mice, closely associated with changes in the gut bacteriophage community.
PubMed: 38852447
DOI: 10.1016/j.foodchem.2024.139988 -
Redox Biology Jul 2024Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection...
Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities.
Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy.
Topics: Male; Animals; Prostatic Neoplasms; Humans; Mice; Oxidative Stress; Fibrosis; Adiponectin; Radiation Injuries; Adipose Tissue; Radiation-Protective Agents
PubMed: 38851001
DOI: 10.1016/j.redox.2024.103219 -
Graefe's Archive For Clinical and... Jun 2024To explore the molecular mechanism underlying the protective effect of hypothermic perfusion on the corneal endothelium during phacoemulsification.
AIM
To explore the molecular mechanism underlying the protective effect of hypothermic perfusion on the corneal endothelium during phacoemulsification.
METHODS
Phacoemulsification was performed on New Zealand white rabbits. Perfusate at different temperatures was used during the operation, and the aqueous humor was collected for proteomic sequencing after the operation. Corneal endothelial cell injury was simulated by a corneal endothelial cell oxygen-glucose deprivation/reoxygenation (OGD/R) model in vitro. Flow cytometry and evaluation of fluorescent LC3B puncta were used to detect apoptosis and autophagy, and western blotting was used to detect protein expression.
RESULTS
A total of 381 differentially expressed proteins were identified between the two groups. In vitro, 4 ℃ hypothermia significantly reduced apoptosis and promoted autophagy. Apoptosis increased after autophagy was inhibited by 3-Methyladenine (3-MA). Furthermore, adiponectin (ADIPOQ) knockdown inhibited phospho-AMPK and blocked the protective effect of hypothermia on corneal endothelial cells.
CONCLUSIONS
We investigated the differential expression of proteins between the hypothermia group and normothermia group by proteomics. Moreover, hypothermia-induced ADIPOQ can reduce apoptosis by promoting AMPK-mediated autophagy.
PubMed: 38850333
DOI: 10.1007/s00417-024-06542-6 -
Clinical and Translational Science Jun 2024Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of non-alcoholic fatty liver disease which has a high potential to progress to cirrhosis and...
Metabolic dysfunction-associated steatohepatitis (MASH) is the severe form of non-alcoholic fatty liver disease which has a high potential to progress to cirrhosis and hepatocellular carcinoma, yet adequate effective therapies are lacking. Hypoadiponectinemia is causally involved in the pathogenesis of MASH. This study investigated the pharmacological effects of adiponectin replacement therapy with the adiponectin-derived peptide ALY688 (ALY688-SR) in a mouse model of MASH. Human induced pluripotent stem (iPS) cell-derived hepatocytes were used to test cytotoxicity and signaling of unmodified ALY688 in vitro. High-fat diet with low methionine and no added choline (CDAHF) was used to induce MASH and test the effects of ALY688-SR in vivo. Histological MASH activity score (NAS) and fibrosis score were determined to assess the effect of ALY688-SR. Transcriptional characterization of mice through RNA sequencing was performed to indicate potential molecular mechanisms involved. In cultured hepatocytes, ALY688 efficiently induced adiponectin-like signaling, including the AMP-activated protein kinase and p38 mitogen-activated protein kinase pathways, and did not elicit cytotoxicity. Administration of ALY688-SR in mice did not influence body weight but significantly ameliorated CDAHF-induced hepatic steatosis, inflammation, and fibrosis, therefore effectively preventing the development and progression of MASH. Mechanistically, ALY688-SR treatment markedly induced hepatic expression of genes involved in fatty acid oxidation, whereas it significantly suppressed the expression of pro-inflammatory and pro-fibrotic genes as demonstrated by transcriptomic analysis. ALY688-SR may represent an effective approach in MASH treatment. Its mode of action involves inhibition of hepatic steatosis, inflammation, and fibrosis, possibly via canonical adiponectin-mediated signaling.
Topics: Animals; Adiponectin; Mice; Humans; Hepatocytes; Disease Models, Animal; Non-alcoholic Fatty Liver Disease; Male; Mice, Inbred C57BL; Signal Transduction; Diet, High-Fat; Metabolism, Inborn Errors; Metabolic Diseases; Liver; Fatty Liver
PubMed: 38847320
DOI: 10.1111/cts.13760 -
Annals of Medicine and Surgery (2012) Jun 2024Pancreatic cancer (PC) is a fatal malignant disease. It is well known that the relationship between PC and type 2 diabetes mellitus (T2DM) is a complicated bidirectional... (Review)
Review
Pancreatic cancer (PC) is a fatal malignant disease. It is well known that the relationship between PC and type 2 diabetes mellitus (T2DM) is a complicated bidirectional relationship. The most important factors causing increased risks of pancreatic cancer are hyperglycaemia, hyperinsulinemia, pancreatitis, and dyslipidemia. Genetics and the immune system also play an important role in the relationship between diabetes mellitus and pancreatic cancer. The primary contributors to this association involve insulin resistance and inflammatory processes within the tumour microenvironment. The combination of diabetes and obesity can contribute to PC by inducing hyperinsulinemia and influencing leptin and adiponectin levels. Given the heightened incidence of pancreatic cancer in diabetes patients compared to the general population, early screening for pancreatic cancer is recommended. Diabetes negatively impacts the survival of pancreatic cancer patients. Among patients receiving chemotherapy, it reduced their survival. The implementation of a healthy lifestyle, including weight management, serves as an initial preventive measure to mitigate the risk of disease development. The role of anti-diabetic drugs on survival is controversial; however, metformin may have a positive impact, especially in the early stages of cancer, while insulin therapy increases the risk of PC.
PubMed: 38846873
DOI: 10.1097/MS9.0000000000002036 -
Cureus May 2024The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular...
BACKGROUND
The onset of cardiovascular complications has increased the mortality rate in rheumatoid arthritis (RA) patients. Presently, there is a need to diagnose cardiovascular co-morbidity in rheumatic disease. While biomarkers such as P-selectin glycoprotein ligand-1 (PSGL-1), fibrinogen, anti-thrombin III (AT-III), hsCRP, lipoprotein (a) (lp(a)), leptin, adiponectin, and asymmetric dimethyl arginine (ADMA) are already established as independent risk factors for the development of atherosclerosis, the association of these biomarkers with disease activity in RA patients is unclear.
METHODS
The case-control study comprised 40 cases along with age- and gender-matched controls recruited from a tertiary care hospital in southern India. Platelet activation in plasma was analyzed by flow cytometry using CD41 per CPCY 5.5 (platelet marker) and human CD62P FITC monoclonal antibody (P-selectin marker). Other parameters were quantified through nephelometry and ELISA. The association between the risk factors and RA disease severity, as per the disease activity score (DAS/DAS28), was analyzed. Furthermore, an ROC analysis was done to assess the utility of these biomarkers in the diagnosis of RA.
RESULTS
With the exception of leptin, adiponectin, and ADMA, there was a significant increase in the levels of PSGL-1, fibrinogen, AT-III, hsCRP, and lp(a) when compared to healthy controls. Conventional risk factors contributing to dyslipidemia were also assessed, in which the low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio was found to be significantly higher in RA patients compared to controls. Moreover, a significant positive correlation was identified between DAS score and activated platelets, fibrinogen, and hsCRP. ROC analysis identified that fibrinogen could predict the RA disease status with 95% accuracy, followed by activated platelets and hsCRP.
CONCLUSION
Several of the studied atherothrombotic risk factors were significantly altered in patients with RA. Activated platelets, fibrinogen, and hsCRP were associated with disease activity and also served as good diagnostic predictors for RA. Based on our findings, further studies could explore the potential of introducing anti-thrombotic agents in the treatment regimen of patients with RA.
PubMed: 38846255
DOI: 10.7759/cureus.59818