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BMC Genomics Jun 2024Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry...
BACKGROUND
Intramuscular fat content is an important index reflecting the quality of mutton, which directly affects the flavor and tenderness of mutton. Livestock and poultry intramuscular fat content is influenced by genetics, nutritional level, and environmental factors. Key regulatory factors play a crucial role in intramuscular fat deposition. However, there is a limited amount of research on the identification and function of key genes involved in intramuscular fat content deposition specifically in sheep.
RESULTS
Histological differences in the longest dorsal muscle of the small-tailed frigid sheep increased in diameter and decreased in several muscle fibers with increasing monthly age; The intramuscular fat content of the longest dorsal muscle of the small-tailed cold sheep varied with age, with a minimum of 1 month of age, a maximum of 6 months of age, and a minimum of 12 months of age. Transcriptomic sequencing and bioinformatics analysis revealed a large number of differential genes in the longest dorsal muscles of little-tailed billy goats of different months of age, which were enriched in multiple GO entries and KEGG pathways. Among them, the pathway associated with intramuscular fat was the AMPK signaling pathway, and the related genes were PPARGC1A and ADIPOQ; Immunohistochemical studies showed that PPARGC1A and ADIPOQ proteins were expressed in connective tissues, cell membranes, and, to a lesser extent, the cytoplasm of the longest dorsal muscle of the little-tailed frigid sheep; Real-time PCR and Western Blot validation showed that PPARGC1A and ADIPOQ were both expressed in the longest dorsal muscle of the little-tailed frigid sheep at different ages, and there were age differences in the amount of expression. The ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle, and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle; As inferred from the above results, the ADIPOQ gene was negatively correlated with the intramuscular fat content of the longest dorsal muscle (r = -0.793, P < 0.05); and the PPARGC1A gene was positively correlated with the intramuscular fat content of the longest dorsal muscle r = 0.923, P < 0.05).
CONCLUSIONS
Based on the above results, it can be inferred that the ADIPOQ gene is negatively correlated with the intramuscular fat content of the longest back muscle (r = -0.793, P < 0.05); the PPARGC1A gene is positively correlated with the intramuscular fat content of the longest back muscle (r = 0.923, P < 0.05).
Topics: Animals; Sheep; Muscle, Skeletal; Adipose Tissue; Adiponectin; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Gene Expression Profiling; Transcriptome
PubMed: 38867146
DOI: 10.1186/s12864-024-10486-w -
Scientific Reports Jun 2024Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver...
Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver fibrosis. This research delved into how aging impacts liver fibrosis mechanisms. The study involved 32 albino rats categorized into four groups: Group I (young controls), Group II (young with liver fibrosis), Group III (old controls), and Group IV (old with liver fibrosis). Various parameters including serum ALT, adiponectin, leptin, and cholesterol levels were evaluated. Histopathological analysis was performed, alongside assessments of TGF-β, FOXP3, and CD133 gene expressions. Markers of fibrosis and apoptosis were the highest in group IV. Adiponectin levels significantly decreased in Group IV compared to all other groups except Group II, while cholesterol levels were significantly higher in liver fibrosis groups than their respective control groups. Group III displayed high hepatic expression of desmin, α-SMA, GFAP and TGF- β and in contrast to Group I. Increased TGF-β and FOXP3 gene expressions were observed in Group IV relative to Group II, while CD133 gene expression decreased in Group IV compared to Group II. In conclusion, aging modulates immune responses, impairs regenerative capacities via HSC activation, and influences adipokine and cholesterol levels, elevating the susceptibility to liver fibrosis.
Topics: Animals; Hepatic Stellate Cells; Liver Cirrhosis; Rats; Aging; Male; Transforming Growth Factor beta; Cholesterol; Apoptosis; Liver
PubMed: 38866800
DOI: 10.1038/s41598-024-63644-1 -
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 -
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 -
Endocrine Regulations Jan 2024Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2...
Sedentary lifestyle increasingly observed in the population contributes to the incremental incidence of obesity, cardiovascular diseases, mental disorders, type 2 diabetes, hyper-tension, dyslipidemia, and others. Physical inactivity together with an imbalance in caloric intake and expenditure leads to a loss of muscle mass, reduced insulin sensitivity, and accumulation of the visceral fat. Organokines (adipokines, myokines, hepatokines, etc.) serve in the organism for inter-organ communication. However, human studies focused on the exercise-related changes in plasma levels of certain myokines have produced contradictory results. In the present study, we verified a hypothesis that myokine irisin, which is expected to increase in response to physical activity, induces brain-derived neurotrophic factor (BDNF) production and by this way mediates the beneficial effect of exercise on several brain functions. Women (n=27) and men (n=10) aged 44.5±12.0 years, who were sedentary and overweight/obese (men ≥25%, women ≥28% body fat), participated in the study. The effect of an 8-week intensive lifestyle intervention (150 minutes of moderate physical activity per week, diet modification, and reduction of caloric intake) on the selected organokines (irisin, BDNF) in the context of an expected improvement in cardiometabolic status was examined. The 8-week lifestyle intervention resulted in a significant (p<0.05) reduction in body mass index, body fat, blood pressure, insulin resistance, lipid and liver parameters, and irisin levels (p<0.001). However, BDNF increase in the whole group did not reach statistical significance. After the improvement of cardiometabolic parameters, a significant decrease in irisin and increase in BDNF levels were also observed in the subgroup with unsatisfactory (≤5%) body weight reduction. Neither relationship between irisin and BDNF levels, nor effect of age or sex on their levels was observed. We cannot confirm the hypothesis that exercise-induced irisin may increase the BDNF levels, whereas, the organokine levels in the periphery may not completely reflect the processes in the brain compartments. The observed decrease in irisin levels after 8-week intensive lifestyle intervention program, which was in contrary to its supposed mechanisms of action and dynamics, suggests the presence of several yet undiscovered impacts on the secretion of irisin.
Topics: Humans; Brain-Derived Neurotrophic Factor; Fibronectins; Sedentary Behavior; Male; Female; Middle Aged; Adult; Exercise; Obesity; Overweight; Life Style
PubMed: 38861537
DOI: 10.2478/enr-2024-0013 -
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 -
BMC Endocrine Disorders Jun 2024Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the...
OBJECTIVE
Meteorin-like (Metrnl), a secreted myokine, is a newly discovered neurotrophic factor. The aim of this study was to determine if there is a correlation between the Metrnl level and diabetic peripheral neuropathy (DPN).
METHODS
The investigation was conducted on a sample of 80 patients with type 2 diabetes mellitus (T2DM) and 60 healthy controls. The T2DM patients were categorized into two subgroups based on skin biopsy: the DPN subgroup (n = 20) and the diabetes without neuropathy subgroup (n = 60).
RESULTS
The T2DM groups had higher serum Metrnl concentrations compared with the controls. The serum Metrnl concentration was significantly lower in the DPN group than in T2DM patients without neuropathy. Logistic regression analysis demonstrated a notable correlation between serum Metrnl and DPN (OR: 0.997, 95% CI: 0.995-1.000, P < 0.05). Serum Metrnl level was negatively correlated with age and SBP after a simple logistic regression analysis.
CONCLUSION
Serum Metrnl concentration is independently correlated with DPN.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Male; Female; Middle Aged; Case-Control Studies; Aged; Biomarkers; Adipokines
PubMed: 38849768
DOI: 10.1186/s12902-024-01616-2 -
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 -
Frontiers in Endocrinology 2024Leptin and its receptors are expressed by the human placenta throughout gestation, yet the role of leptin in early human placental development is not well characterized....
INTRODUCTION
Leptin and its receptors are expressed by the human placenta throughout gestation, yet the role of leptin in early human placental development is not well characterized. Leptin is overexpressed in the placentas from preeclamptic (PE) pregnancies. PE can result from the impaired invasion of fetal placental cells, cytotrophoblasts (CTBs), into the maternal decidua. We hypothesized that elevated leptin levels would impair human CTB invasion.
METHODS
The effects of leptin on the invasion of human CTBs were evaluated in three cell models, HTR-8/SVneo cells, primary CTBs, and placental villous explants using invasion assays. Further, leptin receptor expression was characterized in all three cell models using RT-PCR. Further phosphokinase assays were performed in HTR-8/SVneo cells to determine signaling pathways involved in CTB invasion in response to differential leptin doses.
RESULTS
We found that, prior to 8 weeks gestation, leptin promoted CTB invasion in the explant model. After 11 weeks gestation in explants, primary CTBs and in HTR-8/SVneo cells, leptin promoted invasion at moderate but not at high concentrations. Further, leptin receptor characterization revealed that leptin receptor expression did not vary over gestation, however, STAT, PI3K and MAPK pathways showed different signaling in response to varied leptin doses.
DISCUSSION
These data suggest that the excess placental leptin observed in PE may cause impaired CTB invasion as a second-trimester defect. Leptin's differential effect on trophoblast invasion may explain the role of hyperleptinemia in preeclampsia pathogenesis.
Topics: Humans; Trophoblasts; Leptin; Female; Pregnancy; Gestational Age; Receptors, Leptin; Placenta; Pre-Eclampsia; Dose-Response Relationship, Drug; Signal Transduction; Placentation; Cell Movement
PubMed: 38846494
DOI: 10.3389/fendo.2024.1386309 -
Respiratory Research Jun 2024Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance,...
BACKGROUND
Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH.
METHODS
Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction.
RESULTS
Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27-5.33; P < .0087). Comparisons of ML-derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62-0.79) for PAH.
CONCLUSIONS
This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.
Topics: Humans; Male; Female; Resistin; Middle Aged; Adult; Severity of Illness Index; Biomarkers; Predictive Value of Tests; Pulmonary Arterial Hypertension; Aged; Cohort Studies; Polymorphism, Single Nucleotide; Survival Rate; Hypertension, Pulmonary
PubMed: 38844967
DOI: 10.1186/s12931-024-02861-8