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Antioxidants (Basel, Switzerland) Jun 2024Studies on adolescent rats, when body composition is changing deeply, reveal that the administration of sodium selenite and selenium nanoparticles (SeNPs), at the same...
Studies on adolescent rats, when body composition is changing deeply, reveal that the administration of sodium selenite and selenium nanoparticles (SeNPs), at the same dose, have opposite effects on adipogenesis in white adipose tissue (WAT). To investigate the mechanisms involved in these contrasting effects by means of transcriptomic analysis, three groups of male adolescent rats ( = 18) were used: control (C), selenite supplemented (S), and SeNPs supplemented (NS). Both treated groups received a twofold increase in Se dose compared to the control group through water intake for three weeks. Following treatment, WAT was removed and frozen at -80 °C until subsequent use for RNA extraction, endogenous antioxidant enzymatic activities determination, and quantification of HO and malondialdehyde. NS rats displayed a larger number of differentially expressed genes and cellular processes impacted than S rats. Remarkably, these changes involved upregulation of gene expression associated with the immune system, catabolism, mitochondrial function, and oxidative balance. NS rats presented an increase in antioxidant enzymes activity, alongside an accumulation of HO and malondialdehyde levels. The expression level of 81 genes related to oxidative stress was significantly affected in NS rats. Analyzing the KEGG pathway enrichment revealed that NS rats exhibited increased activity in key catabolic pathways and decreased activity in crucial growth signaling processes. These changes contribute to the mass decrease in WAT found in NS rats. These results suggest a possible application of SeNPs in WAT reduction and induction of the immune response during adolescence.
PubMed: 38929188
DOI: 10.3390/antiox13060750 -
Foods (Basel, Switzerland) Jun 2024has a long history of cultivation in Asia and is widely used in food production for its unique aroma, which has important cultural and economic values. It is rich in...
has a long history of cultivation in Asia and is widely used in food production for its unique aroma, which has important cultural and economic values. It is rich in flavonoids with diverse pharmacological properties, such as antioxidant, anti-tumor, and anti-lipid activities. However, little is known regarding the effects of flavonoid extract (OFFE) on adipogenesis and pre-adipocyte transdifferentiation. Herein, this research aimed to investigate the effect of OFFE on the differentiation, adipogenesis, and beiging of 3T3-L1 adipocytes and to elucidate the underlying mechanism. Results showed that OFFE inhibited adipogenesis, reduced intracellular reactive oxygen species levels in mature adipocytes, and promoted mitochondrial biogenesis as well as beiging/browning in 3T3-L1 adipocytes. This effect was accompanied by increased mRNA and protein levels of the brown adipose-specific marker gene , and the upregulation of the expression of , , and . Moreover, the research observed a dose-dependent reduction in the mRNA expression of adipogenic genes (, , , and ) with increasing concentrations of OFFE. Additionally, OFFE activated the AMPK signaling pathway to inhibit adipogenesis. These findings elucidate that OFFE has an inhibitory effect on adipogenesis and promotes browning in 3T3-L1 adipocytes, which lays the foundation for further investigation of the lipid-lowering mechanism of OFFE in vivo in the future.
PubMed: 38928836
DOI: 10.3390/foods13121894 -
Genes Jun 2024The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in...
The excessive deposition of abdominal adipocytes in chickens is detrimental to poultry production. However, the regulatory factors that affect abdominal adipogenesis in chickens are still poorly understood. is differentially expressed in abdominal preadipocytes and 10-day differentiated adipocytes in chickens, but its role in regulating chicken adipogenesis has not been reported. In this study, the function of in chicken abdominal preadipocytes was investigated. is significantly upregulated during abdominal adipocyte differentiation. The overexpression of upregulated the expression of adipogenic marker genes and proliferation-related genes, and promoted the proliferation of adipocytes and the accumulation of triglycerides. The knockdown of downregulated the expression of adipogenic marker genes and proliferation-related genes, inhibited the proliferation of adipocytes, and impaired the accumulation of triglycerides in adipocytes. In addition, was differentially expressed in abdominal preadipocytes and mature adipocytes, and was significantly positively correlated with the expression of . Interference with inhibits the expression of adipogenic marker genes and proliferation-related genes. The data supported the notion that promotes the differentiation of chicken abdominal adipocytes by cis-regulating the expression of . This study identified the role of in the differentiation and proliferation of chicken adipocytes, providing a potential target for improving abdominal adipogenesis in chickens.
Topics: Animals; Adipocytes; Chickens; Adipogenesis; RNA, Long Noncoding; Cell Differentiation; Cell Proliferation
PubMed: 38927694
DOI: 10.3390/genes15060758 -
Genes May 2024This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during...
This study investigated the transcriptomic responses of subcutaneous adipose tissue (SAT) and liver in newborn Hanwoo calves subjected to maternal overnutrition during mid- to late gestation. Eight Hanwoo cows were randomly assigned to control and treatment groups. The treatment group received a diet of 4.5 kg of concentrate and 6.5 kg of rice straw daily, resulting in intake levels of 8.42 kg DMI, 5.69 kg TDN, and 0.93 kg CP-higher than the control group (6.07 kg DMI, 4.07 kg TDN, and 0.65 kg CP), with respective NEm values of 9.56 Mcal and 6.68 Mcal. Following birth, newly born calves were euthanized humanely as per ethical guidelines, and SAT and liver samples from newborn calves were collected for RNA extraction and analysis. RNA sequencing identified 192 genes that were differentially expressed in the SAT (17 downregulated and 175 upregulated); notably, emerged as the most significantly upregulated gene in the SAT and as the singular upregulated gene in the liver (adj- value < 0.05). Additionally, differential gene expression analysis highlighted extensive changes across genes associated with adipogenesis, fibrogenesis, and stress response. The functional enrichment pathway and protein-protein interaction (PPI) unraveled the intricate networks and biological processes impacted by overnutrition, including extracellular matrix organization, cell surface receptor signaling, and the PI3K-Akt signaling pathway. These findings underscore maternal overnutrition's substantial influence on developmental pathways, suggesting profound cellular modifications with potential lasting effects on health and productivity. Despite the robust insights that are provided, the study's limitations (sample size) underscore the necessity for further research.
Topics: Animals; Female; Pregnancy; Liver; Overnutrition; Cattle; Subcutaneous Fat; Animals, Newborn; Transcriptome; Gene Expression Profiling
PubMed: 38927640
DOI: 10.3390/genes15060704 -
Biology Jun 2024The growing obesity epidemic necessitates increased research on adipocyte and adipose tissue function and disease mechanisms that progress obesity. Historically,... (Review)
Review
The growing obesity epidemic necessitates increased research on adipocyte and adipose tissue function and disease mechanisms that progress obesity. Historically, adipocytes were viewed simply as storage for excess energy. However, recent studies have demonstrated that adipocytes play a critical role in whole-body homeostasis, are involved in cell communication, experience forces in vivo, and respond to mechanical stimuli. Changes to the adipocyte mechanical microenvironment can affect function and, in some cases, contribute to disease. The aim of this review is to summarize the current literature on the mechanobiology of adipocytes. We reviewed over 100 papers on how mechanical stress is sensed by the adipocyte, the effects on cell behavior, and the use of cell culture scaffolds, particularly those with tunable stiffness, to study adipocyte behavior, adipose cell and tissue mechanical properties, and computational models. From our review, we conclude that adipocytes are responsive to mechanical stimuli, cell function and adipogenesis can be dictated by the mechanical environment, the measurement of mechanical properties is highly dependent on testing methods, and current modeling practices use many different approaches to recapitulate the complex behavior of adipocytes and adipose tissue. This review is intended to aid future studies by summarizing the current literature on adipocyte mechanobiology.
PubMed: 38927314
DOI: 10.3390/biology13060434 -
Biomolecules May 2024Bisphenol A (BPA) and bisphenol B (BPB) are widely used in the production of plastics, and their potential adverse health effects, particularly on endocrine disruption...
Bisphenol A (BPA) and bisphenol B (BPB) are widely used in the production of plastics, and their potential adverse health effects, particularly on endocrine disruption and metabolic health, have raised concern. Peroxisome proliferator-activated receptor gamma (PPARγ) plays a pivotal role in metabolic regulation and adipogenesis, making it a target of interest in understanding the development of obesity and associated health impacts. In this study, we employ X-ray crystallography and molecular dynamics (MD) simulations to study the interaction of PPARγ with BPA and BPB. Crystallographic structures reveal the binding of BPA and BPB to the ligand binding domain of PPARγ, next to C285, where binding of partial agonists as well as antagonists and inverse agonists of PPARγ signaling has been previously observed. However, no interaction of BPA and BPB with Y437 in the activation function 2 site is observed, showing that these ligands cannot stabilize the active conformation of helix 12 directly. Furthermore, free energy analyses of the MD simulations revealed that I341 has a large energetic contribution to the BPA and BPB binding modes characterized in this study.
Topics: Phenols; Benzhydryl Compounds; PPAR gamma; Molecular Dynamics Simulation; Crystallography, X-Ray; Protein Binding; Humans; Binding Sites; Ligands
PubMed: 38927044
DOI: 10.3390/biom14060640 -
FEBS Open Bio Jun 2024In multicellular organisms, stem cells are impacted by microenvironmental resources such as nutrient availability and oxygen tension for their survival, growth, and...
In multicellular organisms, stem cells are impacted by microenvironmental resources such as nutrient availability and oxygen tension for their survival, growth, and differentiation. However, the accessibility of these resources in the pericellular environment greatly varies from organ to organ. This divergence in resource availability leads to variations in the potency and differentiation potential of stem cells. This study aimed to explore the distinct effects of glucose and fructose, as well as different oxygen tensions, on the growth dynamics, cytokine production, and differentiation of stem cells. We showed that replacing glucose with fructose subjected stem cells to stress, resulting in increased Hif1α expression and stability, which in turn led to a reduction in cell proliferation, and alterations in cytokine production. However, fructose failed to induce differentiation of human mesenchymal stem cells (hMSCs) as well as mouse fibroblasts into mature adipocytes compared to glucose, despite the upregulation of key markers of adipogenesis, including C/EBPβ, and PPARγ. Conversely, we showed that fructose induced undifferentiated mouse fibroblasts to release cytokines associated with senescence, including IL1α1, IL6, IL8, MCP1, and TNF1α, suggesting that these cells were undergoing lipolysis. Taken together, our results suggest that altering the culture conditions through changes in hexose levels and oxygen tension places considerable stress on stem cells. Additional research is required to further characterize the mechanisms governing stem cell response to their microenvironments.
PubMed: 38923793
DOI: 10.1002/2211-5463.13846 -
Cell Biology International Jun 2024ATAD3 is a vital ATPase of the inner mitochondrial membrane of pluri-cellular eukaryotes, with largely unknown functions but early required for organism development as...
ATAD3 is a vital ATPase of the inner mitochondrial membrane of pluri-cellular eukaryotes, with largely unknown functions but early required for organism development as necessary for mitochondrial biogenesis. ATAD3 knock-down in C. elegans inhibits at first the development of adipocyte-like intestinal tissue so we used mouse adipocyte model 3T3-L1 cells to analyze ATAD3 functions during adipogenesis and lipogenesis in a mammalian model. ATAD3 function was studied by stable and transient modulation of ATAD3 expression in adipogenesis- induced 3T3-L1 cells using Knock-Down and overexpression strategies, exploring different steps of adipocyte differentiation and lipogenesis. We show that (i) an increase in ATAD3 is preceding differentiation-induced mitochondrial biogenesis; (ii) downregulation of ATAD3 inhibits adipogenesis, lipogenesis, and impedes overexpression of many mitochondrial proteins; (iii) ATAD3 re-expression rescues the phenotype of ATAD3 KD, and (iv) differentiation and lipogenesis are accelerated by ATAD3 overexpression, but inhibited by expression of a dominant-negative mutant. We further show that the ATAD3 KD phenotype is not due to altered insulin signal but involves a limitation of mitochondrial biogenesis linked to Drp1. These results demonstrate that ATAD3 is limiting for in vitro mitochondrial biogenesis and adipogenesis/lipogenesis and therefore that ATAD3 mutation/over- or under-expression could be involved in adipogenic and lipogenic pathologies.
PubMed: 38923254
DOI: 10.1002/cbin.12206 -
Die Ophthalmologie Jun 2024Endocrine orbitopathy (EO) is an autoimmune disease mostly associated with a disease of the thyroid gland, which leads to inflammation, adipogenesis and fibrosis. The... (Review)
Review
BACKGROUND
Endocrine orbitopathy (EO) is an autoimmune disease mostly associated with a disease of the thyroid gland, which leads to inflammation, adipogenesis and fibrosis. The severity of EO can vary greatly between individuals, which makes it difficult to exactly predict the natural course of the disease; however, this is important to be able to individually adapt the treatment. The aim of this study was to compare the clinical features, course, treatment and prognosis for patients with EO under 50 years old with older patients. The results of the study with a focus on motility are presented in this special issue.
PATIENTS AND METHODS
The hospital records of a randomly selected sample of 1000 patients from the EO databank in Essen (GODE), which includes 4260 patients, were analyzed. The patients were divided into two groups: group 1 ≤50 years and group 2 >50 years. Only patients with complete data sets were included in the statistical analyses.
RESULTS
Younger patients (n = 484) presented significantly more frequently with milder EO (53% vs. 33%, p < 0.0001), whereas older patients (n = 448) more frequently suffered from moderate or severe forms (44% vs. 64%, p < 0.0001). Older patients showed more severe strabismus, motility and clinical activity scores (5.9 vs. 2.3 prism diopters, PD/310° vs. 330°, both p < 0.0001, CAS 2.1 vs. 1.7, p = 0.001). Proptosis and the occurrence of optic nerve compression showed no significant differences between the groups (3% each). Multiple logistic regression showed that the necessity for a second eye muscle surgery was most strongly associated with a previous decompression (OR = 0.12, 95 % CI 0.1-0.2, p < 0.0001), followed by orbital irradiation and age.
CONCLUSION
In summary, younger patients with EO presented with milder clinical features, such as a lower rate of restrictive motility disorders and weaker expression of signs of inflammation. Therefore, older patients needed steroids, irradiation, eyelid and eye muscle surgery more frequently; however, the risk of dysthyroid optic neuropathy and the necessity of a second eye surgery were not or only slightly associated with age.
PubMed: 38922402
DOI: 10.1007/s00347-024-02073-x -
Current Osteoporosis Reports Jun 2024Along with a strong impact on skeletal integrity, bone marrow adipose tissue (BMAT) is an important modulator of the adult hematopoietic system. This review will... (Review)
Review
PURPOSE OF REVIEW
Along with a strong impact on skeletal integrity, bone marrow adipose tissue (BMAT) is an important modulator of the adult hematopoietic system. This review will summarize the current knowledge on the causal relationship between bone marrow (BM) adipogenesis and the development and progression of hematologic malignancies.
RECENT FINDINGS
BM adipocytes (BMAds) support a number of processes promoting oncogenesis, including the evolution of clonal hematopoiesis, malignant cell survival, proliferation, angiogenesis, and chemoresistance. In addition, leukemic cells manipulate surrounding BMAds by promoting lipolysis and release of free fatty acids, which are then utilized by leukemic cells via β-oxidation. Therefore, limiting BM adipogenesis, blocking BMAd-derived adipokines, or lipid metabolism obstruction have been considered as potential treatment options for hematological malignancies. Leukemic stem cells rely heavily on BMAds within the structural BM microenvironment for necessary signals which foster disease progression. Further development of 3D constructs resembling BMAT at different skeletal regions are critical to better understand these relationships in geometric space and may provide essential insight into the development of hematologic malignancies within the BM niche. In turn, these mechanisms provide promising potential as novel approaches to targeting the microenvironment with new therapeutic strategies.
PubMed: 38922359
DOI: 10.1007/s11914-024-00879-x