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Genes May 2024With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich...
With the rising cost of animal feed protein, finding affordable and effective substitutes is crucial. Walnut kernel cake, a polyphenol-, fiber-, protein- and fat-rich byproduct of walnut oil extraction, has been underexplored as a potential protein replacement in pig feed. In this study, we found that feeding large Diqing Tibetan pigs walnut kernel cake promoted adipose deposition and improved pork quality during pig growth. Transcriptome analysis revealed the upregulation of genes , , , and , associated with adipose deposition. Pathway analysis highlighted enrichment in adipose deposition-related pathways, including PPAR, insulin, PI3K-Akt, Wnt, and MAPK signaling. Further analysis identified DEGs (differentially expressed genes) positively correlated with adipose-related traits, such as and . Single-cell transcriptome data pointed to the specific expression of and in adipocyte progenitor/stem cells (APSCs), pivotal for adipocyte differentiation and adipose deposition regulation. This study demonstrates walnut kernel cake's potential to substitute soybean cake in pig feed, providing high-quality protein and promoting adipose deposition. It offers insights into feed protein replacement, human functional food, fat metabolism, and related diseases, with marker genes and pathways supporting pig breeding and pork quality improvement.
Topics: Animals; Juglans; Swine; Transcriptome; Animal Feed; Adipose Tissue; Gene Expression Profiling; Adipocytes
PubMed: 38927603
DOI: 10.3390/genes15060667 -
Biomedicines Jun 2024Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to... (Review)
Review
Osteoarthritis (OA) is a progressive chronic disease affecting the articular joints, leading to pain and disability. Unlike traditional views that primarily link OA to aging, recent understanding portrays it as a multifactorial degenerative disease of the entire joint. Emerging research highlights metabolic and immune dysregulation in OA pathogenesis, emphasizing the roles of obesity, dyslipidemia, and insulin resistance in altering joint homeostasis. Recent studies have increasingly focused on the complex role of white adipose tissue (WAT) in OA. WAT not only serves metabolic functions but also plays a critical role in systemic inflammation through the release of various adipokines. These adipokines, including leptin and adiponectin, have been implicated in exacerbating cartilage erosion and promoting inflammatory pathways within joint tissues. The overlapping global crises of obesity and metabolic syndrome have significantly impacted joint health. Obesity, now understood to contribute to mechanical joint overload and metabolic dysregulation, heightens the risk of developing OA, particularly in the knee. Metabolic syndrome compounds these risks by inducing chronic inflammation and altering macrophage activity within the joints. The multifaceted effects of obesity and metabolic syndrome extend beyond simple joint loading. These conditions disrupt normal joint function by modifying tissue composition, promoting inflammatory macrophage polarization, and impairing chondrocyte metabolism. These changes contribute to OA progression, highlighting the need for targeted therapeutic strategies that address both the mechanical and biochemical aspects of the disease. Recent advances in understanding the molecular pathways involved in OA suggest potential therapeutic targets. Interventions that modulate macrophage polarization, improve chondrocyte function, or normalize adipokine levels could serve as preventative or disease-modifying therapies. Exploring the role of diet, exercise, and pharmacological interventions in modulating these pathways offers promising avenues for reducing the burden of OA. Furthermore, such methods could prove cost-effective, avoiding the increase in access to healthcare.
PubMed: 38927469
DOI: 10.3390/biomedicines12061262 -
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 2024Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic...
Recent studies increasingly suggest that targeting brown/beige adipose tissues to enhance energy expenditure offers a novel therapeutic approach for treating metabolic diseases. Brown/beige adipocytes exhibit elevated expression of uncoupling protein 1 (UCP1), which is a thermogenic protein that efficiently converts energy into heat, particularly in response to cold stimulation. Polyphenols possess potential anti-obesity properties, but their pharmacological effects are limited by their bioavailability and distribution within tissue. This study discovered , a polyphenol compound with a favorable distribution within adipose tissues, which transcriptionally activates UCP1, thereby promoting thermogenesis and enhancing mitochondrial respiration in brown adipocytes. Furthermore, in vivo studies demonstrated that prevents high-fat-diet-induced weight gain and improves insulin sensitivity. Our research provides strong mechanistic evidence that UCP1 is a complex mediator of -induced thermogenesis, which is a critical process in obesity mitigation. Brown adipose thermogenesis is triggered by via the AMPK-PGC-1α pathway. As a result, our research highlights a thermogenic controlled polyphenol compound and clarifies its underlying mechanisms, thus offering a potential strategy for the thermogenic targeting of adipose tissue to reduce the incidence of obesity and its related metabolic problems.
Topics: Uncoupling Protein 1; Thermogenesis; Animals; Obesity; Polyphenols; Mice; Diet, High-Fat; Adipose Tissue, Brown; Male; Mice, Inbred C57BL; Humans; Energy Metabolism
PubMed: 38927022
DOI: 10.3390/biom14060618 -
Journal of Orthopaedic Surgery and... Jun 2024Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles...
BACKGROUND
Achilles tendon is vital in maintaining the stability and function of ankle joint. It is quite difficult to achieve the structural and functional repair of Achilles tendon in tissue engineering.
METHODS
A tissue-engineered tendon micro-tissue was prepared using rat tail tendon extracellular matrix (TECM) combined with rat adipose stem cells (ADSCs) to repair Achilles tendon injuries. The TECM was prepared by repeated freezing and thawing. The in vitro characteristics of TECM and its effect on ADSCs proliferation were detected. This tissue-engineered tendon micro-tissue for Achilles tendon repair in vivo was evaluated based on general characteristics, gait analysis, ultrasound findings, histological analysis, and biomechanical testing.
RESULTS
The results showed that the TECM scaffold had good biocompatibility for ADSCs. At 2 weeks post-surgery, collagen types I and III and tenomodulin expression were higher, and vascular endothelial growth factor expression was lower in the micro-tissue group than other groups. At 4 and 8 weeks post-surgery, the results of histological analysis and ultrasound findings showed that the repaired tendon tissue was smooth and lustrous, and was arranged regularly and evenly in the micro-tissue group. Gait analysis confirmed that better motor function recovery was noted in micro-tissue group than other groups. In addition, the mechanical properties of the repaired tendon tissue in micro-tissue group were better than other groups.
CONCLUSION
Tissue-engineered tendon micro-tissue fabricated by TECM and ADSCs has good biocompatibility and can promote structural and functional repair of tendon in vivo. This composite biomaterial has broad application prospects in tissue engineering.
Topics: Animals; Tissue Engineering; Achilles Tendon; Tendon Injuries; Extracellular Matrix; Regeneration; Rats; Rats, Sprague-Dawley; Tissue Scaffolds; Male; Adipose Tissue
PubMed: 38926735
DOI: 10.1186/s13018-024-04863-0 -
BMC Cancer Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion...
BACKGROUND
Pancreatic ductal adenocarcinoma (PDAC) is a 'difficult-to-treat' entity. To forecast its prognosis, we introduced a new biomarker, SARIFA (stroma areactive invasion front areas), which are areas at the tumour invasion front lacking desmoplastic stroma reaction upon malignant invasion in the surrounding tissue, leading to direct contact between tumour cells and adipocytes. SARIFA showed its significance in gastric and colorectal carcinoma, revealing lipid metabolism alternations that promote tumour progression.
METHODS
We reviewed the SARIFA status of 166 PDAC cases on all available H&E-stained tumour slides from archival Whipple-resection specimens. SARIFA positivity was defined as SARIFA detection in at least 66% of the available slides. To investigate alterations in tumour metabolism and microenvironment, we performed immunohistochemical staining for FABP4, CD36 and CD68. To verify and quantify a supposed delipidation of adipocytes, adipose tissue was digitally morphometrised.
RESULTS
In total, 53 cases (32%) were classified as SARIFA positive and 113 (68%) as SARIFA negative. Patients with SARIFA-positive PDAC showed a significantly worse overall survival compared with SARIFA-negative cases (median overall survival: 11.0 months vs. 22.0 months, HR: 1.570 (1.082-2.278), 95% CI, p = 0.018), which was independent from other prognostic markers (p = 0.014). At the invasion front of SARIFA-positive PDAC, we observed significantly higher expression of FABP4 (p < 0.0001) and higher concentrations of CD68 macrophages (p = 0.031) related to a higher risk of tumour progression. CD36 staining showed no significant expression differences. The adipocyte areas at the invasion front were significantly smaller, with mean values of 4021 ± 1058 µm and 1812 ± 1008 µm for the SARIFA-negative and -positive cases, respectively (p < 0.001).
CONCLUSIONS
SARIFA is a promising prognostic biomarker for PDAC. Its assessment is characterised by simplicity and low effort. The mechanisms behind SARIFA suggest a tumour-promoting increased lipid metabolism and altered immune background, both showing new therapeutic avenues.
Topics: Humans; Carcinoma, Pancreatic Ductal; Female; Male; Biomarkers, Tumor; Prognosis; Pancreatic Neoplasms; Aged; Middle Aged; Fatty Acid-Binding Proteins; Neoplasm Invasiveness; Tumor Microenvironment; Lipid Metabolism; Antigens, Differentiation, Myelomonocytic; Antigens, CD; Stromal Cells; CD36 Antigens; Adipocytes; Adult; Aged, 80 and over; CD68 Molecule
PubMed: 38926671
DOI: 10.1186/s12885-024-12519-9 -
Scientific Reports Jun 2024Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their...
Adipose-derived stem cells (ADSCs) are promising in regenerative medicine. Their proliferation, survival and activation are influenced by specific signals within their microenvironment, also known as niche. The stem cell niche is regulated by complex interactions between multiple cell types. When transplanted in a specific area, ADSCs can secrete several immunomodulatory factors. At the same time, a tumor microenvironment can influence stem cell behavior, modulating proliferation and their ability to differentiate into a specific phenotype. Whitin this context, we exposed ADSCs to plasma samples derived from human patients diagnosed with prostate cancer (PC), or precancerous lesions (PL), or benign prostatic hyperplasia (BPH) for 4, 7 or 10 days. We then analyzed the expression of main stemness-related markers and cell-cycle regulators. We also measured cytokine production and polyamine secretion in culture medium and evaluated cell morphology and collagen production by confocal microscopy. The results obtained from this study show significant changes in the morphology of ADSCs exposed to plasma samples, especially in the presence of prostate cancer plasma, suggesting important implications in the use of ADSCs for the development of new treatments and application in regenerative medicine.
Topics: Male; Humans; Prostatic Neoplasms; Prostatic Hyperplasia; Stem Cells; Adipose Tissue; Prostate; Cell Differentiation; Cell Proliferation; Cytokines; Cells, Cultured; Aged; Middle Aged
PubMed: 38926454
DOI: 10.1038/s41598-024-64625-0 -
Clinical and Translational Medicine Jul 2024White adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus....
BACKGROUND
White adipose tissue (WAT) has a key role in maintaining energy balance throughout the body, and their dysfunction take part in the regulation of diabetes mellitus. However, the internal regulatory mechanisms underlying are still unknown.
METHODS AND RESULTS
We generated adipocyte-specific FAK KO (FAK-AKO) mice and investigated their phenotype. The cascade of adipocyte, macrophage in adipocyte tissues, and pancreatic β-cells were proposed in FAK-AKO mice and validated by cell line studies using 3T3-L1, Raw264.7 and Min6. The FAK-AKO mice exhibited glucose intolerance, reduced adipose tissue mass and increased apoptosis, lipolysis and inflammatory response in adipose tissue. We further demonstrate that adipocyte FAK deletion increases β cell apoptosis and inflammatory infiltrates into islets, which is potentiated if mice were treated with STZ. In the STZ-induced diabetes model, FAK AKO mice exhibit less serum insulin content and pancreatic β cell area. Moreover, serum pro-inflammatory factors increased and insulin levels decreased after glucose stimulation in FAK AKO mice. In a parallel vitro experiment, knockdown or inhibition of FAK during differentiation also increased apoptosis, lipolysis and inflammatory in 3T3-L1 adipocytes, whereas the opposite was observed upon overexpression of FAK. Moreover, coculturing LPS-treated RAW264.7 macrophages with knockdown FAK of 3T3-L1 adipocytes increased macrophage pro-inflammatory response. Furthermore, conditioned medium from above stimulated Min6 cells apoptosis (with or without STZ), whereas the opposite was observed upon overexpression of FAK. Mechanistically, FAK protein interact with TRAF6 in adipocytes and knockdown or inhibition of FAK activated TRAF6/TAK1/NF-κB signaling, which exacerbates inflammation of adipocytes themselves.
CONCLUSION
Adipocyte FAK deletion promotes both adipocyte apoptosis and adipose tissue inflammation. Pro-inflammatory factors released by the FAK-null adipose tissue further trigger apoptosis in pancreatic islets induced by the administration of STZ, thereby exacerbating the diabetes mellitus. This study reveals a link between FAK-mediated adipose inflammation and diabetes mellitus, a mechanism that has not been previously recognized.
Topics: Animals; Mice; Apoptosis; Insulin-Secreting Cells; Adipocytes; Focal Adhesion Kinase 1; Mice, Knockout; Diabetes Mellitus, Experimental; Inflammation; Male; Adipose Tissue; Disease Models, Animal
PubMed: 38925910
DOI: 10.1002/ctm2.1742 -
Science Advances Jun 2024There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly...
There is a regional preference around lymph nodes (LNs) for adipose beiging. Here, we show that local LN removal within inguinal white adipose tissue (iWAT) greatly impairs cold-induced beiging, and this impairment can be restored by injecting M2 macrophages or macrophage-derived C-C motif chemokine (CCL22) into iWAT. CCL22 injection into iWAT effectively promotes iWAT beiging, while blocking CCL22 with antibodies can prevent it. Mechanistically, the CCL22 receptor, C-C motif chemokine receptor 4 (CCR4), within eosinophils and its downstream focal adhesion kinase/p65/interleukin-4 signaling are essential for CCL22-mediated beige adipocyte formation. Moreover, CCL22 levels are inversely correlated with body weight and fat mass in mice and humans. Acute elevation of CCL22 levels effectively prevents diet-induced body weight and fat gain by enhancing adipose beiging. Together, our data identify the CCL22-CCR4 axis as an essential mediator for LN-controlled adaptive thermogenesis and highlight its potential to combat obesity and its associated complications.
Topics: Thermogenesis; Chemokine CCL22; Animals; Macrophages; Energy Metabolism; Mice; Humans; Lymph Nodes; Adipose Tissue, White; Male; Receptors, CCR4; Obesity; Signal Transduction; Mice, Inbred C57BL; Eosinophils; Female; Adipocytes, Beige
PubMed: 38924414
DOI: 10.1126/sciadv.adn5229 -
Endokrynologia Polska Jun 2024Beyond growth acceleration, growth hormone (GH) therapy improves body composition of GH-deficient (GHD) children due to the interaction of GH with lipid and carbohydrate...
INTRODUCTION
Beyond growth acceleration, growth hormone (GH) therapy improves body composition of GH-deficient (GHD) children due to the interaction of GH with lipid and carbohydrate metabolism, possibly mediated by adipokines secreted by adipose tissue and ghrelin. To promote linear growth, it is essential to have normal phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is a known regulator of serum phosphorus and may be responsible for the increased renal phosphorus reabsorption observed during GH therapy. This study aimed to assess the impact of one-year GH therapy on body composition, adipokines, acylated/unacylated ghrelin (AG/UAG), and FGF23 in GHD children.
MATERIAL AND METHODS
A prospective observational study of 42 prepubertal, non-obese GHD children followed up in the first year of GH replacement therapy, investigating changes in adipokine profiles, AG/UAG, FGF23, and body composition. Data before therapy onset were compared with measurements obtained after 6 and 12 months of GH therapy.
RESULTS
All children with a mean age of 9.2 ± 2.6 years grew at an accelerated pace. Total body fat decreased significantly, while the lipid profile improved, and total bone mineral density (BMD) significantly increased over the 12 months of treatment. Leptin and UAG levels decreased significantly, whereas adiponectin and AG values increased. A significant increase in plasma FGF23 and insulin growth factor 1 (IGF1) was accompanied by increased serum phosphate. Changes in FGF23 concentration did not have an impact on BMD. The strong association of FGF23 with IGF1 and height standard deviation (SD) could reveal a role of FGF23 in linear growth. In regression analysis models, GH therapy influences the changes of leptin and adiponectin, but not ghrelin, independently of body composition - lean or fat mass.
CONCLUSIONS
GH replacement therapy improves body composition and adipokine profile in GHD children and directly impacts leptin and adiponectin concentrations independently of body composition. Also, GHD children have increased serum phosphate, correlated with upregulation rather than with suppression of FGF23, an unexpected observation given the phosphaturic role of FGF23. Further research is needed to identify the molecular mechanisms by which the GH/IGF1 axis influences adipokines secretion and plasma changes of FGF23.
PubMed: 38923900
DOI: 10.5603/ep.98923