Adipocytes Research Articles

A distinct isoform of Msp300/Nesprin organizes the perinuclear microtubule organizing center in adipose cells.

In many cell types, disparate non-centrosomal microtubule-organizing centers (ncMTOCs) replace functional centrosomes and serve the unique needs of the cell types in which they are formed. In Drosophila fat body cells (adipocytes), an ncMTOC is organized on the nuclear surface. This perinuclear ncMTOC is anchored by Msp300, encoded by one of two Nesprin-encoding genes in Drosophila. Msp300 and the spectraplakin short stop (shot) are co-dependent for localization to the nuclear envelope to generate the ncMTOC where they recruit the microtubule minus-end stabilizer Patronin (CAMSAP). The fat body perinuclear ncMTOC requires Patronin, Ninein, and Msps (ortholog of ch-TOG), but does not require γ-tubulin for MT assembly. The Msp300 gene is complex, encoding at least eleven isoforms. Here we show that two Msp300 isoforms, Msp300-PE and -PG, are required and only one, Msp300-PE, appears sufficient for generation of the ncMTOC. Loss of Msp300-PE,-PG retains the presence of the other isoforms at the nuclear surface, indicating that they are not sufficient to generate the ncMTOC. Loss of Msp300-PE,-PG results in severe loss of localization of shot and Patronin, and disruption of the MT array. This results in nuclear mispositioning and loss of endosomal trafficking. Msp300-PE has an unusual domain structure including a lack of a KASH domain and very few spectrin repeats and appears therefore to have a highly derived function suited to generating an ncMTOC on the nuclear surface.

Case Report of Lipomyoma

Report: Uterine lipoleiomyoma are rare forms of leiomyomas that are often only described in literature as case reports. Lipoleiomyomas could increase in size despite menopause and most commonly occur in postmenopausal women with an incidence rate of 0.03% to 0.2% Clinical symptoms of lipoleiomyoma are very similar to leiomyoma. Radiologic imaging can aid in the diagnosis of lipoleiomyoma with smooth muscle confined to the tumor periphery. In our case, we describe a 53y/o G0P0 perimenopausal patient who complained of abnormal uterine bleeding with irregular menses, urinary retention and difficulty completely emptying her bladder due to the large mass compressing her bladder. She was diagnosed with a large 8.8 cm hyperechoic lesion with internal vascularity arising from the central uterus/ endometrium. Radiology recommended a pelvic MRI for further differentiation of mass. Office hysteroscopy with endometrial biopsy was performed. Pathology confirmed limited inactive endometrium, benign endometrial surface epithelium. The patient requested a hysterectomy through a minimally invasive gynecologic surgery approach. A pelvic MRI was performed that revealed a large, round, circumscribed mass measuring 7.3 X 7.2 X 7.5 cm favoring to represent an intramural lipoleiomyoma. The patient had a robotic assisted laparoscopic hysterectomy which was uncomplicated. Final histopathologic diagnosis was uterine lipomyoma. As benign masses, management for lipoleiomyoma are guided by symptoms, fertility preservation desires, and whether or not a patient is a candidate for surgical intervention. Given the rarity of these cases, the histogenesis is still relatively unknown although various theories exist such as differentiation of embryonic fat cells, metaplastic changes of existing cells into fat cells, and pluripotent cell migration. Although there was not evidence of malignancy in our case report, certain literature has suggested the presence of coexisting malignancies and in an even rarer occasion the presence of liposarcoma from a lipoleiomyoma. More information is needed on these rare cases in order to further lead management and any recommendations regarding cancer screening on top of age related recommendations already in place.

Mouse vascularized adipose spheroids: an organotypic model for thermogenic adipocytes.

Adipose tissues, particularly beige and brown adipose tissue, play crucial roles in energy metabolism. Brown adipose tissues' thermogenic capacity and the appearance of beige cells within white adipose tissue have spurred interest in their metabolic impact and therapeutic potential. Brown and beige fat cells, activated by environmental factors like cold exposure or by pharmacology, share metabolic mechanisms that drive non-shivering thermogenesis. Understanding these two cell types requires advanced, yet broadly applicable in vitro models that reflect the complex microenvironment and vasculature of adipose tissues. Here we present mouse vascularized adipose spheroids of the stromal vascular microenvironment from inguinal white adipose tissue, a tissue with 'beiging' capacity in mice and humans. We show that adding a scaffold improves vascular sprouting, enhances spheroid growth, and upregulates adipogenic markers, thus reflecting increased adipocyte maturity. Transcriptional profiling via RNA sequencing revealed distinct metabolic pathways upregulated in our vascularized adipose spheroids, with increased expression of genes involved in glucose metabolism, lipid metabolism, and thermogenesis. Functional assessment demonstrated increased oxygen consumption in vascularized adipose spheroids compared to classical 2D cultures, which was enhanced by β-adrenergic receptor stimulation correlating with elevated β-adrenergic receptor expression. Moreover, stimulation with the naturally occurring adipokine, FGF21, induced Ucp1 mRNA expression in the vascularized adipose spheroids. In conclusion, vascularized inguinal white adipose tissue spheroids provide a physiologically relevant platform to study how the stromal vascular microenvironment shapes adipocyte responses and influence activated thermogenesis in beige adipocytes.

A critical review of health and financial implications of obesity during the COVID-19 pandemic

The coronavirus disease 2019 (COVID-19) was reported in Wuhan, China, in December 2019. There is a link between increased mortality and obese individuals with the disease. The disease has been claimed to have disproportionately affected non-Hispanic blacks and Hispanics. The rise in food accessibility and the drop in the relative cost of junk food items are the two most significant changes in dietary patterns. Around the world, 2.8 million people die from being overweight or obese, and those with more body fat also have a higher risk of diabetes (44%) and heart disease (23%). Obesity weakens the immune system because adipose cells infiltrate the bone marrow, spleen, and thymus. Obesity was substantially more common among COVID-19 patients who were hospitalized than those who were not hospitalized. Over 900,000 adults in the United States are hospitalized due to a COVID-19 infection. Hospitalizations in 271,700 (30.2%) cases have been attributed to obesity. Obese patients may be experiencing reduced thoracic expansion following bariatric surgery. Less tracheal collapse and air-trapping at end-expiration chest CT were observed post-surgery, and patients reported reduced dyspnea. COVID-19 is estimated to cost the European Union €13.9 billion in secondary care, with 76% of that cost attributed to treatment for overweight and obese individuals. The average price per hospitalized patient also increased with increasing body mass index (BMI). Screening for obesity, preventive measures, and recommendations for healthy lifestyle changes should be of the utmost importance to decrease both the health and financial implications of COVID-19.

Interleukin-10 deficiency induces thoracic perivascular adipose tissue whitening and vascular remodeling.

Perivascular adipose tissue (PVAT) is an adipose layer, surrounding blood vessels, with a local modulatory role. Interleukin-10 (IL-10) has been shown to modulate vascular tissue. This study aimed to characterize the endogenous role of IL-10 in vascular remodeling, and PVAT phenotyping. Thoracic aortic segments from control (C57BL/6J) and IL-10 knockout (IL-10-/-) male mice were used. Analyzes of aorta/PVAT morphometry, and elastin, collagen and reticulin deposition were performed. Tissue uncoupling protein 1 (UCP1) was accessed by Western blotting. Endogenous absence of IL-10 reduced total PVAT area (p = 0.0310), and wall/lumen ratio (p = 0.0024), whereas increased vascular area and thickness (p < 0.0001). Total collagen deposition was augmented in IL-10-/-, but under polarized light, the reduction of collagen-I (p = 0.0075) and the increase of collagen-III (p = 0.0055) was found, simultaneously with reduced elastic fibers deposition (p = 0.0282) and increased deposition of reticular fibers (p < 0.0001). Adipocyte area was augmented in the IL-10 absence (p = 0.0225), and UCP1 expression was reduced (p = 0.0420). Moreover, relative frequency of white adipose cells and connective tissue was augmented in IL-10-/- (p < 0.0001), added to a reduction in brown adipose cells (p < 0.0001). Altogether, these data characterize aorta PVAT from IL-10-/- as a white-like adipocyte phenotype. Endogenous IL-10 prevents vascular remodeling and favors a brown-like adipocyte phenotype, suggesting a modulatory role for IL-10 in PVAT plasticity.

Dermatofibrosarcoma protuberance with a unique appearance mimicking neurofibroma arising from a conventional area.

A 21year-old Japanese man had a rapidly growing pedunculated soft tumor in the abdomen within the past year, the base of which had persisted for 17years. A skin biopsy of the soft part resembled neurofibroma. However, the excised specimen showed that the tumor base comprised spindle cells arranged in a storiform fashion and expanded around fat cells with a honeycomb infiltration. All areas of the tumor were positive for CD34 and negative for S-100. Finally, the tumor was diagnosed as a myxoid dermatofibrosarcoma protuberance arising from a conventional area. The pedunculated shape on the conventional part was unique. Myxoid dermatofibrosarcoma protuberances may pose a diagnostic challenge, particularly with a small biopsy. Thus, we should carefully consider dermatofibrosarcoma protuberances or other malignant mesenchymal tumors as a differential diagnosis in cases of low cellularity and abundant stromal tumors resembling neurofibromas.

2α-Substituted Vitamin D Derivatives Effectively Enhance the Osteoblast Differentiation of Dedifferentiated Fat Cells.

The active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], is a principal regulator of calcium homeostasis through activation of the vitamin D receptor (VDR). Previous studies have shown that 2α-(3-hydroxypropyl)-1,25D3 (O1C3) and 2α-(3-hydroxypropoxy)-1,25D3 (O2C3), vitamin D derivatives resistant to inactivation enzymes, can activate VDR, induce leukemic cell differentiation, and increase blood calcium levels in rats more effectively than 1,25(OH)2D3. In this study, to further investigate the usefulness of 2α-substituted vitamin D derivatives, we examined the effects of O2C3, O1C3, and their derivatives on VDR activity in cells and mouse tissues and on osteoblast differentiation of dedifferentiated fat (DFAT) cells, a cell type with potential therapeutic application in regenerative medicine. In cell culture experiments using kidney-derived HEK293 cells, intestinal mucosa-derived CaCO2 cells, and osteoblast-derived MG63 cells, and in mouse experiments, O2C2, O2C3, O1C3, and O1C4 had a weaker effect than or equivalent effect to 1,25(OH)2D3 in VDR transactivation and induction of the VDR target gene CYP24A1, but they enhanced osteoblast differentiation in DFAT cells equally to or more effectively than 1,25(OH)2D3. In long-term treatment with the compound without the medium change (7 days), the derivatives enhanced osteoblast differentiation more effectively than 1,25(OH)2D3. O2C3 and O1C3 were more stable than 1,25(OH)2D3 in DFAT cell culture. These results indicate that 2α-substituted vitamin D derivatives, such as inactivation-resistant O2C3 and O1C3, are more effective than 1,25(OH)2D3 in osteoblast differentiation of DFAT cells, suggesting potential roles in regenerative medicine with DFAT cells and other multipotent cells.

Growth hormone improves insulin resistance in visceral adipose tissue after duodenal-jejunal bypass by regulating adiponectin secretion

BACKGROUND The mechanism of improvement of type 2 diabetes after duodenal-jejunal bypass (DJB) surgery is not clear. AIM To study the morphological and functional changes in adipose tissue after DJB and explore the potential mechanisms contributing to postoperative insulin sensitivity improvement of adipose tissue in a diabetic male rat model. METHODS DJB and sham surgery was performed in a-high-fat-diet/streptozotocin-induced diabetic rat model. All adipose tissue was weighed and observed under microscope. Use inguinal fat to represent subcutaneous adipose tissue (SAT) and mesangial fat to represent visceral adipose tissue. RNA-sequencing was utilized to evaluate gene expression alterations adipocytes. The hematoxylin and eosin staining, reverse transcription-quantitative polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay were used to study the changes. Insulin resistance was evaluated by immunofluorescence. RESULTS After DJB, whole body blood glucose metabolism and insulin sensitivity in adipose tissue improved. Fat cell volume in both visceral adipose tissue (VAT) and SAT increased. Compared to SAT, VAT showed more significantly functional alterations after DJB and KEGG analysis indicated growth hormone (GH) pathway and downstream adiponectin secretion were involved in metabolic regulation. The circulating GH and adiponectin levels and GH receptor and adiponectin levels in VAT increased. Cytological experiment showed that GH stimulated adiponectin secretion and improve insulin sensitivity. CONCLUSION GH improves insulin resistance in VAT in male diabetic rats after receiving DJB, possibly by increasing adiponectin secretion.

362-OR: Divergent Roles of METTL14-Mediated m6A in Regulating Brown and White Adipose Tissue Transcriptomes and Systemic Metabolism

N6-methyladenosine (m6A) is among the most abundant post-transcriptional modifications in mRNA, yet its precise cell-type-specific roles in orchestrating gene expression programs remain elusive. Although brown and white adipocytes are both considered fat cells, their unique properties underscore the importance of context-specific post-transcriptional regulation for whole-body metabolism. Here, we provide the first evidence that m6A methyltransferase-like 14 (METTL14) differentially regulates transcriptomes in brown and white adipose tissue (BAT and WAT), leading to divergent metabolic outcomes. We found that human brown and white adipocytes (hBAT and hWAT) display markedly distinct m6A landscapes; besides, in insulin-resistant humans and mice, METTL14 expression differs significantly between the fat depots in the context of correlation with insulin sensitivity. Mettl14-knockout in BAT via Ucp1-cre promotes secretion of specific prostaglandins and improved peripheral insulin sensitivity in mice. Conversely, Mettl14-deficiency in WAT via Adipoq-cre triggers white adipocyte apoptosis, lipodystrophy, and systemic insulin resistance. Integration of m6A-seq and RNA-seq profiling revealed strikingly distinct transcriptomes and m6A methylomes in Mettl14-deficient BAT versus Mettl14-deficient WAT. More specifically, upregulated prostaglandin biosynthesis pathways were enriched in Mettl14-deficient BAT, and TNF-associated and apoptotic pathways were activated in Mettl14-deficient WAT. Using stable METTL14-knockout hBAT or hWAT cell lines, we report that METTL14-mediated m6A negatively regulates gene expression of PTGES2, CBR1, and PGC1a in hBAT, and TRAIL, TNFR1, RIP, and DFFA in hWAT by promoting mRNA decay. These data shed light on the ability of m6A to impact metabolism in a cell-type-specific manner with implications for influencing the pathophysiology of metabolic diseases. Disclosure L. Xiao: None. D.F. De Jesus: None. C. Ju: None. J. Hu: None. J. Wei: None. A. DiStefano-Forti: None. V.R. Salerno Gonzales: None. T. Tsuji: None. S. Wei: None. M. Blüher: Speaker's Bureau; Amgen Inc., AstraZeneca, Bayer Inc., Daiichi Sankyo. Advisory Panel; Lilly Diabetes. Speaker's Bureau; Novartis AG. Advisory Panel; Novo Nordisk. Speaker's Bureau; Pfizer Inc., Sanofi. Y. Tseng: Other Relationship; Biohaven. Consultant; LyGenesis. C. He: None. R. Kulkarni: Advisory Panel; Novo Nordisk, Biomea Fusion, Inc. Consultant; Inversago Pharma. Advisory Panel; REDD Pharmaceutical. Funding This work is supported by NIH grants R01 DK67536 (R.N.K.), UC4 DK116278 (R.N.K. and C.H.), and RM1 HG008935 (C.H.).

Mechanobiology of Adipocytes.

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.

Reversine enhances the conversion of dedifferentiated fat cells into mature cardiomyocytes.

There is an essential need for cardiomyocyte regeneration among patients with heart failure. Transplantation of dedifferentiated fat (DFAT) cells may lead to an improvement of cardiomyocyte regeneration among heart failure patients. We believe that DFAT cells are promising candidate cell sources for cardiac regeneration. However, the pathway underlying how DFAT cells of the adipose lineage differentiate into mature cardiomyocytes isn't fully understood. We conducted an experimental laboratory study on isolated DFAT cells from adipose tissue of healthy adults. Then, we treated cells with different concentrations of reversine (10, 20 and 40 nM), and performed RNA extraction and cDNA synthesis. Next, we used a ceiling culture method based on the buoyancy properties of mature lipid-filled adipocytes. Stemness expression (Octamer-binding transcription factor 4 [Oct4], brachyury, Fetal liver kinase 1 [Flk-1]) was quantified by reverse transcription-quantitative (RT-q)PCR, while cardiomyocyte expression (Transcription factor GATA-4 [GATA4] and cardiac troponin T [cTnT]) was quantified by immunocytochemistry. ANOVA with Tukey's post-hoc found that 10 nM reversine increased greater Flk-1 expression compared to the control group (MD: 5.037 + 0.998; p < 0.001), but there were no significant changes among Oct4 (MD: 0.013 + 1.244; p = 0.99) and brachyury expression (MD: 0.157 + 0.084; p = 0.252). Kruskal-Wallis revealed that the expression of GATA4 (1.65 [0.41-1.98] to 0.015 [0.007-0.034]; p =0.017) reduced significantly from day 7 until day 21 and cTnT (5.07 [6.62-8.91] to 8.22 [6.81-9.40]; p= 0 .001) increased significantly from day 7 until day 21. Reversine could increase the expression of Flk-1, but it was unable to stimulate the expression of Oct4 and brachyury related to cell stemness. An optimal concentration of 10 nM reversine may have the greatest effect on enhancing the differentiation of DFAT cells into mature cardiomyocytes, as indicated by higher cTnT expression between cells.

Oxylipins in Breast Implant-Associated Systemic Symptoms.

A subset of females with breast implants have reported a myriad of nonspecific systemic symptoms collectively termed systemic symptoms associated with breast implants (SSBI). SSBI symptoms are similar to manifestations associated with autoimmune and connective tissue disorders. Breast tissue is rich in adipose cells, comprised of lipids. Insertion of an implant creates an oxidative environment leading to lipid oxidation. Oxylipins can influence immune responses and inflammatory processes. In this study we explored the abundance of a spectrum of oxylipins in the periprosthetic tissue surrounding the breast implant. Because oxylipins are immunogenic, we sought to determine if they were associated with the SSBI patients. We have also attempted to determine if the common manifestations exhibited by such patients have any association with oxylipin abundance. The study included 120 patients divided into 3 cohorts. We analyzed 46 patients with breast implants exhibiting manifestations associated with SSBI; 29 patients with breast implants not exhibiting manifestations associated with SSBI (control cohort I, non-SSBI); and 45 patients without implants (control cohort II, no-implant tissue). Lipid extraction and oxylipin quantification were performed with liquid chromatography mass spectrometry (LC-MS/MS). LC-MS/MS targeted analysis of the breast adipose tissue was performed. Of the 15 oxylipins analyzed, 5 exhibited increased abundance in the SSBI cohort when compared to the non-SSBI and no-implant cohorts. The study documents the association of the oxylipins with each manifestation reported by the patient. This study provides an objective assessment of the subjective questionnaire, highlighting which symptoms may be more relevant than the others.

Research Note: Sexual dimorphic effect of myostatin mutation on fat accumulation in Japanese quail

As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN mutation on reducing fat deposition in various farm animals suggested a potential application of the MSTN gene on regulating fat deposition in poultry species. Although increase in muscle mass resulted from muscle hyperplasia in the MSTN mutant quail, cellular mechanism behind the decrease in fat deposition was not investigated in the quail model. In the current study, to investigate sexual dimorphic association between fat deposition and Mstn mutation in quail, leg and abdominal fat pads from 4-month-old male and female quail were histologically analyzed. Interestingly, abdominal and leg fat pad weights were significantly decreased by the MSTN mutation only in female quail, but not in male quail, showing sexual dimorphism in regulating fat deposition by the MSTN mutation in quail. Histological analysis also revealed that fat cell sizes of leg and abdominal fats were significantly reduced only in female groups aligning with the decreased fat pad weights. Sexual dimorphic effect of the MSTN mutation on fat cell hypotrophy and reduced fat pad weights in quail provided an important scientific finding to be considered on the usage of the MSTN gene as a genetic marker to reduce fat deposition in poultry species.

A2B adenosine receptor signaling and regulation.

The A2B adenosine receptor (A2BR) is one of the four adenosine-activated G protein-coupled receptors. In addition to adenosine, protein kinase C (PKC) was recently found to activate the A2BR. The A2BR is coupled to both Gs and Gi, as well as Gq proteins in some cell types. Many primary cells and cell lines, such as bladder and breast cancer, bronchial smooth muscle, skeletal muscle, and fat cells, express the A2BR endogenously at high levels, suggesting its potentially important role in asthma, cancer, diabetes, and other conditions. The A2BR has been characterized as both pro- and anti-inflammatory, inducing cell type-dependent secretion of IL-6, IL-8, and IL-10. Theophylline and enprofylline have long been used for asthma treatment, although it is still not entirely clear if their A2BR antagonism contributes to their therapeutic effects or side effects. The A2BR is required in ischemic cardiac preconditioning by adenosine. Both A2BR and protein kinase C (PKC) contribute to cardioprotection, and both modes of A2BR signaling can be blocked byA2BR antagonists. Inhibitors of PKC and A2BR are in clinical cancer trials. Sulforaphane and other isothiocyanates from cruciferous vegetables such asbroccoli and cauliflower have been reported to inhibit A2BR signaling via reaction with an intracellular A2BR cysteine residue (C210). A full, A2BR-selective agonist, critical to elucidate many controversial roles of the A2BR, is still not available, although agonist-bound A2BR structures have recently been reported.

RNA sequencing screening and gene function analysis uncover G protein-coupled receptor 183 as a key mediator for methionine to stimulate milk synthesis in mouse mammary epithelial cells.

Methionine (Met) can activate the mechanistic target of rapamycin (mTOR) to promote milk synthesis in mammary epithelial cells. However, it is largely unknown which G protein-coupled receptor can mediate the stimulation of Met on mTOR activation. In this study, we employed transcriptome sequencing to analyse which G protein-coupled receptors were associated with the role of Met and further used gene function study approaches to explore the role of G protein-coupled receptor 183 (GPR183) in Met stimulation on mTOR activation in HC11 cells. We identified nine G protein-coupled receptors including GPR183 whose expression levels were upregulated by Met treatment through RNA sequencing and subsequent quantitative real-time PCR analysis. Using GPR183 knockdown and overexpression technology, we demonstrate that GPR183 is a positive regulator of milk protein and fat synthesis and proliferation of HC11 cells. Met affected GPR183 expression in a dose-dependent manner, and GPR183 mediated the stimulation of Met (0·6 mM) on milk protein and fat synthesis, cell proliferation and mTOR phosphorylation and mRNA expression. The inhibition of phosphoinositide 3-kinase blocked the phosphorylation of mTOR and AKT stimulated by GPR183 activation. In summary, through RNA sequencing and gene function study, we uncover that GPR183 is a key mediator for Met to activate the phosphoinositide 3-kinase-mTOR signalling and milk synthesis in mouse mammary epithelial cells.

Mitochondrial Thermogenesis Can Trigger Heat Shock Response in the Nucleus.

Mitochondrial thermogenesis is a process in which heat is generated by mitochondrial respiration. In living organisms, the thermogenic mechanisms that maintain body temperature have been studied extensively in fat cells with little knowledge on how mitochondrial heat may act beyond energy expenditure. Here, we highlight that the exothermic oxygen reduction reaction (ΔH f° = -286 kJ/mol) is the main source of the protonophore-induced mitochondrial thermogenesis, and this heat is conducted to other cellular organelles, including the nucleus. As a result, mitochondrial heat that reached the nucleus initiated the classical heat shock response, including the formation of nuclear stress granules and the localization of heat shock factor 1 (HSF1) to chromatin. Consequently, activated HSF1 increases the level of gene expression associated with the response to thermal stress in mammalian cells. Our results illustrate heat generated within the cells as a potential source of mitochondria-nucleus communication and expand our understanding of the biological functions of mitochondria in cell physiology.

MORPHOLOGICAL FEATURES OF THE BRONCHUS OF THE LUNG IN CHILDREN FROM 8 TO 12 YEARS OF AGE

The pulmonary vessels and their endothelium plays the role of a physiological barrier for numerous biologically active substances, then the epithelium and connective tissue basis of the airways perform a barrier-protective function in relation to various environmental factors [1]. The bronchial secret produced by the mucous membrane is the result of the complex integration of the transudation of the plasma components of the blood, the secretory activity of the bronchial epithelium, glands, the cells of the connective tissue and blood cells (neutrophils, fat cells, eosinophils, macrophages, etc.). From the presented few literature presented, it becomes obvious that the structure of the lung function is closely integrated with the lymphatic system. Located in the immediate vicinity of both peribronchial and alveolar blood capillaries, the flow of lymph goes along the bronchial tree and along the subpleural tissue, in its most lungs and the lymph nodes located here, as well as tangential along the plane of the pleura [2.3] .Based on the foregoing, the purpose of this work is to establish in posttal ontogenesis the laws of the formation and involution of bronchial vascular and lymphatic systems in a person, epithelial connective tissue relationships in the air and respiratory parts of the lung (1.4).

Effect of polymethoxylated flavonoids on glucose and lipid metabolism in rat model of obesity induced by a high-fat diet

This study established a rat model of obesity by using a high-fat diet(HFD) to explore the effect of polymethoxylated flavonoids on glucose and lipid metabolism in the model rats and decipher the role and mechanism of polymethoxylated flavonoids in mitigating obesity. Thirty normal SD rats were selected and randomized into normal, model, ezetimibe(0.1 mg·kg~(-1)), and polymethoxylated flavonoids(62.5 mg·kg~(-1) and 125 mg·kg~(-1)) groups based on the body weight. Except the normal group receiving a conventional diet, the other groups received a HFD. Rats were administrated with corresponding doses of drugs by gavage. During the administration period, the body weight of each group of rats was regularly weighed, and the serum lipid and glucose levels were measured by a fully automated biochemical analyzer. Islet homeostasis and serum levels of obesity factors were measured by ELISA. The 16S rRNA high-throughput sequencing was employed to study the gut microbiota. Hematoxylin-eosin staining was employed to observe the histomorphology of white fat, brown fat, and pancreas. After the wet weights of white fat and brown fat were measured, the organ index was calculated. Immunohistochemistry and Western blot were employed to determine the protein levels. The results showed that polymethoxylated flavonoids reduced the body weight and Lee's index and improved blood lipid levels of the model rats. Polymethoxylated flavonoids reduced blood glucose and insulin secretion, increased insulin responsiveness, and alleviated insulin resistance. In addition, polymethoxylated flavonoids regulated the serum levels of obesity factors and reduced the weights and indexes of white fat and brown fat, the diameter of white adipocytes, and the number of fat vacuoles in brown fat and pancreatic islet cells. The intervention with polymethoxylated flavonoids increased the diversity of gut microbiota in the model rats, increasing the beneficial bacteria associated with glucose and lipid metabolism and reduced the harmful bacteria at the genus level. In addition, polymethoxylated flavonoids up-regulated the protein levels of glucose transporter 4(GLUT4), phosphorylated AMP-activated protein kinase(p-AMPK), peroxisome proliferator-activated receptor gamma coactivator-1α(PGC-1α), and uncoupling protein 1(UCP1). In summary, polymethoxylated flavonoids may increase the body utilization of glucose and lipids by regulating the homeostasis of insulin, the serum levels of obesity factors, the diversity of gut microbiota, and the expression of mitochondrial metabolism-related proteins in brown adipocytes, thereby mitigating obesity in rats.

Distinctive characteristics of extracellular vesicles from feline adipose and placenta stromal cells unveil potential for regenerative medicine in cats.

Extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) are promising avenues in regenerative medicine, offering unique immunomodulatory and regenerative properties with lower immunogenicity. This study delves into the distinctive features of EVs extracted from feline adipose-derived MSCs (ASCs) and placenta-derived MSCs (PMSCs). The tissues were collected from 11 female cats aged between 4 and 7 years old. EVs extracted from MSCs from discarded fetal membranes from 7 female cats and SC adipose tissue from 11 cats. We comprehensively explored morphological characteristics, mitochondrial density, surface markers, and pro- and anti-inflammatory mediators, uncovering notable differences between ASCs and PMSCs. Morphologically, ASCs exhibit a spindle-shaped form in contrast to the spherical morphology of PMSCs. Proliferation and clonogenic potential assessments reveal the faster proliferation and robust clonogenic nature of ASCs, suggesting their potential vital role in regenerative processes. Surface marker expression analysis indicates a significantly higher expression of multipotency-associated markers in ASCs, suggesting their superior proregenerative potential. Phenotyping of EVs demonstrates distinctive features, with CD9 expression suggesting varied EV secretion patterns. Notably, PMSCs exhibit superior CD81 expression, indicating their potential as preferred donors of mitochondria. Pro- and anti-inflammatory mediators analyzed at mRNA and microRNA levels reveal higher RNA content in EVs compared to source cells, emphasizing the potential of EVs in directing regenerative processes. Differential microRNA expression in EVs derived from ASCs hints at their regulatory roles in anti-inflammatory and immunometabolic processes. This study lays a foundation for understanding the nuances between ASCs and PMSCs, which is crucial for harnessing the full therapeutic potential of MSCs and their EVs in tissue repair and regeneration.

Clinical and paraclinical approach to community-acquired pneumonia in obese individuals

Introduction. Obesity is a metabolic disease that presents a real challenge for the medical system due to the significant increase in the number of obese people in recent decades. Currently, 38% of the global population is overweight or obese. Obesity is an important risk factor for multiple chronic pathologies and lung infections, especially pneumonia. For obese subjects, chronic proinflammatory status due to an excess of fat cells is characteristic. Material and methods. This prospective cohort study is based on clinical and laboratory examinations of patients hospitalized with community-acquired pneumonia in the Department of Internal Medicine at Holy Trinity Municipal Hospital, Chisinau, Republic of Moldova. The study included 210 patients with community-acquired pneumonia, divided into two groups: the base group (group 1) consisted of 105 patients with varying degrees of obesity, and the control group (group 2) consisted of 105 normal-weight patients. The research was conducted according to the principles of the Helsinki Declaration - WMA Declaration of Helsinki - Ethical Principles for Medical Research Involving Human Subjects. The study was approved by the Research Ethics Committee of the Nicolae Testemiţanu State University of Medicine and Pharmacy, with the issuance of favorable opinion no. 46 from March 27, 2018. All patients were examined clinically and paraclinically (radiological examination, pulse oximetry screening, complete blood count, erythrocyte sedimentation rate, fibrinogen, LDH, C-reactive protein, oxidative stress markers). The obtained data were statistically analyzed using Statistical Package for the Social Sciences (SPSS) version 20. Results. According to the obtained data, the most common comorbidities associated with obesity were cardiovascular and metabolic diseases. The main symptom that prevailed in the obese was dyspnea (97%). Obese subjects showed more frequent signs of acute respiratory failure (86.7%), required oxygen therapy with an average duration of 7.62±6.23 days, showed increased serum levels of LDH (286.31±94.66 U/L) and C-reactive protein (66.08±71.44 mg/l), data that influenced the clinical course of pneumonia. Conclusions. Patients with obesity and community-acquired pneumonia presented with infectious symptoms and acute respiratory failure, increased values of inflammatory markers, and required oxygen therapy more frequently compared to those of normal weight.