Hyaluronic Acid as a LYVE-1 Receptor Ligand in the Lymphatic System of Healthy Human Skin.

Immunohistochemical detection of the LYVE-1 marker in healthy human full-thickness skin (the epidermis and the dermis) was carried out. LYVE-1 expression was found in the endothelium of lymphatic capillaries located in the papillary dermis, in the endothelium of larger lymphatic vessels of the reticular dermis, and in fibroblasts, which indicates their joint participation in hyaluronan metabolism. LYVE-1 staining detected for the first time in cells of the stratum basale, the stratum spinosum, and the stratum granulosum of healthy human epidermis indicates their participation in hyaluronan metabolism and allows us to consider the spaces between epidermis cells as prelimphatics.

Semaglutide 6-months therapy of type 2 diabetes mellitus restores adipose progenitors potential to develop metabolically active adipocytes.

Background: Nowadays type 2 diabetes mellitus (T2DM) leads to population mortality growth. Today glucagon-like peptide type 1 receptor agonists (GLP-1 RA) are one of the most promising glucose-lowered drugs with anorexigenic and cardioprotective effects. The present study aims to determine the effects of GLP-1 RA semaglutide 6-month therapy on T2DM patient metabolic parameters and adipose progenitor cell health.

IL-4 activates the futile triacylglyceride cycle for glucose utilization in white adipocytes.

The development of cardiometabolic complications during obesity is strongly associated with chronic latent inflammation in hypertrophied adipose tissue (AT). IL-4 is an anti-inflammatory cytokine, playing a protective role against insulin resistance, glucose intolerance and weight gain. The positive effects of IL-4 are associated not only with the activation of anti-inflammatory immune cells in AT, but also with the modulation of adipocyte metabolism.

Effect of Melatonin on the Content of CD3 and CD3 T Cells in the Thymus of Mice with Functional Pinealectomy.

Continuous lighting for 14 days (functional pinealectomy model) leads to a decrease in the relative number of CD3 and CD3 T lymphocytes and the CD3/CD3 ratio in the thymus of C57BL/6 mice. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight, 14 days) against the background of functional pinealectomy restores the percentage of CD3 and CD3 thymocytes and CD3/CD3 ratio to the control values. Hence, prolonged continuous illumination inhibits the differentiation and maturation of young thymocytes into mature forms, while melatonin treatment helps to compensate the effects of functional pinealectomy triggering cell proliferation in the thymus from the earliest stages of proliferation and differentiation of T cells.

Visceral mesenchymal stem cells from type 2 diabetes donors activate triglycerides synthesis in healthy adipocytes via metabolites exchange and cytokines secretion.

Background: In recent years, there has been an increase in the prevalence of obesity and type 2 diabetes mellitus (T2DM). Development of visceral instead of subcutaneous adipose tissue is pathogenic and increases the risk of metabolic abnormalities. We hypothesize that visceral adipocytes and stromal cells are able to deteriorate other fat depots metabolism via secretory mechanisms.

Transplantation of Adipose-Tissue-Engineered Constructs with CRISPR-Mediated UCP1 Activation.

Thermogenic adipocytes have potential utility for the development of approaches to treat type 2 diabetes and obesity-associated diseases. Although several reports have proved the positive effect of beige and brown adipocyte transplantation in obese mice, translation to human cell therapy needs improvement. Here, we describe the application of CRISPR activation (CRISPRa) technology for generating safe and efficient adipose-tissue-engineered constructs with enhanced mitochondrial uncoupling protein 1 (UCP1) expression.

The Efficacy of HGF/VEGF Gene Therapy for Limb Ischemia in Mice with Impaired Glucose Tolerance: Shift from Angiogenesis to Axonal Growth and Oxidative Potential in Skeletal Muscle.

Background: Combined non-viral gene therapy (GT) of ischemia and cardiovascular disease is a promising tool for potential clinical translation. In previous studies our group has developed combined gene therapy by vascular endothelial growth factor 165 () + hepatocyte growth factor (). Our recent works have demonstrated that a bicistronic pDNA that carries both human and coding sequences has a potential for clinical application in peripheral artery disease (PAD).

Light-Induced Functional Pinealectomy. Effect on the Thymus of C57BL/6 Mice.

Light-induced functional pinealectomy was simulated in C57BL/6 mice by 14-day exposure to constant lighting. Immunophenotyping of CD3 and CD3 thymocytes was performed by staining with CD3-APC antibodies followed by flow cytofluorometry. To study the cell cycle distribution of thymus cells, the content of intracellular DNA was measured by the level PI inclusion.

Light-Induced Functional Pinealectomy: Expression of MT Receptors in Liver Cells of C57BL/6 Mice after Melatonin Treatment.

We performed an immunohistochemical study of MT melatonin receptor expression in the liver of C57BL/6 mice with modeled light-induced functional pinealectomy and after melatonin administration by the indirect avidin-biotin peroxidase ABC method. The animals were kept for 14 days under constant lighting. Intragastric administration of melatonin in physiological doses (1 mg/kg body weight for 14 days) to mice with light-induced functional pinealectomy resulted in a 2-fold increase in the relative expression area of MT receptors in liver cells in comparison with that in animals kept under standard lighting conditions, 24-h lighting for 14 days, or 24-h lighting receiving placebo (intragastric administration of 200 ml distilled water).

Effect of Melatonin on the Expression of LYVE-1 Receptor in Liver Sinusoidal Endothelial Cells of Mice with the Light-Induced Functional Pinealectomy Model.

Intragastric administration of melatonin in physiological doses (1 mg/kg body weight) for 14 days to C57BL/6 mice with light-induced functional pinealectomy model (24-h lighting for 14 days) results in an increase in the LYVE-1 expression area by 2.4 times and a significant increase in receptor concentration (1.6% decrease in staining brightness) in liver sinusoidal endothelial cells in comparison with animals kept under continuous lighting and not treated with the hormone, which indicates the formation of stability of the endothelial barrier in the organ.

Type 2 Diabetes Mellitus Facilitates Shift of Adipose-Derived Stem Cells Ex Vivo Differentiation toward Osteogenesis among Patients with Obesity.

Objective: Sedentary behavior with overnutrition provokes the development of obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The main progenitor cells of adipose tissue are adipose-derived stem cells (ADSCs) which can change differentiation, metabolic, and secretory phenotypes under obesity conditions. The purpose of this study was to evaluate ADSC osteogenesis activity among patients with obesity in normal glucose tolerance (NGT) and T2DM conditions.

Regulation of Glucose Transport in Adipocytes by Interleukin-4.

Metabolic abnormalities such as obesity, insulin resistance, and type 2 diabetes mellitus are known to be associated with adipose tissue inflammation and impaired secretion of cytokines. Anti-inflammatory cytokine interleukin-4 (IL-4) was found to promote insulin sensitivity, glucose tolerance, and reduce lipid accumulation through multiple mechanisms, including direct regulation of lipolysis in adipocytes. However, little is known about its role in adipocyte glucose metabolism.

Grain-Based Dietary Background Impairs Restoration of Blood Flow and Skeletal Muscle During Hindlimb Ischemia in Comparison With Low-Fat and High-Fat Diets.

Among vascular pathologies associated with obesity, peripheral artery disease (PAD) occupies the important position. In clinical practice, nutritional interventions are recommended for patients with PAD. In this work, we investigated how the different dietary backgrounds affect the regeneration rate of ischemic hindlimb in mice.

NDRG1 Activity in Fat Depots Is Associated With Type 2 Diabetes and Impaired Incretin Profile in Patients With Morbid Obesity.

Objective: We aimed to investigate insulin-, mTOR- and SGK1-dependent signaling basal states in morbidly obese patients' fat. We analyzed the correlation between the signaling activity, carbohydrate metabolism, and incretin profiles of patients.

Methods: The omental and subcutaneous fat was obtained in patients with obesity.

The expression of apoptosis-regulating proteins Bcl-2 and Bad in liver cells of C57Bl/6 mice under light-induced functional pinealectomy and after correction with melatonin.

The presence of humans and animals under long-term continuous lighting leads to a suppression of melatonin synthesis, that is, to light-induced functional pinealectomy (LIFP), and the development of desynchronosis. To create LIFP, C57Bl/6 mice were kept under 24-hour lighting (24hL) for 14 days. The animals in the control group were kept under standard lighting conditions.

hTERT-immortalized adipose-derived stem cell line ASC52Telo demonstrates limited potential for adipose biology research.

In the modern world obesity and insulin resistance contribute to a high impact on the structure of mortality. Basic research and pharmacological screenings for the search of new targets and insulin sensitizers require relevant cell models of adipocytes. Today the 3T3-L1 preadipocytes cell line is a widely used mouse-based model for investigation of adipocyte biology.

Mitochondrial dynamics keep balance of nutrient combustion in thermogenic adipocytes.

Non-shivering thermogenesis takes place in brown and beige adipocytes and facilitates cold tolerance and acclimation. However, thermogenesis in adipose tissue also was found to be activated in metabolic overload states for fast utilization of nutrients excess. This observation spurred research interest in mechanisms of thermogenesis regulation for metabolic overload and obesity prevention.

Effect of Melatonin on Expression of Apoptosis Regulator Proteins Bcl-2 and Bad in Ovarian Follicular Apparatus after High Temperature Exposure.

Expression of proapoptotic Bad and antiapoptotic Bcl-2 proteins in ovarian follicular apparatus of Wistar rats was evaluated on days 3, 7, and 14 after single experimental hyperthermia (EH) followed by therapeutic correction with subcutaneous melatonin (0.1 mg) dissolved in 0.2 ml physiological saline (PS) injected daily for 3 days.

Apoptosis in the liver of male db/db mice during the development of obesity and type 2 diabetes.

Obesity and diabetes mellitus are known to lead to the development of metabolic syndrome and non-alcoholic fatty liver disease (NAFLD). The mechanisms of programmed cell death are actively involved in maintaining cellular homeostasis along development of NAFLD. Proteins of the BCL-2 family are key regulators of physiological and pathological apoptosis.

Decreased UCP-1 expression in beige adipocytes from adipose-derived stem cells of type 2 diabetes patients associates with mitochondrial ROS accumulation during obesity.

Objective: Adipose derived stem cells (ADSC) are defective in metabolic disorders in various functionalities and properties including differentiation, multipotent state, metabolism and immunomodulation. However, the role of ADSC beiging potential in promoting of type 2 diabetes mellitus (T2DM) development remains unclear. Here we uncover association between potential of subcutaneous ADSC to beige differentiation and T2DM in patients with obesity.

Expression of Apoptosis Regulator Proteins Bcl-2 and Bad in Rat Ovarian Follicular Apparatus during Recovery after Extreme Hypothermia.

The expression of molecular and cellular regulators of apoptosis (proapoptotic protein Bad and antiapoptotic protein Bcl-2) was measured in the follicular apparatus of rat ovaries during the recovery period (days 7 and 14) after hyperthermia (up to rectal temperature 43.5°C). The Bcl-2/Bad index was calculated.

Effects of Melatonin on the Body Composition, Physical Performance, and Blood Erythrocyte Indexes of C57Bl/6J Mice Exposed to Continuous Illumination.

Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group.

Effect of Linagliptin on the Ratio of Apoptosis Regulators in the Model of Non-Alcoholic Fatty Liver Disease in db/db Mice.

We studied the effects of dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin on the expression of apoptosis regulator proteins Bcl-2 and Bad in the liver of db/db mice with genetically determined obesity and type 2 diabetes mellitus. The mice received daily linagliptin or saline (placebo) by gavage from week 10 to week 18 of life. In the liver of non-treated mice, the area positively stained for Bad was greater than the area of Bcl-2 expression, which created the conditions for apoptosis activation in liver at this age.

Chemical Inducers of Obesity-Associated Metabolic Stress Activate Inflammation and Reduce Insulin Sensitivity in 3T3-L1 Adipocytes.

Obesity is accompanied by dyslipidemia, hypoxia, endoplasmic reticulum (ER) stress, and inflammation, representing the major risk factor for the development of insulin resistance (IR) and type 2 diabetes. We modeled these conditions in cultured 3T3-L1 adipocytes and studied their effect on insulin signaling, glucose uptake, and inflammatory response via activation of stress-dependent JNK1/2 kinases. Decreased insulin-induced phosphorylation of the insulin cascade components IRS, Akt, and AS160 was observed under all tested conditions (lipid overloading of cells by palmitate, acute inflammation induced by bacterial lipopolysaccharide, hypoxia induced by Co2+, and ER stress induced by brefeldin A).