Innervation Of Tissue Research Articles

Transcriptome analysis of norepinephrine-induced lipolysis in differentiated adipocytes of Bama pig

Sympathetic innervation of white adipose tissue (WAT) plays a key role in the regulation of lipid metabolism. Sympathetic activation promotes release of norepinephrine (NE), which binds to adrenergic receptors on adipocytes, promoting adipocyte lipolysis and enhanced oxidative metabolism. However, the mechanism by which sympathetic nerves regulate lipid metabolism in pig adipose tissue remains unclear. We used NE to simulate the process of sympathetic driving in pig adipocytes. RNA sequencing (RNA-seq) was used to determine the gene expression profile of pig adipocytes responding to NE stimulation. Our data suggests that the lipolytic signaling pathway is activated in pig adipocytes upon acute stimulation of NE, resulting in enhanced lipid metabolism and lipolysis, consistent with the phenomena found in humans and mice. Specifically, differentially expressed protein coding genes (PCGs) (SIRT4, SLC27A1) are mainly associated with functions that inhibit fatty acid oxidation and promote lipid synthesis. Similarly, we investigated the changes in regulatory transcripts such as long non-coding RNAs (lncRNAs) and transcripts of uncertain coding potential (TUCP) in response to NE and found that differentially expressed lncRNAs (lncG47338, lncG30660, lncG29516, lncG3790) and TUCP (TUCP_G38001) were co-expressed with target genes related to the promotion of fatty acid β-oxidation, lipolysis and oxidative metabolism, thus acting as regulators. These results indicate a broad suite of gene expression alterations in response to NE stimulation and promote the understanding of the molecular mechanisms by which NE regulates lipid metabolism in pigs.

Anti-cancer and tissue-neuroprotective potentials of Moringa oleifera and Musa sapientum against in-vivo cadmium chlorideinduced skin toxicity

Background: Cadmium is an established carcinogen. Cadmium exposure resulted in skin carcinogenesis in rats. Furthermore, neurotransmitter-cancer interaction, tissue innervation, and angiogenesis influence cancer prognosis, metastasis, and survival. In this study, we evaluated the anticancer and neuro-protective potentials of MO11 (isolated from Moringa oleifera leaves) and MS06 (isolated from Musa sapientum suckers) against in-vivo Cadmium Chloride (CdCl2)- induced skin toxicity. Methods: Twenty-four adult male wistar rats were randomly divided into six groups (n = 4). Group 1 was control. Groups 2-4 and 6 received a single intraperitoneal administration of 1.5 mg/kg CdCl2 on Day 1. Thereafter, Groups 3, 4, and 6 were post-treated with 15 mg/kg MO11, 15 mg/kg MO11 + 7 mg/kg MS06, and 3.35 mg/kg Doxorubicin respectively (Days 1-17). Group 5 received an olive oil dose (vehicle) (Days 1-17). Skin histopathology and tissue-enzyme-linked-immunosorbent assays (Tissue-ELISA) of neurotransmitters (Dopamine and Glutamate), biomarkers of myelination (Myelin Basic Protein), drug metabolism and carcinogenesis (Cytochrome-p450), apoptosis (Caspase-3 and p53), proliferation (Ki67), and angiogenesis (sVEGFR) were evaluated in skin homogenates. Data were statistically analyzed using the Mann-Whitney-U test at P ≤ 0.05. Results: Histopathological analyses revealed normal skin histology (Groups 3 and 4), mild skin histo-alterations (Group 6), and gross skin histopathological alterations (Group 2). Tissue-ELISA analyses showed upregulations of dopamine, Glutamate and Cytochrome-p450, but downregulations of Myelin Basic Protein, Caspase-3, Ki67, p53, and sVEGFR in groups 3, 4, and 6, compared with group 2. MO11 and MS06 achieved better anticancer effects than doxorubicin. Conclusion: Overall, MO11 and MS06 possess histo-protective, neuro-protective, re-myelination, anti-proliferation, anti-angiogenesis, and anti-cancer potentials.

Changes of biliary cilia, smooth muscle tissue distribution, innervation and extracellular matrices during morphological evolution of hepatic architectures in vertebrates

BackgroundThe liver architecture of vertebrates can be classified into two types, the portal triad type (having periportal bile ducts) and the non-portal triad type (having bile ducts independent of the course of portal veins). The former is typically detectable in livers of tetrapods and cartilaginous fish, and its ancestral state is found in the hagfish, an earliest diverged lineage among vertebrates. Teleosts other than osteoglossomorphs have the latter. The aim of the present study is to reveal the changes of the hepatic innervation, biliary cilia and smooth muscle distribution, and extracellular matrices along vertebrate evolution with attention to the two types of liver architectures. MethodsThe hepatic innervation, biliary cilia and smooth muscle distribution, and collagen deposition were immunohistochemically and histochemically compared among livers of various vertebrates, using anti-acetylated tubulin and anti-α-smooth muscle actin antibodies, and Sirius red staining. These were also ultrastructurally examined. ResultsAlthough the hagfish liver had periportal intrahepatic bile ducts and ductules as detected in mammalian livers, it lacked smooth muscles around bile ducts and portal veins. Extracellular matrices in their connective tissues had thick collagen fibers. Its innervation was restricted to intrahepatic bile ducts and portal veins in the hilum. In livers of other vertebrates, including teleosts, the innervation was broadly detectable, especially around bile ducts, hepatic arteries and portal veins (afferent vessels), but not around central veins (efferent vessels). The chondrichthyans ultrastructurally had smooth muscle tissue around bile ducts. Cilia distribution was confirmed in intrahepatic bile ducts of tetrapods and basal actinopterygians. Teleosts other than osteoglossomorphs lacked cilia in their intrahepatic bile ducts. ConclusionsThe liver architecture of the hagfish may be unique for innervation and extracellular matrices. Hepatic innervation may not have occurred in vertebrate ancestors. Hepatic innervation in bile ducts, hepatic arteries and portal veins may have been conserved among the extant jawed vertebrates. Cilia distribution in bile ducts may have changed during evolution of actinopterygians.

Upscaled Skeletal Muscle Engineered Tissue with In Vivo Vascularization and Innervation Potential.

Engineering functional tissues of clinically relevant size (in mm-scale) in vitro is still a challenge in tissue engineering due to low oxygen diffusion and lack of vascularization. To address these limitations, a perfusion bioreactor was used to generate contractile engineered muscles of a 3 mm-thickness and a 8 mm-diameter. This study aimed to upscale the process to 50 mm in diameter by combining murine skeletal myoblasts (SkMbs) with human adipose-derived stromal vascular fraction (SVF) cells, providing high neuro-vascular potential in vivo. SkMbs were cultured on a type-I-collagen scaffold with (co-culture) or without (monoculture) SVF. Large-scale muscle-like tissue showed an increase in the maturation index over time (49.18 ± 1.63% and 76.63 ± 1.22%, at 9 and 11 days, respectively) and a similar force of contraction in mono- (43.4 ± 2.28 µN) or co-cultured (47.6 ± 4.7 µN) tissues. Four weeks after implantation in subcutaneous pockets of nude rats, the vessel length density within the constructs was significantly higher in SVF co-cultured tissues (5.03 ± 0.29 mm/mm2) compared to monocultured tissues (3.68 ± 0.32 mm/mm2) (p < 0.005). Although no mature neuromuscular junctions were present, nerve-like structures were predominantly observed in the engineered tissues co-cultured with SVF cells. This study demonstrates that SVF cells can support both in vivo vascularization and innervation of contractile muscle-like tissues, making significant progress towards clinical translation.

Functional results and quality of life after oral cavity reconstruction using autografts

The purpose of the study was to conduct a comparative analysis and evaluate the functional results and quality of life of patients with head and neck cancer after radical surgery, depending on the reconstruction techniques used and the feasibility of using autografts for the repair of tissue innervation. Material and Methods. From 2014 to 2021a total of 133 patients with oral cavity cancer underwent simultaneous or delayed reconstruction after radical surgery at Clinical Hospital 1 of Sechenov University. All patients were divided into 4 groups: group 1 (n=37, the main group): reconstruction with free flaps “with reinnervation”, group 2 (n=24): reconstruction with free flaps “without reinnervation”, group 3 (n=23): reconstruction with pedicled axial flaps “with innervation”, and group 4 (n=49): reconstruction with pedicled axial flaps “without innervation”. The QLQ-H&amp;N43 questionnaire was taken as the main tool, speech and swallowing functions were assessed by using scales, and sensibility was assessed by the Semmes-Weinstein and Weber tests, as well as by pain and temperature sensation. Results. In the main group, statistically significant best results were achieved in the following main scales of the QLQ-H&amp;N43 questionnaire: total score - Me=21 (Q1-9; Q3-29) (p=0.038); speech -Me=27 (Q1-7; Q3-37) (p=0.05) and body image - Me=22 (Q1-0; Q3-47) (p=0.049). In group 1, significantly better results were obtained in assessing all sensory tests, except for the temperature sensation. In relation to less discomfort on the donor area and greater satisfaction with the cosmetic result, group 1 also gained better scores than other groups. Conclusion. The use of innervated flaps improves the quality of life and patient satisfaction with the treatment results in long-term follow-up.

The Sympathetic Innervation of Adipose Tissues: Regulation, Functions, and Plasticity.

The sympathetic nervous system (SNS) is a crucial arm of the peripheral nervous system (PNS) and includes catecholaminergic neurons that release norepinephrine (NE) onto numerous effector tissues and organs in the body. SNS innervation of both white (WAT) and brown adipose tissue (BAT) is clearly essential for proper tissue function and metabolic control, as decades of surgical, chemical, and genetic denervation studies have demonstrated. Despite our vast knowledge about adipose sympathetic innervation, especially in the context of cold-stimulated browning and thermogenesis that are under SNS control, newer data now provide a nuanced view of the SNS supply to adipose, including its regulation by local neuroimmune cells and neurotrophic factors, the co-release of modulatory neuropeptides along with NE, the importance of local SNS drive to adipose versus systemic increases in circulating catecholamines, and the long-overlooked interplay between adipose sympathetic and sensory nerves. This article brings a modern view to the regulation of sympathetic innervation patterns in WAT and BAT, how to image and quantify the nerve supply, contributions of adipose SNS to tissue functions, and how adipose tissue nerves respond to tissue remodeling and plasticity with changing energy demands. © 2023 American Physiological Society. Compr Physiol 13:4985-5021, 2023.

596-P: Exercise Increases Plasma Neuronal Growth Regulator 1 (NEGR1) Concentrations in Human Subjects

Recent studies suggest that exercise-induced circulating factors are critical for the health benefits of exercise. In rodent models, we have identified NEGR1 as a cell adhesion molecule that is essential for remodeling white adipose tissue (WAT) innervation via sympathetic neurite outgrowth, and that NEGR1 is a secreted factor that may be involved inter-tissue communication. In humans, exercise training increases NEGR1 mRNA in subcutaneous WAT, but whether exercise regulates circulating NEGR1 in humans is not known. Here, we investigated the effects of a single bout of maximal exercise and exercise training on plasma NEGR1 in two different cohorts of obese subjects. Acute exercise (single bout until VO2MAX achieved) increased NEGR1 in plasma in all subjects (p&amp;lt;0.05; n=M3/F4). For the training study, obese subjects were randomized to one of three protocols: two different high intensity interval training (HIIT) protocols and one moderate continuous training (MCT) (Table), and blood samples were taken four days after the last training session. 1-HIIT and 4-HIIT similarly increased plasma NEGR1 concentrations, while there was no significant effect of MCT on NEGR1. In conclusion, we identify NEGR1 as a novel exercise-induced circulating factor in human subjects. We hypothesize that NEGR1 plays a role in tissue cross-talk mediating neuronal refinement in several tissues. Disclosure P.Nigro: None. N.P.Carbone: None. C.Bueno junior: None. M.Vamvini: None. L.Simpson: None. G.A.Hansbury: None. M.F.Hirshman: Stock/Shareholder; Abbott, AbbVie Inc., Amgen Inc., Colgate-Palmolive, Eli Lilly and Company, Medtronic. R.J.W.Middelbeek: Research Support; Novo Nordisk. L.Goodyear: None. Funding National Institutes of Health (R01DK099511, R01DK101043, K23DK114550, 5T32DK00726042, F32DK12643201); Joslin Diabetes Center (P30DK36836)

Neural innervation in adipose tissue, gut, pancreas, and liver

Abstract Efficient communication between the brain and peripheral organs is indispensable for regulating physiological function and maintaining energy homeostasis. The peripheral nervous system (PNS) in vertebrates, consisting of the autonomic and somatic nervous systems, bridges the peripheral organs and the central nervous system (CNS). Metabolic signals are processed by both vagal sensory nerves and somatosensory nerves. The CNS receives sensory inputs via ascending nerves, serves as the coordination and integration center, and subsequently controls internal organs and glands via descending nerves. The autonomic nervous system consists of sympathetic and parasympathetic branches that project peripheral nerves into various anatomical locations to regulate the energy balance. Sympathetic and parasympathetic nerves typically control the reflexive and involuntary functions in organs. In this review article, we outline the innervation of adipose tissue, gut, pancreas, and liver, to illustrate the neurobiological basis of central–peripheral interactions. We emphasize the importance of understanding the functional atlas of neural control of energy metabolism, and more importantly, provide potential avenues for further research in this area.

Lingual innervation in male and female marmosets

Several gaps in knowledge exists in our understanding of orofacial pain. Some of these include type of peripheral sensory innervation in specific tissues, differences in innervation between sexes and validation of rodent studies in higher order species. The current study addresses these gaps by validating mouse studies for sensory innervation of tongue tissue in non-human primates as well as assesses sex-specific differences. Tongue and trigeminal ganglia were collected from naïve male and female marmosets and tested for nerve fibers using specific markers by immunohistochemistry and number of fibers quantified. We also tested whether specific subgroups of nerve fibers belonged to myelinating or non-myelinating axons. We observed that similar to findings in mice, marmoset tongue was innervated with nerve filaments expressing nociceptor markers like CGRP and TRPV1 as well as non-nociceptor markers like TrkB, parvalbumin (PV) and tyrosine hydroxylase (TH). Furthermore, we found that while portion of TrkB and PV may be sensory fibers, TH-positive fibers were primarily sympathetic nerve fibers. Moreover, number of CGRP, TrkB and TH-positive nerve fibers were similar in both sexes. However, we observed a higher proportion of myelinated TRPV1 positive fibers in females than in males as well as increased number of PV + fibers in females.Taken together, the study for the first time characterizes sensory innervation in non-human primates as well as evaluates sex-differences in innervation of tongue tissue, thereby laying the foundation for future orofacial pain research with new world smaller NHPs like the common marmoset.

HUBUNGAN PENGETAHUAN WUS TENTANG KANKER PAYUDARA DENGAN PERILAKU SADARI

Breast cancer is a malignancy found in breast tissue in cells originating from its glandular components, namely the epithelium and its lobules and components other than glands, namely the innervation of breast tissue, blood vessels and fat tissue. According to the World Health Organization (WHO) in 2020 globally there are 2,3 million women diagnosed with breast cancer and 685.000 deaths. One of the efforts to prevent and control breast cancer is to do breast self-examination behavior (BSE). This study aims to determine the relationship between WUS knowledge about breast cancer and BSE in Desa Karangpucung. This research method is correlational descriptive with cross sectional approach with sampling purposive sampling technique. The number of samples in this research were 97 respondents. Data analysis using Spearman rank test. Collecting data using a breast cancer knowledge questionnaire and BSE behavior. The results showed that there was correlation of knowledge of childbearing age women on breast cancer and BSE with a p-value = 0,000 (p&lt;0,05) with correlation coefficient value = 0,574.

Di-butyl phthalate disrupts muscle, motor and sensory neuron development in embryonic zebrafish

Phthalates are added to plastics to enhance its flexibility, durability and transparency. Phthalates are not covalently bound to plastics and leach into the environment. Phthalates are now pervasive and ubiquitously present in the atmosphere, soil and sediment, surface and wastewater. Phthalates are known endocrine disruptors and their effects on male and female reproduction are well noted. However, studies on the developmental effects of di-butyl phthalate (DBP) are limited. Here we investigated the developmental toxicity of DBP on motor and sensory neuron populations and the muscle structures motor neurons innervate using the zebrafish vertebrate model system. We investigated these effects during the time window of development spanning the period where embryonic patterning determines adult structures. We found that treatment with 2.5 μM DBP from 6 h post-fertilization (hpf) until 72hpf induces loss and disorganization of primary motor neuron innervation of the somatic tissue with concomitant disruptions to muscle fiber organization. Furthermore, we found disruptions to sensory motor neuron development including defects in dorsal root ganglion and their peripherally extending axons. Rohon-Beard sensory neurons were also disrupted showing loss of the bilateral soma positioning along the length of the spinal cord and their afferent axonal projections to the epithelium. Thus, we concluded that DBP is toxic to developing motor and sensory neurons during embryonic development.

Somatosensory innervation of adipose tissues

The increasing prevalence of obesity and type 2 diabetes has led to a greater interest in adipose tissue physiology. Adipose tissue is now understood as an organ with endocrine and thermogenic capacities in addition to its role in fat storage. It plays a critical role in systemic metabolism and energy regulation, and its activity is tightly regulated by the nervous system. Fat is now recognized to receive sympathetic innervation, which transmits information from the brain, as well as sensory innervation, which sends information into the brain. The role of sympathetic innervation in adipose tissue has been extensively studied. However, the extent and the functional significance of sensory innervation have long been unclear. Recent studies have started to reveal that sensory neurons robustly innervate adipose tissue and play an important role in regulating fat activity. This brief review will discuss both historical evidence and recent advances, as well as important remaining questions about the sensory innervation of adipose tissue.

Administration with L-glutamine and L-glutathione protects the nitrergic innervation of the penile tissue of diabetic rats

Erectile dysfunction is caused due to neuropathy, resulting from a high oxidative stress, in this way treatment with antioxidants may be promising. Aim of this work was to investigate the effects of the administration of 2% L-glutamine and 1% L-glutathione on the penile tissue of diabetic rats analyzing the nerve fibers that expressing Nitric Oxide Synthase Neuronal (nNOS). Forty-eight male Wistar rats distributed into six groups were used: normoglycemic, diabetic, normoglycemic administered with 2% L-glutamine, normoglycemic administered with 1% L-glutathione, diabetic administered with 2% L-glutamine, and diabetic administered with 1% L-glutathione. After a 120 days experimental period, the animals were euthanized, and the penile tissues were collected and processed for the subsequent immunohistochemical procedure (nNOS) and posterior varicosities morphometry analysis. Diabetic rats administered with L-glutamine and with L-glutathione displayed larger varicosity areas of 14 and 15% compared to the diabetic group (p &lt; 0.05). On the other hand, the administration of 2% L-glutamine and 1% L-glutathione in normoglycemic animals promoted a reduction of 3.3% and 2.4% compared to the normoglycemic group (p &lt; 0.05). We concluded that both L-glutamine and L-glutathione administrations exerted a protective effect on the penile nitrergic innervation of diabetic rats, which can have a positive impact on the erectile function and that their use in normoglycemic animals should be better investigated.

Age-related changes to adipose tissue and peripheral neuropathy in genetically diverse HET3 mice differ by sex and are not mitigated by rapamycin longevity treatment.

Neural communication between the brain and adipose tissues regulates energy expenditure and metabolism through modulation of adipose tissue functions. We have recently demonstrated that under pathophysiological conditions (obesity, diabetes, and aging), total subcutaneous white adipose tissue (scWAT) innervation is decreased ('adipose neuropathy'). With advanced age in the C57BL/6J mouse, small fiber peripheral nerve endings in adipose tissue die back, resulting in reduced contact with adipose-resident blood vessels and other cells. This vascular neuropathy and parenchymal neuropathy together likely pose a physiological challenge for tissue function. In the current work, we used the genetically diverse HET3 mouse model to investigate the incidence of peripheral neuropathy and adipose tissue dysregulation across several ages in both male and female mice. We also investigated the anti-aging treatment rapamycin, an mTOR inhibitor, as a means to prevent or reduce adipose neuropathy. We found that HET3 mice displayed a reduced neuropathy phenotype compared to inbred C56BL/6J mice, indicating genetic contributions to this aging phenotype. Compared to female HET3 mice, male HET3 mice had worse neuropathic phenotypes by 62 weeks of age. Female HET3 mice appeared to have increased protection from neuropathy until advanced age (126 weeks), after reproductive senescence. We found that rapamycin overall had little impact on neuropathy measures, and actually worsened adipose tissue inflammation and fibrosis. Despite its success as a longevity treatment in mice, higher doses and longer delivery paradigms for rapamycin may lead to a disconnect between life span and beneficial health outcomes.

The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling.

There is evidence of glandular tissue in the region of the anterior vaginal wall-female periurethral tissue (AVW-FPT) that has similar morphology and immunohistochemistry to the prostate in men. Surgical injury to this tissue has been suggested as a potential cause of sexual dysfunction following midurethral sling (MUS) procedures. However, the anatomy and embryology of these glands have not been fully resolved. This has led to difficulties in classifying this tissue as a prostate and defining its clinical significance related to MUS procedures. To describe the histological and immunohistochemical characteristics of the female periurethral glands using markers of prostate tissue and innervation and to examine their anatomical relationships to an implanted MUS. Using gross and fine dissection, the AVW-FPT was dissected from 9 cadavers. Prior to dissection, 2 cadavers underwent simulation of the MUS procedure by a urogynecologist. Samples were paraffin embedded and serially sectioned. Immunohistochemistry was performed using markers of prostate tissue and innervation. Immunohistochemical localization of markers for prostatic tissue and innervation of the glandular tissue of the AVW-FPT, including the region of MUS implantation. Female periurethral glands were immunoreactive for markers of male prostatic tissue, including prostate-specific antigen, androgen receptor, HOXB13, and NKX3.1. Markers of innervation (protein gene product 9.5, choline acetyl transferase, and vasoactive intestinal polypeptide) also localized to certain regions of the glandular tissue and associated blood supply. Surgical simulation of the MUS procedure demonstrated that some periurethral glands are located in close proximity to an implanted sling. The AVW-FPT contains glandular tissue in the surgical field of MUS implantation. Iatrogenic damage to the female periurethral glands and the associated innervation during surgery could explain the negative impacts on sexual dysfunction reported following MUS procedures. This is the first study to characterize the female periurethral glands using markers of prostatic tissue in concert with markers of general and autonomic innervation and characterize their anatomical relationships within the surgical field of MUS implantation. The small sample size is a limitation of this study. We provide further evidence that the AVW-FPT contains innervated glands that are phenotypically similar to the male prostate and may share a common embryonic origin. The microscopic and immunohistochemical features of the periurethral glands may be indicative of their functional capacity in sexual responses. The location of these glands in the surgical field of MUS procedures underscores the clinical significance of this tissue.

Neuregulin 4 as a novel adipokine in energy metabolism.

Adipose tissue has been shown to play a key role in energy metabolism and it has been shown to regulate metabolic homeostasis through the secretion of adipokines. Neuregulin 4 (Nrg4), a novel adipokine secreted mainly by brown adipose tissue (BAT), has recently been characterized as having an important effect on the regulation of energy homeostasis and glucolipid metabolism. Nrg4 can modulate BAT-related thermogenesis by increasing sympathetic innervation of adipose tissue and therefore has potential metabolic benefits. Nrg4 improves metabolic dysregulation in various metabolic diseases such as insulin resistance, obesity, non-alcoholic fatty liver disease, and diabetes through several mechanisms such as anti-inflammation, autophagy regulation, pro-angiogenesis, and lipid metabolism normalization. However, inconsistent findings are found regarding the effects of Nrg4 on metabolic diseases in clinical settings, and this heterogeneity needs to be further clarified by future studies. The potential metabolic protective effect of Nrg4 suggests that it may be a promising endocrine therapeutic target.

Homology in Structural and Functional Organization of the Fibrous Framework of the Derma and Paraneural Connective Tissue Components

Background: The recent increase in hostilities throughout the globe is one of the main factors that damage both the skin and peripheral nerves (PN), mainly of the upper and lower extremities. The duration of treatment of the injured limb and the rate of recovery of its functions are directly related to the structural integrity of the connective tissue (CT) sheath apparatus of the PN, which further actualizes the study of its micromorphological components. The structural integrity of the peripheral nerve includes not only the preservation of its conductive component but also the membranes surrounding it, providing complete morphofunctional unity. Thus, the study of the features of their tissue organization, vascularization and innervation, with the obligatory comparison of data with homologous tissue of different topography and possible extrapolation of data, determined the purpose of this work. The aim of this study was to analyze the dynamics of changes in the fibrous components of the paraneurium and dermis in onto- and phylogenesis under the influence of various factors and to compare the data obtained for their further extrapolation. Methods and Results: The study was conducted on mature male Wistar rats under standard vivarium conditions. The material for the study was the CT sheaths of the PN of the extremities and skin areas, 1x1 cm in size, to the depth of the subcutaneous fascia of animals. The cadaver material was taken on Days 1, 3, 7, 10, and 28 of ontogeny. The resulting biomaterial was fixed in a 10% buffered neutral formalin solution and embedded in paraffin, according to the standard method. Microtomized, the resulting histological sections were stained with hematoxylin and eosin, according to the method of Mallory and Van Gieson. A comprehensive morphological study was performed using light and electron microscopy. The study revealed the presence of two stages in the ontogeny of the CT, forming the dermis of the skin and paraneural CT structures of PN. In the first stage, structural elements are formed, considering the topography of the CT; in the second, they are differentiated, leading to a qualitative-quantitative transformation due to the appearance of a number of additional functions, an active period of body growth, and taking into account the action of various environmental factors. At earlier stages of ontogenesis, thin, flattened fibrous structures without a clear organization are observed in the field of view in the dermis of the skin. In the paraneurium, the components that form it are not sufficiently expressed. At later periods, the shape and architectonics of the fibrous component change, structurization and an increase in the thickness of the fibers occur and pronounced heterogeneity of the cellular component is observed.

Sodium butyrate attenuated diet-induced obesity, insulin resistance and inflammation partly by promoting fat thermogenesis via intro-adipose sympathetic innervation.

Emerging evidence suggests that butyrate, a short-chain fatty acid, may have beneficial effects on obesity and its associated metabolic comorbidities, but the related molecular mechanism is largely unknown. This study aims to investigate the role of butyrate in diet-induced obesity and metabolic disorders and the relevant regulatory mechanisms. Here, dietary supplementation with Sodium butyrate (NaB) was carried out in mice fed with a high-fat diet (HFD) or chow diet. At week 14, mice on HFD displayed an obese phenotype and down-regulated expression of thermogenic regulators including Ucp-1 and Pgc-1α in adipose tissue. Excitingly, NaB add-on treatment abolished these detrimental effects. Moreover, the obesity-induced insulin resistance, inflammation, fatty liver, and intestinal dysfunction were also attenuated by NaB administration. Mechanistically, NaB can promote fat thermogenesis via the increased local sympathetic innervation of adipose tissue, and blocking the β3-adrenergic signaling pathway by 6-hydroxydopamine abolished NaB-induced thermogenesis. Our study reveals a potential pharmacological target for NaB to combat obesity and metabolic disorders.

Ventromedial hypothalamic OGT drives adipose tissue lipolysis and curbs obesity.

The ventromedial hypothalamus (VMH) is known to regulate body weight and counterregulatory response. However, how VMH neurons regulate lipid metabolism and energy balance remains unknown. O-linked β-d-N-acetylglucosamine (O-GlcNAc) modification (O-GlcNAcylation), catalyzed by O-GlcNAc transferase (OGT), is considered a cellular sensor of nutrients and hormones. Here, we report that genetic ablation of OGT in VMH neurons inhibits neuronal excitability. Mice with VMH neuron-specific OGT deletion show rapid weight gain, increased adiposity, and reduced energy expenditure, without significant changes in food intake or physical activity. The obesity phenotype is associated with adipocyte hypertrophy and reduced lipolysis of white adipose tissues. In addition, OGT deletion in VMH neurons down-regulates the sympathetic activity and impairs the sympathetic innervation of white adipose tissues. These findings identify OGT in the VMH as a homeostatic set point that controls body weight and underscore the importance of the VMH in regulating lipid metabolism through white adipose tissue–specific innervation.

Peculiarities of the Innervation of Epicardial Adipose Tissue in a Rat with Aging (Immunohistochemical Study)

Peculiarities of the Innervation of Epicardial Adipose Tissue in a Rat with Aging (Immunohistochemical Study)