Slit3 secreted from M2-like macrophages increases sympathetic activity and thermogenesis in adipose tissue.

Beiging of white adipose tissue (WAT) is associated with an increase of anti-inflammatory M2-like macrophages in WAT. However, mechanisms through which M2-like macrophages affect beiging are incompletely understood. Here, we show that the macrophage cytokine Slit3 is secreted by adipose tissue macrophages and promotes cold adaptation by stimulating sympathetic innervation and thermogenesis in mice. Analysing the transcriptome of M2-like macrophages in murine inguinal WAT (iWAT) after cold exposure, we identify Slit3 as a secreted cytokine. Slit3 binds to the ROBO1 receptor on sympathetic neurons to stimulate Ca2+/calmodulin-dependent protein kinase II signalling and norepinephrine release, which enhances adipocyte thermogenesis. Adoptive transfer of Slit3-overexpressing M2 macrophages to iWAT promotes beiging and thermogenesis, whereas mice that lack Slit3 in myeloid cells are cold-intolerant and gain more weight. Our findings shed new light on the integral role of M2-like macrophages for adipose tissue homeostasis and uncover the macrophage-Slit3-sympathetic neuron-adipocyte signalling axis as a regulator of long-term cold adaptation.

Neuro-mesenchymal units control ILC2 and obesity via a brain-adipose circuit.

Signals from sympathetic neurons and immune cells regulate adipocytes and thereby contribute to fat tissue biology. Interactions between the nervous and immune systems have recently emerged as important regulators of host defence and inflammation1-4. Nevertheless, it is unclear whether neuronal and immune cells co-operate in brain-body axes to orchestrate metabolism and obesity. Here we describe a neuro-mesenchymal unit that controls group 2 innate lymphoid cells (ILC2s), adipose tissue physiology, metabolism and obesity via a brain-adipose circuit. We found that sympathetic nerve terminals act on neighbouring adipose mesenchymal cells via the ß2-adrenergic receptor to control the expression of glial-derived neurotrophic factor (GDNF) and the activity of ILC2s in gonadal fat. Accordingly, ILC2-autonomous manipulation of the GDNF receptor machinery led to alterations in ILC2 function, energy expenditure, insulin resistance and propensity to obesity. Retrograde tracing and chemical, surgical and chemogenetic manipulations identified a sympathetic aorticorenal circuit that modulates ILC2s in gonadal fat and connects to higher-order brain areas, including the paraventricular nucleus of the hypothalamus. Our results identify a neuro-mesenchymal unit that translates cues from long-range neuronal circuitry into adipose-resident ILC2 function, thereby shaping host metabolism and obesity.

Relação anatômica da Bola de Bichat com ramos terminais do nervo facial / Anatomical Correlation among Bichat's fat pad with the Facial Nerve Terminal Branches

Introdução: A cirurgia de Bichectomia está sendo muito procurada por pessoas que visam diminuir o volume facial. O corpo adiposo da bochecha, ou bola de Bichat, possui uma complexa relação anatômica com estruturas faciais. Uma das complicações que o procedimento pode causar é a paralisia facial temporária ou permanente, em decorrência de injúrias causadas aos ramos terminais do nervo facial, devido à proximidade dessas duas estruturas anatômicas. Metodologia: O objetivo do presente artigo é enfatizar a relação anatômica da bola de Bichat com alguns ramos terminais do nervo facial através da dissecação de cadáveres. Foram feitas dissecações em três hemifaces de cadáveres humanos para a exposição do corpo adiposo da bochecha e dos ramos extracranianos do nervo facial. Resultados: A anatomia dos ramos terminais zigomáticos e bucais do nervo facial se mostrou variável em cada hemiface dissecada, mas sempre intimamente relacionados a bola de Bichat. Conclusões: O profissional que realiza a Bichectomia deve ter pleno conhecimento não só da técnica cirúrgica, mas também da variabilidade anatômica da região... (AU)

Introduction: The Buccal Fat Extraction surgery has been sought by people who aim to reduce facial volume. The Buccal fat pad has a complex anatomical correlation among the facial structures. The facial nerve paralysis is one of Bichat's fat extraction complications which might be temporary or permanent, due to the proximity of those anatomical structures. Methodology: The present article aims to emphasize the anatomical correlation between the Buccal fat pad and a few terminal branches of the facial nerve through the human cadaveric dissection. The dissection was performed on three human cadaveric hemifacial to expose the buccal fat pad body and the facial nerve extracranial branches. Results: The zygomatic and buccal terminal branches anatomy of the facial nerve has shown variables in each dissected hemifacial part. However, it has always presented closely related to Bichat's fat pad. Conclusions: The professional that performs the Buccal Fat Removal surgery must have to have the full knowledge not only about the surgical technique but the anatomical variability of the region, as well... (AU)

Sensory Recovery of the Breast following Innervated and Noninnervated DIEP Flap Breast Reconstruction.

BACKGROUND: The sensory recovery of the breast remains an undervalued aspect of autologous breast reconstruction. The aim of this study was to evaluate the effect of nerve coaptation on the sensory recovery of the breast following DIEP flap breast reconstruction and to assess the associations of length of follow-up and timing of the reconstruction. METHODS: A prospective comparative study was conducted of all patients who underwent either innervated or noninnervated DIEP flap breast reconstruction and returned for follow-up between September of 2015 and July of 2017. Nerve coaptation was performed to the anterior cutaneous branch of the third intercostal nerve. Semmes-Weinstein monofilaments were used for sensory testing of the native skin and flap skin. RESULTS: A total of 48 innervated DIEP flaps in 36 patients and 61 noninnervated DIEP flaps in 45 patients were tested at different follow-up time points. Nerve coaptation was significantly associated with lower monofilament values in all areas of the reconstructed breast (adjusted difference, -1.2; p < 0.001), which indicated that sensory recovery of the breast was significantly better in innervated compared with noninnervated DIEP flaps. For every month of follow-up, the mean monofilament value decreased by 0.083 in innervated flaps (p < 0.001) and 0.012 in noninnervated flaps (p < 0.001). Nerve coaptation significantly improved sensation in both immediate and delayed reconstructions. CONCLUSIONS: This study demonstrated that nerve coaptation in DIEP flap breast reconstruction is associated with a significantly better sensory recovery in all areas of the reconstructed breast compared with noninnervated flaps. The length of follow-up was significantly associated with the sensory recovery.

Macrophages in obesity.

Obesity is a worldwide public health concern yet no safe therapies are currently available. The activity of sympathetic neurons is necessary and sufficient for fat mass reduction, via norepinephrine (NE) signaling. Macrophage accumulation in the adipose tissue is thought to play the central role in the onset of obesity, yet their relation to NE has been controversial. We have identified a population of sympathetic neuron-associated macrophages (SAMs) that control obesity via the uptake and clearing of NE. Here we focus on the neuro-immune regulation of obesity by discussing the genetic, cellular and functional signatures of SAMs vis-a-vis adipose tissue macrophages (ATMs).

Nerve detection during surgery: optical spectroscopy for peripheral nerve localization.

Precise nerve localization is of major importance in both surgery and regional anesthesia. Optically based techniques can identify tissue through differences in optical properties, like absorption and scattering. The aim of this study was to evaluate the potential of optical spectroscopy (diffuse reflectance spectroscopy) for clinical nerve identification in vivo. Eighteen patients (8 male, 10 female, age 53 ± 13 years) undergoing inguinal lymph node resection or resection or a soft tissue tumor in the groin were included to measure the femoral or sciatic nerve and the surrounding tissues. In vivo optical measurements were performed using Diffuse Reflectance Spectroscopy (400-1600 nm) on nerve, near nerve adipose tissue, muscle, and subcutaneous fat using a needle-shaped probe. Model-based analyses were used to derive verified quantitative parameters as concentrations of optical absorbers and several parameters describing scattering. A total of 628 optical spectra were recorded. Measured spectra reveal noticeable tissue specific characteristics. Optical absorption of water, fat, and oxy- and deoxyhemoglobin was manifested in the measured spectra. The parameters water and fat content showed significant differences (P < 0.005) between nerve and all surrounding tissues. Classification using k-Nearest Neighbor based on the derived parameters revealed a sensitivity of 85% and a specificity of 79%, for identifying nerve from surrounding tissues. Diffuse Reflectance Spectroscopy identifies peripheral nerve bundles. The differences found between tissue groups are assignable to the tissue composition and structure.

Deciphering adipose tissue heterogeneity.

Obesity is an excess accumulation of adipose tissue mass, and, together with its sequelae, in particular type II diabetes and metabolic syndrome, obesity presents a major health crisis. Although obesity is simply caused by increased adipose mass, the heterogeneity of adipose tissue in humans means that the response to increased energy balance is highly complex. Individual subjects with similar phenotypes may respond very differently to the same treatments; therefore, obesity may benefit from a personalized precision medicine approach. The variability in the development of obesity is indeed driven by differences in sex, genetics, and environment, but also by the various types of adipose tissue as well as the different cell types that compose it. By describing the distinct cell populations that reside in different fat depots, we can interpret the complex effect of these various players in the maintenance of whole-body energy homeostasis. To further understand adipose tissue, adipogenic differentiation and the transcriptional program of lipid accumulation must be investigated. As the cell- and depot-specific functions are described, they can be placed in the context of energy excess to understand how the heterogeneity of adipose tissue shapes individual metabolic status and condition.

Critical review of beige adipocyte thermogenic activation and contribution to whole-body energy expenditure.

Beige (or brite, "brown in white") adipocytes are uncoupling protein 1 (UCP1)-positive cells residing in white adipose depots that, depending on the conditions, behave either as classic white adipocytes, storing energy as lipids, or as brown adipocytes, dissipating energy from oxidative metabolism as heat through non-shivering thermogenesis. Because of their thermogenic potential and, therefore, possible usage to treat metabolic diseases such as obesity and type 2 diabetes, beige cells have attracted the attention of many scientists worldwide aiming to develop strategies to safely recruit and activate their thermogenic activity. Indeed, in recent years, a large variety of conditions, molecules (including nutrients) and signaling pathways were reported to promote the recruitment of beige adipocytes. Despite of those advances, the true contribution of beige adipocyte thermogenesis to whole-body energy expenditure is still not completely defined. Herein, we discuss some important aspects that should be considered when studying beige adipocyte biology and the contribution to energy balance and whole-body metabolism.

The Relationship of the Temporal Branch of the Facial Nerve to the Fascial Planes of Temporal Region in Human Fetuses.

The aim of this study was to obtain information by assessing the relationship between temporal region fascial structures, fat pads, and temporal branches of facial nerve in human fetuses to use the knowledge on treatment of early childhood period surgeries. This anatomic dissection study was conducted on 40 hemifaces with no visible external abnormalities on their faces. Fascial layers and related fat pads of temporal region were dissected layer by layer beginning from superficial to deep. The relations of temporal branches of facial nerve and temporoparietal fascia and the structures of these fascial layers were evaluated. Temporoparietal fascia showed continuity below zygomatic arc with superficial musculoaponeurotic system. Temporal branches of facial nerve showed a multiple branching. Parotid-masseteric fascia became very thin on the superficial of zygomatic arch and ran with superficial layer of temporal fascia above without attaching to periosteum. Temporal branches of facial nerve entered between multilayered layers of temporoparietal fascia. Temporoparietal fascia became thicker on anterior and middle parts because of the localization of superficial temporal fat pad. Temporal fascia was a 2-layered thick and fibrous tissue enveloping intermediate fat pad. Deep layer connected to periosteum of zygomatic arch and superficial layer continued passing superficial of zygomatic arch and connected to the parotid-masseteric fascia. Deep temporal fat pad was found on the deep to deep layer of temporal fascia and surface of temporal muscle. The findings of this study may contribute to the knowledge of the topographical localization of temporal branches of facial nerve with temporal region fascial structures and fat pads in fetuses.

[PLASTIC CLOSURE OF THE WOUND DEFECT IN PATIENTS, SUFFERING THE ORAL AND ORO-PHARYNGEAL CANCER STAGES ІІІ - ІV].

Results of treatment of 124 patients, suffering locally-advanced oral and oropharyngeal cancer were analyzed. In these patients after wide excision of tissues the defect has occurred, which would be impossible to close using simple suturing. To these patients a primary plasty, using musculo-cutaneous or adiposo-cutaneous flap, was performed. The defect, occurring after resection of the oral cavity floor together with the mandibular anterior fragment, constitutes the most complex one for the plasty performance. The main principles of the defects plasty were determined. The plastic material choice depends on peculiar clinical situation, the surgical intervention volume, the defect localization and its size.

Increased Epicardial Adipose Tissue Volume Correlates With Cardiac Sympathetic Denervation in Patients With Heart Failure.

RATIONALE: It has been reported that epicardial adipose tissue (EAT) may affect myocardial autonomic function. OBJECTIVE: The aim of this study was to explore the relationship between EAT and cardiac sympathetic nerve activity in patients with heart failure. METHODS AND RESULTS: In 110 patients with systolic heart failure, we evaluated the correlation between echocardiographic EAT thickness and cardiac adrenergic nerve activity assessed by (123)I-metaiodobenzylguanidine ((123)I-MIBG). The predictive value of EAT thickness on cardiac sympathetic denervation ((123)I-MIBG early and late heart:mediastinum ratio and single-photon emission computed tomography total defect score) was tested in a multivariate analysis. Furthermore, catecholamine levels, catecholamine biosynthetic enzymes, and sympathetic nerve fibers were measured in EAT and subcutaneous adipose tissue biopsies obtained from patients with heart failure who underwent cardiac surgery. EAT thickness correlated with (123)I-MIBG early and late heart:mediastinum ratio and single-photon emission computed tomography total defect score, but not with left ventricular ejection fraction. Moreover, EAT resulted as an independent predictor of (123)I-MIBG early and late heart:mediastinum ratio and single-photon emission computed tomography total defect score and showed a significant additive predictive value on (123)I-MIBG planar and single-photon emission computed tomography results over demographic and clinical data. Although no differences were found in sympathetic innervation between EAT and subcutaneous adipose tissue, EAT showed an enhanced adrenergic activity demonstrated by the increased catecholamine levels and expression of catecholamine biosynthetic enzymes. CONCLUSIONS: This study provides the first evidence of a direct correlation between increased EAT thickness and cardiac sympathetic denervation in heart failure.

Running Injuries: The Infrapatellar Fat Pad and Plica Injuries.

When considering knee pain in runners, clinicians differentiate sources of symptoms and determine their cause. Knee problems arise when a runner increases the amount/frequency of the loading through the lower limb. The way the loading is distributed through the knee determines which tissues are abnormally loaded. Knee problems cannot be considered in isolation, requiring a thorough investigation of static and dynamic lower limb mechanics, and footwear and surfaces. This article examines potential sources of knee pain and explores the role of the infrapatellar fat pad and synovial plica in the mechanics of the knee and its involvement in knee symptoms.

Recent progress in research on the distribution and function of NUCB2/nesfatin-1 in peripheral tissues.

Nesfatin-1 is a polypeptide derived from the posttranslational processing of the N-terminal fragment of nucleobindin 2 (NUCB2), that was originally identified as an anorexigenic hypothalamic neuropeptide. A number of reports have recently shown that NUCB2/nesfatin-1 is widely expressed in various peripheral tissues, including those of the gastrointestinal tract where it may participate in various pathophysiological processes. One of its roles may be regulation of energy homeostasis. As a result, nesfatin-1 may be a novel target for exploring the underlying mechanisms and the treatment of metabolic syndromes.

Glycogen shortage during fasting triggers liver-brain-adipose neurocircuitry to facilitate fat utilization.

During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver-brain-adipose axis activation. Moreover, the blockade of glycogenolysis [corrected] through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver-brain-adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions.

Influence of anterior periaortic fat pad excision on incidence of postoperative atrial fibrillation.

OBJECTIVE: In humans, the existence of an anterior periaortic fat pad (AFP) containing parasympathetic ganglia has been described in the aortopulmonary window. Changes in the autonomic nervous system (ANS) tone can lead to postoperative atrial fibrillation (POAF). The AFP is usually removed during coronary bypass grafting (CABG) to fully expose the aortic root. The purpose of this study was to evaluate the influence of AFP removal during CABG on the ANS tone, incidence of POAF, hospital stay, and in-hospital morbidity and mortality. METHODS: A total of 215 patients were randomized in this prospective, double-blind trial to either removal (n=107) or maintenance (n=108) of the AFP during their first CABG. All patients underwent continuous telemetry monitoring after surgery. They underwent at least 1-h Holter monitoring on the second postoperative day. Heart rate variability measurements of both time-domain and frequency-domain analysis were included. POAF was defined as AF for more than 5min or causing hemodynamic instability. RESULTS: The mean age was nearly 58 years, and 76% were male. There was no difference in the incidence of POAF between the retained and removed AFP groups (19.3% vs 17%, respectively; P=0.664, odds ratio=1.16). Mean heart rate and heart rate variability parameters, in-hospital stay, and postoperative morbidity and mortality were similar in both groups. CONCLUSIONS: Removal of the AFP during CABG has no significant effect on the incidence of POAF, ANS tone, and postoperative morbidity or mortality.

Adipose tissue and reproduction in women.

Adipose tissue has been viewed as the primary source of stored energy, but with the discovery of novel adipose tissue gene products, i.e., adipokines, another equally important role has emerged. Adipose tissue is a key endocrine organ involved in multiple processes, including glucose homeostasis, steroid production, immunoregulation, hematopoesis, and reproduction. The distribution of adipose tissue may also have a significant impact on reproductive function.

Acupuncture and exercise restore adipose tissue expression of sympathetic markers and improve ovarian morphology in rats with dihydrotestosterone-induced PCOS.

Altered activity of the sympathetic nervous system, which innervates adipose and ovarian tissue, may play a role in polycystic ovary syndrome (PCOS). We hypothesize that electro-acupuncture (EA) and physical exercise reduce sympathetic activity by stimulating ergoreceptors and somatic afferent pathways in muscles. Here we investigated the effects of low-frequency EA and physical exercise on mRNA expression of sympathetic markers in adipose tissue and on ovarian morphology in female rats that received dihydrotestosterone (DHT) continuously, starting before puberty, to induce PCOS. At age 11 wk, rats with DHT-induced PCOS were randomly divided into three groups: PCOS, PCOS plus EA, and PCOS plus exercise. The latter two groups received 2-Hz EA (evoking muscle twitches) three times/week or had free access to a running wheel for 4-5 wk. In mesenteric adipose tissue, expression of beta(3)-adrenergic receptor (ADRB3), nerve growth factor (NGF), and neuropeptide Y (NPY) mRNA was higher in untreated PCOS rats than in controls. Low-frequency EA and exercise downregulated mRNA expression of NGF and NPY, and EA also downregulated expression of ADRB3, compared with untreated rats with DHT-induced PCOS. EA and exercise improved ovarian morphology, as reflected in a higher proportion of healthy antral follicles and a thinner theca interna cell layer than in untreated PCOS rats. These findings support the theory that increased sympathetic activity contributes to the development and maintenance of PCOS and that the effects of EA and exercise may be mediated by modulation of sympathetic outflow to the adipose tissue and ovaries.

[Morphological peculiarities of the adipose tissue and their significance for the ultrasound lipodestruction].

Using the autopsy material obtained from 20 human corpses, the samples of subcutaneous adipose tissue of the gluteal, abdominal, inguino-ileal and axillar areas, as well as the samples of mesenterial, retroperitoneal, mediastinal, pararectal and paranephral adipose tissue was studied histologically. The average sizes of the lobes and of adipocytes were measured, and the degree of the development of connective tissue elements was determined. Adipose tissue was found to have a similar general structural plan in all the areas studied, however the differences were noted in the thickness of the interlobular connective tissue septae and in tissue vascularization. The gluteal, inguino-ileal and anterior abdominal wall adipose tissue had the highest density. The lobules of this adipose tissue possessed the minimal numbers of adipocytes that had the smallest size. The mediastinal, retroperitoneal and paranephral adipose tissue was classified as a relatively loose one. The velocity of lipodestruction depended the degree of the development of connective tissue septae: this process proceed most rapidly in the mediastinal adipose tissue and most slowly--in the gluteal adipose tissue. In all the other areas studied, the duration of lipodestruction was the intermediate one.

Impact of amiodarone on the ability of anterior fat pad retention to prevent postcoronary arterial bypass grafting atrial fibrillation incidence: a substudy of the AFIST III (Atrial Fibrillation Suppression Trial III).

BACKGROUND: In the AFIST III (Atrial Fibrillation Suppressions Trial III), anterior fat pad (AFP) retention did not decrease the incidence of postoperative atrial fibrillation (POAF), but prophylaxis with amiodarone did. In order to examine the inter-relationship between amiodarone with AFP retention on POAF, we performed a planned subgroup analysis of AFIST III. METHODS: Coronary artery bypass graft (CABG) patients were randomized to AFP maintenance or removal with prophylactic amiodarone used via the discretion of the caregiver. Patients were categorized into four groups: AFP retention alone, AFP retention plus amiodarone, AFP removal alone and AFP removal plus amiodarone. Multivariate logistic regression was used to calculate adjusted odds ratios with 95% confidence intervals for development of POAF. RESULTS: Amiodarone was used in 28% of the 178 patients (mean age = 66 +/- 10, 80% male, 5% previous atrial fibrillation) undergoing CABG surgery. The overall POAF occurrence rate, regardless of subgroup designation was 35.4%. On multivariate logistic regression, amiodarone plus AFP retention was associated with an 81% reduction in the odds of the patient developing POAF (p = 0.015). Amiodarone prophylaxis without AFP retention was associated with a 68% reduction (p = 0.040). CONCLUSION: Amiodarone prophylaxis with or without AFP retention is an independent negative predictor of POAF. Combining amiodarone with AFP retention may provide a synergistic effect in the prevention of POAF. Further studies are needed to validate the results of this study.

Adipose tissue at entheses: the innervation and cell composition of the retromalleolar fat pad associated with the rat Achilles tendon.

This study set out to determine whether the fat pad at the attachment of the Achilles tendon has features enabling it to function as an immune organ and a mechanosensory device, and to be a source of pain in insertional tendon injuries. Sections for histology and immunohistochemistry were cut from the Achilles tendon enthesis organ of 1 day old, 1 month, 4 month and 24 month old rats. For fluorescence and peroxidase immunohistochemistry, cryosections were labelled with primary antibodies directed against PGP9.5, substance P, neurofilament 200, calcitonin gene related peptide, CD68, CD36, myeloid related protein 14, actin and vinculin. The fat pad contained not only adipocytes, but also fibrous tissue, mast cells, macrophages, fibroblasts and occasional fibrocartilage cells. It was richly innervated with nerve fibres, some of which were likely to be nociceptive, and others mechanoreceptive (myelinated fibres, immunoreactive for neurofilament 200). The fibres lay between individual fat cells and in association with blood vessels. In marked contrast, the enthesis itself and all other components of the enthesis organ were aneural at all ages. The presence of putative mechanoreceptive and nociceptive nerve endings between individual fat cells supports the hypothesis that the fat pad has a proprioceptive role monitoring changes in the insertional angle of the Achilles tendon and that it may be a source of pain in tendon injuries. The abundance of macrophages suggests that the adipose tissue could have a role in combating infection and/or removing debris from the retrocalcaneal bursa.