White adipose tissue browning and obesity

Obesity and metabolic disorders are major health concems worldwide. Although a range of therapies have been developed, these pharmaceutical treatments often have adverse side effects or limited efficacy. Therefore, there is a growing need of novel therapeutics to prevent or treat obesity. Obesity is thought to be caused by an imbalance between energy intake and energy consumption. Increasing energy consumption is considered as a potential therapeutic strategy to treat obesity and its related disorders.

Chchd10 is dispensable for myogenesis but critical for adipose browning

The Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus.Mutations of Chchd10 are associated with ALS,dementia and myopathy in humans and animal models,but how knockout of Chchd10(Chchd10KO)affects various tissues especially skeletal muscle and adipose tissues remains unclear.Here we show that Chchd10 expression increases as myoblasts and preadipocytes dif-ferentiate.During myogenesis,CHCHD10 interacts with TAR DNA binding protein 43(TDP-43)in regenerating myofib-ers in vivo and in newly differentiated myotubes ex vivo.Surprisingly,Chchd10KO mice had normal skeletal muscle development,growth and regeneration,with moderate defects in grip strength and motor performance.Chchd10KO similarly had no effects on development of brown and white adipose tissues(WAT).However,Chchd10KO mice had blunted response to acute cold and attenuated cold-induced browning of WAT,with markedly reduced UCP1 levels.Together,these results demonstrate that Chchd10 is dispensable for normal myogenesis and adipogenesis but is required for normal motility and cold-induced,mitochondrion-dependent browning of adipocytes.The data also sug-gest that human CHCHD10 mutations cause myopathy through a gain-of-function mechanism.

Ginsenoside F1 administration promotes UCP1-dependent fat browning and ameliorates obesity-associated insulin resistance

Obesity-induced type 2 diabetes is mainly due to excessive free fatty acids leading to insulin resistance.Increasing thermogenesis is regarded as an effective strategy for hypolipidemia and hypoglycemia.Ginsenoside is a natural active component in Panax ginseng C.A.Meyer,and some of them enhance thermogenesis.However,there are few studies on the mechanism and target of ginsenosides enhancing thermogenesis.Using thermogenic protein uncoupling protein 1(UCP1)-luciferase reporter assay,we identifi ed ginsenoside F1 as a novel UCP1 activator in the ginsenosides library.Using pull down assay and inhibitor interference,we found F1 binds toβ3-adrenergic receptors(β3-AR)to enhance UCP1 expression via cAMP/PKA/CREB pathway.We also investigated the ability of F1 on energy metabolism in obesity-induced diabetic mice,including body weight,body composition and energy expenditure.The results of proteomics showed that F1 signifi cantly up-regulated thermogenesis proteins and lipolytic proteins,but down-regulated fatty acid synthesis proteins.Ginsenoside F1 increased thermogenesis and ameliorated insulin resistance specifi cally by promoting the browning of white adipose tissue in obese mice.Additionally,ginsenoside F1 improves norepinephrine-induced insulin resistance in adipocytes and hepatocytes,and shows a stronger mitochondria respiration ability than norepinephrine.These fi ndings suggest that ginsenoside F1 is a promising lead compound in the improvement of insulin resistance.

Medium-Chain Triglyceride Activated Brown Adipose Tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-fat Diet

Objective To investigate activation of brown adipose tissue （BAT） stimulated by medium-chain triglyceride （MCT）. Methods 30 Male C57BL/6J obese mice induced by fed high fat diet （HFD） were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride （LCT） respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue （IBAT） mass, expressions of mRNA and protein of beta 3-adrenergic receptors （β3-AR）, uncoupling protein-1 （UCP1）, hormone sensitive lipase （HSL）, protein kinase A （PKA）, and adipose triglyceride lipase （ATGL） in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group （P〈O.05） after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group （P〈O.05）. Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein of β3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group （P〈O.05）. Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

ICA-Unet:An improved U-net network for brown adipose tissue segmentation

Brown adipose tissue(BAT)is a kind of adipose tissue engaging in thermoregulatory thermogenesis,metaboloregulatory thermogenesis,and secretory.Current studies have revealed that BAT activity is negatively correlated with adult body weight and is considered a target tissue for the treatment of obesity and other metabolic-related diseases.Additionally,the activity of BAT presents certain differences between different ages and genders.Clinically,BAT segmentation based on PET/CT data is a reliable method for brown fat research.However,most of the current BAT segmentation methods rely on the experience of doctors.In this paper,an improved U-net network,ICA-Unet,is proposed to achieve automatic and precise segmentation of BAT.First,the traditional 2D convolution layer in the encoder is replaced with a depth-wise overparameterized convolutional(Do-Conv)layer.Second,the channel attention block is introduced between the double-layer convolution.Finally,the image information entropy(IIE)block is added in the skip connections to strengthen the edge features.Furthermore,the performance of this method is evaluated on the dataset of PET/CT images from 368 patients.The results demonstrate a strong agreement between the automatic segmentation of BAT and manual annotation by experts.The average DICE coeffcient(DSC)is 0.9057,and the average Hausdorff distance is 7.2810.Experimental results suggest that the method proposed in this paper can achieve effcient and accurate automatic BAT segmentation and satisfy the clinical requirements of BAT.

Orexin receptor type 2 agonism inhibits thermogenesis in brown adipose tissue by attenuating afferent innervation

Orexin signaling has been associated with energy expenditure and brown adipose tissue(BAT)function.However,conflicting data exist in the field about how orexin signaling regulates BAT thermogenesis.In this study,we show that a specific orexin receptor type 2(OX2R)agonist[Ala11,D-Leu15]-OxB(OB-Ala)inhibited intrascapular brown adipose tissue(iBAT)thermogenesis by reducing sympathetic output to iBAT.This effect is mediated by OX2Rs located on afferent nerve endings innervating iBAT instead of brown adipocyte itself.Microinjection of OB-Ala into iBAT inhibited iBAT thermogenesis in mice upon cold exposure and neuronal activity in the paraventricular nucleus.Findings suggest that OB-Ala could inhibit iBAT thermogenesis by attenuating sensory input thereby inhibiting the sympathetic-sensory iBAT feedback loop.Our study uncovers a novel primary action site of orexin in the regulation of energy balance.

A Statistical Evaluation of Uncoupling Protein 1 in the Limited Area of Brown Adipose Tissue by Immunoelectron Microscopy

Uncoupling protein 1 (UCP1) expressed by the brown adipose tissue (BAT) in the mitochondrial crista acts as a homeostatic thermogenerator of eutherians. The evaluation of UCP1 expression in the BAT offers significant scientific insight, especially in studies targeting limited areas such as the periarterial and pericardial regions of small experimental mammals. However, the negligible amount of this adipose tissue would render the general quantitative evaluation of the protein unreliable because of lipid contamination and low protein concentration. To address this problem, we quantitatively evaluated UCP1 expression in the mitochondrion of the mouse interscapular BAT using immunoelectron microscopy and immunohistochemical studies using a combination of primary and secondary antibodies in scheme A (rabbit anti-UCP1 IgG/gold particle-conjugated goat anti-rabbit IgG), B (rabbit IgG/gold particle-conjugated goat anti-rabbit IgG), C (rabbit anti-UCP1 IgG/gold particle-unconjugated goat anti-rabbit IgG), and D (rabbit IgG/gold particle-unconjugated goat anti-rabbit IgG). Scheme A shows the immunopositive reaction of obvious gold particles in the mitochondrial area, whereas other procedures revealed less distinctive reactions. The distinctive gold particle immunoreaction comprised electrical high-density spots with a mean diameter of >5 nm. However, in scheme B, the electrical high-density spots were scattered outside the mitochondrion and were significantly smaller than 4 nm;schemes C and D demonstrated few immunoreactions. Logistic regression analysis between schemes A and B showed that the threshold diameter of the electrical high-density spots measuring >5 nm indicated a true positive immunoreaction to anti-UCP1 antibody specifically in the mitochondrial area. Minor statistical difference was observed in the primary anti-UCP1 antibody between polyclonal IgG and monoclonal antibodies. Therefore, immunoelectron microscopy might be useful for evaluating negligible protein expression in some limited areas, such as UCP1 expression in the BAT of small experimental animals.

Global gene expression profiling of perirenal brown adipose tissue whitening in goat kids reveals novel genes linked to adipose remodeling

Background Brown adipose tissue(BAT)is known to be capable of non-shivering thermogenesis under cold stimulation,which is related to the mortality of animals.In the previous study,we observed that goat BAT is mainly located around the kidney at birth,and changes to white adipose tissue(WAT)in the perirenal adipose tissue of goats within one month after birth.However,the regulatory factors underlying this change is remain unclear.In this study,we systematically studied the perirenal adipose tissue of goat kids in histological,cytological,and accompanying molecular level changes from 0 to 28 d after birth.Results Our study found a higher mortality rate in winter-born goat kids,with goat birthing data statistics.Then we used thermal imaging revealing high temperature in goat hips at postnatal 0 d and gradually decrease during 28 d.This is consistent with the region of perirenal BAT deposition and highlights its critical role in energy expenditure and body temperature regulation in goat kids.Additionally,we found a series of changes of BAT during the first 28 d after birth,such as whitening,larger lipid droplets,decreased mitochondrial numbers,and down-regulation of key thermogenesis-related genes(UCP1,DIO2,UCP2,CIDEA,PPARGC1a,C/EBPb,and C/EBPa).Then,we used RNA-seq found specific marker genes for goat adipose tissue and identified 12 new marker genes for BAT and 10 new marker genes for WAT of goats.Furthermore,12 candidate genes were found to potentially regulate goat BAT thermogenesis.The mechanism of the change of this biological phenomenon does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.While apoptosis may play a limited role,it is largely not critical in this transition process.Conclusions We concluded that perirenal BAT plays a crucial role in thermoregulation in newborn goat kids,with notable species differences in the expression of adipose tissue marker genes,and we highlighted some potential marker genes for goat BAT and WAT.Additionally,the change from BAT to WAT does not involve a large-scale death of brown adipocytes and subsequent proliferation of white adipocytes.

Recent developments in natural products for white adipose tissue browning

Excess accumulation of white adipose tissue(WAT) causes obesity which is an imbalance between energy intake and energy expenditure. Obesity is a serious concern because it has been the leading causes of death worldwide, including diabetes, stroke,heart disease and cancer. Therefore, uncovering the mechanism of obesity and discovering anti-obesity drugs are crucial to prevent obesity and its complications. Browning, inducing white adipose tissue to brown or beige(brite) fat which is brown-like fat emerging in WAT, becomes an appealing therapeutic strategy for obesity and metabolic disorders. Due to lack of efficacy or intolerable side-effects, the clinical trials that promote brown adipose tissue(BAT) thermogenesis and browning of WAT have not been successful in humans. Obviously, more specific means still need to be developed to activate browning of white adipose tissue. In this review, we summarized seven kinds of natural products(alkaloids, flavonoids, terpenoids, long chain fatty acids, phenolic acids, else and extract) promoting white adipose tissue browning which can ameliorate the metabolic disorders, including obesity, dislipidemia, insulin resistance and diabetes. Since natural products are important drug sources and the browning property plays a significant role in not only obesity treatment but also in type 2 diabetes(T2 DM) improvement, natural products of inducing browning may be an irreplaceable drug discovery orientation for obesity, diabetes and even other metabolic disorders.

Intercellular and inter-organ crosstalk in browning of white adipose tissue:molecular mechanism and therapeutic complications

Adipose tissue(AT)is highly plastic and heterogeneous in response to environmental and nutritional changes.The development of heat-dissipating beige adipocytes in white AT(WAT)through a process known as browning(or beiging)has garnered much attention as a promising therapeutic strategy for obesity and its related metabolic complications.This is due to its inducibility in response to thermogenic stimulation and its association with improved metabolic health.WAT consists of adipocytes,nerves,vascular endothelial cells,various types of immune cells,adipocyte progenitor cells,and fibroblasts.These cells contribute to the formation of beige adipocytes through the release of protein factors that significantly influence browning capacity.In addition,inter-organ crosstalk is also important for beige adipocyte biogenesis.Here,we summarize recent findings on fat depot-specific differences,secretory factors participating in intercellular and inter-organ communications that regulate the recruitment of thermogenic beige adipocytes,as well as challenges in targeting beige adipocytes as a potential anti-obese therapy.

Population genomics reveals that natural variation in PRDM16 contributes to cold tolerance in domestic cattle

Environmental temperature serves as a major driver of adaptive changes in wild organisms.To discover the mechanisms underpinning cold tolerance in domestic animals,we sequenced the genomes of 28 cattle from warm and cold areas across China.By characterizing the population structure and demographic history,we identified two genetic clusters,i.e.,northern and southern groups,as well as a common historic population peak at 30 kilo years ago.Genomic scan of cold-tolerant breeds determined potential candidate genes in the thermogenesis-related pathways that were under selection.Specifically,functional analysis identified a substitution of PRDM16(p.P779 L)in northern cattle,which maintains brown adipocyte formation by boosting thermogenesis-related gene expression,indicating a vital role of this gene in cold tolerance.These findings provide a basis for genetic variation in domestic cattle shaped by environmental temperature and highlight the role of reverse mutation in livestock species.

Role of Nociceptive Arcuate Nucleus Neurons in Chloroquine-induced Pruritic Behaviors in Mice

Despite its clinical importance, the underlying central mechanisms of pruritic behaviors are poorly understood. To investigate the role of nociceptive arcuate nucleus neurons in chloro-quine-induced pruritic behaviors in mice, we tested the effect of arcuate nucleus neurons and interscapular brown adipose tissue (IBAT) on itch produced by intradermal injection of chloroquine in the nape of the neck. Our results provide several lines of evidence for an important role of nociceptive arcuate nucleus neurons in chloroquine-induced pruritic behavior: (1) Intradermal microinjection of chloro-quine resulted in a dramatic increase in itch behaviors accompanied by the activation of c-Fos positive neurons in arcuate nucleus; (2) Microinjection of chloroquine significantly increased IBAT temperature in the mice. These findings suggested that chloroquine-induced pruritic behaviors were associated with the activity of nociceptive arcuate nucleus neurons.

Weight loss induced by whole grain-rich diet is through a gut microbiota-independent mechanism

The prevalence of overweight and obesity has increased worldwide.Obesity is a well-known risk factor of type 2 diabetes mellitus and cardiovascular disease and raises public health concerns.Many dietary guidelines encourage the replacement of refined grains with whole grains(WGs)to enhance body weight management.Current evidence regarding interrelationships among WGs,body weight,and gut microbiota is limited and inconclusive.In this editorial,we comment on the article by Roager et al published in the recent issue of the Gut 2019;68(1):83-93.In the study,obese patients(25<body mass index<35 kg/m2)were randomly assigned to receive two 8-wk dietary controlling periods with WGs and refined grain-rich diet.The results showed significantly decreased body weight in the WG group.Either the composition of gut microbiota or short-chain fatty acids,the leading end product of fermentation of non-digestible carbohydrate by gut microbiota,did not differ between the two groups.The study highly indicated that a WG-rich diet reduced body weight independent of gut microbiota.We then raised some plausible mechanisms of how WGs might influence body weight and demonstrated more literature in line with WGs enhance body weight control through a microbiota-independent pathway.Possible mechanisms include:(1)The abundant dietary fiber contents of WGs increase satiety,satiation,energy excretion from stool,and energy expenditure simultaneously decreasing energy absorption and fat storage;(2)The plentiful amount of polyphenols of WGs improve energy expenditure by hampering adipocyte maturation and function;(3)The sufficient magnesium and zinc of WGs guarantee lean body mass growth and decrease fat mass;(4)The effect of WGs on brown adipose tissue is a key component of non-shivering thermogenesis;and(5)The increase of adiponectin by WGs enhances glucose utilization,lipid oxidation,and energy expenditure.

Insulinoma presenting with postprandial hypoglycemia and a low body mass index:A case report

BACKGROUND Insulinomas are the most common type of functioning endocrine neoplasms of the pancreas presenting hypoglycemic symptoms.Patients characteristically develop symptoms while fasting,but some patients have reported symptoms only in the postprandial state.Repeated and prolonged hypoglycemic episodes can reduce the awareness of adrenergic symptoms,and patients may have amnesia,which delays diagnosis.CASE SUMMARY We describe a case of a 24-year-old underweight patient who showed hypoglycemic symptoms for almost 6 years.Although patients with insulinoma characteristically develop symptoms while fasting,this young man had hypoglycemic symptoms up to one hour postprandially,especially after highsugar meals and after physical activity.The fasting tests and imaging methods performed at local hospitals were evaluated as negative for abnormal results.However,brown adipose tissue exhibited increased metabolic activity,and some muscle groups had histological changes as indicated by positron emission tomography with 2-deoxy-2-[fluorine-18]fluoro-D-glucose integrated with computed tomography.Glycogen deficiency was also histologically confirmed.The patient’s symptoms progressed over the years and occurred more frequently,i.e.,several times a month,and the patient had reduced awareness of adrenergic symptoms.The follow-up fasting test was positive,and the imaging results showed a tumor in the head of the pancreas.The patient underwent laparotomy with enucleation of the insulinoma.CONCLUSION Weight gain and fasting hypoglycemia are not necessarily characteristics of insulinoma.In prolonged cases,adrenergic symptoms can be suppressed.

Mulberry leaf flavonoids activate BAT and induce browning of WAT to improve type 2 diabetes via regulating the AMPK/SIRT1/PGC-1α signaling pathway

Mulberry (Morus alba L.) leaf is a well-established traditional Chinese botanical and culinary resource. It has found widespread application in the management of diabetes. The bioactive constituents of mulberry leaf, specifically mulberry leaf flavonoids (MLFs), exhibit pronounced potential in the amelioration of type 2 diabetes (T2D). This potential is attributed to their ability to safeguard pancreatic β cells, enhance insulin resistance, and inhibit α-glucosidase activity. Our antecedent research findings underscore the substantial therapeutic efficacy of MLFs in treating T2D. However, the precise mechanistic underpinnings of MLF’s anti-T2D effects remain the subject of inquiry. Activation of brown/beige adipocytes is a novel and promising strategy for T2D treatment. In the present study, our primary objective was to elucidate the impact of MLFs on adipose tissue browning in db/db mice and 3T3-L1 cells and elucidate its underlying mechanism. The results manifested that MLFs reduced body weight and food intake, alleviated hepatic steatosis, improved insulin sensitivity, and increased lipolysis and thermogenesis in db/db mice. Moreover, MLFs activated brown adipose tissue (BAT) and induced the browning of inguinal white adipose tissue (IWAT) and 3T3-L1 adipocytes by increasing the expressions of brown adipocyte marker genes and proteins such as uncoupling protein 1 (UCP1) and beige adipocyte marker genes such as transmembrane protein 26 (Tmem26), thereby promoting mitochondrial biogenesis. Mechanistically, MLFs facilitated the activation of BAT and the induction of WAT browning to ameliorate T2D primarily through the activation of AMP-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α) signaling pathway. These findings highlight the unique capacity of MLF to counteract T2D by enhancing BAT activation and inducing browning of IWAT, thereby ameliorating glucose and lipid metabolism disorders. As such, MLFs emerge as a prospective and innovative browning agent for the treatment of T2D.

Visualization of Activated BAT in Mice,with FDG-PET and Its Relation to UCP1

The visualization of symmetric structure by [18F]-FluoroDeoxyGlucose-Positron Emission Tomography (FDG-PET), corresponding to adipose density in computed tomography (CT), has led to the idea that Brown Adipose Tissue (BAT) could be present in adult human. This article studies the FDG uptake in a mice model deficient on Uncoupling Protein 1 (UCP1), in a simple thermal activation protocol. Methods: FDG were injected in mice, control and knock out (K.O.) for the UCP1. Before imaging mice were placed either in cold or warm environment. BAT uptake was evaluated by ratio named RISC. Results: In warm condition, mean value of the Ratio of Inter-Scapular uptake (RISC) was 1.34 +/﹣ 0.27. After cold exposure, RISC increased 2 fold for control mice, male K.O. did not increase their RISC, female K.O. increased their RISC up to 2.45. Conclusion: Our study brought a further confirmation that FDG-PET visualised activated Brown Adipose Tissue. It gives a direct proof of the role of UCP1 in this process. The FDG uptake by cold female K.O. mice was unexpected.

Transcriptomic analysis reveals the effects of maternal exposure to bisphenol AF on hypothalamic development in male neonatal mice

Fragmented data suggest that bisphenol AF(BPAF),a chemical widely used in a variety of products,might have potential impacts on the hypothalamus.Here,we employed male neonatal mice following maternal exposure to explore the effects of low-dose BPAF on hypothalamic development by RNA-sequencing.We found that maternal exposure to approximately 50μg/(kg·day)BPAF from postanal day(PND)0 to PND 15 altered the hypothalamic transcriptome,primarily involving the pathways and genes associated with extracellular matrix(ECM)and intercellular adhesion,neuroendocrine regulation,and neurological processes.Further RNA analysis confirmed the changes in the expression levels of concerned genes.Importantly,we further revealed that low-dose BPAF posed a stimulatory impact on pro-opiomelanocortin(POMC)neurons in the arcuate nucleus of the hypothalamus and induced the browning of inguinal white adipose tissue.All findings indicate that developmental exposure to low-dose BPAF could interfere with hypothalamic development and thereby lead to alterations in the metabolism.Interestingly,5000μg/(kg·day)BPAF caused slighter,non-significant or even inverse alterations than the low dose of 50μg/(kg·day),displaying a dose-independent effect.Further observations suggest that the the dose-independent effects of BPAF might be associated with oxidative stress and inflammatory responses caused by the high dose.Overall,our study highlights a risk of low-dose BPAF to human neuroendocrine regulation and metabolism.

Common and distinct regulation of human and mouse brown and beige adipose tissues： a promising therapeutic target for obesity

Obesity, which underlies various metabolic and cardio- vascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissi- pation. In this review, we summarize the evolution of human brown adipose tissue （hBAT） research and dis- cuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better under- standing of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limi- tations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing ＇metabolic panacea＇.

Role of brown adipose tissue in metabolic syndrome, aging, and cancer cachexia

Brown adipose tissue （BAT） plays a fundamental role in maintaining body temperature by producing heat. BAT that had been know to exist only in mammals and the human neonate has received great attention for the treatment of obesity and diabetes due to its important function in energy metabolism, ever since it is recently reported that human adults have functional BAT. In addition, beige adipocytes, brown adipocytes in white adipose tissue （WAT）, have also been shown to take part in whole body metabolism. Multiple lines of evidence demonstrated that transplantation or activation of BAT or/and beige adipocytes reversed obesity and improved insulin sensitivity. Furthermore, many genes involved in BAT activation and/or the recruitment of beige cells have been found, thereby providing new promising strategies for future clinical application of BAT activation to treat obesity and metabolic diseases. This review focuses on recent advances of BAT function in the metabolic aspect and the relationship between BAT and cancer cachexia, a pathological process accompanied with decreased body weight and increased energy expenditure in cancer patients. The underlying possible mechanisms to reduce BAT mass and its activity in the elderly are also discussed.

Cell-derived extracellular matrix-coated silk fibroin scaffold for cardiogenesis of brown adipose stem cells through modulation of TGF-β pathway

The cell-derived extracellular matrix(ECM)-modified scaffolds have advantages of mimic tissue specificity and been thought to better mimic the native cellular microenvironment in vitro.ECM derived from cardiac fibroblasts(CFs)are considered as key elements that provide a natural cell growth microenvironment and change the fate of cardiomyocytes(CMs).Here,a new hybrid scaffold is designed based on silk fibroin(SF)scaffold and CFs-derived ECM.CFs were seeded on the SF scaffold for 10days culturing and decellularized to produce CFs-derived ECM-coated SF scaffold.The results showed that the cell-derived ECM-modified silk fibroin scaffold material contained collagen,laminin,fibronectin and other ECM components with myocardial-like properties.Further to explore its effects on brown adipose stem cells(BASCs)differentiation into CMs.We found that the CFderived ECM-coated scaffold also increased the expression of CM-specific proteins(e.g.cardiac troponin T and α-actinin)of BASCs.Notably,the b1-integrin-dependent transforming growth factor-β1 signaling pathway was also involved in the regulation of CF-derived ECM by promoting the differentiation of BASCs into CMs.Overall,these findings provide insights into the bionic manufacturing of engineered cardiac tissues(ECTs)and establish a theoretical basis for the construction of ECTs.