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.

Characteristics and mechanisms of subcutaneous and visceral adipose tissue aging

Aging is one of the most significant health challenges worldwide and is a primary cause of chronic diseases and physiological decline.Among the myriad changes that occur with aging,alterations in adipose tissue distribution and function have gained considerable attention because of their profound impact on metabolic health and overall well-being.Subcutaneous adipose tissue(SAT)and visceral adipose tissue(VAT)are the two major depots of white adipose tissue,each with distinct roles in metabolism and health.Understanding the characteristics and underlying mechanisms of SAT and VAT is crucial for elucidating the aging process and developing strategies to promote healthy aging.This review focuses on delineating and analyzing the characteristics and intrinsic mechanisms underlying the aging of subcutaneous and visceral adipose tissue during the aging process,which can contribute to a better understanding of the aging process and enhance healthy aging.

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.

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.

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.

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.

Preliminary PET/CT Study of ^(18)F-FDG Uptake in Cervical and Supraclavicular Brown Adipose Tissue

OBJECTIVE The clinical use of PET/CT in oncology has led to the realization that 18F-FDG uptake in brown adipose tissue(BAT) can be a common cause of potentially misleading false-positive PET scans.The goal of this study was to study 18F-FDG uptake in cervical and supraclavicular regions and its characteristics with PET/CT.METHODSAll the PET/CT scans obtained at our institutionfrom July 2007 to January 2008 were retrospectively reviewed forincreased 18F-FDG uptake in BAT.The cases in which increased18F-FDG in cervical and supraclavicular regions was not localizedto a so -tissue mass or lymph node or muscle on the CT images,were included in this study.The following features were recorded:body weight,body mass index(BMI) and maximal standardizeduptake value(SUVmax).In these selected patients,the BAT uptake in other area of the body was also recorded.RESULTS PET/CT scans were obtained in 457 patients(259 males and 198 females).In all of the scans,cervical and supraclavicular BAT uptake was observed in 12 patients(2 males and 10 females) and was typically bilateral,symmetric and intense.The range of the SUVmax was 3.6～12.82(mean 6.9 ± 2.6).BAT uptake was more common in females than in males,showing a significant difference(P = 0.004).Although 18F-FDG uptake in BAT occurred more o en in underweight patients with low BMI,there was no difference in the body weight(P = 0.607) or BMI(P = 0.491) of these patients with hypermetabolic BAT compared with controls.CONCLUSION Hypermetabolic BAT uptake can be localized in cervical and supraclavicular regions with it occurring more commonly in females compared to males.Knowledge of this potential pitfall with PET/CT is important in improving diagnostic interpretation and accurate staging.

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory disease.Unfortunately,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional surgeries.With advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential limitations.Firstly,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after surgery.This strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off therapy.Consequently,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee YJ and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting of manuscript and final approval of manuscript;Melmed GY,Yarur AJ,Fleshner P,Kallman C and Devkota S were involved in study concept and design,data interpretation,drafting of manuscript and final approval of manuscript;Vasiliauskas EA,Bonthala N,Syal G,Ziring D and Targan SR were involved in data interpretation,drafting of manuscript and final approval of manuscript;Rabizadeh S was involved in study concept and design,drafting of manuscript and final approval of manuscript;McGovern DPB was involved in concept and design,statistical analysis,drafting of manuscript and final approval of manuscript.

Visceral adipose tissue predicts severity and prognosis of acute pancreatitis in obese patients

Acute pancreatitis is a common systemic inflammatory disease, manifested by a spectrum of severity, ranging from mild in the majority of patients to severe acute pancreatitis. Patients with severe acute pancreatitis suffer from severe local and systemic complications and organ failure, leading to a poor prognosis. The early recognition of the severe condition is important to improve prognosis. Obesity has risen in tandem with an increase in the severity of acute pancreatitis in recent years. Studies have revealed that adipose tissue, particularly visceral adipose tissue is associated with the prognosis of acute pancreatitis. This review discussed the role of visceral adipose tissue in obese patients with acute pancreatitis and explored the possible mechanism involved.

microRNA-32 promotes white fat browning through augmenting FGF21 expression in brown adipose tissue

OBJECTIVE To investigate the effect of microRNA-32 on cold-induced thermogenesis and brown adipocyte energy metabolism.METHODS To apply the cold-induced thermogenesis model in mice,8-10 week old male C57Bl6 mice were placed within a 6℃fridge for 7d.Control microRNA inhibitor or miR-32 inhibitor(10mg·kg-1)was administered via intraperitoneal injection 16 hbefore the mice were placed in the fridge.Daily core body temperatures were taken using a rectal temperature probe.Mice were euthanized after 7dand brown adipose tissue(BAT),inguinal and epididymal white adipose tissue(WAT),skeletal muscle and liver tissue analysed for changes in morphology and gene expression.RESULTS miR-32 inhibition in vivoinhibits the emergence of beige cells,which function like BAT cells,within WAT.In silico prediction and gene ontology analysis identified Tob1 as a likely target gene of miR-32.miR-32 inhibition led to increased expression of Tob1 whilst mutation of target sequence abolished this effect.Expression of brown adipose markers such as Ucp1,Pgc1α,Pparαand Prdm16 were significantly reduced in inguinal white adipose tissue(P<0.05).There was also a significant decrease in serumfgf21 levels due to the inhibition of Fgf21 expression in BAT(P<0.05).p38/MAPK signalling in brown adipose tissue was also significantly inhibited within brown adipose tissue leading to decreased fgf21 expression and secretion.CONCLUSION Our study shows that miR-32 plays a crucial role in stimulating beige cell emergence by activating p38/MAPK signalling during cold thermogenesis.miR-32 may prove effective as a treatment for obesity by activating cold-induced thermogenesis leading to increased energy metabolism.

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.

Endotoxin-induced alterations of adipose tissue function:a pathway to bovine metabolic stress

During the periparturient period, dairy cows exhibit negative energy balance due to limited appetite and increased energy requirements for lactogenesis. The delicate equilibrium between energy availability and expenditure puts cows in a state of metabolic stress characterized by excessive lipolysis in white adipose tissues(AT), increased production of reactive oxygen species, and immune cell dysfunction. Metabolic stress, especially in AT, increases the risk for metabolic and inflammatory diseases. Around parturition, cows are also susceptible to endotoxemia. Bacterial-derived toxins cause endotoxemia by promoting inflammatory processes and immune cell infiltration in different organs and systems while impacting metabolic function by altering lipolysis, mitochondrial activity, and insulin sensitivity. In dairy cows, endotoxins enter the bloodstream after overcoming the defense mechanisms of the epithelial barriers, particularly during common periparturient conditions such as mastitis, metritis, and pneumonia, or after abrupt changes in the gut microbiome. In the bovine AT, endotoxins induce a pro-inflammatory response and stimulate lipolysis in AT, leading to the release of free fatty acids into the bloodstream. When excessive and protracted, endotoxin-induced lipolysis can impair adipocyte's insulin signaling pathways and lipid synthesis. Endotoxin exposure can also induce oxidative stress in AT through the production of reactive oxygen species by inflammatory cells and other cellular components. This review provides insights into endotoxins' impact on AT function, highlighting the gaps in our knowledge of the mechanisms underlying AT dysfunction, its connection with periparturient cows' disease risk, and the need to develop effective interventions to prevent and treat endotoxemia-related inflammatory conditions in dairy cattle.

The Role of Adipose Tissue-derived Exosomes in Chronic Metabolic Disorders

Excessive fat deposition in obese subjects promotes the occurrence of metabolic diseases,such as type 2 diabetes mellitus(T2DM),cardiovascular diseases,and non-alcoholic fatty liver disease(NAFLD).Adipose tissue is not only the main form of energy storage but also an endocrine organ that not only secretes adipocytokines but also releases many extracellular vesicles(EVs)that play a role in the regulation of whole-body metabolism.Exosomes are a subtype of EVs,and accumulating evidence indicates that adipose tissue exosomes(AT Exos)mediate crosstalk between adipose tissue and multiple organs by being transferred to targeted cells or tissues through paracrine or endocrine mechanisms.However,the roles of AT Exos in crosstalk with metabolic organs remain to be fully elucidated.In this review,we summarize the latest research progress on the role of AT Exos in the regulation of metabolic disorders.Moreover,we discuss the potential role of AT Exos as biomarkers in metabolic diseases and their clinical application.

Mesenteric adipose tissue B lymphocytes promote intestinal injury in severe acute pancreatitis by mediating enteric pyroptosis

Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.

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

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

Epicardial adipose tissue in obesity with heart failure with preserved ejection fraction: Cardiovascular magnetic resonance biomarker study

BACKGROUND Obesity has become a serious public health issue,significantly elevating the risk of various complications.It is a well-established contributor to Heart failure with preserved ejection fraction(HFpEF).Evaluating HFpEF in obesity is crucial.Epicardial adipose tissue(EAT)has emerged as a valuable tool for validating prognostic biomarkers and guiding treatment targets.Hence,assessing EAT is of paramount importance.Cardiovascular magnetic resonance(CMR)imaging is acknowledged as the gold standard for analyzing cardiac function and mor-phology.We hope to use CMR to assess EAT as a bioimaging marker to evaluate HFpEF in obese patients.AIM To assess the diagnostic utility of CMR for evaluating heart failure with preserved ejection fraction[HFpEF;left ventricular(LV)ejection fraction≥50%]by measuring the epicardial adipose tissue(EAT)volumes and EAT mass in obese patients.METHODS Sixty-two obese patients were divided into two groups for a case-control study based on whether or not they had heart failure with HFpEF.The two groups were defined as HFpEF+and HFpEF-.LV geometry,global systolic function,EAT volumes and EAT mass of all subjects were obtained using cine magnetic resonance sequences.RESULTS Forty-five patients of HFpEF-group and seventeen patients of HFpEF+group were included.LV mass index(g/m2)of HFpEF+group was higher than HFpEF-group(P<0.05).In HFpEF+group,EAT volumes,EAT volume index,EAT mass,EAT mass index and the ratio of EAT/[left atrial(LA)left-right(LR)diameter]were higher compared to HFpEF-group(P<0.05).In multivariate analysis,Higher EAT/LA LR diameter ratio was associated with higher odds ratio of HFpEF.CONCLUSION EAT/LA LR diameter ratio is highly associated with HFpEF in obese patients.It is plausible that there may be utility in CMR for assessing obese patients for HFpEF using EAT/LA LR diameter ratio as a diagnostic biomarker.Further prospective studies,are needed to validate these proof-of-concept findings.

Adipose Tissue and Cachexia: White or Brown

The adipose tissue of the body is classified into two types: white adipose tissue and brown adipose tissue;the former is mainly responsible for storing energy and the latter is to produce heat and dissipate energy. Recent research has shown that there is a third type of adipose tissue, namely white adipose tissue browning, i.e., brown adipose tissue existing inside the white adipose tissue. Brown adipose tissue, which is converted from white adipose tissue, is similar to brown adipocytes in function. Browning is one of the important features of lipid metabolism of cancer cachexia. On the one hand, white adipose tissue affects metabolism through increasing the amount of heat consumption after browning, resulting in a decrease in fat;on the other hand, the browning process participates in the process of the occurrence and development of cancer cachexia. Two driving factors, interleukin-6 and parathyroid hormone related protein, play an important role in this browning process. They are secreted by tumor tissue, mainly through the exciting sympathetic nervous system to release norepinephrine, and act on β3 adrenergic receptor of the adipocytes and further activate the the transcription factors which corresponded heat-production gene expression such as uncoupling protein 1 (UCP1), leading to white adipose tissue browning. The browning process is the early event of the occurrence of cancer cachexia and continues throughout the entire process of cancer cachexia. Therefore, early detection of the browning process will facilitate the development of intervention approach, improving the clinical outcome of diagnosis, prevention, and treatment for cancer cachexia.

Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling

Objective Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs;however,concerns regarding complexities and side effects persist,driving research for more effective,low-risk strategies.The promotion of white adipose tissue(WAT)browning has emerged as a promising approach.Moreover,alisol B 23-acetate(AB23A)has demonstrated efficacy in addressing metabolic disorders,suggesting its potential as a therapeutic agent in obesity management.Therefore,in this study,we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet(HFD).Methods An obesity mouse model was established by administration of an HFD.Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests.Adipocyte size was determined using hematoxylin and eosin staining.The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction.Metabolic cage monitoring involved the assessment of various parameters,including food and water intake,energy metabolism,respiratory exchange rates,and physical activity.Moreover,oil red O staining was used to evaluate intracellular lipid accumulation.A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways.Results AB23A administration significantly reduced the weight of obese mice,decreased the mass of inguinal WAT,epididymal WAT,and perirenal adipose tissue,improved glucose and insulin metabolism,and reduced adipocyte size.Moreover,treatment with AB23A promoted the expression of browning markers in WAT,enhanced overall energy metabolism in mice,and had no discernible effect on food intake,water consumption,or physical activity.In 3T3-L1 cells,AB23A inhibited lipid accumulation,and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1(mTOR-SREBP1)signaling pathway.Furthermore,3-isobutyl-1-methylxanthine,dexamethasone and insulin,at concentrations of 0.25 mmol/L,0.25μmol/L and 1μg/mL,respectively,induced activation of the mTOR-SREBP1 signaling pathway,which was further strengthened by an mTOR activator MHY1485.Notably,MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells.Conclusion AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway,offering a potential strategy to prevent obesity.

Adipose tissue macrophages:implications for obesity-associated cancer

Obesity is one of the most serious global health problems,with an incidence that increases yearly and coincides with the development of cancer.Adipose tissue macrophages(ATMs)are particularly important in this context and contribute to linking obesity-related inflammation and tumor progression.However,the functions of ATMs on the progression of obesity-associated cancer remain unclear.In this review,we describe the origins,phenotypes,and functions of ATMs.Subsequently,we summarize the potential mechanisms on the reprogramming of ATMs in the obesity-associated microenvironment,including the direct exchange of dysfunctional metabolites,inordinate cytokines and other signaling mediators,transfer of extracellular vesicle cargo,and variations in the gut microbiota and its metabolites.A better understanding of the properties and functions of ATMs under conditions of obesity will lead to the development of new therapeutic interventions for obesity-related cancer.

Insulin resistance and adipose tissue interactions as the cornerstone of metabolic(dysfunction)-associated fatty liver disease pathogenesis

The relationship between metabolic derangements and fatty liver development are undeniable,since more than 75% of patients with type 2 diabetes mellitus present with fatty liver.There is also significant epidemiological association between insulin resistance(IR)and metabolic(dysfunction)-associated fatty liver disease(MAFLD).For little more than 2 years,the nomenclature of fatty liver of non-alcoholic origin has been intended to change to MAFLD by multiple groups.While a myriad of reasons for which MAFLD is thought to be of metabolic origin could be exposed,the bottom line relies on the role of IR as an initiator and perpetuator of this disease.There is a reciprocal role in MAFLD development and IR as well as serum glucose concentrations,where increased circulating glucose and insulin result in increased de novo lipogenesis by sterol regulatory elementbinding protein-1c induced lipogenic enzyme stimulation;therefore,increased endogenous production of triglycerides.The same effect is achieved through impaired suppression of adipose tissue(AT)lipolysis in insulin-resistant states,increasing fatty acid influx into the liver.The complementary reciprocal situation occurs when liver steatosis alters hepatokine secretion,modifying fatty acid metabolism as well as IR in a variety of tissues,including skeletal muscle,AT,and the liver.The aim of this review is to discuss the importance of IR and AT interactions in metabolic altered states as perhaps the most important factor in MAFLD pathogenesis.