Adipose Tissue Growth Research Articles

Assessing abdominal aortic aneurysm growth using radiomic features of perivascular adipose tissue after endovascular repair

ObjectivesThe study aimed to investigate the relationship between the radiomic features of perivascular adipose tissue (PVAT) and abdominal aortic aneurysm (AAA) growth after endovascular aneurysm repair (EVAR).MethodsPatients with sub-renal AAA who underwent regular follow-up after EVAR between March 2014 and March 2024 were retrospectively collected. Two radiologists segmented aneurysms and PVAT. Patients were categorised into growing and non-growing groups based on volumetric changes observed in two follow-up computed tomography examinations. One hundred seven radiomic features were automatically extracted from the PVAT region. Univariable and multivariable logistic regression was performed to analyse radiomic features and clinical characteristics. Furthermore, the performance of the integrated clinico-radiological model was compared with models using only radiomic features or clinical characteristics separately.ResultsA total of 79 patients (68 ± 9 years, 89% men) were enroled in this study, 19 of whom had a growing aneurysm. Compared to the non-growing group, PVAT of growing AAA showed a higher surface area to volume ratio (non-growing vs growing, 0.63 vs 0.70, p = 0.04), and a trend of low dependence and high dispersion manifested by texture features (p < 0.05). The area under the curve of the integrated clinico-radiological model was 0.78 (95% confidence intervals 0.65–0.91), with a specificity of 87%. The integrated model outperformed models using only radiomic or clinical features separately (0.78 vs 0.69 vs 0.69).ConclusionsHigher surface area to volume ratio and more heterogeneous texture presentation of PVAT were associated with aneurysm dilation after EVAR. Radiomic features of PVAT have the potential to predict AAA progression.Clinical relevance statementRadiomic features of PVAT are associated with AAA progression and can be an independent risk factor for aneurysm dilatation to assist clinicians in postoperative patient surveillance and management.Key PointsAfter EVAR for AAA, patients require monitoring for progression.PVAT surrounding growing AAA after EVAR exhibits a more heterogeneous texture.Integrating PVAT-related features and clinical features results in better predictive performance.Graphical

Adipogenic-Myogenic Signaling in Engineered Human Muscle Grafts used to Treat Volumetric Muscle Loss.

Tissue-engineered muscle grafts (TEMGs) are a promising treatment for volumetric muscle loss (VML). In this study, human myogenic progenitors (hMPs) cultured on electrospun fibrin microfiber bundles and evaluated the therapeutic potential of engineered hMP TEMGs in the treatment of murine tibialis anterior (TA) VML injuries is employed. In vitro, the hMP TEMGs express mature muscle markers by 21 days. Upon implantation into VML injuries, the hMP TEMGs enable remarkable regeneration. To further promote wound healing and myogenesis, human adipose-derived stem/stromal cells (hASCs) as fibroadipogenic progenitor (FAP)-like cells with the potential to secrete pro-regenerative cytokines are incorporated. The impact of dose and timing of seeding the hASCs on in vitro myogenesis and VML recovery using hMP-hASC TEMGs are investigated. The hASCs increase myogenesis of hMPs when co-cultured at 5% hASCs: 95% hMPs and with delayed seeding. Upon implantation into immunocompromised mice, hMP-hASC TEMGs increase cell survival, collagen IV deposition, and pro-regenerative macrophage recruitment, but result in excessive adipose tissue growth after 28 days. These data demonstrate the interactions of hASCs and hMPs enhance myogenesis in vitro but there remains a need to optimize treatments to minimize adipogenesis and promote full therapeutic recovery following VML treatment.

CTGF Inhibits the Differentiation of Chicken Preadipocytes via the TGFβ/Smad3 Signaling Pathway or by Inducing the Expression of ACTG2.

Chicken is the main source of protein for humans in most parts of the world. However, excessive fat deposition in chickens has become a serious problem. This adversely affects the growth of chickens and causes economic losses. Fat formation mainly occurs through preadipocyte differentiation, and excessive fat deposition results from the accumulation of preadipocytes after differentiation. Our previous studies have found that the connective tissue growth factor (CTGF) may be an important candidate gene for fat deposition. However, its function and mechanism in preadipocyte differentiation are still unclear. In this study, the RT-qPCR and Western blot results showed that the expression of CTGF mRNA and protein in the abdominal adipose of lean chickens was significantly higher than that of fat chickens. Therefore, we studied the function and mechanism of the CTGF in the differentiation of chicken preadipocytes. Functionally, the CTGF inhibited the differentiation of chicken preadipocytes. Mechanistically, the CTGF mediated the TGFβ1/Smad3 signaling pathway, thereby inhibiting the differentiation of chicken preadipocytes. In addition, we used the unique molecular identifier (UMI) RNA-Seq technology to detect genes that can be regulated by the CTGF in the whole genome. Through transcriptome data analysis, we selected actin gamma 2 (ACTG2) as a candidate gene. Regarding the function of the ACTG2 gene, we found that it inhibited the differentiation of chicken preadipocytes. Furthermore, we found that the CTGF can inhibit the differentiation of preadipocytes through the ACTG2 gene. In summary, this study found the CTGF as a new negative regulator of chicken preadipocyte differentiation. The results of this study help improve the understanding of the molecular genetic mechanism of chicken adipose tissue growth and development and also have reference significance for the study of human obesity.

Amphiphilic cytokine traps remodel marrow adipose tissue for hematopoietic microenvironment amelioration

Hematopoietic stem cell transplantation (HSCT) is extensively employed in the treatment of hematological malignancies but is markedly constrained by the paucity of hematopoietic stem/progenitor cells (HSPCs). Recent studies have found that marrow adipose tissue (MAT) acts on hematopoiesis through complicated mechanisms. Therefore, the osteo-organoids fabricated in vivo using biomaterials loaded with recombinant human bone morphogenetic protein 2 (rhBMP-2) have been used as models of MAT for our research. To obtain sufficient amounts of therapeutic HSPCs and healthy MAT, we have developed amphiphilic chitosan (AC)-gelatin as carriers of rhBMP-2 to the regulate type conversion of adipose tissue and trap hematopoietic growth factors. Unlike medicine interventions or cell therapies, the traps based on AC not only attenuate the occupancy of adipocytes within the hematopoietic microenvironment while preserving stem cell factor concentrations, but also improve marrow metabolism by promoting MAT browning. In conclusion, this approach increases the proportion of HSPCs in osteo-organoids, and optimizes the composition and metabolic status of MAT. These findings furnish an experimental basis for regulating hematopoiesis in vivo through materials that promote the development of autologous HSPCs. Additionally, this approach presents a theoretical model of rapid adipogenesis for the study of adipose-related pathologies and potential pharmacological targets.

The molecular signature of the peripheral cannabinoid receptor 1 antagonist AM6545 in adipose, liver and muscle tissue

The endocannabinoid system plays an important role in the regulation of metabolism, growth and regeneration of peripheral tissues, including liver, adipose and muscle tissue. Studies in cells, rodents and humans showed that cannabinoid receptor 1 (CB1) antagonist treatment is an effective strategy to improve features of metabolic health such as substrate metabolism, at least in models of metabolic dysregulation. However, acute signaling events that might induce these metabolic adaptations are not understood. It is not clear whether, and to which extent, a single treatment with a CB1 antagonist induces acute effects in peripheral, metabolic tissues. Therefore, the present study compared the phosphorylation status of signaling pathways and metabolic markers in liver, adipose and muscle tissue of mice treated with the peripherally restricted CB1 antagonist AM6545 and vehicle-treated mice. Protein kinase A phosphorylation was downregulated in white and brown adipose tissue, whereas the mitogen-activated protein kinase, phospho-extracellular signal-regulated kinase, was higher in liver, white adipose and muscle tissue of AM6545-treated mice. Additionally, Akt-mammalian target of rapamycin activation was higher in all tissues of AM6545-treated mice, whereas the phosphorylation status of metabolic markers remained unaffected. These data indicate that acute CB1 antagonism is effective to induce phosphorylation events of signaling cascades and metabolic markers in metabolic tissues of healthy, lean mice within a 90-min time window. The observed adaptations to AM6545 treatment do not fully align with earlier in vitro and in vivo findings, which could be ascribed to differences in cell type, exposure intensity (dose and time), health status and species.

Single-cell sequencing of facial adipose tissue unveils FKBP5 as a therapeutic target for facial infiltrating lipomatosis

BackgroundFacial infiltrating lipomatosis is characterized by excessive growth of adipose tissue. Its etiology is associated with somatic phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) variants, but the specific mechanisms are not yet fully understood.MethodsWe collected facial adipose tissue from both FIL patients and non-FIL individuals, isolated the stromal vascular fraction (SVF) and performed single-cell transcriptome sequencing on these samples.ResultsWe mapped out the cellular landscape within the SVF, with a specific focus on a deeper analysis of fibro-adipogenic precursor cells (FAPs). Our analysis revealed that FAPs from FIL patients (FIL-FAPs) significantly overexpressed FK506 binding protein 51 (FKBP5) compared to FAPs from individuals without FIL. Further experiments indicated that FKBP5 is regulated by the PI3K-AKT signaling pathway. The overactivation of this pathway led to an increase in FKBP5 expression. In vitro experiments demonstrated that FKBP5 promoted adipogenic differentiation of FAPs, a process that could be hindered by FKBP5 knockdown or inhibition. Additionally, in vivo assessments confirmed FKBP5’s role in adipogenesis.ConclusionsThese insights into the pathogenesis of FIL underscore FKBP5 as a promising target for developing non-surgical interventions to manage the excessive adipose tissue growth in FIL.

Diet-Induced Early Inflammatory Response of Visceral Adipose Tissue in Healthy Male Wistar Rats.

The prolonged consumption of a high-fat diet (HFD) leads to abnormal growth of the visceral adipose tissue (VAT), increased macrophage infiltration, and altered secretion of biologically active molecules. This is considered as a precondition for the development of obesity, inflammation, and obesity-related disorders. Therefore, we studied HFD-induced changes in the tissue levels of the inflammatory markers C-reactive protein, serum amyloid-A, and interleukin-4 in healthy male Wistar rats. The animals were first divided at random into two groups subjected to either a standard or a high-fat diet. The initial effect of the diet was evaluated after fourteen weeks. In order to study the diet duration effect, the standard diet was given to twelve animals from the HFD group, while the remaining continued with the HFD for an additional four weeks. Our results showed that the HFD barely affected body mass index, conicity, relative fat mass, and Lee indices, whereas it provoked adipocyte hypertrophy and gradually increased the levels of both the pro- and anti-inflammatory markers. The switch from the high-fat to the standard diet resulted in the comparatively fast restoration of the baseline levels of the studied molecules. Although, the prolonged consumption of an HFD causes adipocyte hypertrophy in healthy male animals, the inflammatory process in VAT is well-coordinated, time-dependent, and reversible.

Epidural lipomatosis with foci of hemorrhage and acute compression of the spinal cord in a child with CLOVES syndrome: illustrative case.

Congenital lipomatous overgrowth, vascular malformations, epidermal nevi, spinal/skeletal anomalies, and/or scoliosis (CLOVES) syndrome is the most recently described combined vascular anomaly characterized by congenital excessive growth of adipose tissue, vascular malformations, epidermal nevi, and skeletal deformities. This condition exhibits a significant variability in clinical manifestations and a tendency for rapid progression and affects extensive anatomical regions. Information regarding the association of epidural lipomatosis with low-flow venous lymphatic malformations is rare, with few reports in the literature. The authors present a case of a 6-year-old girl who was admitted to the emergency department complaining of rapidly progressing weakness in her lower extremities and partial loss of sensation in the inguinal area. Radiologically, an extradural mass was identified at the T2-6 level, causing acute spinal cord compression. Urgent decompression and partial resection of the mass were performed. Despite satisfactory intraoperative hemo- and lymphostasis, postoperative lymphorrhea/seroma leakage was encountered as a delayed complication and was managed conservatively. CLOVES syndrome is characterized by the combination of various clinical symptoms, not all of which are included in the abbreviation, as well as a progressively deteriorating course, the emergence of new symptoms, and complications throughout the patient's life. This necessitates ongoing monitoring of such patients.

Abstract 6632: Adipocyte death drives dormant breast cancer cell reactivation

Abstract Despite significant responses to initial treatments, upwards of 30% of breast cancer patients will experience a recurrence of their disease. Unfortunately, there are few clinical features that predict which patients will recur, relegating patients and their doctors to a wait-and-see approach where they must remain vigilant. Recent studies have reported that the presence of disseminated tumor cells (DTCs) in the bone marrow of early-stage breast cancer patients predicts a higher chance of recurrence and that obese patients experience 35%-40% higher rates of recurrence than lean patients. Interestingly, in addition to increased adipocyte size, obese patients experience higher rates of adipocyte apoptosis, macrophage recruitment to adipocyte tissue, and increased inflammation, shown as the formation of crown-like structures (CLSs). Given the rising prevalence of obesity, the need for mechanistic studies to elucidate its contribution to breast cancer dormancy and recurrence is urgent. To investigate how microenvironmental changes associated with obesity affect breast cancer dormancy, we utilized a well-established syngeneic mouse model of ER+ breast cancer dormancy (D2.0R). We found that D2.0R cells remained dormant in the visceral fat of wildtype mice but were reactivated upon adipocyte death due to obesity or genetic manipulation, and this reactivation required the recruitment of macrophages. To understand why macrophages were recruited to the adipose tissue and how they led to dormant tumor cell reactivation, we profiled the microenvironmental changes in visceral fat using single-cell RNA-sequencing and found that the infiltrating macrophages exhibited unique pro-inflammatory and lipid regulatory phenotypes. Further investigation revealed that macrophages activated the integrin-focal adhesion kinase (FAK) pathway in dormant D2.0R cells and the inhibition of integrin and FAK inhibited this activation. Given tumor cells can metastasize to visceral fat depots in breast cancer patients, our findings provide an important model to determine what drives dormant tumor cell growth in adipose tissue. Our study provides novel insights into how tumor microenvironment (TME) impacts breast cancer dormancy and also highlights the importance of adipose tissue as a unique reservoir that potentiates cancer relapse. Citation Format: Xiaoyu Yuan, Qihao Ren, Sheila A. Stewart. Adipocyte death drives dormant breast cancer cell reactivation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6632.

Mechanisms of obesogens and their impact on adipose tissue, hormones, and inflammation

The complex interactions of genetic, environmental, and behavioral factors that contribute to obesity, a pervasive global health issue, continue to be a severe concern for people all over the world. This manuscript examines the field of obesogen research, seeking to understand the mechanisms by which certain environmental chemicals contribute to the development of obesity. We explore the obesogenic effects by focusing on pathways such as inflammation, hormone interference, and the activation of peroxisome proliferator-activated receptors (PPARs). The text focuses on the significance of PPAR isoforms, especially PPARγ, and how they play a role in adipose tissue growth. We examine how obesogens such as tributyltin (TBT) and bisphenol A (BPA) influence these receptors. Additionally, we examined the impact of obesogens on hormonal regulation, including disruptions to leptin and adiponectin, and investigated the intricate relationship between chronic inflammation and obesity. In the methodology of our study, we utilized a systematic search to identify peer-reviewed articles of relevance. This search spanned various model systems, including in vitro, in vivo, and epidemiological studies, providing insights into the distinct advantages and limitations associated with each. Epigenetic modifications and the influence of obesogens on the development of adipose tissue, metabolism, and appetite control further enrich our understanding of this complex field. Finally, we assess the role of endocrine disruptors in amplifying the risk of obesity, emphasizing the heightened susceptibility during crucial developmental periods. This comprehensive review aims to contribute to the ongoing discourse surrounding obesogens, paving the way for targeted interventions and a more profound comprehension of the global obesity epidemic.

RNA-Seq Analysis Reveals the Molecular Mechanisms Regulating the Development of Different Adipose Tissues in Broiler Chicks.

In an effort to enhance growth rates, chicken breeders have undertaken intensive genetic selection. In the selection process, the primary aim is to accelerate growth, inadvertently leading to new chicken breeds having an increased capacity for rapid adipose tissue accumulation. However, little is known about the relationship between changes in gene expression and adipose tissue accumulation and deposition in chickens. Therefore, in this study, RNA-seq analysis was utilized, and transcriptome data were obtained from the abdominal fat, thoracic subcutaneous fat, and clavicular fat on day 1 (d1), day 4, day 7, day 11, and day 15 to reveal the molecular mechanisms regulating the development and deposition of different adipose tissues in broiler chicks. The results showed that the key period for adipocyte differentiation and proliferation was between d4 and d7 (abdominal fat development) and between d1 and d4 (chest subcutaneous fat and clavicular fat). In addition, candidate genes such as MYOG, S100A9, CIDEC, THRSP, CXCL13, and NMU related to adipose tissue growth and development were identified. Further, genes (HOXC9, AGT, TMEM182, ANGPTL3, CRP, and DSG2) associated with the distribution of adipose tissue were identified, and genes (MN1, ANK2, and CAP2) related to adipose tissue growth were also identified. Taken together, the results from this study provide the basis for future studies on the mechanisms regulating adipose tissue development in chickens. Further, the candidate genes identified could be used in the selection process.

Morphological features of the poultry thymus

This article reviews the literature on the morphological features of the poultry thymus. Since the preservation of livestock and disease prevention is a constant problem, the issue of poultry care will always remain in the forefront. Efforts to preserve the population and increase their productivity are directly related to strengthening poultry immunity and the state of their immune system. The study of the morphology of immune system organs allows us to objectively assess the effectiveness of methods for the prevention and treatment of various diseases, as well as to identify critical periods of development of the immune system and the body as a whole. When assessing the immune status of poultry, much attention is paid to the state of lymphoid organs, including the thymus. Currently, aspects related to the dynamics of development of immunocompetent organs during the postnatal period of ontogenesis and the time frame of their involution remain unresolved. Understanding the morphological features of the thymus and its changes is a key element in assessing the function of the immune system. It was found that with the growth and development of chicks, the absolute and relative weight of the thymus increases. However, at the onset of reproductive maturity, these values decrease significantly. Involution of the thymus mass occurs, the boundary between cortical and cerebral substances becomes less distinct, and the cellular composition of the thymus changes. The process of age-related involution is accompanied by a decrease in lymphoid tissue and T-lymphocytes. It is worth noting that the total number of circulating T-lymphocytes remains stable, as this population includes long-lived cells that do not require constant renewal. In this context, there is a change in the ratio of cortical and cerebral substances, the growth of connective tissue stroma and adipose tissue. It is noted that stress factors are one of the causes of early thymic involution, and the degree of development and morphological state of the thymus significantly affect the body's resistance to infections. Changes in the structure and morphometry of the chicken thymus can be an important criterion for the morphological diagnosis of immunodeficiencies in poultry.

Adipose Tissue Dysfunction in PCOS

Polycystic Ovary Syndrome (PCOS) is one of the most common endocrine diseases among women of reproductive age; however, its aetiology is unclear. PCOS is linked to many metabolic manifestations and alterations such as obesity, insulin resistance, and cardiovascular diseases (CVD). Women with PCOS have intra-ovarian and systemic changes in their metabolite levels. Adipose tissue dysfunction plays a significant role in the pathophysiology of PCOS. Adipose tissue growth is disrupted by metabolic stress, leading to hypertrophy of adipocytes, which begin to express stress signals. Adipose tissue secretes autocrine and paracrine factors, called adipokines or adipocytokines. Adiponectin is an adipocyte-derived protein abundant in the bloodstream. Plasma adiponectin concentration is low in women with PCOS, obesity, CVD, and hypertension. Other adipocytokines with altered secretion in PCOS include leptin, resistin, apelin, visfatin, IL-6, IL-8, and TNF-α. Hormonal imbalance, untimely action of high LH, and consequent hyperandrogenism in women with PCOS may cause metabolic defects associated with adipose tissue dysfunction; however, there are no reports on the role of higher LH levels in adipose dysfunction and altered adipokine secretion. New medications with therapeutic potential have been developed that target adipokines for the treatment of PCOS. This review discusses the association between PCOS and altered adipokine production as a consequence of adipose dysfunction.

ROLE OF AYURVEDA IN THE MANAGEMENT OF OBESITY (STHAULYA): A LITERARY REVIEW

In this era, most people are suffering from lifestyle disorders like cardiovascular diseases, asthma, chronic obstructive pulmonary diseases, diabetes mellitus, etc. unhealthy diet, wrong sleeping patterns, less physical activity, stress all these things are leading people towards lifestyle disorders. The occurrence of these diseases is directly linked to the day-to-day habits of an individual. People are inclined towards a sedentary lifestyle that can lead to various chronic diseases, which can have life-threatening consequences. Today’s generation has become physically inactive due to the modernization and development of multiple technologies, which leads people towards a sedentary lifestyle. Obesity (Sthaulya) is one of the lifestyle disorders which is more complex and invites several complications like hypertension, multiple joint pain, diabetes mellitus, fatty liver, etc. In Ayurveda, it is described under the term medoroga. In Charaka Samhita Acharya Charaka has described sthaulya under ashtoninditiya purusha. The main factor in sthaulya vyadhi is the abnormal function of med-dhatvagni. A metabolic disorder occurs due to an imbalance between the intake of energy and its expenditure, which results in the growth of adipose tissue and increased body weight. Ayurveda is one of the most ancient sciences which describes fundamental and applied principles of health disease and its management. There are many drugs, various formulations, pathya-apathya, dincharya, rutucharya, and yoga which are helpful in the treatment and prevention of obesity. Ayurveda has preventive and treatment aspects about sthaulya (obesity), which this article studies. The objective of this study is to study the effectiveness of ayurvedic management in obesity, to study obesity, to study sthaulya, study medoroga.

Le tissu adipeux dans tous ses états : dernières avancées: The different colours and functions of adipose tissue: what’s new?

Obesity represents a growing global health issue today. Understanding the mechanisms underlying the formation, growth, and function of adipose tissue is crucial in combating this disease and its associated complications, such as type 2 diabetes and cardiovascular diseases. In France, obesity is on the rise, particularly among young adults and children. In this review, we discuss the cellular composition of white adipose tissue, highlighting recent advances in the characterisation of various cell populations. We also explore the metabolic implications of body fat distribution, emphasizing the importance of brown and beige adipose tissues in metabolism regulation. These thermogenic tissues offer significant metabolic benefits, opening up promising opportunities in research and development of therapeutic strategies to address obesity-related metabolic disorders. Furthermore, we discuss the relationship between cellular senescence and obesity-related metabolic dysfunction, along with new research in the field of intercellular communication and mitochondrial recycling. Finally, this review provides a comprehensive overview of recent developments in the understanding of obesity at adipose cells level.© 2023 Société francophone nutrition clinique et métabolisme (SFNCM).Published by Elsevier Masson SAS. All rights reserved.

270 Cellular Response to Heat Exposure: Influences on the Growth Potential of Bovine Skeletal Muscle and Adipose Tissue

Abstract Our lack of understanding regarding how heat exposure affects major tissue growth and meat attributes impedes our ability to counteract more frequent climate extremes and promote profitability in the beef cattle industry. The objective of the study was to determine pathways that heat shock proteins (HSPs) regulate in beef cattle’s skeletal muscle and adipose tissue growth and metabolism. Bovine satellite cells (BSCs) were isolated from the longissimus muscle of 3-month-old Holstein bulls (n = 5). Preadipose cells were isolated from the subcutaneous fat of 18-month-old Angus steers (n = 5) and induced adipogenic differentiation. Satellite, myofibers, and adipose cells were incubated at 38°C (control; CON), 39.5°C (moderate heat stress; MHS), and 41°C (extreme heat stress; EHS) and harvested for mRNA gene expressions, protein level, proteomics, immunostaining. Heat exposure cued bovine satellite cell proliferation and may increase the self-renewing satellite cell population. After 3 h of heat exposure, the mRNA gene expression and protein levels of Pax3 and Myf5 were downregulated, while HSPs 20, 27, 70, and 90 were upregulated. Small heat shock proteins, especially HSP27, appear to be essential in regulating satellite cell activity under heat stress. When HSP27 knock-down BSCs were exposed to EHS for 3 h, Myf5 gene expressions and protein levels returned to normal. This may indicate that HSP27 directly regulates Myf5 under heat stress and temporarily activates the self-renewal mechanism instead of committing myogenic differentiation. Results from proteomics showed that pathways related to oxidative phosphorylation, NADH dehydrogenase activity, and transmembrane transport were upregulated by EHS while MHS upregulated biosynthesis of amino acids, PI3K-Akt signaling pathway. Heat exposure during myogenic differentiation of satellite cells seemingly stimulates the commitment of myogenesis. Heat treatments increased mRNA gene expressions of IGF I, MHC I, MyoD, and myogenin and protein levels. Heat exposure also improved the muscle protein synthesis pathway by regulating the phosphorylation of mTOR, Akt, and P70S6. Heat stress triggered adipogenic differentiation and lipid storage, followed by increased expression of HSP. Extreme heat stress increased adipose cell growth by upregulating C/EBPα and PPARγ, key regulators of adipogenesis. Lipogenic genes FAS and SCD were also increased, accompanied by HSPs. Adipocytes exposed to EHS also increased intracellular lipid accumulation. Proteomic analysis revealed that carbon and pyruvate metabolism pathways were upregulated by MHS, whereas glycolysis/ gluconeogenesis, protein processing in the endoplasmic reticulum, RNA transport, and biosynthesis of amino acids were upregulated by EHS. Cellular mechanisms related to skeletal muscle hypertrophy and adipose tissue growth are responsive in in-vitro settings; however, the results are controversial depending on cell type and animal species. Various factors such as metabolic, hormonal, and immunologic regulation need to be considered to accurately assess the effect of HS on the postnatal growth of major tissues at the animal level.

Guanidinoacetic Acid Attenuates Adipogenesis through Regulation of miR-133a in Sheep.

Guanidinoacetic acid (GAA) is an amino acid derivative, previously described in the skeletal muscle of vertebrates, that serves as an important regulator of cellular bioenergetics and has been widely used as a feed additive. Nevertheless, the effect of GAA on adipose tissue growth remains unclear. Here, we hypothesized that dietary GAA negatively affected adipose tissue development in lambs. Lambs were individually fed diets with (0.09%) or without GAA for 70 d ad libitum, and the subcutaneous adipose tissues were sampled for analysis. The results showed that dietary GAA supplementation decreased the girth rib (GR) value (p < 0.01) of lamb carcasses. Both real-time PCR and Western blot analysis suggested that dietary GAA inhibited the expression of adipogenic markers, including peroxisome proliferator-activated receptor γ (PPARγ, p < 0.05), CCAAT/enhancer-binding protein α (C/EBPα, p < 0.01) and sterol-regulatory-element-binding protein 1c (SREBP1C, p < 0.01) in subcutaneous adipose tissue. In vitro, GAA inhibited sheep stromal vascular fraction (SVF) cell proliferation, which was associated with downregulation of proliferating cell nuclear antigen (PCNA, p < 0.05), cyclin-dependent kinase 4 (CDK 4, p < 0.05) and cyclin D1 (p < 0.01). GAA suppressed adipogenesis of SVF cells. Furthermore, miRNA sequencing revealed that GAA affected the miRNA expression profile, and real-time PCR analysis confirmed that miR-133a expression in both subcutaneous adipose tissue and SVF cell was downregulated by GAA. Meanwhile, miR-133a promoted adipogenic differentiation of SVF cells by targeting Sirt1. miR-133a mimics alleviated the inhibitory effect of GAA on SVF cells' adipogenic differentiation. In summary, GAA attenuated adipogenesis of sheep SVF cells, which might occur through miR-133a-modulated Sirt1 expression.

What's gut got to do with it? The role of the microbiota and inflammation in the development of adiposity and obesity.

Obesity is a complex and heterogeneous disease characterized by increased adiposity, ie, the accumulation of lipids and the growth of adipose tissue. In this mini-review, we explore the important role of the gut microbiota and immune system in the development of adiposity. Dysbiosis of the microbiota leads to increased permeability of the gut barrier and bacterial products in the bloodstream, which triggers metabolic inflammation of adipose tissue, muscle, and liver. Inflammation in these highly metabolic organs exacerbates adiposity and contributes to the development of comorbidities associated with obesity. Studies in animal models that manipulate the microbiota and/or inflammation have shown promise in the treatment of obesity.

236-LB: FHL2-/- Perivascular Adipose Tissue Improves Vessel Tone and Insulin-Stimulated Vasodilation by Inhibiting ERK1/2

Background: Type 2 diabetes, obesity and aging increase risk of developing cardiovascular diseases. Perivascular adipose tissue (PVAT) is a crucial regulator of vascular function. Four and Half Lim domains 2 (FHL2) is a protein upregulated in aging which targets various proteins with established links to adipose tissue growth, potentially regulating metabolic signaling. Objective: we hypothesized that FHL2 regulates adipose tissue regulation of vascular function. Methods: Femoral arteries were isolated from Wild type (WT) and FHL2-/- mice and vasoreactivity to insulin and acetylcholine was studied with and without perivascular adipose tissue. Results: FHL2-/- vessels with PVAT had increased tone compared to WT vessels with PVAT as well as improved insulin-stimulated vasodilation. Exchange experiments using vessels with PVAT from the opposite genotype showed that FHL2-PVAT enhanced tone and insulin-stimulated vasodilatation compared to WT-PVAT. Gene expression analysis showed downregulation of adiponectin in FHL2-PVAT. Western blot analysis of insulin-stimulated phosphorylation of ERK and Akt in human microvascular endothelial cells (HMECs) stimulated with PVAT-conditioned medium revealed that FHL2-PVAT but not WT-PVAT reduced insulin-stimulated phosphorylation of ERK but not activation of Akt. In line with the effect of FHL2 on insulin-induced vasodilatation and activation of ERK1/2, analysis of publicly available RNA sequencing data of peri-aortic PVAT showed that FHL2 expression in PVAT positively correlates with expression of the endothelial vasoconstrictor peptide endothelin-1 (edn1). Conclusion: FHL2 regulates vascular function through enhancement of smooth muscle tone, regulation of adipokine secretion affecting insulin-stimulated ERK1/2 activation and Edn1 expression in endothelial cells. These finding provide a new mechanism for vascular dysfunction in type 2 diabetes. Disclosure J. Habibe: None. D. van Raalte: Consultant; Boehringer Ingelheim and Eli Lilly Alliance, AstraZeneca, Merck &amp; Co., Inc. Research Support; Boehringer Ingelheim and Eli Lilly Alliance, AstraZeneca, Merck &amp; Co., Inc. M. Nieuwdorp: Advisory Panel; caelus health. C. de Vries: None. E. C. Eringa: None. Funding Amsterdam Cardiovascular Sciences (ACS201703)

Association of growth hormone deficiency with an increased number of preadipocytes in subcutaneous fat.

The inhibitory effect of growth hormone (GH) on adipose tissue growth is well known, but the underlying mechanism is not fully understood. In this study, we determined the possibility that GH inhibits adipose tissue growth by inhibiting adipogenesis, the process of formation of adipocytes from stem cells, in the lit/lit mice. The lit/lit mice are GH deficient because of a spontaneous mutation to the GH releasing hormone receptor (ghrhr) gene, and they have more subcutaneous fat despite being smaller than the lit/+ mice at the same age. We found that cells of the stromal vascular fraction (SVF) of subcutaneous fat from the lit/lit mice had greater adipogenic potential than those from the lit/+ mice, as evidenced by forming greater numbers of lipid droplets-containing adipocytes and having greater expression of adipocyte marker genes during induced adipocyte differentiation in culture. However, addition of GH to the culture did not reverse the superior adipogenic potential of subcutaneous SVF from the lit/lit mice. Through florescence-activated cell sorting and quantification of mRNAs of preadipocyte markers, including CD34, CD29, Sca-1, CD24, Pref-1, and PPARγ, we found that subcutaneous SVF from the lit/lit mice contained more preadipocytes than that from the lit/+ mice. These results support the notion that GH inhibits adipose tissue growth in mice at least in part by inhibiting adipogenesis. Furthermore, these results suggest that GH inhibits adipogenesis in mice not by inhibiting the terminal differentiation of preadipocytes into adipocytes, rather by inhibiting the formation of preadipocytes from stem cells or the recruitment of stem cells to the fat depot.