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Sample records for adipose factor fiaf

  1. Influencing Factors of Thermogenic Adipose Tissue Activity

    PubMed Central

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called “brite” or “beige” adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID:26903879

  2. Influencing Factors of Thermogenic Adipose Tissue Activity.

    PubMed

    Zhang, Guoqing; Sun, Qinghua; Liu, Cuiqing

    2016-01-01

    Obesity is an escalating public health challenge and contributes tremendously to the disease burden globally. New therapeutic strategies are required to alleviate the health impact of obesity-related metabolic dysfunction. Brown adipose tissue (BAT) is specialized for dissipating chemical energy for thermogenesis as a defense against cold environment. Intriguingly, the brown-fat like adipocytes that dispersed throughout white adipose tissue (WAT) in rodents and humans, called "brite" or "beige" adipocytes, share similar thermogenic characteristics to brown adipocytes. Recently, researchers have focused on cognition of these thermogenic adipose tissues. Some factors have been identified to regulate the development and function of thermogenic adipose tissues. Cold exposure, pharmacological conditions, and lifestyle can enhance non-shivering thermogenesis and metabolism via some mechanisms. However, environmental pollutants, such as ambient fine particulates and ozone, may impair the function of these thermogenic adipose tissues and thereby induce metabolic dysfunction. In this review, the origin, function and influencing factors of thermogenic adipose tissues were summarized and it will provide insights into identifying new therapeutic strategies for the treatment of obesity and obesity-related diseases. PMID:26903879

  3. Lactobacillus rhamnosus CNCMI-4317 Modulates Fiaf/Angptl4 in Intestinal Epithelial Cells and Circulating Level in Mice

    PubMed Central

    Jacouton, Elsa; Mach, Núria; Cadiou, Julie; Lapaque, Nicolas; Clément, Karine; Doré, Joël; van Hylckama Vlieg, Johan E. T.; Smokvina, Tamara; Blottière, Hervé M

    2015-01-01

    Background and Objectives Identification of new targets for metabolic diseases treatment or prevention is required. In this context, FIAF/ANGPTL4 appears as a crucial regulator of energy homeostasis. Lactobacilli are often considered to display beneficial effect for their hosts, acting on different regulatory pathways. The aim of the present work was to study the effect of several lactobacilli strains on Fiaf gene expression in human intestinal epithelial cells (IECs) and on mice tissues to decipher the underlying mechanisms. Subjects and Methods Nineteen lactobacilli strains have been tested on HT–29 human intestinal epithelial cells for their ability to regulate Fiaf gene expression by RT-qPCR. In order to determine regulated pathways, we analysed the whole genome transcriptome of IECs. We then validated in vivo bacterial effects using C57BL/6 mono-colonized mice fed with normal chow. Results We identified one strain (Lactobacillus rhamnosus CNCMI–4317) that modulated Fiaf expression in IECs. This regulation relied potentially on bacterial surface-exposed molecules and seemed to be PPAR-γ independent but PPAR-α dependent. Transcriptome functional analysis revealed that multiple pathways including cellular function and maintenance, lymphoid tissue structure and development, as well as lipid metabolism were regulated by this strain. The regulation of immune system and lipid and carbohydrate metabolism was also confirmed by overrepresentation of Gene Ontology terms analysis. In vivo, circulating FIAF protein was increased by the strain but this phenomenon was not correlated with modulation Fiaf expression in tissues (except a trend in distal small intestine). Conclusion We showed that Lactobacillus rhamnosus CNCMI–4317 induced Fiaf expression in human IECs, and increased circulating FIAF protein level in mice. Moreover, this effect was accompanied by transcriptome modulation of several pathways including immune response and metabolism in vitro. PMID:26439630

  4. Intronic cis-regulatory modules mediate tissue-specific and microbial control of angptl4/fiaf transcription.

    PubMed

    Camp, J Gray; Jazwa, Amelia L; Trent, Chad M; Rawls, John F

    2012-01-01

    The intestinal microbiota enhances dietary energy harvest leading to increased fat storage in adipose tissues. This effect is caused in part by the microbial suppression of intestinal epithelial expression of a circulating inhibitor of lipoprotein lipase called Angiopoietin-like 4 (Angptl4/Fiaf). To define the cis-regulatory mechanisms underlying intestine-specific and microbial control of Angptl4 transcription, we utilized the zebrafish system in which host regulatory DNA can be rapidly analyzed in a live, transparent, and gnotobiotic vertebrate. We found that zebrafish angptl4 is transcribed in multiple tissues including the liver, pancreatic islet, and intestinal epithelium, which is similar to its mammalian homologs. Zebrafish angptl4 is also specifically suppressed in the intestinal epithelium upon colonization with a microbiota. In vivo transgenic reporter assays identified discrete tissue-specific regulatory modules within angptl4 intron 3 sufficient to drive expression in the liver, pancreatic islet β-cells, or intestinal enterocytes. Comparative sequence analyses and heterologous functional assays of angptl4 intron 3 sequences from 12 teleost fish species revealed differential evolution of the islet and intestinal regulatory modules. High-resolution functional mapping and site-directed mutagenesis defined the minimal set of regulatory sequences required for intestinal activity. Strikingly, the microbiota suppressed the transcriptional activity of the intestine-specific regulatory module similar to the endogenous angptl4 gene. These results suggest that the microbiota might regulate host intestinal Angptl4 protein expression and peripheral fat storage by suppressing the activity of an intestine-specific transcriptional enhancer. This study provides a useful paradigm for understanding how microbial signals interact with tissue-specific regulatory networks to control the activity and evolution of host gene transcription. PMID:22479192

  5. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation.

    PubMed

    Kim, Bong-Sung; Rongisch, Robert; Hager, Stephan; Grieb, Gerrit; Nourbakhsh, Mahtab; Rennekampff, Hans-Oliver; Bucala, Richard; Bernhagen, Juergen; Pallua, Norbert

    2015-01-01

    Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a role in cell

  6. Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I: Rheumatoid adipose tissue.

    PubMed

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Zaniewicz-Kaniewska, Katarzyna; Prohorec-Sobieszek, Monika; Saied, Fadhil; Maśliński, Włodzimierz

    2013-06-01

    For many years, it was thought that synovial cells and chondrocytes are the only sources of proinflammatory cytokines and growth factors found in the synovial fluid in patients suffering from osteoarthritis and rheumatoid arthritis. Currently, it is more and more frequently indicated that adipose tissue plays a significant role in the pathogenesis of these diseases as well as that a range of pathological processes that take place in the adipose tissue, synovial membrane and cartilage are interconnected. The adipose tissue is considered a specialized form of the connective tissue containing various types of cells which produce numerous biologically active factors. The latest studies reveal that, similarly to the synovial membrane, articular adipose tissue may take part in the local inflammatory response and affect the metabolism of the cartilage and subchondral osseous tissue. In in vitro conditions, the explants of this tissue obtained from patients suffering from osteoarthritis and rheumatoid arthritis produce similar pro- and anti-inflammatory cytokines to the explants of the synovial membrane. At this stage already, knowledge translates into imaging diagnostics. In radiological images, the shadowing of the periarticular soft tissues may not only reflect synovial membrane pathologies or joint effusion, but may also suggest inflammatory edema of the adipose tissue. On ultrasound examinations, abnormal presentation of the adipose tissue, i.e. increased echogenicity and hyperemia, may indicate its inflammation. Such images have frequently been obtained during ultrasound scanning and have been interpreted as inflammation, edema, hypertrophy or fibrosis of the adipose tissue. At present, when the knowledge concerning pathogenic mechanisms is taken into account, abnormal echogenicity and hyperemia of the adipose tissue may be considered as a proof of its inflammation. In the authors' own practice, the inflammation of the adipose tissue usually accompanies synovitis

  7. Calcium Sensing Receptor (CaSR) activation elevates proinflammatory factor expression in human adipose cells and adipose tissue

    PubMed Central

    Cifuentes, Mariana; Fuentes, Cecilia; Acevedo, Ingrid; Villalobos, Elisa; Hugo, Eric; Ben Jonathan, Nira; Reyes, Marcela

    2013-01-01

    We have previously established that human adipose cells and the human adipose cell line LS14 express the calcium sensing receptor (CaSR) and that its expression is elevated upon exposure to inflammatory cytokines that are typically elevated in obese humans. Research in recent years has established that an important part of the adverse metabolic and cardiovascular consequences of obesity derive from a dysfunction of the tissue, one of the mechanisms being a disordered secretion pattern leading to an excess of proinflammatory cytokines and chemokines. Given the reported association of the CaSR to inflammatory processes in other tissues, we sought to evaluate its role elevating the adipose expression of inflammatory factors. We exposed adipose tissue and in-vitro cultured LS14 preadipocytes and differentiated adipocytes to the calcimimetic cinacalcet and evaluated the expression or production of the proinflammatory cytokines IL6, IL1β and TNFα as well as the chemoattractant factor CCL2. CaSR activation elicited an elevation in the expression of the inflammatory factors, which was in part reverted by SN50, an inhibitor of the inflammatory mediator NFκB. Our observations suggest that CaSR activation elevates cytokine and chemokine production through a signaling pathway involving activation of NFκB nuclear translocation. These findings confirm the relevance of the CaSR in the pathophysiology of obesity-induced adipose tissue dysfunction, with an interesting potential for pharmacological manipulation in the fight against obesity- associated diseases. PMID:22449852

  8. Role of developmental transcription factors in white, brown and beige adipose tissues.

    PubMed

    Hilton, Catriona; Karpe, Fredrik; Pinnick, Katherine E

    2015-05-01

    In this review we discuss the role of developmental transcription factors in adipose tissue biology with a focus on how these developmental genes may contribute to regional variation in adipose tissue distribution and function. Regional, depot-specific, differences in lipid handling and signalling (lipolysis, lipid storage and adipokine/lipokine signalling) are important determinants of metabolic health. At a cellular level, preadipocytes removed from their original depot and cultured in vitro retain depot-specific functional properties, implying that these are intrinsic to the cells and not a function of their environment in situ. High throughput screening has identified a number of developmental transcription factors involved in embryological development, including members of the Homeobox and T-Box gene families, that are strongly differentially expressed between regional white adipose tissue depots and also between brown and white adipose tissue. However, the significance of depot-specific developmental signatures remains unclear. Developmental transcription factors determine body patterning during embryogenesis. The divergent developmental origins of regional adipose tissue depots may explain their differing functional characteristics. There is evidence from human genetics that developmental genes determine adipose tissue distribution: in GWAS studies a number of developmental genes have been identified as being correlated with anthropometric measures of adiposity and fat distribution. Additionally, compelling functional studies have recently implicated developmental genes in both white adipogenesis and the so-called 'browning' of white adipose tissue. Understanding the genetic and developmental pathways in adipose tissue may help uncover novel ways to intervene with the function of adipose tissue in order to promote health.

  9. Sociodemographic and behavioral factors associated with body adiposity in adolescents☆

    PubMed Central

    Bozza, Rodrigo; de Campos, Wagner; Bacil, Eliane Denise Araújo; Barbosa, Valter Cordeiro; Hardt, Jennifer Morozini; da Silva, Priscila Marques

    2014-01-01

    Objective: To identify sociodemographic and behavioral factors associated with abdominal obesity (AO) and high body fat percentage (high BF%) in adolescents from the city of Curitiba-PR. Methods: The sample consisted of 1,732 adolescents, aged 11 to 19 years, of both genders. The triceps and calf skinfolds were measured for the calculation of BF%, as well as the waist circumference. A questionnaire was completed by adolescents with the following type of residence, socioeconomic status, time spent watching TV on weekdays and weekends, and daily energy expenditure. Logistic regression was used to measure the association of sociodemographic and behavioral variables with abdominal obesity and high BF%. Results: Female were more likely to have high BF% (OR: 2.73; 95% CI: 2.32-3.33), but were less likely to have abdominal obesity (OR: 0.58; 95% CI: 0.44-0.78). Older individuals (1619 have high BF% (OR: 1.36; 95% CI: 1.02-1.83). The older age groups (13-15 years and 16-19 years) had an inverse association with abdominal obesity. Regarding daily energy expenditure, the less active individuals were more likely to present high BF% (OR: 1.36; 95% CI: 1.07-1.71) and obesity (OR: 1.40; 95% CI: 1.09-1.80). Conclusions: Interventions to increase physical activity levels in young people should be designed in order to combat excess body fat should designed to combat excess adiposity. PMID:25479856

  10. Delivery of basic fibroblast growth factors from heparinized decellularized adipose tissue stimulates potent de novo adipogenesis.

    PubMed

    Lu, Qiqi; Li, Mingming; Zou, Yu; Cao, Tong

    2014-01-28

    Scaffolds based on decellularized adipose tissue (DAT) are gaining popularity in adipose tissue engineering due to their high biocompatibility and adipogenic inductive property. However, previous studies involving DAT-derived scaffolds have not fully revealed their potentials for in vivo adipose tissue construction. With the aim of developing a more efficient adipose tissue engineering technique based on DAT, in this study, we investigated the in vivo adipogenic potential of a basic fibroblast growth factor (bFGF) delivery system based on heparinized DAT (Hep-DAT). To generate this system, heparins were cross-linked to mouse DATs by using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide and N-Hydroxysuccinimide. The bFGF-binding Hep-DATs were first tested for controlled release ability in vitro and then transplanted subcutaneously. Highly vascularized adipose tissues were formed 6weeks after transplantation. Histology and gene expression analysis revealed that majority of the Hep-DAT scaffolds were infiltrated with host-derived adipose tissues that possessed similar adipogenic and inflammatory gene expression as endogenous adipose tissues. Additionally, strong de novo adipogenesis could also be induced when bFGF-binding Hep-DATs were thoroughly minced and injected subcutaneously. In conclusion, our study demonstrated that bFGF-binding Hep-DAT could be an efficient, biocompatible and injectable adipogenic system for in vivo adipose tissue engineering.

  11. Central adiposity and associated lifestyle factors in Cree children.

    PubMed

    Downs, Shauna M; Marshall, Dru; Ng, Carmina; Willows, Noreen D

    2008-06-01

    Aboriginal children are prone to central adiposity (CA), a component of the metabolic syndrome. The objective of this study was to determine if lifestyle factors were associated with CA in Canadian Cree children. Children aged 9-12 years were classified as having CA if their waist circumference met or exceeded the 85th percentile of the NHANES III reference. Weight status was determined using the CDC growth reference, dietary intake using three 24 h dietary recalls, physical activity using pedometers, and fitness by completion of the 20 m shuttle run test. Of the 178 children (79% participation rate), 32.6% were normal weight, 23.6% were overweight, and 43.8% were obese. Half (52.2%) of the children had CA (97.4% of obese children, 35.7% of overweight children, and 2.2% of normal weight children). Waist circumference was negatively correlated with pedometer step counts (r = -0.187, p = 0.012) and shuttle run time (r = -0.508, p < 0.001). In children with CA, waist circumference was positively correlated with sweetened beverage intake (r = 0.250, p = 0.016). The odds ratio (adjusted for age and sex) for CA for children consuming 3 or more fruits and vegetables per day was 0.43 (95% CI 0.18 - 0.98), for meeting step recommendations for a healthy body weight was 0.45 (95% CI 0.24 - 0.84), and for relative fitness was 0.12 (95% CI 0.04 - 0.33). CA was prevalent in children who were overweight and obese. Preventive strategies might include promoting a healthy diet, physical activity, and fitness.

  12. Role of adipose secreted factors and kisspeptin in the metabolic control of gonadotropin secretion and puberty

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Factors secreted by adipose tissue continue to be discovered. Evidence indicates a strong link between neural influences and adipocyte expression and secretion of a wide array of cytokines, neurotrophic factors, growth factors, binding proteins, and neuropeptides. These “adipokines” are linked to im...

  13. Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

    PubMed Central

    Fall, Tove; Hägg, Sara; Ploner, Alexander; Mägi, Reedik; Fischer, Krista; Draisma, Harmen H.M.; Sarin, Antti-Pekka; Benyamin, Beben; Ladenvall, Claes; Åkerlund, Mikael; Kals, Mart; Esko, Tõnu; Nelson, Christopher P.; Kaakinen, Marika; Huikari, Ville; Mangino, Massimo; Meirhaeghe, Aline; Kristiansson, Kati; Nuotio, Marja-Liisa; Kobl, Michael; Grallert, Harald; Dehghan, Abbas; Kuningas, Maris; de Vries, Paul S.; de Bruijn, Renée F.A.G.; Willems, Sara M.; Heikkilä, Kauko; Silventoinen, Karri; Pietiläinen, Kirsi H.; Legry, Vanessa; Giedraitis, Vilmantas; Goumidi, Louisa; Syvänen, Ann-Christine; Strauch, Konstantin; Koenig, Wolfgang; Lichtner, Peter; Herder, Christian; Palotie, Aarno; Menni, Cristina; Uitterlinden, André G.; Kuulasmaa, Kari; Havulinna, Aki S.; Moreno, Luis A.; Gonzalez-Gross, Marcela; Evans, Alun; Tregouet, David-Alexandre; Yarnell, John W.G.; Virtamo, Jarmo; Ferrières, Jean; Veronesi, Giovanni; Perola, Markus; Arveiler, Dominique; Brambilla, Paolo; Lind, Lars; Kaprio, Jaakko; Hofman, Albert; Stricker, Bruno H.; van Duijn, Cornelia M.; Ikram, M. Arfan; Franco, Oscar H.; Cottel, Dominique; Dallongeville, Jean; Hall, Alistair S.; Jula, Antti; Tobin, Martin D.; Penninx, Brenda W.; Peters, Annette; Gieger, Christian; Samani, Nilesh J.; Montgomery, Grant W.; Whitfield, John B.; Martin, Nicholas G.; Groop, Leif; Spector, Tim D.; Magnusson, Patrik K.; Amouyel, Philippe; Boomsma, Dorret I.; Nilsson, Peter M.; Järvelin, Marjo-Riitta; Lyssenko, Valeriya; Metspalu, Andres; Strachan, David P.; Salomaa, Veikko; Ripatti, Samuli; Pedersen, Nancy L.; Prokopenko, Inga; McCarthy, Mark I.

    2015-01-01

    Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10−107) and stratified analyses (all P < 3.3 × 10−30). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors. PMID:25712996

  14. The impact of adipose tissue-derived factors on the hypothalamic-pituitary-gonadal (HPG) axis.

    PubMed

    Tsatsanis, Christos; Dermitzaki, Eirini; Avgoustinaki, Pavlina; Malliaraki, Niki; Mytaras, Vasilis; Margioris, Andrew N

    2015-01-01

    Adipose tissue produces factors, including adipokines, cytokines and chemokines which, when released, systemically exert endocrine effects on multiple tissues thereby affecting their physiology. Adipokines also affect the hypothalamic-pituitary-gonadal (HPG) axis both centrally, at the hypothalamic-pituitary level, and peripherally acting on the gonads themselves. Among the adipokines, leptin, adiponectin, resistin, chemerin and the peptide kisspeptin have pleiotropic actions on the HPG axis affecting male and female fertility. Furthermore, adipokines and adipose tissue-produced factors readily affect the immune system resulting in inflammation, which in turn impact the HPG axis, thus evidencing a link between metabolic inflammation and fertility. In this review we provide an overview of the existing extensive bibliography on the crosstalk between adipose tissue-derived factors and the HPG axis, with particular focus on the impact of obesity and the metabolic syndrome on gonadal function and fertility.

  15. Fibroblast growth factor-2 stimulates adipogenic differentiation of human adipose-derived stem cells

    SciTech Connect

    Kakudo, Natsuko . E-mail: kakudon@takii.kmu.ac.jp; Shimotsuma, Ayuko; Kusumoto, Kenji

    2007-07-27

    Adipose-derived stem cells (ASCs) have demonstrated a capacity for differentiating into a variety of lineages, including bone, cartilage, or fat, depending on the inducing stimuli and specific growth and factors. It is acknowledged that fibroblast growth factor-2 (FGF-2) promotes chondrogenic and inhibits osteogenic differentiation of ASCs, but thorough investigations of its effects on adipogenic differentiation are lacking. In this study, we demonstrate at the cellular and molecular levels the effect of FGF-2 on adipogenic differentiation of ASCs, as induced by an adipogenic hormonal cocktail consisting of 3-isobutyl-1-methylxanthine (IBMX), dexamethasone, insulin, and indomethacin. FGF-2 significantly enhances the adipogenic differentiation of human ASCs. Furthermore, in cultures receiving FGF-2 before adipogenic induction, mRNA expression of peroxisome proliferator-activated receptor {gamma}2 (PPAR{gamma}2), a key transcription factor in adipogenesis, was upregulated. The results of FGF-2 supplementation suggest the potential applications of FGF-2 and ASCs in adipose tissue regeneration.

  16. Factors Predicting Adhesion between Renal Capsule and Perinephric Adipose Tissue in Partial Nephrectomy.

    PubMed

    Kobayashi, Yasuyuki; Kurahashi, Hiroaki; Matsumoto, Yuko; Wada, Koichiro; Sasaki, Katsumi; Araki, Motoo; Ebara, Shin; Watanabe, Toyohiko; Nasu, Yasutomo

    2016-01-01

    In minimally invasive partial nephrectomy (MIPN), it is important to preoperatively predict the degree of difficulty of tumor resection. When severe adhesions occur between the renal capsule and perinephric adipose tissue, detachment can be difficult. Preoperative prediction of adhesion is thought to be useful in the selection of surgical procedure. Subjects were 63 patients of a single surgeon who had received MIPN between April 2008 and August 2013 at Okayama University Hospital. Of these patients, this study followed 47 in whom the presence or absence of adhesions between the renal capsule and perinephric adipose tissue was confirmed using intraoperative videos. Data collected included: sex, BMI, CT finding (presence of fi broids in perinephric adipose tissue), comorbidities and lifestyle. Adhesion was observed in 7 patients (14.9%). The mean operative time was 291.6 min in the adhesion group, and 226.3 min in the group without. The increased time in the adhesions group was significant (p<0.05). Predictive factors were a positive CT finding for fibroid structure and comorbidity of hypertension (p<0.05). In MIPN, difficulty of surgery can be affected by the presence of adhesion of the perinephric adipose tissue. Predicting such adhesion from preoperative CT is thus important.

  17. Hypoxia-inducible factor 3A gene expression and methylation in adipose tissue is related to adipose tissue dysfunction.

    PubMed

    Pfeiffer, Susanne; Krüger, Jacqueline; Maierhofer, Anna; Böttcher, Yvonne; Klöting, Nora; El Hajj, Nady; Schleinitz, Dorit; Schön, Michael R; Dietrich, Arne; Fasshauer, Mathias; Lohmann, Tobias; Dreßler, Miriam; Stumvoll, Michael; Haaf, Thomas; Blüher, Matthias; Kovacs, Peter

    2016-01-01

    Recently, a genome-wide analysis identified DNA methylation of the HIF3A (hypoxia-inducible factor 3A) as strongest correlate of BMI. Here we tested the hypothesis that HIF3A mRNA expression and CpG-sites methylation in adipose tissue (AT) and genetic variants in HIF3A are related to parameters of AT distribution and function. In paired samples of subcutaneous AT (SAT) and visceral AT (VAT) from 603 individuals, we measured HIF3A mRNA expression and analyzed its correlation with obesity and related traits. In subgroups of individuals, we investigated the effects on HIF3A genetic variants on its AT expression (N = 603) and methylation of CpG-sites (N = 87). HIF3A expression was significantly higher in SAT compared to VAT and correlated with obesity and parameters of AT dysfunction (including CRP and leucocytes count). HIF3A methylation at cg22891070 was significantly higher in VAT compared to SAT and correlated with BMI, abdominal SAT and VAT area. Rs8102595 showed a nominal significant association with AT HIF3A methylation levels as well as with obesity and fat distribution. HIF3A expression and methylation in AT are fat depot specific, related to obesity and AT dysfunction. Our data support the hypothesis that HIF pathways may play an important role in the development of AT dysfunction in obesity. PMID:27346320

  18. Differing statistical approaches affect the relation between egg consumption, adiposity, and cardiovascular risk factors in adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Associations between food patterns and adiposity are poorly understood. Two statistical approaches were used to examine the potential association between egg consumption and adiposity. Two statistical approaches were used to examine the potential association between egg consumption and adiposity. Pa...

  19. Orthogonal factor coefficient development of subcutaneous adipose tissue topography (SAT-Top) in girls and boys.

    PubMed

    Tafeit, E; Möller, R; Sudi, K; Horejsi, R; Berg, A; Reibnegger, G

    2001-05-01

    The new optical device Lipometer allows noninvasive, quick, and safe determination of the thickness of subcutaneous adipose tissue (SAT) layers (in mm) at any site of the human body. The specification of 15 evenly distributed body sites enables the precise measurement of subcutaneous body fat distribution, so-called subcutaneous adipose tissue topography (SAT-Top). SAT-Top was measured in 980 children aged 7-19 years. In this paper we describe the degree to which SAT-Top body sites are intercorrelated. We consider whether a meaningful reduction of data is possible using factor analysis, which factors can be extracted, and how SAT-Top data of children can be added to a factor value plot, depicting the essential results of age-dependent subcutaneous fat development. SAT layers situated on the same body area provide correlation coefficients up to +r = 0.91. Two factors are extracted: factor 1, containing all upper body sites (from neck to hip); and factor 2, consisting of all leg body sites. When all 980 children are divided into three age groups in a factor value plot, the first age group (7-11 years) shows almost equal SAT-Top development in boys and girls. Afterwards, for the consecutive age groups 2 (11-15 years) and 3 (15-19 years), the age-dependent subcutaneous fat development of boys and girls progresses into nearly orthogonal directions. PMID:11309750

  20. Hypoxia-Inducible Factor 1α Induces Fibrosis and Insulin Resistance in White Adipose Tissue ▿ §

    PubMed Central

    Halberg, Nils; Khan, Tayeba; Trujillo, Maria E.; Wernstedt-Asterholm, Ingrid; Attie, Alan D.; Sherwani, Shariq; Wang, Zhao V.; Landskroner-Eiger, Shira; Dineen, Sean; Magalang, Ulysses J.; Brekken, Rolf A.; Scherer, Philipp E.

    2009-01-01

    Adipose tissue can undergo rapid expansion during times of excess caloric intake. Like a rapidly expanding tumor mass, obese adipose tissue becomes hypoxic due to the inability of the vasculature to keep pace with tissue growth. Consequently, during the early stages of obesity, hypoxic conditions cause an increase in the level of hypoxia-inducible factor 1α (HIF1α) expression. Using a transgenic model of overexpression of a constitutively active form of HIF1α, we determined that HIF1α fails to induce the expected proangiogenic response. In contrast, we observed that HIF1α initiates adipose tissue fibrosis, with an associated increase in local inflammation. “Trichrome- and picrosirius red-positive streaks,” enriched in fibrillar collagens, are a hallmark of adipose tissue suffering from the early stages of hypoxia-induced fibrosis. Lysyl oxidase (LOX) is a transcriptional target of HIF1α and acts by cross-linking collagen I and III to form the fibrillar collagen fibers. Inhibition of LOX activity by β-aminoproprionitrile treatment results in a significant improvement in several metabolic parameters and further reduces local adipose tissue inflammation. Collectively, our observations are consistent with a model in which adipose tissue hypoxia serves as an early upstream initiator for adipose tissue dysfunction by inducing a local state of fibrosis. PMID:19546236

  1. Continuous low-dose infusion of tumor necrosis factor alpha in adipose tissue elevates adipose tissue interleukin 10 abundance and fails to alter metabolism in lactating dairy cows.

    PubMed

    Martel, Cynthia A; Mamedova, Laman K; Minton, J Ernest; Jones, Meredyth L; Carroll, Jeff A; Bradford, Barry J

    2014-01-01

    Repeated bolus doses of tumor necrosis factor-α (TNFα) alters systemic metabolism in lactating cows, but whether chronic release of inflammatory cytokines from adipose tissue has similar effects is unclear. Late-lactation Holstein cows (n=9-10/treatment) were used to evaluate the effects of continuous adipose tissue TNFα administration on glucose and fatty acid (FA) metabolism. Cows were blocked by feed intake and milk yield and randomly assigned within block to control or TNFα treatments. Treatments (4mL of saline or 14µg/kg of TNFα in 4mL of saline) were infused continuously over 7d via 2 osmotic pumps implanted in a subcutaneous adipose depot. Plasma, milk samples, milk yield, and feed intake data were collected daily, and plasma glucose turnover rate was measured on d 7. At the end of d 7, pumps were removed and liver and contralateral tail-head adipose biopsies were collected. Results were modeled with the fixed effect of treatment and the random effect of block. Treatment with TNFα increased plasma concentrations of the acute phase protein haptoglobin, but did not alter plasma TNFα, IL-4, IL-6, or IFN-γ concentrations, feed intake, or rectal temperature. Milk yield and composition were unchanged, and treatments did not alter the proportion of short- versus long-chain FA in milk on d 7. Treatments did not alter plasma free FA concentration, liver triglyceride content, or plasma glucose turnover rate. Surprisingly, TNFα infusion tended to decrease liver TNFα and IL-1 receptor 1 mRNA abundance and significantly increased adipose tissue IL-10 protein concentration. Continuous infusion of TNFα did not induce the metabolic responses previously observed following bolus doses delivered at the same rate per day. Metabolic homeostasis may have been protected by an adaptive anti-inflammatory response to control systemic inflammation.

  2. Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance

    NASA Astrophysics Data System (ADS)

    Hotamisligil, Gokhan S.; Shargill, Narinder S.; Spiegelman, Bruce M.

    1993-01-01

    Tumor necrosis factor-α (TNF-α) has been shown to have certain catabolic effects on fat cells and whole animals. An induction of TNF-α messenger RNA expression was observed in adipose tissue from four different rodent models of obesity and diabetes. TNF-α protein was also elevated locally and systemically. Neutralization of TNF-α in obese fa/fa rats caused a significant increase in the peripheral uptake of glucose in response to insulin. These results indicate a role for TNF-α in obesity and particularly in the insulin resistance and diabetes that often accompany obesity.

  3. Relationship between adiposity and cardiovascular risk factors in prevalent hemodialysis patients

    PubMed Central

    Kaysen, George A.; Kotanko, Peter; Zhu, Fansan; Sarkar, Shubho R; Heymsfield, Steven B.; Kuhlmann, Martin K.; Dwyer, Tjien; Usvyat, Len; Havel, Peter; Levin, Nathan W.

    2009-01-01

    Increased Body Mass Index (BMI) is associated with reduced all cause and cardiovascular (CV) mortality in hemodialysis patients (HD), while CV risk increases with BMI in the general population. In the general population obesity is associated with inflammation, decreased HDL, increased LDL and triglycerides (TGs), all risk factors for CV disease. LDL does not predict CV risk in HD, whereas increased C-reactive protein (CRP), interleukin-6 (IL-6), low HDL or apo AI and increased fasting triglycerides (TG) do predict risk. Renal failure is associated with dyslipidemia and inflammation in normal weight patients. We hypothesized that effects of obesity may be obscured by virtue of renal failure in HD. We explored the relationship between adipose tissue pools and distribution, i.e., subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) (measured by MRI) and measures of inflammation (CRP, IL-6, ceruloplasmin and α 1 acid glycoprotein) HDL and LDL cholesterol, total TGs, apo A I, apo B, apo C II (an activator of lipoprotein lipase (LPL)) and CIII (an inhibitor of LPL) and the adipokines, leptin and adiponectin in 48 patients with prevalent HD. Total TG concentrations were positively correlated with VAT controlled for age, sex and weight. Both apo C II and apo C III correlated only with VAT. Adiponectin was inversely correlated with VAT and leptin was positively associated with SAT. CRP and α 1 acid glycoprotein were weakly associated with SAT while ceruloplasmin was strongly associated with VAT by multiple regression analysis. In contrast, apo B, LDL, apo A I and HDL, and IL-6 were not correlated with any measure of body composition potentially mitigating the effects of obesity in HD PMID:19596588

  4. Patient factors influencing the concentration of stromal vascular fraction (SVF) for adipose-derived stromal cell (ASC) therapy in dogs.

    PubMed

    Astor, Donniel E; Hoelzler, Michael G; Harman, Robert; Bastian, Richard P

    2013-07-01

    The objective of this study was to determine whether patient factors influence the concentration of the stromal vascular fraction (SVF) in fat for adipose-derived stromal cell (ASC) therapy in dogs. A total of 1265 dogs underwent adipose collection surgeries by veterinarians for processing by the Vet-Stem laboratory and data on cell counts and patient factors were collected. Body condition score (BCS) and breed size did not significantly affect the viable cells per gram (VCPG) of adipose tissue that represents the viable SVF. Age significantly affected the VCPG, with dogs in age quartile 1 having a significantly higher VCPG than those in quartile 2 (P = 0.003) and quartile 4 (P = 0.002). Adipose tissue collected at the falciform location had significantly fewer VCPG than tissue collected at the thoracic wall and inguinal locations (P < 0.001). When the interaction of gender and location was evaluated, there were significantly fewer VCPG in tissue collected at the falciform location than at the thoracic wall and inguinal locations in female spayed dogs (P < 0.001) and male neutered dogs (P < 0.001), but not in female intact dogs (P = 0.743) or male intact dogs (P = 0.208). It was concluded that specific patient factors should be taken into consideration in order to obtain the maximal yield of VCPG from an adipose collection procedure.

  5. Obesity, Central Adiposity and Cardiometabolic Risk Factors in Children and Adolescents: a Family-based Study

    PubMed Central

    Cerjak, Diana; Kent, Jack W.; James, Roland; Blangero, John

    2014-01-01

    Objective Assess genetic and phenotypic correlations of obesity-related cardiometabolic risk factors in a family-based cohort. Methods Anthropometric, body composition and biochemical measurements were collected on 999 members of 111 extended Midwestern US families of Northern European origin. Forward stepwise regression was used to identify which of Tanner stage, sex, Tanner stage by sex, BFMI, body fat percent (BF%) (DXA), VF/SubQF (CT scan for adults or MRI for children), VF, SubQF, BMI% and waist to height ratio (WHtR) most influence HOMA, HDL-c, TG, and LDL-c. Results In children and adolescents, subcutaneous adiposity was the most significant covariate for HOMA (p<0.001) and TG (p=0.001) and BMI percentile for HDL-c (p=0.002) and LDL-c (p<0.001). In adults, waist-height ratio (p<0.001), visceral/subcutaneous fat ratio (p=0.001) and BMI (p=0.02) were most significant for HOMA; visceral fat (p<0.001) and BMI (p=0.02) for TG and visceral fat for LDL-c (p=0.001). Conclusion Subcutaneous adiposity at the waist is a more significant predictor of MetS traits in children and adolescents than it is in adults. PMID:24677702

  6. A role for novel adipose tissue-secreted factors in obesity-related carcinogenesis.

    PubMed

    Cabia, B; Andrade, S; Carreira, M C; Casanueva, F F; Crujeiras, A B

    2016-04-01

    Obesity, a pandemic disease, is caused by an excessive accumulation of fat that can have detrimental effects on health. Adipose tissue plays a very important endocrine role, secreting different molecules that affect body physiology. In obesity, this function is altered, leading to a dysfunctional production of several factors, known as adipocytokines. This process has been linked to various comorbidities associated with obesity, such as carcinogenesis. In fact, several classical adipocytokines with increased levels in obesity have been demonstrated to exert a pro-carcinogenic role, including leptin, TNF-α, IL-6 and resistin, whereas others like adiponectin, with decreased levels in obesity, might have an anti-carcinogenic function. In this expanding field, new proteomic techniques and approaches have allowed the identification of novel adipocytokines, a number of which exhibit an altered production in obesity and type 2 diabetes and thus are related to adiposity. Many of these novel adipocytokines have also been identified in various tumour types, such as that of the breast, liver or endometrium, thereby increasing the list of potential contributors to carcinogenesis. This review is focused on the regulation of these novel adipocytokines by obesity, including apelin, endotrophin, FABP4, lipocalin 2, omentin-1, visfatin, chemerin, ANGPTL2 or osteopontin, emphasizing its involvement in tumorigenesis. PMID:26914773

  7. Receptor binding sites for atrial natriuretic factor are expressed by brown adipose tissue

    SciTech Connect

    Bacay, A.C.; Mantyh, C.R.; Vigna, S.R.; Mantyh, P.W. )

    1988-09-01

    To explore the possibility that atrial natriuretic factor (ANF) is involved in thermoregulation we used quantitative receptor autoradiography and homogenate receptor binding assays to identify ANF bindings sites in neonatal rat and sheep brown adipose tissue, respectively. Using quantitative receptor autoradiography were were able to localize high levels of specific binding sites for {sup 125}I-rat ANF in neonatal rat brown adipose tissue. Homogenate binding assays on sheep brown fat demonstrated that the radioligand was binding to the membrane fraction and that the specific binding was not due to a lipophilic interaction between {sup 125}I-rat ANF and brown fat. Specific binding of {sup 125}I-rat ANF to the membranes of brown fat cells was inhibited by unlabeled rat ANF with a Ki of 8.0 x 10(-9) M, but not by unrelated peptides. These studies demonstrate that brown fat cells express high levels of ANF receptor binding sites in neonatal rat and sheep and suggest that ANF may play a role in thermoregulation.

  8. Subcutaneous adipose tissue in relation to subclinical atherosclerosis and cardiometabolic risk factors in midlife women1234

    PubMed Central

    Janssen, Imke; Khan, Unab I; Thurston, Rebecca; Barinas-Mitchell, Emma; El Khoudary, Samar R; Everson-Rose, Susan A; Kazlauskaite, Rasa; Matthews, Karen A; Sutton-Tyrrell, Kim

    2011-01-01

    Background: Limited data suggest that the effects of abdominal subcutaneous adipose tissue (SAT) on cardiovascular disease risk may depend on accompanying amounts of abdominal visceral adipose tissue (VAT). Objective: The objective was to examine whether abdominal VAT area modifies the effects of abdominal SAT area on subclinical atherosclerosis and cardiometabolic risk factors in both whites and African Americans. Design: Computed tomographic measures of abdominal SAT and VAT were examined in relation to carotid intima-media thickness (cIMT) and cardiometabolic risk factor levels in 500 African American and white women in midlife. A VAT × SAT interaction term was evaluated. Results: The mean (±SD) age of the sample was 51.0 ± 2.9 y, and 37% were African American. Higher amounts of SAT and VAT were associated with higher cIMT, blood pressure, homeostasis model assessment insulin resistance index (HOMA-IR), and concentrations of glucose, triglycerides, and insulin and with lower concentrations of HDL cholesterol. However, in African Americans, but not in whites, higher amounts of VAT significantly attenuated associations between higher amounts of SAT and higher insulin concentrations (P for interaction = 0.032) and HOMA-IR (P for interaction = 0.011) and reversed associations with cIMT (P for interaction = 0.005) and glucose (P for interaction = 0.044). Conclusions: These results suggest that in midlife African American but not white women, adverse associations between abdominal SAT and cardiometabolic risk factors are attenuated and, in the case of subclinical atherosclerosis, are reversed as VAT amounts increase. Given that African American women suffer disproportionately from obesity and cardiovascular disease, further research into the role of this effect modification on obesity-associated vascular disease in African American women is warranted. PMID:21346089

  9. The ZEB1 Transcription Factor Is a Novel Repressor of Adiposity in Female Mice

    PubMed Central

    Saykally, Jessica N.; Dogan, Soner; Cleary, Margot P.; Sanders, Michel M.

    2009-01-01

    Background Four genome-wide association studies mapped an “obesity” gene to human chromosome 10p11–12. As the zinc finger E-box binding homeobox 1 (ZEB1) transcription factor is encoded by the TCF8 gene located in that region, and as it influences the differentiation of various mesodermal lineages, we hypothesized that ZEB1 might also modulate adiposity. The goal of these studies was to test that hypothesis in mice. Methodology/Principal Findings To ascertain whether fat accumulation affects ZEB1 expression, female C57BL/6 mice were fed a regular chow diet (RCD) ad libitum or a 25% calorie-restricted diet from 2.5 to 18.3 months of age. ZEB1 mRNA levels in parametrial fat were six to ten times higher in the obese mice. To determine directly whether ZEB1 affects adiposity, wild type (WT) mice and mice heterozygous for TCF8 (TCF8+/−) were fed an RCD or a high-fat diet (HFD) (60% calories from fat). By two months of age on an HFD and three months on an RCD, TCF8+/− mice were heavier than WT controls, which was attributed by Echo MRI to increased fat mass (at three months on an HFD: 0.517±0.081 total fat/lean mass versus 0.313±0.036; at three months on an RCD: 0.175±0.013 versus 0.124±0.012). No differences were observed in food uptake or physical activity, suggesting that the genotypes differ in some aspect of their metabolic activity. ZEB1 expression also increases during adipogenesis in cell culture. Conclusion/Significance These results show for the first time that the ZEB1 transcription factor regulates the accumulation of adipose tissue. Furthermore, they corroborate the genome-wide association studies that mapped an “obesity” gene at chromosome 10p11–12. PMID:20041147

  10. Obesity-associated insulin resistance is correlated to adipose tissue vascular endothelial growth factors and metalloproteinase levels

    PubMed Central

    2012-01-01

    Background The expansion of adipose tissue is linked to the development of its vasculature, which appears to have the potential to regulate the onset of obesity. However, at present, there are no studies highlighting the relationship between human adipose tissue angiogenesis and obesity-associated insulin resistance (IR). Results Our aim was to analyze and compare angiogenic factor expression levels in both subcutaneous (SC) and omentum (OM) adipose tissues from morbidly obese patients (n = 26) with low (OB/L-IR) (healthy obese) and high (OB/H-IR) degrees of IR, and lean controls (n = 17). Another objective was to examine angiogenic factor correlations with obesity and IR. Here we found that VEGF-A was the isoform with higher expression in both OM and SC adipose tissues, and was up-regulated 3-fold, together with MMP9 in OB/L-IR as compared to leans. This up-regulation decreased by 23% in OB/-H-IR compared to OB/L-IR. On the contrary, VEGF-B, VEGF-C and VEGF-D, together with MMP15 was down-regulated in both OB/H-IR and OB/L-IR compared to lean patients. Moreover, MMP9 correlated positively and VEGF-C, VEGF-D and MMP15 correlated negatively with HOMA-IR, in both SC and OM. Conclusion We hereby propose that the alteration in MMP15, VEGF-B, VEGF-C and VEGF-D gene expression may be caused by one of the relevant adipose tissue processes related to the development of IR, and the up-regulation of VEGF-A in adipose tissue could have a relationship with the prevention of this pathology. PMID:22471305

  11. Comparing brain-derived neurotrophic factor and ciliary neurotrophic factor secretion of induced neurotrophic factor secreting cells from human adipose and bone marrow-derived stem cells.

    PubMed

    Razavi, Shahnaz; Razavi, Mohamad Reza; Zarkesh Esfahani, Hamid; Kazemi, Mohammad; Mostafavi, Fatemeh Sadat

    2013-08-01

    Adipose derived stem cells (ADSCs) and bone marrow stem cells (BMSCs) may be equally beneficial in treating neurodegenerative diseases. However, ADSCs have practical advantages. In this study, we aimed to induce neurotrophic factors secreting cells in human ADSCs. Then, we compared the level of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor (CNTF) secretion in neurotrophic factors secreting cells from human adipose and bone marrow-derived stem cells. Isolated human ADSCs and BMSCs were induced to neurotrophic factor (NTF)-secreting cells. The levels of expression and secretion of BDNF and CTNF of induced cells were assessed using immunocytochemical, Real-Time polymerase chain reaction, and enzyme linked immunosorbent assay (ELISA). The level of BDNF significantly increased in both the induced mesenchymal stem cells (MSCs) relative to ADSCs and the BMSCs (P < 0.01). Moreover, ELISA analysis showed that the release of BDNF in the induced BMSCs was almost twofold more than the induced ADSCs. Overall, NTF-secreting factor cells derived BMSCs and ADSCs could secret a range of different growth factors. Therefore, the variation in neurotrophic factors of different induced MSC populations suggest the possible beneficial effect of each specific kind of neurotrophic factor secreting cells for the treatment of a particular neurodegenerative disease. PMID:23944834

  12. Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter.

    PubMed

    Zhong, Juan; Guo, Bin; Xie, Jing; Deng, Shuwen; Fu, Na; Lin, Shiyu; Li, Guo; Lin, Yunfeng; Cai, Xiaoxiao

    2016-01-01

    Adipose-derived stem cells (ASCs) and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity. Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes. However, the paracrine action of ASCs on chondrocytes needs to be further elucidated. In this study, we established a co-culture system to achieve cell-to-cell and cell-to-tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1% fetal bovine serum to mimic the physiological microenvironment. In ASCs, we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor B (VEGFB), hypoxia inducible factor-1α (HIF-1α), fibroblast growth factor-2 (FGF-2), and transforming growth factor-β1 significantly increased after co-culture in comparison with mono-culture. In chondrocytes, VEGFA was significantly enhanced after co-culture. Unexpectedly, the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono-culture group. Meanwhile, among all the growth factors screened, we found that the BMP family members BMP-2, BMP-4, and BMP-5 were down-regulated and that VEGFB, HIF-1α, FGF-2, and PDGF were significantly decreased after co-culture. These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering. PMID:26848404

  13. Crosstalk between adipose-derived stem cells and chondrocytes: when growth factors matter

    PubMed Central

    Zhong, Juan; Guo, Bin; Xie, Jing; Deng, Shuwen; Fu, Na; Lin, Shiyu; Li, Guo; Lin, Yunfeng; Cai, Xiaoxiao

    2016-01-01

    Adipose-derived stem cells (ASCs) and mesenchymal stem cells are promising for tissue repair because of their multilineage differentiation capacity. Our previous data confirmed that the implantation of mixed ASCs and chondrocytes into cartilage defects induced desirable in vivo healing outcomes. However, the paracrine action of ASCs on chondrocytes needs to be further elucidated. In this study, we established a co-culture system to achieve cell-to-cell and cell-to-tissue crosstalk and explored the soluble growth factors in both ASCs and chondrocytes supplemented with 1% fetal bovine serum to mimic the physiological microenvironment. In ASCs, we screened for growth factors by semi-quantitative PCR and quantitative real-time PCR and found that the expression of bone morphogenetic protein 2 (BMP-2), vascular endothelial growth factor B (VEGFB), hypoxia inducible factor-1α (HIF-1α), fibroblast growth factor-2 (FGF-2), and transforming growth factor-β1 significantly increased after co-culture in comparison with mono-culture. In chondrocytes, VEGFA was significantly enhanced after co-culture. Unexpectedly, the expression of collagen II and aggrecan was significantly down-regulated in the co-culture group compared with the mono-culture group. Meanwhile, among all the growth factors screened, we found that the BMP family members BMP-2, BMP-4, and BMP-5 were down-regulated and that VEGFB, HIF-1α, FGF-2, and PDGF were significantly decreased after co-culture. These results suggest that crosstalk between ASCs and chondrocytes is a pathway through the regulated growth factors that might have potential in cartilage repair and regeneration and could be useful for tissue engineering. PMID:26848404

  14. Patterns of gene expression in pig adipose tissue: transforming growth factors, interferons, interleukins and apolipoproteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Total RNA was collected at slaughter from outer s.c. adipose tissue (OSQ), middle s.c. adipose tissue (MSQ), ovary, uterus, hypothalamus, and pituitary tissues samples from gilts at 90, 150, and 210 d ( n =5 / age). Dye labeled cDNA probes were hybridized to custom microarrays (70 mer oligonucleotid...

  15. Mitogenic and chondrogenic effects of fibroblast growth factor-2 in adipose-derived mesenchymal cells

    SciTech Connect

    Chiou, Michael; Xu Yue; Longaker, Michael T. . E-mail: Longaker@stanford.edu

    2006-05-05

    Adipose-derived mesenchymal cells (AMCs) have demonstrated a great capacity for differentiating into bone, cartilage, and fat. Studies using bone marrow-derived mesenchymal cells (BMSCs) have shown that fibroblast growth factor (FGF)-2, a potent mitogenic factor, plays an important role in tissue engineering due to its effects in proliferation and differentiation for mesenchymal cells. The aim of this study was to investigate the function of FGF-2 in AMC chondrogenic differentiation and its possible contributions to cell-based therapeutics in skeletal tissue regeneration. Data demonstrated that FGF-2 significantly promoted the proliferation of AMCs and enhanced chondrogenesis in three-dimensional micromass culture. Moreover, priming AMCs with treatment of FGF-2 at 10 ng/ml demonstrated that cells underwent chondrogenic phenotypic differentiation, possibly by inducing N-Cadherin, FGF-receptor 2, and transcription factor Sox9. Our results indicated that FGF-2 potentiates chondrogenesis in AMCs, similar to its functions in BMSCs, suggesting the versatile potential applications of FGF-2 in skeletal regeneration and cartilage repair.

  16. Adipose Stem Cell Microbeads as Production Sources for Chondrogenic Growth Factors

    PubMed Central

    Lee, Christopher S.D.; Nicolini, Anthony M.; Watkins, Elyse A.; Burnsed, Olivia A.; Boyan, Barbara D.; Schwartz, Zvi

    2014-01-01

    Microencapsulating stem cells in injectable microbeads can enhance delivery and localization, but their ability to act as growth factor production sources is still unknown. To address this concern, growth factor mRNA levels and production from alginate microbeads with encapsulated human adipose stem cells (ASC microbeads) cultured in both growth and chondrogenic media (GM and CM) were measured over a two week period. Human ASCs in microbeads were either commercially purchased (Lonza) or isolated from six human donors and compared to human ASCs on tissue culture polystyrene (TCPS). The effects of crosslinking and alginate compositions on growth factor mRNA levels and production were also determined. Secretion profiles of IGF-I, TGF-β3 and VEGF-A from commercial human ASC microbeads were linear and at a significantly higher rate than TCPS cultures over two weeks. For human ASCs derived from different donors, microencapsulation increased pthlh and both IGF-I and TGF-β3 secretion. CM decreased fgf2 and VEGF-A secretion from ASC microbeads derived from the same donor population. Crosslinking microbeads in BaCl2 instead of CaCl2 did not eliminate microencapsulation’s beneficial effects, but did decrease IGF-I production. Increasing the guluronate content of the alginate microbead increased IGF-I retention. Decreasing alginate molecular weight eliminated the effects microencapsulation had on increasing IGF-I secretion. This study demonstrated that microencapsulation can enhance chondrogenic growth factor production and that chondrogenic medium treatment can decrease angiogenic growth factor production from ASCs, making these cells a potential source for paracrine factors that can stimulate cartilage regeneration. PMID:25705097

  17. Adenovirus-mediated expression of growth and differentiation factor-5 promotes chondrogenesis of adipose stem cells.

    PubMed

    Feng, Gang; Wan, Yuqing; Balian, Gary; Laurencin, Cato T; Li, Xudong

    2008-06-01

    The repair of articular cartilage injuries is impeded by the avascular and non-innervated nature of cartilage. Transplantation of autologous chondrocytes has a limited ability to augment the repair process due to the highly differentiated state of chondrocytes and the risks of donor-site morbidity. Mesenchymal stem cells can undergo chondrogenesis in the presence of growth factors for cartilage defect repair. Growth and differentiation factor-5 (GDF5) plays an important role in chondrogenesis. In this study, we examined the effects of GDF5 on chondrogenesis of adipose-derived stem cells (ADSCs) and evaluate the chondrogenic potentials of GDF5 genetically engineered ADSCs using an in vitro pellet culture model. Rat ADSCs were grown as pellet cultures and treated with chondrogenic media (CM). Induction of GDF5 by an adenovirus (Ad-GDF5) was compared with exogenous supplementation of GDF5 (100 ng/ml) and transforming growth factor-beta (TGF-beta1; 10 ng/ml). The ADSCs underwent chondrogenic differentiation in response to GDF5 exposure as demonstrated by production of proteoglycan, and up-regulation of collagen II and aggrecan at the protein and mRNA level. The chondrogenic potential of a one-time infection with Ad-GDF5 was weaker than exogenous GDF5, but equal to that of TGF-beta1. Stimulation with growth factors or CM alone induced transient expression of the mRNA for collagen X, indicating a need for optimization of the CM. Our findings indicate that GDF5 is a potent inducer of chondrogenesis in ADSCs, and that ADSCs genetically engineered to express prochondrogenic growth factors, such as GDF5, may be a promising therapeutic cell source for cartilage tissue engineering. PMID:18569021

  18. Association of Parental Overweight and Cardiometabolic Diseases and Pediatric Adiposity and Lifestyle Factors with Cardiovascular Risk Factor Clustering in Adolescents

    PubMed Central

    Lee, Chun-Ying; Lin, Wei-Ting; Tsai, Sharon; Hung, Yu-Chan; Wu, Pei-Wen; Yang, Yu-Cheng; Chan, Te-Fu; Huang, Hsiao-Ling; Weng, Yao-Lin; Chiu, Yu-Wen; Huang, Chia-Tsuan; Lee, Chien-Hung

    2016-01-01

    Cardiometabolic risk factors or their precursors are observed in childhood and may continue into adulthood. We investigated the effects of parental overweight and cardiometabolic diseases and pediatric lifestyle factors on the clustering of cardiovascular risk factors among adolescents, and examined the mediating and modifying effects of pediatric adiposity on these associations. Representative adolescents (n = 2727; age, 12–16 years) were randomly recruited through multistage stratified sampling from 36 schools in Southern Taiwan. Adolescent and parent surveys were conducted in schools and participant homes, respectively. Their demographic factors, diet patterns, and physical, anthropometric, and clinical parameters were collected and analyzed. Adolescents with 1–2 and ≥3 risk components for pediatric metabolic syndrome (MetS) were defined as potential MetS (pot-MetS) and MetS, respectively. Adolescents whose parents were overweight/obese, or with diabetes and hypertension had a higher prevalence ratio of pot-MetS and MetS (1.5–1.6 and 1.9–4.2-fold, respectively). Low physical activity (<952.4 MET·min/week), long screen time (≥3 h/day) and high sugar-sweetened beverage intake (>500 mL/day) were associated with a 3.3- (95% confidence intervals (CI) = 1.5–7.3), 2.2- (95% CI = 1.1–4.4), and 26.9-fold (95% CI = 3.2–229.0) odds ratio (OR) of MetS, respectively. Pediatric body mass index (BMI) accounted for 18.8%–95.6% and 16.9%–60.3% increased prevalence ratios of these parental and pediatric risk factors for MetS. The OR of pot-MetS + MetS for sugar-sweetened beverage consumption was multiplicatively enhanced among adolescents with overweight/obesity (combined OR, 8.6-fold (95% CI = 4.3–17.3); p for multiplicative interaction, 0.009). The results suggest that parental overweight and cardiometabolic diseases and pediatric sedentary and high sugar-intake lifestyles correlate with the development of adolescent MetS, and an elevated child BMI

  19. Association of Parental Overweight and Cardiometabolic Diseases and Pediatric Adiposity and Lifestyle Factors with Cardiovascular Risk Factor Clustering in Adolescents.

    PubMed

    Lee, Chun-Ying; Lin, Wei-Ting; Tsai, Sharon; Hung, Yu-Chan; Wu, Pei-Wen; Yang, Yu-Cheng; Chan, Te-Fu; Huang, Hsiao-Ling; Weng, Yao-Lin; Chiu, Yu-Wen; Huang, Chia-Tsuan; Lee, Chien-Hung

    2016-01-01

    Cardiometabolic risk factors or their precursors are observed in childhood and may continue into adulthood. We investigated the effects of parental overweight and cardiometabolic diseases and pediatric lifestyle factors on the clustering of cardiovascular risk factors among adolescents, and examined the mediating and modifying effects of pediatric adiposity on these associations. Representative adolescents (n = 2727; age, 12-16 years) were randomly recruited through multistage stratified sampling from 36 schools in Southern Taiwan. Adolescent and parent surveys were conducted in schools and participant homes, respectively. Their demographic factors, diet patterns, and physical, anthropometric, and clinical parameters were collected and analyzed. Adolescents with 1-2 and ≥3 risk components for pediatric metabolic syndrome (MetS) were defined as potential MetS (pot-MetS) and MetS, respectively. Adolescents whose parents were overweight/obese, or with diabetes and hypertension had a higher prevalence ratio of pot-MetS and MetS (1.5-1.6 and 1.9-4.2-fold, respectively). Low physical activity (<952.4 MET·min/week), long screen time (≥3 h/day) and high sugar-sweetened beverage intake (>500 mL/day) were associated with a 3.3- (95% confidence intervals (CI) = 1.5-7.3), 2.2- (95% CI = 1.1-4.4), and 26.9-fold (95% CI = 3.2-229.0) odds ratio (OR) of MetS, respectively. Pediatric body mass index (BMI) accounted for 18.8%-95.6% and 16.9%-60.3% increased prevalence ratios of these parental and pediatric risk factors for MetS. The OR of pot-MetS + MetS for sugar-sweetened beverage consumption was multiplicatively enhanced among adolescents with overweight/obesity (combined OR, 8.6-fold (95% CI = 4.3-17.3); p for multiplicative interaction, 0.009). The results suggest that parental overweight and cardiometabolic diseases and pediatric sedentary and high sugar-intake lifestyles correlate with the development of adolescent MetS, and an elevated child BMI explains a part of these

  20. Retinol binding protein 4 is associated with adiposity-related co-morbidity risk factors in children

    PubMed Central

    Conroy, Rushika; Espinal, Yomery; Fennoy, Ilene; Accacha, Siham; Boucher-Berry, Claudia; Carey, Dennis E.; Close, Sharron; DeSantis, Deborah; Gupta, Rishi; Hassoun, Abeer A.; Iazzetti, Loretta; Jacques, Fabean J.; Jean, Amy M.; Michel, Lesly; Pavlovich, Katherine; Rapaport, Robert; Rosenfeld, Warren; Shamoon, Elisabeth; Shelov, Steven; Speiser, Phyllis W.; Ten, Svetlana; Rosenbaum, Michael

    2016-01-01

    Objective In adults, elevated levels of retinol binding protein 4 (RBP4) have been associated with biochemical markers of adiposity-related co-morbidities including insulin resistance, dyslipidemia, hypertension, and abdominal obesity. This study examined the relationship between RBP4 and risk factors for co-morbidities of adiposity in a population of ethnically diverse children in early- to mid-adolescence in the public school system of New York City. Materials/methods We analyzed anthropometric (body mass index, % body fat, waist circumference), metabolic (lipids, glucose), and inflammatory (TNF-α, interleukin-6, C-reactive protein, adiponectin) markers for adiposity-related co-morbidities and serum alanine aminotransferase (ALT) in 106 school children (65 males, 41 females) 11–15 years of age (mean ± SD = 13.0 ± 0.1 years) who were enrolled in the Reduce Obesity and Diabetes (ROAD) project. Insulin sensitivity was assessed by quantitative insulin sensitivity check index. Insulin secretory capacity was measured as acute insulin response and glucose disposal index. Results Serum RBP4 was significantly correlated directly with ALT, triglycerides, and triglyceride z-score, and inversely correlated with adiponectin. Correlations with ALT and adiponectin remained significant when corrected for % body fat, age, and gender. There were significant ethnic differences in the relationship of RBP4 to ALT, glucose disposal index and adiponectin. Conclusions In early- to mid-adolescents, circulating concentrations of RBP4 are correlated with multiple risk factors for adiposity-related co-morbidities. The observation that many associations persisted when corrected for % body fat, suggests that RBP4 can be viewed as an independent marker of adiposity-related co-morbidity risk in children. PMID:22308842

  1. Vascular endothelial growth factor is important for brown adipose tissue development and maintenance.

    PubMed

    Bagchi, Mandrita; Kim, Leo A; Boucher, Jeremie; Walshe, Tony E; Kahn, C Ronald; D'Amore, Patricia A

    2013-08-01

    Vascular endothelial growth factor (VEGF) is critical for angiogenesis, but also has pleiotropic effects on several nonvascular cells. Our aim was to investigate the role of VEGF in brown adipose tissue (BAT). We show that VEGF expression increases 2.5-fold during differentiation of cultured murine brown adipocytes and that VEGF receptor-2 is phosphorylated, indicating VEGF signaling. VEGF increased proliferation in brown preadipocytes in vitro by 70%, and blockade of VEGF signaling using anti-VEGFR2 antibody DC101 increased brown adipocyte apoptosis, as determined by cell number and activation of caspase 3. Systemic VEGF neutralization in mice, accomplished by adenoviral expression of soluble Flt1, resulted in 7-fold increase in brown adipocyte apoptosis, mitochondrial degeneration, and increased mitophagy compared to control mice expressing a null adenovirus. Absence of the heparan sulfate-binding VEGF isoforms, VEGF164 and VEGF188, resulted in abnormal BAT development in mice at E15.5, with fewer brown adipocytes and lower mitochondrial protein compared to wild-type littermates. These results suggest a role for VEGF in brown adipocytes and preadipocytes to promote survival, proliferation, and normal mitochondria and development.

  2. Expression and functional analyses of Krüppel-like factor 3 in chicken adipose tissue.

    PubMed

    Zhang, Zhi-Wei; Wu, Chun-Yan; Li, Hui; Wang, Ning

    2014-01-01

    Studies in mammalian species showed that Krüppel-like factor 3 (KLF3) regulated adipose tissue development. However, it was not reported in chicken. In the current study, we found that during the growth and development of abdominal fat tissue, chicken KLF3 (Gallus gallus KLF3, gKLF3) was consecutively expressed, and its transcripts were higher at 7 weeks of age and lower at 10 weeks of age in lean broilers than in fat broilers. In addition, gKLF3 overexpression suppressed chicken CCAAT/enhancer binding protein alpha (C/EBPα), fatty acid binding protein 4 (FABP4), fatty acid synthase (FASN), and lipoprotein lipase (LPL) promoter activities, but increased chicken peroxisome proliferator-activated receptor gamma (PPARγ) promoter activity. Additionally, point mutagenesis analysis showed that the substitution of Asp by Gly within the Pro-Val-Asp-Leu-Thr (PVDLT) motif of gKLF3 significantly reduced the ability of gKLF3 to regulate the promoter activities of FABP4, FASN, LPL, C/EBPα, and PPARγ.

  3. Factors Associated with Adiposity, Lipid Profile Disorders and the Metabolic Syndrome Occurrence in Premenopausal and Postmenopausal Women

    PubMed Central

    Suliga, Edyta; Kozieł, Dorota; Cieśla, Elżbieta; Rębak, Dorota; Głuszek, Stanisław

    2016-01-01

    The aim of the study was the assessment of the dependencies between a woman’s menopausal status and adiposity, lipid profile and metabolic syndrome occurrence, as well as finding out whether the correlations between the socio-demographic profile and lifestyle elements and adiposity, lipid profile and the risk of MetS are the same before and after menopause. A cross-sectional study was carried out on 3636 women, aged between 40–59, which involved a questionnaire interview, anthropometric measurements and fasting blood samples, on the basis of which the concentration of triglycerides, cholesterol and glucose was estimated. Before menopause, a greater adiposity (BMIβ = 0.08; %BFβ = 0.07; WCβ = 0.06) was characteristic for women living in a stable relationship than for single women. Women who smoked in the past were characterized by a higher BMI (β = 0.09) and WC (β = 0.06) in comparison with women who have never smoked, while after menopause a greater adiposity (%BFβ = 0.12) and a worse lipid profile (TCβ = 0.08; LDLβ = 0.07; HDLβ = -0.05; TGβ = 0.14) were present in women currently smoking, in comparison to women who have never smoked. After menopause, in women who had two or more children, a greater adiposity (BMIβ = 0.07 and 0.09; %BFβ = 0.05 and 0.07) and a higher risk of MetS (OR = 1.22, 95%CI: 1.03–1.44) was observed compared to nulliparous women, than before menopause. In women with a higher level of education, the risk of MetS after menopause was significantly lower compared with women with a lower level of education (OR = 0.74, 95%CI: 0.61–0.90). Physical activity after menopause had a higher influence on the decrease in the women’s adiposity (BMIβ = -0.11 v. -0.06; %BFβ = -0.11 v. -0.06; WCβ = -0.14 v. -0.08), than before menopause. In women not undergoing hormone replacement therapy, some of the socio-demographic factors and lifestyle elements affected adiposity, lipid profile and the risk of MetS differently before and after

  4. Pigment epithelium-derived factor regulates microvascular permeability through adipose triglyceride lipase in sepsis.

    PubMed

    He, Ting; Hu, Jiongyu; Yan, Guangning; Li, Lingfei; Zhang, Dongxia; Zhang, Qiong; Chen, Bing; Huang, Yuesheng

    2015-07-01

    The integrity of the vascular barrier, which is essential to blood vessel homoeostasis, can be disrupted by a variety of soluble permeability factors during sepsis. Pigment epithelium-derived factor (PEDF), a potent endogenous anti-angiogenic molecule, is significantly increased in sepsis, but its role in endothelial dysfunction has not been defined. To assess the role of PEDF in the vasculature, we evaluated the effects of exogenous PEDF in vivo using a mouse model of cecal ligation and puncture (CLP)-induced sepsis and in vitro using human dermal microvascular endothelial cells (HDMECs). In addition, PEDF was inhibited using a PEDF-monoclonal antibody (PEDF-mAb) or recombinant lentivirus vectors targeting PEDF receptors, including adipose triglyceride lipase (ATGL) and laminin receptor (LR). Our results showed that exogenous PEDF induced vascular hyperpermeability, as measured by extravasation of Evan's Blue (EB), dextran and microspheres in the skin, blood, trachea and cremaster muscle, both in a normal state and under conditions of sepsis. In control and LR-shRNA-treated HDMECs, PEDF alone or in combination with inflammatory mediators resulted in activation of RhoA, which was accompanied by actin rearrangement and disassembly of intercellular junctions, impairing endothelial barrier function. But in ATGL-shRNA-treated HDMECs, PEDF failed to induce the aforementioned alterations, suggesting that PEDF-induced hyperpermeability was mediated through the ATGL receptor. These results reveal a novel role for PEDF as a potential vasoactive substance in septic vascular hyperpermeability. Furthermore, our results suggest that PEDF and ATGL may serve as therapeutic targets for managing vascular hyperpermeability in sepsis. PMID:25700221

  5. Cloning changes the response to obesity of innate immune factors in blood, liver, and adipose tissues in domestic pigs.

    PubMed

    Rødgaard, Tina; Skovgaard, Kerstin; Stagsted, Jan; Heegaard, Peter M H

    2013-06-01

    The objective of this study was to evaluate the usefulness of cloned pigs as porcine obesity models reflecting obesity-associated changes in innate immune factor gene expression profiles. Liver and adipose tissue expression of 43 innate immune genes as well as serum concentrations of six immune factors were analyzed in lean and diet-induced obese cloned domestic pigs and compared to normal domestic pigs (obese and lean). The number of genes affected by obesity was lower in cloned animals than in control animals. All genes affected by obesity in adipose tissues of clones were downregulated; both upregulation and downregulation were observed in the controls. Cloning resulted in a less differentiated adipose tissue expression pattern. Finally, the serum concentrations of two acute-phase proteins (APPs), haptoglobin (HP) and orosomucoid (ORM), were increased in obese clones as compared to obese controls as well as lean clones and controls. Generally, the variation in phenotype between individual pigs was not reduced in cloned siblings as compared to normal siblings. Therefore, we conclude that cloning limits both the number of genes responding to obesity as well as the degree of tissue-differentiated gene expression, concomitantly with an increase in APP serum concentrations only seen in cloned, obese pigs. This may suggest that the APP response seen in obese, cloned pigs is a consequence of the characteristic skewed gene response to obesity in cloned pigs, as described in this work. This should be taken into consideration when using cloned animals as models for innate responses to obesity.

  6. Adipose tissue angiogenesis assay.

    PubMed

    Rojas-Rodriguez, Raziel; Gealekman, Olga; Kruse, Maxwell E; Rosenthal, Brittany; Rao, Kishore; Min, Soyun; Bellve, Karl D; Lifshitz, Lawrence M; Corvera, Silvia

    2014-01-01

    Changes in adipose tissue mass must be accompanied by parallel changes in microcirculation. Investigating the mechanisms that regulate adipose tissue angiogenesis could lead to better understanding of adipose tissue function and reveal new potential therapeutic strategies. Angiogenesis is defined as the formation of new capillaries from existing microvessels. This process can be recapitulated in vitro, by incubation of tissue in extracellular matrix components in the presence of pro-angiogenic factors. Here, we describe a method to study angiogenesis from adipose tissue fragments obtained from mouse and human tissue. This assay can be used to define effects of diverse factors added in vitro, as well as the role of endogenously produced factors on angiogenesis. We also describe approaches to quantify angiogenic potential for the purpose of enabling comparisons between subjects, thus providing information on the role of physiological conditions of the donor on adipose tissue angiogenic potential.

  7. Augmented expression and secretion of adipose-derived pigment epithelium-derived factor does not alter local angiogenesis or contribute to the development of systemic metabolic derangements.

    PubMed

    Lakeland, Thomas V; Borg, Melissa L; Matzaris, Maria; Abdelkader, Amany; Evans, Roger G; Watt, Matthew J

    2014-06-15

    Impaired coupling of adipose tissue expansion and vascularization is proposed to lead to adipocyte hypoxia and inflammation, which in turn contributes to systemic metabolic derangements. Pigment epithelium-derived factor (PEDF) is a powerful antiangiogenic factor that is secreted by adipocytes, elevated in obesity, and implicated in the development of insulin resistance. We explored the angiogenic and metabolic role of adipose-derived PEDF through in vivo studies of mice with overexpression of PEDF in adipocytes (PEDF-aP2). PEDF expression in white adipocytes and PEDF secretion from adipose tissue was increased in transgenic mice, but circulating levels of PEDF were not increased. Overexpression of PEDF did not alter vascularization, the partial pressure of O2, cellular hypoxia, or gene expression of inflammatory markers in adipose tissue. Energy expenditure and metabolic substrate utilization, body mass, and adiposity were not altered in PEDF-aP2 mice. Whole body glycemic control was normal as assessed by glucose and insulin tolerance tests, and adipocyte-specific glucose uptake was unaffected by PEDF overexpression. Adipocyte lipolysis was increased in PEDF-aP2 mice and associated with increased adipose triglyceride lipase and decreased perilipin 1 expression. Experiments conducted in mice rendered obese by high-fat feeding showed no differences between PEDF-aP2 and wild-type mice for body mass, adiposity, whole body energy expenditure, glucose tolerance, or adipose tissue oxygenation. Together, these data indicate that adipocyte-generated PEDF enhances lipolysis but question the role of PEDF as a major antiangiogenic or proinflammatory mediator in adipose tissue in vivo.

  8. Downstream signaling pathways in mouse adipose tissues following acute in vivo administration of fibroblast growth factor 21.

    PubMed

    Muise, Eric S; Souza, Sandra; Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-Yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P; Hendrickson, Ronald C; Thompson, John R; Mu, James; Berger, Joel P; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation.

  9. Downstream Signaling Pathways in Mouse Adipose Tissues Following Acute In Vivo Administration of Fibroblast Growth Factor 21

    PubMed Central

    Chi, An; Tan, Yejun; Zhao, Xuemei; Liu, Franklin; Dallas-yang, Qing; Wu, Margaret; Sarr, Tim; Zhu, Lan; Guo, Hongbo; Li, Zhihua; Li, Wenyu; Hu, Weiwen; Jiang, Guoqiang; Paweletz, Cloud P.; Hendrickson, Ronald C.; Thompson, John R.; Mu, James; Berger, Joel P.; Mehmet, Huseyin

    2013-01-01

    FGF21 is a novel secreted protein with robust anti-diabetic, anti-obesity, and anti-atherogenic activities in preclinical species. In the current study, we investigated the signal transduction pathways downstream of FGF21 following acute administration of the growth factor to mice. Focusing on adipose tissues, we identified FGF21-mediated downstream signaling events and target engagement biomarkers. Specifically, RNA profiling of adipose tissues and phosphoproteomic profiling of adipocytes, following FGF21 treatment revealed several specific changes in gene expression and post-translational modifications, specifically phosphorylation, in several relevant proteins. Affymetrix microarray analysis of white adipose tissues isolated from both C57BL/6 (fed either regular chow or HFD) and db/db mice identified over 150 robust potential RNA transcripts and over 50 potential secreted proteins that were changed greater than 1.5 fold by FGF21 acutely. Phosphoprofiling analysis identified over 130 phosphoproteins that were modulated greater than 1.5 fold by FGF21 in 3T3-L1 adipocytes. Bioinformatic analysis of the combined gene and phosphoprotein profiling data identified a number of known metabolic pathways such as glucose uptake, insulin receptor signaling, Erk/Mapk signaling cascades, and lipid metabolism. Moreover, a number of novel events with hitherto unknown links to FGF21 signaling were observed at both the transcription and protein phosphorylation levels following treatment. We conclude that such a combined "omics" approach can be used not only to identify robust biomarkers for novel therapeutics but can also enhance our understanding of downstream signaling pathways; in the example presented here, novel FGF21-mediated signaling events in adipose tissue have been revealed that warrant further investigation. PMID:24039848

  10. Metabolic factors, adipose tissue, and plasminogen activator inhibitor-1 levels in Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plasminogen activator inhibitor-1 (PAI-1) production by adipose tissue is increased in obesity, and its circulating levels are high in type 2 diabetes. PAI-1 increases cardiovascular risk by favoring clot stability, interfering with vascular remodeling, or both. We investigated in obese diabetic per...

  11. Adiposity is associated with DNA methylation profile in adipose tissue

    PubMed Central

    Agha, Golareh; Houseman, E Andres; Kelsey, Karl T; Eaton, Charles B; Buka, Stephen L; Loucks, Eric B

    2015-01-01

    Background: Adiposity is a risk factor for type 2 diabetes and cardiovascular disease, suggesting an important role for adipose tissue in the development of these conditions. The epigenetic underpinnings of adiposity are not well understood, and studies of DNA methylation in relation to adiposity have rarely focused on target adipose tissue. Objectives were to evaluate whether genome-wide DNA methylation profiles in subcutaneous adipose tissue and peripheral blood leukocytes are associated with measures of adiposity, including central fat mass, body fat distribution and body mass index. Methods: Participants were 106 men and women (mean age 47 years) from the New England Family Study. DNA methylation was evaluated using the Infinium HumanMethylation450K BeadChip. Adiposity phenotypes included dual-energy X-ray absorptiometry-assessed android fat mass, android:gynoid fat ratio and trunk:limb fat ratio, as well as body mass index. Results: Adipose tissue genome-wide DNA methylation profiles were associated with all four adiposity phenotypes, after adjusting for race, sex and current smoking (omnibus p-values <0.001). After further adjustment for adipose cell-mixture effects, associations with android fat mass, android:gynoid fat ratio, and trunk:limb fat ratio remained. In gene-specific analyses, adiposity phenotypes were associated with adipose tissue DNA methylation in several genes that are biologically relevant to the development of adiposity, such as AOC3, LIPE, SOD3, AQP7 and CETP. Blood DNA methylation profiles were not associated with adiposity, before or after adjustment for blood leukocyte cell mixture effects. Conclusion: Findings show that DNA methylation patterns in adipose tissue are associated with adiposity. PMID:25541553

  12. An adipoinductive role of inflammation in adipose tissue engineering: key factors in the early development of engineered soft tissues.

    PubMed

    Lilja, Heidi E; Morrison, Wayne A; Han, Xiao-Lian; Palmer, Jason; Taylor, Caroline; Tee, Richard; Möller, Andreas; Thompson, Erik W; Abberton, Keren M

    2013-05-15

    Tissue engineering and cell implantation therapies are gaining popularity because of their potential to repair and regenerate tissues and organs. To investigate the role of inflammatory cytokines in new tissue development in engineered tissues, we have characterized the nature and timing of cell populations forming new adipose tissue in a mouse tissue engineering chamber (TEC) and characterized the gene and protein expression of cytokines in the newly developing tissues. EGFP-labeled bone marrow transplant mice and MacGreen mice were implanted with TEC for periods ranging from 0.5 days to 6 weeks. Tissues were collected at various time points and assessed for cytokine expression through ELISA and mRNA analysis or labeled for specific cell populations in the TEC. Macrophage-derived factors, such as monocyte chemotactic protein-1 (MCP-1), appear to induce adipogenesis by recruiting macrophages and bone marrow-derived precursor cells to the TEC at early time points, with a second wave of nonbone marrow-derived progenitors. Gene expression analysis suggests that TNFα, LCN-2, and Interleukin 1β are important in early stages of neo-adipogenesis. Increasing platelet-derived growth factor and vascular endothelial cell growth factor expression at early time points correlates with preadipocyte proliferation and induction of angiogenesis. This study provides new information about key elements that are involved in early development of new adipose tissue.

  13. Patterns of gene expression in pig adipose tissue: insulin-like growth factor system proteins, neuropeptide Y (NPY), NPY receptors, neurotrophic factors and other secreted factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Total RNA was collected at slaughter from outer subcutaneous adipose tissue (OSQ) and middle subcutaneous adipose tissue (MSQ) samples from gilts at 90, 150, and 210 d ( n =5 / age). Dye labeled cDNA probes were hybridized to custom microarrays (70 mer oligonucleotides) representing over 600 pig gen...

  14. Neuroendocrine factors in the regulation of inflammation: excessive adiposity and calorie restriction.

    PubMed

    Fontana, Luigi

    2009-01-01

    Acute inflammation is usually a self-limited life preserving response, triggered by pathogens and/or traumatic injuries. This transient response normally leads to removal of harmful agents and to healing of the damaged tissues. In contrast, unchecked or chronic inflammation can lead to persistent tissue and organ damage by activated leukocytes, cytokines, or collagen deposition. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction without malnutrition exerts a potent anti-inflammatory effect. As individuals accumulate fat and their adipocytes enlarge, adipose tissue undergoes molecular and cellular alterations, macrophages accumulate, and inflammation ensues. Overweight/obese subjects have significantly higher plasma concentrations of C-reactive protein and several cytokines, including IL-6, IL-8, IL-18, and TNF-alpha. Experimental animals on a chronic CR regimen, instead, have low levels of circulating inflammatory cytokines, low blood lymphocyte levels, reduced production of inflammatory cytokines by the white blood cells in response to stimulation, and cortisol levels in the high normal range. Recent data demonstrate that CR exerts a powerful anti-inflammatory effect also in non-human primates and humans. Multiple metabolic and neuroendocrine mechanisms are responsible for the CR-mediated anti-inflammatory effects, including reduced adiposity and secretion of pro-inflammatory adipokines, enhanced glucocorticoid production, reduced plasma glucose and advanced glycation end-product concentrations, increased parasympathetic tone, and increased ghrelin production. Measuring tissue specific effects of CR using genomic, proteomic, and metabolomic techniques in humans will foster the understanding of the complex biological processes involved in the anti-inflammatory and anti-aging effects of CR.

  15. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    SciTech Connect

    Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  16. The effects of BMP6 overexpression on adipose stem cell chondrogenesis: Interactions with dexamethasone and exogenous growth factors.

    PubMed

    Diekman, Brian O; Estes, Bradley T; Guilak, Farshid

    2010-06-01

    Adipose-derived stem cells (ASCs) are multipotent progenitors that can be chondrogenically induced by growth factors such as bone morphogenetic protein 6 (BMP-6). We hypothesized that nonviral transfection of a BMP-6 construct (pcDNA3-BMP6) would induce chondrogenic differentiation of ASCs encapsulated in alginate beads and that differentiation would be enhanced by the presence of the synthetic glucocorticoid dexamethasone (DEX) or the combination of epidermal growth factor (EGF), fibroblast growth factor-2 (FGF-2), and transforming growth factor beta-1 (TGF-beta1), collectively termed expansion factors (EFs). Chondrogenesis was assessed using quantitative real-time polymerase chain reaction for types I, II, and X collagen, aggrecan, and BMP6. Immunohistochemistry was performed with antibodies for types I, II, and X collagen and chondroitin-4-sulfate. BMP6 overexpression alone induced a moderate chondrogenic response. The inclusion of EFs promoted robust type II collagen expression but also increased type I and X collagen deposition, consistent with a hypertrophic chondrocyte phenotype. Early gene expression data indicated that DEX was synergistic with BMP-6 for chondrogenesis, but immunohistochemistry at 28 days showed that DEX reduced glycosaminoglycan accumulation. These results suggest that chondrogenic differentiation of ASCs depends on complex interactions among various growth factors and media supplements, as well as the concentration and duration of growth factor exposure. PMID:19722282

  17. Replication of Early B-cell Factor 1 (EBF1) Gene-by-psychosocial Stress Interaction Effects on Central Adiposity in a Korean Population

    PubMed Central

    Min, Jin-Young

    2016-01-01

    Objectives Central obesity plays a major role in the development of many chronic diseases, including cardiovascular disease and cancer. Chronic stress may be involved in the pathophysiology of central obesity. Although several large-scale genome-wide association studies have reported susceptibility genes for central adiposity, the effects of interactions between genes and psychosocial stress on central adiposity have rarely been examined. A recent study focusing on Caucasians discovered the novel gene early B-cell factor 1 (EBF1), which was associated with central obesity-related traits via interactions with stress levels. We aimed to evaluate EBF1 gene-by-stress interaction effects on central adiposity traits, including visceral adipose tissue (VAT), in Korean adults. Methods A total of 1467 Korean adults were included in this study. We selected 22 single-nucleotide polymorphisms (SNPs) in the EBF1 gene and analyzed their interactions with stress on central adiposity using additive, dominant, and recessive genetic modeling. Results The four SNPs that had strong linkage disequilibrium relationships (rs10061900, rs10070743, rs4704967, and rs10056564) demonstrated significant interactions with the waist-hip ratio in the dominant model (pint<0.007). In addition, two other SNPs (rs6556377 and rs13180086) were associated with VAT by interactions with stress levels, especially in the recessive genetic model (pint<0.007). As stress levels increased, the mean values of central adiposity traits according to SNP genotypes exhibited gradual but significant changes (p<0.05). Conclusions These results suggest that the common genetic variants for EBF1 are associated with central adiposity through interactions with stress levels, emphasizing the importance of managing stress in the prevention of central obesity. PMID:27744667

  18. Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model.

    PubMed

    Lu, Zijing; Yuan, Yi; Gao, Jianhua; Lu, Feng

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation.

  19. Regulation of visceral adipose tissue-derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue.

    PubMed

    González, C R; Caminos, J E; Vázquez, M J; Garcés, M F; Cepeda, L A; Angel, A; González, A C; García-Rendueles, M E; Sangiao-Alvarellos, S; López, M; Bravo, S B; Nogueiras, R; Diéguez, C

    2009-07-15

    Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a recently discovered adipocytokine mainly secreted from visceral adipose tissue, which plays a main role in insulin sensitivity. In this study, we have investigated the regulation of vaspin gene expression in rat white adipose tissue (WAT) in different physiological (nutritional status, pregnancy, age and gender) and pathophysiological (gonadectomy, thyroid status and growth hormone deficiency) settings known to be associated with energy homeostasis and alterations in insulin sensitivity. We have determined vaspin gene expression by real-time PCR. Vaspin was decreased after fasting and its levels were partially recovered after leptin treatment. Chronic treatment with metformin increased vaspin gene expression. Vaspin mRNA expression reached the highest peak at 45 days in both sexes after birth and its expression was higher in females than males, but its levels did not change throughout pregnancy. Finally, decreased levels of growth hormone and thyroid hormones suppressed vaspin expression. These findings suggest that WAT vaspin mRNA expression is regulated by nutritional status, and leptin seems to be the nutrient signal responsible for those changes. Vaspin is influenced by age and gender, and its expression is increased after treatment with insulin sensitizers. Finally, alterations in pituitary functions modify vaspin levels. Understanding the molecular mechanisms regulating vaspin will provide new insights into the pathogenesis of the metabolic syndrome.

  20. Comparative analysis of paracrine factor expression in human adult mesenchymal stem cells derived from bone marrow, adipose, and dermal tissue.

    PubMed

    Hsiao, Sarah Tzu-Feng; Asgari, Azar; Lokmic, Zerina; Sinclair, Rodney; Dusting, Gregory James; Lim, Shiang Yong; Dilley, Rodney James

    2012-08-10

    Human adult mesenchymal stem cells (MSCs) support the engineering of functional tissue constructs by secreting angiogenic and cytoprotective factors, which act in a paracrine fashion to influence cell survival and vascularization. MSCs have been isolated from many different tissue sources, but little is known about how paracrine factor secretion varies between different MSC populations. We evaluated paracrine factor expression patterns in MSCs isolated from adipose tissue (ASCs), bone marrow (BMSCs), and dermal tissues [dermal sheath cells (DSCs) and dermal papilla cells (DPCs)]. Specifically, mRNA expression analysis identified insulin-like growth factor-1 (IGF-1), vascular endothelial growth factor-D (VEGF-D), and interleukin-8 (IL-8) to be expressed at higher levels in ASCs compared with other MSC populations whereas VEGF-A, angiogenin, basic fibroblast growth factor (bFGF), and nerve growth factor (NGF) were expressed at comparable levels among the MSC populations examined. Analysis of conditioned media (CM) protein confirmed the comparable level of angiogenin and VEGF-A secretion in all MSC populations and showed that DSCs and DPCs produced significantly higher concentrations of leptin. Functional assays examining in vitro angiogenic paracrine activity showed that incubation of endothelial cells in ASC(CM) resulted in increased tubulogenic efficiency compared with that observed in DPC(CM). Using neutralizing antibodies we concluded that VEGF-A and VEGF-D were 2 of the major growth factors secreted by ASCs that supported endothelial tubulogenesis. The variation in paracrine factors of different MSC populations contributes to different levels of angiogenic activity and ASCs maybe preferred over other MSC populations for augmenting therapeutic approaches dependent upon angiogenesis.

  1. Tissue engineering of bone: Clinical observations with adipose-derived stem cells, resorbable scaffolds, and growth factors

    PubMed Central

    Sándor, George K. B.

    2012-01-01

    Introduction: Tissue engineering offers a simple, nonallergenic, and viable solution for the reconstruction of human tissues such as bone. With deeper understanding of the stem cell's pathobiology, the unique properties of these tissues can be effectively harnessed for the benefit of the patients. A primary source of mesenchymal stem cells (MSCs) for bone regeneration is from adipose tissue to provide adipose-derived stem cells (ASCs). The interdependency between adipogenesis and osteogenesis has been well established. The objective of this article is to present the preliminary clinical observation with reconstruction of craniofacial osseous defects larger than critical size with ASC. Materials and Methods: Patients with large craniofacial osseous defects only were included in this study. Autogenous fat from the anterior abdominal wall of the patients was harvested from 23 patients, taken to a central tissue banking laboratory and prepared. All patients were reconstructed with ASCs, resorbable scaffolds, and growth factor as required. Vascularized soft tissue beds were prepared for ectopic bone formation and later microvascular translocation as indicated. Results: 23 ASC seeded resorbable scaffolds have been combined with rhBMP-2 and successfully implanted into humans to reconstruct their jaws except for three failures. The failures included one infection and two cases of inadequate bone formation. Discussion: The technique of ASC-aided reconstruction of large defects still remains extremely sensitive as it takes longer duration and is costlier than the conventional standard immediate reconstruction. Preliminary results and clinical observations of these cases are extremely encouraging. In future, probably with evolving technological advances, ASC-aided reconstruction will be regularly used in clinical practise. PMID:23483030

  2. Visceral adiposity syndrome.

    PubMed

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M

    2016-01-01

    The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of

  3. Regulation of adipogenesis by paracrine factors from adipose stromal-vascular fraction - a link to fat depot-specific differences.

    PubMed

    Meissburger, Bettina; Perdikari, Aliki; Moest, Hansjörg; Müller, Sebastian; Geiger, Matthias; Wolfrum, Christian

    2016-09-01

    Visceral and subcutaneous adipose tissue depots have distinct features and contribute differentially to the development of metabolic dysfunction. We show here that adipocyte differentiation in subcutaneous stromal-vascular fraction (SVF) is increased compared to visceral SVF, however this increased differentiation capacity seems not to be due to changes in the number of adipocyte precursor cells. Rather, we demonstrate that secreted heat-sensitive factors from the SVF can inhibit adipocyte differentiation and that this effect is higher in visceral than in subcutaneous SVF, suggesting that visceral SVF is a source of secreted factors that can inhibit adipocyte formation. In order to explore secreted proteins that potentially inhibit differentiation in visceral preadipocytes we analyzed the secretome of both SVFs which led to the identification of 113 secreted proteins with an overlap of 42%. Further expression analysis in both depots revealed 16 candidates that were subsequently analyzed in a differentiation screen using an adenoviral knockdown system. From this analysis we were able to identify two potential inhibitory candidates, namely decorin (Dcn) and Sparc-like 1 (Sparcl1). We could show that ablation of either candidate enhanced adipogenesis in visceral preadipocytes, while treatment of primary cultures with recombinant Sparcl1 and Dcn blocked adipogenesis in a dose dependent manner. In conclusion, our data suggests that the differences in adipogenesis between depots might be due to paracrine and autocrine feedback mechanisms which could in turn contribute to metabolic homeostasis. PMID:27317982

  4. Waist Circumference, Body Mass Index, and Other Measures of Adiposity in Predicting Cardiovascular Disease Risk Factors among Peruvian Adults

    PubMed Central

    Knowles, K. M.; Paiva, L. L.; Sanchez, S. E.; Revilla, L.; Lopez, T.; Yasuda, M. B.; Yanez, N. D.; Gelaye, B.; Williams, M. A.

    2011-01-01

    Objectives. To examine the extent to which measures of adiposity can be used to predict selected components of metabolic syndrome (MetS) and elevated C-reactive protein (CRP). Methods. A total of 1,518 Peruvian adults were included in this study. Waist circumference (WC), body mass index (BMI), waist-hip ratio (WHR), waist-height ratio (WHtR), and visceral adiposity index (VAI) were examined. The prevalence of each MetS component was determined according to tertiles of each anthropometric measure. ROC curves were used to evaluate the extent to which measures of adiposity can predict cardiovascular risk. Results. All measures of adiposity had the strongest correlation with triglyceride concentrations (TG). For both genders, as adiposity increased, the prevalence of Mets components increased. Compared to individuals with low-BMI and low-WC, men and women with high-BMI and high- WC had higher odds of elevated fasting glucose, blood pressure, TG, and reduced HDL, while only men in this category had higher odds of elevated CRP. Overall, the ROCs showed VAI, WC, and WHtR to be the best predictors for individual MetS components. Conclusions. The results of our study showed that measures of adiposity are correlated with cardiovascular risk although no single adiposity measure was identified as the best predictor for MetS. PMID:21331161

  5. Virally and physically transgenized equine adipose-derived stromal cells as a cargo for paracrine secreted factors

    PubMed Central

    2010-01-01

    Background Adipose-Derived Stromal Cells have been shown to have multiple lineage differentiation properties and to be suitable for tissues regeneration in many degenerative processes. Their use has been proposed for the therapy of joint diseases and tendon injuries in the horse. In the present report the genetic manipulation of Equine Adipose-Derived Stromal Cells has been investigated. Results Equine Adipose-Derived Stromal Cells were successfully virally transduced as well as transiently and stably transfected with appropriate parameters, without detrimental effect on their differentiation properties. Moreover, green fluorescent protein alone, fused to neo gene, or co-expressed as bi-cistronic reporter constructs, driven by viral and house-keeping gene promoters, were tested. The better expressed cassette was employed to stably transfect Adipose-Derived Stromal Cells for cell therapy purposes. Stably transfected Equine Adipose-Derived Stromal Cells with a heterologous secreted viral antigen were able to immunize horses upon injection into the lateral wall of the neck. Conclusion This study provides the methods to successfully transgenize Adipose-Derived Stromal Cells both by lentiviral vector and by transfection using optimized constructs with suitable promoters and reporter genes. In conclusion these findings provide a working platform for the delivery of potentially therapeutic proteins to the site of cells injection via transgenized Equine Adipose-Derived Stromal Cells. PMID:20863390

  6. Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and β-klotho expression decrease with fasting in northern elephant seals.

    PubMed

    Suzuki, Miwa; Lee, Andrew Y; Vázquez-Medina, José Pablo; Viscarra, Jose A; Crocker, Daniel E; Ortiz, Rudy M

    2015-05-15

    Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), β-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting.

  7. Plasma FGF21 Concentrations, Adipose Fibroblast Growth Factor Receptor-1 and β-Klotho Expression Decrease with Fasting in Northern Elephant Seals

    PubMed Central

    Suzuki, Miwa; Lee, Andrew; Vázquez-Medina, Jose Pablo; Viscarra, Jose A.; Crocker, Daniel E.; Ortiz, Rudy M.

    2015-01-01

    Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), β-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting. PMID:25857751

  8. Plasma FGF21 concentrations, adipose fibroblast growth factor receptor-1 and β-klotho expression decrease with fasting in northern elephant seals.

    PubMed

    Suzuki, Miwa; Lee, Andrew Y; Vázquez-Medina, José Pablo; Viscarra, Jose A; Crocker, Daniel E; Ortiz, Rudy M

    2015-05-15

    Fibroblast growth factor (FGF)-21 is secreted from the liver, pancreas, and adipose in response to prolonged fasting/starvation to facilitate lipid and glucose metabolism. Northern elephant seals naturally fast for several months, maintaining a relatively elevated metabolic rate to satisfy their energetic requirements. Thus, to better understand the impact of prolonged food deprivation on FGF21-associated changes, we analyzed the expression of FGF21, FGF receptor-1 (FGFR1), β-klotho (KLB; a co-activator of FGFR) in adipose, and plasma FGF21, glucose and 3-hydroxybutyrate in fasted elephant seal pups. Expression of FGFR1 and KLB mRNA decreased 98% and 43%, respectively, with fasting duration. While the 80% decrease in mean adipose FGF21 mRNA expression with fasting did not reach statistical significance, it paralleled the 39% decrease in plasma FGF21 concentrations suggesting that FGF21 is suppressed with fasting in elephant seals. Data demonstrate an atypical response of FGF21 to prolonged fasting in a mammal suggesting that FGF21-mediated mechanisms have evolved differentially in elephant seals. Furthermore, the typical fasting-induced, FGF21-mediated actions such as the inhibition of lipolysis in adipose may not be required in elephant seals as part of a naturally adapted mechanism to support their unique metabolic demands during prolonged fasting. PMID:25857751

  9. Increased Visceral Adipose Tissue as a Potential Risk Factor in Patients with Embolic Stroke of Undetermined Source (ESUS)

    PubMed Central

    Muuronen, Antti T.; Taina, Mikko; Hedman, Marja; Marttila, Jarkko; Kuusisto, Johanna; Onatsu, Juha; Vanninen, Ritva; Jäkälä, Pekka; Sipola, Petri; Mustonen, Pirjo

    2015-01-01

    Purpose The etiology of an ischemic stroke remains undetermined in 20–35% of cases and many patients do not have any of the conventional risk factors. Increased visceral adipose tissue (VAT) is a suggested new risk factor for both carotid artery atherosclerosis (CAA) and atrial fibrillation (AF), but its role in the remaining stroke population is unknown. We assessed the amount of VAT in patients with embolic stroke of undetermined source (ESUS) after excluding major-risk cardioembolic sources, occlusive atherosclerosis, and lacunar stroke. Methods Altogether 58 patients (mean age 57.7±10.2 years, 44 men) with ischemic stroke of unknown etiology but without CAA, known AF or small vessel disease underwent computed tomography angiography and assessment of VAT. For comparison VAT values from three different reference populations were used. Conventional risk factors (smoking, hypertension, diabetes, increased total and LDL-cholesterol, decreased HDL-cholesterol) were also registered. Results Mean VAT area was significantly higher in stroke patients (205±103 cm2 for men and 168±99 cm2 for women) compared to all reference populations (P<0.01). 50% of male and 57% of female patients had an increased VAT area. In male patients, VAT was significantly higher despite similar body mass index (BMI). Increased VAT was more common than any of the conventional risk factors. Conclusion Increased VAT was found in over half of our patients with ESUS suggesting it may have a role in the pathogenesis of thromboembolism in this selected group of patients. PMID:25756793

  10. Platelet-derived growth factor and spatiotemporal cues induce development of vascularized bone tissue by adipose-derived stem cells.

    PubMed

    Hutton, Daphne L; Moore, Erika M; Gimble, Jeffrey M; Grayson, Warren L

    2013-09-01

    Vasculature is essential to the functional integration of a tissue-engineered bone graft to enable sufficient nutrient delivery and viability after implantation. Native bone and vasculature develop through intimately coupled, tightly regulated spatiotemporal cell-cell signaling. The complexity of these developmental processes has been a challenge for tissue engineers to recapitulate, resulting in poor codevelopment of both bone and vasculature within a unified graft. To address this, we cultured adipose-derived stromal/stem cells (ASCs), a clinically relevant, single cell source that has been previously investigated for its ability to give rise to vascularized bone grafts, and studied the effects of initial spatial organization of cells, the temporal addition of growth factors, and the presence of exogenous platelet-derived growth factor-BB (PDGF-BB) on the codevelopment of bone and vascular tissue structures. Human ASCs were aggregated into multicellular spheroids via the hanging drop method before encapsulation and subsequent outgrowth in fibrin gels. Cellular aggregation substantially increased vascular network density, interconnectivity, and pericyte coverage compared to monodispersed cultures. To form robust vessel networks, it was essential to culture ASCs in a purely vasculogenic medium for at least 8 days before the addition of osteogenic cues. Physiologically relevant concentrations of exogenous PDGF-BB (20 ng/mL) substantially enhanced both vascular network stability and osteogenic differentiation. Comparisons with the bone morphogenetic protein-2, another pro-osteogenic and proangiogenic growth factor, indicated that this potential to couple the formation of both lineages might be unique to PDGF-BB. Furthermore, the resulting tissue structure demonstrated the close association of mineral deposits with pre-existing vascular structures that have been described for developing tissues. This combination of a single cell source with a potent induction factor

  11. Characterization of the expression profiles of adipogenesis-related factors, ZNF423, KLFs and FGF10, during preadipocyte differentiation and abdominal adipose tissue development in chickens.

    PubMed

    Matsubara, Yusuke; Aoki, Michiru; Endo, Tonami; Sato, Kan

    2013-07-01

    Adipogenesis is controlled by a complicated process involving certain transcriptional events. In chicken adipogenesis, peroxisome proliferator-activated receptor γ (PPARγ) is a key regulator of preadipocyte differentiation and abdominal fat accumulation. However, in a recent study in mammals, some novel factors related to regulation of adipogenesis, including preadipocyte differentiation, were identified in mammals. Therefore, in this study, we aimed to determine the expression profiles of these mammalian adipogenesis-related factors, such as zinc-finger protein 423 (ZNF423), Krüppel-like factor -2, -5, and -15 (KLF-2, -5, -15), and FGF10, in the chicken (Gallus gallus). Specifically, we analyzed their expression in primary preadipocyte differentiation in vitro and also analyzed their tissue distribution and their temporal expression in adipose tissue development in vivo. During chicken adipocyte differentiation, the gene expression of ZNF423, KLF-2, KLF-5 and FGF10 was found to rapidly decrease in the early stage of preadipocyte differentiation. Expression of ZNF423 then increased in the late stage of differentiation. KLF-15 expression increased in a time-dependent manner for 48 h. Protein expressions of these factors were reflected by Western blot analysis. High levels of aP2, PPARγ and FGF10 mRNA were found in adipose tissue. In addition, aP2, PPARγ and ZNF423 mRNA levels in the adipose tissue were elevated at days 10 and 20. These expression profiles of the adipogenesis-related factors in chicken are, in part, different from mammalian adipogenesis but this seems to reflect the differences in the regulation of adipogenesis and in adipose tissue functions between avians and mammals.

  12. Transcription factor PU.1 is expressed in white adipose and inhibits adipocyte differentiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    PU.1 transcription factor is a critical regulator of hematopoiesis and leukemogenesis. Because PU.1 interacts with transcription factors GATA-2 and C/EBPa, both of which are involved in the regulation of adipogenesis, we investigated whether PU.1 also plays a role in the regulation of adipocyte diff...

  13. Hip Osteoarthritis in Dogs: A Randomized Study Using Mesenchymal Stem Cells from Adipose Tissue and Plasma Rich in Growth Factors

    PubMed Central

    Cuervo, Belen; Rubio, Monica; Sopena, Joaquin; Dominguez, Juan Manuel; Vilar, Jose; Morales, Manuel; Cugat, Ramón; Carrillo, Jose Maria

    2014-01-01

    Purpose: The aim of this study was to compare the efficacy and safety of a single intra-articular injection of adipose mesenchymal stem cells (aMSCs) versus plasma rich in growth factors (PRGF) as a treatment for reducing symptoms in dogs with hip osteoarthritis (OA). Methods: This was a randomized, multicenter, blinded, parallel group. Thirty-nine dogs with symptomatic hip OA were assigned to one of the two groups, to receive aMSCs or PRGF. The primary outcome measures were pain and function subscales, including radiologic assessment, functional limitation and joint mobility. The secondary outcome measures were owners’ satisfaction questionnaire, rescue analgesic requirement and overall safety. Data was collected at baseline, then, 1, 3 and 6 months post-treatment. Results: OA degree did not vary within groups. Functional limitation, range of motion (ROM), owner’s and veterinary investigator visual analogue scale (VAS), and patient’s quality of life improved from the first month up to six months. The aMSCs group obtained better results at 6 months. There were no adverse effects during the study. Our findings show that aMSCs and PRGF are safe and effective in the functional analysis at 1, 3 and 6 months; provide a significant improvement, reducing dog’s pain, and improving physical function. With respect to basal levels for every parameter in patients with hip OA, aMSCs showed better results at 6 months. PMID:25089877

  14. Age-Related Yield of Adipose-Derived Stem Cells Bearing the Low-Affinity Nerve Growth Factor Receptor

    PubMed Central

    González-Garza, Maria Teresa; Cardenas-Lopez, Alejandro; Chavez-Castilla, Luis; Cruz-Vega, Delia Elva; Moreno-Cuevas, Jorge E.

    2013-01-01

    Adipose-derived stem cells (ADSCs) are a heterogeneous cell population that may be enriched by positive selection with antibodies against the low-affinity nerve growth factor receptor (LNGFR or CD271), yielding a selective cell universe with higher proliferation and differentiation potential. This paper addresses the need for determining the quantity of ADSCs positive for the CD271 receptor and its correlation with donor's age. Mononuclear cells were harvested from the lower backs of 35 female donors and purified using magnetic beads. Multipotency capacity was tested by the expression of stemness genes and through differentiation into preosteoblasts and adipocytes. A significant statistical difference was found in CD271+ concentrations between defined age intervals. The highest yield was found within women on the 30–40-year-old age range. CD271+ ADSCs from all age groups showed differentiation capabilities as well as expression of typical multipotent stem cell genes. Our data suggest that the amount of CD271+ cells correlates inversely with age. However, the ability to obtain these cells was maintained through all age ranges with a yield higher than what has been reported from bone marrow. Our findings propose CD271+ ADSCs as the primary choice for tissue regeneration and autologous stem cell therapies in older subjects. PMID:24376462

  15. Tumor Necrosis Factor Improves Vascularization in Osteogenic Grafts Engineered with Human Adipose-Derived Stem/Stromal Cells

    PubMed Central

    Hutton, Daphne L.; Kondragunta, Renu; Moore, Erika M.; Hung, Ben P.; Jia, Xiaofeng; Grayson, Warren L.

    2014-01-01

    The innate immune response following bone injury plays an important role in promoting cellular recruitment, revascularization, and other repair mechanisms. Tumor necrosis factor-α (TNF) is a prominent pro-inflammatory cytokine in this cascade, and has been previously shown to improve bone formation and angiogenesis in a dose- and timing-dependent manner. This ability to positively impact both osteogenesis and vascular growth may benefit bone tissue engineering, as vasculature is essential to maintaining cell viability in large grafts after implantation. Here, we investigated the effects of exogenous TNF on the induction of adipose-derived stem/stromal cells (ASCs) to engineer pre-vascularized osteogenic tissue in vitro with respect to dose, timing, and co-stimulation with other inflammatory mediators. We found that acute (2-day), low-dose exposure to TNF promoted vascularization, whereas higher doses and continuous exposure inhibited vascular growth. Co-stimulation with platelet-derived growth factor (PDGF), another key factor released following bone injury, increased vascular network formation synergistically with TNF. ASC-seeded grafts were then cultured within polycaprolactone-fibrin composite scaffolds and implanted in nude rats for 2 weeks, resulting in further tissue maturation and increased angiogenic ingrowth in TNF-treated grafts. VEGF-A expression levels were significantly higher in TNF-treated grafts immediately prior to implantation, indicating a long-term pro-angiogenic effect. These findings demonstrate that TNF has the potential to promote vasculogenesis in engineered osteogenic grafts both in vitro and in vivo. Thus, modulation and/or recapitulation of the immune response following bone injury may be a beneficial strategy for bone tissue engineering. PMID:25248109

  16. Bioengineering Beige Adipose Tissue Therapeutics.

    PubMed

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  17. Bioengineering Beige Adipose Tissue Therapeutics.

    PubMed

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  18. Bioengineering Beige Adipose Tissue Therapeutics

    PubMed Central

    Tharp, Kevin M.; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  19. A longitudinal analysis of the effects of socioeconomic factors, foreign media, and attitude toward appearance on general and central adiposity in Chinese adolescents

    PubMed Central

    Felicitas, Jamie Q.; Tanenbaum, Hilary C.; Li, Yawen; Chou, Chih-Ping; Palmer, Paula H.; Spruijt-Metz, Donna; Reynolds, Kim D.; Johnson, C. Anderson; Xie, Bin

    2015-01-01

    This paper explores the longitudinal effects of socioeconomic factors (i.e., parent education and family income level), foreign media, and attitude toward appearance on general and central adiposity among Chinese adolescents. A longitudinal analysis was performed using data from the China Seven Cities Study, a health promotion and smoking prevention study conducted in seven cities across Mainland China between 2002 and 2005. Participants included 5,020 middle and high school students and their parents. Explanatory variables included foreign media exposure, attitude toward appearance, parent education, and family income. Three-level, random-effect models were used to predict general adiposity (i.e., body mass index) and central adiposity (i.e., waist circumference). The Generalized Estimating Equation approach was utilized to determine the effect of explanatory variables on overweight status. Among girls, foreign media exposure was significantly negatively associated with general adiposity over time (β = − 0.06, p = 0.01 for middle school girls; β = − 0.06, p = 0.03 for high school girls). Attitude toward appearance was associated with lesser odds of being overweight, particularly among high school girls (OR = 0.86, p < 0.01). Among boys, parental education was significantly positively associated with general adiposity (β = 0.62, p < 0.01 for middle school boys; β = 0.37, p = 0.02 for high school boys) and associated with greater odds of being overweight (OR = 1.55, p < 0.01 for middle school boys; OR = 1.26, p = 0.04 for high school boys). Across all gender and grade levels, family income was significantly negatively associated with central adiposity over time. Interventions addressing Chinese adolescent overweight/obesity should consider these factors as potential focus areas. PMID:26279973

  20. Prevalence of Adiposity and Associated Cardiometabolic Risk Factors in the Samoan Genome-Wide Association Study

    PubMed Central

    HAWLEY, NICOLA L.; MINSTER, RYAN L.; WEEKS, DANIEL E.; VIALI, SATUPAITEA; REUPENA, MUAGUTUTIA SEFUIVA; SUN, GUANGYUN; CHENG, HONG; DEKA, RANJAN; MCGARVEY, STEPHEN T.

    2015-01-01

    Objective To describe the prevalence of obesity-related noncommunicable diseases (NCDs) and associated risk factors in a sample of Samoan adults studied in 2010 as part of a genome-wide assocation study (GWAS) for obesity related traits. Methods Anthropometric and biochemical data collected from n = 3,475 participants (n = 1,437 male; n = 2,038 female) aged 24.5 to <65 years were used to describe the prevalence of obesity, diabetes, hypertension, and dyslipidemia within the study sample. One way analysis of variance, χ2 tests, and binary logistic regression were used to identify differences in disease and risk factor prevalence by 10-year age group, gender, or by census region of residence. Results Obesity was highly prevalent among the study sample; 64.6% of females and 41.2% of males were obese according to Polynesian cutoffs (BMI ≥ 32 kg/m2). Females were less likely than males to have hypertension (31.7% vs. 36.7%) but equally likely to have diabetes (17.8% vs. 16.4%). With the exception of obesity and low HDL-cholesterol in females only, there were significant differences in the prevalence of all NCDs and associated risk factors by age group, with the oldest age group (55 to <65 years) most affected. In both sexes, residents of the Apia Urban Area were at significantly greater risk of obesity, diabetes, low HDL-cholesterol, and high triglycerides than residents of the more rural Savaii region. Conclusions The phenotypic characteristics of this sample provide evidence of a continuation of previously reported temporal trends toward obesity and its associated disorders. Attention must be paid to the critical NCD situation in Samoa. PMID:24799123

  1. Sequential hepatogenic transdifferentiation of adipose tissue-derived stem cells: relevance of different extracellular signaling molecules, transcription factors involved, and expression of new key marker genes.

    PubMed

    Bonora-Centelles, A; Jover, R; Mirabet, V; Lahoz, A; Carbonell, F; Castell, J V; Gómez-Lechón, M J

    2009-01-01

    Adipose tissue contains a mesenchymal stem cell (MSC) population known as adipose-derived stem cells (ASCs) capable of differentiating into different cell types. Our aim was to induce hepatic transdifferentiation of ASCs by sequential exposure to several combinations of cytokines, growth factors, and hormones. The most efficient hepatogenic protocol includes fibroblastic growth factors (FGF) 2 and 4 and epidermal growth factor (EGF) (step 1), hepatocyte growth factor (HGF), FGF2, FGF4, and nicotinamide (Nic) (step 2), and oncostatin M (OSM), dexamethasone (Dex), and insulin-tranferrin-selenium (step 3). This protocol activated transcription factors [GATA6, Hex, CCAAT/enhancer binding protein alpha and beta (CEBPalpha and beta), peroxisome proliferator-activated receptor-gamma, coactivator 1 alpha (PGC1alpha), and hepatocyte nuclear factor 4 alpha (HNF4alpha)], which promoted a characteristic hepatic phenotype, as assessed by new informative markers for the step-by-step hepatic transdifferentiation of hMSC [early markers: albumin (ALB), alpha-2-macroglobuline (alpha2M), complement protein C3 (C3), and selenoprotein P1 (SEPP1); late markers: cytochrome P450 3A4 (CYP3A4), apolipoprotein E (APOE), acyl-CoA synthetase long-chain family member 1 (ACSL1), and angiotensin II receptor, type 1 (AGTR1)]. The loss of adipose adult stem cell phenotype was detected by losing expression of Thy1 and inhibitor of DNA binding 3 (Id3). The reexpression of phosphoenolpyruvate corboxykinase (PEPCK), apolipoprotein C3 (APOCIII), aldolase B (ALDOB), and cytochrome P450 1A2 (CYP1A2) was achieved by transduction with a recombinant adenovirus for HNF4alpha and finally hepatic functionality was also assessed by analyzing specific biochemical markers. We conclude that ASCs could represent an alternative tool in clinical therapy for liver dysfunction and regenerative medicine.

  2. Hepatocyte growth factor-modified adipose tissue-derived stem cells improve erectile function in streptozotocin-induced diabetic rats.

    PubMed

    Liu, Tao; Peng, Yifeng; Jia, Chao; Fang, Xiang; Li, Jing; Zhong, Wan

    2015-01-01

    TGFβ1-Smad signaling pathway is closely related to various tissues fibrosis. Hepatocyte growth factor (HGF) has been shown to antagonize TGFβ1-Smad signaling and may improve kidney tissue fibrosis in diabetic models. Penile fibrosis is a pathological condition which occurs during diabetic erectile dysfunction (ED). The aim of this study was to examine the effect of the treatment of ED in diabetic rats with a combination of HGF and adipose tissue-derived stem cells (ADSC). In this diabetes model, rats were injected intraperitoneally with 60 mg streptozotocin (STZ) to induce diabetes. Three months later, the diabetic rats were divided into a negative control(NC) group, an ADSC-treated group and an ADSC + HGF-treated group while normal rats were assigned into a sham group. Rats in the sham and NC groups were injected in the corpus cavernosum with phosphate-buffered saline, while rats in the other groups were injected with either ADSC or ADSC + HGF. One month later, erectile function was examined in each group and penile tissues were collected for experiments. The expression of smooth muscle actin (SMA) and platelet-endothelial cell adhesion molecule-1 (PECAM-1) was analyzed by Western blotting. The smooth muscle and collagen deposition in corpus cavernosum was evaluated by Masson staining, while endothelial changes were assessed immunohistochemically. Cell apoptosis was detected by the TdT-mediated dUTP nick-end labeling (TUNEL) assay. The results revealed that ADSC alone can significantly improve erectile function in diabetic rats, but in combination with HGF the improvement was more prominent, showing higher content of smooth muscle and endothelial cells and lower cell apoptotic index in corpus cavernosum. Treatment with HGF can significantly enhance the beneficial effect of ADSC on erectile function in diabetic rats, and this effect might be closely related to the down-regulation of TGFβ1-Smad signaling. PMID:26339935

  3. Stromal cell-derived factor-1 promotes human adipose tissue-derived stem cell survival and chronic wound healing

    PubMed Central

    LI, QIANG; GUO, YANPING; CHEN, FEIFEI; LIU, JING; JIN, PEISHENG

    2016-01-01

    Adipose tissue-derived stem cells (ADSCs) hold great potential for the stem cell-based therapy of cutaneous wound healing. Stromal cell-derived factor-1 (SDF-1) activates CXC chemokine receptor (CXCR)4+ and CXCR7+ cells and plays an important role in wound healing. Increasing evidence suggests a critical role for SDF-1 in cell apoptosis and the survival of mesenchymal stem cells. However, the function of SDF-1 in the apoptosis and wound healing ability of ADSCs is not well understood. The aim of this study was to analyze the effect of SDF-1 on the apoptosis and therapeutic effect of ADSCs in cutaneous chronic wounds in vitro and in vivos. By flow cytometric analysis, it was found that hypoxia and serum free promoted the apoptosis of ADSCs. When pretreated with SDF-1, the apoptosis of ADSCs induced by hypoxia and serum depletion was partly recovered. Furthermore, in vivo experiments established that the post-implantation cell survival and chronic wound healing ability of ADSCs were increased following pretreatment with SDF-1 in a diabetic mouse model of chronic wound healing. To explore the potential mechanism underlying the effect of SDF-1 on ADSC apoptosis, western blot analysis was employed and the results indicate that SDF-1 may protect against cell apoptosis in hypoxic and serum-free conditions through activation of the caspase signaling pathway in ADSCs. This study provides evidence that SDF-1 pretreatment can increase the therapeutic effect of ADSCs in cutaneous chronic wounds in vitro and in vivo. PMID:27347016

  4. Determinants of intrathoracic adipose tissue volume and associations with cardiovascular disease risk factors in Amish

    PubMed Central

    Liu, Xinggang; Post, Wendy S.; McLenithan, John; Terrin, Michael; Magder, Laurence; Zeb, Irfan; Budoff, Matthew; Mitchell, Braxton D.

    2014-01-01

    Objective Hypothesizing that intrathoracic fat might exert local effects on the coronary vasculature, we assessed the association of intrathoracic fat volume and its two subcomponents with coronary artery calcification (CAC) in 909 relatively healthy Amish adults. Design and Methods Intrathoracic fat, which is comprised of fat between the surface of the heart and the visceral epicardium (epicardial fat) and fat around the heart but outside of the fibrous pericardium (pericardial fat), was measured from electron beam CT scans. We examined the association between intrathoracic fat volume and cardiovascular disease risk factors in multivariate regression model. Results Fat volume in the epicardial and pericardial compartments were highly correlated with each other and with body mass index. Neither CAC extent nor CAC presence (Agatston score>0) was associated with increased intrathoracic fat volume in sex-stratified models adjusting for age (p>0.10). Intrathoracic fat volume was significantly correlated with higher systolic/diastolic blood pressure, pulse pressure, fasting glucose, insulin, triglyceride and lower high-density lipoprotein cholesterol in sex-stratified models adjusting for age (p<0.05). However, associations were attenuated after further adjustment for body mass index. Conclusions These data do not provide support for a significant role for intrathoracic fat in the development of CAC. PMID:24477004

  5. [Adiposity as a risk factor of non alcoholic fat disease; systematic review].

    PubMed

    Jiménez-Cruz, Arturo; Gómez-Miranda, Luis Mario; Díaz Ramírez, Glenda; Carvalí Meza, Nuris Yohana; Bacardí-Gascón, Montserrat

    2014-04-01

    Introducción: Se ha descrito que la adiposidad es un factor de riesgo del hígado graso no alcohólico (HGNA). Objetivo: Realizar una revisión sistemática de estudios prospectivos que evaluaran la asociación de indicadores de adiposidad con el desarrollo del HGNA. Metodología: Se revisaron todos los artículos originales encontrados en inglés y en español publicados de enero de 2005 a diciembre de 2013, en la base de datos de MEDLINE/ PubMed, de estudios prospectivos con una duración igual o mayor a un año de seguimiento. La calidad de los artículos fue evaluada mediante los criterios de GRADE. Resultados: La población total estudiada fue de 10.640 (6.394 hombres y 4.246 mujeres), y el rango de edad fue de 20-88 años. Cumplieron con los criterios de inclusión cinco estudios prospectivos, y el seguimiento osciló entre uno y siete años. Los criterios de diagnóstico utilizados fueron la ultrasonografía (4) y la tomografía computarizada (1). Los OR de IMC, circunferencia de cintura y ganancia de peso oscilaron entre 1,19 a 1,43, 1,04 a 2,15 y 1,21 a 1,57 respectivamente. Conclusión: Se observó una relación consistente entre los indicadores de adiposidad y el HGNA.

  6. Is the body adiposity index (hip circumference/height(1.5)) more strongly related to skinfold thicknesses and risk factor levels than is BMI? The Bogalusa Heart Study.

    PubMed

    Freedman, David S; Blanck, Heidi M; Dietz, William H; DasMahapatra, Pronabesh; Srinivasan, Sathanur R; Berenson, Gerald S

    2013-01-28

    Because of its strong association (r 0.85) with percentage of body fat determined by dual-energy X-ray absorptiometry, hip circumference divided by height(1.5) (the body adiposity index) has recently been proposed as an index of body fatness among adults. We examined whether this proposed index was more strongly associated with skinfold thicknesses and levels of CVD risk factors (lipids, fasting insulin and glucose, and blood pressure) than was BMI among 2369 18- to 49-year-olds in the Bogalusa Heart Study. All analyses indicated that the body adiposity index was less strongly associated with skinfold thicknesses and CVD risk factors than was either waist circumference or BMI. Correlations with the skinfold sum, for example, were r 0.81 (BMI) v. r 0.75 (body adiposity index) among men, and r 0.87 (BMI) v. r 0.80 among women; P< 0.001 for both differences. An overall index of seven CVD risk factors was also more strongly associated with BMI (r 0.58) and waist circumference (r 0.61) than with the body adiposity index (r 0.49). The weaker associations with the body adiposity index were observed in analyses stratified by sex, race, age and year of examination. Multivariable analyses indicated that if either BMI or waist circumference were known, the body adiposity index provided no additional information on skinfold thicknesses or risk factor levels. These findings indicate that the body adiposity index is likely to be an inferior index of adiposity than is either BMI or waist circumference.

  7. Obesity with no metabolic syndrome and adipose tissue expansion based solely on risk factors and inflammatory marker of coronary heart disease in premenopausal women.

    PubMed

    Alves Ramos, Sabrina; Sabino, Adriano de Paula; Corrêa Ferreira, Daniela; Alvarez-Leite, Jacqueline Isaura

    2012-09-01

    The objective of this study was to analyze whether obese women with no metabolic syndrome (MetS) have increased cardiometabolic risk compared to non-obese women and to observe the correlations between adiposity and coronary heart disease (CHD) risk factors in metabolically healthy women. 20-40 year old non-obese (n=41), obese with no MetS (n=30) and obese with MetS (n=28) women were studied. Lipid profile, blood pressure, CHD family history, physical inactivity, high-sensitivity C-reactive protein (hs-CRP), fibrinogen, interleukin-1beta and tumor necrosis factor-alpha were analyzed. A subset of obese (13) and non-obese (33) women with no major components of MetS (except waist circumference) were further compared. Obese women with no MetS and non-obese women presented a similar metabolic profile that was statistically different from those seen in obese women with MetS. The number of obese women with no MetS and non-obese women presenting two or more risk factors (23.3 and 19.5%, respectively) or presenting high Framingham Risk Score (6.7 and 2.4%, respectively) were also similar. The only pro inflammatory protein correlated to waist circumference was hs-CRP. These data suggest that obesity with no MetS induce a CHD risk comparable to the risk seen in non-obese women. However, when women with no major components of MetS alone were considered, adiposity was positively correlated to blood pressure and hs-CRP. Although CHD risk of obese women with no MetS is closer to non-obese women, adipose tissue expansion was positively correlated to blood pressure and hs-CRP that are important risk factors for CHD.

  8. Enhanced Healing of Diabetic Wounds by Topical Administration of Adipose Tissue-Derived Stromal Cells Overexpressing Stromal-Derived Factor-1: Biodistribution and Engraftment Analysis by Bioluminescent Imaging

    PubMed Central

    Di Rocco, Giuliana; Gentile, Antonietta; Antonini, Annalisa; Ceradini, Francesca; Wu, Joseph C.; Capogrossi, Maurizio C.; Toietta, Gabriele

    2011-01-01

    Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production. PMID:21234108

  9. Enhanced healing of diabetic wounds by topical administration of adipose tissue-derived stromal cells overexpressing stromal-derived factor-1: biodistribution and engraftment analysis by bioluminescent imaging.

    PubMed

    Di Rocco, Giuliana; Gentile, Antonietta; Antonini, Annalisa; Ceradini, Francesca; Wu, Joseph C; Capogrossi, Maurizio C; Toietta, Gabriele

    2010-01-01

    Chronic ulcers represent a major health problem in diabetic patients resulting in pain and discomfort. Conventional therapy does not guarantee adequate wound repair. In diabetes, impaired healing is partly due to poor endothelial progenitor cells mobilisation and homing, with altered levels of the chemokine stromal-derived factor-1 (SDF-1) at the wound site. Adipose tissue-associated stromal cells (AT-SCs) can provide an accessible source of progenitor cells secreting proangiogenic factors and differentiating into endothelial-like cells. We demonstrated that topical administration of AT-SCs genetically modified ex vivo to overexpress SDF-1, promotes wound healing into diabetic mice. In particular, by in vivo bioluminescent imaging analysis, we monitored biodistribution and survival after transplantation of luciferase-expressing cells. In conclusion, this study indicates the therapeutic potential of AT-SCs administration in wound healing, through cell differentiation, enhanced cellular recruitment at the wound site, and paracrine effects associated with local growth-factors production. PMID:21234108

  10. Adipose tissues and thyroid hormones

    PubMed Central

    Obregon, Maria-Jesus

    2014-01-01

    The maintenance of energy balance is regulated by complex homeostatic mechanisms, including those emanating from adipose tissue. The main function of the adipose tissue is to store the excess of metabolic energy in the form of fat. The energy stored as fat can be mobilized during periods of energy deprivation (hunger, fasting, diseases). The adipose tissue has also a homeostatic role regulating energy balance and functioning as endocrine organ that secretes substances that control body homeostasis. Two adipose tissues have been identified: white and brown adipose tissues (WAT and BAT) with different phenotype, function and regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and white adipocytes have different ontogenetic origin and lineage and specific markers of WAT and BAT have been identified. “Brite” or beige adipose tissue has been identified in WAT with some properties of BAT. Thyroid hormones exert pleiotropic actions, regulating the differentiation process in many tissues including the adipose tissue. Adipogenesis gives raise to mature adipocytes and is regulated by several transcription factors (c/EBPs, PPARs) that coordinately activate specific genes, resulting in the adipocyte phenotype. T3 regulates several genes involved in lipid mobilization and storage and in thermogenesis. Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial function, transcription factors, the availability of nutrients. T3 acts directly through specific TREs in the gene promoters, regulating transcription factors. The deiodinases D3, D2, and D1 regulate the availability of T3. D3 is activated during proliferation, while D2 is linked to the adipocyte differentiation program, providing T3 needed for lipogenesis and thermogenesis. We examine the differences between BAT, WAT and brite/beige adipocytes and the process that lead to activation of UCP1 in WAT

  11. Conversion of Adipose Tissue-Derived Mesenchymal Stem Cells to Neural Stem Cell-Like Cells by a Single Transcription Factor, Sox2

    PubMed Central

    Qin, Yiren; Zhou, Chikai; Wang, Nianhong; Yang, Hao

    2015-01-01

    Abstract Adipose tissue is an attractive source of easily accessible adult candidate cells for regenerative medicine. Adipose tissue–derived mesenchymal stem cells (ADSCs) have multipotency and strong proliferation and differentiation capabilities in vitro. However, as mesodermal multipotent stem cells, whether the ADSCs can convert into induced neural stem cells (NSCs) has so far not been demonstrated. In this study, we found that normally the naïve ADSCs cultured as either monolayer or spheres in NSC medium did not express Sox2 and Pax6 genes and proteins, and could not differentiate to neuron-like cells. However, when we introduced the Sox2 gene into ADSCs by retrovirus, they exhibited a typical NSC-like morphology, and could be passaged continuously, and expressed NSC specific markers Sox2 and Pax6. In addition, the ADSC-derived NSC-like cells displayed the ability to differentiate into neuron-like cells when switched to the differentiation culture medium, expressing neuronal markers, including Tuj1 and MAP2 genes and proteins. Our results suggest the ADSCs can be converted into induced NSC-like cells with a single transcription factor Sox2. This finding could provide another alternative cell source for cell therapy of neurological disorders. PMID:26053521

  12. Grafting and Early Expression of Growth Factors from Adipose-Derived Stem Cells Transplanted into the Cochlea, in a Guinea Pig Model of Acoustic Trauma

    PubMed Central

    Fetoni, Anna Rita; Lattanzi, Wanda; Eramo, Sara Letizia Maria; Barba, Marta; Paciello, Fabiola; Moriconi, Chiara; Rolesi, Rolando; Michetti, Fabrizio; Troiani, Diana; Paludetti, Gaetano

    2014-01-01

    Noise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery. Loads of evidence indicate adipose-derived stem cells (ASCs) as promising tools in diversified regenerative medicine applications, due to the high degree of plasticity and trophic features. This study was aimed at identifying the path of in vivo cell migration and expression of trophic growth factors, upon ASCs transplantation into the cochlea, following noise-induced injury. ASCs were isolated in primary culture from the adipose tissue of a guinea pig, transduced using a viral vector to express the green fluorescent protein, and implanted into the scala tympani of deafened animals. Auditory function was assessed 3 and 7 days after surgery. The expression of trophic growth factors was comparatively analyzed using real-time PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to assess the in vivo localization and expression of trophic growth factors in ASCs and cochleae, 3 and 7 days following homologous implantation. ASC implantation did not modify auditory function. ASCs migrated from the perilymphatic to the endolymphatic compartment, during the analyzed time course. Upon noise exposure, the expression of chemokine ligands and receptors related to the PDGF, VEGF, and TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo cell migration. Immunofluorescence confirmed the increased expression, which appeared to be further strengthened by ASCs’ implantation. These results indicated that ASCs are able to migrate at the site of tissue damage and express trophic factors, upon intracochlear implantation, providing an original proof of principle, which could pave the way for further developments of ASC-based treatments of

  13. Grafting and early expression of growth factors from adipose-derived stem cells transplanted into the cochlea, in a Guinea pig model of acoustic trauma.

    PubMed

    Fetoni, Anna Rita; Lattanzi, Wanda; Eramo, Sara Letizia Maria; Barba, Marta; Paciello, Fabiola; Moriconi, Chiara; Rolesi, Rolando; Michetti, Fabrizio; Troiani, Diana; Paludetti, Gaetano

    2014-01-01

    Noise exposure causes damage of multiple cochlear cell types producing permanent hearing loss with important social consequences. In mammals, no regeneration of either damaged hair cells or auditory neurons has been observed and no successful treatment is available to achieve a functional recovery. Loads of evidence indicate adipose-derived stem cells (ASCs) as promising tools in diversified regenerative medicine applications, due to the high degree of plasticity and trophic features. This study was aimed at identifying the path of in vivo cell migration and expression of trophic growth factors, upon ASCs transplantation into the cochlea, following noise-induced injury. ASCs were isolated in primary culture from the adipose tissue of a guinea pig, transduced using a viral vector to express the green fluorescent protein, and implanted into the scala tympani of deafened animals. Auditory function was assessed 3 and 7 days after surgery. The expression of trophic growth factors was comparatively analyzed using real-time PCR in control and noise-injured cochlear tissues. Immunofluorescence was used to assess the in vivo localization and expression of trophic growth factors in ASCs and cochleae, 3 and 7 days following homologous implantation. ASC implantation did not modify auditory function. ASCs migrated from the perilymphatic to the endolymphatic compartment, during the analyzed time course. Upon noise exposure, the expression of chemokine ligands and receptors related to the PDGF, VEGF, and TGFbeta pathways, increased in the cochlear tissues, possibly guiding in vivo cell migration. Immunofluorescence confirmed the increased expression, which appeared to be further strengthened by ASCs' implantation. These results indicated that ASCs are able to migrate at the site of tissue damage and express trophic factors, upon intracochlear implantation, providing an original proof of principle, which could pave the way for further developments of ASC-based treatments of

  14. Characterization of brown adipose tissue ¹⁸F-FDG uptake in PET/CT imaging and its influencing factors in the Chinese population.

    PubMed

    Shao, Xiaonan; Shao, Xiaoliang; Wang, Xiaosong; Wang, Yuetao

    2016-01-01

    (18)F-FDG PET/CT has been widely applied for tumor imaging. However, it is reported that many normal tissues, e.g., brown adipose tissue, can also uptake (18)F-FDG. The purpose of this study was to determine the imaging characteristics of (18)F-FDG uptake in brown adipose tissue (BAT) in PET/CT. A total of 2,944 patients who underwent PET/CT from September 2011 to March 2013 were analyzed retrospectively. Imaging features of (18)F-FDG uptake in BAT were analyzed. Univariate analysis and logistic regression analysis were performed to evaluate the effect of age, gender, cancer status, body mass index (BMI), average daily maximum temperature of imaging month and fasting plasma glucose (Glu) on the positive rate of (18)F-FDG uptake in BAT. The results showed that 1.9% (57/2944) patients had (18)F-FDG uptake in BAT. (18)F-FDG, manifested as flaky, nodular and beaded shape, was symmetrically distributed in the adipose tissues of cervical and supraclavicular, mediastinal, paravertebral, and perirenal areas. Uptake of (18)F-FDG within cervical/supraclavicular area was most common (89.5%, 51/57) with an SUVmax ranging from 2.8 to 31.4. Univariate analysis showed that gender and cancer status were not significantly correlated with the BAT (18)F-FDG uptake rate. In contrast, age, BMI, Glu and average daily maximum temperature in the imaging month were significantly correlated with the BAT (18)F-FDG uptake rate (P<0.05). Further logistic regression analysis showed that only age, BMI and average daily maximum temperature were significant (OR<1, P<0.05). Based on the value of OR, the most significant factor that affects BAT (18)F-FDG uptake rate was age, followed by the average daily maximum temperature and BMI. We concluded that Chinese adult has low positive rate of (18)F-FDG uptake in BAT. Cervical/Supraclavicular is the most common area with BAT (18)F-FDG uptake. Age, average daily maximum temperature and BMI are independent factors affecting (18)F-FDG uptake. PMID:26702781

  15. Characterization of brown adipose tissue ¹⁸F-FDG uptake in PET/CT imaging and its influencing factors in the Chinese population.

    PubMed

    Shao, Xiaonan; Shao, Xiaoliang; Wang, Xiaosong; Wang, Yuetao

    2016-01-01

    (18)F-FDG PET/CT has been widely applied for tumor imaging. However, it is reported that many normal tissues, e.g., brown adipose tissue, can also uptake (18)F-FDG. The purpose of this study was to determine the imaging characteristics of (18)F-FDG uptake in brown adipose tissue (BAT) in PET/CT. A total of 2,944 patients who underwent PET/CT from September 2011 to March 2013 were analyzed retrospectively. Imaging features of (18)F-FDG uptake in BAT were analyzed. Univariate analysis and logistic regression analysis were performed to evaluate the effect of age, gender, cancer status, body mass index (BMI), average daily maximum temperature of imaging month and fasting plasma glucose (Glu) on the positive rate of (18)F-FDG uptake in BAT. The results showed that 1.9% (57/2944) patients had (18)F-FDG uptake in BAT. (18)F-FDG, manifested as flaky, nodular and beaded shape, was symmetrically distributed in the adipose tissues of cervical and supraclavicular, mediastinal, paravertebral, and perirenal areas. Uptake of (18)F-FDG within cervical/supraclavicular area was most common (89.5%, 51/57) with an SUVmax ranging from 2.8 to 31.4. Univariate analysis showed that gender and cancer status were not significantly correlated with the BAT (18)F-FDG uptake rate. In contrast, age, BMI, Glu and average daily maximum temperature in the imaging month were significantly correlated with the BAT (18)F-FDG uptake rate (P<0.05). Further logistic regression analysis showed that only age, BMI and average daily maximum temperature were significant (OR<1, P<0.05). Based on the value of OR, the most significant factor that affects BAT (18)F-FDG uptake rate was age, followed by the average daily maximum temperature and BMI. We concluded that Chinese adult has low positive rate of (18)F-FDG uptake in BAT. Cervical/Supraclavicular is the most common area with BAT (18)F-FDG uptake. Age, average daily maximum temperature and BMI are independent factors affecting (18)F-FDG uptake.

  16. The combined effects of matrix stiffness and growth factor immobilization on the bioactivity and differentiation capabilities of adipose-derived stem cells.

    PubMed

    Banks, Jessica M; Mozdzen, Laura C; Harley, Brendan A C; Bailey, Ryan C

    2014-10-01

    Biomaterial designs are increasingly incorporating multiple instructive signals to induce a desired cell response. However, many approaches do not allow orthogonal manipulation of immobilized growth factor signals and matrix stiffness. Further, few methods support patterning of biomolecular signals across a biomaterial in a spatially-selective manner. Here, we report a sequential approach employing carbodiimide crosslinking and benzophenone photoimmobilization chemistries to orthogonally modify the stiffness and immobilized growth factor content of a model collagen-GAG (CG) biomaterial. We subsequently examined the singular and combined effects of bone morphogenetic protein (BMP-2), platelet derived growth factor (PDGF-BB), and CG membrane stiffness on the bioactivity and osteogenic/adipogenic lineage-specific gene expression of adipose derived stem cells, an increasingly popular cell source for regenerative medicine studies. We found that the stiffest substrates direct osteogenic lineage commitment of ASCs regardless of the presence or absence of growth factors, while softer substrates require biochemical cues to direct cell fate. We subsequently describe the use of this approach to create overlapping patterns of growth factors across a single substrate. These results highlight the need for versatile approaches to selectively manipulate the biomaterial microenvironment to identify synergies between biochemical and mechanical cues for a range of regenerative medicine applications.

  17. The combined effects of matrix stiffness and growth factor immobilization on the bioactivity and differentiation capabilities of adipose-derived stem cells

    PubMed Central

    Banks, Jessica M.; Mozdzen, Laura C.; Harley, Brendan A.C.; Bailey, Ryan C.

    2015-01-01

    Biomaterial designs are increasingly incorporating multiple instructive signals to induce a desired cell response. However, many approaches do not allow orthogonal manipulation of immobilized growth factor signals and matrix stiffness. Further, few methods support patterning of biomolecular signals across a biomaterial in a spatially-selective manner. Here, we report a sequential approach employing carbodiimide crosslinking and benzophenone photoimmobilization chemistries to orthogonally modify the stiffness and immobilized growth factor content of a model collagen-GAG (CG) biomaterial. We subsequently examined the singular and combined effects of bone morphogenetic protein (BMP-2), platelet derived growth factor (PDGF-BB), and CG membrane stiffness on the bioactivity and osteogenic/adipogenic lineage-specific gene expression of adipose derived stem cells, an increasingly popular cell source for regenerative medicine studies. We found that the stiffest substrates direct osteogenic lineage commitment of ASCs regardless of the presence or absence of growth factors, while softer substrates require biochemical cues to direct cell fate. We subsequently describe the use of this approach to create overlapping patterns of growth factors across a single substrate. These results highlight the need for versatile approaches to selectively manipulate the biomaterial microenvironment to identify synergies between biochemical and mechanical cues for a range of regenerative medicine applications. PMID:25085859

  18. Influence of epidermal growth factor (EGF) and hydrocortisone on the co-culture of mature adipocytes and endothelial cells for vascularized adipose tissue engineering.

    PubMed

    Huber, Birgit; Czaja, Alina Maria; Kluger, Petra Juliane

    2016-05-01

    The composition of vascularized adipose tissue is still an ongoing challenge as no culture medium is available to supply adipocytes and endothelial cells appropriately. Endothelial cell medium is typically supplemented with epidermal growth factor (EGF) as well as hydrocortisone (HC). The effect of EGF on adipocytes is discussed controversially. Some studies say it inhibits adipocyte differentiation while others reported of improved adipocyte lipogenesis. HC is known to have lipolytic activities, which might result in mature adipocyte dedifferentiation. In this study, we evaluated the influence of EGF and HC on the co-culture of endothelial cells and mature adipocytes regarding their cell morphology and functionality. We showed in mono-culture that high levels of HC promoted dedifferentiation and proliferation of mature adipocytes, whereas EGF seemed to have no negative influence. Endothelial cells kept their typical cobblestone morphology and showed a proliferation rate comparable to the control independent of EGF and HC concentration. In co-culture, HC promoted dedifferentiation of mature adipocytes, which was shown by a higher glycerol release. EGF had no negative impact on adipocyte morphology. No negative impact on endothelial cell morphology and functionality could be seen with reduced EGF and HC supplementation in co-culture with mature adipocytes. Taken together, our results demonstrate that reduced levels of HC are needed for co-culturing mature adipocytes and endothelial cells. In co-culture, EGF had no influence on mature adipocytes. Therefore, for the composition of vascularized adipose tissue constructs, the media with low levels of HC and high or low levels of EGF can be used.

  19. Influence of epidermal growth factor (EGF) and hydrocortisone on the co-culture of mature adipocytes and endothelial cells for vascularized adipose tissue engineering.

    PubMed

    Huber, Birgit; Czaja, Alina Maria; Kluger, Petra Juliane

    2016-05-01

    The composition of vascularized adipose tissue is still an ongoing challenge as no culture medium is available to supply adipocytes and endothelial cells appropriately. Endothelial cell medium is typically supplemented with epidermal growth factor (EGF) as well as hydrocortisone (HC). The effect of EGF on adipocytes is discussed controversially. Some studies say it inhibits adipocyte differentiation while others reported of improved adipocyte lipogenesis. HC is known to have lipolytic activities, which might result in mature adipocyte dedifferentiation. In this study, we evaluated the influence of EGF and HC on the co-culture of endothelial cells and mature adipocytes regarding their cell morphology and functionality. We showed in mono-culture that high levels of HC promoted dedifferentiation and proliferation of mature adipocytes, whereas EGF seemed to have no negative influence. Endothelial cells kept their typical cobblestone morphology and showed a proliferation rate comparable to the control independent of EGF and HC concentration. In co-culture, HC promoted dedifferentiation of mature adipocytes, which was shown by a higher glycerol release. EGF had no negative impact on adipocyte morphology. No negative impact on endothelial cell morphology and functionality could be seen with reduced EGF and HC supplementation in co-culture with mature adipocytes. Taken together, our results demonstrate that reduced levels of HC are needed for co-culturing mature adipocytes and endothelial cells. In co-culture, EGF had no influence on mature adipocytes. Therefore, for the composition of vascularized adipose tissue constructs, the media with low levels of HC and high or low levels of EGF can be used. PMID:26888598

  20. Pre-Exposure of Human Adipose Mesenchymal Stem Cells to Soluble Factors Enhances Their Homing to Brain Cancer

    PubMed Central

    Smith, Chris L.; Chaichana, Kaisorn L.; Lee, Young M.; Lin, Benjamin; Stanko, Kevin M.; O’Donnell, Thomas; Gupta, Saksham; Shah, Sagar R.; Wang, Joanne; Wijesekera, Olindi; Delannoy, Michael

    2015-01-01

    Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood-brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture-based approach to enhance human adipose-derived MSC (hAMSC) engraftment to brain tumors. We used micro- and nanotechnological tools to systematically model several steps in the putative homing process. By pre-exposing hAMSCs to glioma-conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell-conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders. PMID:25646527

  1. Pre-exposure of human adipose mesenchymal stem cells to soluble factors enhances their homing to brain cancer.

    PubMed

    Smith, Chris L; Chaichana, Kaisorn L; Lee, Young M; Lin, Benjamin; Stanko, Kevin M; O'Donnell, Thomas; Gupta, Saksham; Shah, Sagar R; Wang, Joanne; Wijesekera, Olindi; Delannoy, Michael; Levchenko, Andre; Quiñones-Hinojosa, Alfredo

    2015-03-01

    Recent research advances have established mesenchymal stem cells (MSCs) as a promising vehicle for therapeutic delivery. Their intrinsic tropism for brain injury and brain tumors, their lack of immunogenicity, and their ability to breach the blood-brain barrier make these cells an attractive potential treatment of brain disorders, including brain cancer. Despite these advantages, the efficiency of MSC homing to the brain has been limited in commonly used protocols, hindering the feasibility of such therapies. In the present study, we report a reproducible, comprehensive, cell culture-based approach to enhance human adipose-derived MSC (hAMSC) engraftment to brain tumors. We used micro- and nanotechnological tools to systematically model several steps in the putative homing process. By pre-exposing hAMSCs to glioma-conditioned media and the extracellular matrix proteins fibronectin and laminin, we achieved significant enhancements of the individual homing steps in vitro. This homing was confirmed in an in vivo rodent model of brain cancer. This comprehensive, cell-conditioning approach provides a novel method to enhance stem cell homing to gliomas and, potentially, other neurological disorders.

  2. Adipose-derived stem cells could sense the nano-scale cues as myogenic-differentiating factors.

    PubMed

    Bayati, V; Altomare, L; Tanzi, M C; Farè, S

    2013-10-01

    Microenvironmental cues, such as surface topography and substrate stiffness, may affect stem cells adhesion, morphology, alignment, proliferation and differentiation. Adipose derived stem cells (ASCs) have attracted considerable interest in regenerative medicine due to their easy isolation, extensive in vitro expandability and ability to differentiate along a number of different tissue-specific lineages. The aim of this work was to investigate ASCs adhesion, alignment and differentiation into myogenic lineage on nanofibrous polymeric scaffolds with anisotropic topography. Nanostructured scaffolds with randomized or parallel fibers were fabricated by electrospinning using polycaprolactone (PCL) and the polycarbonate-urethane ChronoFlex AL 80A (CFAL). Cells expressed myosin (fast skeletal) and tropomyosin in all surface topographies 7 days after seeding but myotube formation was only observed on CFAL scaffolds and only few myotubes were formed on PCL scaffolds. The different cell behavior could be ascribed to two main parameters: fibers dimensions and fibers orientation of the substrates that could result in a better myotube formation on CFAL scaffolds. PMID:23793565

  3. Cinnamon extract regulates plasma levels of adipose-derived factors and expression of multiple genes related to carbohydrate metabolism and lipogenesis in adipose tissue of fructose-fed rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We reported previously that a dietary cinnamon extract (CE) improves systemic insulin sensitivity and dyslipidemia by enhancing insulin signaling. In the present study, we examined the effects of CE on several biomarkers including plasma levels of adipose-derived adipokines, and the potential molec...

  4. Adipose tissue: cell heterogeneity and functional diversity.

    PubMed

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. PMID:23834768

  5. Adipose tissue: cell heterogeneity and functional diversity.

    PubMed

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases.

  6. [Adipose tissue inflammation and atherosclerosis].

    PubMed

    Shwarts, V

    2009-01-01

    Adipose tissue is an endocrine organ secreting more than 30 various adipokines which regulate wide spectrum of metabolic and immune processes. Obesity is associated with development of adipose tissue inflammation. This inflammation is characterized by infiltration with macrophages, alterations of adipokine secretion, development of insulin resistance. All these factors promote atherosclerosis. Inflammation of perivascular adipose tissue is especially important. Adipokines damage vascular endothelium via paracrine pathway. Cytokines released by macrophages as well as changes of adipokine secretion lead to endothelial dysfunction - the first stage of atherogenesis. Besides specific action curative factors used in obesity, metabolic syndrome, and diabetes mellitus also produce anti-inflammatory effect and thus diminish risk factors of cardiovascular diseases, rate of their development, and alleviate manifestations of atherosclerosis. Inflammation of adipose tissue is a connecting link between obesity and atherosclerosis. This review contains an outline of roles of various major adipokines in development of atherosclerosis as well as synopsis of anti-inflammatory and antiatherogenic effects of glytazones , metformin, rimonabant, statins, and of lowering of body weight.

  7. The role of adipose protein derived hydrogels in adipogenesis.

    PubMed

    Uriel, Shiri; Huang, Jung-Ju; Moya, Monica L; Francis, Megan E; Wang, Rui; Chang, Shu-Ying; Cheng, Ming-Huei; Brey, Eric M

    2008-09-01

    Biomaterials that induce adipogenesis may ultimately serve as alternatives to traditional tissue reconstruction and regeneration techniques. In addition, these materials can provide environments for studying factors that regulate adipogenesis. The present study investigates the potential of adipose-derived matrices to induce adipogenesis in vitro and in vivo. Solutions containing basement membrane proteins and growth factors were extracted from subcutaneous adipose tissue. These extracts could be induced to form gels by either incubating the solutions at 37 degrees C or adjusting the pH to 4.0. The adipose extracts promoted rapid preadipocyte aggregation and formation of lipid-loaded colonies in vitro. Differentiation on adipose-derived gels was greater than tissue culture dishes and the tumor-derived product Matrigel (p < 0.05). Significant adipose formation was observed when adipose-derived gels were implanted around a rat epigastric pedicle bundle. Adipose levels in these gels were significantly greater than Matrigel (p < 0.05). The duration of adipose formation depended on the mechanism for gelling the solutions, with acid gelled matrices having greater adipose levels at 6 weeks than temperature gelled matrices. These adipose-derived hydrogels promote rapid adipogenesis in vitro and in vivo. They may lead to new materials for adipose tissue engineering, and provide an environment for studying cell-matrix interactions in adipogenesis.

  8. Adipocyte-Specific Hypoxia-Inducible Factor 2α Deficiency Exacerbates Obesity-Induced Brown Adipose Tissue Dysfunction and Metabolic Dysregulation.

    PubMed

    García-Martín, Rubén; Alexaki, Vasileia I; Qin, Nan; Rubín de Celis, María F; Economopoulou, Matina; Ziogas, Athanasios; Gercken, Bettina; Kotlabova, Klara; Phieler, Julia; Ehrhart-Bornstein, Monika; Bornstein, Stefan R; Eisenhofer, Graeme; Breier, Georg; Blüher, Matthias; Hampe, Jochen; El-Armouche, Ali; Chatzigeorgiou, Antonios; Chung, Kyoung-Jin; Chavakis, Triantafyllos

    2016-02-01

    Angiogenesis is a central regulator for white (WAT) and brown (BAT) adipose tissue adaptation in the course of obesity. Here we show that deletion of hypoxia-inducible factor 2α (HIF2α) in adipocytes (by using Fabp4-Cre transgenic mice) but not in myeloid or endothelial cells negatively impacted WAT angiogenesis and promoted WAT inflammation, WAT dysfunction, hepatosteatosis, and systemic insulin resistance in obesity. Importantly, adipocyte HIF2α regulated vascular endothelial growth factor (VEGF) expression and angiogenesis of obese BAT as well as its thermogenic function. Consistently, obese adipocyte-specific HIF2α-deficient mice displayed BAT dysregulation, associated with reduced levels of uncoupling protein 1 (UCP1) and a dysfunctional thermogenic response to cold exposure. VEGF administration reversed WAT and BAT inflammation and BAT dysfunction in adipocyte HIF2α-deficient mice. Together, our findings show that adipocyte HIF2α is protective against maladaptation to obesity and metabolic dysregulation by promoting angiogenesis in both WAT and BAT and by counteracting obesity-mediated BAT dysfunction. PMID:26572826

  9. Adipocyte-Specific Hypoxia-Inducible Factor 2α Deficiency Exacerbates Obesity-Induced Brown Adipose Tissue Dysfunction and Metabolic Dysregulation

    PubMed Central

    Alexaki, Vasileia I.; Qin, Nan; Rubín de Celis, María F.; Economopoulou, Matina; Ziogas, Athanasios; Gercken, Bettina; Kotlabova, Klara; Phieler, Julia; Ehrhart-Bornstein, Monika; Bornstein, Stefan R.; Eisenhofer, Graeme; Breier, Georg; Blüher, Matthias; Hampe, Jochen; El-Armouche, Ali; Chatzigeorgiou, Antonios; Chung, Kyoung-Jin

    2015-01-01

    Angiogenesis is a central regulator for white (WAT) and brown (BAT) adipose tissue adaptation in the course of obesity. Here we show that deletion of hypoxia-inducible factor 2α (HIF2α) in adipocytes (by using Fabp4-Cre transgenic mice) but not in myeloid or endothelial cells negatively impacted WAT angiogenesis and promoted WAT inflammation, WAT dysfunction, hepatosteatosis, and systemic insulin resistance in obesity. Importantly, adipocyte HIF2α regulated vascular endothelial growth factor (VEGF) expression and angiogenesis of obese BAT as well as its thermogenic function. Consistently, obese adipocyte-specific HIF2α-deficient mice displayed BAT dysregulation, associated with reduced levels of uncoupling protein 1 (UCP1) and a dysfunctional thermogenic response to cold exposure. VEGF administration reversed WAT and BAT inflammation and BAT dysfunction in adipocyte HIF2α-deficient mice. Together, our findings show that adipocyte HIF2α is protective against maladaptation to obesity and metabolic dysregulation by promoting angiogenesis in both WAT and BAT and by counteracting obesity-mediated BAT dysfunction. PMID:26572826

  10. Rat cortex and hippocampus-derived soluble factors for the induction of adipose-derived mesenchymal stem cells into neuron-like cells.

    PubMed

    Han, Chao; Song, Lin; Liu, Yang; Zou, Wei; Jiang, Chen; Liu, Jing

    2014-06-01

    To simulate brain microenvironment, adipose-derived mesenchymal stem cells (AMSC) were induced to differentiate to neuronal-like cells in rat cortex and hippocampus medium (Cox + Hip). First, isolated AMSC were characterized by flow cytometer and the capacity of adipogenesis and osteogenesis. After induction in rat cortex and hippocampus conditioned medium, the cell morphological change was examined and neural marker proteins (β-Ш-Tubulin, NSE, Nissl body) expression was detected by immunofluorescence staining. A variety of synaptic marker proteins, including GAP43, SHANK2, SHANK3 and Bassoon body, were detected. ELISA was used to measure brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) secretion at different time-points. AMSCs positively expressed CD13, CD44 and CD90 and could differentiate into osteoblasts or adipocytes. After induction in Cox + Hip medium for 14 days, cells had a typical neuronal perikaryal appearance, which was suggestive of neuronal differentiation. After 14 days of Cox + Hip treatment, the percentage of cells expressing β-Ⅲ-Tubulin, NSE and Nissl was 53.9 ± 0.8%, 51.3 ± 1.7% and 16.4 ± 2.1%, respectively. Expression of GAP43, SHANK2, SHANK3 and Bassoon body was detected, indicating synapse formation after treatment in Cox + Hip medium. Differentiated AMSCs secreted neurotrophic factors NGF and BDNF. Thus rat cortex and hippocampus-derived soluble factors can induce AMSCs to a neuronal-like phenotype, suggesting that AMSCs have a dual role in supplementing newborn neurons and secreting neurotrophic factors, and therefore could be help as a potential treatment for nervous system diseases.

  11. Adipose tissue as an endocrine organ.

    PubMed

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling.

  12. Sex dimorphism and depot differences in adipose tissue function.

    PubMed

    White, Ursula A; Tchoukalova, Yourka D

    2014-03-01

    Obesity, characterized by excessive adiposity, is a risk factor for many metabolic pathologies, such as type 2 diabetes mellitus (T2DM). Numerous studies have shown that adipose tissue distribution may be a greater predictor of metabolic health. Upper-body fat (visceral and subcutaneous abdominal) is commonly associated with the unfavorable complications of obesity, while lower-body fat (gluteal-femoral) may be protective. Current research investigations are focused on analyzing the metabolic properties of adipose tissue, in order to better understand the mechanisms that regulate fat distribution in both men and women. This review will highlight the adipose tissue depot- and sex-dependent differences in white adipose tissue function, including adipogenesis, adipose tissue developmental patterning, the storage and release of fatty acids, and secretory function. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  13. Preliminary study on non-viral transfection of F9 (factor IX) gene by nucleofection in human adipose-derived mesenchymal stem cells

    PubMed Central

    Olmedillas López, Susana; Garcia-Arranz, Mariano; Garcia-Olmo, Damian

    2016-01-01

    Background. Hemophilia is a rare recessive X-linked disease characterized by a deficiency of coagulation factor VIII or factor IX. Its current treatment is merely palliative. Advanced therapies are likely to become the treatment of choice for the disease as they could provide a curative treatment. Methods. The present study looks into the use of a safe non-viral transfection method based on nucleofection to express and secrete human clotting factor IX (hFIX) where human adipose tissue derived mesenchymal stem cells were used as target cells in vitro studies and NOD. Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice were used to analyze factor IX expression in vivo studies. Previously, acute liver injury was induced by an injected intraperitoneal dose of 500 mg/kg body weight of acetaminophen. Results. Nucleofection showed a percentage of positive cells ranging between 30.7% and 41.9% and a cell viability rate of 29.8%, and cells were shown to secrete amounts of hFIX between 36.8 and 71.9 ng/mL. hFIX levels in the blood of NSG mice injected with ASCs transfected with this vector, were 2.7 ng/mL 48 h after injection. Expression and secretion of hFIX were achieved both in vitro cell culture media and in vivo in the plasma of mice treated with the transfected ASCs. Such cells are capable of eventually migrating to a previously damaged target tissue (the liver) where they secrete hFIX, releasing it to the bloodstream over a period of at least five days from administration. Conclusions. The results obtained in the present study may form a preliminary basis for the establishment of a future ex vivo non-viral gene/cellular safe therapy protocol that may eventually contribute to advancing the treatment of hemophilia. PMID:27114871

  14. Modifiable early-life risk factors for childhood adiposity and overweight: an analysis of their combined impact and potential for prevention1234

    PubMed Central

    Crozier, Sarah R; Harvey, Nicholas C; Barton, Benjamin D; Law, Catherine M; Godfrey, Keith M; Cooper, Cyrus; Inskip, Hazel M

    2015-01-01

    Background: Early life may be a “critical period” when appetite and regulation of energy balance are programmed, with lifelong consequences for obesity risk. Insight into the potential impact of modifying early-life risk factors on later obesity can be gained by evaluating their combined effects. Objective: The objective was to examine the relation between the number of early-life risk factors and obesity outcomes among children in a prospective birth cohort (Southampton Women's Survey). Design: Five risk factors were defined: maternal obesity [prepregnant body mass index (BMI; in kg/m2) >30], excess gestational weight gain (Institute of Medicine, 2009), smoking during pregnancy, low maternal vitamin D status (<64 nmol/L), and short duration of breastfeeding (none or <1 mo). Obesity outcomes examined when the children were aged 4 and 6 y were BMI, dual-energy X-ray absorptiometry–assessed fat mass, overweight, or obesity (International Obesity Task Force). Data were available for 991 mother-child pairs, with children born between 1998 and 2003. Results: Of the children, 148 (15%) had no early-life risk factors, 330 (33%) had 1, 296 (30%) had 2, 160 (16%) had 3, and 57 (6%) had 4 or 5. At both 4 and 6 y, there were positive graded associations between number of early-life risk factors and each obesity outcome (all P < 0.001). After taking account of confounders, the relative risk of being overweight or obese for children who had 4 or 5 risk factors was 3.99 (95% CI: 1.83, 8.67) at 4 y and 4.65 (95% CI: 2.29, 9.43) at 6 y compared with children who had none (both P < 0.001). Conclusions: Having a greater number of early-life risk factors was associated with large differences in adiposity and risk of overweight and obesity in later childhood. These findings suggest that early intervention to change these modifiable risk factors could make a significant contribution to the prevention of childhood obesity. PMID:25646335

  15. Programmed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose-Derived Stem Cells for Osteochondral Defect Repair

    PubMed Central

    Zhu, Shouan; Chen, Pengfei; Wu, Yan; Xiong, Si; Sun, Heng; Xia, Qingqing; Shi, Libing

    2014-01-01

    Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose-derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro-lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell-based strategy for articular cartilage repair. PMID:25154784

  16. Effect of an Adipose-Derived Stem Cell and Nerve Growth Factor-Incorporated Hydrogel on Recovery of Erectile Function in a Rat Model of Cavernous Nerve Injury

    PubMed Central

    Kim, In Gul; Piao, Shuyu; Lee, Ji Young; Hong, Sung Hoo; Hwang, Tae-Kon; Kim, Sae Woong; Kim, Choung Soo; Ra, Jeong Chan; Noh, Insup

    2013-01-01

    Postprostatectomy erectile dysfunction (ED) is the major problem for patients with clinically localized prostate cancer. Recently, gene and stem cell-based therapy of the corpus cavernosum has been attempted for postprostatectomy ED, but those therapies are limited by rapid blood flow and disruption of the normal architecture of the corpus cavernosum. In this study, we attempted to regenerate the damaged cavernous nerve (CN), which is the main cause of ED. We investigated the effectiveness of human adipose-derived stem cell (hADSC) and nerve growth factor-incorporated hyaluronic acid-based hydrogel (NGF-hydrogel) application on the CN in a rat model of bilateral cavernous nerve crush injury. Four weeks after the operation, erectile function was assessed by detecting the intracavernous pressure (ICP)/arterial pressure level by CN electrostimulation. The ICP was significantly increased by application of hADSC with NGF-hydrogel compared to the other experimental groups. CN and penile tissue were collected for histological examination. PKH-26 labeled hADSC colocalized with beta III tubulin were shown in CN tissue sections. hADSC/NGF-hydrogel treatment prevented smooth muscle atrophy in the corpus cavernosum. In addition, the hADSC/NGF-hydrogel group showed increased endothelial nitric oxide synthase protein expression. This study suggests that application of hADSCs with NGF-hydrogel on the CN might be a promising treatment for postprostatectomy ED. PMID:22834730

  17. Programmed Application of Transforming Growth Factor β3 and Rac1 Inhibitor NSC23766 Committed Hyaline Cartilage Differentiation of Adipose-Derived Stem Cells for Osteochondral Defect Repair.

    PubMed

    Zhu, Shouan; Chen, Pengfei; Wu, Yan; Xiong, Si; Sun, Heng; Xia, Qingqing; Shi, Libing; Liu, Huanhuan; Ouyang, Hong Wei

    2014-10-01

    Hyaline cartilage differentiation is always the challenge with application of stem cells for joint repair. Transforming growth factors (TGFs) and bone morphogenetic proteins can initiate cartilage differentiation but often lead to hypertrophy and calcification, related to abnormal Rac1 activity. In this study, we developed a strategy of programmed application of TGFβ3 and Rac1 inhibitor NSC23766 to commit the hyaline cartilage differentiation of adipose-derived stem cells (ADSCs) for joint cartilage repair. ADSCs were isolated and cultured in a micromass and pellet culture model to evaluate chondrogenic and hypertrophic differentiation. The function of Rac1 was investigated with constitutively active Rac1 mutant and dominant negative Rac1 mutant. The efficacy of ADSCs with programmed application of TGFβ3 and Rac1 inhibitor for cartilage repair was studied in a rat model of osteochondral defects. The results showed that TGFβ3 promoted ADSCs chondro-lineage differentiation and that NSC23766 prevented ADSC-derived chondrocytes from hypertrophy in vitro. The combination of ADSCs, TGFβ3, and NSC23766 promoted quality osteochondral defect repair in rats with much less chondrocytes hypertrophy and significantly higher International Cartilage Repair Society macroscopic and microscopic scores. The findings have illustrated that programmed application of TGFβ3 and Rac1 inhibitor NSC23766 can commit ADSCs to chondro-lineage differentiation and improve the efficacy of ADSCs for cartilage defect repair. These findings suggest a promising stem cell-based strategy for articular cartilage repair.

  18. Associations between anthropometric indices of adiposity and atherogenic risk factors in Japanese working women aged 21-40 years.

    PubMed

    Nakamura, K; Shimai, S; Kikuchi, S; Maeda, A; Motohashi, Y; Tanaka, M; Nakano, S

    1998-10-01

    This study was conducted to explore whether anthropometric indices of obesity are associated with atherogenic risk factors in young adult working women in Japan. The subjects were 492 women in an occupational setting. Predictor variables were body mass index (BMI), the sum of triceps and subscapular skinfold thickness (SFT), and the waist to hip ratio (WHR). Outcome variables were serum total cholesterol, triglyceride and blood pressures. The average age of the subjects was 26.3 (SD 3.9) years. The upper quartiles of BMI and SFT were significantly associated with all atherogenic risk factors, while the upper quartiles of WHR were not. Multiple comparisons revealed the 4th quartiles of BMI (> 22.25) and SFT (> 39 mm) to have significantly higher values for all atherogenic risk factors. We found that BMI and skinfold thickness were more relevant to the prediction of atherogenic risk factors than WHR in young adult Japanese women.

  19. Platelet-derived growth factor BB enhances osteogenesis of adipose-derived but not bone marrow-derived mesenchymal stromal/stem cells

    PubMed Central

    Hung, Ben P.; Hutton, Daphne L.; Kozielski, Kristen L.; Bishop, Corey J.; Naved, Bilal; Green, Jordan J.; Caplan, Arnold I.; Gimble, Jeffrey M.; Dorafshar, Amir H.; Grayson, Warren L.

    2015-01-01

    Tissue engineering using mesenchymal stem cells holds great promise for regenerating critically sized bone defects. While the bone marrow-derived mesenchymal stem cell (MSC) is the most widely studied stromal/stem cell type for this application, its rarity within bone marrow and painful isolation procedure have motivated investigation of alternative cell sources. Adipose-derived stromal/stem cells (ASCs) are more abundant and more easily procured; furthermore, they also possess robust osteogenic potency. While these two cell types are widely considered very similar, there is a growing appreciation of possible innate differences in their biology and response to growth factors. In particular, reports indicate that their osteogenic response to platelet-derived growth factor BB (PDGF-BB) is markedly different: MSCs responded negatively or not at all to PDGF-BB while ASCs exhibited enhanced mineralization in response to physiological concentrations of PDGF-BB. In this study, we directly tested whether a fundamental difference existed between the osteogenic responses of MSCs and ASCs to PDGF-BB. MSCs and ASCs cultured under identical osteogenic conditions responded disparately to 20 ng/mL of PDGF-BB: MSCs exhibited no difference in mineralization while ASCs produced more calcium per cell. siRNA-mediated knockdown of PDGFRβ within ASCs abolished their ability to respond to PDGF-BB. Gene expression was also different; MSCs generally downregulated and ASCs generally upregulated osteogenic genes in response to PDGF-BB. ASCs transduced to produce PDGF-BB resulted in more regenerated bone within a critically sized murine calvarial defect compared to control ASCs, indicating PDGF-BB used specifically in conjunction with ASCs might enhance tissue engineering approaches for bone regeneration. PMID:26013357

  20. The Effect of Vitamin D Supplementation on Adiposity, Blood Glycated Hemoglobin, Serum Leptin and Tumor Necrosis Factor-α in Type 2 Diabetic Patients

    PubMed Central

    Ghavamzadeh, Saeid; Mobasseri, Majid; Mahdavi, Reza

    2014-01-01

    Background: Since tumor necrosis factor-α (TNF-α) could be one of the risk factors at the development of diabetes complications; as well as serum leptin deficiency is related to increased susceptibility to infections in diabetic patients, they are potential indices from the preventive medicine viewpoint. This study was conducted to represent the effect of supplemental vitamin D3 on serum leptin, TNF-α and adiposity in type 2 diabetic patients. Methods: In this randomized double-blind placebo-controlled trial, study sample was selected through type 2 diabetic patients (n = 51). A total of 26 patients were orally supplemented by vitamin D3 (400 IU/d) (vitamin D group) and 25 patients by placebo (placebo group) for 14 weeks. The blood glycated hemoglobin (HbA1c) and the serum ionized Ca, leptin, TNF-α, and serum 25-hydroxyvitamin D (25[OH] D) were measured at the two groups in the baseline and postintervention stages. Results: It was shown that despite of theplacebo group, serum 25(OH) D and serum leptin was significantly increased (P = 0.001 and P = 0.002, respectively), while serum TNF-α was decreased significantly (P = 0.001) in vitamin D group. The remaining parameters, including body fat mass and HbA1c had no alterations between baseline and postintervention stages in vitamin D group. Conclusions: This study may advocate vitamin D supplementation among type 2 diabetic patients due to its beneficial effects on prevention of diabetes complications. PMID:25317290

  1. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors.

    PubMed

    Maroni, Paola; Brini, Anna Teresa; Arrigoni, Elena; de Girolamo, Laura; Niada, Stefania; Matteucci, Emanuela; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2012-11-16

    The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) γ. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPARγ and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPARγ/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPARγ target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal a role for HDACs in orchestrating osteo-differentiation of hASCs at transcriptional level, and might provide new insights into the modulation of hASCs-based regenerative therapy. PMID:23085045

  2. Interaction Between Osteoarthritic Chondrocytes and Adipose-Derived Stem Cells Is Dependent on Cell Distribution in Three-Dimension and Transforming Growth Factor-β3 Induction

    PubMed Central

    Lai, Janice H.; Rogan, Heather; Kajiyama, Glen; Goodman, Stuart B.; Smith, R. Lane; Maloney, William

    2015-01-01

    Stem cells hold great promise for treating cartilage degenerative diseases such as osteoarthritis (OA). The efficacy of stem cell-based therapy for cartilage repair is highly dependent on their interactions with local cells in the joint. This study aims at evaluating the interactions between osteoarthritic chondrocytes (OACs) and adipose-derived stem cells (ADSCs) using three dimensional (3D) biomimetic hydrogels. To examine the effects of cell distribution on such interactions, ADSCs and OACs were co-cultured in 3D using three co-culture models: conditioned medium (CM), bi-layered, and mixed co-culture with varying cell ratios. Furthermore, the effect of transforming growth factor (TGF)-β3 supplementation on ADSC–OAC interactions and the resulting cartilage formation was examined. Outcomes were analyzed using quantitative gene expression, cell proliferation, cartilage matrix production, and histology. TGF-β3 supplementation led to a substantial increase in cartilage matrix depositions in all groups, but had differential effects on OAC–ADSC interactions in different co-culture models. In the absence of TGF-β3, CM or bi-layered co-culture had negligible effects on gene expression or cartilage formation. With TGF-β3 supplementation, CM and bi-layered co-culture inhibited cartilage formation by both ADSCs and OACs. In contrast, a mixed co-culture with moderate OAC ratios (25% and 50%) resulted in synergistic interactions with enhanced cartilage matrix deposition and reduced catabolic marker expression. Our results suggested that the interaction between OACs and ADSCs is highly dependent on cell distribution in 3D and soluble factors, which should be taken into consideration when designing stem cell-based therapy for treating OA patients. PMID:25315023

  3. Driving Cartilage Formation in High-Density Human Adipose-Derived Stem Cell Aggregate and Sheet Constructs Without Exogenous Growth Factor Delivery

    PubMed Central

    Dang, Phuong N.; Solorio, Loran D.

    2014-01-01

    An attractive cell source for cartilage tissue engineering, human adipose-derived stem cells (hASCs) can be easily expanded and signaled to differentiate into chondrocytes. This study explores the influence of growth factor distribution and release kinetics on cartilage formation within 3D hASC constructs incorporated with transforming growth factor-β1 (TGF-β1)-loaded gelatin microspheres. The amounts of microspheres, TGF-β1 concentration, and polymer degradation rate were varied within hASC aggregates. Microsphere and TGF-β1 loading concentrations were identified that resulted in glycosaminoglycan (GAG) production comparable to those of control aggregates cultured in TGF-β1-containing medium. Self-assembling hASC sheets were then engineered for the production of larger, more clinically relevant constructs. Chondrogenesis was observed in hASC-only sheets cultured with exogenous TGF-β1 at 3 weeks. Importantly, sheets with incorporated TGF-β1-loaded microspheres achieved GAG production similar to sheets treated with exogenous TGF-β1. Cartilage formation was confirmed histologically via observation of cartilage-like morphology and GAG staining. This is the first demonstration of the self-assembly of hASCs into high-density cell sheets capable of forming cartilage in the presence of exogenous TGF-β1 or with TGF-β1-releasing microspheres. Microsphere incorporation may bypass the need for extended in vitro culture, potentially enabling hASC sheets to be implanted more rapidly into defects to regenerate cartilage in vivo. PMID:24873753

  4. Post-mortem stability of RNA in skeletal muscle and adipose tissue and the tissue-specific expression of myostatin, perilipin and associated factors in the horse.

    PubMed

    Morrison, Philippa K; Bing, Chen; Harris, Patricia A; Maltin, Charlotte A; Grove-White, Dai; Argo, Caroline McG

    2014-01-01

    Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue

  5. Post-mortem stability of RNA in skeletal muscle and adipose tissue and the tissue-specific expression of myostatin, perilipin and associated factors in the horse.

    PubMed

    Morrison, Philippa K; Bing, Chen; Harris, Patricia A; Maltin, Charlotte A; Grove-White, Dai; Argo, Caroline McG

    2014-01-01

    Obesity, a major concern for equine welfare, is highly prevalent in the leisure horse population. Skeletal-muscle and adipose tissues are important determinants of maintenance energy requirements. The myostatin and perilipin pathways play key roles in the regulation of muscle mass and lipolysis respectively and have both been associated with obesity predisposition in other mammalian species. High quality samples, suitable for molecular biology, are an essential prerequisite for detailed investigations of gene and protein expression. Hence, this study has evaluated a) the post-mortem stability of RNA extracted from skeletal-muscle and adipose-tissues collected under commercial conditions and b) the tissue-specific presence of myostatin, the moystatin receptor (activin receptor IIB, ActRIIB), follistatin and perilipin, genes and proteins across a range of equine tissues. Objectives were addressed using tissues from 7 Thoroughbred horses presented for slaughter at a commercial abattoir; a) samples were collected at 7 time-points from Masseter muscle and perirenal adipose from 5 minutes to 6 hours post-mortem. Extracted RN was appraised by Optical Density analysis and agarose-gel electrophoresis. b) Quantitative real time PCR and Western Blotting were used to evaluate gene and protein expression in anatomically-defined samples collected from 17 tissues (6 organs, 4 skeletal muscles and 7 discrete adipose depots). The results indicate that, under the present collection conditions, intact, good quality RNA could be extracted from skeletal-muscle for up to 2 hours post-mortem. However, RNA from adipose tissue may be more susceptible to degradation/contamination and samples should be collected no later than 30 minutes post-mortem. The data also show that myostatin and ActRIIB genes and proteins were almost exclusively expressed in skeletal muscle. The follistatin gene showed a more diverse gene expression profile, with expression evident in several organs, adipose tissue

  6. [Human brown adipose tissue].

    PubMed

    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  7. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes.

    PubMed

    Corvera, Silvia; Gealekman, Olga

    2014-03-01

    The growth and function of tissues are critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in turn increases type-2 diabetes risk. In addition, genetic and developmental factors involved in vascular patterning may define the size and expandability of diverse adipose tissue depots, which are also associated with type-2 diabetes risk. Moreover, the adipose tissue vasculature appears to be the niche for pre-adipocyte precursors, and factors that affect angiogenesis may directly impact the generation of new adipocytes. Here we review recent advances on the basic mechanisms of angiogenesis, and on the role of angiogenesis in adipose tissue development and obesity. A substantial amount of data points to a deficit in adipose tissue angiogenesis as a contributing factor to insulin resistance and metabolic disease in obesity. These emerging findings support the concept of the adipose tissue vasculature as a source of new targets for metabolic disease therapies. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  8. Impact of embryo number and periconceptional undernutrition on factors regulating adipogenesis, lipogenesis, and metabolism in adipose tissue in the sheep fetus.

    PubMed

    Lie, Shervi; Morrison, Janna L; Williams-Wyss, Olivia; Ozanne, Susan E; Zhang, Song; Walker, Simon K; Kleemann, David O; MacLaughlin, Severence M; Roberts, Claire T; McMillen, I Caroline

    2013-10-15

    Maternal undernutrition around the time of conception is associated with an increased risk of insulin resistance in adulthood. We hypothesized that maternal undernutrition during the periconceptional (PCUN: -60 to 7 days) and/or preimplantation (PIUN: 0-7 days) periods would result in a decrease in UCP1 expression and the abundance of insulin signaling molecules and an increase in the abundance of factors that regulate adipogenesis and lipogenesis in fetal perirenal adipose tissue (PAT) and that these effects would be different in singletons and twins. Maternal PCUN and PIUN resulted in a decrease in UCP1 expression in PAT, and PIUN resulted in higher circulating insulin concentrations, an increased abundance of pPKCζ and PDK4, and a decreased abundance of Akt1, phosphorylated mTOR, and PPARγ in PAT in singleton and twin fetuses. In singletons, there was also a decrease in the abundance of p110β in PAT in the PCUN and PIUN groups and an increase in total AMPKα in PAT in the PIUN group. In twins, however, there was an increase in the abundance of mTOR in the PCUN group and an increase in PDK2 and decrease in total AMPKα in the PIUN group. Thus exposure to periconceptional undernutrition programs changes in the thermogenic capacity and the insulin and fatty acid oxidation signaling pathway in visceral fat, and these effects are different in singletons and twins. These findings are important, as the thermogenic capacity of brown fat and the insulin sensitivity of visceral fat are important determinants of the risk of developing obesity and an insulin resistance phenotype in later life. PMID:23921136

  9. Increased responses to the actions of fibroblast growth factor 21 on energy balance and body weight in a seasonal model of adiposity.

    PubMed

    Murphy, M; Samms, R; Warner, A; Bolborea, M; Barrett, P; Fowler, M J; Brameld, J M; Tsintzas, K; Kharitonenkov, A; Adams, A C; Coskun, T; Ebling, F J P

    2013-02-01

    The present study aimed to investigate the actions of fibroblast growth factor 21 (FGF21) on energy balance in a natural model of relative fatness, the Siberian hamster. Hamsters were studied under long days (LD) to promote weight gain, or short days to induce weight loss, and treated with rhFGF21 (3 mg/kg/day) via s.c. minipumps for 14 days. On days 7-9, detailed assessments of ingestive behaviour, metabolic gas exchange and locomotor activity were made. FGF21 caused substantial (P < 0.0001) weight loss in the fat LD state but not in the lean SD state: at the end of the study, FGF21-treated hamsters in LD lost 18% of body weight compared to vehicle controls, which is comparable to the natural body weight loss observed in SD. Epididymal fat pads, a correlate of total carcass fat content, were reduced by 19% in FGF21 treated hamsters in LD, whereas no difference was found in SD. Body weight loss in LD was associated with a reduction in food intake (P < 0.001) and a decreased respiratory exchange ratio (P < 0.001), indicating increased fat oxidation. Treatment with FGF21 maintained the normal nocturnal increase in oxygen consumption and carbon dioxide production into the early light phase in hamsters in LD, indicating increased energy expenditure, although locomotor activity was unaffected. These data suggest a greater efficacy of FGF21 in hamsters in LD compared to those in SD, which is consistent with both the peripheral and possibly central actions of FGF21 with respect to promoting a lean phenotype. The observed differences in FGF21 sensitivity may relate to day length-induced changes in adipose tissue mass.

  10. Fibroblast Growth Factor 21 Improves Insulin Sensitivity and Synergizes with Insulin in Human Adipose Stem Cell-Derived (hASC) Adipocytes

    PubMed Central

    Lee, Darwin V.; Li, Dongmei; Yan, Qingyun; Zhu, Yimin; Goodwin, Bryan; Calle, Roberto; Brenner, Martin B.; Talukdar, Saswata

    2014-01-01

    Fibroblast growth factor 21 (FGF21) has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC) adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR), insulin receptor substrate-1 (IRS-1), and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway. PMID:25365322

  11. PPARs and Adipose Cell Plasticity

    PubMed Central

    Casteilla, Louis; Cousin, Béatrice; Carmona, Mamen

    2007-01-01

    Due to the importance of fat tissues in both energy balance and in the associated disorders arising when such balance is not maintained, adipocyte differentiation has been extensively investigated in order to control and inhibit the enlargement of white adipose tissue. The ability of a cell to undergo adipocyte differentiation is one particular feature of all mesenchymal cells. Up until now, the peroxysome proliferator-activated receptor (PPAR) subtypes appear to be the keys and essential players capable of inducing and controlling adipocyte differentiation. In addition, it is now accepted that adipose cells present a broad plasticity that allows them to differentiate towards various mesodermal phenotypes. The role of PPARs in such plasticity is reviewed here, although no definite conclusion can yet be drawn. Many questions thus remain open concerning the definition of preadipocytes and the relative importance of PPARs in comparison to other master factors involved in the other mesodermal phenotypes. PMID:17710234

  12. White blood cell count in women: relation to inflammatory biomarkers, haematological profiles, visceral adiposity, and other cardiovascular risk factors.

    PubMed

    Farhangi, Mahdieh Abbasalizad; Keshavarz, Seyyed-Ali; Eshraghian, Mohammadreza; Ostadrahimi, Alireza; Saboor-Yaraghi, Ali-Akbar

    2013-03-01

    The role of white blood cell (WBC) count in pathogenesis of diabetes, cardiovascular disease, and obesity-related disorders has been reported earlier. Recent studies revealed that higher WBC contributes to atherosclerotic progression and impaired fasting glucose. However, it is unknown whether variations in WBC and haematologic profiles can occur in healthy obese individuals. The aim of this study is to further evaluate the influence of obesity on WBC count, inflammatory biomarkers, and metabolic risk factors in healthy women to establish a relationship among variables analyzed. The sample of the present study consisted of 84 healthy women with mean age of 35.56 +/- 6.83 years. They were categorized into two groups based on their body mass index (BMI): obese group with BMI > 30 kg/m2 and non-obese group with BMI < 30 kg/m2. We evaluated the relationship between WBC and platelet count (PLT) with serum interleukin 6 (IL-6), C-reactive protein (CRP), angiotensin pi (Ang pi), body fat percentage (BF %), waist-circumference (WC), and lipid profile. WBC, PLT, CRP, and IL-6 in obese subjects were significantly higher than in non-obese subjects (p < 0.05). The mean WBC count in obese subjects was 6.4 +/- 0.3 (x10(9)/L) compared to 4.4 +/- 0.3 (x10(9)/L) in non-obese subjects (p = 0.035). WBC correlated with BF% (r = 0.31, p = 0.004), CRP (r = 0.25, P = 0.03), WC (r = 0.22, p = 0.04), angiotensin 11 (r = 0.24, p = 0.03), triglyceride (r = 0.24, p = 0.03), and atherogenic index of plasma (AIP) levels (r = 0.3, p = 0.028) but not with IL-6. Platelet count was also associated with WC and waist-to-hip ratio (p < 0.05). Haemoglobin and haematocrit were in consistent relationship with LDL-cholesterol (p < 0.05). In conclusion, obesity was associated with higher WBC count and inflammatory parameters. There was also a positive relationship between WBC count and several inflammatory and metabolic risk factors in healthy women.

  13. BODY ADIPOSITY INDEX AND ASSOCIATED FACTORS IN ADULTS: METHOD AND LOGISTICS OF A POPULATION-BASED STUDY.

    PubMed

    Segheto, Wellington; Cristina Guimarães da Silva, Danielle; Araújo Coelho, France; Guimarães Reis, Vanessa; Helena Oliveira Morais, Silvia; Carlos Bouzas Marins, João; Queiroz Ribeiro, Andreia; Zarbato Longo, Giana

    2015-07-01

    Introducción: la obesidad es un problema de salud pública que ha aumentado considerablemente. Se han desarrollado distintas técnicas para medir la cantidad de grasa corporal, o una combinación de exceso de grasa con ciertas comorbilidades. El Índice de Adiposidad Corporal es un nuevo método propuesto para determinar la grasa corporal y su validación es aún limitada. Solo hay algunos métodos y logísticas de estudios poblacionales recogidos en la bibliografía, la mayoría de equipos multidisciplinares. Objetivo: el objetivo consistió en informar de los procedimientos de un estudio poblacional, para concluir en el índice de adiposidad en adultos. Diseño: el diseño de este estudio fue transversal, con una muestra de 1.085 adultos con edades entre 20 y 59 años, que vivían en la ciudad de Viçosa, MG. Se aplicó un cuestionario para completar en casa, con aspectos sociodemográficos, conductuales, de salud y del nivel de actividad física. Después se recopilaron los valores antropométricos y bioquímicos. La formación para la recogida de datos incluyó el calibrado de los evaluadores, estableciéndose la correlación entre las mediciones a partir de una comprobación mediante una prueba de correlación intraclase, siendo 0,60 el valor definido como aceptable. Resultados: se observa que, a excepción del evaluador 1, para los pliegues cutáneos subescapulares, y del evaluador 4, para los pliegues cutáneos pectorales y suprailiacos, el resto de mediciones alcanzaron un nivel aceptable de acuerdo entre los evaluadores. Conclusiones: la investigación multidisciplinar es importante para comprender los distintos factores que podrían intervenir en la herramienta de evaluación de salud y enfermedad. Se deberían seguir los aspectos metodológicos y logísticos descritos en este estudio, los cuales llevan a una reducción continua de los sesgos de la investigación.

  14. Evidence that nesfatin-1 is a satiety factor in the pig and that the hypothalamus controls its expression in adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two experiments (Exp) were conducted to test if nesfatin-1 is part of the adipose tissue-hypothalamic loop regulating appetite and energy balance of the pig. In Exp 1, prepuberal gilts were adapted to a twice-daily feeding schedule (0800 and 1600 h) and received intracerebroventricular (i.c.v.) inje...

  15. Chemical and genetic blockade of HDACs enhances osteogenic differentiation of human adipose tissue-derived stem cells by oppositely affecting osteogenic and adipogenic transcription factors

    SciTech Connect

    Maroni, Paola; Brini, Anna Teresa; Arrigoni, Elena; Girolamo, Laura de; Niada, Stefania; Matteucci, Emanuela; Bendinelli, Paola; Desiderio, Maria Alfonsina

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Acetylation affected hASCs osteodifferentiation through Runx2-PPAR{gamma}. Black-Right-Pointing-Pointer HDACs knocking-down favoured the commitment effect of osteogenic medium. Black-Right-Pointing-Pointer HDACs silencing early activated Runx2 and ALP. Black-Right-Pointing-Pointer PPAR{gamma} reduction and calcium/collagen deposition occurred later. Black-Right-Pointing-Pointer Runx2/PPAR{gamma} target genes were modulated in line with HDACs role in osteo-commitment. -- Abstract: The human adipose-tissue derived stem/stromal cells (hASCs) are an interesting source for bone-tissue engineering applications. Our aim was to clarify in hASCs the role of acetylation in the control of Runt-related transcription factor 2 (Runx2) and Peroxisome proliferator activated receptor (PPAR) {gamma}. These key osteogenic and adipogenic transcription factors are oppositely involved in osteo-differentiation. The hASCs, committed or not towards bone lineage with osteoinductive medium, were exposed to HDACs chemical blockade with Trichostatin A (TSA) or were genetically silenced for HDACs. Alkaline phosphatase (ALP) and collagen/calcium deposition, considered as early and late osteogenic markers, were evaluated concomitantly as index of osteo-differentiation. TSA pretreatment, useful experimental protocol to analyse pan-HDAC-chemical inhibition, and switch to osteogenic medium induced early-osteoblast maturation gene Runx2, while transiently decreased PPAR{gamma} and scarcely affected late-differentiation markers. Time-dependent effects were observed after knocking-down of HDAC1 and 3: Runx2 and ALP underwent early activation, followed by late-osteogenic markers increase and by PPAR{gamma}/ALP activity diminutions mostly after HDAC3 silencing. HDAC1 and 3 genetic blockade increased and decreased Runx2 and PPAR{gamma} target genes, respectively. Noteworthy, HDACs knocking-down favoured the commitment effect of osteogenic medium. Our results reveal

  16. Effects of brain-derived neurotrophic factor and neurotrophin-3 on the neuronal differentiation of rat adipose-derived stem cells

    PubMed Central

    JI, WENCHEN; ZHANG, XIAOWEI; JI, LE; WANG, KUNZHENG; QIU, YUSHENG

    2015-01-01

    Tissue engineering is a promising method that may be used to treat spinal cord injury (SCI). The underlying repair mechanism of tissue engineering involves the stable secretion of neurotrophins from seed cells, which eventually differentiate into neurons; therefore, the selection of appropriate seed cells, which stably secrete neurotrophins that easily differentiate into neurons requires investigation. Adipose-derived stem cells (ADSCs), which are adult SCs, are advantageous due to convenience sampling and easy expansion; therefore, ADSCs are currently the most popular type of seed cell. Brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) possess superior properties, when compared with other neurotrophic factors, in the maintenance of neuronal survival and promotion of SC differentiation into neurons. The present study used two lentiviruses, which specifically express BDNF and NT-3 [Lenti-BDNF-green fluorescent protein (GFP), Lenti-NT-3-red fluorescent protein (RFP)], to transfect third-generation ADSCs. Three types of seed cell were obtained: i) Seed cells overexpressing BDNF (ADSC/Lenti-BDNF-GFP); ii) seed cells overexpressing NT-3 (ADSC/Lenti-NT-3-RFP); and iii) seed cells overexpressing BDNF and NT-3 (ADSC/Lenti-BDNF-GFP and NT-3-RFP). The transfected cells were then induced to differentiate into neurons and were divided into a further four groups: i) The BDNF and NT-3 co-overexpression group; ii) the BDNF overexpression group; iii) the NT-3 overexpression group; and iv) the control group, which consisted of untransfected ADSCs. The results of the present study demonstrate that BDNF and NT-3 expression was higher 10 days after induction, as detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. Neuron-specific enolase is a neuronal marker, the expression of which was highest in the BDNF and NT-3 co-overexpression group, followed by the BDNF overexpression group and then by the NT-3 overexpression

  17. Short-term exposure to tumor necrosis factor-alpha enables human osteoblasts to direct adipose tissue-derived mesenchymal stem cells into osteogenic differentiation.

    PubMed

    Lu, ZuFu; Wang, Guocheng; Dunstan, Colin R; Zreiqat, Hala

    2012-09-01

    Tumor necrosis factor-alpha (TNF-α) is one major inflammatory factor peaking at 24 h after bone fracture in response to injury; its role in bone healing is controversial. The aims of this study were to investigate whether the duration of exposure to TNF-α is crucial for the initiation of bone regeneration and to determine its underlying mechanism(s). We demonstrated that 24 h of TNF-α treatment significantly abrogated osteocalcin gene expression by human primary osteoblasts (HOBs). However, when TNF-α was withdrawn after 24 h, bone sialoprotein and osteocalcin gene expression levels in HOBs at day 7 were significantly up-regulated compared with the HOBs without TNF-α treatment. In contrast, continuous TNF-α treatment down-regulated bone sialoprotein and osteocalcin gene expression. In addition, in an indirect co-culture system, HOBs pretreated with TNF-α for 24 h induced significantly greater osteogenic differentiation of adipose tissue-derived mesenchymal stem cells (ASCs) than the HOBs without TNF-α treatment. TNF-α treatment also promoted endogenous bone morphogenetic protein 2 (BMP-2) production in HOBs, while blocking the BMP-2 signaling pathway with Noggin inhibited osteogenic differentiation of ASCs in the co-culture system. Furthermore, activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway after TNF-α treatment occurred earlier than BMP-2 protein expression. BMP-2 production by HOBs and osteogenic differentiation of ASCs in the co-culture system with HOBs was significantly decreased when HOBs were pretreated with TNF-α in combination with the p38 MAPK-specific inhibitor (SB203580). Taken together, we provide evidence that exposure duration is a critical element in determining TNF-α's effects on bone regeneration. We also demonstrate that the p38 MAPK signaling pathway regulates the expression of BMP-2 in osteoblasts, which then acts through a paracrine loop, to direct the osteoblast lineage commitment of mesenchymal

  18. Gene expression profiling in developing pig adipose tissue: non-secreted regulatory proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The expression of many genes encoding secreted and non-secreted factors have been studied in human and rodent adipose tissue with cDNA microarrays, but few such studies in adipose tissue from growing pigs have been reported. Total RNA was collected at slaughter from outer subcutaneous adipose tissue...

  19. Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking.

    PubMed

    Tsuji, Takao; Kelly, Neil J; Takahashi, Saeko; Leme, Adriana S; Houghton, A McGarry; Shapiro, Steven D

    2014-12-01

    Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.

  20. Macrophage Elastase Suppresses White Adipose Tissue Expansion with Cigarette Smoking

    PubMed Central

    Tsuji, Takao; Kelly, Neil J.; Takahashi, Saeko; Leme, Adriana S.; McGarry Houghton, A.

    2014-01-01

    Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots. PMID:24914890

  1. Sulfasalazine and BAY 11-7082 interfere with the nuclear factor-kappa B and I kappa B kinase pathway to regulate the release of proinflammatory cytokines from human adipose tissue and skeletal muscle in vitro.

    PubMed

    Lappas, Martha; Yee, Kirin; Permezel, Michael; Rice, Gregory E

    2005-03-01

    There is much evidence to indicate a role for adipocytokines in insulin resistance and/or type 2 diabetes mellitus. In experimental models, oral salicylates, through their ability to interfere with the nuclear factor-kappa B (NF-kappa B) transcription pathway, have been demonstrated to reverse insulin resistance. The aim of this study was to investigate whether NF-kappa B regulates the release of adipocytokines in human adipose tissue and skeletal muscle. Human sc adipose tissue and skeletal muscle (obtained from normal pregnant women) were incubated in the absence (control) or presence of two NF-kappa B inhibitors sulfasalazine (1.25, 2.5, and 5 mm) and BAY 11-7082 (25, 50, and 100 microm). After an 18-h incubation, the tissues were collected, and NF-kappa B p65 DNA-binding activity and I kappa B kinase (IKK-beta) and insulin receptor-beta protein expression were assessed by ELISA and Western blotting, respectively. The incubation medium was collected, and the release of TNF-alpha, IL-6, IL-8, resistin, adiponectin, and leptin was quantified by ELISA. Treatment of adipose tissue and skeletal muscle with sulfasalazine and BAY 11-7082 significantly inhibited the release of IL-6, IL-8, and TNF-alpha; NF-kappa B p65 DNA-binding activity; and IKK-beta protein expression (P < 0.05, by Newman-Keuls test). There was no effect of sulfasalazine and BAY 11-7082 on resistin, adiponectin, or leptin release. Both sulfasalazine and BAY 11-7082 increased the adipose tissue and skeletal muscle expression of insulin receptor-beta. The data presented in this study demonstrate that the IKK-beta/NF-kappa B transcription pathway is a key regulator of IL-6, IL-8, and TNF-alpha release from adipose tissue and skeletal muscle. Control of the IKK-beta/NF-kappa B pathway may therefore provide an alternative therapeutic strategy for regulating aberrant cytokine release and thereby alleviating insulin resistance in type 2 diabetes mellitus.

  2. Brown adipose tissue growth and development.

    PubMed

    Symonds, Michael E

    2013-01-01

    Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  3. Genome-wide analysis of microRNAs identifies the lipid metabolism pathway to be a defining factor in adipose tissue from different sheep

    PubMed Central

    Miao, Xiangyang; Luo, Qingmiao; Qin, Xiaoyu; Guo, Yuntao

    2015-01-01

    MicroRNAs are short (17–24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. In recent years, deep sequencing of the transcriptome is increasingly being utilized with the promise of higher sensitivity for the identification of differential expression patterns as well as the opportunity to discover new transcripts, including new alternative isoforms and miRNAs. Here, we utilized RNA-seq technology to perform a genome-wide analysis of miRNAs from the adipose tissue of the two species of sheep to look for clues that might explain the fat deposition differences between the sheep. The RNA-seq analysis detected 3132 miRNAs from the adipose tissue of the Small-tail Han and Dorset sheep, of which 2893 were defined as potential new miRNAs. In addition, 54 miRNAs were differentially expressed between the two breeds of sheep. Gene ontology and pathway analyses of the predicted target genes that negatively associated with the differentially expressed miRNAs revealed that there was less active lipid metabolism in the adipose tissue of Small Tail Han sheep. This study can help understand the underling mechanisms responsible for the morphological differences related to fat deposition between two breeds of sheep. PMID:26690086

  4. Adipose tissue and metabolic syndrome: too much, too little or neither.

    PubMed

    Grundy, Scott M

    2015-11-01

    Obesity is strongly associated with metabolic syndrome. Recent research suggests that excess adipose tissue plays an important role in development of the syndrome. On the other hand, persons with a deficiency of adipose tissue (e.g. lipodystrophy) also manifest the metabolic syndrome. In some animal models, expansion of adipose tissue pools mitigates adverse metabolic components (e.g. insulin resistance, hyperglycaemia and dyslipidemia). Hence, there are conflicting data as to whether adipose tissue worsens the metabolic syndrome or protects against it. This conflict may relate partly to locations of adipose tissue pools. For instance, lower body adipose tissue may be protective whereas upper body adipose tissue may promote the syndrome. One view holds that in either case, the accumulation of ectopic fat in muscle and liver is the driving factor underlying the syndrome. If so, there may be some link between adipose tissue fat and ectopic fat. But the mechanisms underlying this connection are not clear. A stronger association appears to exist between excessive caloric intake and ectopic fat accumulation. Adipose tissue may act as a buffer to reduce the impact of excess energy consumption by fat storage; but once a constant weight has been achieved, it is unclear whether adipose tissue influences levels of ectopic fat. Another mechanism whereby adipose tissue could worsen the metabolic syndrome is through release of adipokines. This is an intriguing mechanism, but the impact of adipokines on metabolic syndrome risk factors is uncertain. Thus, many potential connections between adipose tissue and metabolic syndrome remain to unravelled.

  5. Correlates of adiposity among Latino preschool children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Childhood obesity is at record high levels in the US and disproportionately affects Latino children; however, studies examining Latino preschool children's obesity-related risk factors are sparse. This study determined correlates of Latino preschoolers' (ages 3-5 years) adiposity to inform future ob...

  6. Habituation to a stressor predicts adolescents' adiposity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background and Objectives: Stress is associated with gains in adiposity. One factor that determines how much stress is experienced is how quickly an adolescent reduces responding (habituates) across repeated stressors. The purpose of this study was to determine the association of body mass index pe...

  7. Enzymatic intracrine regulation of white adipose tissue

    PubMed Central

    DiSilvestro, David; Petrosino, Jennifer; Aldoori, Ayat; Melgar-Bermudez, Emiliano; Wells, Alexandra; Ziouzenkova, Ouliana

    2015-01-01

    Abdominal fat formation has become a permanent risk factor for metabolic syndrome and various cancers in one-third of the world's population of obese and even lean patients. Formation of abdominal fat involves additional mechanisms beyond an imbalance in energy intake and expenditure, which explains systemic obesity. In this review, we briefly summarized autonomous regulatory circuits that locally produce hormones from inactive precursors or nutrients for intra-/auto-/paracrine signaling in white adipose depots. Enzymatic pathways activating steroid and thyroid hormones in adipose depots were compared with enzymatic production of retinoic acid from vitamin A. We discussed the role of intracrine circuits in fat-depot functions and strategies to reduce abdominal adiposity through thermogenic adipocytes with interrupted generation of retinoic acid. PMID:25390015

  8. Adipokines and the Endocrine Role of Adipose Tissues.

    PubMed

    Giralt, Marta; Cereijo, Rubén; Villarroya, Francesc

    2016-01-01

    The last two decades have witnessed a shift in the consideration of white adipose tissue as a mere repository of fat to be used when food becomes scarce to a true endocrine tissue releasing regulatory signals, the so-called adipokines, to the whole body. The control of eating behavior, the peripheral insulin sensitivity, and even the development of the female reproductive system are among the physiological events controlled by adipokines. Recently, the role of brown adipose tissue in human physiology has been recognized. The metabolic role of brown adipose tissue is opposite to white fat; instead of storing fat, brown adipose tissue is a site of energy expenditure via adaptive thermogenesis. There is growing evidence that brown adipose tissue may have its own pattern of secreted hormonal factors, the so-called brown adipokines, having distinctive biological actions on the overall physiological adaptations to enhance energy expenditure.

  9. Adipose cell-adrenal interactions: current knowledge and future perspectives.

    PubMed

    Ronconi, Vanessa; Turchi, Federica; Bujalska, Iwona J; Giacchetti, Gilberta; Boscaro, Marco

    2008-04-01

    The central role of adipose tissue in the development of cardiovascular and metabolic pathology has been highlighted by the discovery of mediators (adipokines) secreted by adipose tissue and their involvement in the regulation of various biological processes. In light of recent experimental data, cross-talk between adipose tissue and the adrenal gland, particularly via the mineralocorticoid aldosterone, has been proposed. Aldosterone can induce adipogenesis, and human white adipose tissue is reported to release as-yet-uncharacterized factors that stimulate adrenocortical steroidogenesis and aldosterone production. These data could provide new insights into the pathophysiology of obesity-related disorders, including hypertension and aldosterone excess, with further studies necessary for confirming and better defining such adipose-adrenal interactions.

  10. Role of adipose tissue in haemostasis, coagulation and fibrinolysis.

    PubMed

    Faber, D R; de Groot, Ph G; Visseren, F L J

    2009-09-01

    Obesity is associated with an increased incidence of insulin resistance (IR), type 2 diabetes mellitus and cardiovascular diseases. The increased risk for cardiovascular diseases could partly be caused by a prothrombotic state that exists because of abdominal obesity. Adipose tissue induces thrombocyte activation by the production of adipose tissue-derived hormones, often called adipokines, of which some such as leptin and adiponectin have been shown to directly interfere with platelet function. Increased adipose tissue mass induces IR and systemic low-grade inflammation, also affecting platelet function. It has been demonstrated that adipose tissue directly impairs fibrinolysis by the production of plasminogen activator inhibitor-1 and possibly thrombin-activatable fibrinolysis inhibitor. Adipose tissue may contribute to enhanced coagulation by direct tissue factor production, but hypercoagulability is likely to be primarily caused by affecting hepatic synthesis of the coagulation factors fibrinogen, factor VII, factor VIII and tissue factor, by releasing free fatty acids and pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukin-1beta and interleukin-6) into the portal circulation and by inducing hepatic IR. Adipose tissue dysfunction could thus play a causal role in the prothrombotic state observed in obesity, by directly and indirectly affecting haemostasis, coagulation and fibrinolysis. PMID:19460118

  11. Targeting adipose tissue

    PubMed Central

    2012-01-01

    Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT) is generally known and stores excess energy in the form of triacylglycerol (TG), insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT) helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP). The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET), however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs), activators of peroxisome proliferator-activated receptor γ (PPARγ) a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity. PMID:23102228

  12. Co-methylated Genes in Different Adipose Depots of Pig are Associated with Metabolic, Inflammatory and Immune Processes

    PubMed Central

    Li, Mingzhou; Wu, Honglong; Wang, Tao; Xia, Yudong; Jin, Long; Jiang, Anan; Zhu, Li; Chen, Lei; Li, Ruiqiang; Li, Xuewei

    2012-01-01

    It is well established that the metabolic risk factors of obesity and its comorbidities are more attributed to adipose tissue distribution rather than total adipose mass. Since emerging evidence suggests that epigenetic regulation plays an important role in the aetiology of obesity, we conducted a genome-wide methylation analysis on eight different adipose depots of three pig breeds living within comparable environments but displaying distinct fat level using methylated DNA immunoprecipitation sequencing. We aimed to investigate the systematic association between anatomical location-specific DNA methylation status of different adipose depots and obesity-related phenotypes. We show here that compared to subcutaneous adipose tissues which primarily modulate metabolic indicators, visceral adipose tissues and intermuscular adipose tissue, which are the metabolic risk factors of obesity, are primarily associated with impaired inflammatory and immune responses. This study presents epigenetic evidence for functionally relevant methylation differences between different adipose depots. PMID:22719223

  13. CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

    PubMed Central

    Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG in the liver of patients with nonalcoholic fatty liver diseases. Here we show that the liver-enriched transcription factor CREBH is activated by TG accumulation and induces FGF21, which suppresses adipose tissue lipolysis, ameliorating hepatic steatosis. CREBH-deficient mice developed severe hepatic steatosis due to increased adipose tissue lipolysis, when fasted or fed a high-fat low-carbohydrate ketogenic diet. FGF21 production was impaired in CREBH-deficient mice, and adenoviral overexpression of FGF21 suppressed adipose tissue lipolysis and improved hepatic steatosis in these mice. Thus, our results uncover a negative feedback loop in which CREBH regulates NEFA flux from adipose tissue to the liver via FGF21. PMID:27301791

  14. Independent stem cell lineages regulate adipose organogenesis and adipose homeostasis

    PubMed Central

    Jiang, Yuwei; Berry, Daniel C.; Tang, Wei; Graff, Jonathan M.

    2014-01-01

    Summary Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments, Developmental and Adult. These two compartments are sequentially required for organ formation and maintenance. Although both Developmental and Adult progenitors are specified during the developmental period and express PPARγ, they have distinct micro-anatomical, functional, morphogenetic and molecular profiles. Further, the two compartments derive from different lineages, while adult adipose progenitors fate map from an SMA+ mural lineage, Developmental progenitors do not. Remarkably, the Adult progenitor compartment appears to be specified earlier than the Developmental cells, and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide discrete therapeutic target for childhood and adult obesity. PMID:25437556

  15. Adipose Tissue - Adequate, Accessible Regenerative Material

    PubMed Central

    Kolaparthy, Lakshmi Kanth.; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-01-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  16. Adipose Tissue - Adequate, Accessible Regenerative Material.

    PubMed

    Kolaparthy, Lakshmi Kanth; Sanivarapu, Sahitya; Moogla, Srinivas; Kutcham, Rupa Sruthi

    2015-11-01

    The potential use of stem cell based therapies for the repair and regeneration of various tissues offers a paradigm shift that may provide alternative therapeutic solutions for a number of diseases. The use of either embryonic stem cells (ESCs) or induced pluripotent stem cells in clinical situations is limited due to cell regulations and to technical and ethical considerations involved in genetic manipulation of human ESCs, even though these cells are highly beneficial. Mesenchymal stem cells seen to be an ideal population of stem cells in particular, Adipose derived stem cells (ASCs) which can be obtained in large number and easily harvested from adipose tissue. It is ubiquitously available and has several advantages compared to other sources as easily accessible in large quantities with minimal invasive harvesting procedure, and isolation of adipose derived mesenchymal stem cells yield a high amount of stem cells which is essential for stem cell based therapies and tissue engineering. Recently, periodontal tissue regeneration using ASCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because various secreted growth factors from ASCs might not only promote the regeneration of periodontal tissues but also encourage neovascularization of the damaged tissues. This review summarizes the sources, isolation and characteristics of adipose derived stem cells and its potential role in periodontal regeneration is discussed. PMID:26634060

  17. [White adipose tissue dysfunction observed in obesity].

    PubMed

    Lewandowska, Ewa; Zieliński, Andrzej

    2016-05-01

    Obesity is a disease with continuingly increasing prevalence. It occurs worldwide independently of age group, material status or country of origin. At these times the most common reasons for obesity are bad eating habits and dramatic reduction of physical activity, which cause the energy imbalance of organism. Fundamental alteration observed in obese subjects is white adipose tissue overgrowth, which is linked to increased incidence of obesity-related comorbidities, such as: cardiovascular diseases, type 2 diabetes or digestive tract diseases. What is more, obesity is also a risk factor for some cancers. Special risk for diseases linked to excessive weight is associated with overgrowth of visceral type of adipose tissue. Adipose tissue, which is the main energy storehouse in body and acts also as an endocrine organ, undergoes both the morphological and the functional changes in obesity, having a negative impact on whole body function. In this article we summarize the most important alterations in morphology and function of white adipose tissue, observed in obese subjects.

  18. [White adipose tissue dysfunction observed in obesity].

    PubMed

    Lewandowska, Ewa; Zieliński, Andrzej

    2016-05-01

    Obesity is a disease with continuingly increasing prevalence. It occurs worldwide independently of age group, material status or country of origin. At these times the most common reasons for obesity are bad eating habits and dramatic reduction of physical activity, which cause the energy imbalance of organism. Fundamental alteration observed in obese subjects is white adipose tissue overgrowth, which is linked to increased incidence of obesity-related comorbidities, such as: cardiovascular diseases, type 2 diabetes or digestive tract diseases. What is more, obesity is also a risk factor for some cancers. Special risk for diseases linked to excessive weight is associated with overgrowth of visceral type of adipose tissue. Adipose tissue, which is the main energy storehouse in body and acts also as an endocrine organ, undergoes both the morphological and the functional changes in obesity, having a negative impact on whole body function. In this article we summarize the most important alterations in morphology and function of white adipose tissue, observed in obese subjects. PMID:27234867

  19. Steroid biosynthesis in adipose tissue.

    PubMed

    Li, Jiehan; Papadopoulos, Vassilios; Vihma, Veera

    2015-11-01

    Tissue-specific expression of steroidogenic enzymes allows the modulation of active steroid levels in a local manner. Thus, the measurement of local steroid concentrations, rather than the circulating levels, has been recognized as a more accurate indicator of the steroid action within a specific tissue. Adipose tissue, one of the largest endocrine tissues in the human body, has been established as an important site for steroid storage and metabolism. Locally produced steroids, through the enzymatic conversion from steroid precursors delivered to adipose tissue, have been proven to either functionally regulate adipose tissue metabolism, or quantitatively contribute to the whole body's steroid levels. Most recently, it has been suggested that adipose tissue may contain the steroidogenic machinery necessary for the initiation of steroid biosynthesis de novo from cholesterol. This review summarizes the evidence indicating the presence of the entire steroidogenic apparatus in adipose tissue and discusses the potential roles of local steroid products in modulating adipose tissue activity and other metabolic parameters.

  20. [New insights into adipose cell biology].

    PubMed

    Dugail, I

    2004-03-01

    During the last past Years, obesity had become a major public health problem, and new aspects of fat cells biology have been unraveled. First, since the discovery of leptin, adipocytes have been recognized as true endocrine cells secreting a variety of factors in a regulated manner. The role of these factors on the development of obesity-associated metabolic complications is becoming increasingly clear. Also, the process of fat cell differentiation has been uncovered, leading to the possibility of efficient targeting protein expression in adipose tIssue. Finally, lines of transgenic mice have been created, some of which are totally resistant to obesity. These models led to the identification of new potential adipose targets for the treatment of obesity.

  1. Sp1 Transcription Factor Interaction with Accumulated Prelamin A Impairs Adipose Lineage Differentiation in Human Mesenchymal Stem Cells: Essential Role of Sp1 in the Integrity of Lipid Vesicles

    PubMed Central

    Ruiz de Eguino, Garbiñe; Infante, Arantza; Schlangen, Karin; Aransay, Ana M.; Fullaondo, Ane; Soriano, Mario; García-Verdugo, José Manuel; Martín, Ángel G.

    2012-01-01

    Lamin A (LMNA)-linked lipodystrophies may be either genetic (associated with LMNA mutations) or acquired (associated with the use of human immunodeficiency virus protease inhibitors [PIs]), and in both cases they share clinical features such as anomalous distribution of body fat or generalized loss of adipose tissue, metabolic alterations, and early cardiovascular complications. Both LMNA-linked lipodystrophies are characterized by the accumulation of the lamin A precursor prelamin A. The pathological mechanism by which prelamin A accumulation induces the lipodystrophy associated phenotypes remains unclear. Since the affected tissues in these disorders are of mesenchymal origin, we have generated an LMNA-linked experimental model using human mesenchymal stem cells treated with a PI, which recapitulates the phenotypes observed in patient biopsies. This model has been demonstrated to be a useful tool to unravel the pathological mechanism of the LMNA-linked lipodystrophies, providing an ideal system to identify potential targets to generate new therapies for drug discovery screening. We report for the first time that impaired adipogenesis is a consequence of the interaction between accumulated prelamin A and Sp1 transcription factor, sequestration of which results in altered extracellular matrix gene expression. In fact, our study shows a novel, essential, and finely tuned role for Sp1 in adipose lineage differentiation in human mesenchymal stem cells. These findings define a new physiological experimental model to elucidate the pathological mechanisms LMNA-linked lipodystrophies, creating new opportunities for research and treatment not only of LMNA-linked lipodystrophies but also of other adipogenesis-associated metabolic diseases. PMID:23197810

  2. Adipose tissue as an endocrine organ.

    PubMed

    Galic, Sandra; Oakhill, Jon S; Steinberg, Gregory R

    2010-03-25

    Obesity is characterized by increased storage of fatty acids in an expanded adipose tissue mass and is closely associated with the development of insulin resistance in peripheral tissues such as skeletal muscle and the liver. In addition to being the largest source of fuel in the body, adipose tissue and resident macrophages are also the source of a number of secreted proteins. Cloning of the obese gene and the identification of its product, leptin, was one of the first discoveries of an adipocyte-derived signaling molecule and established an important role for adipose tissue as an endocrine organ. Since then, leptin has been found to have a profound role in the regulation of whole-body metabolism by stimulating energy expenditure, inhibiting food intake and restoring euglycemia, however, in most cases of obesity leptin resistance limits its biological efficacy. In contrast to leptin, adiponectin secretion is often diminished in obesity. Adiponectin acts to increase insulin sensitivity, fatty acid oxidation, as well as energy expenditure and reduces the production of glucose by the liver. Resistin and retinol binding protein-4 are less well described. Their expression levels are positively correlated with adiposity and they are both implicated in the development of insulin resistance. More recently it has been acknowledged that macrophages are an important part of the secretory function of adipose tissue and the main source of inflammatory cyokines, such as TNFalpha and IL-6. An increase in circulating levels of these macrophage-derived factors in obesity leads to a chronic low-grade inflammatory state that has been linked to the development of insulin resistance and diabetes. These proteins commonly known as adipokines are central to the dynamic control of energy metabolism, communicating the nutrient status of the organism with the tissues responsible for controlling both energy intake and expenditure as well as insulin sensitivity. PMID:19723556

  3. Efficient generation of smooth muscle cells from adipose-derived stromal cells by 3D mechanical stimulation can substitute the use of growth factors in vascular tissue engineering.

    PubMed

    Parvizi, Mojtaba; Bolhuis-Versteeg, Lydia A M; Poot, André A; Harmsen, Martin C

    2016-07-01

    Occluding artery disease causes a high demand for bioartificial replacement vessels. We investigated the combined use of biodegradable and creep-free poly (1,3-trimethylene carbonate) (PTMC) with smooth muscle cells (SMC) derived by biochemical or mechanical stimulation of adipose tissue-derived stromal cells (ASC) to engineer bioartificial arteries. Biochemical induction of cultured ASC to SMC was done with TGF-β1 for 7d. Phenotype and function were assessed by qRT-PCR, immunodetection and collagen contraction assays. The influence of mechanical stimulation on non-differentiated and pre-differentiated ASC, loaded in porous tubular PTMC scaffolds, was assessed after culturing under pulsatile flow for 14d. Assays included qRT-PCR, production of extracellular matrix and scanning electron microscopy. ASC adhesion and TGF-β1-driven differentiation to contractile SMC on PTMC did not differ from tissue culture polystyrene controls. Mesenchymal and SMC markers were increased compared to controls. Interestingly, pre-differentiated ASC had only marginal higher contractility than controls. Moreover, in 3D PTMC scaffolds, mechanical stimulation yielded well-aligned ASC-derived SMC which deposited ECM. Under the same conditions, pre-differentiated ASC-derived SMC maintained their SMC phenotype. Our results show that mechanical stimulation can replace TGF-β1 pre-stimulation to generate SMC from ASC and that pre-differentiated ASC keep their SMC phenotype with increased expression of SMC markers.

  4. The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice.

    PubMed

    List, Edward O; Berryman, Darlene E; Funk, Kevin; Gosney, Elahu S; Jara, Adam; Kelder, Bruce; Wang, Xinyue; Kutz, Laura; Troike, Katie; Lozier, Nicholas; Mikula, Vincent; Lubbers, Ellen R; Zhang, Han; Vesel, Clare; Junnila, Riia K; Frank, Stuart J; Masternak, Michal M; Bartke, Andrzej; Kopchick, John J

    2013-03-01

    GH receptor (GHR) gene-disrupted mice (GHR-/-) have provided countless discoveries as to the numerous actions of GH. Many of these discoveries highlight the importance of GH in adipose tissue. For example GHR-/- mice are insulin sensitive yet obese with preferential enlargement of the sc adipose depot. GHR-/- mice also have elevated levels of leptin, resistin, and adiponectin, compared with controls leading some to suggest that GH may negatively regulate certain adipokines. To help clarify the role that GH exerts specifically on adipose tissue in vivo, we selectively disrupted GHR in adipose tissue to produce Fat GHR Knockout (FaGHRKO) mice. Surprisingly, FaGHRKOs shared only a few characteristics with global GHR-/- mice. Like the GHR-/- mice, FaGHRKO mice are obese with increased total body fat and increased adipocyte size. However, FaGHRKO mice have increases in all adipose depots with no improvements in measures of glucose homeostasis. Furthermore, resistin and adiponectin levels in FaGHRKO mice are similar to controls (or slightly decreased) unlike the increased levels found in GHR-/- mice, suggesting that GH does not regulate these adipokines directly in adipose tissue in vivo. Other features of FaGHRKO mice include decreased levels of adipsin, a near-normal GH/IGF-1 axis, and minimal changes to a large assortment of circulating factors that were measured such as IGF-binding proteins. In conclusion, specific removal of GHR in adipose tissue is sufficient to increase adipose tissue and decrease circulating adipsin. However, removal of GHR in adipose tissue alone is not sufficient to increase levels of resistin or adiponectin and does not alter glucose metabolism. PMID:23349524

  5. Morphological and inflammatory changes in visceral adipose tissue during obesity.

    PubMed

    Revelo, Xavier S; Luck, Helen; Winer, Shawn; Winer, Daniel A

    2014-03-01

    Obesity is a major health burden worldwide and is a major factor in the development of insulin resistance and metabolic complications such as type II diabetes. Chronic nutrient excess leads to visceral adipose tissue (VAT) expansion and dysfunction in an active process that involves the adipocytes, their supporting matrix, and immune cell infiltrates. These changes contribute to adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death. Accumulation of lymphocytes, macrophages, and other immune cells around dying adipocytes forms the so-called "crown-like structure", a histological hallmark of VAT in obesity. Cross talk between immune cells in adipose tissue dictates the overall inflammatory response, ultimately leading to the production of pro-inflammatory mediators which directly induce insulin resistance in VAT. In this review, we summarize recent studies demonstrating the dramatic changes that occur in visceral adipose tissue during obesity leading to low-grade chronic inflammation and metabolic disease.

  6. Hypoxia and adipose tissue function and dysfunction in obesity.

    PubMed

    Trayhurn, Paul

    2013-01-01

    The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po(2) levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.

  7. Is visceral adiposity a significant correlate of subcutaneous adipose cell lipolysis in men?

    PubMed

    Mauriège, P; Brochu, M; Prud'homme, D; Tremblay, A; Nadeau, A; Lemieux, S; Després, J P

    1999-02-01

    The aim of the present study was to examine whether site differences in s.c. adipose tissue (AT) lipolysis may be considered a contributing factor to the altered metabolic risk profile of visceral compared to peripheral obese men once the concomitant variation in adipose cell size is taken into account. For this purpose, sc abdominal and femoral fat cell lipolytic responses were investigated in two groups of men (body mass index, 28 +/- 2 kg/m2), aged 36 +/- 3 yr, who were matched for both s.c. abdominal AT area (256 +/- 64 cm2) and s.c. abdominal adipose cell weight (0.55 +/- 0.08 microg lipid/cell) but were characterized by either a high (162 +/- 29 cm2; n = 18) or a low (101 +/- 21 cm2; n = 18) visceral AT deposition. The maximal lipolytic response to epinephrine or to isoproterenol (beta-adrenergic agonist) as well as the maximal antilipolytic effect of either epinephrine or clonidine (alpha2-adrenergic agonist) assessed in s.c. adipocytes were similar among men with low vs. high levels of visceral AT. However, the beta-adrenoceptor sensitivity was increased in s.c. abdominal adipose cells of individuals with a high visceral AT accumulation compared to those with a low intraabdominal fat deposition. Positive relationships were also found between the lipolytic sensitivity of s.c. abdominal adipocytes and plasma insulin concentrations measured in the fasting state and after an oral glucose load. These results suggest that variation in the degree of visceral adiposity in men does not seem to be associated with differences in regional adipose cell maximal lipolytic capacity once fat cell size is taken into account. However, the greater beta-adrenoceptor lipolytic sensitivity of s.c. abdominal adipocytes could be considered a significant correlate of the increased insulinemia observed among men characterized by high levels of visceral AT.

  8. Profiling of chicken adipose tissue gene expression by genome array

    PubMed Central

    Wang, Hong-Bao; Li, Hui; Wang, Qi-Gui; Zhang, Xin-Yu; Wang, Shou-Zhi; Wang, Yu-Xiang; Wang, Xiu-Ping

    2007-01-01

    Background Excessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity. In this study, Chicken Genome Arrays were used to construct an adipose tissue gene expression profile of 7-week-old broilers, and to screen adipose tissue genes that are differentially expressed in lean and fat lines divergently selected over eight generations for high and low abdominal fat weight. Results The gene expression profiles detected 13,234–16,858 probe sets in chicken adipose tissue at 7 weeks, and genes involved in lipid metabolism and immunity such as fatty acid binding protein (FABP), thyroid hormone-responsive protein (Spot14), lipoprotein lipase(LPL), insulin-like growth factor binding protein 7(IGFBP7) and major histocompatibility complex (MHC), were highly expressed. In contrast, some genes related to lipogenesis, such as leptin receptor, sterol regulatory element binding proteins1 (SREBP1), apolipoprotein B(ApoB) and insulin-like growth factor 2(IGF2), were not detected. Moreover, 230 genes that were differentially expressed between the two lines were screened out; these were mainly involved in lipid metabolism, signal transduction, energy metabolism, tumorigenesis and immunity. Subsequently, real-time RT-PCR was performed to validate fifteen differentially expressed genes screened out by the microarray approach and high consistency was observed between the two methods. Conclusion Our results establish the groundwork for further studies of the basic genetic control of growth and development of chicken adipose tissue, and will be beneficial in clarifying the molecular mechanism of obesity in chickens. PMID

  9. n-3 PUFA: bioavailability and modulation of adipose tissue function.

    PubMed

    Kopecky, Jan; Rossmeisl, Martin; Flachs, Pavel; Kuda, Ondrej; Brauner, Petr; Jilkova, Zuzana; Stankova, Barbora; Tvrzicka, Eva; Bryhn, Morten

    2009-11-01

    Adipose tissue has a key role in the development of metabolic syndrome (MS), which includes obesity, type 2 diabetes, dyslipidaemia, hypertension and other disorders. Systemic insulin resistance represents a major factor contributing to the development of MS in obesity. The resistance is precipitated by impaired adipose tissue glucose and lipid metabolism, linked to a low-grade inflammation of adipose tissue and secretion of pro-inflammatory adipokines. Development of MS could be delayed by lifestyle modifications, while both dietary and pharmacological interventions are required for the successful therapy of MS. The n-3 long-chain (LC) PUFA, EPA and DHA, which are abundant in marine fish, act as hypolipidaemic factors, reduce cardiac events and decrease the progression of atherosclerosis. Thus, n-3 LC PUFA represent healthy constituents of diets for patients with MS. In rodents n-3 LC PUFA prevent the development of obesity and impaired glucose tolerance. The effects of n-3 LC PUFA are mediated transcriptionally by AMP-activated protein kinase and by other mechanisms. n-3 LC PUFA activate a metabolic switch toward lipid catabolism and suppression of lipogenesis, i.e. in the liver, adipose tissue and small intestine. This metabolic switch improves dyslipidaemia and reduces ectopic deposition of lipids, resulting in improved insulin signalling. Despite a relatively low accumulation of n-3 LC PUFA in adipose tissue lipids, adipose tissue is specifically linked to the beneficial effects of n-3 LC PUFA, as indicated by (1) the prevention of adipose tissue hyperplasia and hypertrophy, (2) the induction of mitochondrial biogenesis in adipocytes, (3) the induction of adiponectin and (4) the amelioration of adipose tissue inflammation by n-3 LC PUFA. PMID:19698199

  10. SFRP2 Is Associated with Increased Adiposity and VEGF Expression

    PubMed Central

    Crowley, Rachel K.; Bujalska, Iwona J.; Hassan-Smith, Zaki K.; Hazlehurst, Jonathan M.; Foucault, Danielle R.; Stewart, Paul M.; Tomlinson, Jeremy W.

    2016-01-01

    Aims The aim of this study was to assess depot-specific expression and secretion of secreted frizzled-related protein 2 (sFRP2) by adipose tissue and its effect on adipocyte biology. We measured serum sFRP2 concentrations in 106 patients in vivo to explore its relationship to fat mass, glycaemia and insulin resistance. Methods Expression of sFRP2 in mouse and human tissues was assessed using polymerase chain reaction and Western blot. Western blot confirmed secretion of sFRP2 by adipose tissue into cell culture medium. Effects of recombinant sFRP2 on lipogenesis and preadipocyte proliferation were measured. Preadipocyte expression of the angiogenic genes vascular endothelial growth factor (VEGF) and nuclear factor of activated T-cells 3 (NFATC3) was measured after recombinant sFRP2 exposure. Complementary clinical studies correlating human serum sFRP2 with age, gender, adiposity and insulin secretion were also performed. Results sFRP2 messenger RNA (mRNA) was expressed in mouse and human adipose tissue. In humans, sFRP2 mRNA expression was 4.2-fold higher in omental than subcutaneous adipose. Omental adipose tissue secreted 63% more sFRP2 protein than subcutaneous. Treatment with recombinant sFRP2 did not impact on lipogenesis or preadipocyte proliferation but was associated with increased VEGF mRNA expression. In human subjects, circulating insulin levels positively correlated with serum sFRP2, and levels were higher in patients with abnormal glucose tolerance (34.2ng/ml) compared to controls (29.5ng/ml). A positive correlation between sFRP2 and BMI was also observed. Conclusions Circulating sFRP2 is associated with adipose tissue mass and has a potential role to drive adipose angiogenesis through enhanced VEGF expression. PMID:27685706

  11. Fascia Origin of Adipose Cells.

    PubMed

    Su, Xueying; Lyu, Ying; Wang, Weiyi; Zhang, Yanfei; Li, Danhua; Wei, Suning; Du, Congkuo; Geng, Bin; Sztalryd, Carole; Xu, Guoheng

    2016-05-01

    Adipocytes might arise from vascular stromal cells, pericytes and endothelia within adipose tissue or from bone marrow cells resident in nonadipose tissue. Here, we identified adipose precursor cells resident in fascia, an uninterrupted sheet of connective tissue that extends throughout the body. The cells and fragments of superficial fascia from the rat hindlimb were highly capable of spontaneous and induced adipogenic differentiation but not myogenic and osteogenic differentiation. Fascial preadipocytes expressed multiple markers of adipogenic progenitors, similar to subcutaneous adipose-derived stromal cells (ASCs) but discriminative from visceral ASCs. Such preadipocytes resided in fascial vasculature and were physiologically active in vivo. In growing rats, adipocytes dynamically arose from the adventitia to form a thin adipose layer in the fascia. Later, some adipocytes appeared to overlay on top of other adipocytes, an early sign for the formation of three-dimensional adipose tissue in fascia. The primitive adipose lobules extended invariably along blood vessels toward the distal fascia areas. At the lobule front, nascent capillaries wrapped and passed ahead of mature adipocytes to form the distal neovasculature niche, which might replenish the pool of preadipocytes and supply nutrients and hormones necessary for continuous adipogenesis. Our findings suggest a novel model for the origin of adipocytes from the fascia, which explains both neogenesis and expansion of adipose tissue. Fascial preadipocytes generate adipose cells to form primitive adipose lobules in superficial fascia, a subcutaneous nonadipose tissue. With continuous adipogenesis, these primitive adipose lobules newly formed in superficial fascia may be the rudiment of subcutaneous adipose tissue. Stem Cells 2016;34:1407-1419.

  12. Adiposity and spinal cord injury

    PubMed Central

    Gorgey, Ashraf S; Wells, Kathryn M; Austin, Timothy L

    2015-01-01

    The drastic changes in body composition following spinal cord injury (SCI) have been shown to play a significant role in cardiovascular and metabolic health. The pattern of storage and distribution of different types of adipose tissue may impact metabolic health variables similar to carbohydrate, lipid and bone metabolism. The use of magnetic resonance imaging provides insights on the interplay among different regional adipose tissue compartments and their role in developing chronic diseases. Regional adipose tissue can be either distributed centrally or peripherally into subcutaneous and ectopic sites. The primary ectopic adipose tissue sites are visceral, intramuscular and bone marrow. Dysfunction in the central nervous system following SCI impacts the pattern of distribution of adiposity especially between tetraplegia and paraplegia. The current editorial is focused primarily on introducing different types of adipose tissue and establishing scientific basis to develop appropriate dietary, rehabilitation or pharmaceutical interventions to manage the negative consequences of increasing adiposity after SCI. We have also summarized the clinical implications and future recommendations relevant to study adiposity after SCI. PMID:26396933

  13. Regulation of adipose cell development in utero.

    PubMed

    Martin, R J; Hausman, G J; Hausman, D B

    1998-12-01

    The condition of obesity is impacted by increases in fat cell number, fat cell size, or a combination of the two. It is generally believed that fat cell number is dependent on the age of onset and the degree of obesity. This review provides an update on intrauterine growth of fetal adipose tissue, the earliest period of proliferation onset, and the factors that interact to enhance or suppress development. Fetal adipose tissue development is regulated by the complex interaction of maternal, endocrine, and paracrine influences that initiate specific changes in angiogenesis, adipogenesis, and metabolism. Developmental stages and metabolic processes influenced by specific hormones and paracrine factors have been identified through examination of the offspring of obese and diabetic pregnancies, hormonal manipulation during late pregnancy in animal models, and the use of cell culture. Collectively, the results of the studies cited herein delineate the basis for imprinting or conditioning of fetal preadipocytes at the paracrine/autocrine level and a role of thyroxine, glucocorticoids, and other hormones in fetal adipose tissue development and metabolism.

  14. Exercise-Induced Skeletal Muscle Adaptations Alter the Activity of Adipose Progenitor Cells

    PubMed Central

    Graff, Jonathan M.

    2016-01-01

    Exercise decreases adiposity and improves metabolic health; however, the physiological and molecular underpinnings of these phenomena remain unknown. Here, we investigate the effect of endurance training on adipose progenitor lineage commitment. Using mice with genetically labeled adipose progenitors, we show that these cells react to exercise by decreasing their proliferation and differentiation potential. Analyses of mouse models that mimic the skeletal muscle adaptation to exercise indicate that muscle, in a non-autonomous manner, regulates adipose progenitor homeostasis, highlighting a role for muscle-derived secreted factors. These findings support a humoral link between skeletal muscle and adipose progenitors and indicate that manipulation of adipose stem cell function may help address obesity and diabetes. PMID:27015423

  15. Exercise-Induced Skeletal Muscle Adaptations Alter the Activity of Adipose Progenitor Cells.

    PubMed

    Zeve, Daniel; Millay, Douglas P; Seo, Jin; Graff, Jonathan M

    2016-01-01

    Exercise decreases adiposity and improves metabolic health; however, the physiological and molecular underpinnings of these phenomena remain unknown. Here, we investigate the effect of endurance training on adipose progenitor lineage commitment. Using mice with genetically labeled adipose progenitors, we show that these cells react to exercise by decreasing their proliferation and differentiation potential. Analyses of mouse models that mimic the skeletal muscle adaptation to exercise indicate that muscle, in a non-autonomous manner, regulates adipose progenitor homeostasis, highlighting a role for muscle-derived secreted factors. These findings support a humoral link between skeletal muscle and adipose progenitors and indicate that manipulation of adipose stem cell function may help address obesity and diabetes. PMID:27015423

  16. Endoplasmic reticulum stress in adipose tissue augments lipolysis.

    PubMed

    Bogdanovic, Elena; Kraus, Nicole; Patsouris, David; Diao, Li; Wang, Vivian; Abdullahi, Abdikarim; Jeschke, Marc G

    2015-01-01

    The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca(2+) homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24-48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.

  17. Exercise and Adipose Tissue Macrophages: New Frontiers in Obesity Research?

    PubMed

    Goh, Jorming; Goh, Kian Peng; Abbasi, Asghar

    2016-01-01

    Obesity is a major public health problem in the twenty-first century. Mutations in genes that regulate substrate metabolism, subsequent dysfunction in their protein products, and other factors, such as increased adipose tissue inflammation, are some underlying etiologies of this disease. Increased inflammation in the adipose tissue microenvironment is partly mediated by the presence of cells from the innate and adaptive immune system. A subset of the innate immune population in adipose tissue include macrophages, termed adipose tissue macrophages (ATMs), which are central players in adipose tissue inflammation. Being extremely plastic, their responses to diverse molecular signals in the microenvironment dictate their identity and functional properties, where they become either pro-inflammatory (M1) or anti-inflammatory (M2). Endurance exercise training exerts global anti-inflammatory responses in multiple organs, including skeletal muscle, liver, and adipose tissue. The purpose of this review is to discuss the different mechanisms that drive ATM-mediated inflammation in obesity and present current evidence of how exercise training, specifically endurance exercise training, modulates the polarization of ATMs from an M1 to an M2 anti-inflammatory phenotype. PMID:27379017

  18. Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice.

    PubMed

    Seale, Patrick; Conroe, Heather M; Estall, Jennifer; Kajimura, Shingo; Frontini, Andrea; Ishibashi, Jeff; Cohen, Paul; Cinti, Saverio; Spiegelman, Bruce M

    2011-01-01

    The white adipose organ is composed of both subcutaneous and several intra-abdominal depots. Excess abdominal adiposity is a major risk factor for metabolic disease in rodents and humans, while expansion of subcutaneous fat does not carry the same risks. Brown adipose produces heat as a defense against hypothermia and obesity, and the appearance of brown-like adipocytes within white adipose tissue depots is associated with improved metabolic phenotypes. Thus, understanding the differences in cell biology and function of these different adipose cell types and depots may be critical to the development of new therapies for metabolic disease. Here, we found that Prdm16, a brown adipose determination factor, is selectively expressed in subcutaneous white adipocytes relative to other white fat depots in mice. Transgenic expression of Prdm16 in fat tissue robustly induced the development of brown-like adipocytes in subcutaneous, but not epididymal, adipose depots. Prdm16 transgenic mice displayed increased energy expenditure, limited weight gain, and improved glucose tolerance in response to a high-fat diet. shRNA-mediated depletion of Prdm16 in isolated subcutaneous adipocytes caused a sharp decrease in the expression of thermogenic genes and a reduction in uncoupled cellular respiration. Finally, Prdm16 haploinsufficiency reduced the brown fat phenotype in white adipose tissue stimulated by β-adrenergic agonists. These results demonstrate that Prdm16 is a cell-autonomous determinant of a brown fat-like gene program and thermogenesis in subcutaneous adipose tissues.

  19. Tree nut consumption is associated with better adiposity measures and cardiovascular and metabolic syndrome health risk factors in U.S adults: NHANES 2005-2010

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previous research has shown inconsistencies in the association of tree nut consumption with risk factors for cardiovascular disease (CVD) and metabolic syndrome (MetS). To determine the association of tree nut consumption with risk factors for CVD and for MetS in adults. NHANES 2005-2010 data were u...

  20. Viral mechanisms of adipose dysfunction: lessons from HIV-1 Vpr

    PubMed Central

    Agarwal, N; Balasubramanyam, A

    2014-01-01

    HIV-associated lipodystrophy is a heterogeneous, evolving condition associated with fundamental defects in adipose tissue differentiation, turnover and function. Although many antiretroviral drugs can affect adipose tissues adversely, clinical evidence suggests that factors associated with the virus per se could play a role. We have focused on the possibility that an HIV accessory protein, viral protein R (Vpr) could dysregulate metabolically critical transcription factors to cause the adipose dysfunction. In a recent study published in Science Translational Medicine, we utilized 2 animal models to show that Vpr, produced in tissues that sequester HIV after antiretroviral therapy, can act in a paracrine or endocrine fashion to disrupt adipocyte differentiation and function by inhibiting PPARγ target gene expression and activating glucocorticoid target gene expression. The phenotypic consequences included many features typical of the human syndrome, including accelerated lipolysis, increased macrophage infiltration in adipose tissue, diminished size of white adipose depots and hepatic steatosis. In this commentary, we summarize the background, results, and implications of these studies, and raise important questions for future investigation. More broadly, these studies suggest that chronic viral infections may be a causative factor in the pathogenesis of some forms of lipid metabolic disease, insulin resistance, and diabetes. PMID:26167403

  1. Visceral and subcutaneous adiposity measurements in adults: Influence of measurement site

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Excess abdominal adiposity is a known risk factor for cardiovascular diseases. Computed tomography can be used to examine the visceral (VAT) and subcutaneous (SAT) components of abdominal adiposity, but it is unresolved whether single-slice or multi-slice protocols are needed. Nine computed tomograp...

  2. Equine Metabolic Syndrome Affects Viability, Senescence, and Stress Factors of Equine Adipose-Derived Mesenchymal Stromal Stem Cells: New Insight into EqASCs Isolated from EMS Horses in the Context of Their Aging

    PubMed Central

    Marycz, Krzysztof; Kornicka, Katarzyna; Basinska, Katarzyna; Czyrek, Aleksandra

    2016-01-01

    Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses suffering from EMS (ASCEMS). ASCEMS displayed senescent phenotype associated with β-galactosidase accumulation, enlarged cell bodies and nuclei, increased apoptosis, and reduced heterochromatin architecture. Moreover, we observed increased amounts of nitric oxide (NO) and reactive oxygen species (ROS) in these cells, accompanied by reduced superoxide dismutase (SOD) activity. We also found in ASCEMS an elevated number of impaired mitochondria, characterized by membrane raptures, disarrayed cristae, and vacuole formation. Our results suggest that the toxic compounds, accumulating in the mitochondria under oxidative stress, lead to alternations in their morphology and may be partially responsible for the senescent phenotype and decreased proliferation potential of ASCEMS. PMID:26682006

  3. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    PubMed

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

  4. Tissue engineering chamber promotes adipose tissue regeneration in adipose tissue engineering models through induced aseptic inflammation.

    PubMed

    Peng, Zhangsong; Dong, Ziqing; Chang, Qiang; Zhan, Weiqing; Zeng, Zhaowei; Zhang, Shengchang; Lu, Feng

    2014-11-01

    Tissue engineering chamber (TEC) makes it possible to generate significant amounts of mature, vascularized, stable, and transferable adipose tissue. However, little is known about the role of the chamber in tissue engineering. Therefore, to investigate the role of inflammatory response and the change in mechanotransduction started by TEC after implantation, we placed a unique TEC model on the surface of the groin fat pads in rats to study the expression of cytokines and tissue development in the TEC. The number of infiltrating cells was counted, and vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) expression levels in the chamber at multiple time points postimplantation were analyzed by enzyme-linked immunosorbent assay. Tissue samples were collected at various time points and labeled for specific cell populations. The result showed that new adipose tissue formed in the chamber at day 60. Also, the expression of MCP-1 and VEGF in the chamber decreased slightly from an early stage as well as the number of the infiltrating cells. A large number of CD34+/perilipin- perivascular cells could be detected at day 30. Also, the CD34+/perilipin+ adipose precursor cell numbers increased sharply by day 45 and then decreased by day 60. CD34-/perilipin+ mature adipocytes were hard to detect in the chamber content at day 30, but their number increased and then peaked at day 60. Ki67-positive cells could be found near blood vessels and their number decreased sharply over time. Masson's trichrome showed that collagen was the dominant component of the chamber content at early stage and was replaced by newly formed small adipocytes over time. Our findings suggested that the TEC implantation could promote the proliferation of adipose precursor cells derived from local adipose tissue, increase angiogenesis, and finally lead to spontaneous adipogenesis by inducing aseptic inflammation and changing local mechanotransduction.

  5. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    PubMed

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

  6. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    PubMed Central

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone–fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues – subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT – is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat

  7. Subcutaneous adipose tissue fatty acid desaturation in adults with and without rare adipose disorders

    PubMed Central

    2012-01-01

    Background Elevated stearoyl-CoA desaturase activity has been described in obese states, with an increased desaturation index (DI) suggesting enhanced lipogenesis. Differences in the DI among various phenotypes of abnormal adiposity have not been studied. Abnormal accumulation of subcutaneous adipose tissue occurs in rare adipose disorders (RADs) including Dercum's disease (DD), multiple symmetric lipomatosis (MSL), and familial multiple lipomatosis (FML). Examining the DI in subcutaneous fat of people with DD, MSL and FML may provide information on adipose tissue fatty acid metabolism in these disorders. The aims of this pilot study were: 1) to determine if differences in adipose tissue DIs are present among RADs, and 2) to determine if the DIs correlate to clinical or biochemical parameters. Methods Subcutaneous adipose tissue was obtained from human participants with DD (n = 6), MSL (n = 5), FML (n = 8) and obese Controls (n = 6). Fatty acid composition was determined by gas chromatography/mass spectrometry. The DIs (palmitoleic/palmitic, oleic/stearic, vaccenic/stearic ratios) were calculated from the gas chromatogram peak intensities. SCD1 gene expression was determined. Spearman's correlations between the DIs and available clinical or biochemical data were performed. Results In DD subjects, the vaccenic/stearic index was lower (p < 0.05) in comparison to Controls. Percent of total of the saturated fatty acid myristic acid was higher in DD compared with Controls and FML. Percent of monounsaturated vaccenic acid in DD trended lower when compared with Controls, and was decreased in comparison to FML. In MSL, total percent of the polyunsaturated fatty acids was significantly lower than in the Control group (p < 0.05). In the total cohort of subjects, the palmitoleic/palmitic and oleic/stearic DIs positively correlated with age, BMI, and percent body fat. Conclusions The positive associations between the DIs and measures of adiposity (BMI and percent body fat

  8. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber.

    PubMed

    Zhan, Weiqing; Chang, Qiang; Xiao, Xiaolian; Dong, Ziqing; Zeng, Zhaowei; Gao, Jianhua; Lu, Feng

    2015-01-01

    The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a tissue engineering chamber consist mostly of connective rather than adipose tissue. Here, we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration.

  9. Co-delivery of adipose-derived stem cells and growth factor-loaded microspheres in RGD-grafted N-methacrylate glycol chitosan gels for focal chondral repair.

    PubMed

    Sukarto, Abby; Yu, Claire; Flynn, Lauren E; Amsden, Brian G

    2012-08-13

    The coencapsulation of growth factor-loaded microspheres with adipose-derived stem cells (ASCs) within a hydrogel matrix was studied as a potential means to enhance ASC chondrogenesis in the development of a cell-based therapeutic strategy for the regeneration of partial thickness chondral defects. A photopolymerizable N-methacrylate glycol chitosan (MGC) was employed to form an in situ gel used to encapsulate microspheres loaded with bone morphogenetic protein 6 (BMP-6) and transforming growth factor-β3 (TGF-β3) with human ASCs. ASC viability and retention were enhanced when the Young's modulus of the MGC ranged between 225 and 380 kPa. Grafting an RGD-containing peptide onto the MGC backbone (RGD-MGC) improved ASC viability within the gels, remaining at greater than 90% over 14 days in culture. The effects of BMP-6 and TGF-β3 released from the polymer microspheres on ASC chondrogenesis were assessed, and the level of differentiation was compared to ASCs in control gels containing nongrowth factor-loaded microspheres cultured with and without the growth factors supplied in the medium. There was enhanced expression of chondrogenic markers at earlier time points when the ASCs were induced with the sustained and local release of BMP-6 and TGF-β3 from the microspheres. More specifically, the normalized glycosaminoglycan and collagen type II protein expression levels were significantly higher than in the controls. In addition, the ratio of collagen type II to type I was significantly higher in the microsphere delivery group and increased over time. End-point RT-PCR analysis supported that there was a more rapid induction and enhancement of ASC chondrogenesis in the controlled release group. Interestingly, in all of the assays, there was evidence of chondrogenic differentiation when the ASCs were cultured in the gels in the absence of growth factor stimulation. Overall, the co-delivery of growth-factor-loaded microspheres and ASCs in RGD-modified MGC gels

  10. Candy consumption in childhood is not predictive of weight, adiposity measures or cardiovascular risk factors in young adults: the Bogalusa Heart Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    There are limited data available on the longitudinal relationship between candy consumption by children on weight and other cardiovascular risk factors (CVRF) in young adults. The present study investigated whether candy consumption in children was predictive of weight and CVRF in young adults. A lo...

  11. Effects of resveratrol on gut microbiota and fat storage in a mouse model with high-fat-induced obesity.

    PubMed

    Qiao, Yi; Sun, Jin; Xia, Shufang; Tang, Xue; Shi, Yonghui; Le, Guowei

    2014-06-01

    Recent studies have investigated the anti-obesity effect of resveratrol, but the pathways through which resveratrol resists obesity are not clear. In the present study, we hypothesize that resveratrol exerts anti-obesity effects that are likely mediated by mechanisms of regulating gut microbes, and in turn, improving fat storage and metabolism. Gut microbes, glucose and lipid metabolism in high-fat diet (HF) mice in vivo are investigated after resveratrol treatment. Several biochemical markers are measured. Fluorescence in situ hybridization and flow cytometry are used to monitor and quantify the changes in gut microbiota. The key genes related to fat storage and metabolism in the liver and visceral adipose tissues are measured by real-time PCR. The results show that resveratrol (200 mg per kg per day) significantly lowers both body and visceral adipose weights, and reduces blood glucose and lipid levels in HF mice. Resveratrol improves the gut microbiota dysbiosis induced by the HF diet, including increasing the Bacteroidetes-to-Firmicutes ratios, significantly inhibiting the growth of Enterococcus faecalis, and increasing the growth of Lactobacillus and Bifidobacterium. Furthermore, resveratrol significantly increases the fasting-induced adipose factor (Fiaf, a key gene negatively regulated by intestinal microbes) expression in the intestine. Resveratrol significantly decreases mRNA expression of Lpl, Scd1, Ppar-γ, Acc1, and Fas related to fatty acids synthesis, adipogenesis and lipogenesis, which may be driven by increased Fiaf expression. The Pearson's correlation coefficient shows that there is a negative correlation between the body weight and the ratios of Bacteroidetes-to-Firmicutes. Therefore, resveratrol mediates the composition of gut microbes, and in turn, through the Fiaf signaling pathway, accelerates the development of obesity.

  12. Adipose-derived stem cells and periodontal tissue engineering.

    PubMed

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-01-01

    Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

  13. Comparison of human adipose-derived stem cells isolated from subcutaneous, omental, and intrathoracic adipose tissue depots for regenerative applications.

    PubMed

    Russo, Valerio; Yu, Claire; Belliveau, Paul; Hamilton, Andrew; Flynn, Lauren E

    2014-02-01

    Adipose tissue is an abundant source of multipotent progenitor cells that have shown promise in regenerative medicine. In humans, fat is primarily distributed in the subcutaneous and visceral depots, which have varying biochemical and functional properties. In most studies to date, subcutaneous adipose tissue has been investigated as the adipose-derived stem cell (ASC) source. In this study, we sought to develop a broader understanding of the influence of specific adipose tissue depots on the isolated ASC populations through a systematic comparison of donor-matched abdominal subcutaneous fat and omentum, and donor-matched pericardial adipose tissue and thymic remnant samples. We found depot-dependent and donor-dependent variability in the yield, viability, immunophenotype, clonogenic potential, doubling time, and adipogenic and osteogenic differentiation capacities of the ASC populations. More specifically, ASCs isolated from both intrathoracic depots had a longer average doubling time and a significantly higher proportion of CD34(+) cells at passage 2, as compared with cells isolated from subcutaneous fat or the omentum. Furthermore, ASCs from subcutaneous and pericardial adipose tissue demonstrated enhanced adipogenic differentiation capacity, whereas ASCs isolated from the omentum displayed the highest levels of osteogenic markers in culture. Through cell culture analysis under hypoxic (5% O(2)) conditions, oxygen tension was shown to be a key mediator of colony-forming unit-fibroblast number and osteogenesis for all depots. Overall, our results suggest that depot selection is an important factor to consider when applying ASCs in tissue-specific cell-based regenerative therapies, and also highlight pericardial adipose tissue as a potential new ASC source. PMID:24361924

  14. The adipose organ: morphological perspectives of adipose tissues.

    PubMed

    Cinti, S

    2001-08-01

    Anatomically, an organ is defined as a series of tissues which jointly perform one or more interconnected functions. The adipose organ qualifies for this definition as it is made up of two tissue types, the white and brown adipose tissues, which collaborate in partitioning the energy contained in lipids between thermogenesis and the other metabolic functions. In rats and mice the adipose organ consists of several subcutaneous and visceral depots. Some areas of these depots are brown and correspond to brown adipose tissue, while many are white and correspond to white adipose tissue. The number of brown adipocytes found in white areas varies with age, strain of animal and environmental conditions. Brown and white adipocyte precursors are morphologically dissimilar. Together with a rich vascular supply, brown areas receive abundant noradrenergic parenchymal innervation. The gross anatomy and histology of the organ vary considerably in different physiological (cold acclimation, warm acclimation, fasting) and pathological conditions such as obesity; many important genes, such as leptin and uncoupling protein-1, are also expressed very differently in the two cell types. These basic mechanisms should be taken into account when addressing the physiopathology of obesity and its treatment. PMID:11681806

  15. [Interests and potentials of adipose tissue in scleroderma].

    PubMed

    Daumas, A; Eraud, J; Hautier, A; Sabatier, F; Magalon, G; Granel, B

    2013-12-01

    Systemic sclerosis is a disorder involving the connective tissue, arterioles and microvessels. It is characterized by skin and visceral fibrosis and ischemic phenomena. Currently, therapy is limited and no antifibrotic treatment has proven its efficacy. Beyond some severe organ lesions (pulmonary arterial hypertension, pulmonary fibrosis, scleroderma renal crisis), which only concern a minority of patients, the skin sclerosis of hands and face and the vasculopathy lead to physical and psychological disability in most patients. Thus, functional improvement of hand motion and face represents a priority for patient therapy. Due to its easy obtention by fat lipopaspirate and adipocytes survival, re injection of adipose tissue is a common therapy used in plastic surgery for its voluming effect. Identification and characterization of the adipose tissue-derived stroma vascular fraction, mainly including mesenchymal stem cells, have revolutionized the science showing that adipose tissue is a valuable source of multipotent stem cells, able to migrate to site of injury and to differentiate according to the receiver tissue's needs. Due to easy harvest by liposuction, its abundance in mesenchymal cells far higher that the bone marrow, and stroma vascular fraction's ability to differentiate and secrete growth angiogenic and antiapoptotic factors, the use of adipose tissue is becoming more attractive in regenerative medicine. We here present the interest of adipose tissue use in the treatment of the hands and face in scleroderma. PMID:24050783

  16. Epicardial adipose tissue in endocrine and metabolic diseases.

    PubMed

    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  17. An alternative splicing program promotes adipose tissue thermogenesis.

    PubMed

    Vernia, Santiago; Edwards, Yvonne Jk; Han, Myoung Sook; Cavanagh-Kyros, Julie; Barrett, Tamera; Kim, Jason K; Davis, Roger J

    2016-01-01

    Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a splicing program that suppresses adipose tissue thermogenesis. Together, these data provide quantitative analysis of gene expression at exon-level resolution in obesity and identify a novel mechanism that contributes to the regulation of adipose tissue function and the maintenance of normal glycemia. PMID:27635635

  18. Emerging role of Nrf2 in adipocytes and adipose biology.

    PubMed

    Schneider, Kevin S; Chan, Jefferson Y

    2013-01-01

    Maintenance of a balanced redox state within the cell is of critical importance to a wide variety of biological systems. Nuclear factor erythroid-derived 2-like 2 (Nrf2) is a critical regulator of key aspects of the antioxidant defense pathway and has long been a subject of interest regarding conditions of chronic stress such as inflammation and cancer. Recent data have emerged demonstrating that oxidative stress and Nrf2 also play critical roles in the biology of adipose tissue. This review examines data identifying the roles of Nrf2 and oxidative stress in the biological process of adipose cell differentiation as well as the implications of Nrf2 modulation on obesity. Working to understand the complex interplay among Nrf2, oxidative stress, and adipose biology could lead to a variety of possible treatments for obesity and other related disorders.

  19. Physiological and pathological impact of exosomes of adipose tissue.

    PubMed

    Zhang, Yan; Yu, Mei; Tian, Weidong

    2016-02-01

    Exosomes are nanovesicles that have emerged as a new intercellular communication system for transporting proteins and RNAs; recent studies have shown that they play a role in many physiological and pathological processes such as immune regulation, cell differentiation, infection and cancer. By transferring proteins, mRNAs and microRNAs, exosomes act as information vehicles that alter the behavior of recipient cells. Compared to direct cell-cell contact or secreted factors, exosomes can affect recipient cells in more efficient ways. In whole adipose tissues, it has been shown that exosomes exist in supernatants of adipocytes and adipose stromal cells (ADSCs). Adipocyte exosomes are linked to lipid metabolism and obesity-related insulin resistance and exosomes secreted by ADSCs are involved in angiogenesis, immunomodulation and tumor development. This review introduces characteristics of exosomes in adipose tissue, summarizes their functions in different physiological and pathological processes and provides the further insight into potential application of exosomes to disease diagnosis and treatment.

  20. Estimating adipose tissue in the chest wall using ultrasonic and alternate /sup 40/K and biometric measurements

    SciTech Connect

    Anderson, A.L.; Campbell, G.W.

    1982-01-22

    The percentage of adipose (fat) tissue in the chest wall must be known to accurately measure Pu in the human lung. Correction factors of 100% or more in x-ray detection efficiency are common. Methods using simple /sup 40/K and biometric measurement techniques were investigated to determine the adipose content in the human chest wall. These methods predict adipose content to within 15% of the absolute ultrasonic value. These new methods are discussed and compared with conventional ultrasonic measurement techniques. (ERB)

  1. Critical illness induces alternative activation of M2 macrophages in adipose tissue

    PubMed Central

    2011-01-01

    Introduction We recently reported macrophage accumulation in adipose tissue of critically ill patients. Classically activated macrophage accumulation in adipose tissue is a known feature of obesity, where it is linked with increasing insulin resistance. However, the characteristics of adipose tissue macrophage accumulation in critical illness remain unknown. Methods We studied macrophage markers with immunostaining and gene expression in visceral and subcutaneous adipose tissue from healthy control subjects (n = 20) and non-surviving prolonged critically ill patients (n = 61). For comparison, also subcutaneous in vivo adipose tissue biopsies were studied from 15 prolonged critically ill patients. Results Subcutaneous and visceral adipose tissue biopsies from non-surviving prolonged critically ill patients displayed a large increase in macrophage staining. This staining corresponded with elevated gene expression of "alternatively activated" M2 macrophage markers arginase-1, IL-10 and CD163 and low levels of the "classically activated" M1 macrophage markers tumor necrosis factor (TNF)-α and inducible nitric-oxide synthase (iNOS). Immunostaining for CD163 confirmed positive M2 macrophage staining in both visceral and subcutaneous adipose tissue biopsies from critically ill patients. Surprisingly, circulating levels and tissue gene expression of the alternative M2 activators IL-4 and IL-13 were low and not different from controls. In contrast, adipose tissue protein levels of peroxisome proliferator-activated receptor-γ (PPARγ), a nuclear receptor required for M2 differentiation and acting downstream of IL-4, was markedly elevated in illness. In subcutaneous abdominal adipose tissue biopsies from surviving critically ill patients, we could confirm positive macrophage staining with CD68 and CD163. We also could confirm elevated arginase-1 gene expression and elevated PPARγ protein levels. Conclusions Unlike obesity, critical illness evokes adipose tissue

  2. Secretory function of adipose tissue.

    PubMed

    Kuryszko, J; Sławuta, P; Sapikowski, G

    2016-01-01

    There are two kinds of adipose tissue in mammals: white adipose tissue - WAT and brown adipose tissue - BAT. The main function of WAT is accumulation of triacylglycerols whereas the function of BAT is heat generation. At present, WAT is also considered to be an endocrine gland that produces bioactive adipokines, which take part in glucose and lipid metabolism. Considering its endocrine function, the adipose tissue is not a homogeneous gland but a group of a few glands which act differently. Studies on the secretory function of WAT began in 1994 after discovery of leptin known as the satiation hormone, which regulates body energy homeostasis and maintainence of body mass. Apart from leptin, the following belong to adipokines: adiponectin, resistin, apelin, visfatin and cytokines: TNF and IL 6. Adiponectin is a polypeptide hormone of antidiabetic, anti-inflammatory and anti-atherogenic activity. It plays a key role in carbohydrate and fat metabolism. Resistin exerts a counter effect compared to adiponectin and its physiological role is to maintain fasting glycaemia. Visfatin stimulates insulin secretion and increases insulin sensitivity and glucose uptake by muscle cells and adipocytes. Apelin probably increases the insulin sensitivity of tissues. TNF evokes insulin resistance by blocking insulin receptors and inhibits insulin secretion. Approximately 30% of circulating IL 6 comes from adipose tissue. It causes insulin resistance by decreasing the expression of insulin receptors, decreases adipogenesis and adiponectin and visfatin secretion, and stimulates hepatic gluconeogenesis. In 2004, Bays introduced the notion of adiposopathy, defined as dysfunction of the adipose tissue, whose main feature is insulin and leptin resistance as well as the production of inflammatory cytokines: TNF and IL 6 and monocyte chemoattractant protein. This means that excess of adipose tissue, especially visceral adipose tissue, leads to the development of a chronic subclinical

  3. Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues

    PubMed Central

    Hausman, Gary J; Basu, Urmila; Du, Min; Fernyhough-Culver, Melinda; Dodson, Michael V

    2014-01-01

    Human studies of the influence of aging and other factors on intermuscular fat (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain, or with no weight change with age in humans. An increase in INTMF represents a similar threat to type 2 diabetes and insulin resistance as does visceral adipose tissue (VAT). Studies of INTMF in animals covered topics such as quantitative deposition and genetic relationships with other fat depots. The relationship between leanness and higher proportions of INTMF fat in pigs was not observed in human studies and was not corroborated by other pig studies. In humans, changes in muscle mass, strength and quality are associated with INTMF accretion with aging. Gene expression profiling and intrinsic methylation differences in pigs demonstrated that INTMF and VAT are primarily associated with inflammatory and immune processes. It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat animals were reviewed. Gene expression analysis and genetic analysis have identified candidate genes involved in IM adipocyte development. Intramuscular (IM) adipocyte development in human muscle is only seen during aging and some pathological circumstance. Several genetic links between human and meat animal adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have strong genetic effects on IM accumulation. Lipin1 deficiency results in immature adipocyte development in human lipodystrophy. In humans, overexpression of Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may influence intramuscular lipid regardless of species. PMID:26317048

  4. Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues.

    PubMed

    Hausman, Gary J; Basu, Urmila; Du, Min; Fernyhough-Culver, Melinda; Dodson, Michael V

    2014-01-01

    Human studies of the influence of aging and other factors on intermuscular fat (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain, or with no weight change with age in humans. An increase in INTMF represents a similar threat to type 2 diabetes and insulin resistance as does visceral adipose tissue (VAT). Studies of INTMF in animals covered topics such as quantitative deposition and genetic relationships with other fat depots. The relationship between leanness and higher proportions of INTMF fat in pigs was not observed in human studies and was not corroborated by other pig studies. In humans, changes in muscle mass, strength and quality are associated with INTMF accretion with aging. Gene expression profiling and intrinsic methylation differences in pigs demonstrated that INTMF and VAT are primarily associated with inflammatory and immune processes. It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat animals were reviewed. Gene expression analysis and genetic analysis have identified candidate genes involved in IM adipocyte development. Intramuscular (IM) adipocyte development in human muscle is only seen during aging and some pathological circumstance. Several genetic links between human and meat animal adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have strong genetic effects on IM accumulation. Lipin1 deficiency results in immature adipocyte development in human lipodystrophy. In humans, overexpression of Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may influence intramuscular lipid regardless of species.

  5. FGF receptor antagonism does not affect adipose tissue development in nutritionally induced obesity.

    PubMed

    Scroyen, Ilse; Vranckx, Christine; Lijnen, Henri Roger

    2014-01-01

    The fibroblast growth factor (FGF)-FGF receptor (FGFR) system plays a role in angiogenesis and maintenance of vascular integrity, but its potential role in adipose tissue related angiogenesis and development is still unknown. Administration of SSR, a low molecular weight inhibitor of multiple FGFRs, did not significantly affect body weight nor weight of subcutaneous or gonadal (GON) fat, as compared with pair-fed control mice. Adipocyte hypertrophy and reduced adipocyte density were only observed in GON adipose tissues of treated mice. Adipose tissue angiogenesis was not affected by SSR treatment, as normalized blood vessel density was comparable in adipose tissues of both groups. Blocking the FGF-FGFR system in vivo does not markedly affect adipose tissue development in mice with nutritionally induced obesity.

  6. Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues

    SciTech Connect

    Yamada, Tomoya Higuchi, Mikito; Nakanishi, Naoto

    2015-08-07

    Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere length of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner. - Highlights: • Visceral adipose tissue express higher pref-1 mRNA than other anatomical sites. • Telomere length in visceral adipose tissue is longer than other anatomical sites. • Telomere length of adipose tissue is not associated with adipocyte size. • Pref-1 mRNA is negatively correlated with intramuscular and visceral adipocyte size.

  7. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    PubMed

    Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

    2015-01-01

    It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

  8. Obesity, adiposity, and dyslipidemia: a consensus statement from the National Lipid Association.

    PubMed

    Bays, Harold E; Toth, Peter P; Kris-Etherton, Penny M; Abate, Nicola; Aronne, Louis J; Brown, W Virgil; Gonzalez-Campoy, J Michael; Jones, Steven R; Kumar, Rekha; La Forge, Ralph; Samuel, Varman T

    2013-01-01

    The term "fat" may refer to lipids as well as the cells and tissue that store lipid (ie, adipocytes and adipose tissue). "Lipid" is derived from "lipos," which refers to animal fat or vegetable oil. Adiposity refers to body fat and is derived from "adipo," referring to fat. Adipocytes and adipose tissue store the greatest amount of body lipids, including triglycerides and free cholesterol. Adipocytes and adipose tissue are active from an endocrine and immune standpoint. Adipocyte hypertrophy and excessive adipose tissue accumulation can promote pathogenic adipocyte and adipose tissue effects (adiposopathy), resulting in abnormal levels of circulating lipids, with dyslipidemia being a major atherosclerotic coronary heart disease risk factor. It is therefore incumbent upon lipidologists to be among the most knowledgeable in the understanding of the relationship between excessive body fat and dyslipidemia. On September 16, 2012, the National Lipid Association held a Consensus Conference with the goal of better defining the effect of adiposity on lipoproteins, how the pathos of excessive body fat (adiposopathy) contributes to dyslipidemia, and how therapies such as appropriate nutrition, increased physical activity, weight-management drugs, and bariatric surgery might be expected to impact dyslipidemia. It is hoped that the information derived from these proceedings will promote a greater appreciation among clinicians of the impact of excess adiposity and its treatment on dyslipidemia and prompt more research on the effects of interventions for improving dyslipidemia and reducing cardiovascular disease risk in overweight and obese patients.

  9. A Novel Role for Adipose Ephrin-B1 in Inflammatory Response

    PubMed Central

    Mori, Takuya; Maeda, Norikazu; Inoue, Kana; Sekimoto, Ryohei; Tsushima, Yu; Matsuda, Keisuke; Yamaoka, Masaya; Suganami, Takayoshi; Nishizawa, Hitoshi; Ogawa, Yoshihiro; Funahashi, Tohru; Shimomura, Iichiro

    2013-01-01

    Aims Ephrin-B1 (EfnB1) was selected among genes of unknown function in adipocytes or adipose tissue and subjected to thorough analysis to understand its role in the development of obesity. Methods and Results EfnB1 mRNA and protein levels were significantly decreased in adipose tissues of obese mice and such reduction was mainly observed in mature adipocytes. Exposure of 3T3-L1 adipocytes to tumor necrosis factor-α (TNF-α) and their culture with RAW264.7 cells reduced EFNB1 levels. Knockdown of adipose EFNB1 increased monocyte chemoattractant protein-1 (Mcp-1) mRNA level and augmented the TNF-α-mediated THP-1 monocyte adhesion to adipocytes. Adenovirus-mediated adipose EFNB1-overexpression significantly reduced the increase in Mcp-1 mRNA level induced by coculture of 3T3-L1 adipocytes with RAW264.7 cells. Monocyte adherent assay showed that adipose EfnB1-overexpression significantly decreased the increase of monocyte adhesion by coculture with RAW264.7 cells. TNF-α-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) was reduced by EFNB1-overexpression. Conclusions EFNB1 contributes to the suppression of adipose inflammatory response. In obesity, reduction of adipose EFNB1 may accelerate the vicious cycle involved in adipose tissue inflammation. PMID:24098442

  10. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis

    PubMed Central

    Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

    2015-01-01

    It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS) prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP) activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2) and MMPs (MMP-2 and MMP-9), whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2) in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors. PMID:26599360

  11. Surrogate markers of visceral adiposity in young adults: waist circumference and body mass index are more accurate than waist hip ratio, model of adipose distribution and visceral adiposity index.

    PubMed

    Borruel, Susana; Moltó, José F; Alpañés, Macarena; Fernández-Durán, Elena; Álvarez-Blasco, Francisco; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

    2014-01-01

    Surrogate indexes of visceral adiposity, a major risk factor for metabolic and cardiovascular disorders, are routinely used in clinical practice because objective measurements of visceral adiposity are expensive, may involve exposure to radiation, and their availability is limited. We compared several surrogate indexes of visceral adiposity with ultrasound assessment of subcutaneous and visceral adipose tissue depots in 99 young Caucasian adults, including 20 women without androgen excess, 53 women with polycystic ovary syndrome, and 26 men. Obesity was present in 7, 21, and 7 subjects, respectively. We obtained body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), model of adipose distribution (MOAD), visceral adiposity index (VAI), and ultrasound measurements of subcutaneous and visceral adipose tissue depots and hepatic steatosis. WC and BMI showed the strongest correlations with ultrasound measurements of visceral adiposity. Only WHR correlated with sex hormones. Linear stepwise regression models including VAI were only slightly stronger than models including BMI or WC in explaining the variability in the insulin sensitivity index (yet BMI and WC had higher individual standardized coefficients of regression), and these models were superior to those including WHR and MOAD. WC showed 0.94 (95% confidence interval 0.88-0.99) and BMI showed 0.91 (0.85-0.98) probability of identifying the presence of hepatic steatosis according to receiver operating characteristic curve analysis. In conclusion, WC and BMI not only the simplest to obtain, but are also the most accurate surrogate markers of visceral adiposity in young adults, and are good indicators of insulin resistance and powerful predictors of the presence of hepatic steatosis.

  12. Triacylglycerol metabolism in adipose tissue

    PubMed Central

    Ahmadian, Maryam; Duncan, Robin E; Jaworski, Kathy; Sarkadi-Nagy, Eszter; Sul, Hei Sook

    2009-01-01

    Triacylglycerol (TAG) in adipose tissue serves as the major energy storage form in higher eukaryotes. Obesity, resulting from excess white adipose tissue, has increased dramatically in recent years resulting in a serious public health problem. Understanding of adipocyte-specific TAG synthesis and hydrolysis is critical to the development of strategies to treat and prevent obesity and its closely associated diseases, for example, Type 2 diabetes, hypertension and atherosclerosis. In this review, we present an overview of the major enzymes in TAG synthesis and lipolysis, including the recent discovery of a novel adipocyte TAG hydrolase. PMID:19194515

  13. Adipose tissues as endocrine target organs.

    PubMed

    Lanthier, Nicolas; Leclercq, Isabelle A

    2014-08-01

    In the context of obesity, white adipocyte hypertrophy and adipose tissue macrophage infiltration result in the production of pro-inflammatory adipocytokines inducing insulin resistance locally but also in distant organs and contributing to low grade inflammatory status associated with the metabolic syndrome. Visceral adipose tissue is believed to play a prominent role. Brown and beige adipose tissues are capable of energy dissipation, but also of cytokine production and their role in dysmetabolic syndrome is emerging. This review focuses on metabolic and inflammatory changes in these adipose depots and contribution to metabolic syndrome. Also we will review surgical and pharmacological procedures to target adiposity as therapeutic interventions to treat obesity-associated disorders.

  14. Preadipocyte and adipose tissue differentiation in meat animals: influence of species and anatomical location.

    PubMed

    Hausman, G J; Basu, U; Wei, S; Hausman, D B; Dodson, M V

    2014-02-01

    Early in porcine adipose tissue development, the stromal-vascular (SV) elements control and dictate the extent of adipogenesis in a depot-dependent manner. The vasculature and collagen matrix differentiate before overt adipocyte differentiation. In the fetal pig, subcutaneous (SQ) layer development is predictive of adipocyte development, as the outer, middle, and inner layers of dorsal SQ adipose tissue develop and maintain layered morphology throughout postnatal growth of SQ adipose tissue. Bovine and ovine fetuses contain brown adipose tissue but SQ white adipose tissue is poorly developed structurally. Fetal adipose tissue differentiation is associated with the precocious expression of several genes encoding secreted factors and key transcription factors like peroxisome proliferator activated receptor (PPAR)γ and CCAAT/-enhancer-binding protein. Identification of adipocyte-associated genes differentially expressed by age, depot, and species in vivo and in vitro has been achieved using single-gene analysis, microarrays, suppressive subtraction hybridization, and next-generation sequencing applications. Gene polymorphisms in PPARγ, cathepsins, and uncoupling protein 3 have been associated with back fat accumulation. Genome scans have mapped several quantitative trait loci (QTL) predictive of adipose tissue-deposition phenotypes in cattle and pigs.

  15. Adiposity, obesity, and arterial aging: longitudinal study of aortic stiffness in the Whitehall II cohort.

    PubMed

    Brunner, Eric J; Shipley, Martin J; Ahmadi-Abhari, Sara; Tabak, Adam G; McEniery, Carmel M; Wilkinson, Ian B; Marmot, Michael G; Singh-Manoux, Archana; Kivimaki, Mika

    2015-08-01

    We sought to determine whether adiposity in later midlife is an independent predictor of accelerated stiffening of the aorta. Whitehall II study participants (3789 men; 1383 women) underwent carotid-femoral applanation tonometry at the mean age of 66 and again 4 years later. General adiposity by body mass index, central adiposity by waist circumference and waist:hip ratio, and fat mass percent by body impedance were assessed 5 years before and at baseline. In linear mixed models adjusted for age, sex, ethnicity, and mean arterial pressure, all adiposity measures were associated with aortic stiffening measured as increase in pulse wave velocity (PWV) between baseline and follow-up. The associations were similar in the metabolically healthy and unhealthy, according to Adult Treatment Panel-III criteria excluding waist circumference. C-reactive protein and interleukin-6 levels accounted for part of the longitudinal association between adiposity and PWV change. Adjusting for chronic disease, antihypertensive medication and risk factors, standardized effects of general and central adiposity and fat mass percent on PWV increase (m/s) were similar (0.14, 95% confidence interval: 0.05-0.24, P=0.003; 0.17, 0.08-0.27, P<0.001; 0.14, 0.05-0.22, P=0.002, respectively). Previous adiposity was associated with aortic stiffening independent of change in adiposity, glycaemia, and lipid levels across PWV assessments. We estimated that the body mass index-linked PWV increase will account for 12% of the projected increase in cardiovascular risk because of high body mass index. General and central adiposity in later midlife were strong independent predictors of aortic stiffening. Our findings suggest that adiposity is an important and potentially modifiable determinant of arterial aging. PMID:26056335

  16. Adipose tissue, diet and aging.

    PubMed

    Zamboni, Mauro; Rossi, Andrea P; Fantin, Francesco; Zamboni, Giulia; Chirumbolo, Salvatore; Zoico, Elena; Mazzali, Gloria

    2014-01-01

    Age related increase in body fat mass, visceral adipose tissue (AT), and ectopic fat deposition are strongly related to worse health conditions in the elderly. Moreover, with aging higher inflammation in adipose tissue may be observed and may contribute to inflammaging. Aging may significantly affect AT function by modifying the profile of adipokines produced by adipose cells, reducing preadipocytes number and their function and increasing AT macrophages infiltration. The initiating events of the inflammatory cascade promoting a greater AT inflammatory profile are not completely understood. Nutrients may determine changes in the amount of body fat, in its distribution as well as in AT function with some nutrients showing a pro-inflammatory effect on AT. Evidences are sparse and quite controversial with only a few studies performed in older subjects. Different dietary patterns are the result of the complex interaction of foods and nutrients, thus more studies are needed to evaluate the association between dietary patterns and changes in adipose tissue structure, distribution and function in the elderly.

  17. Hypothalamic control of adipose tissue.

    PubMed

    Stefanidis, A; Wiedmann, N M; Adler, E S; Oldfield, B J

    2014-10-01

    A detailed appreciation of the control of adipose tissue whether it be white, brown or brite/beige has never been more important to the development of a framework on which to build therapeutic strategies to combat obesity. This is because 1) the rate of fatty acid release into the circulation from lipolysis in white adipose tissue (WAT) is integrally important to the development of obesity, 2) brown adipose tissue (BAT) has now moved back to center stage with the realization that it is present in adult humans and, in its activated form, is inversely proportional to levels of obesity and 3) the identification and characterization of "brown-like" or brite/beige fat is likely to be one of the most exciting developments in adipose tissue biology in the last decade. Central to all of these developments is the role of the CNS in the control of different fat cell functions and central to CNS control is the integrative capacity of the hypothalamus. In this chapter we will attempt to detail key issues relevant to the structure and function of hypothalamic and downstream control of WAT and BAT and highlight the importance of developing an understanding of the neural input to brite/beige fat cells as a precursor to its recruitment as therapeutic target.

  18. Adipose tissue macrophages: amicus adipem?

    PubMed Central

    Odegaard, Justin I.; Ganeshan, Kirthana; Chawla, Ajay

    2014-01-01

    Chronic overnutrition drives complex adaptations within both professional metabolic and bystander tissues that, despite intense investigation, are still poorly understood. Xu et al. (2013) now describe the unexpected ability of adipose tissue macrophages to buffer lipids released from obese adipocytes in a manner independent of inflammatory macrophage activation. PMID:24315364

  19. Quantification of adipose tissue insulin sensitivity.

    PubMed

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses.

  20. Assessment of brown adipose tissue function

    PubMed Central

    Virtue, Sam; Vidal-Puig, Antonio

    2013-01-01

    In this review we discuss practical considerations for the assessment of brown adipose tissue in rodent models, focusing on mice. The central aim of the review is to provide a critical appraisal of the utility of specialized techniques for assessing brown adipose tissue function in vivo. We cover several of the most common specialized methods for analysing brown adipose tissue function in vivo, including assessment of maximal thermogenic capacity by indirect calorimetry and the measurement of sympathetic tone to brown adipose tissue. While these techniques are powerful, they are not readily available to all laboratories; therefore we also cover several simple measurements that, particularly in combination, can be used to determine if a mouse model is likely to have alterations in brown adipose tissue function. Such techniques include: pair feeding, analysis of brown adipose tissue lipid content and mRNA and protein markers of brown adipose tissue activation. PMID:23760815

  1. Exendin-4 enhances the migration of adipose-derived stem cells to neonatal rat ventricular cardiomyocyte-derived conditioned medium via the phosphoinositide 3-kinase/Akt-stromal cell-derived factor-1α/CXC chemokine receptor 4 pathway

    PubMed Central

    ZHOU, HAO; YANG, JUNJIE; XIN, TING; ZHANG, TAO; HU, SHUNYIN; ZHOU, SHANSHAN; CHEN, GUANGHUI; CHEN, YUNDAI

    2015-01-01

    Adipose-derived stem cells (ADSCs) are considered a suitable source of cells for the repair of tissue following acute myocardial infarction (AMI); however, the transplantation efficiency of ADSCs remains low. Therefore, identification of an efficient method to enhance the migration of engrafted cells to the target site is required. The present study used exendin-4 (Ex-4), a glucagon-like peptide-1 receptor agonist, to optimize the migratory capacity of ADSCs. The aim was to determine the effect and mechanisms of Ex-4 on the migration of ADSCs to neonatal rat ventricular cardiomyocyte-derived conditioned medium (NRVC-CM). The ADSCs and cardiomyocytes were cultured in vitro. Following incubation of the ADSCs with Ex-4, cell proliferation was measured using an MTT assay and the expression levels of CXC chemokine receptor 4 (CXCR4) were investigated by reverse transctiption quantitative polymerase chain reaction (RT-qPCR), western blot analysis and flow cytometry. In addition, the expression levels of stromal cell-derived factor-1α (SDF-1α) were evaluated in the NRVC-CM treated with Ex-4 by ELISA, RT-qPCR and western blot analysis. The migration of the ADSCs to the NRVC-CM was examined using a Transwell assay. Changes in the protein expression levels of phosphorylated (p−)Akt were examined in the two types of cell by western blot analysis. The results suggested that Ex-4 promoted the proliferation and expression of CXCR4 in the ADSCs, increased the secretion of SDF-1α in the cardiomyocytes and increased the expression levels of p-Akt in both cells. However, the alterations to the SDF-1α/C XC R4 cascade in the cells were abrogated following pretreatment with LY-294002, a phosphoinositide 3-kinase(PI3K) inhibitor. Furthermore, a Transwell migration assay revealed marked translocation of the ADSCs through the membranes, towards the NRVC-CM, following treatment with Ex-4. However, these effects were reduced significantly by pretreatment of the cells with the SDF-1

  2. Endocrine and Metabolic Effects of Adipose Tissue in Children and Adolescents

    PubMed Central

    KOTNIK, Primož; FISCHER POSOVSZKY, Pamela; WABITSCH, Martin

    2015-01-01

    Adipose tissue is implicated in many endocrine and metabolic processes. Leptin was among the first identified adipose-secreted factors, which act in an auto-, para- and endocrine manner. Since leptin, many other adipose tissue factors were determined, some primarily secreted from the adipocytes, some from other cells of the adipose tissue. So-called adipokines are not only involved in obesity and its complications, as are insulin resistance, type 2 diabetes and other components of the metabolic syndrome, but also in growth, reproduction, bone metabolism, immune response, cancer development and many other important biological processes. Research in the field of adipokines has revealed new insights into the physiological and pathophysiologal processes and opened new therapeutic possibilities. In the present article, a special emphasis is devoted to research in children and adolescents. PMID:27646920

  3. Endocrine and Metabolic Effects of Adipose Tissue in Children and Adolescents.

    PubMed

    Kotnik, Primož; Fischer Posovszky, Pamela; Wabitsch, Martin

    2015-06-01

    Adipose tissue is implicated in many endocrine and metabolic processes. Leptin was among the first identified adipose-secreted factors, which act in an auto-, para- and endocrine manner. Since leptin, many other adipose tissue factors were determined, some primarily secreted from the adipocytes, some from other cells of the adipose tissue. So-called adipokines are not only involved in obesity and its complications, as are insulin resistance, type 2 diabetes and other components of the metabolic syndrome, but also in growth, reproduction, bone metabolism, immune response, cancer development and many other important biological processes. Research in the field of adipokines has revealed new insights into the physiological and pathophysiologal processes and opened new therapeutic possibilities. In the present article, a special emphasis is devoted to research in children and adolescents. PMID:27646920

  4. Adiposity and the Development of Premenstrual Syndrome

    PubMed Central

    Hankinson, Susan E.; Willett, Walter C.; Johnson, Susan R.; Manson, JoAnn E.

    2010-01-01

    Abstract Background Moderate to severe premenstrual syndrome (PMS) affects 8%–20% of premenopausal women and causes substantial levels of impairment, but few modifiable risk factors for PMS have been identified. Adiposity may impact risk through the complex interaction of hormonal and neurochemical factors, but it is not known if adiposity increases a woman's risk of developing PMS. We have addressed these issues in a prospective study nested within the Nurses' Health Study 2. Methods Participants were a subset of women aged 27–44 and free from PMS at baseline, including 1057 women who developed PMS over 10 years of follow-up and 1968 controls. Body mass index (BMI), weight change and weight cycling were assessed biennially via questionnaire. Results We observed a strong linear relationship between BMI at baseline and risk of incident PMS, with each 1 kg/m2 increase in BMI associated with a significant 3% increase in PMS risk (95% confidence interval [CI] 1.01-1.05). After adjustment for age, smoking, physical activity, and other factors, women with BMI ≥27.5 kg/m2 at baseline had significantly higher risks of PMS than women with BMI <20 kg/m2 (ptrend = 0.003). A large weight change between age 18 and the year 1991 was significantly associated with PMS risk, whereas weight cycling during this period was not. BMI was positively associated with specific symptoms, including swelling of extremities, backache, and abdominal cramping (all p < 0.001). Conclusions Our findings suggest that maintaining a healthy body mass may be important for preventing the development of PMS. Additional studies are needed to assess whether losing weight would benefit overweight and obese women who currently experience PMS. PMID:20874240

  5. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    PubMed

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. PMID:26884438

  6. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    PubMed

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance.

  7. Leptin selectively decreases visceral adiposity and enhances insulin action.

    PubMed Central

    Barzilai, N; Wang, J; Massilon, D; Vuguin, P; Hawkins, M; Rossetti, L

    1997-01-01

    Intraabdominal adiposity and insulin resistance are risk factors for diabetes mellitus, dyslipidemia, arteriosclerosis, and mortality. Leptin, a fat-derived protein encoded by the ob gene, has been postulated to be a sensor of energy storage in adipose tissue capable of mediating a feedback signal to sites involved in the regulation of energy homeostasis. Here, we provide evidence for specific effects of leptin on fat distribution and in vivo insulin action. Leptin (LEP) or vehicle (CON) was administered by osmotic minipumps for 8 d to pair-fed adult rats. During the 8 d of the study, body weight and total fat mass decreased similarly in LEP and in CON. However, while moderate calorie restriction (CON) resulted in similar decreases in whole body (by 20%) and visceral (by 21%) fat, leptin administration led to a specific and marked decrease (by 62%) in visceral adiposity. During physiologic hyperinsulinemia (insulin clamp), leptin markedly enhanced insulin action on both inhibition of hepatic glucose production and stimulation of glucose uptake. Finally, leptin exerted complex effects on the hepatic gene expression of key metabolic enzymes and on the intrahepatic partitioning of metabolic fluxes, which are likely to represent a defense against excessive storage of energy in adipose depots. These studies demonstrate novel actions of circulating leptin in the regulation of fat distribution, insulin action, and hepatic gene expression and suggest that it may play a role in the pathophysiology of abdominal obesity and insulin resistance. PMID:9399957

  8. Differential Hematopoietic Activity in White Adipose Tissue Depending on its Localization.

    PubMed

    Luche, Elodie; Sengenès, Coralie; Arnaud, Emmanuelle; Laharrague, Patrick; Casteilla, Louis; Cousin, Beatrice

    2015-12-01

    White adipose tissue (WAT) can be found in different locations in the body, and these different adipose deposits exhibit specific physiopathological importance according to the subcutaneous or abdominal locations. We have shown previously the presence of functional hematopoietic stem/progenitor cells (HSPC) in subcutaneous adipose tissue (SCAT). These cells exhibit a specific hematopoietic activity that contributes to the renewal of the immune cell compartment within this adipose deposit. In this study, we investigated whether HSPC can be found in visceral adipose tissue (VAT) and whether a putative difference in in situ hematopoiesis may be related to anatomical location and to site-specific immune cell content in VAT compared to SCAT. Therein, we identified for the first time the presence of HSPC in VAT. Using both in vitro assays and in vivo competitive repopulation experiments with sorted HSPC from VAT or SCAT, we showed that the hematopoietic activity of HSPC was lower in VAT, compared to SCAT. In addition, this altered hematopoietic activity of HSPC in VAT was due to their microenvironment, and may be related to a specific combination of secreted factors and extracellular matrix molecules expressed by adipose derived stromal cells. Our results indicate that WAT specific hematopoietic activity may be generalized to all adipose deposits, although with specificity according to the fat pad location. Considering the abundance of WAT in the body, this emphasizes the potential importance of this hematopoietic activity in physiopathological situations.

  9. A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism

    PubMed Central

    Herman, Mark A.; Peroni, Odile D.; Villoria, Jorge; Schön, Michael R.; Abumrad, Nada A.; Blüher, Matthias; Klein, Samuel; Kahn, Barbara B.

    2012-01-01

    Summary The prevalence of obesity and type 2-diabetes is increasing worldwide and threatens to shorten lifespan. Impaired insulin action in peripheral tissues is a major pathogenic factor. Insulin stimulates glucose uptake in adipose tissue through the Glut4-glucose transporter and alterations in adipose-Glut4 expression or function regulate systemic insulin sensitivity. Downregulation of adipose tissue-Glut4 occurs early in diabetes development. Here we report that adipose tissue-Glut4 regulates the expression of carbohydrate responsive-element binding protein (ChREBP), a transcriptional regulator of lipogenic and glycolytic genes. Furthermore, adipose-ChREBP is a major determinant of adipose tissue fatty acid synthesis and systemic insulin sensitivity. We discovered a new mechanism for glucose-regulation of ChREBP: Glucose-mediated activation of the canonical ChREBP isoform (ChREBPα) induces expression of a novel, potent isoform (ChREBPβ) that is transcribed from an alternative promoter. ChREBPβ expression in human adipose tissue predicts insulin sensitivity indicating that it may be an effective target for treating diabetes. PMID:22466288

  10. Adipose tissue immunity and cancer.

    PubMed

    Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2013-10-02

    Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete pro-inflammatory adipokines and cytokines providing a microenvironment favorable for tumor growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching toward M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumor growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumor cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumor microenvironment with more sophisticated and selective anti-tumoral drugs.

  11. Characterization and comparison of adipose tissue-derived cells from human subcutaneous and omental adipose tissues.

    PubMed

    Toyoda, Mito; Matsubara, Yoshinori; Lin, Konghua; Sugimachi, Keizou; Furue, Masutaka

    2009-10-01

    Different fat depots contribute differently to disease and function. These differences may be due to the regional variation in cell types and inherent properties of fat cell progenitors. To address the differences of cell types in the adipose tissue from different depots, the phenotypes of freshly isolated adipose tissue-derived cells (ATDCs) from subcutaneous (SC) and omental (OM) adipose tissues were compared using flow cytometry. Our results showed that CD31(-)CD34(+)CD45(-)CD90(-)CD105(-)CD146(+) population, containing vascular smooth muscle cells and pericytes, was specifically defined in the SC adipose tissue while no such population was observed in OM adipose tissue. On the other hand, CD31(-)CD34(+)CD45(-)CD90(-)CD105(-)CD146(-) population, which is an undefined cell population, were found solely in OM adipose tissue. Overall, the SC adipose tissue contained more ATDCs than OM adipose tissue, while OM adipose tissue contained more blood-derived cells. Regarding to the inherent properties of fat cell progenitors from the two depots, adipose-derived stem cells (ADSCs) from SC had higher capacity to differentiate into both adipogenic and osteogenic lineages than those from OM, regardless of that the proliferation rates of ADSCs from both depots were similar. The higher differentiation capacity of ADSCs from SC adipose tissue suggests that SC tissue is more suitable cell source for regenerative medicine than OM adipose tissue.

  12. Linoleic acid content in adipose tissue and coronary heart disease.

    PubMed Central

    Riemersma, R A; Wood, D A; Butler, S; Elton, R A; Oliver, M; Salo, M; Nikkari, T; Vartiainen, E; Puska, P; Gey, F

    1986-01-01

    The possibility of an inverse relation between essential fatty acids in adipose tissue, in particular linoleic acid, and mortality from coronary heart disease was studied by a cross sectional survey of random population samples of apparently healthy men aged 40-49 from four European regions with differing mortality from coronary heart disease. The proportion of linoleic acid in adipose tissue was lowest in men from north Karelia, Finland, where mortality from coronary heart disease is highest, and highest in men from Italy, where mortality is lowest, with intermediate proportions in men from Scotland and south west Finland. Similar gradients were observed for the desaturation and elongation products dihomo-gamma-linolenic and arachidonic acid. The proportion of saturated fatty acids in adipose tissue was highest in Finland, intermediate in Scotland, and lowest in Italy. Italian men also had the highest proportion of oleate in their adipose tissue and the lowest proportion of myristoleate and palmitoleate. Finnish men were more obese and had a higher blood pressure. Serum cholesterol concentration was higher in north Karelia and south west Finland than in Scotland or Italy. High density lipoprotein (HDL) cholesterol concentrations reflected the regional differences in serum cholesterol, being higher in Finland and lower in Italy. The ratios of HDL cholesterol to total cholesterol, however, did not differ. The regional differences in linoleic acid in adipose tissue remained highly significant when the observed differences in other known risk factors for coronary heart disease among the four areas were taken into account by multivariate analysis. The gradients in proportions of polyunsaturated fatty acids probably reflect differences in dietary intake of linoleic acid. PMID:3087455

  13. Myocardial regeneration potential of adipose tissue-derived stem cells

    SciTech Connect

    Bai, Xiaowen; Alt, Eckhard

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

  14. Simple and longstanding adipose tissue engineering in rabbits.

    PubMed

    Tsuji, Wakako; Inamoto, Takashi; Ito, Ran; Morimoto, Naoki; Tabata, Yasuhiko; Toi, Masakazu

    2013-03-01

    Adipose tissue engineering for breast reconstruction can be performed for patients who have undergone breast surgery. We have previously confirmed adipogenesis in mice implanted with type I collagen sponge with controlled release of fibroblast growth factor 2 (FGF2) and human adipose tissue-derived stem cells. However, in order to use this approach to treat breast cancer patients, a large amount of adipose tissue is needed, and FGF2 is not readily available. Thus, we aimed to regenerate large amounts of adipose tissue without FGF2 for a long period. Under general anesthesia, cages made of polypropylene mesh were implanted into the rabbits' bilateral fat pads. Each cage was 10 mm in radius and 10 mm in height. Minced type I collagen sponge was injected as a scaffold into the cage. Regenerated tissue in the cage was examined with ultrasonography, and the cages were harvested 3, 6, and 12 months after the implantation. Ultrasonography revealed a gradually increasing homogeneous high-echo area in the cage. Histology of the specimen was assessed with hematoxylin and eosin staining. The percentages of regenerated adipose tissue area were 76.2 ± 13.0 and 92.8 ± 6.6 % at 6 and 12 months after the implantation, respectively. Our results showed de novo adipogenesis 12 months after the implantation of only type I collagen sponge inside the space. Ultrasonography is a noninvasive and useful method of assessing the growth of the tissue inside the cage. This simple method could be a promising clinical modality in breast reconstruction. PMID:23114565

  15. Human mediastinal adipose tissue displays certain characteristics of brown fat

    PubMed Central

    Cheung, L; Gertow, J; Werngren, O; Folkersen, L; Petrovic, N; Nedergaard, J; Franco-Cereceda, A; Eriksson, P; Fisher, R M

    2013-01-01

    Background: The amount of intra-thoracic fat, of which mediastinal adipose tissue comprises the major depot, is related to various cardiometabolic risk factors. Autopsy and imaging studies indicate that the mediastinal depot in adult humans could contain brown adipose tissue (BAT). To gain a better understanding of this intra-thoracic fat depot, we examined possible BAT characteristics of human mediastinal in comparison with subcutaneous adipose tissue. Materials and methods: Adipose tissue biopsies from thoracic subcutaneous and mediastinal depots were obtained during open-heart surgery from 33 subjects (26 male, 63.7±13.8 years, body mass index 29.3±5.1 kg m−2). Microarray analysis was performed on 10 patients and genes of interest confirmed by quantitative PCR (qPCR) in samples from another group of 23 patients. Adipocyte size was determined and uncoupling protein 1 (UCP1) protein expression investigated with immunohistochemistry. Results: The microarray data showed that a number of BAT-specific genes had significantly higher expression in the mediastinal depot than in the subcutaneous depot. Higher expression of UCP1 (24-fold, P<0.001) and PPARGC1A (1.7-fold, P=0.0047), and lower expression of SHOX2 (0.12-fold, P<0.001) and HOXC8 (0.14-fold, P<0.001) in the mediastinal depot was confirmed by qPCR. Gene set enrichment analysis identified two gene sets related to mitochondria, which were significantly more highly expressed in the mediastinal than in the subcutaneous depot (P<0.01). No significant changes in UCP1 gene expression were observed in the subcutaneous or mediastinal depots following lowering of body temperature during surgery. UCP1 messenger RNA levels in the mediastinal depot were lower than those in murine BAT and white adipose tissue. In some mediastinal adipose tissue biopsies, a small number of multilocular adipocytes that stained positively for UCP1 were observed. Adipocytes were significantly smaller in the mediastinal than the

  16. Circadian Clocks and the Interaction between Stress Axis and Adipose Function

    PubMed Central

    Kolbe, Isa; Dumbell, Rebecca

    2015-01-01

    Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism's environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed. PMID:26000016

  17. Hair Regeneration Treatment Using Adipose-Derived Stem Cell Conditioned Medium: Follow-up With Trichograms

    PubMed Central

    Suga, Hirotaka

    2015-01-01

    Objective: Adipose-derived stem cells secrete various growth factors that promote hair growth. This study examined the effects of adipose-derived stem cell-conditioned medium on alopecia. Methods: Adipose-derived stem cell-conditioned medium was intradermally injected in 22 patients (11 men and 11 women) with alopecia. Patients received treatment every 3 to 5 weeks for a total of 6 sessions. Hair numbers were counted using trichograms before and after treatment. A half-side comparison study was also performed in 10 patients (8 men and 2 women). Results: Hair numbers were significantly increased after treatment in both male (including those without finasteride administration) and female patients. In the half-side comparison study, the increase in hair numbers was significantly higher on the treatment side than on the placebo side. Conclusion: Treatment using adipose-derived stem cell-conditioned medium appears highly effective for alopecia and may represent a new therapy for hair regeneration. PMID:25834689

  18. Adipose-derived Mesenchymal Stem Cells and Their Reparative Potential in Ischemic Heart Disease.

    PubMed

    Badimon, Lina; Oñate, Blanca; Vilahur, Gemma

    2015-07-01

    Adipose tissue has long been considered an energy storage and endocrine organ; however, in recent decades, this tissue has also been considered an abundant source of mesenchymal cells. Adipose-derived stem cells are easily obtained, show a strong capacity for ex vivo expansion and differentiation to other cell types, release a large variety of angiogenic factors, and have immunomodulatory properties. Thus, adipose tissue is currently the focus of considerable interest in the field of regenerative medicine. In the context of coronary heart disease, numerous experimental studies have supported the safety and efficacy of adipose-derived stem cells in the setting of myocardial infarction. These results have encouraged the clinical use of these stem cells, possibly prematurely. Indeed, the presence of cardiovascular risk factors, such as hypertension, coronary disease, diabetes mellitus, and obesity, alter and reduce the functionality of adipose-derived stem cells, putting in doubt the efficacy of their autologous implantation. In the present article, white adipose tissue is described, the stem cells found in this tissue are characterized, and the use of these cells is discussed according to the preclinical and clinical trials performed so far. PMID:26028258

  19. EBF2 promotes the recruitment of beige adipocytes in white adipose tissue

    PubMed Central

    Stine, Rachel R.; Shapira, Suzanne N.; Lim, Hee-Woong; Ishibashi, Jeff; Harms, Matthew; Won, Kyoung-Jae; Seale, Patrick

    2015-01-01

    Objective The induction of beige/brite adipose cells in white adipose tissue (WAT) is associated with protection against high fat diet-induced obesity and insulin resistance in animals. The helix-loop-helix transcription factor Early B-Cell Factor-2 (EBF2) regulates brown adipose tissue development. Here, we asked if EBF2 regulates beige fat cell biogenesis and protects animals against obesity. Methods In addition to primary cell culture studies, we used ​Ebf2 knockout mice and mice overexpressing EBF2 in the adipose tissue to study the necessity and sufficiency of EBF2 to induce beiging in vivo. Results We found that EBF2 is required for beige adipocyte development in mice. Subcutaneous WAT or primary adipose cell cultures from Ebf2 knockout mice did not induce Uncoupling Protein 1 (UCP1) or a thermogenic program following adrenergic stimulation. Conversely, over-expression of EBF2 in adipocyte cultures induced UCP1 expression and a brown-like/beige fat-selective differentiation program. Transgenic expression of Ebf2 in adipose tissues robustly stimulated beige adipocyte development in the WAT of mice, even while housed at thermoneutrality. EBF2 overexpression was sufficient to increase mitochondrial function in WAT and protect animals against high fat diet-induced weight gain. Conclusions Taken together, our results demonstrate that EBF2 controls the beiging process and suggest that activation of EBF2 in WAT could be used to reduce obesity. PMID:26844207

  20. Adipose-derived Mesenchymal Stem Cells and Their Reparative Potential in Ischemic Heart Disease.

    PubMed

    Badimon, Lina; Oñate, Blanca; Vilahur, Gemma

    2015-07-01

    Adipose tissue has long been considered an energy storage and endocrine organ; however, in recent decades, this tissue has also been considered an abundant source of mesenchymal cells. Adipose-derived stem cells are easily obtained, show a strong capacity for ex vivo expansion and differentiation to other cell types, release a large variety of angiogenic factors, and have immunomodulatory properties. Thus, adipose tissue is currently the focus of considerable interest in the field of regenerative medicine. In the context of coronary heart disease, numerous experimental studies have supported the safety and efficacy of adipose-derived stem cells in the setting of myocardial infarction. These results have encouraged the clinical use of these stem cells, possibly prematurely. Indeed, the presence of cardiovascular risk factors, such as hypertension, coronary disease, diabetes mellitus, and obesity, alter and reduce the functionality of adipose-derived stem cells, putting in doubt the efficacy of their autologous implantation. In the present article, white adipose tissue is described, the stem cells found in this tissue are characterized, and the use of these cells is discussed according to the preclinical and clinical trials performed so far.

  1. Human adipose stem cells: current clinical applications.

    PubMed

    Gir, Phanette; Oni, Georgette; Brown, Spencer A; Mojallal, Ali; Rohrich, Rod J

    2012-06-01

    Adipose-derived stem cells are multipotent cells that can easily be extracted from adipose tissue, are capable of expansion in vitro, and have the capacity to differentiate into multiple cell lineages, which have the potential for use in regenerative medicine. However, several issues need to be studied to determine safe human use. For example, there are questions related to isolation and purification of adipose-derived stem cells, their effect on tumor growth, and the enforcement of U.S. Food and Drug Administration regulations. Numerous studies have been published, with the interest in the potential for regenerative medicine continually growing. Several clinical trials using human adipose stem cell therapy are currently being performed around the world, and there has been a rapid evolution and expansion of their number. The purpose of this article was to review the current published basic science evidence and ongoing clinical trials involving the use of adipose-derived stem cells in plastic surgery and in regenerative medicine in general. The results of the studies and clinical trials using adipose-derived stem cells reported in this review seem to be promising not only in plastic surgery but also in a wide variety of other specialties. Nevertheless, those reported showed disparity in the way adipose-derived stem cells were used. Further basic science experimental studies with standardized protocols and larger randomized trials need to be performed to ensure safety and efficacy of adipose-derived stem cells use in accordance with U.S. Food and Drug Administration guidelines.

  2. Sex differences in adipose tissue

    PubMed Central

    Fuente-Martín, Esther; Argente-Arizón, Pilar; Ros, Purificación; Argente, Jesús; Chowen, Julie A

    2013-01-01

    Obesity and its associated secondary complications are active areas of investigation in search of effective treatments. As a result of this intensified research numerous differences between males and females at all levels of metabolic control have come to the forefront. These differences include not only the amount and distribution of adipose tissue, but also differences in its metabolic capacity and functions between the sexes. Here, we review some of the recent advances in our understanding of these dimorphisms and emphasize the fact that these differences between males and females must be taken into consideration in hopes of obtaining successful treatments for both sexes. PMID:23991358

  3. Adipocytes under Assault: Environmental Disruption of Adipose Physiology

    PubMed Central

    Regnier, Shane M.; Sargis, Robert M.

    2013-01-01

    The burgeoning obesity epidemic has placed enormous strains on individual and societal health mandating a careful search for pathogenic factors, including the contributions made by endocrine disrupting chemicals (EDCs). In addition to evidence that some exogenous chemicals have the capacity to modulate classical hormonal signaling axes, there is mounting evidence that several EDCs can also disrupt metabolic pathways and alter energy homeostasis. Adipose tissue appears to be a particularly important target of these metabolic disruptions. A diverse array of compounds has been shown to alter adipocyte differentiation, and several EDCs have been shown to modulate adipocyte physiology, including adipocytic insulin action and adipokine secretion. This rapidly emerging evidence demonstrating that environmental contaminants alter adipocyte function emphasizes the potential role that disruption of adipose physiology by EDCs may play in the global epidemic of metabolic disease. Further work is required to better characterize the molecular targets responsible for mediating the effects of EDCs on adipose tissue. Improved understanding of the precise signaling pathways altered by exposure to environmental contaminants will enhance our understanding of which chemicals pose a threat to metabolic health and how those compounds synergize with lifestyle factors to promote obesity and its associated complications. This knowledge may also improve our capacity to predict which synthetic compounds may alter energy homeostasis before they are released into the environment while also providing critical evidentiary support for efforts to restrict the production and use of chemicals that pose the greatest threat to human metabolic health. PMID:23735214

  4. Heterogeneity of white adipose tissue: molecular basis and clinical implications

    PubMed Central

    Kwok, Kelvin H M; Lam, Karen S L; Xu, Aimin

    2016-01-01

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity. PMID:26964831

  5. A role of active brown adipose tissue in cancer cachexia?

    PubMed Central

    Beijer, Emiel; Schoenmakers, Janna; Vijgen, Guy; Kessels, Fons; Dingemans, Anne-Marie; Schrauwen, Patrick; Wouters, Miel; van Marken Lichtenbelt, Wouter; Teule, Jaap; Brans, Boudewijn

    2012-01-01

    Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT). Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and so-called brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluoro- deoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity. PMID:25992201

  6. Regional differences in perivascular adipose tissue impacting vascular homeostasis.

    PubMed

    Gil-Ortega, Marta; Somoza, Beatriz; Huang, Yu; Gollasch, Maik; Fernández-Alfonso, Maria S

    2015-07-01

    Perivascular adipose tissue (PVAT) releases several important vasoactive factors with physiological and pathophysiological paracrine effects. A large body of evidence suggests regional phenotypic and functional differences among PVAT depots, depending on the specific vascular bed or different regions in the vascular bed where the PVAT is located. These non-uniform and separate PVATs exert various paracrine effects on vascular structure and function that largely impact disease states, such as endothelial dysfunction, atherosclerosis, or insulin resistance. This emerging view of PVAT function requires considering heterogeneous PVAT as a specialized organ that can differentially regulate vascular function depending on its anatomical location. In this context, the adipose-vascular axis may represent a novel target for pharmacological intervention in vasculopathy in cardiometabolic disorders.

  7. Heterogeneity of white adipose tissue: molecular basis and clinical implications.

    PubMed

    Kwok, Kelvin H M; Lam, Karen S L; Xu, Aimin

    2016-03-11

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity.

  8. Prolactin (PRL) in adipose tissue: regulation and functions.

    PubMed

    Ben-Jonathan, Nira; Hugo, Eric

    2015-01-01

    New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance.

  9. Fully automated adipose tissue measurement on abdominal CT

    NASA Astrophysics Data System (ADS)

    Yao, Jianhua; Sussman, Daniel L.; Summers, Ronald M.

    2011-03-01

    Obesity has become widespread in America and has been associated as a risk factor for many illnesses. Adipose tissue (AT) content, especially visceral AT (VAT), is an important indicator for risks of many disorders, including heart disease and diabetes. Measuring adipose tissue (AT) with traditional means is often unreliable and inaccurate. CT provides a means to measure AT accurately and consistently. We present a fully automated method to segment and measure abdominal AT in CT. Our method integrates image preprocessing which attempts to correct for image artifacts and inhomogeneities. We use fuzzy cmeans to cluster AT regions and active contour models to separate subcutaneous and visceral AT. We tested our method on 50 abdominal CT scans and evaluated the correlations between several measurements.

  10. Hypothalamic control of brown adipose tissue thermogenesis

    PubMed Central

    Labbé, Sebastien M.; Caron, Alexandre; Lanfray, Damien; Monge-Rofarello, Boris; Bartness, Timothy J.; Richard, Denis

    2015-01-01

    It has long been known, in large part from animal studies, that the control of brown adipose tissue (BAT) thermogenesis is insured by the central nervous system (CNS), which integrates several stimuli in order to control BAT activation through the sympathetic nervous system (SNS). SNS-mediated BAT activity is governed by diverse neurons found in brain structures involved in homeostatic regulations and whose activity is modulated by various factors including oscillations of energy fluxes. The characterization of these neurons has always represented a challenging issue. The available literature suggests that the neuronal circuits controlling BAT thermogenesis are largely part of an autonomic circuitry involving the hypothalamus, brainstem and the SNS efferent neurons. In the present review, we recapitulate the latest progresses in regards to the hypothalamic regulation of BAT metabolism. We briefly addressed the role of the thermoregulatory pathway and its interactions with the energy balance systems in the control of thermogenesis. We also reviewed the involvement of the brain melanocortin and endocannabinoid systems as well as the emerging role of steroidogenic factor 1 (SF1) neurons in BAT thermogenesis. Finally, we examined the link existing between these systems and the homeostatic factors that modulate their activities. PMID:26578907

  11. Adipose and mammary epithelial tissue engineering.

    PubMed

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

  12. Imaging white adipose tissue with confocal microscopy.

    PubMed

    Martinez-Santibañez, Gabriel; Cho, Kae Won; Lumeng, Carey N

    2014-01-01

    Adipose tissue is composed of a variety of cell types that include mature adipocytes, endothelial cells, fibroblasts, adipocyte progenitors, and a range of inflammatory leukocytes. These cells work in concert to promote nutrient storage in adipose tissue depots and vary widely based on location. In addition, overnutrition and obesity impart significant changes in the architecture of adipose tissue that are strongly associated with metabolic dysfunction. Recent studies have called attention to the importance of adipose tissue microenvironments in regulating adipocyte function and therefore require techniques that preserve cellular interactions and permit detailed analysis of three-dimensional structures in fat. This chapter summarizes our experience with the use of laser scanning confocal microscopy for imaging adipose tissue in rodents.

  13. Mitochondria and endocrine function of adipose tissue.

    PubMed

    Medina-Gómez, Gema

    2012-12-01

    Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications. White adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose tissue with higher oxidative capacity. Nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis. Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D. This review discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future. PMID:23168280

  14. Adipose and mammary epithelial tissue engineering

    PubMed Central

    Zhu, Wenting; Nelson, Celeste M.

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast. PMID:23628872

  15. Persistent organic pollutants meet adipose tissue hypoxia: does cross-talk contribute to inflammation during obesity?

    PubMed

    Myre, M; Imbeault, P

    2014-01-01

    Lipophilic persistent organic pollutants (POPs) accumulate in lipid-rich tissues such as human adipose tissue. This is particularly problematic in individuals with excess adiposity, a physiological state that may be additionally characterized by local adipose tissue hypoxia. Hypoxic patches occur when oxygen diffusion is insufficient to reach all hypertrophic adipocytes. POPs and hypoxia independently contribute to the development of adipose tissue-specific and systemic inflammation often associated with obesity. Inflammation is induced by increased proinflammatory mediators such as tumour necrosis factor-alpha, interleukin-6, and monocyte chemotactic protein-1, as well as reduced adiponectin release, an anti-inflammatory and insulin-sensitizing adipokine. The aryl hydrocarbon receptor (AhR) mediates the cellular response to some pollutants, while hypoxia responses occur through the oxygen-sensitive transcription factor hypoxia-inducible factor (HIF)-1. There is some overlap between the two signalling pathways since both require a common subunit called the AhR nuclear translocator. As such, it is unclear how adipocytes respond to simultaneous POP and hypoxia exposure. This brief review explores the independent contribution of POPs and adipose tissue hypoxia as factors underlying the inflammatory response from adipocytes during obesity. It also highlights that the combined effect of POPs and hypoxia through the AhR and HIF-1 signalling pathways remains to be tested. PMID:23998203

  16. Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol.

    PubMed

    Pektas, Mehmet Bilgehan; Koca, Halit Bugra; Sadi, Gokhan; Akar, Fatma

    2016-01-01

    The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling including IR, IRS-1, IRS-2, Akt, PI3K, eNOS, mTOR, and PPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well as iNOS, Nrf2, and PI3K mRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes.

  17. Dietary Fructose Activates Insulin Signaling and Inflammation in Adipose Tissue: Modulatory Role of Resveratrol

    PubMed Central

    Pektas, Mehmet Bilgehan; Koca, Halit Bugra; Sadi, Gokhan; Akar, Fatma

    2016-01-01

    The effects of high-fructose diet on adipose tissue insulin signaling and inflammatory process have been poorly documented. In this study, we examined the influences of long-term fructose intake and resveratrol supplementation on the expression of genes involved in insulin signaling and the levels of inflammatory cytokines and sex hormones in the white adipose tissues of male and female rats. Consumption of high-fructose diet for 24 weeks increased the expression of genes involved in insulin signaling including IR, IRS-1, IRS-2, Akt, PI3K, eNOS, mTOR, and PPARγ, despite induction of proinflammatory markers, iNOS, TNFα, IL-1β, IL-18, MDA, and ALT, as well as anti-inflammatory factors, IL-10 and Nrf2 in adipose tissues from males and females. Total and free testosterone concentrations of adipose tissues were impaired in males but increased in females, although there were no changes in their blood levels. Resveratrol supplementation markedly restored the levels of MDA, IL6, IL-10, and IL-18, as well as iNOS, Nrf2, and PI3K mRNA, in adipose tissues of both genders. Dietary fructose activates both insulin signaling and inflammatory pathway in the adipose tissues of male and female rats proposing no correlation between the tissue insulin signaling and inflammation. Resveratrol has partly modulatory effects on fructose-induced changes. PMID:27066503

  18. Concise review: The obesity cancer paradigm: exploration of the interactions and crosstalk with adipose stem cells.

    PubMed

    Strong, Amy L; Burow, Matthew E; Gimble, Jeffrey M; Bunnell, Bruce A

    2015-02-01

    With the recognition of obesity as a global health crisis, researchers have devoted greater effort to defining and understanding the pathophysiological molecular pathways regulating the biology of adipose tissue and obesity. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, has been linked to an increased incidence and aggressiveness of colon, hematological, prostate, and postmenopausal breast cancers. The increased morbidity and mortality of obesity-associated cancers have been attributed to higher levels of hormones, adipokines, and cytokines secreted by the adipose tissue. The increased amount of adipose tissue also results in higher numbers of adipose stromal/stem cells (ASCs). These ASCs have been shown to impact cancer progression directly through several mechanisms, including the increased recruitment of ASCs to the tumor site and increased production of cytokines and growth factors by ASCs and other cells within the tumor stroma. Emerging evidence indicates that obesity induces alterations in the biologic properties of ASCs, subsequently leading to enhanced tumorigenesis and metastasis of cancer cells. This review will discuss the links between obesity and cancer tumor progression, including obesity-associated changes in adipose tissue, inflammation, adipokines, and chemokines. Novel topics will include a discussion of the contribution of ASCs to this complex system with an emphasis on their role in the tumor stroma. The reciprocal and circular feedback loop between obesity and ASCs as well as the mechanisms by which ASCs from obese patients alter the biology of cancer cells and enhance tumorigenesis will be discussed.

  19. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

    PubMed Central

    Salas, Anna; Noé, Véronique; Ciudad, Carlos J; Romero, M Mar; Remesar, Xavier; Esteve, Montserrat

    2007-01-01

    Background Short-term OE (oleoyl-estrone) treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours) was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL) were decreased by 52%, those of Fatty Acid Synthase (FAS) by 95%, those of Hormone Sensible Lipase (HSL) by 32%, those of Acetyl CoA Carboxylase (ACC) by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b) by 45%, and those of Fatty Acid Transport Protein 1 (FATP1) and Adipocyte Fatty Acid Binding Protein (FABP4) by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα) values showed overexpression (198%). Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism. PMID:17725831

  20. In Utero Programming of Later Adiposity: The Role of Fetal Growth Restriction

    PubMed Central

    Sarr, Ousseynou; Yang, Kaiping; Regnault, Timothy R. H.

    2012-01-01

    Intrauterine growth restriction (IUGR) is strongly associated with obesity in adult life. The mechanisms contributing to the onset of IUGR-associated adult obesity have been studied in animal models and humans, where changes in fetal adipose tissue development, hormone levels and epigenome have been identified as principal areas of alteration leading to later life obesity. Following an adverse in utero development, IUGR fetuses display increased lipogenic and adipogenic capacity in adipocytes, hypoleptinemia, altered glucocorticoid signalling, and chromatin remodelling, which subsequently all contribute to an increased later life obesity risk. Data suggest that many of these changes result from an enhanced activity of the adipose master transcription factor regulator, peroxisome proliferator-activated receptor-γ (PPARγ) and its coregulators, increased lipogenic fatty acid synthase (FAS) expression and activity, and upregulation of glycolysis in fetal adipose tissue. Increased expression of fetal hypothalamic neuropeptide Y (NPY), altered hypothalamic leptin receptor expression and partitioning, reduced adipose noradrenergic sympathetic innervations, enhanced adipose glucocorticoid action, and modifications in methylation status in the promoter of hepatic and adipose adipogenic and lipogenic genes in the fetus also contribute to obesity following IUGR. Therefore, interventions that inhibit these fetal developmental changes will be beneficial for modulation of adult body fat accumulation. PMID:23251802

  1. Prognostic Impact of Changes in Adipose Tissue Areas after Colectomy in Colorectal Cancer Patients.

    PubMed

    Choe, Eun Kyung; Park, Kyu Joo; Ryoo, Seung Bum; Moon, Sang Hui; Oh, Heung Kwon; Han, Eon Chul

    2016-10-01

    There have been few studies assessing the changes in the body components of patients after colectomy in colorectal cancer (CRC). The purpose of this study was to verify the trends in the adipose tissue areas of CRC patients before and after surgery and to determine their clinical relevance. Computed tomography (CT)-assessed subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) areas were recorded before and after curative resection in stage I to III CRC patients. Changes in the adipose tissue were assessed by calculating the difference in the adipose tissue area between preoperative CT and the most recent postoperative CT, which is disease-free state. Regarding obesity before surgery, there were no prognostic effect of body mass index (BMI), VAT and SAT, and 47.3% of patients had increases in VAT after colectomy. By multivariate analysis, adjusting sex, age, stage, differentiation, VAT change was the only obesity related factor to predict the prognosis, that patients who had increase in VAT after colectomy had better overall survival (HR, 0.557; 95% CI, 0.317-0.880) and disease-free survival (HR, 0.602; 95% CI, 0.391-0.927). BMI and SAT change had no significant association. In subgroup analysis of stage III CRC patients, VAT change had significance for prognosis only in patients who had adjuvant chemotherapy but not in those who did not receive postoperative chemotherapy. Increase in visceral adipose tissue after surgery is a favorable predictor of prognosis for CRC patients. PMID:27550485

  2. Alternative measures to BMI: Exploring income-related inequalities in adiposity in Great Britain.

    PubMed

    Davillas, Apostolos; Benzeval, Michaela

    2016-10-01

    Socio-economic inequalities in adiposity are of particular interest themselves but also because they may be associated with inequalities in overall health status. Using cross-sectional representative data from Great Britain (1/2010-3/2012) for 13,138 adults (5652 males and 7486 females) over age 20, we aimed to explore the presence of income-related inequalities in alternative adiposity measures by gender and to identify the underlying factors contributing to these inequalities. For this reason, we employed concentration indexes and regression-based decomposition techniques. To control for non-homogeneity in body composition, we employed a variety of adiposity measures including body fat (absolute and percentage) and central adiposity (waist circumference) in addition to the conventional body mass index (BMI). The body fat measures allowed us to distinguish between the fat- and lean-mass components of BMI. We found that the absence of income-related obesity inequalities for males in the existing literature may be attributed to their focus on BMI-based measures. Pro-rich inequalities were evident for the fat-mass and central adiposity measures for males, while this was not the case for BMI. Irrespective of the adiposity measure applied, pro-rich inequalities were evident for females. The decomposition analysis showed that these inequalities were mainly attributable to subjective financial well-being measures (perceptions of financial strain and material deprivation) and education, with the relative contribution of the former being more evident in females. Our findings have important implications for the measurement of socio-economic inequalities in adiposity and indicate that central adiposity and body composition measures should be included health policy agendas. Psycho-social mechanisms, linked to subjective financial well-being, and education -rather than income itself-are more relevant for tackling inequalities.

  3. Alternative measures to BMI: Exploring income-related inequalities in adiposity in Great Britain.

    PubMed

    Davillas, Apostolos; Benzeval, Michaela

    2016-10-01

    Socio-economic inequalities in adiposity are of particular interest themselves but also because they may be associated with inequalities in overall health status. Using cross-sectional representative data from Great Britain (1/2010-3/2012) for 13,138 adults (5652 males and 7486 females) over age 20, we aimed to explore the presence of income-related inequalities in alternative adiposity measures by gender and to identify the underlying factors contributing to these inequalities. For this reason, we employed concentration indexes and regression-based decomposition techniques. To control for non-homogeneity in body composition, we employed a variety of adiposity measures including body fat (absolute and percentage) and central adiposity (waist circumference) in addition to the conventional body mass index (BMI). The body fat measures allowed us to distinguish between the fat- and lean-mass components of BMI. We found that the absence of income-related obesity inequalities for males in the existing literature may be attributed to their focus on BMI-based measures. Pro-rich inequalities were evident for the fat-mass and central adiposity measures for males, while this was not the case for BMI. Irrespective of the adiposity measure applied, pro-rich inequalities were evident for females. The decomposition analysis showed that these inequalities were mainly attributable to subjective financial well-being measures (perceptions of financial strain and material deprivation) and education, with the relative contribution of the former being more evident in females. Our findings have important implications for the measurement of socio-economic inequalities in adiposity and indicate that central adiposity and body composition measures should be included health policy agendas. Psycho-social mechanisms, linked to subjective financial well-being, and education -rather than income itself-are more relevant for tackling inequalities. PMID:27580342

  4. Nutritional manipulations in the perinatal period program adipose tissue in offspring.

    PubMed

    Lukaszewski, Marie-Amélie; Eberlé, Delphine; Vieau, Didier; Breton, Christophe

    2013-11-15

    Epidemiological studies demonstrated initially that maternal undernutrition results in low birth weight with increased risk for long-lasting energy balance disorders. Maternal obesity and diabetes associated with high birth weight, excessive nutrition in neonates, and rapid catchup growth also increase the risk of adult-onset obesity. As stated by the Developmental Origin of Health and Disease concept, nutrient supply perturbations in the fetus or neonate result in long-term programming of individual body weight set point. Adipose tissue is a key fuel storage unit involved mainly in the maintenance of energy homeostasis. Studies in numerous animal models have demonstrated that the adipose tissue is the focus of developmental programming events in a sex- and depot-specific manner. In rodents, adipose tissue development is particularly active during the perinatal period, especially during the last week of gestation and during early postnatal life. In contrast to rodents, this process essentially takes place before birth in bigger mammals. Despite these different developmental time windows, altricial and precocial species share several mechanisms of adipose tissue programming. Offspring from malnourished dams present adipose tissue with a series of alterations: impaired glucose uptake, insulin and leptin resistance, low-grade inflammation, modified sympathetic activity with reduced noradrenergic innervations, and thermogenesis. These modifications reprogram adipose tissue metabolism by changing fat distribution and composition and by enhancing adipogenesis, predisposing the offspring to fat accumulation. Subtle adipose tissue circadian rhythm changes are also observed. Inappropriate hormone levels, modified tissue sensitivity (especially glucocorticoid system), and epigenetic mechanisms are key factors for adipose tissue programming during the perinatal period.

  5. Human adipose dynamics and metabolic health

    PubMed Central

    Feng, Bin; Zhang, Tracy; Xu, Haiyan

    2013-01-01

    The two types of adipose tissue in humans, white and brown, have distinct developmental origins and functions. Human white adipose tissue plays a pivotal role in maintaining whole-body energy homeostasis by storing triglycerides when energy is in surplus, releasing free fatty acids as a fuel during energy shortage, and secreting adipokines that are important for regulating lipid and glucose metabolism. The size of white adipose mass needs to be kept at a proper set point. Dramatic expansion of white fat mass causes obesity—now become a global epidemic disease—and increases the risk for the development of many life-threatening diseases. The absence of white adipose tissue or abnormal white adipose tissue redistribution leads to lipodystrophy, a condition often associated with metabolic disorders. Brown adipose tissue is a thermogenic organ whose mass is inversely correlated with body mass index and age. Therapeutic approaches targeting adipose tissue have been proven to be effective in improving obesity-related metabolic disorders, and promising new therapies could be developed in the near future. PMID:23317303

  6. Overeating styles and adiposity among multiethnic youth

    PubMed Central

    Ledoux, Tracey; Watson, Kathy; Baranowski, Janice; Tepper, Beverly J.; Baranowski, Tom

    2010-01-01

    Reasons for inconsistent associations between overeating styles and adiposity among youth may include differences in effects by age, gender, or ethnicity; failure to control for social desirability of response; or adiposity measurement limitations. This study examined the relationship between overeating styles and multiple measures of adiposity, after controlling for social desirability and testing for moderation by ethnicity, age, and gender. Data from 304 9–10 year old children and 264 17–18 year old adolescents equally representing African American, Hispanic, and White ethnic groups were extracted from a larger cross-sectional study. Measures included the Dutch Eating Behavior Questionnaire (restrained, external, and emotional overeating subscales), the “Lie Scale” from the Revised Children’s Manifest Anxiety Scale, and measured weight, height, waist circumference, and triceps skinfold. BMI z-score and a global adiposity index were calculated. Mixed model linear regression showed restraint was positively and external eating was negatively related to measures of adiposity. African American youth had a stronger inverse association between emotional eating and adiposity than White or Hispanic youth. Relationships were not influenced by social desirability nor moderated by age or gender. Overeating styles are related to adiposity in nearly all youth but the nature of these associations are moderated by ethnicity. PMID:21115080

  7. Adipose tissue plasticity from WAT to BAT and in between.

    PubMed

    Lee, Yun-Hee; Mottillo, Emilio P; Granneman, James G

    2014-03-01

    Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  8. An alternative splicing program promotes adipose tissue thermogenesis

    PubMed Central

    Vernia, Santiago; Edwards, Yvonne JK; Han, Myoung Sook; Cavanagh-Kyros, Julie; Barrett, Tamera; Kim, Jason K; Davis, Roger J

    2016-01-01

    Alternative pre-mRNA splicing expands the complexity of the transcriptome and controls isoform-specific gene expression. Whether alternative splicing contributes to metabolic regulation is largely unknown. Here we investigated the contribution of alternative splicing to the development of diet-induced obesity. We found that obesity-induced changes in adipocyte gene expression include alternative pre-mRNA splicing. Bioinformatics analysis associated part of this alternative splicing program with sequence specific NOVA splicing factors. This conclusion was confirmed by studies of mice with NOVA deficiency in adipocytes. Phenotypic analysis of the NOVA-deficient mice demonstrated increased adipose tissue thermogenesis and improved glycemia. We show that NOVA proteins mediate a splicing program that suppresses adipose tissue thermogenesis. Together, these data provide quantitative analysis of gene expression at exon-level resolution in obesity and identify a novel mechanism that contributes to the regulation of adipose tissue function and the maintenance of normal glycemia. DOI: http://dx.doi.org/10.7554/eLife.17672.001 PMID:27635635

  9. Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects.

    PubMed

    Honek, Jennifer; Lim, Sharon; Fischer, Carina; Iwamoto, Hideki; Seki, Takahiro; Cao, Yihai

    2014-07-01

    The number of obese and overweight individuals is globally rising, and obesity-associated disorders such as type 2 diabetes, cardiovascular disease and certain types of cancer are among the most common causes of death. While white adipose tissue is the key player in the storage of energy, active brown adipose tissue expends energy due to its thermogenic capacity. Expanding and activating brown adipose tissue using pharmacological approaches therefore might offer an attractive possibility for therapeutic intervention to counteract obesity and its consequences for metabolic health.

  10. Technical note: Alternatives to reduce adipose tissue sampling bias.

    PubMed

    Cruz, G D; Wang, Y; Fadel, J G

    2014-10-01

    Understanding the mechanisms by which nutritional and pharmaceutical factors can manipulate adipose tissue growth and development in production animals has direct and indirect effects in the profitability of an enterprise. Adipocyte cellularity (number and size) is a key biological response that is commonly measured in animal science research. The variability and sampling of adipocyte cellularity within a muscle has been addressed in previous studies, but no attempt to critically investigate these issues has been proposed in the literature. The present study evaluated 2 sampling techniques (random and systematic) in an attempt to minimize sampling bias and to determine the minimum number of samples from 1 to 15 needed to represent the overall adipose tissue in the muscle. Both sampling procedures were applied on adipose tissue samples dissected from 30 longissimus muscles from cattle finished either on grass or grain. Briefly, adipose tissue samples were fixed with osmium tetroxide, and size and number of adipocytes were determined by a Coulter Counter. These results were then fit in a finite mixture model to obtain distribution parameters of each sample. To evaluate the benefits of increasing number of samples and the advantage of the new sampling technique, the concept of acceptance ratio was used; simply stated, the higher the acceptance ratio, the better the representation of the overall population. As expected, a great improvement on the estimation of the overall adipocyte cellularity parameters was observed using both sampling techniques when sample size number increased from 1 to 15 samples, considering both techniques' acceptance ratio increased from approximately 3 to 25%. When comparing sampling techniques, the systematic procedure slightly improved parameters estimation. The results suggest that more detailed research using other sampling techniques may provide better estimates for minimum sampling.

  11. Integrator complex plays an essential role in adipose differentiation

    SciTech Connect

    Otani, Yuichiro; Nakatsu, Yusuke; Sakoda, Hideyuki; Fukushima, Toshiaki; Fujishiro, Midori; Kushiyama, Akifumi; Okubo, Hirofumi; Tsuchiya, Yoshihiro; Ohno, Haruya; Takahashi, Shin-Ichiro; Nishimura, Fusanori; Kamata, Hideaki; Katagiri, Hideki; Asano, Tomoichiro

    2013-05-03

    Highlights: •IntS6 and IntS11 are subunits of the Integrator complex. •Expression levels of IntS6 and IntS11 were very low in 3T3-L1 fibroblast. •IntS6 and IntS11 were upregulated during adipose differentiation. •Suppression of IntS6 or IntS11 expression inhibited adipose differentiation. -- Abstract: The dynamic process of adipose differentiation involves stepwise expressions of transcription factors and proteins specific to the mature fat cell phenotype. In this study, it was revealed that expression levels of IntS6 and IntS11, subunits of the Integrator complex, were increased in 3T3-L1 cells in the period when the cells reached confluence and differentiated into adipocytes, while being reduced to basal levels after the completion of differentiation. Suppression of IntS6 or IntS11 expression using siRNAs in 3T3-L1 preadipocytes markedly inhibited differentiation into mature adipocytes, based on morphological findings as well as mRNA analysis of adipocyte-specific genes such as Glut4, perilipin and Fabp4. Although Pparγ2 protein expression was suppressed in IntS6 or IntS11-siRNA treated cells, adenoviral forced expression of Pparγ2 failed to restore the capacity for differentiation into mature adipocytes. Taken together, these findings demonstrate that increased expression of Integrator complex subunits is an indispensable event in adipose differentiation. Although further study is necessary to elucidate the underlying mechanism, the processing of U1, U2 small nuclear RNAs may be involved in cell differentiation steps.

  12. Energy Expenditure and Adiposity in Nigerian and African American Women

    PubMed Central

    Ebersole, Kara; Dugas, Lara; Durazo-Arvizu, Ramon A.; Adeyemo, Adebowale A.; Tayo, Bamidele O.; Omotade, Olayemi O.; Brieger, William; Schoeller, Dale A.; Cooper, Richard S.; Luke, Amy

    2010-01-01

    Objective Obesity is a prevalent condition in industrialized societies and is increasing around the world. We sought to assess the relative importance of resting energy expenditure (REE) and activity energy expenditure (AEE) in two populations with different rates of obesity. Methods Women of African descent between 18 and 60 were recruited from rural Nigeria and from metropolitan Chicago. Total energy expenditure (TEE) was measured using the doubly labeled water technique and REE by indirect calorimetry; AEE was calculated as the difference between TEE and the sum of REE plus a factor for the thermic effect of food. In the analyses all EE parameters were adjusted for body size using a regression method. Comparisons were made between the groups and associations between EE and adiposity examined. Results A total of 149 Nigerian and 172 African-American women completed the protocol. All body size measurements were lower in the Nigerian women. Adjusted TEE and REE were higher in the Nigerian cohort but adjusted AEE did not differ significantly. Adjustment for parity, seasonality and recent illness did not modify mean AEE or adiposity. In neither cohort was there a meaningful association between measures of AEE and adiposity. Conclusion In these cohorts of women from very different environments, AEE did not differ significantly nor was it associated cross-sectionally with adiposity. If generalizable, these findings suggest that reduction in AEE may have less of a role in the development of obesity than anticipated. The possibility remains that variation in type and duration of activity plays a role not captured by total AEE. PMID:19186335

  13. Brown adipose tissue and bone

    PubMed Central

    Lidell, M E; Enerbäck, S

    2015-01-01

    Brown adipose tissue (BAT) is capable of transforming chemically stored energy, in the form of triglycerides, into heat. Recent studies have shown that metabolically active BAT is present in a large proportion of adult humans, where its activity correlates with a favorable metabolic status. Hence, the tissue is now regarded as an interesting target for therapies against obesity and associated diseases such as type 2 diabetes, the hypothesis being that an induction of BAT would be beneficial for these disease states. Apart from the association between BAT activity and a healthier metabolic status, later studies have also shown a positive correlation between BAT volume and both bone cross-sectional area and bone mineral density, suggesting that BAT might stimulate bone anabolism. The aim of this review is to give the reader a brief overview of the BAT research field and to summarize and discuss recent findings regarding BAT being a potential player in bone metabolism. PMID:27152171

  14. Stevioside ameliorates high-fat diet-induced insulin resistance and adipose tissue inflammation by downregulating the NF-{kappa}B pathway

    SciTech Connect

    Wang, Zhiquan; Xue, Liqiong; Guo, Cuicui; Han, Bing; Pan, Chunming; Zhao, Shuangxia; Song, Huaidong; Ma, Qinyun

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer Stevioside ameliorates high-fat diet-induced insulin resistance. Black-Right-Pointing-Pointer Stevioside alleviates the adipose tissue inflammation. Black-Right-Pointing-Pointer Stevioside reduces macrophages infiltration into the adipose tissue. Black-Right-Pointing-Pointer Stevioside suppresses the activation of NF-{kappa}B in the adipose tissue. -- Abstract: Accumulating evidence suggests that adipose tissue is the main source of pro-inflammatory molecules that predispose individuals to insulin resistance. Stevioside (SVS) is a widely used sweetener with multiple beneficial effects for diabetic patients. In this study, we investigated the effect of SVS on insulin resistance and the pro-inflammatory state of adipose tissue in mice fed with a high-fat diet (HFD). Oral administration of SVS for 1 month had no effect on body weight, but it significantly improved fasting glucose, basal insulin levels, glucose tolerance and whole body insulin sensitivity. Interestingly, these changes were accompanied with decreased expression levels of several inflammatory cytokines in adipose tissue, including TNF-{alpha}, IL6, IL10, IL1{beta}, KC, MIP-1{alpha}, CD11b and CD14. Moreover, macrophage infiltration in adipose tissue was remarkably reduced by SVS. Finally, SVS significantly suppressed the nuclear factor-kappa b (NF-{kappa}B) signaling pathway in adipose tissue. Collectively, these results suggested that SVS may ameliorate insulin resistance in HFD-fed mice by attenuating adipose tissue inflammation and inhibiting the NF-{kappa}B pathway.

  15. Human adipose tissue-derived mesenchymal stem cells differentiate into insulin, somatostatin, and glucagon expressing cells

    SciTech Connect

    Timper, Katharina; Seboek, Dalma; Eberhardt, Michael; Linscheid, Philippe; Christ-Crain, Mirjam; Keller, Ulrich; Mueller, Beat; Zulewski, Henryk . E-mail: henryk.zulewski@unibas.ch

    2006-03-24

    Mesenchymal stem cells (MSC) from mouse bone marrow were shown to adopt a pancreatic endocrine phenotype in vitro and to reverse diabetes in an animal model. MSC from human bone marrow and adipose tissue represent very similar cell populations with comparable phenotypes. Adipose tissue is abundant and easily accessible and could thus also harbor cells with the potential to differentiate in insulin producing cells. We isolated human adipose tissue-derived MSC from four healthy donors. During the proliferation period, the cells expressed the stem cell markers nestin, ABCG2, SCF, Thy-1 as well as the pancreatic endocrine transcription factor Isl-1. The cells were induced to differentiate into a pancreatic endocrine phenotype by defined culture conditions within 3 days. Using quantitative PCR a down-regulation of ABCG2 and up-regulation of pancreatic developmental transcription factors Isl-1, Ipf-1, and Ngn3 were observed together with induction of the islet hormones insulin, glucagon, and somatostatin.

  16. Immunological contributions to adipose tissue homeostasis.

    PubMed

    DiSpirito, Joanna R; Mathis, Diane

    2015-09-01

    Adipose tissue is composed of many functionally and developmentally distinct cell types, the metabolic core of which is the adipocyte. The classification of "adipocyte" encompasses three primary types - white, brown, and beige - with distinct origins, anatomic distributions, and homeostatic functions. The ability of adipocytes to store and release lipids, respond to insulin, and perform their endocrine functions (via secretion of adipokines) is heavily influenced by the immune system. Various cell populations of the innate and adaptive arms of the immune system can resist or exacerbate the development of the chronic, low-grade inflammation associated with obesity and metabolic dysfunction. Here, we discuss these interactions, with a focus on their consequences for adipocyte and adipose tissue function in the setting of chronic overnutrition. In addition, we will review the effects of diet composition on adipose tissue inflammation and recent evidence suggesting that diet-driven disruption of the gut microbiota can trigger pathologic inflammation of adipose tissue.

  17. Interleukin-17A Differentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice

    PubMed Central

    Qu, Yine; Zhang, Qiuyang; Ma, Siqi; Liu, Sen; Chen, Zhiquan; Mo, Zhongfu; You, Zongbing

    2016-01-01

    The functions of interleukin-17A (IL-17A) in adipose tissues and adipocytes have not been well understood. In the present study, male mice were fed with a regular diet (n = 6, lean mice) or a high-fat diet (n = 6, obese mice) for 30 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were analyzed for IL-17A levels. SAT and VAT were treated with IL-17A and analyzed for inflammatory and metabolic gene expression. Mouse 3T3-L1 pre-adipocytes were differentiated into adipocytes, followed with IL-17A treatment and analysis for inflammatory and metabolic gene expression. We found that IL-17A levels were higher in obese SAT than lean SAT; the basal expression of inflammatory and metabolic genes was different between SAT and VAT and between lean and obese adipose tissues. IL-17A differentially induced expression of inflammatory and metabolic genes, such as tumor necrosis factor α, Il-6, Il-1β, leptin, and glucose transporter 4, in adipose tissues of lean and obese mice. IL-17A also differentially induced expression of inflammatory and metabolic genes in pre-adipocytes and adipocytes, and IL-17A selectively activated signaling pathways in adipose tissues and adipocytes. These findings suggest that IL-17A differentially induces inflammatory and metabolic gene expression in the adipose tissues of lean and obese mice. PMID:27070576

  18. Effect of the anatomical site on telomere length and pref-1 gene expression in bovine adipose tissues.

    PubMed

    Yamada, Tomoya; Higuchi, Mikito; Nakanishi, Naoto

    2015-08-01

    Adipose tissue growth is associated with preadipocyte proliferation and differentiation. Telomere length is a biological marker for cell proliferation. Preadipocyte factor-1 (pref-1) is specifically expressed in preadipocytes and acts as a molecular gatekeeper of adipogenesis. In the present study, we investigated the fat depot-specific differences in telomere length and pref-1 gene expression in various anatomical sites (subcutaneous, intramuscular and visceral) of fattening Wagyu cattle. Visceral adipose tissue expressed higher pref-1 mRNA than did subcutaneous and intramuscular adipose tissues. The telomere length in visceral adipose tissue tended to be longer than that of subcutaneous and intramuscular adipose tissues. The telomere length of adipose tissue was not associated with adipocyte size from three anatomical sites. No significant correlation was found between the pref-1 mRNA level and the subcutaneous adipocyte size. In contrast, the pref-1 mRNA level was negatively correlated with the intramuscular and visceral adipocyte size. These results suggest that anatomical sites of adipose tissue affect the telomere length and expression pattern of the pref-1 gene in a fat depot-specific manner.

  19. Overexpression of TNF-α converting enzyme promotes adipose tissue inflammation and fibrosis induced by high fat diet.

    PubMed

    Matsui, Yuki; Tomaru, Utano; Miyoshi, Arina; Ito, Tomoki; Fukaya, Shinji; Miyoshi, Hideaki; Atsumi, Tatsuya; Ishizu, Akihiro

    2014-12-01

    Obesity is a state in which chronic low-grade inflammation persists in adipose tissues. Pro-inflammatory cytokines, including TNF-α, produced by adipose tissues have been implicated as active participants in the development of obesity-related diseases. Since TNF-α converting enzyme (TACE) is the major factor that induces soluble TNF-α, TACE has been noted as a pivotal regulator in this field. To reveal the role of TACE in adipose tissue inflammation, TACE-transgenic (TACE-Tg) and wild type (WT) mice were fed with high fat diet (HFD) or control diet for 16 weeks. At 13 weeks after the beginning of the diet, serum TNF-α and macrophage-related cytokine/chemokine levels were elevated in TACE-Tg mice fed with HFD (Tg-HFD mice), and the number of the so-called crown-like adipocyte was significantly increased in adipose tissues of Tg-HFD mice at the end of the experiment. Although macrophage infiltration was not detected in the adipose tissues at this time, fibrosis was observed around the crown-like adipocytes. These findings suggested that TACE overexpression induced macrophage infiltration and subsequent fibrosis in adipose tissues under HFD regimen. The collective evidence suggested that TACE could be a therapeutic target of HFD-induced obesity-related adipose tissue inflammation.

  20. Interleukin-17A Differentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice.

    PubMed

    Qu, Yine; Zhang, Qiuyang; Ma, Siqi; Liu, Sen; Chen, Zhiquan; Mo, Zhongfu; You, Zongbing

    2016-04-07

    The functions of interleukin-17A (IL-17A) in adipose tissues and adipocytes have not been well understood. In the present study, male mice were fed with a regular diet (n = 6, lean mice) or a high-fat diet (n = 6, obese mice) for 30 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were analyzed for IL-17A levels. SAT and VAT were treated with IL-17A and analyzed for inflammatory and metabolic gene expression. Mouse 3T3-L1 pre-adipocytes were differentiated into adipocytes, followed with IL-17A treatment and analysis for inflammatory and metabolic gene expression. We found that IL-17A levels were higher in obese SAT than lean SAT; the basal expression of inflammatory and metabolic genes was different between SAT and VAT and between lean and obese adipose tissues. IL-17A differentially induced expression of inflammatory and metabolic genes, such as tumor necrosis factor α, Il-6, Il-1β, leptin, and glucose transporter 4, in adipose tissues of lean and obese mice. IL-17A also differentially induced expression of inflammatory and metabolic genes in pre-adipocytes and adipocytes, and IL-17A selectively activated signaling pathways in adipose tissues and adipocytes. These findings suggest that IL-17A differentially induces inflammatory and metabolic gene expression in the adipose tissues of lean and obese mice.

  1. Gene expression profiles reveal effect of a high-fat diet on the development of white and brown adipose tissues.

    PubMed

    Kim, Hyeng-Soo; Ryoo, Zae Young; Choi, Sang Un; Lee, Sanggyu

    2015-07-01

    Because of the recent discovery of brown adipose tissues tissue in adult humans, brown adipose tissues have garnered additional attention. Many studies have attempted to transform the precursor cells within the white adipocyte cultures to Brite (brown-in-white) cells by using genomic modification or pharmacological activation in order to determine the therapeutic effect of obesity. However, genome-scale analysis of the genetic factors governing the development of white and brown adipose tissues remains incomplete. In order to identify the key genes that regulate the development of white and brown adipose tissues in mice, a transcriptome analysis was performed on the adipose tissues. Network analysis of differentially expressed genes indicated that Trim30 and Ucp3 play pivotal roles in energy balance and glucose homeostasis. In addition, it was discovered that identical biological processes and pathways in the white and brown adipose tissues might be regulated by different genes. Trim30 and Ucp3 might be used as genetic markers to precisely represent the stage of obesity during the early and late stages of adipose tissue development, respectively. These results may provide a stepping-stone for future obesity-related studies.

  2. Interleukin-17A Differentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice.

    PubMed

    Qu, Yine; Zhang, Qiuyang; Ma, Siqi; Liu, Sen; Chen, Zhiquan; Mo, Zhongfu; You, Zongbing

    2016-01-01

    The functions of interleukin-17A (IL-17A) in adipose tissues and adipocytes have not been well understood. In the present study, male mice were fed with a regular diet (n = 6, lean mice) or a high-fat diet (n = 6, obese mice) for 30 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were analyzed for IL-17A levels. SAT and VAT were treated with IL-17A and analyzed for inflammatory and metabolic gene expression. Mouse 3T3-L1 pre-adipocytes were differentiated into adipocytes, followed with IL-17A treatment and analysis for inflammatory and metabolic gene expression. We found that IL-17A levels were higher in obese SAT than lean SAT; the basal expression of inflammatory and metabolic genes was different between SAT and VAT and between lean and obese adipose tissues. IL-17A differentially induced expression of inflammatory and metabolic genes, such as tumor necrosis factor α, Il-6, Il-1β, leptin, and glucose transporter 4, in adipose tissues of lean and obese mice. IL-17A also differentially induced expression of inflammatory and metabolic genes in pre-adipocytes and adipocytes, and IL-17A selectively activated signaling pathways in adipose tissues and adipocytes. These findings suggest that IL-17A differentially induces inflammatory and metabolic gene expression in the adipose tissues of lean and obese mice. PMID:27070576

  3. New concepts in white adipose tissue physiology.

    PubMed

    Proença, A R G; Sertié, R A L; Oliveira, A C; Campaña, A B; Caminhotto, R O; Chimin, P; Lima, F B

    2014-02-01

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

  4. Perivascular adipose tissue-secreted angiopoietin-like protein 2 (Angptl2) accelerates neointimal hyperplasia after endovascular injury.

    PubMed

    Tian, Zhe; Miyata, Keishi; Tazume, Hirokazu; Sakaguchi, Hisashi; Kadomatsu, Tsuyoshi; Horio, Eiji; Takahashi, Otowa; Komohara, Yoshihiro; Araki, Kimi; Hirata, Yoichiro; Tabata, Minoru; Takanashi, Shuichiro; Takeya, Motohiro; Hao, Hiroyuki; Shimabukuro, Michio; Sata, Masataka; Kawasuji, Michio; Oike, Yuichi

    2013-04-01

    Much attention is currently focused on the role of perivascular adipose tissue in development of cardiovascular disease (CVD). Some researchers view it as promoting CVD through secretion of cytokines and growth factors called adipokines, while recent reports reveal that perivascular adipose tissue can exert a protective effect on CVD development. Furthermore, adiponectin, an anti-inflammatory adipokine, reportedly suppresses neointimal hyperplasia after endovascular injury, whereas such vascular remodeling is enhanced by pro-inflammatory adipokines secreted by perivascular adipose, such as tumor necrosis factor-α (TNF-α). These findings suggest that extent of vascular remodeling, a pathological process associated with CVD development, depends on the balance between pro- and anti-inflammatory adipokines secreted from perivascular adipose tissue. We previously demonstrated that angiopoietin-like protein 2 (Angptl2), a pro-inflammatory factor secreted by adipose tissue, promotes adipose tissue inflammation and subsequent systemic insulin resistance in obesity. Here, we examined whether Angptl2 secreted by perivascular adipose tissue contributes to vascular remodeling after endovascular injury in studies of transgenic mice expressing Angptl2 in adipose tissue (aP2-Angptl2 transgenic mice) and Angptl2 knockout mice (Angptl2(-/-) mice). To assess the role of Angptl2 secreted by perivascular adipose tissue on vascular remodeling after endovascular injury, we performed adipose tissue transplantation experiments using these mice. Wild-type mice with perivascular adipose tissue derived from aP2-Angptl2 mice exhibited accelerated neointimal hyperplasia after endovascular injury compared to wild-type mice transplanted with wild-type tissue. Conversely, vascular inflammation and neointimal hyperplasia after endovascular injury were significantly attenuated in wild-type mice transplanted with Angptl2(-/-) mouse-derived perivascular adipose tissue compared to wild-type mice

  5. The Effect of Age on Osteogenic and Adipogenic Differentiation Potential of Human Adipose Derived Stromal Stem Cells (hASCs) and the Impact of Stress Factors in the Course of the Differentiation Process.

    PubMed

    Kornicka, Katarzyna; Marycz, Krzysztof; Tomaszewski, Krzysztof Andrzej; Marędziak, Monika; Śmieszek, Agnieszka

    2015-01-01

    Human adipose tissue is a great source of autologous mesenchymal stem cells (hASCs), which are recognized for their vast therapeutic applications. Their ability to self-renew and differentiate into several lineages makes them a promising tool for cell-based therapies in different types of degenerative diseases. Thus it is crucial to evaluate age-related changes in hASCs, as the elderly are a group that will benefit most from their considerable potential. In this study we investigated the effect of donor age on growth kinetics, cellular senescence marker levels, and osteogenic and adipogenic potential of hASCs. It also has been known that, during life, organisms accumulate oxidative damage that negatively affects cell metabolism. Taking this into consideration, we evaluated the levels of nitric oxide, reactive oxygen species, and superoxide dismutase activity. We observed that ROS and NO increase with aging, while SOD activity is significantly reduced. Moreover cells obtained from older patients displayed senescence associated features, for example, β-galactosidase activity, enlarged morphology, and p53 protein upregulation. All of those characteristics seem to contribute to decreased proliferation potential of those cells. Our results suggest that due to aging some cellular modification may be required before applying aged cells efficiently in therapies such as tissue engineering and regenerative medicine. PMID:26246868

  6. Plerocercoid growth factor (PGF), a human growth hormone (hGH) analogue produced by the tapeworm Spirometra mansonoides, has direct insulin-like action in adipose tissue of normal rats in vitro

    SciTech Connect

    Salem, M.A.M.; Phares, C.K.

    1986-03-01

    The metabolic actions of GH can be divided into acute (insulin-like) and chronic (lipolytic/anti-insulin). The insulin-like actions of GH are most readily elicited in GH-deficient animals as GH induces resistance to its own insulin-like action. Like GH, PGF stimulates growth and cross-reacts with anti-hGH antibodies. Independent experiments were conducted comparing the direct actions of PGF to insulin or hGH in vitro. Insulin-like effects were determined by the ability of PGF, insulin or hGH to stimulate (U-/sup 14/C)glucose metabolism in epidydimal fat pads from normal rats and by inhibition of epinephrine-stimulated lipolysis. Direct stimulation of lipolysis was used as anti-insulin activity. To determine if PGF competes for insulin or GH receptors, adipocytes (3 x 10/sup 5/ cells/ml) were incubated with either (/sup 125/I)insulin or (/sup 125/I)hGH +/- PGF, +/- insulin or +/- hGH. PGF stimulated glucose oxidation and /sup 14/C-incorporation into lipids. Insulin, hGH and PGF inhibited lipolysis (33%, 29% and 34%, respectively). Adipose tissue was very sensitive to the lipolytic effect of hGH but PGF was neither lipolytic nor did it confer refractoriness to its insulin-like action. PGF bound to GH but not to insulin receptors. Therefore, PGF had direct insulin-like effects but did not stimulate lipolysis in tissue from normal rats in vitro.

  7. Brown adipose tissue and its therapeutic potential.

    PubMed

    Lidell, M E; Betz, M J; Enerbäck, S

    2014-10-01

    Obesity and related diseases are a major cause of human morbidity and mortality and constitute a substantial economic burden for society. Effective treatment regimens are scarce, and new therapeutic targets are needed. Brown adipose tissue, an energy-expending tissue that produces heat, represents a potential therapeutic target. Its presence is associated with low body mass index, low total adipose tissue content and a lower risk of type 2 diabetes mellitus. Knowledge about the development and function of thermogenic adipocytes in brown adipose tissue has increased substantially in the last decade. Important transcriptional regulators have been identified, and hormones able to modulate the thermogenic capacity of the tissue have been recognized. Intriguingly, it is now clear that humans, like rodents, possess two types of thermogenic adipocytes: the classical brown adipocytes found in the interscapular brown adipose organ and the so-called beige adipocytes primarily found in subcutaneous white adipose tissue after adrenergic stimulation. The presence of two distinct types of energy-expending adipocytes in humans is conceptually important because these cells might be stimulated and recruited by different signals, raising the possibility that they might be separate potential targets for therapeutic intervention. In this review, we will discuss important features of the energy-expending brown adipose tissue and highlight those that may serve as potential targets for pharmacological intervention aimed at expanding the tissue and/or enhancing its function to counteract obesity.

  8. Adipose Clocks: Burning the Midnight Oil.

    PubMed

    Henriksson, Emma; Lamia, Katja A

    2015-10-01

    Circadian clocks optimize the timing of physiological processes in synchrony with daily recurring and therefore predictable changes in the environment. Until the late 1990s, circadian clocks were thought to exist only in the central nervous systems of animals; elegant studies in cultured fibroblasts and using genetically encoded reporters in Drosophila melanogaster and in mice showed that clocks are ubiquitous and cell autonomous. These findings inspired investigations of the advantages construed by enabling each organ to independently adjust its function to the time of day. Studies of rhythmic gene expression in several organs suggested that peripheral organ clocks might play an important role in optimizing metabolic physiology by synchronizing tissue-intrinsic metabolic processes to cycles of nutrient availability and energy requirements. The effects of clock disruption in liver, pancreas, muscle, and adipose tissues support that hypothesis. Adipose tissues coordinate energy storage and utilization and modulate behavior and the physiology of other organs by secreting hormones known as "adipokines." Due to behavior- and environment-driven diurnal variations in supply and demand for chemical and thermal energy, adipose tissues might represent an important peripheral location for coordinating circadian energy balance (intake, storage, and utilization) over the whole organism. Given the complexity of adipose cell types and depots, the sensitivity of adipose tissue biology to age and diet composition, and the plethora of known and yet-to-be-discovered adipokines and lipokines, we have just begun to scratch the surface of understanding the role of circadian clocks in adipose tissues.

  9. Physical inactivity, excess adiposity and premature mortality.

    PubMed

    Katzmarzyk, P T; Janssen, I; Ardern, C I

    2003-11-01

    The purpose of this report is to review the evidence that physical inactivity and excess adiposity are related to an increased risk of all-cause mortality, and to better identify the independent contributions of each to all-cause mortality rates. A variance-based method of meta-analysis was used to summarize the relationships from available studies. The summary relative risk of all-cause mortality for physical activity from the 55 analyses (31 studies) that included an index of adiposity as a covariate was 0.80 [95% confidence interval (CI) 0.78-0.821, whereas it was 0.82 [95% CI 0.80-0.84] for the 44 analyses (26 studies) that did not include an index of adiposity. Thus, physically active individuals have a lower risk of mortality by comparison to physically inactive peers, independent of level of adiposity. The summary relative risk of all-cause mortality for an elevated body mass index (BMI) from the 25 analyses (13 studies) that included physical activity as a covariate was 1.23 [95% CI 1.18-1.29], and it was 1.24 [95% CI 1.21-1.28] for the 81 analyses (36 studies) that did not include physical activity as a covariate. Studies that used a measure of adiposity other than the BMI show similar relationships with mortality, and stratified analyses indicate that both physical inactivity and adiposity are important determinants of mortality risk.

  10. Cold-Induced Changes in Gene Expression in Brown Adipose Tissue, White Adipose Tissue and Liver

    PubMed Central

    Shore, Andrew M.; Karamitri, Angeliki; Kemp, Paul; Speakman, John R.; Graham, Neil S.; Lomax, Michael A.

    2013-01-01

    Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT), white adipose (WAT) and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05) up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver). Gene ontology analysis revealed for the first time significant (P<0.05) down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production. PMID:23894377

  11. Normal weight adiposity in a Swedish population: how well is cardiovascular risk associated with excess body fat captured by BMI?

    PubMed Central

    Strandhagen, Elisabeth; Mehlig, Kirsten; Subramoney, Sreevidya; Lissner, Lauren; Björck, Lena

    2015-01-01

    Summary Objective The aim of this study was to examine how well body mass index (BMI) reflects cardiovascular risk associated with excess adiposity in a Swedish population by examining the association between body fat, BMI and cardiovascular risk factors. Methods A total of 3,010 adults participated. Normal weight adiposity was defined as the combination of BMI < 25 kg/m2 and percentage body fat ≥35% for women and ≥25% for men. Associations with blood pressure, blood lipids, apolipoproteins and C‐reactive protein were analysed in age‐adjusted regression models. Results The majority of the individuals with overweight and obesity were correctly classified to adiposity, while a wide range of body fat was observed among the normal weight subjects. In total, 9% of the participants were categorised as normal weight with adiposity. Compared with the normal weight leanness group, participants with normal weight adiposity had higher levels of serum triglycerides, low‐density lipoprotein cholesterol, C‐reactive protein, apolipoptotein B and the apolipoprotein B/A‐I ratio. In normal weight men, adiposity was also associated with higher blood pressure and lower high‐density lipoprotein cholesterol. Conclusions Higher percentage of body fat was associated with less favourable risk factor profile even in subjects who were normal weight. Thus, it might be relevant to screen for metabolic risk factors in the upper end of the normal weight category.

  12. Associations of overall and abdominal adiposity with area and volumetric mammographic measures among postmenopausal women.

    PubMed

    Woolcott, Christy G; Cook, Linda S; Courneya, Kerry S; Boyd, Norman F; Yaffe, Martin J; Terry, Tim; Brant, Rollin; McTiernan, Anne; Bryant, Heather E; Magliocco, Anthony M; Friedenreich, Christine M

    2011-07-15

    Whereas mammographic density and adiposity are positively associated with postmenopausal breast cancer risk, they are inversely associated with one another. To examine the association between these two risk factors, a secondary analysis of data from a randomized controlled trial of a year-long aerobic exercise intervention was done. Participants were 302 postmenopausal women aged 50-74 years. Dense fibroglandular and nondense fatty tissue were measured from mammograms using computer-assisted thresholding software for area measurements and a technique relying on the calibration of mammography machines with a tissue-equivalent phantom for volumetric measurements. Adiposity was measured by anthropometry (body mass index, waist circumference), whole-body dual x-ray absorptiometry scans (body fat) and computed tomography scans (abdominal adiposity). Correlations were estimated between and within women, the latter representing the association between the 1-year change in adiposity and mammographic measures. Adiposity was correlated with nondense area and volume (0.50 ≤ r ≤ 0.66 between women; 0.18 ≤ r ≤ 0.46 within women). Between women, adiposity was correlated with dense area and volume (-0.12 ≤ r ≤ -0.30) and with percent dense area and volume (-0.28 ≤ r ≤ -0.48). Because measurements made with scans explained at most only 3% more of the variation in absolute or percent density beyond that explained by anthropometric measurements, anthropometric measurements are likely sufficient for adjustment of the association between mammographic density and breast cancer risk. Adiposity is associated with breast fatty tissue and possibly weakly inversely associated with fibroglandular tissue. PMID:20848591

  13. Effects of Sit Up Exercise Training on Adipose Cell Size and Adiposity.

    ERIC Educational Resources Information Center

    Katch, Frank I.; And Others

    1984-01-01

    This article reports on an experiment that evaluated the effects of a 27-day sit up exercise training program on adipose cell size and adiposity. Fat biopsies were taken by needle aspiration from male subjects before and after a progressive training regimen. Results are discussed. (Author/DF)

  14. Intravenous transplants of human adipose-derived stem cell protect the brain from traumatic brain injury-induced neurodegeneration and motor and cognitive impairments: cell graft biodistribution and soluble factors in young and aged rats.

    PubMed

    Tajiri, Naoki; Acosta, Sandra A; Shahaduzzaman, Md; Ishikawa, Hiroto; Shinozuka, Kazutaka; Pabon, Mibel; Hernandez-Ontiveros, Diana; Kim, Dae Won; Metcalf, Christopher; Staples, Meaghan; Dailey, Travis; Vasconcellos, Julie; Franyuti, Giorgio; Gould, Lisa; Patel, Niketa; Cooper, Denise; Kaneko, Yuji; Borlongan, Cesar V; Bickford, Paula C

    2014-01-01

    Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 10(6) hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1' dioactadecyl-3-3-3',3'-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen.

  15. Intravenous Transplants of Human Adipose-Derived Stem Cell Protect the Brain from Traumatic Brain Injury-Induced Neurodegeneration and Motor and Cognitive Impairments: Cell Graft Biodistribution and Soluble Factors in Young and Aged Rats

    PubMed Central

    Tajiri, Naoki; Acosta, Sandra A.; Shahaduzzaman, Md; Ishikawa, Hiroto; Shinozuka, Kazutaka; Pabon, Mibel; Hernandez-Ontiveros, Diana; Kim, Dae Won; Metcalf, Christopher; Staples, Meaghan; Dailey, Travis; Vasconcellos, Julie; Franyuti, Giorgio; Gould, Lisa; Patel, Niketa

    2014-01-01

    Traumatic brain injury (TBI) survivors exhibit motor and cognitive symptoms from the primary injury that can become aggravated over time because of secondary cell death. In the present in vivo study, we examined the beneficial effects of human adipose-derived stem cells (hADSCs) in a controlled cortical impact model of mild TBI using young (6 months) and aged (20 months) F344 rats. Animals were transplanted intravenously with 4 × 106 hADSCs (Tx), conditioned media (CM), or vehicle (unconditioned media) at 3 h after TBI. Significant amelioration of motor and cognitive functions was revealed in young, but not aged, Tx and CM groups. Fluorescent imaging in vivo and ex vivo revealed 1,1′ dioactadecyl-3-3-3′,3′-tetramethylindotricarbocyanine iodide-labeled hADSCs in peripheral organs and brain after TBI. Spatiotemporal deposition of hADSCs differed between young and aged rats, most notably reduced migration to the aged spleen. Significant reduction in cortical damage and hippocampal cell loss was observed in both Tx and CM groups in young rats, whereas less neuroprotection was detected in the aged rats and mainly in the Tx group but not the CM group. CM harvested from hADSCs with silencing of either NEAT1 (nuclear enriched abundant transcript 1) or MALAT1 (metastasis associated lung adenocarcinoma transcript 1), long noncoding RNAs (lncRNAs) known to play a role in gene expression, lost the efficacy in our model. Altogether, hADSCs are promising therapeutic cells for TBI, and lncRNAs in the secretome is an important mechanism of cell therapy. Furthermore, hADSCs showed reduced efficacy in aged rats, which may in part result from decreased homing of the cells to the spleen. PMID:24381292

  16. The role of JAK-STAT signaling in adipose tissue function.

    PubMed

    Richard, Allison J; Stephens, Jacqueline M

    2014-03-01

    Adipocytes play important roles in lipid storage, energy homeostasis and whole body insulin sensitivity. The JAK-STAT (Janus Kinase-Signal Transducer and Activator of Transcription) pathway mediates a variety of physiological processes including development, hematopoiesis, and inflammation. Although the JAK-STAT signaling pathway occurs in all cells, this pathway can mediate cell specific responses. Studies in the last two decades have identified hormones and cytokines that activate the JAK-STAT signaling pathway. These cytokines and hormones have profound effects on adipocytes. The content of this review will introduce the types of adipocytes and immune cells that make up adipose tissue, the impact of obesity on adipose cellular composition and function, and the general constituents of the JAK-STAT pathway and how its activators regulate adipose tissue development and physiology. A summary of the identification of STAT target genes in adipocytes reveals how these transcription factors impact various areas of adipocyte metabolism including insulin action, modulation of lipid stores, and glucose homeostasis. Lastly, we will evaluate exciting new data linking the JAK-STAT pathway and brown adipose tissue and consider the future outlook in this area of investigation. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  17. Nutrition-/diet-induced changes in gene expression in white adipose tissue.

    PubMed

    Al-Hasani, Hadi; Joost, Hans-Georg

    2005-12-01

    Nutrients regulate metabolic fluxes and homeostasis through transcriptional and translational control of enzyme concentrations and allosteric modulation of enzyme activity. Dietary omega-3 polyunsaturated fatty acids (PUFAs) have been shown to exert a variety of beneficial health effects such as reducing adiposity and increasing insulin sensitivity in rodents. It is now clear that PUFAs regulate fundamental adipose cell and liver functions through modulation of activity and abundance of key transcription factors that act as nutrient sensors, including peroxisome proliferator-activated receptors (PPARalpha/delta/gamma), sterol regulatory element binding proteins (SREBP-1/2), and liver X receptors (LXRalpha/beta). However, in the state of obesity, where adipose tissue shows elevated storage of triglycerides, many lipogenic genes that are essential for adipose cell function including PPARgamma, SREBP-1c, CCAAT-enhancer binding protein alpha and stearoyl-CoA desaturase-1 are downregulated, apparently due to desensitization of the very same crucial nutrient sensors. This chapter will summarize recent studies of PUFA- and obesity-induced changes in gene expression in white adipose tissue.

  18. The Circulatory and Metabolic Responses to Hypoxia in Humans – With Special Reference to Adipose Tissue Physiology and Obesity

    PubMed Central

    Heinonen, Ilkka H. A.; Boushel, Robert; Kalliokoski, Kari K.

    2016-01-01

    Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology.

  19. The Circulatory and Metabolic Responses to Hypoxia in Humans - With Special Reference to Adipose Tissue Physiology and Obesity.

    PubMed

    Heinonen, Ilkka H A; Boushel, Robert; Kalliokoski, Kari K

    2016-01-01

    Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology. PMID:27621722

  20. The Circulatory and Metabolic Responses to Hypoxia in Humans – With Special Reference to Adipose Tissue Physiology and Obesity

    PubMed Central

    Heinonen, Ilkka H. A.; Boushel, Robert; Kalliokoski, Kari K.

    2016-01-01

    Adipose tissue metabolism and circulation play an important role in human health. It is well-known that adipose tissue mass is increased in response to excess caloric intake leading to obesity and further to local hypoxia and inflammatory signaling. Acute exercise increases blood supply to adipose tissue and mobilization of fat stores for energy. However, acute exercise during systemic hypoxia reduces subcutaneous blood flow in healthy young subjects, but the response in overweight or obese subjects remains to be investigated. Emerging evidence also indicates that exercise training during hypoxic exposure may provide additive benefits with respect to many traditional cardiovascular risk factors as compared to exercise performed in normoxia, but unfavorable effects of hypoxia have also been documented. These topics will be covered in this brief review dealing with hypoxia and adipose tissue physiology. PMID:27621722

  1. Increased adiposity induced by high dietary butter oil increases vertebrae trabecular structural indices in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Obesity has been associated with both improved and impaired bone health, and other dietary factors apparently affect the nature of the association. An experiment was performed to determine whether increased adiposity induced by high dietary butter oil impairs bone structure and whether that effect ...

  2. Gooey Stuff, Intra-Activity, and Differential Obesities: Foregrounding Agential Adiposity within Childhood Obesity Stories

    ERIC Educational Resources Information Center

    Land, Nicole

    2015-01-01

    In Canada, forces such as the media, medical discourse, and public policy work to position childhood obesity as increased body fat content or excess adiposity due to various personal, social, and economic factors. Drawing on Barad's "agential realist ontology", this article aims to inhabit-with obesity in an effort to disrupt dominant…

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

    PubMed Central

    Izumida, Yoshihiko; Yahagi, Naoya; Takeuchi, Yoshinori; Nishi, Makiko; Shikama, Akito; Takarada, Ayako; Masuda, Yukari; Kubota, Midori; Matsuzaka, Takashi; Nakagawa, Yoshimi; Iizuka, Yoko; Itaka, Keiji; Kataoka, Kazunori; Shioda, Seiji; Niijima, Akira; Yamada, Tetsuya; Katagiri, Hideki; Nagai, Ryozo; Yamada, Nobuhiro; Kadowaki, Takashi; Shimano, Hitoshi

    2013-01-01

    During fasting, animals maintain their energy balance by shifting their energy source from carbohydrates to triglycerides. However, the trigger for this switch has not yet been entirely elucidated. Here we show that a selective hepatic vagotomy slows the speed of fat consumption by attenuating sympathetic nerve-mediated lipolysis in adipose tissue. Hepatic glycogen pre-loading by the adenoviral overexpression of glycogen synthase or the transcription factor TFE3 abolished this liver–brain–adipose axis activation. Moreover, the blockade of glycolysis through the knockdown of the glycogen phosphorylase gene and the resulting elevation in the glycogen content abolished the lipolytic signal from the liver, indicating that glycogen is the key to triggering this neurocircuitry. These results demonstrate that liver glycogen shortage activates a liver–brain–adipose neural axis that has an important role in switching the fuel source from glycogen to triglycerides under prolonged fasting conditions. PMID:23939267

  4. Fat body, fat pad and adipose tissues in invertebrates and vertebrates: the nexus

    PubMed Central

    2014-01-01

    The fat body in invertebrates was shown to participate in energy storage and homeostasis, apart from its other roles in immune mediation and protein synthesis to mention a few. Thus, sharing similar characteristics with the liver and adipose tissues in vertebrates. However, vertebrate adipose tissue or fat has been incriminated in the pathophysiology of metabolic disorders due to its role in production of pro-inflammatory cytokines. This has not been reported in the insect fat body. The link between the fat body and adipose tissue was examined in this review with the aim of determining the principal factors responsible for resistance to inflammation in the insect fat body. This could be the missing link in the prevention of metabolic disorders in vertebrates, occasioned by obesity. PMID:24758278

  5. Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression.

    PubMed

    Gucalp, Ayca; Iyengar, Neil M; Hudis, Clifford A; Dannenberg, Andrew J

    2016-02-01

    The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies.

  6. The impact of adiposity on adipose tissue-resident lymphocyte activation in humans

    PubMed Central

    Travers, R L; Motta, A C; Betts, J A; Bouloumié, A; Thompson, D

    2015-01-01

    Background/objectives: The presence of T lymphocytes in human adipose tissue has only recently been demonstrated and relatively little is known of their potential relevance in the development of obesity-related diseases. We aimed to further characterise these cells and in particular to investigate how they interact with modestly increased levels of adiposity typical of common overweight and obesity. Subjects/methods: Subcutaneous adipose tissue and fasting blood samples were obtained from healthy males aged 35–55 years with waist circumferences in lean (<94 cm), overweight (94–102 cm) and obese (>102 cm) categories. Adipose tissue-resident CD4+ and CD8+ T lymphocytes together with macrophages were identified by gene expression and flow cytometry. T lymphocytes were further characterised by their expression of activation markers CD25 and CD69. Adipose tissue inflammation was investigated using gene expression analysis and tissue culture. Results: Participants reflected a range of adiposity from lean to class I obesity. Expression of CD4 (T-helper cells) and CD68 (macrophage), as well as FOXP3 RNA transcripts, was elevated in subcutaneous adipose tissue with increased levels of adiposity (P<0.001, P<0.001 and P=0.018, respectively). Flow cytometry revealed significant correlations between waist circumference and levels of CD25 and CD69 expression per cell on activated adipose tissue-resident CD4+ and CD8+ T lymphocytes (P-values ranging from 0.053 to <0.001). No such relationships were found with blood T lymphocytes. This increased T lymphocyte activation was related to increased expression and secretion of various pro- and anti-inflammatory cytokines from subcutaneous whole adipose tissue explants. Conclusions: This is the first study to demonstrate that even modest levels of overweight/obesity elicit modifications in adipose tissue immune function. Our results underscore the importance of T lymphocytes during adipose tissue expansion, and the presence of

  7. Developmental regulation of adipose tissue growth through hyperplasia and hypertrophy in the embryonic Leghorn and broiler.

    PubMed

    Chen, Paula; Suh, Yeunsu; Choi, Young Min; Shin, Sangsu; Lee, Kichoon

    2014-07-01

    The United States is a world leader in poultry production, which is the reason why achieving better performance and muscle growth each year is a necessity. Reducing accretion of adipose tissue is another important factor for poultry producers because this allows more nutrients to be directed toward muscle growth, but the effect of embryonic adipose growth on posthatch development has not been fully understood. The purpose of this study was to investigate the total DNA mass, morphological characteristics, differentiation markers, and triglyceride breakdown factors of embryonic adipose tissue, and their relation to hyperplastic and hypertrophic growth within layers (Leghorn) and meat-type chickens (broilers). After embryonic day (E) 12, broiler weight was significantly higher than Leghorn, and this trend continued throughout the rest of incubation and posthatch (P < 0.05). Neck and leg fat pad weights between the 2 breeds did not differ at most of the time points. A remarkable increase in total DNA mass was observed between E12 and E14 in both Leghorn and broilers (P < 0.05), indicating a high potential for hyperplastic growth during this time. Histological analysis revealed clusters of preadipocytes at E12; however, the majority of these cells differentiated by E14 and continued to grow until the time of hatch. The adipocyte sizes between both breeds did not generally differ, even though broilers are known to have larger adipocytes posthatch. Fatty acid-binding protein 4 expression levels in Leghorn and broilers continued to rise with each time point, which paralleled the expansion of mature adipocytes. Adipose triglyceride lipase was highly expressed at E20 and d 1 posthatch to mobilize triglyceride degradation for energy during hatching. Thus, embryonic chicken adipose tissue was found to develop by hyperplastic mechanisms followed by hypertrophy. At embryonic stages and early posthatch, layer- and meat-type chicken adipose growth does not differ, which suggests

  8. Studies on Lipolysis in Human Adipose Cells *

    PubMed Central

    Galton, David J.; Bray, George A.

    1967-01-01

    Epinephrine stimulated lipolysis and the uptake of oxygen by subcutaneous adipose cells of man. When glucose-14C was present in the medium, its utilization was not increased by epinephrine, although lipolysis was accelerated. Insulin did not reduce the production of fatty acids that had been stimulated by epinephrine. The combination of human growth hormone and cortisol stimulated the production of fatty acids by isolated human adipose cells to a lesser extent than epinephrine. When human growth hormone or cortisol was used singly, or when bovine growth hormone was added in combination with cortisol, no effect on fatty acid production was observed. Furthermore, an acetone-dried preparation of human pituitary glands, which was shown to stimulate lipolysis in rat adipose cells, had no effect on fatty acid formation in human adipose cells. This suggested that the human pituitary gland contained no more potent lipolytic agents than growth hormone and was supported by the lack of response of human adipose cells to purified corticotropin. PMID:6021210

  9. Carotenoids in Adipose Tissue Biology and Obesity.

    PubMed

    Bonet, M Luisa; Canas, Jose A; Ribot, Joan; Palou, Andreu

    2016-01-01

    Cell, animal and human studies dealing with carotenoids and carotenoid derivatives as nutritional regulators of adipose tissue biology with implications for the etiology and management of obesity and obesity-related metabolic diseases are reviewed. Most studied carotenoids in this context are β-carotene, cryptoxanthin, astaxanthin and fucoxanthin, together with β-carotene-derived retinoids and some other apocarotenoids. Studies indicate an impact of these compounds on essential aspects of adipose tissue biology including the control of adipocyte differentiation (adipogenesis), adipocyte metabolism, oxidative stress and the production of adipose tissue-derived regulatory signals and inflammatory mediators. Specific carotenoids and carotenoid derivatives restrain adipogenesis and adipocyte hypertrophy while enhancing fat oxidation and energy dissipation in brown and white adipocytes, and counteract obesity in animal models. Intake, blood levels and adipocyte content of carotenoids are reduced in human obesity. Specifically designed human intervention studies in the field, though still sparse, indicate a beneficial effect of carotenoid supplementation in the accrual of abdominal adiposity. In summary, studies support a role of specific carotenoids and carotenoid derivatives in the prevention of excess adiposity, and suggest that carotenoid requirements may be dependent on body composition. PMID:27485231

  10. Contributions of maternal and paternal adiposity and smoking to adult offspring adiposity and cardiovascular risk: the Midspan Family Study

    PubMed Central

    Han, T S; Hart, C L; Haig, C; Logue, J; Upton, M N; Watt, G C M; Lean, M E J

    2015-01-01

    Objective Obesity has some genetic basis but requires interaction with environmental factors for phenotypic expression. We examined contributions of gender-specific parental adiposity and smoking to adiposity and related cardiovascular risk in adult offspring. Design Cross-sectional general population survey. Setting Scotland. Participants 1456 of the 1477 first generation families in the Midspan Family Study: 2912 parents (aged 45–64 years surveyed between 1972 and 1976) who had 1025 sons and 1283 daughters, aged 30–59 years surveyed in 1996. Main measures Offspring body mass index (BMI), waist circumference (WC), cardiometabolic risk (lipids, blood pressure and glucose) and cardiovascular disease as outcome measures, and parental BMI and smoking as determinants. All analyses adjusted for age, socioeconomic status and family clustering and offspring birth weight. Results Regression coefficients for BMI associations between father–son (0.30) and mother–daughter (0.33) were greater than father–daughter (0.23) or mother–son (0.22). Regression coefficient for the non-genetic, shared-environment or assortative-mating relationship between BMIs of fathers and mothers was 0.19. Heritability estimates for BMI were greatest among women with mothers who had BMI either <25 or ≥30 kg/m2. Compared with offspring without obese parents, offspring with two obese parents had adjusted OR of 10.25 (95% CI 6.56 to 13.93) for having WC ≥102 cm for men, ≥88 cm women, 2.46 (95% CI 1.33 to 4.57) for metabolic syndrome and 3.03 (95% CI 1.55 to 5.91) for angina and/or myocardial infarct (p<0.001). Neither parental adiposity nor smoking history determined adjusted offspring individual cardiometabolic risk factors, diabetes or stroke. Maternal, but not paternal, smoking had significant effects on WC in sons (OR=1.50; 95% CI 1.13 to 2.01) and daughters (OR=1.42; 95% CI 1.10 to 1.84) and metabolic syndrome OR=1.68; 95% CI 1.17 to 2.40) in sons. Conclusions There are

  11. Proline oxidase–adipose triglyceride lipase pathway restrains adipose cell death and tissue inflammation

    PubMed Central

    Lettieri Barbato, D; Aquilano, K; Baldelli, S; Cannata, S M; Bernardini, S; Rotilio, G; Ciriolo, M R

    2014-01-01

    The nutrient-sensing lipolytic enzyme adipose triglyceride lipase (ATGL) has a key role in adipose tissue function, and alterations in its activity have been implicated in many age-related metabolic disorders. In adipose tissue reduced blood vessel density is related to hypoxia state, cell death and inflammation. Here we demonstrate that adipocytes of poorly vascularized enlarged visceral adipose tissue (i.e. adipose tissue of old mice) suffer from limited nutrient delivery. In particular, nutrient starvation elicits increased activity of mitochondrial proline oxidase/dehydrogenase (POX/PRODH) that is causal in triggering a ROS-dependent induction of ATGL. We demonstrate that ATGL promotes the expression of genes related to mitochondrial oxidative metabolism (peroxisome proliferator-activated receptor-α, peroxisome proliferator-activated receptor-γ coactivator-1α), thus setting a metabolic switch towards fat utilization that supplies energy to starved adipocytes and prevents cell death, as well as adipose tissue inflammation. Taken together, these results identify ATGL as a stress resistance mediator in adipocytes, restraining visceral adipose tissue dysfunction typical of age-related metabolic disorders. PMID:24096872

  12. Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues.

    PubMed

    Chen, Yu-Jen; Liu, Hui-Yu; Chang, Yun-Tsui; Cheng, Ying-Hung; Mersmann, Harry J; Kuo, Wen-Hung; Ding, Shih-Torng

    2016-03-31

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. The dorsal white fat depot of porcine subcutaneous adipose tissues is sliced, minced and collagenase digested. These pADSC exhibit strong potential to differentiate into adipocytes. Moreover, the pADSC also possess multipotency, assessed by selective stem cell markers, to differentiate into various mesenchymal cell types including adipocytes, osteocytes, and chondrocytes. These pADSC can be used for clarification of molecular switches in regulating classical adipocyte differentiation or in direction to other mesenchymal cell types of mesodermal origin. Furthermore, extended lineages into cells of ectodermal and endodermal origin have recently been achieved. Therefore, pADSC derived in this protocol provide an abundant and assessable source of adult mesenchymal stem cells with full multipotency for studying adipose development and application to tissue engineering of regenerative medicine.

  13. Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues

    PubMed Central

    Chen, Yu-Jen; Liu, Hui-Yu; Chang, Yun-Tsui; Cheng, Ying-Hung; Mersmann, Harry J.; Kuo, Wen-Hung; Ding, Shih-Torng

    2016-01-01

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. The dorsal white fat depot of porcine subcutaneous adipose tissues is sliced, minced and collagenase digested. These pADSC exhibit strong potential to differentiate into adipocytes. Moreover, the pADSC also possess multipotency, assessed by selective stem cell markers, to differentiate into various mesenchymal cell types including adipocytes, osteocytes, and chondrocytes. These pADSC can be used for clarification of molecular switches in regulating classical adipocyte differentiation or in direction to other mesenchymal cell types of mesodermal origin. Furthermore, extended lineages into cells of ectodermal and endodermal origin have recently been achieved. Therefore, pADSC derived in this protocol provide an abundant and assessable source of adult mesenchymal stem cells with full multipotency for studying adipose development and application to tissue engineering of regenerative medicine. PMID:27077225

  14. Age-Associated Increase in Cytokine Production During Systemic Inflammation-II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue.

    PubMed

    Starr, Marlene E; Saito, Mizuki; Evers, B Mark; Saito, Hiroshi

    2015-12-01

    Expression of interleukin-6 (IL-6) upon acute inflammatory stress is significantly augmented by aging in adipose tissue, a major source of this cytokine. In the present study, we examined the mechanism of age-dependent IL-6 overproduction using visceral white adipose tissue from C57BL/6 mice. Upon treatment with lipopolysaccharide (LPS) in vitro, IL-6 was produced by adipose tissue explants, and secreted levels were significantly higher in cultures from aged (24 months) mice compared to young (4 months). Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNFα), two inducers of IL-6, were mainly produced by the lungs and spleen rather than adipose tissue in mice after LPS injection. Treatment of adipose explants with physiological levels of IL-1β induced significant age-dependent secretion of IL-6, while treatment with TNFα had little effect, demonstrating an augmented response of adipose tissues to IL-1β in the aged. In vitro experiments utilizing a neutralizing antibody against IL-1β and in vivo experiments utilizing IL-1-receptor-1 deficient mice, confirmed that IL-6 overproduction in the aged is regulated by autocrine/paracrine action of IL-1β which specifically occurs in aged adipose tissues. These findings indicate an elevated inflammatory potential of adipose tissue in the aged and a unique IL-1β-mediated mechanism for IL-6 overproduction, which may impact age-associated vulnerability to acute inflammatory diseases such as sepsis.

  15. The relationship between adiposity-associated inflammation and coronary artery and abdominal aortic calcium differs by strata of central adiposity: The Multi-Ethnic Study of Atherosclerosis (MESA).

    PubMed

    Hughes-Austin, Jan M; Wassel, Christina L; Jiménez, Jessica; Criqui, Michael H; Ix, Joachim H; Rasmussen-Torvik, Laura J; Budoff, Matthew J; Jenny, Nancy S; Allison, Matthew A

    2014-06-01

    Adipokines regulate metabolic processes linked to coronary artery (CAC) and abdominal aorta calcification (AAC). Because adipokine and other adiposity-associated inflammatory marker (AAIM) secretions differ between visceral and subcutaneous adipose tissue, we hypothesized that central adiposity modifies associations between AAIMs and CAC and AAC. We evaluated 1878 MESA participants with complete measures of AAIMs, anthropometry, CAC, and AAC. Associations of AAIMs with CAC and AAC prevalence and severity were analyzed per standard deviation of predictors (SD) using log binomial and linear regression models. The waist-to-hip ratio (WHR) was dichotomized at median WHR values based on sex/ethnicity. CAC and AAC prevalence were defined as any calcium (Agatston score >0). Severity was defined as ln (Agatston score). Analyses examined interactions with WHR and were adjusted for traditional cardiovascular disease risk factors. Each SD higher interleukin-6 (IL-6), fibrinogen and CRP was associated with 5% higher CAC prevalence; and each SD higher IL-6 and fibrinogen was associated with 4% higher AAC prevalence. Associations of IL-6 and fibrinogen with CAC severity, but not CAC prevalence, were significantly different among WHR strata. Median-and-above WHR: each SD higher IL-6 was associated with 24.8% higher CAC severity. Below-median WHR: no association (p interaction=0.012). Median-and-above WHR: each SD higher fibrinogen was associated with 19.6% higher CAC severity. Below-median WHR: no association (p interaction=0.034). Adiponectin, leptin, resistin, and tumor necrosis factor-alpha were not associated with CAC or AAC prevalence or severity. These results support findings that adiposity-associated inflammation is associated with arterial calcification, and further add that central adiposity may modify this association. PMID:24907349

  16. IRF3 promotes adipose inflammation and insulin resistance and represses browning.

    PubMed

    Kumari, Manju; Wang, Xun; Lantier, Louise; Lyubetskaya, Anna; Eguchi, Jun; Kang, Sona; Tenen, Danielle; Roh, Hyun Cheol; Kong, Xingxing; Kazak, Lawrence; Ahmad, Rasheed; Rosen, Evan D

    2016-08-01

    The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular and secreted factors promote the inflammatory milieu of obesity, but the transcriptional pathways that drive these processes are not well described. Although the canonical inflammatory transcription factor NF-κB is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family may also play a role in this process. Here, we determined that IRF3 expression is upregulated in the adipocytes of obese mice and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was associated with reductions in intra-adipose and systemic inflammation in the high fat-fed state, enhanced browning of subcutaneous fat, and increased adipose expression of GLUT4. Taken together, the data indicate that IRF3 is a major transcriptional regulator of adipose inflammation and is involved in maintaining systemic glucose and energy homeostasis. PMID:27400129

  17. IRF3 promotes adipose inflammation and insulin resistance and represses browning

    PubMed Central

    Wang, Xun; Lyubetskaya, Anna; Eguchi, Jun; Kang, Sona; Tenen, Danielle; Roh, Hyun Cheol; Kong, Xingxing; Kazak, Lawrence; Ahmad, Rasheed; Rosen, Evan D.

    2016-01-01

    The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular and secreted factors promote the inflammatory milieu of obesity, but the transcriptional pathways that drive these processes are not well described. Although the canonical inflammatory transcription factor NF-κB is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family may also play a role in this process. Here, we determined that IRF3 expression is upregulated in the adipocytes of obese mice and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was associated with reductions in intra-adipose and systemic inflammation in the high fat–fed state, enhanced browning of subcutaneous fat, and increased adipose expression of GLUT4. Taken together, the data indicate that IRF3 is a major transcriptional regulator of adipose inflammation and is involved in maintaining systemic glucose and energy homeostasis. PMID:27400129

  18. Role of adipose-derived stem cells in wound healing.

    PubMed

    Hassan, Waqar Ul; Greiser, Udo; Wang, Wenxin

    2014-01-01

    Impaired wound healing remains a challenge to date and causes debilitating effects with tremendous suffering. Recent advances in tissue engineering approaches in the area of cell therapy have provided promising treatment options to meet the challenges of impaired skin wound healing such as diabetic foot ulcers. Over the last few years, stem cell therapy has emerged as a novel therapeutic approach for various diseases including wound repair and tissue regeneration. Several different types of stem cells have been studied in both preclinical and clinical settings such as bone marrow-derived stem cells, adipose-derived stem cells (ASCs), circulating angiogenic cells (e.g., endothelial progenitor cells), human dermal fibroblasts, and keratinocytes for wound healing. Adipose tissue is an abundant source of mesenchymal stem cells, which have shown an improved outcome in wound healing studies. ASCs are pluripotent stem cells with the ability to differentiate into different lineages and to secrete paracrine factors initiating tissue regeneration process. The abundant supply of fat tissue, ease of isolation, extensive proliferative capacities ex vivo, and their ability to secrete pro-angiogenic growth factors make them an ideal cell type to use in therapies for the treatment of nonhealing wounds. In this review, we look at the pathogenesis of chronic wounds, role of stem cells in wound healing, and more specifically look at the role of ASCs, their mechanism of action and their safety profile in wound repair and tissue regeneration.

  19. [Use of adipose tissue in regenerative medicine].

    PubMed

    Casteilla, L; Planat-Benard, V; Bourin, P; Laharrague, P; Cousin, B

    2011-04-01

    Adipose tissue is abundant and well known for its involvement in obesity and associated metabolic disorders. Its uses in regenerative medicine recently attracted many investigators, as large amounts of this tissue can be easily obtained using liposuction and it contains several populations of immature cells. The largest pool of such cells corresponds to immature stromal cells, called adipose-derived stromal cells (ADSCs). These cells are purified after proteolytic digestion of adipose tissue and selection by an adherent step. ADSCs display many common features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but with some specific features, among which a greater angiogenic potential. This potential is now investigating at clinical level to treat critical ischemic hindlimb by autologous cells. Other potentials are also investigated and the treatment of fistula associated or not with Crohn's disease is reaching now phase III level.

  20. Chronic glucocorticoid exposure-induced epididymal adiposity is associated with mitochondrial dysfunction in white adipose tissue of male C57BL/6J mice.

    PubMed

    Yu, Jie; Yu, Bing; He, Jun; Zheng, Ping; Mao, Xiangbing; Han, Guoquan; Chen, Daiwen

    2014-01-01

    Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue. PMID:25389775

  1. Chronic Glucocorticoid Exposure-Induced Epididymal Adiposity Is Associated with Mitochondrial Dysfunction in White Adipose Tissue of Male C57BL/6J Mice

    PubMed Central

    Yu, Jie; Yu, Bing; He, Jun; Zheng, Ping; Mao, Xiangbing; Han, Guoquan; Chen, Daiwen

    2014-01-01

    Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue. PMID:25389775

  2. The development and endocrine functions of adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    White adipose tissue is a mesenchymal tissue that begins developing in the fetus. Classically known for storing the body’s fuel reserves, adipose tissue is now recognized as an endocrine organ. As such, the secretions from adipose tissue are known to affect several systems such as the vascular and...

  3. Studies of human adipose tissue. Adipose cell size and number in nonobese and obese patients.

    PubMed

    Salans, L B; Cushman, S W; Weismann, R E

    1973-04-01

    The cellular character of the adipose tissue of 21 nonobese and 78 obese patients has been examined. Adipose cell size (lipid per cell) was determined in three different subcutaneous and deep fat depots in each patient and the total number of adipose cells in the body estimated by division of total body fat by various combinations of the adipose cell sizes at six different sites. Cell number has also been estimated on the basis of various assumed distribution of total fat between the subcutaneous and deep fat depots. Obese patients, as a group, have larger adipose cells than do nonobese patients; cell size, however, varies considerably among the fat depots of individuals of either group. The variation in cell size exists not only between, but also within subcutaneous and deep sites. Estimates of total adipose cell number for a given individual based upon cell size can, therefore, vary by as much as 85%. On the basis of these studies it is suggested that the total adipose number of an individual is best and most practically estimated, at this time, by division of total body fat by the mean of the adipose cell sizes of at least three subcutaneous sites. IRRESPECTIVE OF THE METHOD BY WHICH TOTAL ADIPOSE CELL NUMBER IS ESTIMATED, TWO PATTERNS OF OBESITY EMERGE WITH RESPECT TO THE CELLULAR CHARACTER OF THE ADIPOSE TISSUE MASS OF THESE PATIENTS: hyperplastic, with increased adipose cell number and normal or increased size, and hypertrophic, with increased cell size alone. These two cellular patterns of obesity are independent of a variety of assumed distributions of fat among the subcutaneous and deep depots. When these different cellular patterns are examined in terms of various aspects of body size, body composition, and the degree, duration, and age of onset of obesity, only the latter uniquely distinguishes the hyperplastic from the hypertrophic: hyperplastic obesity is characterized by an early age of onset, hypertrophic, by a late age of onset. These studies

  4. Developmental programming, adiposity, and reproduction in ruminants.

    PubMed

    Symonds, M E; Dellschaft, N; Pope, M; Birtwistle, M; Alagal, R; Keisler, D; Budge, H

    2016-07-01

    Although sheep have been widely adopted as an animal model for examining the timing of nutritional interventions through pregnancy on the short- and long-term outcomes, only modest programming effects have been seen. This is due in part to the mismatch in numbers of twins and singletons between study groups as well as unequal numbers of males and females. Placental growth differs between singleton and twin pregnancies which can result in different body composition in the offspring. One tissue that is especially affected is adipose tissue which in the sheep fetus is primarily located around the kidneys and heart plus the sternal/neck region. Its main role is the rapid generation of heat due to activation of the brown adipose tissue-specific uncoupling protein 1 at birth. The fetal adipose tissue response to suboptimal maternal food intake at defined stages of development differs between the perirenal abdominal and pericardial depots, with the latter being more sensitive. Fetal adipose tissue growth may be mediated in part by changes in leptin status of the mother which are paralleled in the fetus. Then, over the first month of life plasma leptin is higher in females than males despite similar adiposity, when fat is the fastest growing tissue with the sternal/neck depot retaining uncoupling protein 1, whereas other depots do not. Future studies should take into account the respective effects of fetal number and sex to provide more detailed insights into the mechanisms by which adipose and related tissues can be programmed in utero. PMID:27173959

  5. Adiposity and Insufficient MVPA Predict Cardiometabolic Abnormalities in Adults

    PubMed Central

    Peterson, Mark D.; Snih, Soham Al; Stoddard, Jonathan; McClain, James; Lee, IMin

    2014-01-01

    Objectives To compare the extent to which different combinations of objectively measured sedentary behavior (SB) and physical activity contribute to cardiometabolic health. Design and Methods A population representative sample of 5,268 individuals, aged 20-85 years, was included from the combined 2003-2006 NHANES datasets. Activity categories were created on the combined basis of objectively measured SB and moderate-to-vigorous physical activity (MVPA) tertiles. Cardiometabolic abnormalities included elevated blood pressure, levels of triglycerides, fasting plasma glucose, C-reactive protein, homeostasis model assessment (HOMA) of insulin resistance value, and low HDL-cholesterol level. BMI, and DXA-derived percent body fat (% BF) and android adiposity were also compared across groups. Predictors for a metabolically abnormal phenotype (≥3 cardiometabolic abnormalities, or insulin resistance) were determined. Results Adults with the least SB and greatest MVPA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest MVPA were older and had elevated risk. Time spent in SB was not a predictor of the metabolically abnormal phenotype when MVPA was accounted for. Adults with the highest MVPA across SB tertiles did not differ markedly in prevalence of obesity, adiposity, and/or serum cardiometabolic risk factors; however, less MVPA was associated with substantial elevations of obesity and cardiometabolic risk. Android adiposity (per kilogram) was independently associated with the metabolically abnormal phenotype in both men (OR: 2.36 [95% CI, 1.76-3.17], p<0.001) and women (OR: 2.00 [95% CI, 1.63-2.45], p<0.001). Among women, greater SB, and less lifestyle moderate activity and MVPA were each independently associated with the metabolically abnormal phenotype, whereas only less MVPA was associated with it in men. Conclusions MVPA is a strong predictor of cardiometabolic health among adults, independent of time spent in SB. PMID

  6. Intermuscular Adipose Tissue and Metabolic Associations in HIV Infection

    PubMed Central

    Scherzer, Rebecca; Shen, Wei; Heymsfield, Steven B.; Lewis, Cora E.; Kotler, Donald P.; Punyanitya, Mark; Bacchetti, Peter; Shlipak, Michael G.; Grunfeld, Carl

    2013-01-01

    Intermuscular adipose tissue (IMAT) is associated with metabolic abnormalities similar to those associated with visceral adipose tissue (VAT). Increased IMAT has been found in obese human immunodeficiency virus (HIV)-infected women. We hypothesized that IMAT, like VAT, would be similar or increased in HIV-infected persons compared with healthy controls, despite decreases in subcutaneous adipose tissue (SAT) found in HIV infection. In the second FRAM (Study of Fat Redistribution and Metabolic Change in HIV infection) exam, we studied 425 HIV-infected subjects and 211 controls (from the Coronary Artery Risk Development in Young Adults study) who had regional AT and skeletal muscle (SM) measured by magnetic resonance imaging (MRI). Multivariable linear regression identified factors associated with IMAT and its association with metabolites. Total IMAT was 51% lower in HIV-infected participants compared with controls (P = 0.003). The HIV effect was attenuated after multivariable adjustment (to −28%, P < 0.0001 in men and −3.6%, P = 0.70 in women). Higher quantities of leg SAT, upper-trunk SAT, and VAT were associated with higher IMAT in HIV-infected participants, with weaker associations in controls. Stavudine use was associated with lower IMAT and SAT, but showed little relationship with VAT. In multivariable analyses, regional IMAT was associated with insulin resistance and triglycerides (TGs). Contrary to expectation, IMAT is not increased in HIV infection; after controlling for demographics, lifestyle, VAT, SAT, and SM, HIV+ men have lower IMAT compared with controls, whereas values for women are similar. Stavudine exposure is associated with both decreased IMAT and SAT, suggesting that IMAT shares cellular origins with SAT. PMID:20539305

  7. Rectal tone and compliance affected in patients with fecal incontinence after fistulotomy

    PubMed Central

    Awad, Richard Alexander; Camacho, Santiago; Flores, Francisco; Altamirano, Evelyn; García, Mario Antonio

    2015-01-01

    AIM: To investigate the anal sphincter and rectal factors that may be involved in fecal incontinence that develops following fistulotomy (FIAF). METHODS: Eleven patients with FIAF were compared with 11 patients with idiopathic fecal incontinence and with 11 asymptomatic healthy subjects (HS). All of the study participants underwent anorectal manometry and a barostat study (rectal sensitivity, tone, compliance and capacity). The mean time since surgery was 28 ± 26 mo. The postoperative continence score was 14 ± 2.5 (95%CI: 12.4-15.5, St Mark’s fecal incontinence grading system). RESULTS: Compared with the HS, the FIAF patients showed increased rectal tone (42.63 ± 27.69 vs 103.5 ± 51.13, P = 0.002) and less rectal compliance (4.95 ± 3.43 vs 11.77 ± 6.9, P = 0.009). No significant differences were found between the FIAF patients and the HS with respect to the rectal capacity; thresholds for the non-noxious stimuli of first sensation, gas sensation and urge-to-defecate sensation or the noxious stimulus of pain; anal resting pressure or squeeze pressure; or the frequency or percentage of relaxation of the rectoanal inhibitory reflex. No significant differences were found between the FIAF patients and the patients with idiopathic fecal incontinence. CONCLUSION: In patients with FIAF, normal motor anal sphincter function and rectal sensitivity are preserved, but rectal tone and compliance are impaired. The results suggest that FIAF is not due to alterations in rectal sensitivity and that the rectum is more involved than the anal sphincters in the genesis of FIAF. PMID:25852287

  8. The role of adipose cell size and adipose tissue insulin sensitivity in the carbohydrate intolerance of human obesity.

    PubMed

    Salans, L B; Knittle, J L; Hirsch, J

    1968-01-01

    Glucose metabolism and insulin sensitivity of isolated human adipose tissue was studied as a function of adipose cell size and number. Glucose metabolism by these tissues was closely related to the number of cells in the fragment, irrespective of cell size. Adipose cells of obese individuals metabolized glucose to carbon dioxide and triglyceride at rates similar to adipose cells of nonobese subjects. In contrast, insulin responsiveness of adipose tissue was dependent upon adipose cell size. The larger its adipose cells the less insulin sensitive was the tissue. Thus, adipose tissue of obese subjects, with enlarged cells, showed a diminished response to insulin. After weight loss and reduction in adipose cell size, insulin sensitivity of the adipose tissue of obese patients was restored to normal. When adipose tissue of obese individuals showed impaired responsiveness to insulin, their plasma insulin levels, after oral glucose, were elevated. Weight loss and reduction in adipose cell size restored plasma insulin concentration to normal, concomitant with the return of normal tissue insulin sensitivity.

  9. Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism.

    PubMed

    Tang, Yuefeng; Wallace, Martina; Sanchez-Gurmaches, Joan; Hsiao, Wen-Yu; Li, Huawei; Lee, Peter L; Vernia, Santiago; Metallo, Christian M; Guertin, David A

    2016-01-01

    Adipose tissue de novo lipogenesis (DNL) positively influences insulin sensitivity, is reduced in obesity, and predicts insulin resistance. Therefore, elucidating mechanisms controlling adipose tissue DNL could lead to therapies for type 2 diabetes. Here, we report that mechanistic target of rapamycin complex 2 (mTORC2) functions in white adipose tissue (WAT) to control expression of the lipogenic transcription factor ChREBPβ. Conditionally deleting the essential mTORC2 subunit Rictor in mature adipocytes decreases ChREBPβ expression, which reduces DNL in WAT, and impairs hepatic insulin sensitivity. Mechanistically, Rictor/mTORC2 promotes ChREBPβ expression in part by controlling glucose uptake, but without impairing pan-AKT signalling. High-fat diet also rapidly decreases adipose tissue ChREBPβ expression and insulin sensitivity in wild-type mice, and does not further exacerbate insulin resistance in adipose tissue Rictor knockout mice, implicating adipose tissue DNL as an early target in diet-induced insulin resistance. These data suggest mTORC2 functions in WAT as part of an extra-hepatic nutrient-sensing mechanism to control glucose homeostasis. PMID:27098609

  10. In vivo adeno-associated viral vector-mediated genetic engineering of white and brown adipose tissue in adult mice.

    PubMed

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-12-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes. PMID:24043756

  11. Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism

    PubMed Central

    Tang, Yuefeng; Wallace, Martina; Sanchez-Gurmaches, Joan; Hsiao, Wen-Yu; Li, Huawei; Lee, Peter L.; Vernia, Santiago; Metallo, Christian M.; Guertin, David A.

    2016-01-01

    Adipose tissue de novo lipogenesis (DNL) positively influences insulin sensitivity, is reduced in obesity, and predicts insulin resistance. Therefore, elucidating mechanisms controlling adipose tissue DNL could lead to therapies for type 2 diabetes. Here, we report that mechanistic target of rapamycin complex 2 (mTORC2) functions in white adipose tissue (WAT) to control expression of the lipogenic transcription factor ChREBPβ. Conditionally deleting the essential mTORC2 subunit Rictor in mature adipocytes decreases ChREBPβ expression, which reduces DNL in WAT, and impairs hepatic insulin sensitivity. Mechanistically, Rictor/mTORC2 promotes ChREBPβ expression in part by controlling glucose uptake, but without impairing pan-AKT signalling. High-fat diet also rapidly decreases adipose tissue ChREBPβ expression and insulin sensitivity in wild-type mice, and does not further exacerbate insulin resistance in adipose tissue Rictor knockout mice, implicating adipose tissue DNL as an early target in diet-induced insulin resistance. These data suggest mTORC2 functions in WAT as part of an extra-hepatic nutrient-sensing mechanism to control glucose homeostasis. PMID:27098609

  12. In vivo adeno-associated viral vector-mediated genetic engineering of white and brown adipose tissue in adult mice.

    PubMed

    Jimenez, Veronica; Muñoz, Sergio; Casana, Estefania; Mallol, Cristina; Elias, Ivet; Jambrina, Claudia; Ribera, Albert; Ferre, Tura; Franckhauser, Sylvie; Bosch, Fatima

    2013-12-01

    Adipose tissue is pivotal in the regulation of energy homeostasis through the balance of energy storage and expenditure and as an endocrine organ. An inadequate mass and/or alterations in the metabolic and endocrine functions of adipose tissue underlie the development of obesity, insulin resistance, and type 2 diabetes. To fully understand the metabolic and molecular mechanism(s) involved in adipose dysfunction, in vivo genetic modification of adipocytes holds great potential. Here, we demonstrate that adeno-associated viral (AAV) vectors, especially serotypes 8 and 9, mediated efficient transduction of white (WAT) and brown adipose tissue (BAT) in adult lean and obese diabetic mice. The use of short versions of the adipocyte protein 2 or uncoupling protein-1 promoters or micro-RNA target sequences enabled highly specific, long-term AAV-mediated transgene expression in white or brown adipocytes. As proof of concept, delivery of AAV vectors encoding for hexokinase or vascular endothelial growth factor to WAT or BAT resulted in increased glucose uptake or increased vessel density in targeted depots. This method of gene transfer also enabled the secretion of stable high levels of the alkaline phosphatase marker protein into the bloodstream by transduced WAT. Therefore, AAV-mediated genetic engineering of adipose tissue represents a useful tool for the study of adipose pathophysiology and, likely, for the future development of new therapeutic strategies for obesity and diabetes.

  13. Adipose hypothermia in obesity and its association with period homolog 1, insulin sensitivity, and inflammation in fat.

    PubMed

    Yamaoka, Masaya; Maeda, Norikazu; Takayama, Yasunori; Sekimoto, Ryohei; Tsushima, Yu; Matsuda, Keisuke; Mori, Takuya; Inoue, Kana; Nishizawa, Hitoshi; Tominaga, Makoto; Funahashi, Tohru; Shimomura, Iichiro

    2014-01-01

    Visceral fat adiposity plays an important role in the development of metabolic syndrome. We reported previously the impact of human visceral fat adiposity on gene expression profile of peripheral blood cells. Genes related to circadian rhythm were highly associated with visceral fat area and period homolog 1 (PER1) showed the most significant negative correlation with visceral fat area. However, regulation of adipose Per1 remains poorly understood. The present study was designed to understand the regulation of Per1 in adipose tissues. Adipose Per1 mRNA levels of ob/ob mice were markedly low at 25 and 35 weeks of age. The levels of other core clock genes of white adipose tissues were also low in ob/ob mice at 25 and 35 weeks of age. Per1 mRNA was mainly expressed in the mature adipocyte fraction (MAF) and it was significantly low in MAF of ob/ob mice. To examine the possible mechanisms, 3T3-L1 adipocytes were treated with H2O2, tumor necrosis factor-α (TNF-α), S100A8, and lipopolysaccharide (LPS). However, no significant changes in Per1 mRNA level were observed by these agents. Exposure of cultured 3T3-L1 adipocytes to low temperature (33°C) decreased Per1 and catalase, and increased monocyte chemoattractant protein-1 (Mcp-1) mRNA levels. Hypothermia also worsened insulin-mediated Akt phosphorylation in 3T3-L1 adipocytes. Finally, telemetric analysis showed low temperature of adipose tissues in ob/ob mice. In obesity, adipose hypothermia seems to accelerate adipocyte dysfunction.

  14. A Stratified Transcriptomics Analysis of Polygenic Fat and Lean Mouse Adipose Tissues Identifies Novel Candidate Obesity Genes

    PubMed Central

    Morton, Nicholas M.; Nelson, Yvonne B.; Michailidou, Zoi; Di Rollo, Emma M.; Ramage, Lynne; Hadoke, Patrick W. F.; Seckl, Jonathan R.; Bunger, Lutz; Horvat, Simon; Kenyon, Christopher J.; Dunbar, Donald R.

    2011-01-01

    Background Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F) mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L) strain. Results To enrich for adipose tissue obesity genes a ‘snap-shot’ pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney) was performed. Known obesity quantitative trait loci (QTL) information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r) as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr) that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity. Conclusions A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes

  15. Intra-abdominal fat. Part I. The images of the adipose tissue localized beyond organs

    PubMed Central

    Kołaczyk, Katarzyna; Bernatowicz, Elżbieta

    2015-01-01

    Unaltered fat is a permanent component of the abdominal cavity, even in slim individuals. Visceral adiposity is one of the important factors contributing to diabetes, cardiovascular diseases and certain neoplasms. Moreover, the adipose tissue is an important endocrine and immune organ of complex function both when normal and pathological. Its role in plastic surgery, reconstruction and transplantology is a separate issue. The adipose tissue has recently drawn the attention of research institutes owing to being a rich source of stem cells. This review, however, does not include these issues. The identification of fat is relatively easy using computed tomography and magnetic resonance imaging. It can be more difficult in an ultrasound examination for several reasons. The aim of this paper is to present various problems associated with US imaging of unaltered intra-abdominal fat located beyond organs. Based on the literature and experience, it has been demonstrated that the adipose tissue in the abdominal cavity has variable echogenicity, which primarily depends on the amount of extracellular fluid and the number of connective tissue septa, i.e. elements that potentiate the number of areas that reflect and scatter ultrasonic waves. The normal adipose tissue presents itself on a broad gray scale: from a hyperechoic area, through numerous structures of lower reflection intensity, to nearly anechoic regions mimicking the presence of pathological fluid collections. The features that facilitate proper identification of this tissue are: sharp margins, homogeneous structure, high compressibility under transducer pressure, no signs of infiltration of the surrounding structures and no signs of vascularization when examined with the color and power Doppler. The accumulation of fat tissue in the abdominal cavity can be generalized, regional or focal. The identification of the adipose tissue in the abdominal cavity using ultrasonography is not always easy. When in doubt, the

  16. Broiler chicken adipose tissue dynamics during the first two weeks post-hatch.

    PubMed

    Bai, Shiping; Wang, Guoqing; Zhang, Wei; Zhang, Shuai; Rice, Brittany Breon; Cline, Mark Andrew; Gilbert, Elizabeth Ruth

    2015-11-01

    Selection of broiler chickens for growth has led to increased adipose tissue accretion. To investigate the post-hatch development of adipose tissue, the abdominal, clavicular, and subcutaneous adipose tissue depots were collected from broiler chicks at 4 and 14 days post-hatch. As a percent of body weight, abdominal fat increased (P<0.001) with age. At day 4, clavicular and subcutaneous fat depots were heavier (P<0.003) than abdominal fat whereas at day 14, abdominal and clavicular weighed more (P<0.003) than subcutaneous fat. Adipocyte area and diameter were greater in clavicular and subcutaneous than abdominal fat at 4 and 14 days post-hatch (P<0.001). Glycerol-3-phosphate dehydrogenase (G3PDH) activity increased (P<0.001) in all depots from day 4 to 14, and at both ages was greatest in subcutaneous, intermediate in clavicular, and lowest in abdominal fat (P<0.05). In clavicular fat, peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer binding protein (CEBP)α, CEBPβ, fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), lipoprotein lipase (LPL), neuropeptide Y (NPY), and NPY receptor 5 (NPYR5) mRNA increased and NPYR2 mRNA decreased from day 4 to 14 (P<0.001). Thus, there are site-specific differences in broiler chick adipose development, with larger adipocytes and greater G3PDH activity in subcutaneous fat at day 4, more rapid growth of abdominal fat, and clavicular fat intermediate for most traits. Adipose tissue expansion was accompanied by changes in gene expression of adipose-associated factors.

  17. Intra-abdominal fat. Part I. The images of the adipose tissue localized beyond organs.

    PubMed

    Smereczyński, Andrzej; Kołaczyk, Katarzyna; Bernatowicz, Elżbieta

    2015-09-01

    Unaltered fat is a permanent component of the abdominal cavity, even in slim individuals. Visceral adiposity is one of the important factors contributing to diabetes, cardiovascular diseases and certain neoplasms. Moreover, the adipose tissue is an important endocrine and immune organ of complex function both when normal and pathological. Its role in plastic surgery, reconstruction and transplantology is a separate issue. The adipose tissue has recently drawn the attention of research institutes owing to being a rich source of stem cells. This review, however, does not include these issues. The identification of fat is relatively easy using computed tomography and magnetic resonance imaging. It can be more difficult in an ultrasound examination for several reasons. The aim of this paper is to present various problems associated with US imaging of unaltered intra-abdominal fat located beyond organs. Based on the literature and experience, it has been demonstrated that the adipose tissue in the abdominal cavity has variable echogenicity, which primarily depends on the amount of extracellular fluid and the number of connective tissue septa, i.e. elements that potentiate the number of areas that reflect and scatter ultrasonic waves. The normal adipose tissue presents itself on a broad gray scale: from a hyperechoic area, through numerous structures of lower reflection intensity, to nearly anechoic regions mimicking the presence of pathological fluid collections. The features that facilitate proper identification of this tissue are: sharp margins, homogeneous structure, high compressibility under transducer pressure, no signs of infiltration of the surrounding structures and no signs of vascularization when examined with the color and power Doppler. The accumulation of fat tissue in the abdominal cavity can be generalized, regional or focal. The identification of the adipose tissue in the abdominal cavity using ultrasonography is not always easy. When in doubt, the

  18. Intra-abdominal fat. Part I. The images of the adipose tissue localized beyond organs.

    PubMed

    Smereczyński, Andrzej; Kołaczyk, Katarzyna; Bernatowicz, Elżbieta

    2015-09-01

    Unaltered fat is a permanent component of the abdominal cavity, even in slim individuals. Visceral adiposity is one of the important factors contributing to diabetes, cardiovascular diseases and certain neoplasms. Moreover, the adipose tissue is an important endocrine and immune organ of complex function both when normal and pathological. Its role in plastic surgery, reconstruction and transplantology is a separate issue. The adipose tissue has recently drawn the attention of research institutes owing to being a rich source of stem cells. This review, however, does not include these issues. The identification of fat is relatively easy using computed tomography and magnetic resonance imaging. It can be more difficult in an ultrasound examination for several reasons. The aim of this paper is to present various problems associated with US imaging of unaltered intra-abdominal fat located beyond organs. Based on the literature and experience, it has been demonstrated that the adipose tissue in the abdominal cavity has variable echogenicity, which primarily depends on the amount of extracellular fluid and the number of connective tissue septa, i.e. elements that potentiate the number of areas that reflect and scatter ultrasonic waves. The normal adipose tissue presents itself on a broad gray scale: from a hyperechoic area, through numerous structures of lower reflection intensity, to nearly anechoic regions mimicking the presence of pathological fluid collections. The features that facilitate proper identification of this tissue are: sharp margins, homogeneous structure, high compressibility under transducer pressure, no signs of infiltration of the surrounding structures and no signs of vascularization when examined with the color and power Doppler. The accumulation of fat tissue in the abdominal cavity can be generalized, regional or focal. The identification of the adipose tissue in the abdominal cavity using ultrasonography is not always easy. When in doubt, the

  19. Noncultured Autologous Adipose-Derived Stem Cells Therapy for Chronic Radiation Injury

    PubMed Central

    Akita, Sadanori; Akino, Kozo; Hirano, Akiyoshi; Ohtsuru, Akira; Yamashita, Shunichi

    2010-01-01

    Increasing concern on chronic radiation injuries should be treated properly for life-saving improvement of wound management and quality of life. Recently, regenerative surgical modalities should be attempted with the use of noncultured autologous adipose-derived stem cells (ADSCs) with temporal artificial dermis impregnated and sprayed with local angiogenic factor such as basic fibroblast growth factor, and secondary reconstruction can be a candidate for demarcation and saving the donor morbidity. Autologous adipose-derived stem cells, together with angiogenic and mitogenic factor of basic fibroblast growth factor and an artificial dermis, were applied over the excised irradiated skin defect and tested for Patients who were uneventfully healed with minimal donor-site morbidity, which lasts more than 1.5 years. PMID:21151652

  20. Implantation of Autologous Adipose-Derived Cells Reconstructs Functional Urethral Sphincters in Rabbit Cryoinjured Urethra

    PubMed Central

    Silwal Gautam, Sudha; Ishizuka, Osamu; Lei, Zhang; Yamagishi, Takahiro; Yokoyama, Hitoshi; Minagawa, Tomonori; Ogawa, Teruyuki; Kurizaki, Yoshiki; Kato, Haruaki; Nishizawa, Osamu

    2014-01-01

    We investigated the ability of autologous adipose-derived cells injected into cryoinjured rabbit urethras to improve urinary continence and explored the possible mechanisms by which it occurred. Adipose tissue was harvested from the perivesical region of nine 10-week-old female New Zealand White rabbits and cultured for 7 days. Immediately after harvesting the tissue, we injured the internal urethral orifice by spraying liquid nitrogen for 20 s. The cultured cells expressed the mesenchymal cell marker STRO1, but not muscle cell markers myoglobin or smooth muscle actin (SMA). Just before implantation, the adipose-derived cells were labeled with the PKH26 fluorescent cell linker. Autologous 2.0×106 adipose-derived cells (five rabbits) or a cell-free control solution (four rabbits) was injected around the cryoinjured urethras at 7 days after injury. Fourteen days later, the leak point pressure (LPP) was measured, and the urethras were harvested for immunohistochemical analyses. At 14 days after implantation, LPP of the cell-implanted group was significantly higher compared with the cell-free control group (p<0.05). In immunohistochemical examination, the reconstructed skeletal and smooth muscle areas in the cell-implanted regions were significantly more developed than those in controls (p<0.01). Implanted PKH26-labeled adipose-derived cells were immunohistochemically positive for myoglobin, SMA, and Pax7 antibodies, which are markers for skeletal muscles, smooth muscles, and myoblast progenitor cells, respectively. In addition, these implanted cells were positive for the nerve cell markers, tubulin β3, S100, and the vascular endothelial cell marker, von Willebrand factor. Furthermore, some of the implanted cells were positive for the transforming growth factor β1, nerve growth factor, and vascular endothelial growth factor. In conclusion, implantation of autologous adipose-derived cells into the cryoinjured rabbit urethras promoted the recovery of urethral

  1. Altered somatotroph feedback regulation improves metabolic efficiency and limits adipose deposition in male mice.

    PubMed

    Romero, Christopher J; Wolfe, Andrew; Law, Yi Ying; Costelloe, ChenChen Z; Miller, Ryan; Wondisford, Fredric; Radovick, Sally

    2016-04-01

    Several transgenic mouse models with disruption in the growth hormone (GH) axis support the role of GH in augmenting metabolic homeostasis. Specifically, interest has focused on GH's lipolytic properties and ability to affect adipose deposition. Furthermore, both GH and insulin growth factor 1 (IGF-1) may also play a direct or indirect role in adipose development. The somatotroph insulin-like growth factor-1 receptor knockout (SIGFRKO) mouse with only a modest increase in serum GH and IGF-1 demonstrates less adipose tissue than controls. In order to characterize the metabolic phenotype of SIGFRKO mice, histologic analysis of fat depots confirmed a smaller average diameter of adipocytes in the SIGFRKO mice compared to controls. These changes were accompanied by an increase in lipolytic gene expression in fat depots. Indirect calorimetry performed on 6-8week old male mice and again at 25weeks of age demonstrated that SIGFRKO mice, at both ages, had a higher VO2 and increased energy expenditure when compared with controls. The calculated respiratory exchange ratio (RER) was lower in the younger SIGFRKO mice compared to controls. No differences in food consumption or in either ambulatory or total activity were seen between SIGFRKO and control mice in either age group. These studies highlight the role of GH in adipose deposition and its influence on the expression of lipolytic genes resulting in an altered metabolic state, thus providing a mechanism for the decrease in weight gain seen in the SIGFRKO mouse model.

  2. Brown adipose tissue: The heat is on the heart.

    PubMed

    Thoonen, Robrecht; Hindle, Allyson G; Scherrer-Crosbie, Marielle

    2016-06-01

    The study of brown adipose tissue (BAT) has gained significant scientific interest since the discovery of functional BAT in adult humans. The thermogenic properties of BAT are well recognized; however, data generated in the last decade in both rodents and humans reveal therapeutic potential for BAT against metabolic disorders and obesity. Here we review the current literature in light of a potential role for BAT in beneficially mediating cardiovascular health. We focus mainly on BAT's actions in obesity, vascular tone, and glucose and lipid metabolism. Furthermore, we discuss the recently discovered endocrine factors that have a potential beneficial role in cardiovascular health. These BAT-secreted factors may have a favorable effect against cardiovascular risk either through their metabolic role or by directly affecting the heart. PMID:27084389

  3. Adipose-derived stem cells in cartilage regeneration: current perspectives.

    PubMed

    Bielli, Alessandra; Scioli, Maria Giovanna; Gentile, Pietro; Cervelli, Valerio; Orlandi, Augusto

    2016-10-01

    Repair of cartilage injuries represents a musculoskeletal medicine criticism because of the poor ability to self-renewal of adult cartilage. Therefore, research focuses on developing new regenerative strategies combining chondrocytes or stem cells, scaffolds and growth factors. Because of the low proliferation capability of explanted chondrocytes, new chondrogenesis models, employing human adipose-derived stem cells (ASCs), have been investigated. ASCs are readily accessible with no morbidity and display the capability to differentiate into several cell lineages, including the spontaneous chondrogenic differentiation when entrapped in collagen gel scaffolds. Recent studies also defined some biomolecular mechanisms involved in ASC chondrogenesis in vitro, and their regenerative properties in bioengineered scaffolds and in the presence of growth factors. However, further investigations are required to validate these exciting preclinical results for the application of bioenginereed ASCs in the clinical practice. PMID:27599358

  4. Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity.

    PubMed

    Lee, Byung-Cheol; Kim, Myung-Sunny; Pae, Munkyong; Yamamoto, Yasuhiko; Eberlé, Delphine; Shimada, Takeshi; Kamei, Nozomu; Park, Hee-Sook; Sasorith, Souphatta; Woo, Ju Rang; You, Jia; Mosher, William; Brady, Hugh J M; Shoelson, Steven E; Lee, Jongsoon

    2016-04-12

    Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNFα, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/-) mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNFα, and thereby contribute to the development of obesity-induced insulin resistance.

  5. Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity.

    PubMed

    Peinado, Juan R; Pardo, María; de la Rosa, Olga; Malagón, Maria M

    2012-02-01

    The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells. It is known that not only mature adipocytes but also the components of SVF produce adipokines. Furthermore, adipokine production, proliferative and metabolic activities and response to regulatory signals (i.e. insulin, catecholamines) differ between the different fat depots, which have been proposed to underlie their distinct association to specific diseases. Herein, we discuss the recent proteomic studies on adipose tissue focused on the analysis of the separate cellular components and their secretory products, with the aim of identifying the basic features and the contribution of each component to different adipose tissue-associated pathologies.

  6. Injectable Biomaterials for Adipose Tissue Engineering

    PubMed Central

    Young, D. Adam; Christman, Karen L.

    2012-01-01

    Adipose tissue engineering has recently gained significant attention from materials scientists as a result of the exponential growth of soft tissue filler procedures being performed within the clinic. While several injectable materials are currently being marketed for filling subcutaneous voids, they often face limited longevity due to rapid resorption. Their inability to encourage natural adipose formation or ingrowth necessitates repeated injections for a prolonged effect, and thus classifies them as temporary fillers. As a result, a significant need for injectable materials that not only act as fillers, but also promote in vivo adipogenesis is beginning to be realized. This review will discuss the advantages and disadvantages of commercially available soft tissue fillers. It will then summarize the current state of research using injectable synthetic materials, biopolymers, and extracellular matrix-derived materials for adipose tissue engineering. Furthermore, the successful attributes observed across each of these materials will be outlined along with a discussion of the current difficulties and future directions for adipose tissue engineering. PMID:22456805

  7. Does bariatric surgery improve adipose tissue function?

    PubMed

    Frikke-Schmidt, H; O'Rourke, R W; Lumeng, C N; Sandoval, D A; Seeley, R J

    2016-09-01

    Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.

  8. The metabolic syndrome as a concept of adipose tissue disease.

    PubMed

    Oda, Eiji

    2008-07-01

    The metabolic syndrome is a constellation of interrelated metabolic risk factors that appear to directly promote the development of diabetes and cardiovascular disease. However, in 2005, the American Diabetes Association and the European Association for the Study of Diabetes jointly stated that no existing definition of the metabolic syndrome meets the criteria of a syndrome, and there have been endless debates on the pros and cons of using the concept of this syndrome. The controversy may stem from confusion between the syndrome and obesity. Obesity is an epidemic, essentially contagious disease caused by an environment of excess nutritional energy and reinforced by deeply rooted social norms. The epidemic of obesity should be prevented or controlled by social and political means, similar to the approaches now being taken to combat global warming. The diagnosis of metabolic syndrome is useless for this public purpose. The purpose of establishing criteria for diagnosing metabolic syndrome is to find individuals who are at increased risk of diabetes and cardiovascular disease and who require specific therapy including diet and exercise. The syndrome may be an adipose tissue disease different from obesity; in that case, it would be characterized by inflammation clinically detected through systemic inflammatory markers such as high-sensitivity C-reactive protein and insulin resistance reflecting histological changes in adipose tissue. However, many problems in defining the optimal diagnostic criteria remain unresolved.

  9. Impaired mitochondrial function in human placenta with increased maternal adiposity

    PubMed Central

    Mele, James; Muralimanoharan, Sribalasubashini; Maloyan, Alina

    2014-01-01

    The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18.5 to 45 following C-section at term with no labor. Increasing maternal adiposity was associated with excessive production of reactive oxygen species and a significant reduction in placental ATP levels in placentae with male and female fetuses. To explore the potential mechanism of placental mitochondrial dysfunction, levels of transcription factors regulating the expression of genes involved in electron transport and mitochondrial biogenesis were measured. Our in vitro studies showed significant reduction in mitochondrial respiration in cultured primary trophoblasts with increasing maternal obesity along with an abnormal metabolic flexibility of these cells. This reduction in placental mitochondrial respiration in pregnancies complicated by maternal obesity could compromise placental function and potentially underlie the increased susceptibility of these pregnancies to fetal demise in late gestation and to developmental programming. PMID:25028397

  10. Adipose tissue: from lipid storage compartment to endocrine organ.

    PubMed

    Scherer, Philipp E

    2006-06-01

    Adipose tissue, when carried around in excessive amounts, predisposes to a large number of diseases. Epidemiological data show that the prevalence of obesity has significantly increased over the past 20 years and continues to do so at an alarming rate. Here, some molecular aspects of the key constituent of adipose tissue, the adipocyte, are reviewed. While the adipocyte has been studied for many years and remarkable insights have been gained about some processes, many areas of the physiology of the fat cell remain unexplored. Our understanding of how cellular events in the adipocyte affect the local environment through paracrine interactions and how systemic effects are achieved through endocrine interactions is rudimentary. While storage and release of lipids are major functions of adipocytes, the adipocyte also uses specific lipid molecules for intracellular signaling and uses a host of protein factors to communicate with essentially every organ system in the body. The intensity and complexity of these signals are highly regulated, differ in each fat pad, and are dramatically affected by various disease states. PMID:16731815

  11. Adipose Tissue-Derived Stem Cells in Regenerative Medicine

    PubMed Central

    Frese, Laura; Dijkman, Petra E.; Hoerstrup, Simon P.

    2016-01-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted. PMID:27721702

  12. Organotypic culture of human bone marrow adipose tissue.

    PubMed

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was <0.8 ng/mL under all culture conditions. Dexamethasone promoted adiponectin gene expression, while insulin inhibited it. This finding suggests that dexamethasone, but not insulin, may serve as a powerful adipogenic factor for BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  13. The influence of growth hormone on bone and adipose programming.

    PubMed

    Oberbauer, Anita M

    2014-01-01

    In utero growth hormone exposure is associated with distinct immediate growth responses and long term impacts on adult physiological parameters that include obesity, insulin resistance, and bone function. Growth hormone accelerates cellular proliferation in many tissues but is exemplified by increases in the number of cells within the cartilaginous growth plate of bone. In some cases growth hormone also potentiates differentiation as seen in the differentiation of adipocytes that rapidly fill upon withdrawal of growth hormone. Growth hormone provokes these changes either by direct action or through intermediaries such as insulin-like growth factor-I and other downstream effector molecules. The specific mechanism used by growth hormone in programming tissues is not yet fully characterized and likely represents a multipronged approach involving DNA modification, altered adult hormonal milieu, and the development of an augmented stem cell pool capable of future engagement as is seen in adipose accrual. This review summarizes findings of growth hormone's influence on in utero and neonatal cellular and metabolic profiles related to bone and adipose tissue.

  14. Model of adipose tissue cellularity dynamics during food restriction.

    PubMed

    Soula, H A; Géloën, A; Soulage, C O

    2015-01-01

    Adipose tissue and adipocytes play a central role in the pathogenesis of metabolic diseases related to obesity. Size of fat cells depends on the balance of synthesis and mobilization of lipids and can undergo important variations throughout the life of the organism. These variations usually occur when storing and releasing lipids according to energy demand. In particular when confronted to severe food restriction, adipocyte releases its lipid content via a process called lipolysis. We propose a mathematical model that combines cell diameter distribution and lipolytic response to show that lipid release is a surface (radius squared) limited mechanism. Since this size-dependent rate affects the cell׳s shrinkage speed, we are able to predict the cell size distribution evolution when lipolysis is the only factor at work: such as during an important food restriction. Performing recurrent surgical biopsies on rats, we measured the evolution of adipose cell size distribution for the same individual throughout the duration of the food restriction protocol. We show that our microscopic model of size dependent lipid release can predict macroscopic size distribution evolution.

  15. Visceral adipose tissue inflammation is associated with age-related brain changes and ischemic brain damage in aged mice.

    PubMed

    Shin, Jin A; Jeong, Sae Im; Kim, Minsuk; Yoon, Joo Chun; Kim, Hee-Sun; Park, Eun-Mi

    2015-11-01

    Visceral adipose tissue is accumulated with aging. An increase in visceral fat accompanied by low-grade inflammation is associated with several adult-onset diseases. However, the effects of visceral adipose tissue inflammation on the normal and ischemic brains of aged are not clearly defined. To examine the role of visceral adipose tissue inflammation, we evaluated inflammatory cytokines in the serum, visceral adipose tissue, and brain as well as blood-brain barrier (BBB) permeability in aged male mice (20 months) underwent sham or visceral fat removal surgery compared with the young mice (2.5 months). Additionally, ischemic brain injury was compared in young and aged mice with sham and visceral fat removal surgery. Interleukin (IL)-1β, IL-6, and tumor necrosis factor-α levels in examined organs were increased in aged mice compared with the young mice, and these levels were reduced in the mice with visceral fat removal. Increased BBB permeability with reduced expression of tight junction proteins in aged sham mice were also decreased in mice with visceral fat removal. After focal ischemic injury, aged mice with visceral fat removal showed a reduction in infarct volumes, BBB permeability, and levels of proinflammatory cytokines in the ischemic brain compared with sham mice, although the neurological outcomes were not significantly improved. In addition, further upregulated visceral adipose tissue inflammation in response to ischemic brain injury was attenuated in mice with visceral fat removal. These results suggest that visceral adipose tissue inflammation is associated with age-related changes in the brain and contributes to the ischemic brain damage in the aged mice. We suggest that visceral adiposity should be considered as a factor affecting brain health and ischemic brain damage in the aged population.

  16. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats.

    PubMed

    Molanouri Shamsi, M; Mahdavi, M; Quinn, L S; Gharakhanlou, R; Isanegad, A

    2016-09-01

    Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue. PMID:27245165

  17. Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats.

    PubMed

    Molanouri Shamsi, M; Mahdavi, M; Quinn, L S; Gharakhanlou, R; Isanegad, A

    2016-09-01

    Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle. On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue.

  18. Psoriasis strikes back! Epicardial adipose tissue: another contributor to the higher cardiovascular risk in psoriasis.

    PubMed

    Raposo, Inês; Torres, Tiago

    2015-10-01

    For many years psoriasis was considered an inflammatory condition restricted to the skin. However, nowadays it is considered an immune-mediated, systemic inflammatory condition associated with numerous medical comorbidities, particularly cardiometabolic diseases, and overall cardiovascular mortality. Several studies have suggested that psoriasis may be an independent risk factor for atherosclerosis, indicating that psoriasis itself poses an intrinsic risk for cardiovascular disease, probably due to the disease's inflammatory burden. However, other causes beyond systemic inflammation and traditional cardiovascular risk factors may be implicated in cardiovascular disease in psoriasis. Recently, epicardial adipose tissue, an emerging cardiovascular risk factor, has been shown to be increased in psoriasis patients and to be associated with subclinical atherosclerosis, providing another possible link between psoriasis and atherosclerosis. The reason for the increase in epicardial adipose tissue in patients with psoriasis is unknown, but it is probably multifactorial, with genetic, immune-mediated and behavioral factors having a role. Thus, along with the increased prevalence of cardiometabolic risk factors and systemic inflammation in psoriasis, epicardial adipose tissue is probably another important contributor to the higher cardiovascular risk observed in psoriasis.

  19. Free Fatty Acid Storage in Human Visceral and Subcutaneous Adipose Tissue

    PubMed Central

    Ali, Asem H.; Koutsari, Christina; Mundi, Manpreet; Stegall, Mark D.; Heimbach, Julie K.; Taler, Sandra J.; Nygren, Jonas; Thorell, Anders; Bogachus, Lindsey D.; Turcotte, Lorraine P.; Bernlohr, David; Jensen, Michael D.

    2011-01-01

    OBJECTIVE Because direct adipose tissue free fatty acid (FFA) storage may contribute to body fat distribution, we measured FFA (palmitate) storage rates and fatty acid (FA) storage enzymes/proteins in omental and abdominal subcutaneous fat. RESEARCH DESIGN AND METHODS Elective surgery patients received a bolus of [1-14C]palmitate followed by omental and abdominal subcutaneous fat biopsies to measure direct FFA storage. Long chain acyl-CoA synthetase (ACS) and diacylglycerol acyltransferase activities, CD36, fatty acid-binding protein, and fatty acid transport protein 1 were measured. RESULTS Palmitate tracer storage (dpm/g adipose lipid) and calculated palmitate storage rates were greater in omental than abdominal subcutaneous fat in women (1.2 ± 0.8 vs. 0.7 ± 0.4 μmol ⋅ kg adipose lipid−1 ⋅ min−1, P = 0.005) and men (0.7 ± 0.2 vs. 0.2 ± 0.1, P < 0.001), and both were greater in women than men (P < 0.0001). Abdominal subcutaneous adipose tissue palmitate storage rates correlated with ACS activity (women: r = 0.66, P = 0.001; men: r = 0.70, P = 0.007); in men, CD36 was also independently related to palmitate storage rates. The content/activity of FA storage enzymes/proteins in omental fat was dramatically lower in those with more visceral fat. In women, only omental palmitate storage rates were correlated (r = 0.54, P = 0.03) with ACS activity. CONCLUSIONS Some adipocyte FA storage factors correlate with direct FFA storage, but sex differences in this process in visceral fat do not account for sex differences in visceral fatness. The reduced storage proteins in those with greater visceral fat suggest that the storage factors we measured are not a predominant cause of visceral adipose tissue accumulation. PMID:21810594

  20. Paracrine Mechanism of Angiogenesis in Adipose-derived Stem Cell Transplantation

    PubMed Central

    Suga, Hirotaka; Glotzbach, Jason P.; Sorkin, Michael; Longaker, Michael T.; Gurtner, Geoffrey C.

    2012-01-01

    Introduction Adipose-derived stem cells (ASCs) have shown potential for cell-based therapy in the field of plastic surgery. However, the fate of ASCs after transplantation and the mechanism(s) of their biologic capabilities remain unclear. Methods We isolated and cultured ASCs from transgenic mice that express both luciferase and green fluorescent protein (GFP) and injected the cells into the inguinal fat pads of wild-type mice. We tested four experimental groups: ischemic fat pads with/without ASCs and control fat pads with/without ASCs. Results Transplanted ASCs were tracked with bioluminescence imaging. The luminescence gradually decreased over 28 days, indicating cell death after transplantation. More ASCs were retained in ischemic fat pads on day 7 compared to control fat pads. On day 14, adipose tissue vascular density was higher in the ASC transplantation groups compared to those without ASCs. On day 28, there was decreased atrophy of adipose tissue in ASC-treated ischemic fat pads. Transplanted ASCs were detected as non-proliferating GFP+ cells, whereas native endothelial cells adjacent to the transplanted ASCs were proliferative. Protein analysis demonstrated higher expression of hepatocyte growth factor and vascular endothelial growth factor in the ASC transplantation groups, suggesting a paracrine mechanism, which was confirmed by in vitro experiments with conditioned media from ASCs. Conclusions Transplanted ASCs are preferentially retained in ischemic adipose tissue, although most of the cells eventually undergo cell death. They exert an angiogenic effect on adipose tissue mainly through a paracrine mechanism. Increased understanding of these effects will help develop ASCs as a tool for cell-based therapy. PMID:23636112

  1. Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion.

    PubMed

    Senol-Cosar, Ozlem; Flach, Rachel J Roth; DiStefano, Marina; Chawla, Anil; Nicoloro, Sarah; Straubhaar, Juerg; Hardy, Olga T; Noh, Hye Lim; Kim, Jason K; Wabitsch, Martin; Scherer, Philipp E; Czech, Michael P

    2016-01-01

    Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity. PMID:26880110

  2. Hdac3 Deficiency Increases Marrow Adiposity and Induces Lipid Storage and Glucocorticoid Metabolism in Osteochondroprogenitor Cells

    PubMed Central

    McGee-Lawrence, Meghan E; Carpio, Lomeli R; Schulze, Ryan J; Pierce, Jessica L; McNiven, Mark A; Farr, Joshua N; Khosla, Sundeep; Oursler, Merry Jo; Westendorf, Jennifer J

    2016-01-01

    Bone loss and increased marrow adiposity are hallmarks of aging skeletons. Conditional deletion of histone deacetylase 3 (Hdac3) in murine osteochondroprogenitor cells causes osteopenia and increases marrow adiposity, even in young animals, but the origins of the increased adiposity are unclear. To explore this, bone marrow stromal cells (BMSCs) from Hdac3-depleted and control mice were cultured in osteogenic medium. Hdac3-deficient cultures accumulated lipid droplets in greater abundance than control cultures and expressed high levels of genes related to lipid storage (Fsp27/Cidec, Plin1) and glucocorticoid metabolism (Hsd11b1) despite normal levels of Pparγ2. Approximately 5% of the lipid containing cells in the wild-type cultures expressed the master osteoblast transcription factor Runx2, but this population was threefold greater in the Hdac3-depleted cultures. Adenoviral expression of Hdac3 restored normal gene expression, indicating that Hdac3 controls glucocorticoid activation and lipid storage within osteoblast lineage cells. HDAC3 expression was reduced in bone cells from postmenopausal as compared to young women, and in osteoblasts from aged as compared to younger mice. Moreover, phosphorylation of S424 in Hdac3, a posttranslational mark necessary for deacetylase activity, was suppressed in osseous cells from old mice. Thus, concurrent declines in transcription and phosphorylation combine to suppress Hdac3 activity in aging bone, and reduced Hdac3 activity in osteochondroprogenitor cells contributes to increased marrow adiposity associated with aging. PMID:26211746

  3. Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion

    PubMed Central

    Senol-Cosar, Ozlem; Flach, Rachel J. Roth; DiStefano, Marina; Chawla, Anil; Nicoloro, Sarah; Straubhaar, Juerg; Hardy, Olga T.; Noh, Hye Lim; Kim, Jason K.; Wabitsch, Martin; Scherer, Philipp E.; Czech, Michael P.

    2016-01-01

    Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity. PMID:26880110

  4. mRNA Expression of Ovine Angiopoietin-like Protein 4 Gene in Adipose Tissues.

    PubMed

    Zhang, Jing; Jing, Jiong-Jie; Jia, Xia-Li; Qiao, Li-Ying; Liu, Jian-Hua; Liang, Chen; Liu, Wen-Zhong

    2016-05-01

    Angiopoietin-like protein 4 (ANGPTL4) is involved in a variety of functions, including lipoprotein metabolism and angiogenesis. To reveal the role of ANGPTL4 in fat metabolism of sheep, ovine ANGPTL4 mRNA expression was analyzed in seven adipose tissues from two breeds with distinct tail types. Forty-eight animals with the gender ratio of 1:1 for both Guangling Large Tailed (GLT) and Small Tailed Han (STH) sheep were slaughtered at 2, 4, 6, 8, 10, and 12 months of age, respectively. Adipose tissues were collected from greater and lesser omental, subcutaneous, retroperitoneal, perirenal, mesenteric, and tail fats. Ontogenetic mRNA expression of ANGPTL4 in these adipose tissues from GTL and STH was studied by quantitative real time polymerase chain reaction. The results showed that ANGPTL4 mRNA expressed in all adipose tissues studied with the highest in subcutaneous and the lowest in mesenteric fat depots. Months of age, tissue and breed are the main factors that significantly influence the mRNA expression. These results provide new insights into ovine ANGPTL4 gene expression and clues for its function mechanism.

  5. [Adipose tissue secretory function: implication in metabolic and cardiovascular complications of obesity].

    PubMed

    Guerre-Millo, Michèle

    2006-01-01

    The adipose tissue exerts a double function that is crucial for energy homeostasis. On the one hand, it is the only organ suited to stock triglycerides in highly specialized cells, the adipocytes. On the other hand, the adipose tissue produces biologically active molecules, collectively named "adipokines", which have been implicated in energy balance and glucose and lipid metabolism. Both adipocytes and cells of the stromal fraction participate in this function of secretion. The adipokines acts locally, in an autocrine or paracrine manner, and distantly (endocrine), on various targets, including muscles, the liver and the hypothalamus. Some adipokines, as TNFalpha and IL6, promote insulin resistance and inflammation, whereas others, as leptin and adiponectin, are required for energy and glucose homeostasis. In obesity, adipose cell hypertrophy and the recruitment of macrophages alter the secretory function and induce an inflammatory profile in the adipose tissue. Analyses of gene expression suggest that hypoxia is one of the factors favoring the attraction of the macrophages. The local and systemic consequences of interactions between macrophages and adipocytes are currently actively studied, to understand their potential implication in the metabolic and cardiovascular complications associated with obesity.

  6. HIV-1 Infection and the PPARγ-Dependent Control of Adipose Tissue Physiology

    PubMed Central

    Giralt, Marta; Domingo, Pere; Villarroya, Francesc

    2009-01-01

    PPARγ is a ligand-dependent master transcription factor controlling adipocyte differentiation as well as multiple biological processes taking place in other cells present in adipose tissue depots such as macrophages. Recent research indicates that HIV-1 infection-related events may alter adipose tissue biology through several mechanisms involving PPARγ, ranging from direct effects of HIV-1-encoded proteins on adipocytes to the promotion of a proinflammatory environment that interferes with PPARγ actions. This effect of HIV-1 on adipose tissue cells can occur even in the absence of direct infection of adipocytes, as soluble HIV-1-encoded proteins such as Vpr may enter cells and inhibit PPARγ action. Moreover, repression of PPARγ actions may relieve inhibitory pathways of HIV-1 gene transcription, thus enhancing HIV-1 effects in infected cells. HIV-1 infection-mediated interference of PPARγ-dependent pathways in adipocytes and other cells inside adipose depots such as macrophages is likely to create an altered local environment that, after antiretroviral treatment, leads to lipodystrophy in HIV-1-infected and HAART-treated patients. PMID:19081837

  7. Coordinated gene expression between skeletal muscle and intramuscular adipose tissue in growing beef cattle.

    PubMed

    Roberts, S L; Lancaster, P A; DeSilva, U; Horn, G W; Krehbiel, C R

    2015-09-01

    Previous research indicates that metabolism and fiber type of skeletal muscle is related to intramuscular lipid content. It is hypothesized that changes in skeletal muscle gene expression influence adipose tissue development. The objective of this study was to determine differences in the metabolism and intercellular signaling of skeletal muscle fibers within the same muscle group that could be responsible for the initiation of intramuscular adipose tissue development and differentiation. Longissimus dorsi muscle samples were collected from steers ( = 12; 385 d of age; 378 kg BW) grazing wheat pasture. Longissimus muscle samples were dissected under magnification and sorted into 3 categories based on visual stage of adipose tissue development: immature intramuscular adipose tissue (MM), intermediate intramuscular adipose tissue (ME), and mature intramuscular adipose tissue (MA). Additionally, muscle fibers lying adjacent to each intramuscular adipose tissue (IM) category and those not associated with IM tissue were collected and stored separately. Quantitative real-time PCR was used to determine relative fold change in genes involved in metabolism, angiogenesis, formation of extracellular matrix, and intercellular signaling pathways in both LM and IM samples. Gene expression data were analyzed using a GLM that included the fixed effect of tissue. Pearson correlation coefficients were also computed between gene expression in LM and IM tissue samples that were at the same stage of development. and γ mRNA expression were 3.56- and 1.97-fold greater ( < 0.05) in ME and MA IM compared with MM IM whereas mRNA expression was 1.43-fold less ( < 0.01) in MA IM compared with MM IM, indicating successful separation into different development categories. Genes associated with metabolism and angiogenesis in LM tissue showed no differences among stages of development. Myostatin expression did not change in LM tissue; however, expression of and mRNA decreased ( < 0.01) as IM

  8. Longitudinal displacement of the carotid wall and cardiovascular risk factors: associations with aging, adiposity, blood pressure and periodontal disease independent of cross-sectional distensibility and intima-media thickness.

    PubMed

    Zahnd, Guillaume; Vray, Didier; Sérusclat, André; Alibay, Djhianne; Bartold, Mark; Brown, Alex; Durand, Marion; Jamieson, Lisa M; Kapellas, Kostas; Maple-Brown, Louise J; O'Dea, Kerin; Moulin, Philippe; Celermajer, David S; Skilton, Michael R

    2012-10-01

    The recently discovered longitudinal displacement of the common carotid arterial wall (i.e., the motion along the same plane as the blood flow), may be associated with incident cardiovascular events and represents a novel and relevant clinical information. At present, there have only been a few studies that have been conducted to investigate this longitudinal movement. We propose here a method to assess noninvasively the wall bi-dimensional (two-dimensional [2-D], cross-sectional and longitudinal) motion and present an original approach that combines a robust speckle tracking scheme to guidance by minimal path contours segmentation. Our method is well suited to large clinical population studies as it does not necessitate strong imaging prerequisites. The aim of this study is to describe the association between the longitudinal displacement of the carotid arterial wall and cardiovascular risk factors, among which periodontal disease. Some 126 Indigenous Australians with periodontal disease, an emerging risk factor, and 27 healthy age- and sex-matched non-indigenous control subjects had high-resolution ultrasound scans of the common carotid artery. Carotid intima-media thickness and arterial wall 2-D motion were then assessed using our method in ultrasound B-mode sequences. Carotid longitudinal displacement was markedly lower in the periodontal disease group than the control group (geometric mean (IQR): 0.15 mm (0.13) vs. 0.42 mm (0.30), respectively; p < 0.0001), independent of cardiovascular risk factors, cross-sectional distensibility and carotid intima-media thickness (p < 0.0001). A multivariable model indicated that the strongest correlates of carotid longitudinal displacement in adults with periodontal disease were age (β-coefficient = -.235, p = .03), waist (β-coefficient = -.357, p = 0.001), and pulse pressure (β-coefficient = .175, p = 0.07), independent of other cardiovascular risk factors, cross-sectional distensibility and pulse wave velocity. Carotid

  9. IL-21 is a major negative regulator of IRF4-dependent lipolysis affecting Tregs in adipose tissue and systemic insulin sensitivity.

    PubMed

    Fabrizi, Marta; Marchetti, Valentina; Mavilio, Maria; Marino, Arianna; Casagrande, Viviana; Cavalera, Michele; Moreno-Navarrete, Josè Maria; Mezza, Teresa; Sorice, Gian Pio; Fiorentino, Loredana; Menghini, Rossella; Lauro, Renato; Monteleone, Giovanni; Giaccari, Andrea; Fernandez Real, José Manuel; Federici, Massimo

    2014-06-01

    Obesity elicits immune cell infiltration of adipose tissue provoking chronic low-grade inflammation. Regulatory T cells (Tregs) are specifically reduced in adipose tissue of obese animals. Since interleukin (IL)-21 plays an important role in inducing and maintaining immune-mediated chronic inflammatory processes and negatively regulates Treg differentiation/activity, we hypothesized that it could play a role in obesity-induced insulin resistance. We found IL-21 and IL-21R mRNA expression upregulated in adipose tissue of high-fat diet (HFD) wild-type (WT) mice and in stromal vascular fraction from human obese subjects in parallel to macrophage and inflammatory markers. Interestingly, a larger infiltration of Treg cells was seen in the adipose tissue of IL-21 knockout (KO) mice compared with WT animals fed both normal diet and HFD. In a context of diet-induced obesity, IL-21 KO mice, compared with WT animals, exhibited lower body weight, improved insulin sensitivity, and decreased adipose and hepatic inflammation. This metabolic phenotype is accompanied by a higher induction of interferon regulatory factor 4 (IRF4), a transcriptional regulator of fasting lipolysis in adipose tissue. Our data suggest that IL-21 exerts negative regulation on IRF4 and Treg activity, developing and maintaining adipose tissue inflammation in the obesity state.

  10. Prenatal low-protein and postnatal high-fat diets induce rapid adipose tissue growth by inducing Igf2 expression in Sprague Dawley rat offspring.

    PubMed

    Claycombe, Kate J; Uthus, Eric O; Roemmich, James N; Johnson, Luann K; Johnson, W Thomas

    2013-10-01

    Maternal low-protein diets result in lower birth weight followed by accelerated catch-up growth that is accompanied by the development of obesity and glucose intolerance in later life. Whether postnatal high-fat (HF) diets further contribute to the development of obesity and insulin resistance in offspring by affecting adipose tissue metabolism and DNA methylation is currently unknown. Obese-prone Sprague-Dawley rats were fed 8% low protein (LP) or 20% normal protein diets for 3 wk prior to conception and throughout pregnancy and lactation to investigate whether prenatal LP and postnatal HF diets affect the rate of adipose tissue growth, insulin-like growth factor 2 (Igf2) expression, and DNA methylation in male offspring. At weaning, the offspring were fed 10% normal fat or 45% HF diets for 12 wk. The adipose tissue growth rate was increased (up to 26-fold) by the LP prenatal and HF postnatal diets. Adipose tissue Igf2 mRNAs and DNA methylation were increased by the LP prenatal and HF postnatal diets. The LP prenatal and HF postnatal diet increased the number of small adipocytes in adipose tissue and decreased insulin sensitivity. These findings suggest that prenatal LP and postnatal HF intake result in adipose tissue catch-up growth through alterations in the expression of the Igf2 gene and DNA methylation within adipocytes. These alterations in adiposity are accompanied by an increased risk of development of type 2 diabetes.

  11. Quantitative relationship between the octanol/water partition coefficient and the diffusion limitation of the exchange between adipose and blood

    PubMed Central

    2010-01-01

    Background The goal of physiologically based pharmacokinetics (PBPK) is to predict drug kinetics from an understanding of the organ/blood exchange. The standard approach is to assume that the organ is "flow limited" which means that the venous blood leaving the organ equilibrates with the well-stirred tissue compartment. Although this assumption is valid for most solutes, it has been shown to be incorrect for several very highly fat soluble compounds which appear to be "diffusion limited". This paper describes the physical basis of this adipose diffusion limitation and its quantitative dependence on the blood/water (Kbld-wat) and octanol/water (Kow) partition coefficient. Methods Experimental measurements of the time dependent rat blood and adipose concentration following either intravenous or oral input were used to estimate the "apparent" adipose perfusion rate (FA) assuming that the tissue is flow limited. It is shown that the ratio of FA to the anatomic perfusion rate (F) provides a measure of the diffusion limitation. A quantitative relationship between this diffusion limitation and Kbld-wat and Kow is derived. This analysis was applied to previously published data, including the Oberg et. al. measurements of the rat plasma and adipose tissue concentration following an oral dose of a mixture of 13 different polychlorinated biphenyls. Results Solutes become diffusion limited at values of log Kow greater than about 5.6, with the adipose-blood exchange rate reduced by a factor of about 30 for a solute with a log Kow of 7.36. Quantitatively, a plot of FA/F versus Kow is well described assuming an adipose permeability-surface area product (PS) of 750/min. This PS corresponds to a 0.14 micron aqueous layer separating the well-stirred blood from the adipose lipid. This is approximately equal to the thickness of the rat adipose capillary endothelium. Conclusions These results can be used to quantitate the adipose-blood diffusion limitation as a function of Kow. This

  12. The adjuvant use of stromal vascular fraction and platelet-rich fibrin for autologous adipose tissue transplantation.

    PubMed

    Liu, Bin; Tan, Xin-Ying; Liu, Yan-Pu; Xu, Xiao-Fang; Li, Long; Xu, Hai-Yan; An, Ran; Chen, Fa-Ming

    2013-01-01

    Autologous adipose transplantation is rapidly gaining popularity for the restoration of soft tissue defects and lipoatrophy as well as for aesthetic improvements (e.g., facial reconstruction and rejuvenation). However, the current technique is crude that suffers from serious demerits, particularly the long-term unpredictability of volume maintenance due to resorption of the grafted adipose tissue and limited adipogenesis. We hypothesized that the adjuvant use of patient-derived adipose stromal vascular fraction (SVF) and platelet-rich fibrin (PRF) may enhance the overall outcome of autologous fat grafting in plastic and reconstructive surgery. Autologous SVF, with a mean cell number of (4.8±3.79)×10⁷ cells/mL and a mean cell viability of 71.8%, and autologous PRF, with sustained release of multiple angiogenic growth factors, were created before surgical use. The following adipose tissue implants were injected subcutaneously into a rabbit ear's auricula according to the following study design: 2 mL adipose granules and 0.2 mL normal saline solution (AG+NS group), 2 mL adipose granules and 0.2 mL SVF (AG+SVF group), 2 mL adipose granules and 0.2 mL PRF (AG+PRF group), or 2 mL adipose granules combined with 0.1 mL SVF and 0.1 mL PRF (AG+SVF+PRF group). Histological examinations showed that the implanted adipose granules were well engrafted in the AG+SVF+PRF group, with a higher microvessel density 4 weeks postimplantation compared with the other three groups (p<0.01). Twenty-four weeks postimplantation, the resorption rates of implanted tissue in each group were 49.39%±9.47%, 27.25%±4.37%, 36.41%±8.47%, and 17.37%±6.22%, respectively, and were significantly different (p<0.01). The results demonstrated that the efficacy of adipose tissue implantation can be enhanced by using autologous PRF and SVF as therapeutic adjuvants, offering a clinically translatable strategy for soft tissue augmentation and reconstruction.

  13. Relationships between Rodent White Adipose Fat Pads and Human White Adipose Fat Depots

    PubMed Central

    Chusyd, Daniella E.; Wang, Donghai; Huffman, Derek M.; Nagy, Tim R.

    2016-01-01

    The objective of this review was to compare and contrast the physiological and metabolic profiles of rodent white adipose fat pads with white adipose fat depots in humans. Human fat distribution and its metabolic consequences have received extensive attention, but much of what has been tested in translational research has relied heavily on rodents. Unfortunately, the validity of using rodent fat pads as a model of human adiposity has received less attention. There is a surprisingly lack of studies demonstrating an analogous relationship between rodent and human adiposity on obesity-related comorbidities. Therefore, we aimed to compare known similarities and disparities in terms of white adipose tissue (WAT) development and distribution, sexual dimorphism, weight loss, adipokine secretion, and aging. While the literature supports the notion that many similarities exist between rodents and humans, notable differences emerge related to fat deposition and function of WAT. Thus, further research is warranted to more carefully define the strengths and limitations of rodent WAT as a model for humans, with a particular emphasis on comparable fat depots, such as mesenteric fat. PMID:27148535

  14. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    PubMed

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  15. Intrauterine Programming of Diabetes and Adiposity.

    PubMed

    Tomar, Ashutosh Singh; Tallapragada, Divya Sri Priyanka; Nongmaithem, Suraj Singh; Shrestha, Smeeta; Yajnik, Chittaranjan S; Chandak, Giriraj Ratan

    2015-12-01

    The prevalence of diabetes and adiposity has increased at an alarming rate and together they contribute to the rise in morbidity and mortality worldwide. Genetic studies till date have succeeded in explaining only a proportion of heritability, while a major component remains unexplained. Early life determinants of future risk of these diseases are likely contributors to the missing heritability and thus have a significant potential in disease prevention. Epidemiological and animal studies show the importance of intrauterine and early postnatal environment in programming of the fetus to adverse metabolic outcomes and support the notion of Developmental Origins of Health and Disease (DOHaD). Emerging evidence highlights the role of epigenetic mechanisms in mediating effects of environmental exposures, which in certain instances may exhibit intergenerational transmission even in the absence of exposure. In this article, we will discuss the complexity of diabetes and increased adiposity and mechanisms of programming of these adverse metabolic conditions.

  16. [Cancer cachexia and white adipose tissue browning].

    PubMed

    Zhang, S T; Yang, H M

    2016-08-01

    Cancer cachexia occurs in a majority of advanced cancer patients. These patients with impaired physical function are unable to tolerance cancer treatment well and have a significantly reduced survival rate. Currently, there is no effective clinical treatment available for cancer cachexia, therefore, it is necessary to clarify the molecular mechanisms of cancer cachexia, moreover, new therapeutic targets for cancer cachexia treatment are urgently needed. Very recent studies suggest that, during cancer cachexia, white adipose tissue undergo a 'browning' process, resulting in increased lipid mobilization and energy expenditure, which may be necessary for the occurrence of cancer cachexia. In this article, we summarize the definition and characteristics of cancer cachexia and adipose tissue 'browning', then, we discuss the new study directions presented in latest research. PMID:27531474

  17. Intrauterine Programming of Diabetes and Adiposity.

    PubMed

    Tomar, Ashutosh Singh; Tallapragada, Divya Sri Priyanka; Nongmaithem, Suraj Singh; Shrestha, Smeeta; Yajnik, Chittaranjan S; Chandak, Giriraj Ratan

    2015-12-01

    The prevalence of diabetes and adiposity has increased at an alarming rate and together they contribute to the rise in morbidity and mortality worldwide. Genetic studies till date have succeeded in explaining only a proportion of heritability, while a major component remains unexplained. Early life determinants of future risk of these diseases are likely contributors to the missing heritability and thus have a significant potential in disease prevention. Epidemiological and animal studies show the importance of intrauterine and early postnatal environment in programming of the fetus to adverse metabolic outcomes and support the notion of Developmental Origins of Health and Disease (DOHaD). Emerging evidence highlights the role of epigenetic mechanisms in mediating effects of environmental exposures, which in certain instances may exhibit intergenerational transmission even in the absence of exposure. In this article, we will discuss the complexity of diabetes and increased adiposity and mechanisms of programming of these adverse metabolic conditions. PMID:26349437

  18. Iron homeostasis: a new job for macrophages in adipose tissue?

    PubMed

    Hubler, Merla J; Peterson, Kristin R; Hasty, Alyssa H

    2015-02-01

    Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron-handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity.

  19. Iron homeostasis: a new job for macrophages in adipose tissue?

    PubMed Central

    Hubler, Merla J.; Peterson, Kristin R.; Hasty, Alyssa H.

    2015-01-01

    Elevated serum ferritin and increased cellular iron concentrations are risk factors for diabetes; however, the etiology of this association is unclear. Metabolic tissues such as pancreas, liver, and adipose tissue (AT), as well as the immune cells resident in these tissues, may be involved. Recent studies demonstrate that the polarization status of macrophages has important relevance to their iron handling capabilities. Furthermore, a subset of macrophages in AT have elevated iron concentrations and a gene expression profile indicative of iron handling, a capacity diminished in obesity. Because iron overload in adipocytes increases systemic insulin resistance, iron handling by AT macrophages may have relevance not only to adipocyte iron stores but also to local and systemic insulin sensitivity. PMID:25600948

  20. Adipose tissue macrophages in insulin-resistant subjects are associated with collagen VI and fibrosis and demonstrate alternative activation.

    PubMed

    Spencer, Michael; Yao-Borengasser, Aiwei; Unal, Resat; Rasouli, Neda; Gurley, Catherine M; Zhu, Beibei; Peterson, Charlotte A; Kern, Philip A

    2010-12-01

    Adipose tissue macrophages are associated with insulin resistance and are linked to changes in the extracellular matrix. To better characterize adipose macrophages, the extracellular matrix, and adipocyte-macrophage interactions, gene expression from adipose tissue and the stromal vascular fraction was assessed for markers of inflammation and fibrosis, and macrophages from obese and lean subjects were counted and characterized immunohistochemically. Coculture experiments examined the effects of adipocyte-macrophage interaction. Collagen VI gene expression was associated with insulin sensitivity and CD68 (r = -0.56 and 0.60, P < 0.0001) and with other markers of inflammation and fibrosis. Compared with adipose tissue from lean subjects, adipose tissue from obese subjects contained increased areas of fibrosis, which correlated inversely with insulin sensitivity (r = -0.58, P < 0.02) and positively with macrophage number (r = 0.70, P < 0.01). Although macrophages in crownlike structures (CLS) were more abundant in obese adipose tissue, the majority of macrophages were associated with fibrosis and were not organized in CLS. Macrophages in CLS were predominantly M1, but most other macrophages, particularly those in fibrotic areas, were M2 and also expressed CD150, a marker of M2c macrophages. Coculture of THP-1 macrophages with adipocytes promoted the M2 phenotype, with a lower level of IL-1 expression and a higher ratio of IL-10 to IL-12. Transforming growth factor-β (TGF-β) was more abundant in M2 macrophages and was further increased by coculture with adipocytes. Downstream effectors of TGF-β, such as plasminogen activator inhibitor-1, collagen VI, and phosphorylated Smad, were increased in macrophages and adipocytes. Thus adipose tissue of insulin-resistant humans demonstrated increased fibrosis, M2 macrophage abundance, and TGF-β activity.

  1. Increased GIP signaling induces adipose inflammation via a HIF-1α-dependent pathway and impairs insulin sensitivity in mice.

    PubMed

    Chen, Shu; Okahara, Fumiaki; Osaki, Noriko; Shimotoyodome, Akira

    2015-03-01

    Glucose-dependent insulinotropic polypeptide (GIP) is a gut hormone secreted in response to dietary fat and glucose. The blood GIP level is elevated in obesity and diabetes. GIP stimulates proinflammatory gene expression and impairs insulin sensitivity in cultured adipocytes. In obesity, hypoxia within adipose tissue can induce inflammation. The aims of this study were 1) to examine the proinflammatory effect of increased GIP signaling in adipose tissues in vivo and 2) to clarify the association between GIP and hypoxic signaling in adipose tissue inflammation. We administered GIP intraperitoneally to misty (lean) and db/db (obese) mice and examined adipose tissue inflammation and insulin sensitivity. We also examined the effects of GIP and hypoxia on expression of the GIP receptor (GIPR) gene and proinflammatory genes in 3T3-L1 adipocytes. GIP administration increased monocyte chemoattractant protein-1 (MCP-1) expression and macrophage infiltration into adipose tissue and increased blood glucose in db/db mice. GIPR and hypoxia-inducible factor-1α (HIF-1α) expressions were positively correlated in the adipose tissue in mice. GIPR expression increased dramatically in differentiated adipocytes. GIP treatment of adipocytes increased MCP-1 and interleukin-6 (IL-6) production. Adipocytes cultured either with RAW 264 macrophages or under hypoxia expressed more GIPR and HIF-1α, and GIP treatment increased gene expression of plasminogen activator inhibitor 1 and IL-6. HIF-1α gene silencing diminished both macrophage- and hypoxia-induced GIPR expression and GIP-induced IL-6 expression in adipocytes. Thus, increased GIP signaling plays a significant role in adipose tissue inflammation and thereby insulin resistance in obese mice, and HIF-1α may contribute to this process. PMID:25537494

  2. Poor sleep quality potentiates stress-induced cytokine reactivity in postmenopausal women with high visceral abdominal adiposity.

    PubMed

    Prather, Aric A; Puterman, Eli; Epel, Elissa S; Dhabhar, Firdaus S

    2014-01-01

    Sleep disturbance is a key behavioral risk factor for chronic medical conditions observed at high rates among overweight and obese individuals. Systemic inflammation, including that induced by stress, may serve as a common biological mechanism linking sleep, adiposity, and disease risk. To investigate these relationships, 48 postmenopausal women (mean age=61.8) completed a standardized laboratory stress task during which time blood was collected at baseline and 30, 50 and 90+ min after stressor onset to assess circulating levels of interleukin (IL)-6, IL-10, and IL-6/IL-10 ratio. Self-reported global sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) while adiposity was estimated by body mass index. Sagittal diameter was obtained in clinic to estimate visceral abdominal adiposity. Multi-level growth curve models revealed that poorer self-reported sleep quality was associated with greater stress-induced increases in IL-6/IL-10 ratio. In terms of adiposity, higher sagittal diameter, but not BMI, was associated with greater IL-6 reactivity (p's<0.05). Further, associations between sleep quality and cytokine reactivity varied as a function of sagittal diameter. Among poor sleepers (1 SD above mean of PSQI score), stress-induced increases in IL-6 and IL-6/IL-10 ratio were significantly steeper in those with high visceral adiposity (1 SD above the mean of sagittal diameter) compared to those with low visceral adiposity (1 SD below the mean of sagittal diameter). In sum, poorer sleep quality and greater visceral adiposity, separately and especially in combination, are associated with greater stress-related increases in systemic inflammation. This research may help elucidate the complex link between sleep, obesity and inflammatory disease risk. PMID:24060585

  3. Aquaglyceroporins: implications in adipose biology and obesity.

    PubMed

    Madeira, Ana; Moura, Teresa F; Soveral, Graça

    2015-02-01

    Aquaporins (AQPs) are membrane water/glycerol channels that are involved in many physiological processes. Their primary function is to facilitate the bidirectional transfer of water and small solutes across biological membranes in response to osmotic gradients. Aquaglyceroporins, a subset of the AQP family, are the only mammalian proteins with the ability to permeate glycerol. For a long time, AQP7 has been the only aquaglyceroporin associated with the adipose tissue, which is the major source of circulating glycerol in response to the energy demand. AQP7 dysregulation was positively correlated with obesity onset and adipocyte glycerol permeation through AQP7 was appointed as a novel regulator of adipocyte metabolism and whole-body fat mass. Recently, AQP3, AQP9, AQP10 and AQP11 were additionally identified in human adipocytes and proposed as additional glycerol pathways in these cells. This review contextualizes the importance of aquaglyceroporins in adipose tissue biology and highlights aquaglyceroporins' unique structural features which are relevant for the design of effective therapeutic compounds. We also refer to the latest advances in the identification and characterization of novel aquaporin isoforms in adipose tissue. Finally, considerations on the actual progress of aquaporin research and its implications on obesity therapy are suggested. PMID:25359234

  4. Increased Adipose Protein Carbonylation in Human Obesity

    PubMed Central

    Frohnert, Brigitte I.; Sinaiko, Alan R.; Serrot, Federico J.; Foncea, Rocio E.; Moran, Antoinette; Ikramuddin, Sayeed; Choudry, Umar; Bernlohr, David A.

    2015-01-01

    Insulin resistance is associated with obesity but mechanisms controlling this relationship in humans are not fully understood. Studies in animal models suggest a linkage between adipose reactive oxygen species (ROS) and insulin resistance. ROS oxidize cellular lipids to produce a variety of lipid hydroperoxides that in turn generate reactive lipid aldehydes that covalently modify cellular proteins in a process termed carbonylation. Mammalian cells defend against reactive lipid aldehydes and protein carbonylation by glutathionylation using glutathione-S-transferase A4 (GSTA4) or carbonyl reduction/oxidation via reductases and/or dehydrogenases. Insulin resistance in mice is linked to ROS production and increased level of protein carbonylation, mitochondrial dysfunction, decreased insulin-stimulated glucose transport, and altered adipokine secretion. To assess protein carbonylation and insulin resistance in humans, eight healthy participants underwent subcutaneous fat biopsy from the periumbilical region for protein analysis and frequently sampled intravenous glucose tolerance testing to measure insulin sensitivity. Soluble proteins from adipose tissue were analyzed using two-dimensional gel electrophoresis and the major carbonylated proteins identified as the adipocyte and epithelial fatty acid–binding proteins. The level of protein carbonylation was directly correlated with adiposity and serum free fatty acids (FFAs). These results suggest that in human obesity oxidative stress is linked to protein carbonylation and such events may contribute to the development of insulin resistance. PMID:21593812

  5. Adipose stromal cells-secreted neuroprotective media against neuronal apoptosis.

    PubMed

    Wei, X; Zhao, L; Zhong, J; Gu, H; Feng, D; Johnstone, B H; March, K L; Farlow, M R; Du, Y

    2009-10-01

    Transplantation of pluripotent adipose stem/stromal cells (ASC) alleviates tissue damage and improves functional deficits in both stroke and cardiovascular disease animal models. Recent studies indicate that the primary mechanism of ASC-induced repair may not be directly related to tissue regeneration through differentiation, but rather through paracrine mechanisms provided by secreted pro-survival and repair-inducing trophic factors. In this study, we have found that ASC-conditioned medium (ASC-CM) potently protected cerebellar granule neurons (CGN) from apoptosis induced by serum and potassium deprivation. Neural cell protection was mostly attributable to activated caspase-3 and Akt-mediated neuroprotective pathway signaling. Specific neutralization of neurotrophic factor activity demonstrated that serum and potassium deprivation-induced Akt-mediated neuroprotection and caspase-3-dependent apoptosis were mainly modulated by IGF-1. These data suggest that of the many neuroprotective factors secreted by ASC, IGF-1 is the major factor that mediates protection against serum and potassium deprivation-induced CGN apoptosis. This study establishes a mechanistic basis supporting the therapeutic application of ASC for neurological disorders, specifically through paracrine support provided by trophic factor secretion. PMID:19549558

  6. Adipose-derived stem cell differentiation as a basic tool for vascularized adipose tissue engineering.

    PubMed

    Volz, Ann-Cathrin; Huber, Birgit; Kluger, Petra J

    2016-01-01

    The development of in vitro adipose tissue constructs is highly desired to cope with the increased demand for substitutes to replace damaged soft tissue after high graded burns, deformities or tumor removal. To achieve clinically relevant dimensions, vascularization of soft tissue constructs becomes inevitable but still poses a challenge. Adipose-derived stem cells (ASCs) represent a promising cell source for the setup of vascularized fatty tissue constructs as they can be differentiated into adipocytes and endothelial cells in vitro and are thereby available in sufficiently high cell numbers. This review summarizes the currently known characteristics of ASCs and achievements in adipogenic and endothelial differentiation in vitro. Further, the interdependency of adipogenesis and angiogenesis based on the crosstalk of endothelial cells, stem cells and adipocytes is addressed at the molecular level. Finally, achievements and limitations of current co-culture conditions for the construction of vascularized adipose tissue are evaluated. PMID:26976717

  7. Abalation of ghrelin receptor reduces adiposity and improves insulin sensitivity during aging by regulating fat metabolism in white and brown adipose tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Aging is associated with increased adiposity in white adipose tissues and impaired thermogenesis in brown adipose tissues; both contribute to increased incidences of obesity and type 2 diabetes. Ghrelin is the only known circulating orexigenic hormone that promotes adiposity. In this study, we show ...

  8. Undernutrition and stage of gestation influence fetal adipose tissue gene expression

    PubMed Central

    Wallace, Jacqueline M.; Milne, John S.; Aitken, Raymond P.; Redmer, Dale A.; Reynolds, Lawrence P.; Luther, Justin S.; Horgan, GW; Adam, Clare L.

    2015-01-01

    Low birthweight is a risk factor for neonatal mortality and adverse metabolic health, both associated with inadequate prenatal adipose tissue development. Here we investigated the impact of maternal undernutrition on expression of genes regulating fetal perirenal adipose tissue (PAT) development and function at gestation days 89 and 130 (term=145d). Singleton fetuses were taken from adolescent ewes fed control (C) intake to maintain adiposity throughout pregnancy or undernourished (UN) to maintain conception weight but deplete maternal reserves (n=7/group). Fetal weight was independent of maternal intake at day 89 but by day 130 fetuses from UN dams were 17% lighter with lower PAT mass containing fewer unilocular adipocytes. Relative PAT expression of IGF1, IGF2, IGF2R and peroxisome-proliferator-activated receptor-gamma (PPARG) mRNA was lower in UN than in C, predominantly at day 89. Independent of maternal nutrition, PAT gene expression of PPARG, glycerol-3-phosphate dehydrogenase, hormone sensitive lipase, leptin, uncoupling protein-1 and prolactin receptor increased and IGF1, IGF2, IGF1R, IGF2R decreased between 89 and 130 days. Fatty acid synthase and lipoprotein lipase (LPL) mRNAs were not influenced by nutrition or stage of pregnancy. Females had greater LPL and leptin mRNA than males, and LPL, leptin and PPARG mRNAs were decreased by UN at day 89 in females only. PAT gene expression correlations with PAT mass were stronger at day 89 than day 130. These data suggest that key genes regulating adipose tissue development and function are active from mid-gestation when they are sensitive to maternal undernutrition. This leads to reduced fetal adiposity by late pregnancy. PMID:25917833

  9. A pilot study of sampling subcutaneous adipose tissue to examine biomarkers of cancer risk.

    PubMed

    Campbell, Kristin L; Makar, Karen W; Kratz, Mario; Foster-Schubert, Karen E; McTiernan, Anne; Ulrich, Cornelia M

    2009-01-01

    Examination of adipose tissue biology may provide important insight into mechanistic links for the observed association between higher body fat and risk of several types of cancer, in particular colorectal and breast cancer. We tested two different methods of obtaining adipose tissue from healthy individuals. Ten overweight or obese (body mass index, 25-40 kg/m(2)), postmenopausal women were recruited. Two subcutaneous abdominal adipose tissue samples were obtained per individual (i.e., right and left lower abdominal regions) using two distinct methods (method A: 14-gauge needle with incision, versus method B: 16-gauge needle without incision). Gene expression was examined at the mRNA level for leptin, adiponectin, aromatase, interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in flash-frozen tissue, and at the protein level for leptin, adiponectin, IL-6, and TNF-alpha following short-term culture. Participants preferred biopsy method A and few participants reported any of the usual minor side effects. Gene expression was detectable for leptin, adiponectin, and aromatase, but was below detectable limits for IL-6 and TNF-alpha. For detectable genes, relative gene expression in adipose tissue obtained by methods A and B was similar for adiponectin (r = 0.64, P = 0.06) and leptin (r = 0.80, P = 0.01), but not for aromatase (r = 0.37,P = 0.34). Protein levels in tissue culture supernatant exhibited good intra-assay agreement [coefficient of variation (CV), 1-10%], with less agreement for intraindividual agreement (CV, 17-29%) and reproducibility, following one freeze-thaw cycle (CV, >14%). Subcutaneous adipose tissue biopsies from healthy, overweight individuals provide adequate amounts for RNA extraction, gene expression, and other assays of relevance to cancer prevention research. PMID:19139016

  10. Myostatin Inhibition in Muscle, but Not Adipose Tissue, Decreases Fat Mass and Improves Insulin Sensitivity

    PubMed Central

    Guo, Tingqing; Jou, William; Chanturiya, Tatyana; Portas, Jennifer; Gavrilova, Oksana; McPherron, Alexandra C.

    2009-01-01

    Myostatin (Mstn) is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn−/− mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn−/− mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn−/− mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn−/− mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn−/− mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn−/− mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes. PMID:19295913

  11. Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue.

    PubMed

    Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta

    2016-03-22

    Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3's expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids.

  12. Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning.

    PubMed

    Bartelt, Alexander; Weigelt, Clara; Cherradi, M Lisa; Niemeier, Andreas; Tödter, Klaus; Heeren, Joerg; Scheja, Ludger

    2013-05-01

    Efficient storage of dietary and endogenous fatty acids is a prerequisite for a healthy adipose tissue function. Lipoprotein lipase (LPL) is the master regulator of fatty acid uptake from triglyceride-rich lipoproteins. In addition to LPL-mediated fatty acid uptake, adipocytes are able to synthesize fatty acids from non-lipid precursor, a process called de novo lipogenesis (DNL). As the physiological relevance of fatty acid uptake versus DNL for brown and white adipocyte function remains unclear, we studied the role of adipocyte LPL using adipocyte-specific LPL knockout animals (aLKO). ALKO mice displayed a profound increase in DNL-fatty acids, especially palmitoleate and myristoleate in brown adipose tissue (BAT) and white adipose tissue (WAT) depots while essential dietary fatty acids were markedly decreased. Consequently, we found increased expression in adipose tissues of genes encoding DNL enzymes (Fasn, Scd1, and Elovl6) as well as the lipogenic transcription factor carbohydrate response element binding protein-β. In a high-fat diet (HFD) study aLKO mice were characterized by reduced adiposity and improved plasma insulin and adipokines. However, neither glucose tolerance nor inflammatory markers were ameliorated in aLKO mice compared to controls. No signs of increased BAT activation or WAT browning were detected in aLKO mice either on HFD or after 1 week of β3-adrenergic stimulation using CL316,243. We conclude that despite a profound increase in DNL-derived fatty acids, proposed to be metabolically favorable, aLKO mice are not protected from metabolic disease per se. In addition, induction of DNL alone is not sufficient to promote browning of WAT. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  13. Efficient Targeting of Adipose Tissue Macrophages in Obesity with Polysaccharide Nanocarriers.

    PubMed

    Ma, Liang; Liu, Tzu-Wen; Wallig, Matthew A; Dobrucki, Iwona T; Dobrucki, Lawrence W; Nelson, Erik R; Swanson, Kelly S; Smith, Andrew M

    2016-07-26

    Obesity leads to an increased risk for type 2 diabetes, heart disease, stroke, and cancer. The causal link between obesity and these pathologies has recently been identified as chronic low-grade systemic inflammation initiated by pro-inflammatory macrophages in visceral adipose tissue. Current medications based on small-molecule drugs yield significant off-target side effects with long-term use, and therefore there is a major need for targeted therapies. Here we report that nanoscale polysaccharides based on biocompatible glucose polymers can efficiently target adipose macrophages in obese mice. We synthesized a series of dextran conjugates with tunable size linked to contrast agents for positron emission tomography, fluorophores for optical microscopy, and anti-inflammatory drugs for therapeutic modulation of macrophage phenotype. We observed that larger conjugates efficiently distribute to visceral adipose tissue and selectively associate with macrophages after regional peritoneal administration. Up to 63% of the injected dose remained in visceral adipose tissue 24 h after administration, resulting in >2-fold higher local concentration compared to liver, the dominant site of uptake for most nanomedicines. Furthermore, a single-dose treatment of anti-inflammatory conjugates significantly reduced pro-inflammatory markers in adipose tissue of obese mice. Importantly, all components of these therapeutic agents are approved for clinical use. This work provides a promising nanomaterials-based delivery strategy to inhibit critical factors leading to obesity comorbidities and demonstrates a unique transport mechanism for drug delivery to visceral tissues. This approach may be further applied for high-efficiency targeting of other inflammatory diseases of visceral organs. PMID:27281538

  14. Characterization of major elements of insulin signaling cascade in chicken adipose tissue: apparent insulin refractoriness.

    PubMed

    Dupont, Joëlle; Métayer-Coustard, Sonia; Ji, Bo; Ramé, Christelle; Gespach, Christian; Voy, Brynn; Simon, Jean

    2012-03-01

    The role of insulin in chicken adipose tissue appears weak or questionable. In a first study, proximal and distal components of the insulin signaling cascade were characterized in abdominal adipose tissue of fasted or fed chickens for the first time. Similar measurements were performed on epididymal adipose tissue from fasted or fed rats for comparison. Tyrosine phosphorylation of IR beta subunit, IRS-1 and Shc and phosphorylation of downstream components (Akt and MAPK ERK1/2) were significantly reduced as expected by fasting in rat, but not in chicken. Phosphorylation of MAPK P38 was increased by fasting in chicken but not in rat. Phosphorylation of AMPK was not affected in the conditions investigated in either species. Whatever the nutritional state, the protein levels of IR and IRS-1 were lower in chicken than in rat, whereas those of Shc, Akt, AMPK, MAPK ERK2 and MAPK P38 were similar in both species. In fed state, PI3K activity was higher in chicken than in rat. Insulin sensitivity of insulin cascade was further investigated in chicken adipose tissue following in vivo insulin neutralization for 1 or 5h in fed chickens. Insulin privation did not alter early insulin signaling steps (IRβ, IRS-1 and Shc) or downstream elements (Akt, P70S6K, S6 ribosomal protein, AMPK, MAPK ERK2 and MAPK P38). Finally, phosphorylation of the transcription factor Creb was increased by 2-fold by 5h fasting or 5h insulin privation, most likely in response to an increase in plasma glucagon levels. Thus, insulin signaling is markedly different in chicken abdominal adipose tissue from that operating in mammals making chicken an interesting model of insulin resistance or refractoriness. PMID:22233773

  15. Lack of soluble fiber drives diet-induced adiposity in mice

    PubMed Central

    Chassaing, Benoit; Miles-Brown, Jennifer; Pellizzon, Michael; Ulman, Edward; Ricci, Matthew; Zhang, Limin; Patterson, Andrew D.; Vijay-Kumar, Matam

    2015-01-01

    Diet-induced obesity is often modeled by comparing mice fed high-fat diet (HFD), which is made from purified ingredients, vs. normal chow diet (NCD), which is a low-fat assemblage of relatively unrefined plant and animal products. The mechanism by which HFD promotes adiposity is complex but thought to involve low-grade inflammation and altered gut microbiota. The goal of this study was to investigate the extent to which HFD-induced adiposity is driven by fat content vs. other factors that differentiate HFD vs. NCD. Mice were fed NCD, HFD, or other compositionally defined diets (CDD), designed to mimic NCD and/or explore the role of HFD components. A range of metabolic parameters reflecting low-grade inflammation and adiposity were assayed. Relative to NCD, HFD, and to a lesser, but, nonetheless, significant extent, CDD induced increased adiposity, indicating both lipid content and other aspects of HFD are obesogenic. Moreover, HFD and CDD induced a rapid and marked loss of cecal and colonic mass. Such CDD-induced effects were not affected by adjusting dietary protein levels/types but could be largely eliminated by exchanging insoluble fiber (cellulose) for soluble fiber (inulin). Replacing cellulose with inulin in HFD also protected mice against decreased intestinal mass, hyperphagia, and increased adiposity. Such beneficial effects of inulin were microbiota dependent, correlated with elevated fecal short-chain fatty acid levels analyzed via 1H-NMR-based metabolomics and were partially recapitulated by administration of short-chain fatty acid. HFD-induced obesity is strongly promoted by its lack of soluble fiber, which supports microbiota-mediated intestinal tissue homeostasis that prevents inflammation driving obesity and metabolic syndrome. PMID:26185332

  16. Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue

    PubMed Central

    Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta

    2016-01-01

    Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3’s expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids. PMID:26957608

  17. Adipose tissue and its role in organ crosstalk.

    PubMed

    Romacho, T; Elsen, M; Röhrborn, D; Eckel, J

    2014-04-01

    The discovery of adipokines has revealed adipose tissue as a central node in the interorgan crosstalk network, which mediates the regulation of multiple organs and tissues. Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes, and cardiovascular diseases. Besides the well-acknowledged role of adipokines in metabolic diseases, and the increasing number of adipokines being discovered in the last years, the mechanisms underlying the release of many adipokines from adipose tissue remain largely unknown. To combat metabolic diseases, it is crucial to better understand how adipokines can modulate adipose tissue growth and function. Therefore, we will focus on adipokines with a prominent role in auto-/paracrine crosstalk within the adipose tissue such as RBP4, HO-1, WISP2, SFRPs and chemerin. To depict the endocrine crosstalk between adipose tissue with skeletal muscle, the cardiovascular system and the pancreas, we will report the main findings regarding the direct effects of adiponectin, leptin, DPP4 and visfatin on skeletal muscle insulin resistance, cardiovascular function and β-cell growth and function.

  18. Adipose tissue-derived cells: from physiology to regenerative medicine.

    PubMed

    Casteilla, L; Dani, C

    2006-11-01

    During the last past years, the importance and the role of adipose tissues have been greatly expanded. After finding that adipose tissues are metabolically very active, the discovery of leptin moved the status of adipose tissue towards an endocrine tissue able to interact with all major organs via secretion of adipokines. Some years ago, the presence of adipocyte precursors, termed preadipocytes, has been described in all adipose tissue depots from various species of different age. More recently, the discovery that different phenotypes can be obtained from stroma cells of adipose tissue has largely emphazised the concept of adipose tissue plasticity. Therefore, raising great hope in regenerative medicine as adipose tissue can be easily harvested in adults it could represent an abundant source of therapeutic cells. Thus, adipose tissue plays the dual role of Mr Obese Hyde as a main actor of obesity and of Dr Regenerative Jekyll as a source of therapeutic cells. Adipose tissue has not yet revealed all its mysteries although one facet could not be well understood without the other one. PMID:17110894

  19. Associations of Adiponectin with Adiposity, Insulin Sensitivity, and Diet in Young, Healthy, Mexican Americans and Non-Latino White Adults.

    PubMed

    Pereira, Rocio I; Low Wang, Cecilia C; Wolfe, Pamela; Havranek, Edward P; Long, Carlin S; Bessesen, Daniel H

    2015-12-22

    Low circulating adiponectin levels may contribute to higher diabetes risk among Mexican Americans (MA) compared to non-Latino whites (NLW). Our objective was to determine if among young healthy adult MAs have lower adiponectin than NLWs, independent of differences in adiposity. In addition, we explored associations between adiponectin and diet. This was an observational, cross-sectional study of healthy MA and NLW adults living in Colorado (U.S.A.). We measured plasma total adiponectin, adiposity (BMI, and visceral adipose tissue), insulin sensitivity (IVGTT), and self-reported dietary intake in 43 MA and NLW adults. Mean adiponectin levels were 40% lower among MA than NLW (5.8 ± 3.3 vs. 10.7 ± 4.2 µg/mL, p = 0.0003), and this difference persisted after controlling for age, sex, BMI, and visceral adiposity. Lower adiponectin in MA was associated with lower insulin sensitivity (R² = 0.42, p < 0.01). Lower adiponectin was also associated with higher dietary glycemic index, lower intake of vegetables, higher intake of trans fat, and higher intake of grains. Our findings confirm that ethnic differences in adiponectin reflect differences in insulin sensitivity, but suggest that these are not due to differences in adiposity. Observed associations between adiponectin and diet support the need for future studies exploring the regulation of adiponectin by diet and other environmental factors.

  20. Comparison of Stromal/Stem Cells Isolated from Human Omental and Subcutaneous Adipose Depots: Differentiation and Immunophenotypic Characterization.

    PubMed

    Shah, Forum S; Li, Jie; Dietrich, Marilyn; Wu, Xiying; Hausmann, Mark G; LeBlanc, Karl A; Wade, James W; Gimble, Jeffrey M

    2014-01-01

    The emerging field of regenerative medicine has identified adipose tissue as an abundant source of stromal/stem cells for tissue engineering applications. Therefore, we have compared the differentiation and immunophenotypic features of adipose-derived stromal/stem cells (ASC) isolated from either omental or subcutaneous adipose depots. Human tissue samples were obtained from bariatric and plastic surgical practices at a university-affiliated teaching hospital and a private practice, respectively, with informed patient consent. Primary cultures of human ASC were isolated from adipose specimens within 24 h of surgery and culture expanded in vitro. The passaged ASC were induced to undergo adipogenic or osteogenic differentiation as assessed by histochemical methods or evaluated for surface antigen expression profiles by flow cytometry. ASC yields per unit weight of tissue were comparable between omental and subcutaneous depots. At passage 0, the immunophenotype of omental and subcutaneous ASC were not significantly different with the exception of CD105 and endoglin, a component of the transforming growth factor β receptor. The adipogenic differentiation of omental ASC was less robust than that of subcutaneous ASC based on in vitro histochemical and PCR assays. Although the yield and immunophenotype of ASC from omental adipose depots resembled that of subcutaneous ASC, omental ASC displayed significantly reduced adipogenic differentiation capacity following chemical induction. Further studies are necessary to evaluate and optimize the differentiation function of omental ASC in vitro and in vivo. Pending such analyses, omental ASC should not be used interchangeably with subcutaneous ASC for regenerative medical applications. PMID:26089088

  1. EATING OURSELVES TO DEATH AND DESPAIR: THE CONTRIBUTION OF ADIPOSITY AND INFLAMMATION TO DEPRESSION

    PubMed Central

    Shelton, Richard C.; Miller, Andrew H.

    2010-01-01

    Obesity and related metabolic conditions are of epidemic proportions in most of the world, affecting both adults and children. The accumulation of lipids in the body in the form of white adipose tissue in the abdomen is now known to activate innate immune mechanisms. Lipid accumulation causes adipocytes to directly secrete the cytokines interleukin (IL) 6 and tumor necrosis factor α (TNFα), but also monocyte chemoattractant protein 1 (MCP-1), which results in the accumulation of leukocytes in fat tissue. This sets up a chronic inflammatory state which is known to mediate the association between obesity and conditions such as cardiovascular disease, type 2 diabetes, and cancer. There is also a substantial literature linking inflammation with risk for depression. This includes the observations that: 1. People with inflammatory diseases such as multiple sclerosis, cardiovascular disease, and psoriasis have elevated rates of depression; 2. Many people administered inflammatory cytokines such as interferon α develop depression that is indistinguishable from depression in non-medically ill populations; 3. A significant proportion of depressed persons show upregulation of inflammatory factors such as IL-6, C-reactive protein, and TNFα; and 4) Inflammatory cytokines can interact with virtually every pathophysiologic domain relevant to depression, including neurotransmitter metabolism, neuroendocrine function, and synaptic plasticity. While many factors may contribute to the association between inflammatory mediators and depression, we hypothesize that increased adiposity may be one causal pathway. Mediational analysis suggests a bi-directional association between adiposity and depression, with inflammation possibly playing an intermediary role. PMID:20417247

  2. Human Adipose Tissue Macrophages Display Activation of Cancer-related Pathways*

    PubMed Central

    Mayi, Thérèse Hérvée; Daoudi, Mehdi; Derudas, Bruno; Gross, Barbara; Bories, Gael; Wouters, Kristiaan; Brozek, John; Caiazzo, Robert; Raverdi, Violeta; Pigeyre, Marie; Allavena, Paola; Mantovani, Alberto; Pattou, François; Staels, Bart; Chinetti-Gbaguidi, Giulia

    2012-01-01

    Obesity is associated with a significantly increased risk for cancer suggesting that adipose tissue dysfunctions might play a crucial role therein. Macrophages play important roles in adipose tissue as well as in cancers. Here, we studied whether human adipose tissue macrophages (ATM) modulate cancer cell function. Therefore, ATM were isolated and compared with monocyte-derived macrophages (MDM) from the same obese patients. ATM, but not MDM, were found to secrete factors inducing inflammation and lipid accumulation in human T47D and HT-29 cancer cells. Gene expression profile comparison of ATM and MDM revealed overexpression of functional clusters, such as cytokine-cytokine receptor interaction (especially CXC-chemokine) signaling as well as cancer-related pathways, in ATM. Comparison with gene expression profiles of human tumor-associated macrophages showed that ATM, but not MDM resemble tumor-associated macrophages. Indirect co-culture experiments demonstrated that factors secreted by preadipocytes, but not mature adipocytes, confer an ATM-like phenotype to MDM. Finally, the concentrations of ATM-secreted factors related to cancer are elevated in serum of obese subjects. In conclusion, ATM may thus modulate the cancer cell phenotype. PMID:22511784

  3. Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    SciTech Connect

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

    2011-03-04

    Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

  4. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    PubMed

    Huang, Zhi H; Reardon, Catherine A; Getz, Godfrey S; Maeda, Nobuyo; Mazzone, Theodore

    2015-02-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.

  5. Obesity-associated proinflammatory cytokines increase calcium sensing receptor (CaSR) protein expression in primary human adipocytes and LS14 human adipose cell line.

    PubMed

    Cifuentes, Mariana; Fuentes, Cecilia; Mattar, Pamela; Tobar, Nicolas; Hugo, Eric; Ben-Jonathan, Nira; Rojas, Cecilia; Martínez, Jorge

    2010-08-15

    Obesity-associated health complications are thought to be in part due to the low-grade proinflammatory state that characterizes this disease. The calcium sensing receptor (CaSR), which is expressed in human adipose cells, plays an important role in diseases involving inflammation. To assess the relevance of this protein in adipose pathophysiology, we evaluated its expression in adipocytes under obesity-related proinflammatory conditions. As in primary adipose cells, we established that LS14, a recently described human adipose cell line, expresses the CaSR. Differentiated LS14 and primary adipose cells were exposed overnight to cytokines typically involved in obesity-related inflammation (interleukin (IL)1beta, IL6 and tumor necrosis factor (TNF)alpha). The cytokines increased CaSR abundance in differentiated adipocytes. We incubated LS14 cells with medium previously conditioned (CM) by adipose tissue from subjects with a wide range of body mass index (BMI). Cells exposed to CM from subjects of higher BMI underwent a greater increase in CaSR protein, likely resulting from the greater proinflammatory cytokines secreted from obese tissue. Our observations that proinflammatory factors increase CaSR levels in adipocytes, and the reported ability of CaSR to elevate cytokine levels, open new aspects in the study of obesity inflammatory state pathophysiology, providing a potential novel therapeutic prevention and treatment target.

  6. Human adipose tissue-resident monocytes exhibit an endothelial-like phenotype and display angiogenic properties

    PubMed Central

    2014-01-01

    Introduction Adipose tissue has the unique property of expanding throughout adult life, and angiogenesis is required for its growth. However, endothelial progenitor cells contribute minimally to neovascularization. Because myeloid cells have proven to be angiogenic, and monocytes accumulate in expanding adipose tissue, they might contribute to vascularization. Methods The stromal vascular fraction (SVF) cells from human adipose tissue were magnetically separated according to CD45 or CD14 expression. Adipose-derived mesenchymal stromal cells (MSCs) were obtained from SVF CD45- cells. CD14+ monocytes were isolated from peripheral blood (PB) mononuclear cells and then cultured with SVF-derived MSCs. Freshly isolated or cultured cells were characterized with flow cytometry; the conditioned media were analyzed for the angiogenic growth factors, angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), hepatocyte growth factor (HGF), granulocyte colony-stimulating factor (G-CSF), and granulocyte macrophage colony-stimulating factor (GM-CSF) with Luminex Technology; their angiogenic capacity was determined in an in vivo gelatinous protein mixture (Matrigel) plug angiogenesis assay. Results CD45+ hematopoietic cells within the SVF contain CD14+ cells that co-express the CD34 progenitor marker and the endothelial cell antigens VEGF receptor 2 (VEGFR2/KDR), VEGFR1/Flt1, and Tie2. Co-culture experiments showed that SVF-derived MSCs promoted the acquisition of KDR and Tie-2 in PB monocytes. MSCs secreted significant amounts of Ang-2 and HGF, but minimal amounts of bFGF, G-CSF, or GM-CSF, whereas the opposite was observed for SVF CD14+ cells. Additionally, SVF CD14+ cells secreted significantly higher levels of VEGF and bFGF than did MSCs. Culture supernatants of PB monocytes cultured with MSCs contained significantly higher concentrations of VEGF, HGF, G-CSF, and GM-CSF than did the supernatants from cultures without MSCs

  7. Relationship between adiposity and cognitive performance in 9-10 year old children in south India

    PubMed Central

    Veena, Sargoor R; Hegde, Bhavya G; Ramachandraiah, Somashekara; Krishnaveni, Ghattu V; Fall, Caroline HD; Srinivasan, Krishnamachari

    2014-01-01

    Background Studies in high-income countries have shown inverse associations between adiposity and cognitive performance in children. We aimed to examine the relationship between adiposity and cognitive function in Indian children. Methods At a mean age of 9.7 years, height, weight, triceps and subscapular skinfold thicknesses and waist circumference were recorded for 540 children born in Mysore, India. Body fat percentage was estimated using bio-impedance. Cognitive function was assessed using 3 core tests from the Kaufman Assessment Battery for children-II edition and additional tests measuring learning, short-term memory, reasoning, verbal and visuo-spatial abilities, attention and concentration. Data on the parents’ socio-economic status, education, occupation and income were collected. Results According to WHO definitions, 3.5% of the children were overweight/obese (BMI>+1SD) and 27% underweight (BMI<−2SD). Compared to normal children, overweight/obese children scored higher in tests of learning/long-term retrieval, reasoning and verbal ability (unadjusted p<0.05 for all). All the cognitive test scores increased with increase in BMI and skinfold thickness, (unadjusted β=0.10 to 0.20 SD; p<0.05 for all). The effects, though attenuated, remained mainly significant after adjustment for age, sex and socio-economic factors. Similar associations were found for waist circumference and percentage body fat. Conclusions In this Indian population, in which obesity was uncommon, greater adiposity predicted higher cognitive ability. These associations were only partly explained by socio-economic factors. Our findings suggest that better nutrition is associated with better cognitive function, and that inverse associations between adiposity and cognitive function in high-income countries reflect confounding by socio-economic factors. PMID:24146284

  8. Ovariectomy in mature mice does not increase food intake, but increases adiposity and adipose tissue inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause, characterized by reduced estrogen (E2), is associated with increased adiposity and metabolic pathology. Molecular mechanisms underlying this association between low E2 status and metabolic disease are not fully elucidated. When mice are fed a high fat diet (HFD) to induce obesity and diab...

  9. Adipose Tissue Residing Progenitors (Adipocyte Lineage Progenitors and Adipose Derived Stem Cells (ADSC)

    PubMed Central

    Berry, Ryan; Rodeheffer, Matthew S.; Rosen, Clifford J.; Horowitz, Mark C.

    2015-01-01

    The formation of brown, white and beige adipocytes have been a subject of intense scientific interest in recent years due to the growing obesity epidemic in the United States and around the world. This interest has led to the identification and characterization of specific tissue resident progenitor cells that give rise to each adipocyte population in vivo. However, much still remains to be discovered about each progenitor population in terms of their “niche” within each tissue and how they are regulated at the cellular and molecular level during healthy and diseased states. While our knowledge of brown, white and beige adipose tissue is rapidly increasing, little is still known about marrow adipose tissue and its progenitor despite recent studies demonstrating possible roles for marrow adipose tissue in regulating the hematopoietic space and systemic metabolism at large. This chapter focuses on our current knowledge of brown, white, beige and marrow adipose tissue with a specific focus on the formation of each tissue from tissue resident progenitor cells. PMID:26526875

  10. Angiogenesis in adipose tissues and skeletal muscles with rebound weight-gain after diet-restriction in rabbits.

    PubMed

    Morimura, M; Ishiko, O; Sumi, T; Yoshida, H; Ogita, S

    2001-11-01

    The mechanisms of excessive body weight gain after diet-restriction are still unclear. In this study, we investigated expression of angiogenic factors in adipose tissue and skeletal muscle of rabbits which had rebound weight gains; trying to make inquiries into the mechanisms of this rebound weight gain. Ten rabbits were divided into two groups. One group had free food intake (group C), and the other group had restricted food intake until day 40 of the experiments and then had free food intake (group DR). Specimens of adipose tissue and skeletal muscle were collected from each rabbit on days 20, 40, and 60 after the initial examination, and expressions of CD34, vascular endothelial growth factor (VEGF), and platelet-derived endothelial cell growth factor (PD-ECGF) were investigated. Expression of VEGF was significantly strong in the adipose tissue of group DR at the recovery period of body weight. In conclusion, rebound weight gain after a restricted-diet may be associated with angiogenesis in adipose tissue, and the angiogenesis may be induced by VEGF.

  11. Brown Adipose YY1 Deficiency Activates Expression of Secreted Proteins Linked to Energy Expenditure and Prevents Diet-Induced Obesity

    PubMed Central

    Verdeguer, Francisco; Soustek, Meghan S.; Hatting, Maximilian; Blättler, Sharon M.; McDonald, Devin; Barrow, Joeva J.

    2015-01-01

    Mitochondrial oxidative and thermogenic functions in brown and beige adipose tissues modulate rates of energy expenditure. It is unclear, however, how beige or white adipose tissue contributes to brown fat thermogenic function or compensates for partial deficiencies in this tissue and protects against obesity. Here, we show that the transcription factor Yin Yang 1 (YY1) in brown adipose tissue activates the canonical thermogenic and uncoupling gene expression program. In contrast, YY1 represses a series of secreted proteins, including fibroblast growth factor 21 (FGF21), bone morphogenetic protein 8b (BMP8b), growth differentiation factor 15 (GDF15), angiopoietin-like 6 (Angptl6), neuromedin B, and nesfatin, linked to energy expenditure. Despite substantial decreases in mitochondrial thermogenic proteins in brown fat, mice lacking YY1 in this tissue are strongly protected against diet-induced obesity and exhibit increased energy expenditure and oxygen consumption in beige and white fat depots. The increased expression of secreted proteins correlates with elevation of energy expenditure and promotion of beige and white fat activation. These results indicate that YY1 in brown adipose tissue controls antagonistic gene expression programs associated with energy balance and maintenance of body weight. PMID:26503783

  12. Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation.

    PubMed

    Burhans, Maggie S; Flowers, Matthew T; Harrington, Kristin R; Bond, Laura M; Guo, Chang-An; Anderson, Rozalyn M; Ntambi, James M

    2015-02-01

    Hepatic steatosis is associated with detrimental metabolic phenotypes including enhanced risk for diabetes. Stearoyl-CoA desaturases (SCDs) catalyze the synthesis of MUFAs. In mice, genetic ablation of SCDs reduces hepatic de novo lipogenesis (DNL) and protects against diet-induced hepatic steatosis and adiposity. To understand the mechanism by which hepatic MUFA production influences adipose tissue stores, we created two liver-specific transgenic mouse models in the SCD1 knockout that express either human SCD5 or mouse SCD3, that synthesize oleate and palmitoleate, respectively. We demonstrate that hepatic de novo synthesized oleate, but not palmitoleate, stimulate hepatic lipid accumulation and adiposity, reversing the protective effect of the global SCD1 knockout under lipogenic conditions. Unexpectedly, the accumulation of hepatic lipid occurred without induction of the hepatic DNL program. Changes in hepatic lipid composition were reflected in plasma and in adipose tissue. Importantly, endogenously synthesized hepatic oleate was associated with suppressed DNL and fatty acid oxidation in white adipose tissue. Regression analysis revealed a strong correlation between adipose tissue lipid fuel utilization and hepatic and adipose tissue lipid storage. These data suggest an extrahepatic mechanism where endogenous hepatic oleate regulates lipid homeostasis in adipose tissues.

  13. Altered autophagy in human adipose tissues in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  14. Involvement of mast cells in adipose tissue fibrosis.

    PubMed

    Hirai, Shizuka; Ohyane, Chie; Kim, Young-Il; Lin, Shan; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kim, Chu-Sook; Kang, Jihey; Yu, Rina; Kawada, Teruo

    2014-02-01

    Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis remains to be clarified. Obese adipose tissue is characterized by chronic inflammation with massive accumulation of immune cells including mast cells. The objective of the present study was to clarify the relationship between fibrosis and mast cells in obese adipose tissue, as well as to determine the origin of infiltrating mast cells. We observed the enhancement of mast cell accumulation and fibrosis in adipose tissue of severely obese diabetic db/db mice. Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3 fibroblasts, and this enhancement was suppressed by the addition of an anti-mast cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V among various types of collagen inhibited preadipocyte differentiation. Moreover, we found that ATCM from the nonobese but not obese stages of db/db mice significantly enhanced the migration of bone marrow-derived mast cells (BMMCs). These findings suggest that immature mast cells that infiltrate into adipose tissue at the nonobese stage gradually mature with the progression of obesity and diabetes and that MCP-6 secreted from mature mast cells induces collagen V expression in obese adipose tissue, which may contribute to the process of adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate insulin resistance via the suppression of preadipocyte differentiation.

  15. Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

    PubMed

    Pallikkuth, Suresh; Mohan, Mahesh

    2015-12-01

    This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented.

  16. Cell supermarket: Adipose tissue as a source of stem cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue is derived from numerous sources, and in recent years has been shown to provide numerous cells from what seemingly was a population of homogeneous adipocytes. Considering the types of cells that adipose tissue-derived cells may form, these cells may be useful in a variety of clinical ...

  17. Sagittal Abdominal Diameter and Visceral Adiposity

    PubMed Central

    Kahn, Henry S.; Gasevic, Danijela; Liang, Zhe; Frediani, Jennifer K.; Torres, William E.; Ziegler, Thomas R.; Phillips, Lawrence S.; Lin, Edward

    2013-01-01

    Background In the context of increasing obesity prevalence, the relationship between large visceral adipose tissue (VAT) volumes and type 2 diabetes mellitus (T2DM) is unclear. In a clinical sample of severely obese women (mean body mass index [BMI], 46 kg/m2) with fasting normoglycemia (n=40) or dysglycemia (impaired fasting glucose+diabetes; n=20), we sought to determine the usefulness of anthropometric correlates of VAT and associations with dysglycemia. Methods VAT volume was estimated using multi-slice computer tomography; anthropometric surrogates included sagittal abdominal diameter (SAD), waist circumference (WC) and BMI. Insulin sensitivity (Si), and beta-cell dysfunction, measured by insulin secretion (AIRg) and the disposition index (DI), were determined by frequently sampled intravenous glucose tolerance test. Results Compared to fasting normoglycemic women, individuals with dysglycemia had greater VAT (P<0.001) and SAD (P=0.04), but BMI, total adiposity and Si were similar. VAT was inversely associated with AIRg and DI after controlling for ancestry, Si, and total adiposity (standardized beta, −0.32 and −0.34, both P<0.05). In addition, SAD (beta=0.41, P=0.02) was found to be a better estimate of VAT volume than WC (beta=0.32, P=0.08) after controlling for covariates. Receiver operating characteristic analysis showed that VAT volume, followed by SAD, outperformed WC and BMI in identifying dysglycemic participants. Conclusions Increasing VAT is associated with beta-cell dysfunction and dysglycemia in very obese women. In the presence of severe obesity, SAD is a simple surrogate of VAT, and an indicator of glucose dysregulation. PMID:23408092

  18. Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment.

    PubMed

    Hu, Xiaoming; Zhou, Yuanfei; Yang, Yang; Peng, Jie; Song, Tongxing; Xu, Tao; Wei, Hongkui; Jiang, Siwen; Peng, Jian

    2016-06-01

    Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPδ, C/EBPα and PPARγ). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 (STAT1), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment. PMID:27251748

  19. Identification of zinc finger protein Bcl6 as a novel regulator of early adipose commitment

    PubMed Central

    Hu, Xiaoming; Zhou, Yuanfei; Yang, Yang; Peng, Jie; Song, Tongxing; Xu, Tao; Wei, Hongkui; Jiang, Siwen; Peng, Jian

    2016-01-01

    Adipose tissue is a key determinant of whole-body metabolism and energy homeostasis. Unravelling the transcriptional regulatory process during adipogenesis is therefore highly relevant from a biomedical perspective. In these studies, zinc finger protein B-cell lymphoma 6 (Bcl6) was demonstrated to have a role in early adipogenesis of mesenchymal stem cells. Bcl6 is enriched in preadipose versus non-preadipose fibroblasts and shows upregulated expression in the early stage of adipogenesis. Gain- and loss-of-function studies revealed that Bcl6 acts as a key regulator of adipose commitment and differentiation both in vitro and ex vivo. RNAi-mediated knockdown of Bcl6 in C3H10T1/2 cells greatly inhibited adipogenic potential, whereas Bcl6 overexpression enhanced adipogenic differentiation. This transcription factor also directly or indirectly targets and controls the expression of some early and late adipogenic regulators (i.e. Zfp423, Zfp467, KLF15, C/EBPδ, C/EBPα and PPARγ). We further identified that Bcl6 transactivated the signal transducers and activators of transcription 1 (STAT1), which was determined as a required factor for adipogenesis. Moreover, overexpression of STAT1 rescued the impairment of adipogenic commitment and differentiation induced by Bcl6 knockdown in C3H10T1/2 cells, thereby confirming that STAT1 is a downstream direct target of Bcl6. This study identifies Bcl6 as a positive transcriptional regulator of early adipose commitment. PMID:27251748

  20. Adipose progenitor cells increase fibronectin matrix strain and unfolding in breast tumors

    NASA Astrophysics Data System (ADS)

    Chandler, E. M.; Saunders, M. P.; Yoon, C. J.; Gourdon, D.; Fischbach, C.

    2011-02-01

    Increased stiffness represents a hallmark of breast cancer that has been attributed to the altered physicochemical properties of the extracellular matrix (ECM). However, the role of fibronectin (Fn) in modulating the composition and mechanical properties of the tumor-associated ECM remains unclear. We have utilized a combination of biochemical and physical science tools to evaluate whether paracrine signaling between breast cancer cells and adipose progenitor cells regulates Fn matrix assembly and stiffness enhancement in the tumor stroma. In particular, we utilized fluorescence resonance energy transfer imaging to map the molecular conformation and stiffness of Fn that has been assembled by 3T3-L1 preadipocytes in response to conditioned media from MDA-MB231 breast cancer cells. Our results reveal that soluble factors secreted by tumor cells promote Fn expression, unfolding, and stiffening by adipose progenitor cells and that transforming growth factor-β serves as a soluble cue underlying these changes. In vivo experiments using orthotopic co-transplantation of primary human adipose-derived stem cells and MDA-MB231 into SCID mice support the pathological relevance of our results. Insights gained by these studies advance our understanding of the role of Fn in mammary tumorigenesis and may ultimately lead to improved anti-cancer therapies.

  1. The role of adipose tissue in insulin resistance in women of African ancestry.

    PubMed

    Goedecke, Julia H; Levitt, Naomi S; Evans, Juliet; Ellman, Nicole; Hume, David John; Kotze, Liske; Tootla, Mehreen; Victor, Hendriena; Keswell, Dheshnie

    2013-01-01

    Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry.

  2. Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged mice

    PubMed Central

    Mirsoian, Annie; Bouchlaka, Myriam N.; Sckisel, Gail D.; Chen, Mingyi; Pai, Chien-Chun Steven; Maverakis, Emanuel; Spencer, Richard G.; Fishbein, Kenneth W.; Siddiqui, Sana; Monjazeb, Arta M.; Martin, Bronwen; Maudsley, Stuart; Hesdorffer, Charles; Ferrucci, Luigi; Longo, Dan L.; Blazar, Bruce R.; Wiltrout, Robert H.; Taub, Dennis D.

    2014-01-01

    Aging is a contributing factor in cancer occurrence. We recently demonstrated that systemic immunotherapy (IT) administration in aged, but not young, mice resulted in induction of rapid and lethal cytokine storm. We found that aging was accompanied by increases in visceral fat similar to that seen in young obese (ob/ob or diet-induced obese [DIO]) mice. Yet, the effects of aging and obesity on inflammatory responses to immunotherapeutics are not well defined. We determine the effects of adiposity on systemic IT tolerance in aged compared with young obese mice. Both young ob/ob- and DIO-generated proinflammatory cytokine levels and organ pathologies are comparable to those in aged ad libitum mice after IT, culminating in lethality. Young obese mice exhibited greater ratios of M1/M2 macrophages within the peritoneal and visceral adipose tissues and higher percentages of TNF+ macrophages in response to αCD40/IL-2 as compared with young lean mice. Macrophage depletion or TNF blockade in conjunction with αCD40/IL-2 prevented cytokine storms in young obese mice and protected from lethality. Calorie-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality upon αCD40/IL-2 administration. Our data demonstrate that adiposity is a critical factor in the age-associated pathological responses to systemic anti-cancer IT. PMID:25366964

  3. Adiposity and stroke among older adults of low socioeconomic status: the Chicago Stroke Study.

    PubMed Central

    DiPietro, L; Ostfeld, A M; Rosner, G L

    1994-01-01

    OBJECTIVES. The purpose of this study was to test the hypothesis that overall and truncal adiposity increase the risk of stroke independent of their association with cardiovascular disease risk factors and other preexisting illnesses. METHODS. Analyses were conducted of longitudinal data from a poor, biracial cohort of noninstitutionalized adults 65 to 74 years of age who participated in the Chicago Stroke Study from 1965 to 1970. RESULTS. Ponderal index (cm/kg1/3) and chest skinfold were significantly associated with systolic and diastolic blood pressure, serum cholesterol and triglycerides, plasma glucose, and smoking. Ponderal index was also associated with diabetes and risk of stroke. After potential confounders were controlled, the following variables showed significant independent associations with risk of stroke: Black race, female gender, and age 70+; hypertensive heart disease; and diabetes. Neither adiposity variable was associated with risk of stroke in the presence of these powerful predictors. CONCLUSIONS. Control of hypertension and diabetes continues to be important among older adults. Since excess adiposity seems to influence risk of stroke through its association with these disorders and other cardiovascular disease risk factors, control of weight and fat remains an important concern as well. PMID:8279605

  4. Roles of FGFs as Adipokines in Adipose Tissue Development, Remodeling, and Metabolism.

    PubMed

    Ohta, Hiroya; Itoh, Nobuyuki

    2014-01-01

    White and brown adipose tissues (BATs), which store and burn lipids, respectively, play critical roles in energy homeostasis. Fibroblast growth factors (FGFs) are signaling proteins with diverse functions in development, metabolism, and neural function. Among 22 FGFs, FGF1, FGF10, and FGF21 play roles as adipokines, adipocyte-secreted proteins, in the development and function of white and BATs. FGF1 is a critical transducer in white adipose tissue (WAT) remodeling. The peroxisome proliferator-activated receptor γ-FGF1 axis is critical for energy homeostasis. FGF10 is essential for embryonic white adipocyte development. FGF21 activates BAT in response to cold exposure. FGF21 also stimulates the accumulation of brown-like cells in WAT during cold exposure and is an upstream effector of adiponectin, which controls systemic energy metabolism. These findings provide new insights into the roles of FGF signaling in white and BATs and potential therapeutic strategies for metabolic disorders.

  5. Redox implications in adipose tissue (dys)function—A new look at old acquaintances

    PubMed Central

    Jankovic, Aleksandra; Korac, Aleksandra; Buzadzic, Biljana; Otasevic, Vesna; Stancic, Ana; Daiber, Andreas; Korac, Bato

    2015-01-01

    Obesity is an energy balance disorder associated with dyslipidemia, insulin resistance and diabetes type 2, also summarized with the term metabolic syndrome or syndrome X. Increasing evidence points to “adipocyte dysfunction”, rather than fat mass accretion per se, as the key pathophysiological factor for metabolic complications in obesity. The dysfunctional fat tissue in obesity characterizes a failure to safely store metabolic substrates into existing hypertrophied adipocytes and/or into new preadipocytes recruited for differentiation. In this review we briefly summarize the potential of redox imbalance in fat tissue as an instigator of adipocyte dysfunction in obesity. We reveal the challenge of the adipose redox changes, insights in the regulation of healthy expansion of adipose tissue and its reduction, leading to glucose and lipids overflow. PMID:26177468

  6. Aromatase overexpression in dysfunctional adipose tissue links obesity to postmenopausal breast cancer.

    PubMed

    Wang, Xuyi; Simpson, Evan R; Brown, Kristy A

    2015-09-01

    The number of breast cancer cases has increased in the last a few decades and this is believed to be associated with the increased prevalence of obesity worldwide. The risk of breast cancer increases with age beyond menopause and the relationship between obesity and the risk of breast cancer in postmenopausal women is well established. The majority of postmenopausal breast cancers are estrogen receptor (ER) positive and estrogens produced in the adipose tissue promotes tumor formation. Obesity results in the secretion of inflammatory factors that stimulate the expression of the aromatase enzyme, which converts androgens into estrogens in the adipose tissue. Evidence demonstrating a link between obesity and breast cancer has led to the investigation of metabolic pathways as novel regulators of estrogen production, including pathways that can be targeted to inhibit aromatase specifically within the breast. This review aims to present some of the key findings in this regard.

  7. Adipose tissue distribution, plasma insulin, and cardiovascular disease.

    PubMed

    Björntorp, P

    1987-07-01

    Hyperinsulinaemia is of great importance, being a primary risk factor for cardiovascular disease and non-insulin dependent diabetes (NIDDM). Furthermore, unwanted effects of increased exposure of tissues to insulin are known. Hyperinsulinaemia may, in principle, be caused by primary hypersecretion, or be a secondary consequence of diminished effectiveness of insulin in the periphery. Obesity is the commonest condition characterized by insulin resistance, which is seen most frequently when excess adipose tissue is localized to the abdominal region. Insulin resistance in obesity is found in several tissues, however, with liver and muscle being quantitative the most important. Muscle insulin sensitivity is regulated by genetic factors, hormonal effects, and the influence of free fatty acids, as well as the state of physical activity. There is evidence for the action of each of these factors in obesity. The pathogenetic mechanisms linking hyperinsulinaemia with cardiovascular disease and NIDDM are unknown. Comparisons between development of NIDDM in experimental animal models and in humans in prospective studies however, provide useful hypotheses for further studies.

  8. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    PubMed

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-01-01

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis. PMID:25864946

  9. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    PubMed

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-04-13

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

  10. Adipose-derived stem cells: current findings and future perspectives.

    PubMed

    Tobita, Morikuni; Orbay, Hakan; Mizuno, Hiroshi

    2011-02-01

    Adipose tissue is an abundant source of mesenchymal stem cells, which have shown promise in the field of regenerative medicine. Furthermore, these cells can be readily harvested in large numbers with low donor-site morbidity. During the past decade, numerous studies have provided preclinical data on the safety and efficacy of adipose-derived stem cells, supporting the use of these cells in future clinical applications. Various clinical trials have shown the regenerative capability of adipose-derived stem cells in subspecialties of medical fields such as plastic surgery, orthopedic surgery, oral and maxillofacial surgery, and cardiac surgery. In addition, a great deal of knowledge concerning the harvesting, characterization, and culture of adipose-derived stem cells has been reported. This review will summarize data from in vitro studies, pre-clinical animal models, and recent clinical trials concerning the use of adipose-derived stem cells in regenerative medicine.

  11. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    PubMed

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  12. Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src.

    PubMed

    Uchiyama, Tsuyoshi; Tomono, Shoichi; Sato, Koichi; Nakamura, Tetsuya; Kurabayashi, Masahiko; Okajima, Fumikazu

    2015-01-01

    Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes-all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome. PMID:26447765

  13. Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src

    PubMed Central

    Uchiyama, Tsuyoshi; Tomono, Shoichi; Sato, Koichi; Nakamura, Tetsuya; Kurabayashi, Masahiko; Okajima, Fumikazu

    2015-01-01

    Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG)- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes—all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL) catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII) on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4), protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome. PMID:26447765

  14. Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth.

    PubMed

    Jo, Junghyo; Gavrilova, Oksana; Pack, Stephanie; Jou, William; Mullen, Shawn; Sumner, Anne E; Cushman, Samuel W; Periwal, Vipul

    2009-03-01

    Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. In this study, the size distributions of epididymal adipose cells from two mouse strains, obesity-resistant FVB/N and obesity-prone C57BL/6, were measured after 2, 4, and 12 weeks under regular and high-fat feeding conditions. The total cell number in the epididymal fat pad was estimated from the fat pad mass and the normalized cell-size distribution. The cell number and volume-weighted mean cell size increase as a function of fat pad mass. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet- and genetics-dependent model parameters. Compared to the FVB/N strain, the C57BL/6 strain has greater recruitment of small adipose cells. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reflecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size fluctuations of adipose cells through lipid turnover.

  15. The sexually dimorphic role of adipose and adipocyte estrogen receptors in modulating adipose tissue expansion, inflammation, and fibrosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our data demonstrate that estrogens, estrogen receptor-alpha (ERalpha), and estrogen receptor-ßeta (ERßeta) regulate adipose tissue distribution, inflammation, fibrosis, and glucose homeostasis, by determining that alphaERKO mice have increased adipose tissue inflammation and fibrosis prior to obesi...

  16. Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain.

    PubMed

    Roumans, Nadia J T; Camps, Stefan G; Renes, Johan; Bouwman, Freek G; Westerterp, Klaas R; Mariman, Edwin C M

    2016-03-14

    Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain. In vivo findings were compared with results from in vitro cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up. In vitro differentiated SGBS adipocytes were starved for 96 h with low (0·55 mm) glucose. Levels of stress proteins were determined by Western blotting. WR showed increased expressions of β-actin, calnexin, heat shock protein (HSP) 27, HSP60 and HSP70. Changes of β-actin, HSP27 and HSP70 are linked to HSP60, a proposed key factor in weight regain after weight loss. SGBS adipocytes showed increased levels of β-actin and HSP60 after 96 h of glucose restriction. The increased level of cellular stress proteins in the adipose tissue of WR probably resides in the adipocytes as shown by in vitro experiments. Cellular stress accumulated in adipose tissue during weight loss may be a risk factor for weight regain. PMID:26759119

  17. Weight loss-induced stress in subcutaneous adipose tissue is related to weight regain.

    PubMed

    Roumans, Nadia J T; Camps, Stefan G; Renes, Johan; Bouwman, Freek G; Westerterp, Klaas R; Mariman, Edwin C M

    2016-03-14

    Initial successful weight loss is often followed by weight regain after the dietary intervention. Compared with lean people, cellular stress in adipose tissue is increased in obese subjects. However, the relation between cellular stress and the risk for weight regain after weight loss is unclear. Therefore, we determined the expression levels of stress proteins during weight loss and weight maintenance in relation to weight regain. In vivo findings were compared with results from in vitro cultured human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. In total, eighteen healthy subjects underwent an 8-week diet programme with a 10-month follow-up. Participants were categorised as weight maintainers or weight regainers (WR) depending on their weight changes during the intervention. Abdominal subcutaneous adipose tissue biopsies were obtained before and after the diet and after the follow-up. In vitro differentiated SGBS adipocytes were starved for 96 h with low (0·55 mm) glucose. Levels of stress proteins were determined by Western blotting. WR showed increased expressions of β-actin, calnexin, heat shock protein (HSP) 27, HSP60 and HSP70. Changes of β-actin, HSP27 and HSP70 are linked to HSP60, a proposed key factor in weight regain after weight loss. SGBS adipocytes showed increased levels of β-actin and HSP60 after 96 h of glucose restriction. The increased level of cellular stress proteins in the adipose tissue of WR probably resides in the adipocytes as shown by in vitro experiments. Cellular stress accumulated in adipose tissue during weight loss may be a risk factor for weight regain.

  18. Differential modulation of the functionality of white adipose tissue of obese Zucker (fa/fa) rats by the type of protein and the amount and type of fat.

    PubMed

    Díaz-Villaseñor, Andrea; Granados, Omar; González-Palacios, Berenice; Tovar-Palacio, Claudia; Torre-Villalvazo, Ivan; Olivares-García, Verónica; Torres, Nimbe; Tovar, Armando R

    2013-11-01

    Recent evidence indicates that several metabolic abnormalities developed during obesity are associated with the presence of dysfunctional adipose tissue. Diet is a key factor that modulates several functions of adipose tissue; however, each nutrient in the diet produces specific changes. Thus, the aim of this work was to study the effect of the interaction of the type (coconut or soybean oil) and amount (5% or 10%) of fat with the type of dietary protein (casein or soy protein) on the functionality of white adipose tissue of Zucker (fa/fa) rats. The results showed that soybean oil reduced adipocyte size and decreased esterified saturated fatty acids in white adipose tissue. Excess dietary fat also modified the composition of esterified fatty acids in white adipose tissue, increased the secretion of saturated fatty acids to serum from white adipose tissue and reduced the process of fatty acids re-esterification. On the other hand, soy protein sensitized the activation of the hormone-sensitive lipase by increasing the phosphorylation of this enzyme (Ser 563) despite rats fed soy protein were normoglucagonemic, in contrast with rats fed casein that showed hyperglucagonemia but reduced hormone-sensitive lipase phosphorylation. Finally, in white adipose tissue, the interaction between the tested dietary components modulated the transcription/translation process of lipid and carbohydrate metabolism genes via the activity of the PERK-endoplasmic reticulum stress response. Therefore, our results showed that the type of protein and the type and amount of dietary fat selectively modify the activity of white adipose tissue, even in a genetic model of obesity.

  19. Android Adiposity and Lack of Moderate and Vigorous Physical Activity Are Associated With Insulin Resistance and Diabetes in Aging Adults

    PubMed Central

    Al Snih, Soham; Serra-Rexach, José A.; Burant, Charles

    2015-01-01

    Background. Physical inactivity and excess adiposity are thought to be interdependent “lifestyle” factors and thus, many older adults are at exaggerated risk for preventable diseases. The purposes of this study were to determine the degree of discordance between body mass index (BMI) and adiposity among adults older than 50 years, and to determine the extent to which direct measures of adiposity, and objectively measured sedentary behavior (SB) and physical activity (PA) are associated with insulin resistance (IR) or diabetes. Methods. A population representative sample of 2,816 individuals, aged 50–85 years, was included from the combined 2003–2006 National Health and Nutrition Examination Survey (NHANES) datasets. BMI, percent body fat (%BF) and android adiposity as determined by dual energy x-ray absorptiometry, objectively measured SB and PA, established markers of cardiometabolic risk, IR, and type 2 diabetes were analyzed. Results. Approximately 50% of the men and 64% of the women who were normal weight according to BMI had excessive %BF. Adults with the least SB and greatest moderate and vigorous PA exhibited the healthiest cardiometabolic profiles, whereas adults with the greatest SB and lowest activity had highest risk. Greater android adiposity stores were robustly associated with IR or diabetes in all adults, independent of SB and activity. Among men, less moderate-to-vigorous PA was associated with IR or diabetes; whereas among women, less lifestyle moderate activity was associated with IR or diabetes. Conclusions. Android adiposity and low moderate and vigorous PA are the strongest predictors of IR or diabetes among aging adults. PMID:25711528

  20. Mechanisms Linking Excess Adiposity and Carcinogenesis Promotion

    PubMed Central

    Pérez-Hernández, Ana I.; Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2014-01-01

    Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well established for several tumor types, such as breast cancer in post-menopausal women, colorectal, and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15–20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: (i) inflammatory changes leading to macrophage polarization and altered adipokine profile; (ii) insulin resistance development; and (iii) adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases. PMID:24829560

  1. Mechanisms linking excess adiposity and carcinogenesis promotion.

    PubMed

    Pérez-Hernández, Ana I; Catalán, Victoria; Gómez-Ambrosi, Javier; Rodríguez, Amaia; Frühbeck, Gema

    2014-01-01

    Obesity constitutes one of the most important metabolic diseases being associated to insulin resistance development and increased cardiovascular risk. Association between obesity and cancer has also been well established for several tumor types, such as breast cancer in post-menopausal women, colorectal, and prostate cancer. Cancer is the first death cause in developed countries and the second one in developing countries, with high incidence rates around the world. Furthermore, it has been estimated that 15-20% of all cancer deaths may be attributable to obesity. Tumor growth is regulated by interactions between tumor cells and their tissue microenvironment. In this sense, obesity may lead to cancer development through dysfunctional adipose tissue and altered signaling pathways. In this review, three main pathways relating obesity and cancer development are examined: (i) inflammatory changes leading to macrophage polarization and altered adipokine profile; (ii) insulin resistance development; and (iii) adipose tissue hypoxia. Since obesity and cancer present a high prevalence, the association between these conditions is of great public health significance and studies showing mechanisms by which obesity lead to cancer development and progression are needed to improve prevention and management of these diseases.

  2. Laser-induced lipolysis on adipose cells

    NASA Astrophysics Data System (ADS)

    Solarte, Efrain; Gutierrez, O.; Neira, Rodrigo; Arroyave, J.; Isaza, Carolina; Ramirez, Hugo; Rebolledo, Aldo F.; Criollo, Willian; Ortiz, C.

    2004-10-01

    Recently, a new liposuction technique, using a low-level laser (LLL) device and Ultrawet solution prior to the procedure, demonstrated the movement of fat from the inside to the outside of the adipocyte (Neira et al., 2002). To determine the mechanisms involved, we have performed Scanning and Transmission Electron Microscopy studies; Light transmittance measurements on adipocyte dilutions; and a study of laser light propagation in adipose tissue. This studies show: 1. Cellular membrane alterations. 2. LLL is capable to reach the deep adipose tissue layer, and 3. The tumescence solution enhances the light propagation by clearing the tissue. MRI studies demonstrated the appearance of fat on laser treated abdominal tissue. Besides, adipocytes were cultivated and irradiated to observe the effects on isolated cells. These last studies show: 1. 635 nm-laser alone is capable of mobilizing cholesterol from the cell membrane; this action is enhanced by the presence of adrenaline and lidocaine. 2. Intracellular fat is released from adipocytes by co joint action of adrenaline, aminophyline and 635 nm-laser. Results are consistent with a laser induced cellular process, which causes fat release from the adipocytes into the intercellular space, besides the modification of the cellular membranes.

  3. Rare adipose disorders (RADs) masquerading as obesity

    PubMed Central

    Herbst, Karen L

    2012-01-01

    Rare adipose disorders (RADs) including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD) may be misdiagnosed as obesity. Lifestyle changes, such as reduced caloric intake and increased physical activity are standard care for obesity. Although lifestyle changes and bariatric surgery work effectively for the obesity component of RADs, these treatments do not routinely reduce the abnormal subcutaneous adipose tissue (SAT) of RADs. RAD SAT likely results from the growth of a brown stem cell population with secondary lymphatic dysfunction in MSL, or by primary vascular and lymphatic dysfunction in lipedema and DD. People with RADs do not lose SAT from caloric limitation and increased energy expenditure alone. In order to improve recognition of RADs apart from obesity, the diagnostic criteria, histology and pathophysiology of RADs are presented and contrasted to familial partial lipodystrophies, acquired partial lipodystrophies and obesity with which they may be confused. Treatment recommendations focus on evidence-based data and include lymphatic decongestive therapy, medications and supplements that support loss of RAD SAT. Associated RAD conditions including depression, anxiety and pain will improve as healthcare providers learn to identify and adopt alternative treatment regimens for the abnormal SAT component of RADs. Effective dietary and exercise regimens are needed in RAD populations to improve quality of life and construct advanced treatment regimens for future generations. PMID:22301856

  4. Adiposity significantly modifies genetic risk for dyslipidemia.

    PubMed

    Cole, Christopher B; Nikpay, Majid; Lau, Paulina; Stewart, Alexandre F R; Davies, Robert W; Wells, George A; Dent, Robert; McPherson, Ruth

    2014-11-01

    Recent genome-wide association studies have identified multiple loci robustly associated with plasma lipids, which also contribute to extreme lipid phenotypes. However, these common genetic variants explain <12% of variation in lipid traits. Adiposity is also an important determinant of plasma lipoproteins, particularly plasma TGs and HDL cholesterol (HDLc) concentrations. Thus, interactions between genes and clinical phenotypes may contribute to this unexplained heritability. We have applied a weighted genetic risk score (GRS) for both plasma TGs and HDLc in two large cohorts at the extremes of BMI. Both BMI and GRS were strongly associated with these lipid traits. A significant interaction between obese/lean status and GRS was noted for each of TG (P(Interaction) = 2.87 × 10(-4)) and HDLc (P(Interaction) = 1.05 × 10(-3)). These interactions were largely driven by SNPs tagging APOA5, glucokinase receptor (GCKR), and LPL for TG, and cholesteryl ester transfer protein (CETP), GalNAc-transferase (GALNT2), endothelial lipase (LIPG), and phospholipid transfer protein (PLTP) for HDLc. In contrast, the GRSLDL cholesterol × adiposity interaction was not significant. Sexual dimorphism was evident for the GRSHDL on HDLc in obese (P(Interaction) = 0.016) but not lean subjects. SNP by BMI interactions may provide biological insight into specific genetic associations and missing heritability. PMID:25225679

  5. Cytokine-Rich Adipose Tissue Extract Production from Water-Assisted Lipoaspirate: Methodology for Clinical Use

    PubMed Central

    Lopez, Jenny; Huttala, Outi; Sarkanen, Jertta-Riina; Kaartinen, Ilkka; Kuokkanen, Hannu; Ylikomi, Timo

    2016-01-01

    Abstract Proper functioning wound healing strategies are sparse. Adequate vascular formation to the injured area, as well as replacement of the volume loss, is fundamental in soft tissue repair. Tissue engineering strategies have been proposed for the treatment of these injury sites. Novel cell-free substance, human adipose tissue extract (ATE), has been previously shown to induce in vitro angiogenesis and adipogenesis and in vivo soft tissue formation. This study reports the translation of ATE preparation from laboratory to the operating room (OR). ATE samples for this study were derived from adipose tissue obtained with the water-jet assisted liposuction technique from 27 healthy patients. The variables studied included incubation time (15, 30, and 45 min), temperature (room temperature vs. 37°C), and filter type to determine the optimal method yielding the most consistent total protein content, as well as consistent and high expression of adipose-derived growth factors and cytokines, including: vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, adiponectin, leptin, and insulin-like growth factor. Following the optimization, samples were produced in the OR and tested for their sterility. No significant differences were observed when comparing extract incubation time points or incubation temperature. Nonetheless, when studying the different filter types used, a syringe filter with PES membrane with larger filter area showed significantly higher protein concentration (p ≤ 0.018). When studying the different growth factor concentrations, ELISA results showed less variation in cytokine concentrations in the OR samples with the optimized protocol. All of the OR samples were tested sterile. The devised protocol is an easy and reproducible OR-ready method for ATE generation. As an attractive source of growth factors, ATE is a promising alternative in the vast field of tissue engineering. Its clinical applications include volume

  6. Cytokine-Rich Adipose Tissue Extract Production from Water-Assisted Lipoaspirate: Methodology for Clinical Use.

    PubMed

    Lopez, Jenny; Huttala, Outi; Sarkanen, Jertta-Riina; Kaartinen, Ilkka; Kuokkanen, Hannu; Ylikomi, Timo

    2016-01-01

    Proper functioning wound healing strategies are sparse. Adequate vascular formation to the injured area, as well as replacement of the volume loss, is fundamental in soft tissue repair. Tissue engineering strategies have been proposed for the treatment of these injury sites. Novel cell-free substance, human adipose tissue extract (ATE), has been previously shown to induce in vitro angiogenesis and adipogenesis and in vivo soft tissue formation. This study reports the translation of ATE preparation from laboratory to the operating room (OR). ATE samples for this study were derived from adipose tissue obtained with the water-jet assisted liposuction technique from 27 healthy patients. The variables studied included incubation time (15, 30, and 45 min), temperature (room temperature vs. 37°C), and filter type to determine the optimal method yielding the most consistent total protein content, as well as consistent and high expression of adipose-derived growth factors and cytokines, including: vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, adiponectin, leptin, and insulin-like growth factor. Following the optimization, samples were produced in the OR and tested for their sterility. No significant differences were observed when comparing extract incubation time points or incubation temperature. Nonetheless, when studying the different filter types used, a syringe filter with PES membrane with larger filter area showed significantly higher protein concentration (p ≤ 0.018). When studying the different growth factor concentrations, ELISA results showed less variation in cytokine concentrations in the OR samples with the optimized protocol. All of the OR samples were tested sterile. The devised protocol is an easy and reproducible OR-ready method for ATE generation. As an attractive source of growth factors, ATE is a promising alternative in the vast field of tissue engineering. Its clinical applications include volume

  7. Cytokine-Rich Adipose Tissue Extract Production from Water-Assisted Lipoaspirate: Methodology for Clinical Use

    PubMed Central

    Lopez, Jenny; Huttala, Outi; Sarkanen, Jertta-Riina; Kaartinen, Ilkka; Kuokkanen, Hannu; Ylikomi, Timo

    2016-01-01

    Abstract Proper functioning wound healing strategies are sparse. Adequate vascular formation to the injured area, as well as replacement of the volume loss, is fundamental in soft tissue repair. Tissue engineering strategies have been proposed for the treatment of these injury sites. Novel cell-free substance, human adipose tissue extract (ATE), has been previously shown to induce in vitro angiogenesis and adipogenesis and in vivo soft tissue formation. This study reports the translation of ATE preparation from laboratory to the operating room (OR). ATE samples for this study were derived from adipose tissue obtained with the water-jet assisted liposuction technique from 27 healthy patients. The variables studied included incubation time (15, 30, and 45 min), temperature (room temperature vs. 37°C), and filter type to determine the optimal method yielding the most consistent total protein content, as well as consistent and high expression of adipose-derived growth factors and cytokines, including: vascular endothelial growth factor, basic fibroblast growth factor, interleukin-6, adiponectin, leptin, and insulin-like growth factor. Following the optimization, samples were produced in the OR and tested for their sterility. No significant differences were observed when comparing extract incubation time points or incubation temperature. Nonetheless, when studying the different filter types used, a syringe filter with PES membrane with larger filter area showed significantly higher protein concentration (p ≤ 0.018). When studying the different growth factor concentrations, ELISA results showed less variation in cytokine concentrations in the OR samples with the optimized protocol. All of the OR samples were tested sterile. The devised protocol is an easy and reproducible OR-ready method for ATE generation. As an attractive source of growth factors, ATE is a promising alternative in the vast field of tissue engineering. Its clinical applications include volume

  8. Adipose Tissue Promotes a Serum Cytokine Profile Related to Lower Insulin Sensitivity after Chronic Central Leptin Infusion

    PubMed Central

    Burgos-Ramos, Emma; Canelles, Sandra; Perianes-Cachero, Arancha; Arilla-Ferreiro, Eduardo; Argente, Jesús; Barrios, Vicente

    2012-01-01

    Obesity is an inflammatory state characterized by an augment in circulating inflammatory factors. Leptin may modulate the synthesis of these factors by white adipose tissue decreasing insulin sensitivity. We have examined the effect of chronic central administration of leptin on circulating levels of cytokines and the possible relationship with cytokine expression and protein content as well as with leptin and insulin signaling in subcutaneous and visceral adipose tissues. In addition, we analyzed the possible correlation between circulating levels of cytokines and peripheral insulin resistance. We studied 18 male Wistar rats divided into controls (C), those treated icv for 14 days with a daily dose of 12 μg of leptin (L) and a pair-fed group (PF) that received the same food amount consumed by the leptin group. Serum leptin and insulin were measured by ELISA, mRNA levels of interferon-γ (IFN-γ), interleukin-2 (IL-2), IL-4, IL-6, IL-10 and tumor necrosis factor-α (TNF-α) by real time PCR and serum and adipose tissue levels of these cytokines by multiplexed bead immunoassay. Serum leptin, IL-2, IL-4, IFN-γ and HOMA-IR were increased in L and TNF-α was decreased in PF and L. Serum leptin and IL-2 levels correlate positively with HOMA-IR index and negatively with serum glucose levels during an ip insulin tolerance test. In L, an increase in mRNA levels of IL-2 was found in both adipose depots and IFN-γ only in visceral tissue. Activation of leptin signaling was increased and insulin signaling decreased in subcutaneous fat of L. In conclusion, leptin mediates the production of inflammatory cytokines by adipose tissue independent of its effects on food intake, decreasing insulin sensitivity. PMID:23056516

  9. Maternal low glycaemic index diet, fat intake and postprandial glucose influences neonatal adiposity – secondary analysis from the ROLO study

    PubMed Central

    2014-01-01

    Background The in utero environment is known to affect fetal development however many of the mechanisms by which this occurs remain unknown. The aim of this study was to examine the association between maternal dietary macronutrient intake and lifestyle throughout pregnancy and neonatal weight and adiposity. Methods This was an analysis of 542 mother and infant pairs from the ROLO study (Randomised cOntrol trial of LOw glycaemic index diet versus no dietary intervention to prevent recurrence of fetal macrosomia). Food diaries as well as food frequency and lifestyle and physical activity questionnaires were completed during pregnancy. Maternal anthropometry was measured throughout pregnancy and neonatal anthropometry was measured at birth. Results Multiple linear regression analysis revealed the main maternal factor associated with increased birth weight was greater gestational weight gain R2adj23.3% (F = 11.547, p < 0.001). The main maternal factor associated with increased birth length was non-smoking status R2adj27.8% (F = 6.193, p < 0.001). Neonatal central adiposity (determined using waist:length ratio) was negatively associated with maternal age, and positively associated with the following parameters: smoking status, maternal pre-pregnancy arm circumference, percentage energy from saturated fat in late pregnancy, postprandial glucose at 28 weeks gestation and membership of the control group with a positive trend towards association with trimester 2 glycaemic load R2adj 38.1% (F = 8.000, p < 0.001). Conclusions Several maternal diet and lifestyle factors were associated with neonatal anthropometry . Low glycaemic index dietary intervention in pregnancy was found to have a beneficial effect on neonatal central adiposity. Additionally, central adiposity was positively associated with maternal dietary fat intake and postprandial glucose highlighting the important role of healthy diet in pregnancy in promoting normal neonatal adiposity

  10. Spatial structural integrity is important for adipose regeneration after transplantation.

    PubMed

    Yuan, Yi; Zhang, Shu; Gao, Jianhua; Lu, Feng

    2015-10-01

    Advances in structural fat transplantation technology have significantly improved the survival rate and stability of grafts. This study investigated the importance of the spatial structural integrity of adipose tissue for adipose regeneration after fat transplantation. We sought to enhance understanding of structural fat transplantation and optimize procedures used for the clinical acquisition, purification, and transplantation of adipose tissue. In an inactivated structuration adipose tissue model established by freezing at -20 °C for 3 days, nearly all cells were dead but the structure was intact. We transplanted this adipose tissue model (group A) or non-treated adipose tissue (group B) into GFP-expressing mice. Group B showed a higher graft survival percentage and less fibrosis than group A. The macrophage infiltration (F4/80) peak period was longer in group A than in group B. The change in vessel density (CD31) was similar in the two groups: it peaked at 4 weeks after transplantation and decreased thereafter. In both groups, the number of Ki67+ cells showed a similar trend. In comparison to group B, group A had more Ki67+ cells at 4-8 weeks after transplantation, but fewer of these cells at 12 weeks after transplantation. The intact spatial structure of adipose tissue, which is supported by adipocytes and extracellular matrix, provides a niche for adipogenesis and angiogenesis after fat transplantation.

  11. Adipose tissue and skeletal muscle blood flow during mental stress

    SciTech Connect

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  12. Our Fat Future: Translating Adipose Stem Cell Therapy

    PubMed Central

    Nordberg, Rachel C.

    2015-01-01

    Summary Human adipose stem cells (hASCs) have the potential to treat patients with a variety of clinical conditions. Recent advancements in translational research, regulatory policy, and industry have positioned hASCs on the threshold of clinical translation. We discuss the progress and challenges of bringing adipose stem cell therapy into mainstream clinical use. Significance This article details the advances made in recent years that have helped move human adipose stem cell therapy toward mainstream clinical use from a translational research, regulatory policy, and industrial standpoint. Four recurrent themes in translational technology as they pertain to human adipose stem cells are discussed: automated