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Sample records for adipose tissue muscles

  1. 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.

  2. Developmental Programming of Fetal Skeletal Muscle and Adipose Tissue Development

    PubMed Central

    Yan, Xu; Zhu, Mei-Jun; Dodson, Michael V.; Du, Min

    2013-01-01

    All important developmental milestones are accomplished during the fetal stage, and nutrient fluctuation during this stage produces lasting effects on offspring health, so called fetal programming or developmental programming. The fetal stage is critical for skeletal muscle development, as well as adipose and connective tissue development. Maternal under-nutrition at this stage affects the proliferation of myogenic precursor cells and reduces the number of muscle fibers formed. Maternal over-nutrition results in impaired myogenesis and elevated adipogenesis. Because myocytes, adipocytes and fibrocytes are all derived from mesenchymal stem cells, molecular events which regulate the commitment of stem cells to different lineages directly impact fetal muscle and adipose tissue development. Recent studies indicate that microRNA is intensively involved in myogenic and adipogenic differentiation from mesenchymal stem cells, and epigenetic changes such as DNA methylation are expected to alter cell lineage commitment during fetal muscle and adipose tissue development. PMID:25031653

  3. Clonogenic multipotent stem cells in human adipose tissue differentiate into functional smooth muscle cells

    PubMed Central

    Rodríguez, Larissa V.; Alfonso, Zeni; Zhang, Rong; Leung, Joanne; Wu, Benjamin; Ignarro, Louis J.

    2006-01-01

    Smooth muscle is a major component of human tissues and is essential for the normal function of a multitude of organs including the intestine, urinary tract and the vascular system. The use of stem cells for cell-based tissue engineering and regeneration strategies represents a promising alternative for smooth muscle repair. For such strategies to succeed, a reliable source of smooth muscle precursor cells must be identified. Adipose tissue provides an abundant source of multipotent cells. In this study, the capacity of processed lipoaspirate (PLA) and adipose-derived stem cells to differentiate into phenotypic and functional smooth muscle cells was evaluated. To induce differentiation, PLA cells were cultured in smooth muscle differentiation medium. Smooth muscle differentiation of PLA cells induced genetic expression of all smooth muscle markers and further confirmed by increased protein expression of smooth muscle cell-specific α actin (ASMA), calponin, caldesmon, SM22, myosin heavy chain (MHC), and smoothelin. Clonal studies of adipose derived multipotent cells demonstrated differentiation of these cells into smooth muscle cells in addition to trilineage differentiation capacity. Importantly, smooth muscle-differentiated cells, but not their precursors, exhibit the functional ability to contract and relax in direct response to pharmacologic agents. In conclusion, adipose-derived cells have the potential to differentiate into functional smooth muscle cells and, thus, adipose tissue can be a useful source of cells for treatment of injured tissues where smooth muscle plays an important role. PMID:16880387

  4. 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

  5. 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

  6. Weaning marginally affects glucose transporter (GLUT4) expression in calf muscles and adipose tissues.

    PubMed

    Hocquette, J F; Castiglia-Delavaud, C; Graulet, B; Ferré, P; Picard, B; Vermorel, M

    1997-08-01

    The nutritional regulation of glucose transporter GLUT4 was studied in eight muscles and four adipose tissues from two groups of preruminant (PR) or ruminant (R) calves of similar age (170 d), empty body weight (194 kg) at slaughter, and level of net energy intake from birth onwards. Isocitrate dehydrogenase (EC 1.1.1.41) activity in muscles was not different between PR and R except in masseter muscle from the cheek (+71% in R; P < 0.003), which becomes almost constantly active at weaning for food chewing. Basal and maximally-insulin-stimulated glucose transport rate (GTR) per g tissue wet weight in rectus abdominis muscle were significantly higher in R calves (+31 and 41% respectively; P < 0.05). GLUT4 protein contents did not differ in muscles from PR and R except in masseter (+74% in R; P < 0.05) indicating that the increased GTR in rectus abdominis cannot be accounted for by an enhanced GLUT4 expression. GLUT4 mRNA levels did not differ between the two groups of animals in all muscles suggesting a regulation of GLUT4 at the protein level in masseter. GLUT4 number expressed on a per cell basis was lower in adipose tissue from R calves (-39%; P < 0.05) and higher in internal than in peripheral adipose tissues. In summary, the regulation of GLUT4 in calves at weaning differs markedly from that previously described in rodents (for review, see Girard et al. 1992). Furthermore, significant inter-individual variations were shown for metabolic activities in muscle and for biochemical variables in adipose tissue.

  7. Insulin action in morbid obesity: a focus on muscle and adipose tissue.

    PubMed

    Mitrou, Panayota; Raptis, Sotirios A; Dimitriadis, George

    2013-01-01

    The aim of this review is to summarize the mechanisms underlying insulin resistance in morbid obesity. Glucose regulation by insulin depends on the suppression of endogenous glucose production and stimulation of glucose disposal. In morbid obesity, glucose production by the liver is increased. Moreover, the sensitivity of glucose metabolism to insulin is impaired both in muscle (due to defects in insulin-stimulated glucose utilization and decreased blood flow) and in adipose tissue (due to decreased blood flow). However, recent studies suggest that expanded total fat mass becomes a major consumer of glucose providing a sink for glucose and compensating for insulin resistance. Metabolism and immunity are closely linked. Bearing in mind the crosstalk between inflammatory pathways and the insulin signaling cascade, adipose tissue derived cytokines may represent a link between inflammation and metabolic signals and mediate, at least in part, insulin resistance. Adipose tissue plays a crucial role by buffering daily influx of dietary fat, suppressing the release of non-esterified fatty acids into the circulation and increasing triacylglycerol clearance. However, in morbid obesity there is an impairment of the normal ability of adipose tissue to buffer fatty acids, despite hyperinsulinemia. Lipotoxicity gradually impairs insulin action in the liver and muscle, aggravating insulin resistance.

  8. Regulation of HSL serine phosphorylation in skeletal muscle and adipose tissue.

    PubMed

    Watt, Matthew J; Holmes, Anna G; Pinnamaneni, Srijan K; Garnham, Andrew P; Steinberg, Gregory R; Kemp, Bruce E; Febbraio, Mark A

    2006-03-01

    Hormone-sensitive lipase (HSL) is important for the degradation of triacylglycerol in adipose and muscle tissue, but the tissue-specific regulation of this enzyme is not fully understood. We investigated the effects of adrenergic stimulation and AMPK activation in vitro and in circumstances where AMPK activity and catecholamines are physiologically elevated in humans in vivo (during physical exercise) on HSL activity and phosphorylation at Ser(563) and Ser(660), the PKA regulatory sites, and Ser(565), the AMPK regulatory site. In human experiments, skeletal muscle, subcutaneous adipose and venous blood samples were obtained before, at 15 and 90 min during, and 120 min after exercise. Skeletal muscle HSL activity was increased by approximately 80% at 15 min compared with rest and returned to resting rates at the cessation of and 120 min after exercise. Consistent with changes in plasma epinephrine, skeletal muscle HSL Ser(563) and Ser(660) phosphorylation were increased by 27% at 15 min (P < 0.05), remained elevated at 90 min, and returned to preexercise values postexercise. Skeletal muscle HSL Ser(565) phosphorylation and AMPK signaling were increased at 90 min during, and after, exercise. Phosphorylation of adipose tissue HSL paralleled changes in skeletal muscle in vivo, except HSL Ser(660) was elevated 80% in adipose compared with 35% in skeletal muscle during exercise. Studies in L6 myotubes and 3T3-L1 adipocytes revealed important tissue differences in the regulation of HSL. AMPK inhibited epinephrine-induced HSL activity in L6 myotubes and was associated with reduced HSL Ser(660) but not Ser(563) phosphorylation. HSL activity was reduced in L6 myotubes expressing constitutively active AMPK, confirming the inhibitory effects of AMPK on HSL activity. Conversely, in 3T3-L1 adipocytes, AMPK activation after epinephrine stimulation did not prevent HSL activity or glycerol release, which coincided with maintenance of HSL Ser(660) phosphorylation. Taken together

  9. Metformin and resveratrol ameliorate muscle insulin resistance through preventing lipolysis and inflammation in hypoxic adipose tissue.

    PubMed

    Zhao, Wenjun; Li, Aiyun; Feng, Xin; Hou, Ting; Liu, Kang; Liu, Baolin; Zhang, Ning

    2016-09-01

    This study aims to investigate the effects of metformin and resveratrol on muscle insulin resistance with emphasis on the regulation of lipolysis in hypoxic adipose tissue. ICR mice were fed with high fat diet (HFD) for 10days with administration of metformin, resveratrol, or intraperitoneal injection of digoxin. Adipose hypoxia, inflammation and cAMP/PKA-dependent lipolysis were investigated. Moreover, lipid deposition and insulin resistance were examined in the muscle. Metformin and resveratrol attenuated adipose hypoxia, inhibited HIF-1α expression and inflammation in the adipose tissue of HFD-fed mice. Metformin and resveratrol inhibited lipolysis through prevention of PKA/HSL activation by decreasing the accumulation of cAMP via preserving PDE3B. Metformin and resveratrol reduced FFAs influx and DAG accumulation, and thus improved insulin signaling in the muscle by inhibiting PKCθ translocation. This study presents a new view of regulating lipid metabolism to ameliorate insulin resistance and provides the clinical guiding significance for obesity and type 2 diabetes with metformin and resveratrol treatment. PMID:27343375

  10. Simulation of muscle and adipose tissue deformation in the passive human pharynx.

    PubMed

    Carrigy, Nicholas B; Carey, Jason P; Martin, Andrew R; Remmers, John E; Zareian, Ali; Topor, Zbigniew; Grosse, Joshua; Noga, Michelle; Finlay, Warren H

    2016-01-01

    Quantifying the contribution of passive mechanical deformation in the human pharynx to upper airway collapse is fundamental to understanding the competing biomechanical processes that maintain airway patency. This study uses finite element analysis to examine deformation in the passive human pharynx using an intricate 3D anatomical model based on computed tomography scan images. Linear elastic properties are assigned to bone, cartilage, ligament, tendon, and membrane structures based on a survey of values reported in the literature. Velopharyngeal and oropharyngeal cross-sectional area versus airway pressure slopes are determined as functions of Young's moduli of muscle and adipose tissue. In vivo pharyngeal mechanics for small deformations near atmospheric pressure are matched by altering Young's moduli of muscle and adipose tissue. The results indicate that Young's moduli ranging from 0.33 to 14 kPa for muscle and adipose tissue matched the in vivo range of area versus pressure slopes. The developed anatomical model and determined Young's moduli range are expected to be useful as a starting point for more complex simulations of human upper airway collapse and obstructive sleep apnea therapy.

  11. Comparison of Metabolic Network between Muscle and Intramuscular Adipose Tissues in Hanwoo Beef Cattle Using a Systems Biology Approach.

    PubMed

    Lee, Hyun-Jeong; Park, Hye-Sun; Kim, Woonsu; Yoon, Duhak; Seo, Seongwon

    2014-01-01

    The interrelationship between muscle and adipose tissues plays a major role in determining the quality of carcass traits. The objective of this study was to compare metabolic differences between muscle and intramuscular adipose (IMA) tissues in the longissimus dorsi (LD) of Hanwoo (Bos taurus coreanae) using the RNA-seq technology and a systems biology approach. The LD sections between the 6th and 7th ribs were removed from nine (each of three cows, steers, and bulls) Hanwoo beef cattle (carcass weight of 430.2 ± 40.66 kg) immediately after slaughter. The total mRNA from muscle, IMA, and subcutaneous adipose and omental adipose tissues were isolated and sequenced. The reads that passed quality control were mapped onto the bovine reference genome (build bosTau6), and differentially expressed genes across tissues were identified. The KEGG pathway enrichment tests revealed the opposite direction of metabolic regulation between muscle and IMA. Metabolic gene network analysis clearly indicated that oxidative metabolism was upregulated in muscle and downregulated in IMA. Interestingly, pathways for regulating cell adhesion, structure, and integrity and chemokine signaling pathway were upregulated in IMA and downregulated in muscle. It is thus inferred that IMA may play an important role in the regulation of development and structure of the LD tissues and muscle/adipose communication.

  12. Differential regulation of oxytocin receptor in various adipose tissue depots and skeletal muscle types in obese Zucker rats.

    PubMed

    Gajdosechova, L; Krskova, K; Olszanecki, R; Zorad, S

    2015-07-01

    Multifunctional peptide oxytocin currently undergoes intensive research due to its proposed anti-obesity properties. Until now, little is known about regulation of oxytocin receptor in metabolically active tissues in obesity. The aim of the present study was to measure expression of oxytocin receptor upon obese phenotype with respect to the variety among adipose tissue and skeletal muscles with distinct anatomical localisation. Total homogenates were prepared from epididymal, retroperitoneal and inguinal adipose tissues as well as quadriceps and soleus muscle from lean and obese Zucker rats. Oxytocin receptor protein was determined by immunoblot. Interestingly, elevated oxytocin receptor was observed in epididymal adipose tissue of obese rats in contrast to its downregulation in subcutaneous and no change in retroperitoneal fat. In lean animals, oxytocin receptor protein was expressed at similar levels in all adipose depots. This uniformity was not observed in the case of skeletal muscle in which fibre type composition seems to be determinant of oxytocin receptor expression. Quadriceps muscle with the predominance of glycolytic fibres exhibits higher oxytocin receptor expression than almost exclusively oxidative soleus muscle. Oxytocin receptor protein levels were decreased in both skeletal muscles analysed upon obese phenotype. The present work demonstrates that even under identical endocrine circumstances, oxytocin receptor is differentially regulated in adipose tissue of obese rats depending on fat depot localisation. These results also imply which tissues may be preferentially targeted by oxytocin treatment in metabolic disease.

  13. Adipose triglyceride lipase expression in human adipose tissue and muscle. Role in insulin resistance and response to training and pioglitazone

    PubMed Central

    Yao-Borengasser, Aiwei; Varma, Vijayalakshmi; Coker, Robert H.; Ranganathan, Gouri; Phanavanh, Bounleut; Rasouli, Neda; Kern, Philip A.

    2010-01-01

    Objective Adipose triglyceride lipase (ATGL) catalyzes the first step in adipocyte and muscle triglyceride hydrolysis, and Comparative Gene Identification-58 (CGI-58) is an essential cofactor. We studied the expression of ATGL and CGI-58 in human adipose and muscle, and examined correlations with markers of muscle fatty acid oxidation. Materials/Methods Non diabetic volunteers were studied. Subjects with impaired glucose tolerance were treated with pioglitazone or metformin for 10 weeks. Normal glucose tolerant subjects underwent a 12 week training program. We examined changes in ATGL and CGI-58 with obesity and insulin resistance, and effects of exercise and pioglitazone. Results ATGL mRNA expression showed no correlation with either body mass index (BMI) or insulin sensitivity (SI) in either adipose or muscle. However, adipose ATGL protein levels were inversely correlated with BMI (r=−0.64, p<0.02), and positively correlated with SI (r=0.67, p<0.02). In muscle, ATGL mRNA demonstrated a strong positive relationship with carnitine palmitoyltransferase I mRNA (r=0.82, p<0.0001), and the adiponectin receptors AdipoR1 mRNA (r=0.71, p<0.0001), and AdipoR2 mRNA (r=0.74, p<0.0001). Muscle CGI-58 mRNA was inversely correlated with intramyocellular triglyceride in both type 1 (r=−0.35, p<0.05) and type 2 (r=−0.40, p<0.05) fibers. Exercise training resulted in increased muscle ATGL and pioglitazone increased adipose ATGL by 31% (p<0.05). Pioglitazone also increased ATGL in adipocytes. Conclusions Adipose ATGL protein is decreased with insulin resistance and obesity, and muscle ATGL mRNA is associated with markers of fatty acid oxidation in muscle, as is CGI-58. The regulation of ATGL and CGI-58 have important implications for the control of lipotoxicity. PMID:21129760

  14. Cessation of daily wheel running differentially alters fat oxidation capacity in liver, muscle, and adipose tissue.

    PubMed

    Laye, Matthew J; Rector, R Scott; Borengasser, Sarah J; Naples, Scott P; Uptergrove, Grace M; Ibdah, Jamal A; Booth, Frank W; Thyfault, John P

    2009-01-01

    Physical inactivity is associated with the increased risk of developing chronic metabolic diseases. To understand early alterations caused by physical inactivity, we utilize an animal model in which rats are transitioned from daily voluntary wheel running to a sedentary condition. In the hours and days following this transition, adipose tissue mass rapidly increases, due in part to increased lipogenesis. However, whether a concurrent decrease in fatty acid oxidative capacity (FAO) in skeletal muscle, liver, and adipose tissue occurs during this period is unknown. Following 6 wk of access to voluntary running wheels (average distance of approximately 6 km a night), rats were rapidly transitioned to a sedentary state by locking the wheels for 5 h (WL5) or 173 h (WL173). Complete ([(14)C]palmitate oxidation to (14)CO(2)) and incomplete ([(14)C]palmitate oxidation to (14)C-labeled acid soluble metabolites) was determined in isolated mitochondrial and whole homogenate preparations from skeletal muscle and liver and in isolated adipocytes. Strikingly, the elevated complete FAO in the red gastrocnemius at WL5 fell to that of rats that never ran (SED) by WL173. In contrast, hepatic FAO was elevated at WL173 above both WL5 and SED groups, while in isolated adipocytes, FAO remained higher in both running groups (WL5 and WL173) compared with the SED group. The alterations in muscle and liver fat oxidation were associated with changes in carnitine palmitoyl transferase-1 activity and inhibition, but not significant changes in other mitochondrial enzyme activities. In addition, peroxisome proliferator-activated receptor coactivator-1alpha mRNA levels that were higher in both skeletal muscle and liver at WL5 fell to SED levels at WL173. This study is the first to demonstrate that the transition from high to low daily physical activity causes rapid, tissue-specific changes in FAO.

  15. Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.

    PubMed

    Bal, Naresh C; Maurya, Santosh K; Singh, Sushant; Wehrens, Xander H T; Periasamy, Muthu

    2016-08-12

    Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca(2+) cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35-37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and decreased body weight and fat mass, suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca(2+) handling and mitochondrial metabolism. These changes, along with increased sarcolipin expression, provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST when BAT activity is minimized.

  16. Increased Reliance on Muscle-based Thermogenesis upon Acute Minimization of Brown Adipose Tissue Function.

    PubMed

    Bal, Naresh C; Maurya, Santosh K; Singh, Sushant; Wehrens, Xander H T; Periasamy, Muthu

    2016-08-12

    Skeletal muscle has been suggested as a site of nonshivering thermogenesis (NST) besides brown adipose tissue (BAT). Studies in birds, which do not contain BAT, have demonstrated the importance of skeletal muscle-based NST. However, muscle-based NST in mammals remains poorly characterized. We recently reported that sarco/endoplasmic reticulum Ca(2+) cycling and that its regulation by SLN can be the basis for muscle NST. Because of the dominant role of BAT-mediated thermogenesis in rodents, the role of muscle-based NST is less obvious. In this study, we investigated whether muscle will become an important site of NST when BAT function is conditionally minimized in mice. We surgically removed interscapular BAT (iBAT, which constitutes ∼70% of total BAT) and exposed the mice to prolonged cold (4 °C) for 9 days. The iBAT-ablated mice were able to maintain optimal body temperature (∼35-37 °C) during the entire period of cold exposure. After 4 days in the cold, both sham controls and iBAT-ablated mice stopped shivering and resumed routine physical activity, indicating that they are cold-adapted. The iBAT-ablated mice showed higher oxygen consumption and decreased body weight and fat mass, suggesting an increased energy cost of cold adaptation. The skeletal muscles in these mice underwent extensive remodeling of both the sarcoplasmic reticulum and mitochondria, including alteration in the expression of key components of Ca(2+) handling and mitochondrial metabolism. These changes, along with increased sarcolipin expression, provide evidence for the recruitment of NST in skeletal muscle. These studies collectively suggest that skeletal muscle becomes the major site of NST when BAT activity is minimized. PMID:27298322

  17. 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

  18. 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

  19. Long-term stability of RNA in post-mortem bovine skeletal muscle, liver and subcutaneous adipose tissues

    PubMed Central

    Bahar, Bojlul; Monahan, Frank J; Moloney, Aidan P; Schmidt, Olaf; MacHugh, David E; Sweeney, Torres

    2007-01-01

    Background Recovering high quality intact RNA from post-mortem tissue is of major concern for gene expression studies in animals and humans. Since the availability of post-mortem tissue is often associated with substantial delay, it is important that we understand the temporal variation in the stability of total RNA and of individual gene transcripts so as to be able to appropriately interpret the data generated from such studies. Hence, the objective of this experiment was to qualitatively and quantitatively assess the integrity of total and messenger RNA extracted from bovine skeletal muscle, subcutaneous adipose tissue and liver stored at 4°C at a range of time points up to 22 days post-mortem. These conditions were designed to mimic the environment prevailing during the transport of beef from the abattoir to retail outlets. Results The 28S and 18S rRNA molecules of total RNA were intact for up to 24 h post-mortem in liver and adipose tissues and up to 8 days post-mortem in skeletal muscle. The mRNA of housekeeping genes (GAPDH and ACTB) and two diet-related genes (RBP5 and SCD) were detectable up to 22 days post-mortem in skeletal muscle. While the mRNA stability of the two housekeeping genes was different in skeletal muscle and liver, they were similar to each other in adipose tissue. After 22 days post-mortem, the relative abundance of RBP5 gene was increased in skeletal muscle and in adipose tissue and decreased in liver. During this period, the relative abundance of SCD gene also increased in skeletal muscle whereas it decreased in both adipose tissue and liver. Conclusion Stability of RNA in three tissues (skeletal muscle, subcutaneous adipose tissue and liver) subjected to long-term post-mortem storage at refrigeration temperature indicated that skeletal muscle can be a suitable tissue for recovering biologically useful RNA for gene expression studies even if the tissue is subjected to post-mortem storage for weeks, whereas adipose tissue and liver

  20. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland.

    PubMed

    Alves, Susana P; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J B; Almeida, André M

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases.

  1. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland.

    PubMed

    Alves, Susana P; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J B; Almeida, André M

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

  2. Fatty Acid Composition of Muscle, Adipose Tissue and Liver from Muskoxen (Ovibos moschatus) Living in West Greenland

    PubMed Central

    Alves, Susana P.; Raundrup, Katrine; Cabo, Ângelo; Bessa, Rui J. B.; Almeida, André M.

    2015-01-01

    Information about lipid content and fatty acid (FA) composition of muskoxen (Ovibos moschatos) edible tissues is very limited in comparison to other meat sources. Thus, this work aims to present the first in-depth characterization of the FA profile of meat, subcutaneous adipose tissue and liver of muskoxen living in West Greenland. Furthermore, we aim to evaluate the effect of sex in the FA composition of these edible tissues. Samples from muscle (Longissimus dorsi), subcutaneous adipose tissue and liver were collected from female and male muskoxen, which were delivered at the butchery in Kangerlussuaq (West Greenland) during the winter hunting season. The lipid content of muscle, adipose tissue and liver averaged 284, 846 and 173 mg/g of dry tissue, respectively. This large lipid contents confirms that in late winter, when forage availability is scarce, muskoxen from West Greenland still have high fat reserves, demonstrating that they are well adapted to seasonal feed restriction. A detailed characterization of FA and dimethylacetal composition of muskoxen muscle, subcutaneous adipose tissue and liver showed that there are little differences on FA composition between sexes. Nevertheless, the 18:1cis-9 was the most abundant FA in muscle and adipose tissue, reaching 43% of total FA in muscle. The high content of 18:1cis-9 suggests that it can be selectively stored in muskoxen tissues. Regarding the nutritional composition of muskoxen edible tissues, they are not a good source of polyunsaturated FA; however, they may contribute to a higher fat intake. Information about the FA composition of muskoxen meat and liver is scarce, so this work can contribute to the characterization of the nutritional fat properties of muskoxen edible tissues and can be also useful to update food composition databases. PMID:26678792

  3. Insulin-resistant subjects have normal angiogenic response to aerobic exercise training in skeletal muscle, but not in adipose tissue

    PubMed Central

    Walton, R Grace; Finlin, Brian S; Mula, Jyothi; Long, Douglas E; Zhu, Beibei; Fry, Christopher S; Westgate, Philip M; Lee, Jonah D; Bennett, Tamara; Kern, Philip A; Peterson, Charlotte A

    2015-01-01

    Reduced vessel density in adipose tissue and skeletal muscle is associated with obesity and may result in decreased perfusion, decreased oxygen consumption, and insulin resistance. In the presence of VEGFA, Angiopoietin-2 (Angpt2) and Angiopoietin-1 (Angpt1) are central determinants of angiogenesis, with greater Angpt2:Angpt1 ratios promoting angiogenesis. In skeletal muscle, exercise training stimulates angiogenesis and modulates transcription of VEGFA, Angpt1, and Angpt2. However, it remains unknown whether exercise training stimulates vessel growth in human adipose tissue, and it remains unknown whether adipose angiogenesis is mediated by angiopoietin signaling. We sought to determine whether insulin-resistant subjects would display an impaired angiogenic response to aerobic exercise training. Insulin-sensitive (IS, N = 12) and insulin-resistant (IR, N = 14) subjects had subcutaneous adipose and muscle (vastus lateralis) biopsies before and after 12 weeks of cycle ergometer training. In both tissues, we measured vessels and expression of pro-angiogenic genes. Exercise training did not increase insulin sensitivity in IR Subjects. In skeletal muscle, training resulted in increased vessels/muscle fiber and increased Angpt2:Angpt1 ratio in both IR and IS subjects. However, in adipose, exercise training only induced angiogenesis in IS subjects, likely due to chronic suppression of VEGFA expression in IR subjects. These results indicate that skeletal muscle of IR subjects exhibits a normal angiogenic response to exercise training. However, the same training regimen is insufficient to induce angiogenesis in adipose tissue of IR subjects, which may help to explain why we did not observe improved insulin sensitivity following aerobic training. PMID:26038468

  4. 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

  5. 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.

  6. beta3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet.

    PubMed

    Darimont, Christian; Turini, Marco; Epitaux, Micheline; Zbinden, Irène; Richelle, Myriam; Montell, Eulàlia; Ferrer-Martinez, Andreu; Macé, Katherine

    2004-08-17

    BACKGROUND: Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of beta3-adrenoceptor (beta3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective beta3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. METHODS: Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the beta3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. RESULTS: In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. CONCLUSIONS: These results show that activation of the beta3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with beta3-AR activation. PMID:15507149

  7. β3-adrenoceptor agonist prevents alterations of muscle diacylglycerol and adipose tissue phospholipids induced by a cafeteria diet

    PubMed Central

    Darimont, Christian; Turini, Marco; Epitaux, Micheline; Zbinden, Irène; Richelle, Myriam; Montell, Eulàlia; Ferrer-Martinez, Andreu; Macé, Katherine

    2004-01-01

    Background Insulin resistance induced by a high fat diet has been associated with alterations in lipid content and composition in skeletal muscle and adipose tissue. Administration of β3-adrenoceptor (β3-AR) agonists was recently reported to prevent insulin resistance induced by a high fat diet, such as the cafeteria diet. The objective of the present study was to determine whether a selective β3-AR agonist (ZD7114) could prevent alterations of the lipid profile of skeletal muscle and adipose tissue lipids induced by a cafeteria diet. Methods Male Sprague-Dawley rats fed a cafeteria diet were treated orally with either the β3-AR agonist ZD7114 (1 mg/kg per day) or the vehicle for 60 days. Rats fed a chow diet were used as a reference group. In addition to the determination of body weight and insulin plasma level, lipid content and fatty acid composition in gastronemius and in epididymal adipose tissue were measured by gas-liquid chromatography, at the end of the study. Results In addition to higher body weights and plasma insulin concentrations, rats fed a cafeteria diet had greater triacylglycerol (TAG) and diacylglycerol (DAG) accumulation in skeletal muscle, contrary to animals fed a chow diet. As expected, ZD7114 treatment prevented the excessive weight gain and hyperinsulinemia induced by the cafeteria diet. Furthermore, in ZD7114 treated rats, intramyocellular DAG levels were lower and the proportion of polyunsaturated fatty acids, particularly arachidonic acid, in adipose tissue phospholipids was higher than in animals fed a cafeteria diet. Conclusions These results show that activation of the β3-AR was able to prevent lipid alterations in muscle and adipose tissue associated with insulin resistance induced by the cafeteria diet. These changes in intramyocellular DAG levels and adipose tissue PL composition may contribute to the improved insulin sensitivity associated with β3-AR activation. PMID:15507149

  8. The role of matrix metalloproteinases in muscle and adipose tissue development and meat quality: A review.

    PubMed

    Christensen, Sara; Purslow, Peter P

    2016-09-01

    Matrix metalloproteinases (MMPs) are a group of enzymes that degrade extracellular matrix components but are also important signaling molecules that regulate many biological processes including muscle, adipose and connective tissue development. Most recently it has been discovered that MMPs act as intracellular signaling molecules inducing gene expression and altering related proteins in the nucleus. Several single nucleotide polymorphisms of MMPs and their inhibitors are known to exist and most of the research on MMPs to date has focused on their activity in relation to human health and disease. Nevertheless there is a growing body of evidence identifying important roles of MMPs as regulators of myogenesis, fibrogenesis and adipogenesis. The aim of this review is to highlight the currently known functions of the MMPs that have a direct bearing on the deposition of meat components and their relationship with meat quality. Some central pathways by which these enzymes can affect the tenderness, the amount and type of fatty acids are highlighted. PMID:27180222

  9. The role of matrix metalloproteinases in muscle and adipose tissue development and meat quality: A review.

    PubMed

    Christensen, Sara; Purslow, Peter P

    2016-09-01

    Matrix metalloproteinases (MMPs) are a group of enzymes that degrade extracellular matrix components but are also important signaling molecules that regulate many biological processes including muscle, adipose and connective tissue development. Most recently it has been discovered that MMPs act as intracellular signaling molecules inducing gene expression and altering related proteins in the nucleus. Several single nucleotide polymorphisms of MMPs and their inhibitors are known to exist and most of the research on MMPs to date has focused on their activity in relation to human health and disease. Nevertheless there is a growing body of evidence identifying important roles of MMPs as regulators of myogenesis, fibrogenesis and adipogenesis. The aim of this review is to highlight the currently known functions of the MMPs that have a direct bearing on the deposition of meat components and their relationship with meat quality. Some central pathways by which these enzymes can affect the tenderness, the amount and type of fatty acids are highlighted.

  10. Peripheral effects of the endocannabinoid system in energy homeostasis: adipose tissue, liver and skeletal muscle.

    PubMed

    Silvestri, Cristoforo; Ligresti, Alessia; Di Marzo, Vincenzo

    2011-09-01

    The endocannabinoid system (ECS) is composed of lipid signalling ligands, their G-protein coupled receptors and the enzymes involved in ligand generation and metabolism. Increasingly, the ECS is emerging as a critical agent of energy metabolism regulation through its ability to modulate caloric intake centrally as well as nutrient transport, cellular metabolism and energy storage peripherally. Visceral obesity has been associated with an upregulation of ECS activity in several systems and inhibition of the ECS, either pharmacologically or genetically, results in decreased energy intake and increased metabolic output. This review aims to summarize the recent advances that have been made regarding our understanding of the role the ECS plays in crucial peripheral systems pertaining to energy homeostasis: adipose tissues, the liver and skeletal muscle.

  11. Attenuated adipose tissue and skeletal muscle inflammation in obese mice with combined CD4+ and CD8+ T cell deficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    High-fat diet feeding in mice is characterized by accumulation of alpha Beta Y+T cells in adipose tissue. However, the contribution of ab T cells to obesity-induced inflammation of skeletal muscle, a major organ of glucose uptake, is unknown. This study was undertaken to evaluate the effect of alpha...

  12. Intermuscular adipose tissue and thigh muscle area dynamics during an 18-month randomized weight loss trial.

    PubMed

    Yaskolka Meir, Anat; Shelef, Ilan; Schwarzfuchs, Dan; Gepner, Yftach; Tene, Lilac; Zelicha, Hila; Tsaban, Gal; Bilitzky, Avital; Komy, Oded; Cohen, Noa; Bril, Nitzan; Rein, Michal; Serfaty, Dana; Kenigsbuch, Shira; Chassidim, Yoash; Zeller, Lior; Ceglarek, Uta; Stumvoll, Michael; Blüher, Matthias; Thiery, Joachim; Stampfer, Meir J; Rudich, Assaf; Shai, Iris

    2016-08-01

    It remains unclear whether intermuscular adipose tissue (IMAT) has any metabolic influence or whether it is merely a marker of abnormalities, as well as what are the effects of specific lifestyle strategies for weight loss on the dynamics of both IMAT and thigh muscle area (TMA). We followed the trajectory of IMAT and TMA during 18-mo lifestyle intervention among 278 sedentary participants with abdominal obesity, using magnetic resonance imaging. We measured the resting metabolic rate (RMR) by an indirect calorimeter. Among 273 eligible participants (47.8 ± 9.3 yr of age), the mean IMAT was 9.6 ± 4.6 cm(2) Baseline IMAT levels were directly correlated with waist circumference, abdominal subdepots, C-reactive protein, and leptin and inversely correlated with baseline TMA and creatinine (P < 0.05 for all). After 18 mo (86.3% adherence), both IMAT (-1.6%) and TMA (-3.3%) significantly decreased (P < 0.01 vs. baseline). The changes in both IMAT and TMA were similar across the lifestyle intervention groups and directly corresponded with moderate weight loss (P < 0.001). IMAT change did not remain independently associated with decreased abdominal subdepots or improved cardiometabolic parameters after adjustments for age, sex, and 18-mo weight loss. In similar models, 18-mo TMA loss remained associated with decreased RMR, decreased activity, and with increased fasting glucose levels and IMAT (P < 0.05 for all). Unlike other fat depots, IMAT may not represent a unique or specific adipose tissue, instead largely reflecting body weight change per se. Moderate weight loss induced a significant decrease in thigh muscle area, suggesting the importance of resistance training to accompany weight loss programs. PMID:27402560

  13. IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis

    PubMed Central

    Pierce, Joseph R.; Maples, Jill M.

    2015-01-01

    Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m2; n = 10) and obese (BMI: 34.7 ± 3.5 kg/m2; n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects (P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects (P = 0.02) and was correlated with SCAT lipolysis (r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese (P < 0.01), but exercise-induced SCAT lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean (P = 0.04) but suppressed lipolysis in obese (P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown. PMID:25921578

  14. Chronic hindlimb suspension unloading markedly decreases turnover rates of skeletal and cardiac muscle proteins and adipose tissue triglycerides.

    PubMed

    Bederman, Ilya R; Lai, Nicola; Shuster, Jeffrey; Henderson, Leigh; Ewart, Steven; Cabrera, Marco E

    2015-07-01

    We previously showed that a single bolus of "doubly-labeled" water ((2)H2 (18)O) can be used to simultaneously determine energy expenditure and turnover rates (synthesis and degradation) of tissue-specific lipids and proteins by modeling labeling patterns of protein-bound alanine and triglyceride-bound glycerol (Bederman IR, Dufner DA, Alexander JC, Previs SF. Am J Physiol Endocrinol Metab 290: E1048-E1056, 2006). Using this novel method, we quantified changes in the whole body and tissue-specific energy balance in a rat model of simulated "microgravity" induced by hindlimb suspension unloading (HSU). After chronic HSU (3 wk), rats exhibited marked atrophy of skeletal and cardiac muscles and significant decrease in adipose tissue mass. For example, soleus muscle mass progressively decreased 11, 43, and 52%. We found similar energy expenditure between control (90 ± 3 kcal · kg(-1)· day(-1)) and hindlimb suspended (81 ± 6 kcal/kg day) animals. By comparing food intake (∼ 112 kcal · kg(-1) · day(-1)) and expenditure, we found that animals maintained positive calorie balance proportional to their body weight. From multicompartmental fitting of (2)H-labeling patterns, we found significantly (P < 0.005) decreased rates of synthesis (percent decrease from control: cardiac, 25.5%; soleus, 70.3%; extensor digitorum longus, 44.9%; gastrocnemius, 52.5%; and adipose tissue, 39.5%) and rates of degradation (muscles: cardiac, 9.7%; soleus, 52.0%; extensor digitorum longus, 27.8%; gastrocnemius, 37.4%; and adipose tissue, 50.2%). Overall, HSU affected growth of young rats by decreasing the turnover rates of proteins in skeletal and cardiac muscles and adipose tissue triglycerides. Specifically, we found that synthesis rates of skeletal and cardiac muscle proteins were affected to a much greater degree compared with the decrease in degradation rates, resulting in large negative balance and significant tissue loss. In contrast, we found a small decrease in adipose tissue

  15. Identification and comparison of microRNAs from skeletal muscle and adipose tissues from two porcine breeds.

    PubMed

    Li, Hong-Yi; Xi, Qian-Yun; Xiong, Yuan-Yan; Liu, Xiao-Long; Cheng, Xiao; Shu, Gang; Wang, Song-Bo; Wang, Li-Na; Gao, Ping; Zhu, Xiao-Tong; Jiang, Qing-Yan; Yuan, Li; Zhang, Yong-Liang

    2012-12-01

    MicroRNAs (miRNAs) are an abundant class of small regulatory RNAs that negatively regulate gene expression at the post-transcriptional level. Although an increasing number of porcine miRNAs recently have been identified, research has yet to identify the full repertoire of miRNAs in pig skeletal and adipose tissues and their differences between breeds. We extracted small RNA from skeletal muscle and adipose tissues of Landrace and Lantang pigs, and the expression of a total of 184 known porcine miRNAs (113 from Solexa sequencing and 171 from miRNA chip hybridization) as well as 521 novel miRNA candidates was detected. Moreover, 20 miRNAs were selected randomly from the 184 miRNAs and analysed by quantitative real-time PCR to confirm the aforementioned results. In the skeletal muscle tissues, 21 miRNAs were up-regulated in Lantang and another 33 were highly expressed in Landrace pigs. In the adipose tissues, 25 miRNAs were down-regulated in Lantang and another 23 were lowly expressed in Landrace pigs. miRNA divergence between tissues was also detected in this study. Ten miRNAs were highly expressed in the skeletal muscle tissue in comparison with adipose tissue, and another 10 miRNAs exhibited the opposite expression profile. To investigate the regulatory mechanism of the miRNAs in muscle and adipose tissues, the 10 miRNAs with the most divergent expression profiles were functionally categorized using the Kyoto Encyclopedia of Genes and Genomes database. Most of the miRNAs strongly corresponded to myogenesis and adipogenesis processes. In addition, 84 of the 521 miRNA candidates were potentially porcine-specific miRNAs. This study adds new valuable information to comparative miRNA profiles of skeletal muscle and adipose tissues in porcine species. The great diversity of miRNA composition and expression levels both between breeds and between tissues suggests that a complex regulatory network exists in porcine subcutaneous fat development.

  16. CONTRAST-ENHANCED ULTRASOUND ASSESSMENT OF IMPAIRED ADIPOSE TISSUE AND MUSCLE PERFUSION IN INSULIN-RESISTANT MICE

    PubMed Central

    Belcik, J. Todd; Davidson, Brian P.; Foster, Ted; Qi, Yue; Zhao, Yan; Peters, Dawn; Lindner, Jonathan R.

    2015-01-01

    Background In diabetes mellitus reduced perfusion and capillary surface area in skeletal muscle, which is a major glucose storage site, contributes to abnormal glucose homeostasis. Using contrast-enhanced ultrasound (CEU) we investigated whether abdominal adipose tissue perfusion is abnormal in insulin resistance (IR) and correlates with glycemic control. Methods and Results Abdominal adipose tissue and skeletal muscle CEU perfusion imaging was performed in obese IR (db/db) mice at 11-12 or 14-16 weeks of age, and in control lean mice. Time-intensity data were analyzed to quantify microvascular blood flow (MBF) and capillary blood volume (CBV). Blood glucose response over one hour was measured after insulin challenge (1 u/Kg, I.P.). Compared to control mice, db/db mice at 11-12 and 14-16 weeks had a higher glucose concentration area-under-the-curve after insulin (11.8±2.8, 20.6±4.3, and 28.4±5.9 mg·min/dL [×1000], respectively, p=0.0002), and also had lower adipose MBF (0.094±0.038, 0.035±0.010, and 0.023±0.01 mL/min/g, p=0.0002) and CBV (1.6±0.6, 1.0±0.3, and 0.5±0.1 mL/100 g, p=0.0017). The glucose area-under-the-curve correlated in a non-linear fashion with both adipose and skeletal muscle MBF and CBV. There were significant linear correlations between adipose and muscle MBF (r=0.81) and CBV (r=0.66). Adipocyte cell volume on histology was 25-fold higher in 14-16 week db/db versus control mice. Conclusions Abnormal adipose MBF and CBV in IR can be detected by CEU and correlates with the degree of impairment in glucose storage. Abnormalities in adipose tissue and muscle appear to be coupled. Impaired adipose tissue perfusion is in part explained by an increase in adipocyte size without proportional vascular response. PMID:25855669

  17. Thigh fat and muscle each contribute to excess cardiometabolic risk in South Asians, independent of visceral adipose tissue

    PubMed Central

    Eastwood, Sophie V; Tillin, Therese; Wright, Andrew; Mayet, Jamil; Godsland, Ian; Forouhi, Nita G; Whincup, Peter; Hughes, Alun D; Chaturvedi, Nishi

    2014-01-01

    Objective To compare fat distribution and associations between fat depots and cardiometabolic traits in South Asians and Europeans. Methods Five hundred and fourteen South Asians and 669 Europeans, aged 56-86. Questionnaires, record review, blood testing, and coronary artery calcification scores provided diabetes and clinical plus subclinical coronary heart disease (CHD) diagnoses. Abdominal visceral (VAT) and subcutaneous adipose tissue, thigh subcutaneous adipose tissue (TSAT), intermuscular and intramuscular thigh fat and thigh muscle were measured by CT. Results Accounting for body size, South Asians had greater VAT and TSAT than Europeans, but less thigh muscle. Associations between depots and disease were stronger in South Asians than Europeans. In multivariable analyses in South Asians, VAT was positively associated with diabetes and CHD, while TSAT and thigh muscle were protective for diabetes, and thigh muscle for CHD. Differences in VAT and thigh muscle only partially explained the excess diabetes and CHD in South Asians versus Europeans. Insulin resistance did not account for the effects of TSAT or thigh muscle. Conclusions Greater VAT and TSAT and lesser thigh muscle in South Asians contributed to ethnic differences in cardiometabolic disease. Effects of TSAT and thigh muscle were independent of insulin resistance. PMID:24862429

  18. Mass dynamics of wintering Pacific Black Brant: Body, adipose tissue, organ, and muscle masses vary with location

    USGS Publications Warehouse

    Mason, D.D.; Barboza, P.S.; Ward, D.H.

    2007-01-01

    We compared body size and mass of the whole body, organs, adipose tissue, and muscles of adult Pacific Black Brant (Branta bernicla nigricans (Lawrence, 1846)) collected concurrently in Alaska and Baja California during the fall, winter, and spring of 2002-2003. Head and tarsal lengths of males were similar between sites and slightly larger for females in Alaska than in Baja California. Brant appear to operate under similar physiological bounds, but patterns of nutrient allocation differ between sites. Birds wintering in Alaska lost similar amounts of adipose tissue during early winter as birds in Baja California gained during late winter before migration. Masses of the body, adipose tissue, and flight muscles during mid-winter were similar between sites. Seasonal adipose tissue deposition may, therefore, equally favor winter residency or long-distance migration. Gonad and liver masses increased in late winter for birds in Alaska but not for those in Baja California, suggesting birds wintering in Baja may delay reproductive development in favor of allocating reserves needed for migration. Phenotypic flexibility allows Brant to use widely divergent wintering sites. The wintering location of Brant likely depends more upon changes in environmental conditions and food availability, than upon physiological differences between the two wintering populations. ?? 2007 NRC.

  19. FNDC5 expression and circulating irisin levels are modified by diet and hormonal conditions in hypothalamus, adipose tissue and muscle

    PubMed Central

    Varela-Rodríguez, B. M.; Pena-Bello, L.; Juiz-Valiña, P.; Vidal-Bretal, B.; Cordido, F.; Sangiao-Alvarellos, S.

    2016-01-01

    Irisin is processed from fibronectin type III domain-containing protein 5 (FNDC5). However, a controversy exists concerning irisin origin, regulation and function. To elucidate the relationship between serum irisin and FNDC5 mRNA expression levels, we evaluated plasma irisin levels and FNDC5 gene expression in the hypothalamus, gastrocnemius muscle and different depots of adipose tissue in models of altered metabolism. In normal rats, blood irisin levels diminished after 48-h fast and with leptin, insulin and alloxan treatments, and serum irisin concentrations increased in diabetic rats after insulin treatment and acute treatments of irisin increased blood insulin levels. No changes were observed during long-term experiments with different diets. We suggested that levels of circulating irisin are the result of the sum of the irisin produced by different depots of adipose tissue and skeletal muscle. This study shows for the first time that there are differences in FNDC5 expression depending on white adipose tissue depots. Moreover, a considerable decrease in visceral and epididymal adipose tissue depots correlated with increased FNDC5 mRNA expression levels, probably in an attempt to compensate the decrease that occurs in their mass. Hypothalamic FNDC5 expression did not change for any of the tested diets but increased with leptin, insulin and metformin treatments suggesting that the regulation of central and peripheral FNDC5/irisin expression and functions are different. PMID:27432282

  20. 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.

  1. 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.

  2. Lipid composition of muscle and adipose tissue from crossbred ram, wether and cryptorchid lambs.

    PubMed

    Solomon, M B; Lynch, G P; Ono, K; Paroczay, E

    1990-01-01

    Lambs from rams (R), cryptorchids (C) and wethers (W) were examined to compare with the dietary guidelines for humans on fat and cholesterol intake. Twenty-four lambs were assigned to treatments as R, C or W at weaning (60 d). Each lamb had ad libitum access to a 77:23% forage:concentrate diet containing 11.7% crude protein and 1.84 Mcal ME/kg. The experiment was terminated when the lambs reached 50 kg body weight. Lipid composition of the longissimus muscle (LM) and s.c. adipose tissue was determined by gas-liquid chromatography. Rams has less (P less than .01) s.c. fat (cm) and i.m. lipid (%) (.26 cm; 3.*%) than W (.56 cm; 4.9%). Total polyunsaturated fatty acids were greater (P less than .01) in the LM of R (7.06%) than in LM of W (5.21%). Rams had higher percentages of C18:2, C18:3, C20:4 and C18:1 in their LM than W did. On the basis of a 100-g serving of LM, R had 1.73, C had 2.15 and W had 2.21 g saturated fatty acids. There were no (P less than .01) differences among sex types for cholesterol content of LM, which averaged 66.6 mg/100 g wet tissue. The only major difference of the s.c. fat lipid composition was in saturated fatty acids. Wethers had higher (P less than .01) saturated fatty acids (51.4%) than C 46.8%) and R (43.3%). Based on the lipid composition of these three types of lambs, the LM muscle from young R lambs approached dietary fat guidelines for humans more closely than did that from castrates.

  3. Effect of 2,4-Thiazolidinedione on Limousin Cattle Growth and on Muscle and Adipose Tissue Metabolism

    PubMed Central

    Arévalo-Turrubiarte, M.; González-Dávalos, L.; Yabuta, A.; Garza, J. D.; Dávalos, J. L.; Mora, O.; Shimada, A.

    2012-01-01

    The main adipogenic transcription factor PPARγ possesses high affinity to 2,4-TZD, a member of the Thiazolidinedione family of insulin-sensitizing compounds used as adipogenic agents. We evaluated 2,4-TZD's effect on bovine growth and PPAR tissue expression. Seventeen Limousin bulls (18 month-old; 350 kg body weight (BW)) were assigned into 2 treatments: control and 2,4-TZD (8 mg/70 kg BW) and were fed until bulls reached 500 kg BW. They were weighed and their blood was sampled. DNA, RNA, and protein were determined in liver; skeletal muscle; subcutaneous (SC), omental, perirenal adipose tissues (AT) to determine protein synthesis rate and cellular size. Expression of PPAR mRNA was measured in liver and muscle (PPARα, -δ, and -γ) and SC adipose tissue (γ) by real-time PCR. No significant differences were found (P > 0.1) in weight gain, days on feed, and carcass quality. Muscle synthesis was greater in controls (P < 0.05); cell size was larger with 2,4-TZD (P < 0.05). PPARα, -δ, and -γ expressions with 2,4-TZD in liver were lower (P < 0.01) than in muscle. No differences were found for PPARγ mRNA expression in SCAT. The results suggest the potential use of 2,4-TZD in beef cattle diets, because it improves AT differentiation, liver, and muscle fatty acid oxidation that, therefore, might improve energy efficiency. PMID:23304114

  4. 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.

  5. Between-slice intervals in quantification of adipose tissue and muscle in children

    PubMed Central

    Shen, Wei; Chen, Jun; Kwak, Sofia; Punyanitya, Mark; Heymsfield, Steven B.

    2010-01-01

    Magnetic Resonance Imaging (MRI) is increasingly being used in children to quantify adipose tissue (AT) and skeletal muscle (SM) in vivo. it is unclear whether the every 5 cm whole body MRI protocol used in adults is appropriate when applied in children. Whole body MRI continuous 1 cm thick slices were acquired in 73, aged 5–17-year-old healthy children. images were segmented into subcutaneous (SAT), visceral (VAT), intermuscular At (IMAT), and SM. the percentage difference between volumes measured by the continuous protocol and volumes estimated with protocols of different between-slice intervals (i.e., interval = 2, 3, 4 and 5 cm) was larger with an increase in interval size, depot size, weight and body mass index percentile. For group comparisons, studies will require less than 5.4% more subjects if an every 5 cm protocol is used for equivalent power as the every 1 cm protocol. For individual subject comparisons, interval protocols can be used to reliably distinguish between subjects who differ in SM or SAT volume by 0.14 to 0.64 l (i.e., 1 to 5% of SM or SAT volume) or more, or in VAT or IMAT volume by 0.06 to 0.21 l (i.e., 10 to 30% of VAT or IMAT volume) or more. the every 5 cm image acquisition protocol can be considered as accurate as the contiguous protocol for group comparisons in children, as well as for comparison of SM and SAT among individual children. however, a smaller slice interval protocol would be more accurate for comparison of VAT or IMAT among individual children. PMID:20528126

  6. Lactate and the GPR81 receptor in metabolic regulation: implications for adipose tissue function and fatty acid utilisation by muscle during exercise.

    PubMed

    Rooney, Kieron; Trayhurn, Paul

    2011-11-01

    Lactate is increasingly recognised to be more than a simple end product of anaerobic glycolysis. Skeletal muscle and white adipose tissue are considered to be the main sites of lactate production and release. Recent studies have demonstrated that there is a specific G-protein coupled receptor for lactate, GPR81, which is expressed primarily in adipose tissue, and also in muscle. Lactate inhibits lipolysis in adipose tissue by mediating, through GPR81, the anti-lipolytic action of insulin. A high proportion (50 % or more) of the glucose utilised by white adipose tissue is converted to lactate and lactate production by the tissue increases markedly in obesity; this is likely to reflect a switch towards anaerobic metabolism with the development of hypoxia in the tissue. During exercise, there is a shift in fuel utilisation by muscle from lipid to carbohydrate, but this does not appear to be a result of the inhibition of lipolysis in the main adipose tissue depots by muscle-derived lactate. It is suggested instead that a putative autocrine lactate loop in myocytes may regulate fuel utilisation by muscle during exercise, operating via a muscle GPR81 receptor. In addition to being an important substrate, lactate is a key signal in metabolic regulation.

  7. Evaluation of adipose-derived stem cells for tissue-engineered muscle repair construct-mediated repair of a murine model of volumetric muscle loss injury.

    PubMed

    Kesireddy, Venu

    2016-01-01

    Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR-MDC constructs as previously reported. PMID:27114706

  8. Evaluation of adipose-derived stem cells for tissue-engineered muscle repair construct-mediated repair of a murine model of volumetric muscle loss injury

    PubMed Central

    Kesireddy, Venu

    2016-01-01

    Volumetric muscle loss (VML) can occur from congenital defects, muscle wasting diseases, civilian or military injuries, and as a result of surgical removal of muscle tissue (eg, cancer), all of which can lead to irrevocable functional and cosmetic defects. Current tissue engineering strategies to repair VML often employ muscle-derived progenitor cells (MDCs) as one component. However, there are some inherent limitations in their in vitro culture expansion. Thus, this study explores the potential of adipose-derived stem cells (ADSCs) as an alternative cell source to MDCs for tissue engineering of skeletal muscle. A reproducible VML injury model in murine latissimus dorsi muscle was used to evaluate tissue-engineered muscle repair (TEMR) constructs incorporating MDCs or ADSCs. Importantly, histological analysis revealed that ADSC-seeded constructs displayed regeneration potential that was comparable to those seeded with MDCs 2 months postrepair. Furthermore, morphological analysis of retrieved constructs demonstrated signs of neotissue formation, including cell fusion, fiber formation, and scaffold remodeling. Immunohistochemistry demonstrated positive staining for both structural and functional proteins. Positive staining for vascular structures indicated the potential for long-term neotissue survival and integration with existing musculature. Qualitative observation of lentivirus-Cherry-labeled donor cells by immunohistochemistry indicates that participation of ADSCs in new hybrid myofiber formation incorporating donor cells was relatively low, compared to donor MDCs. However, ADSCs appear to participate in vascularization. In summary, I have demonstrated that TEMR constructs generated with ADSCs displayed skeletal muscle regeneration potential comparable to TEMR–MDC constructs as previously reported. PMID:27114706

  9. [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.

  10. Human Adipose Tissue Derived Stem Cells as a Source of Smooth Muscle Cells in the Regeneration of Muscular Layer of Urinary Bladder Wall

    PubMed Central

    SALEM, Salah Abood; HWIE, Angela Ng Min; SAIM, Aminuddin; CHEE KONG, Christopher Ho; SAGAP, Ismail; SINGH, Rajesh; YUSOF, Mohd Reusmaazran; MD ZAINUDDIN, Zulkifili; HJ IDRUS, Ruszymah

    2013-01-01

    Background: Adipose tissue provides an abundant source of multipotent cells, which represent a source of cell-based regeneration strategies for urinary bladder smooth muscle repair. Our objective was to confirm that adipose-derived stem cells (ADSCs) can be differentiated into smooth muscle cells. Methods: In this study, adipose tissue samples were digested with 0.075% collagenase, and the resulting ADSCs were cultured and expanded in vitro. ADSCs at passage two were differentiated by incubation in smooth muscle inductive media (SMIM) consisting of MCDB I31 medium, 1% FBS, and 100 U/mL heparin for three and six weeks. ADSCs in non-inductive media were used as controls. Characterisation was performed by cell morphology and gene and protein expression. Result: The differentiated cells became elongated and spindle shaped, and towards the end of six weeks, sporadic cell aggregation appeared that is typical of smooth muscle cell culture. Smooth muscle markers (i.e. alpha smooth muscle actin (ASMA), calponin, and myosin heavy chain (MHC)) were used to study gene expression. Expression of these genes was detected by PCR after three and six weeks of differentiation. At the protein expression level, ASMA, MHC, and smoothelin were expressed after six weeks of differentiation. However, only ASMA and smoothelin were expressed after three weeks of differentiation. Conclusion: Adipose tissue provides a possible source of smooth muscle precursor cells that possess the potential capability of smooth muscle differentiation. This represents a promising alternative for urinary bladder smooth muscle repair. PMID:24044001

  11. Differential regulation of adipose tissue glucose transporters in genetic obesity (fatty rat). Selective increase in the adipose cell/muscle glucose transporter (GLUT 4) expression.

    PubMed

    Hainault, I; Guerre-Millo, M; Guichard, C; Lavau, M

    1991-03-01

    Adipocytes from young obese Zucker rats exhibit a hyperresponsive insulin-mediated glucose transport, together with a marked increase in cytochalasin B binding as compared with lean rat adipocytes. Here, we examined in these cells the expression of two isoforms of glucose transporter, the erythroid (GLUT 1) and the adipose cell/muscle (GLUT 4) types, in rats aged 16 or 30 d, i.e., before and after the emergence of hyperinsulinemia. GLUT 1 protein and mRNA levels were identical in the two genotypes at both ages. In contrast, the levels of GLUT 4 protein in obese rat adipocytes were 2.4- and 4.5-fold those of lean littermates at 16 and 30 d of age, respectively, in perfect agreement with the genotype effect on insulin-stimulated glucose transport activity. The levels of GLUT 4 mRNA per fat pad were increased 2.3- and 6.2-fold in obese vs. lean rats 16- and 30-d-old, indicating a pretranslational level of regulation. The obese phenotype was not associated with overexpression of GLUT 4 mRNA in gastrocnemius muscle. This work indicates that the fa gene exerts a differential control on the expression of GLUT 1 and GLUT 4 in adipose tissue and provides evidence that independent of hyperinsulinemia, genotype is a major regulatory factor of GLUT 4 expression in this tissue.

  12. 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

  13. Butyrate supplementation to gestating sows and piglets induces muscle and adipose tissue oxidative genes and improves growth performance.

    PubMed

    Lu, H; Su, S; Ajuwon, K M

    2012-12-01

    Weaned pigs often experience growth reduction immediately after weaning due to multiple stress factors associated with weaning. We tested the effect of prenatal and postnatal butyrate supplementation on growth performance of piglets. In study 1, piglets were orally gavaged with 0.3% butyrate from day 4 after birth to weaning (day 21). Butyrate increased ADG by 13% compared to saline treated control. Expression of peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α) was higher in muscle, adipose tissue, and ileum of butyrate-supplemented animals. Also, peroxisome proliferator activated receptor alpha (PPARα) was induced (P < 0.05) in the subcutaneous adipose tissue (SCAT) and muscle (longissimus dorsi [LD]) of butyrate-supplemented piglets. In vitro, butyrate increased (P < 0.05) fatty acid oxidation in primary adipocytes and suppressed basal lipolysis by 62% compared to untreated cells. Butyrate suppressed (P < 0.05) lipogenesis ((14)C-glucose incorporation into lipids) in adipocytes. This was accompanied by an approximately 30% reduction in the mRNA expression of fatty acid synthase (P < 0.05) in butyrate-treated cells vs. controls. Piglets born to sows that were supplemented with 0.3% butyrate during the last trimester of gestation had a 15% higher (P < 0.05) body weight at 12 wk than controls. In summary, butyrate supplementation to gestating sows and piglets enhanced postweaning growth performance, which may be mediated by increased substrate oxidation in butyrate treated animals.

  14. Transcript profiles in longissimus dorsi muscle and subcutaneous adipose tissue: a comparison of pigs with different postweaning growth rates.

    PubMed

    Pilcher, C M; Jones, C K; Schroyen, M; Severin, A J; Patience, J F; Tuggle, C K; Koltes, J E

    2015-05-01

    Although most pigs recover rapidly from stresses associated with the transition of weaning, a portion of the population lags behind their contemporaries in growth performance. The underlying biological and molecular mechanisms involved in postweaning differences in growth performance are poorly understood. The objective of this experiment was to use transcriptional profiling of skeletal muscle and adipose tissue to develop a better understanding of the metabolic basis for poor weaned-pig transition. A total of 1,054 pigs was reared in commercial conditions and weighed at birth, weaning, and 3 wk postweaning. Transition ADG (tADG) was calculated as the ADG for the 3-wk period postweaning. Nine pigs from both the lowest 10th percentile (low tADG) and the 60th to 70th percentile (high tADG) were harvested at 3 wk postweaning. Differential expression analysis was conducted in longissimus dorsi muscle (LM) and subcutaneous adipose tissue using RNA-Seq methodology. In LM, 768 transcripts were differentially expressed (DE), 327 with higher expression in low tADG and 441 with higher expression in high tADG pigs (q < 0.10). Expression patterns measured in LM by RNA-Seq were verified in 30 of 32 transcripts using quantitative PCR. No DE transcripts were identified in adipose tissue. To identify biological functions potentially underlying the effects of tADG on skeletal muscle metabolism and physiology, functional annotation analysis of the DE transcripts was conducted using DAVID and Pathway Studio analytic tools. The group of DE genes with lower expression in LM of low tADG pigs was enriched in genes with functions related to muscle contraction, glucose metabolism, cytoskeleton organization, muscle development, and response to hormone stimulus (enrichment score > 1.3). The list of DE genes with higher expression in low tADG LM was enriched in genes with functions related to protein catabolism (enrichment score > 1.3). Analysis of known gene-gene interactions identified

  15. 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.

  16. Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anaemia.

    PubMed

    Di Sebastiano, Katie M; Yang, Lin; Zbuk, Kevin; Wong, Raimond K; Chow, Tom; Koff, David; Moran, Gerald R; Mourtzakis, Marina

    2013-01-28

    Weight loss leading to cachexia is associated with poor treatment response and reduced survival in pancreatic cancer patients. We aim to identify indicators that allow for early detection that will advance our understanding of cachexia and will support targeted anti-cachexia therapies. A total of fifty pancreatic cancer patients were analysed for skeletal muscle and visceral adipose tissue (VAT) changes using computed tomography (CT) scans. These changes were related to physical characteristics, secondary disease states and treatment parameters. Overall, patients lost 1.72 (SD 3.29) kg of muscle and 1.04 (SD 1.08) kg of VAT during the disease trajectory (413 (SD 213) d). After sorting patients into tertiles by rate of VAT and muscle loss, patients losing VAT at > -0.40 kg/100 d had poorer survival outcomes compared with patients with < -0.10 kg/100 d of VAT loss (P= 0.020). Patients presenting with diabetes at diagnosis demonstrated significantly more and accelerated VAT loss compared with non-diabetic patients. In contrast, patients who were anaemic at the first CT scan lost significantly more muscle tissue and at accelerated rates compared with non-anaemic patients. Accelerated rates of VAT loss are associated with reduced survival. Identifying associated features of cachexia, such as diabetes and anaemia, is essential for the early detection of cachexia and may facilitate the attenuation of complications associated with cachexia. PMID:23021109

  17. Adipose and Muscle Tissue Gene Expression of Two Genes (NCAPG and LCORL) Located in a Chromosomal Region Associated with Cattle Feed Intake and Gain

    PubMed Central

    Lindholm-Perry, Amanda K.; Kuehn, Larry A.; Oliver, William T.; Sexten, Andrea K.; Miles, Jeremy R.; Rempel, Lea A.; Cushman, Robert A.; Freetly, Harvey C.

    2013-01-01

    A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG) and average daily feed intake (ADFI) in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only), cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01). These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues. PMID:24278337

  18. Adipose and muscle tissue gene expression of two genes (NCAPG and LCORL) located in a chromosomal region associated with cattle feed intake and gain.

    PubMed

    Lindholm-Perry, Amanda K; Kuehn, Larry A; Oliver, William T; Sexten, Andrea K; Miles, Jeremy R; Rempel, Lea A; Cushman, Robert A; Freetly, Harvey C

    2013-01-01

    A region on bovine chromosome 6 has been implicated in cattle birth weight, growth, and length. Non-SMC conodensin I complex subunit G (NCAPG) and ligand dependent nuclear receptor corepressor-like protein (LCORL) are positional candidate genes within this region. Previously identified genetic markers in both genes were associated with average daily gain (ADG) and average daily feed intake (ADFI) in a crossbred population of beef steers. These markers were also associated with hot carcass weight, ribeye area and adjusted fat thickness suggesting that they may have a role in lean muscle growth and/or fat deposition. The purpose of this study was to determine whether the transcript abundance of either of these genes in cattle adipose and muscle tissue was associated with variation in feed intake and average daily gain phenotypes. Transcript abundance for NCAPG and LCORL in adipose and muscle tissue was measured in heifers (adipose only), cows and steers using real-time polymerase chain reaction. In the adipose tissue from cows and heifers, a negative correlation between LCORL transcript abundance and ADFI were detected (P = 0.05). In the muscle tissue from cows, transcript abundance of NCAPG was associated with ADG (r = 0.26; P = 0.009). A positive correlation between LCORL transcript abundance from muscle tissue of steers and ADFI was detected (P = 0.04). LCORL protein levels in the muscle of steers were investigated and were associated with ADFI (P = 0.01). These data support our earlier genetic associations with ADFI and ADG within this region and represent the potential for biological activity of these genes in the muscle and adipose tissues of beef cattle; however, they also suggest that sex, age and/or nutrition-specific interactions may affect the expression of NCAPG and LCORL in these tissues.

  19. Melatonin increases intracellular calcium in the liver, muscle, white adipose tissues and pancreas of diabetic obese rats.

    PubMed

    Agil, A; Elmahallawy, E K; Rodríguez-Ferrer, J M; Adem, A; Bastaki, S M; Al-Abbadi, I; Fino Solano, Y A; Navarro-Alarcón, M

    2015-08-01

    Melatonin, a widespread substance with antioxidant and anti-inflammatory properties, has been found to act as an antidiabetic agent in animal models, regulating the release and action of insulin. However, the molecular bases of this antidiabetic action are unknown, limiting its application in humans. Several studies have recently shown that melatonin can modify calcium (Ca(2+)) in diabetic animals, and Ca(2+) has been reported to be involved in glucose homeostasis. The objective of the present study was to assess whether the antidiabetic effect of chronic melatonin at pharmacological doses is established via Ca(2+) regulation in different tissues in an animal model of obesity-related type 2 diabetes, using Zücker diabetic fatty (ZDF) rats and their lean littermates, Zücker lean (ZL) rats. After the treatments, flame atomic absorption spectrometry was used to determine Ca(2+) levels in the liver, muscle, main types of internal white adipose tissue, subcutaneous lumbar fat, pancreas, brain, and plasma. This study reports for the first time that chronic melatonin administration (10 mg per kg body weight per day for 6 weeks) increases Ca(2+) levels in muscle, liver, different adipose tissues, and pancreas in ZDF rats, although there were no significant changes in their brain or plasma Ca(2+) levels. We propose that this additional peripheral dual action mechanism underlies the improvement in insulin sensitivity and secretion previously documented in samples from the same animals. According to these results, indoleamine may be a potential candidate for the treatment of type 2 diabetes mellitus associated with obesity.

  20. Ligand binding properties of putative beta 3-adrenoceptors compared in brown adipose tissue and in skeletal muscle membranes.

    PubMed Central

    Sillence, M. N.; Moore, N. G.; Pegg, G. G.; Lindsay, D. B.

    1993-01-01

    1. The beta-adrenoceptor population was characterized in membrane preparations from rat brown adipose tissue (BAT) and from soleus muscle by use of the radioligand [125I]-iodocyanopindolol ([125I]-ICYP). In addition, atypical binding sites for [125I]-ICYP found in both tissues were examined, and the relationship between these sites and the putative rat beta 3-adrenoceptor is discussed. 2. It was established that BAT membranes host a mixed population of beta 1- and beta 2-adrenoceptors. Of these two sites, 55% showed a high affinity for the beta 1-selective ligand CGP 20712A (pK 8.5), and 45% showed a high affinity for the beta 2-selective antagonist ICI 118551 (pK 8.6). Soleus muscle membranes were found to host a population of beta 2-adrenoceptors, characterized by a high affinity for ICI 118551 (pK 9.1), but beta 1-adrenoceptors could not be detected in this preparation. 5-Hydroxytryptamine receptors were not detected in either preparation. 3. In addition to beta 1- and beta 2-adrenoceptors, atypical binding sites were identified in both tissues using high concentrations of radioligand (0.5-0.6 nM) and in the presence of 1 microM (-)-propranolol. The atypical sites were abundant, representing 80 and 81% of the total [125I]-ICYP binding sites in BAT and soleus muscle respectively. When the pK values for 11 ligands were compared, the correlation coefficient for atypical sites in BAT and soleus muscle was 0.94.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8104645

  1. 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

  2. Effects of a Diet Enriched with Polyunsaturated, Saturated, or Trans Fatty Acids on Cytokine Content in the Liver, White Adipose Tissue, and Skeletal Muscle of Adult Mice

    PubMed Central

    dos Santos, Bruno; Estadella, Debora; Hachul, Ana Cláudia Losinskas; Okuda, Marcos Hiromu; Moreno, Mayara Franzoi; Oyama, Lila Missae; Ribeiro, Eliane Beraldi; Oller do Nascimento, Claudia Maria da Penha

    2013-01-01

    This study analyzed the effect of diet enriched with 30% lipids on cytokines content in different tissues. Swiss male mice were distributed into four groups treated for 8 weeks with control (C, normolipidic diet); soybean oil (S); lard (L); and hydrogenated vegetable fat (H). We observed an increase in carcass fat in groups S and L, and the total amount of fatty deposits was only higher in group L compared with C group. The serum levels of free fatty acids were lower in the L group, and insulin, adiponectin, lipid profile, and glucose levels were similar among the groups. IL-10 was lower in group L in mesenteric and retroperitoneal adipose tissues. H reduced IL-10 only in retroperitoneal adipose tissue. There was an increase in IL-6 in the gastrocnemius muscle of the L group, and a positive correlation between TNF-α and IL-10 was observed in the livers of groups C, L, and H and in the muscles of all groups studied. The results suggested relationships between the quantity and quality of lipids ingested with adiposity, the concentration of free fatty acids, and cytokine production in white adipose tissue, gastrocnemius muscle, and liver. PMID:24027356

  3. Weaning affects lipoprotein lipase activity and gene expression in adipose tissues and in masseter but not in other muscles of the calf.

    PubMed

    Hocquette, J F; Graulet, B; Vermorel, M; Bauchart, D

    2001-10-01

    The nutritional and physiological modifications that occur during the weaning period induce adaptations of tissue metabolism in all mammal species. Among the adaptations due to weaning in ruminants, the regulation of lipoprotein lipase (LPL) activity, one of the rate-limiting steps of fatty acid utilization by tissues, was still unknown. The present study aimed at comparing LPL activity and gene expression in the heart, seven skeletal muscles and three adipose tissue sites between two groups of seven preruminant (PR) or ruminant (R) calves having a similar age (170 d), similar empty body weight (194 kg) at slaughter, and similar net energy intake from birth onwards. Triacylglycerol content of adipose tissues was 16 % lower in R than in PR calves, This could be partly the result from a lower LPL activity (-57 %, ). LPL mRNA levels were also lower in R calves (-48 % to -68 %, ) suggesting a pretranslational regulation of LPL activity. Activity and mRNA levels of LPL did not differ significantly in the heart and skeletal muscles except in the masseter in which LPL activity and mRNA levels were higher (+50 % and +120 % respectively, ) in the R calves. Regulation of LPL in masseter could be explained by the high contractile activity of this muscle after weaning due to solid food chewing. In conclusion, weaning in the calf affects LPL activity and expression in adipose tissues, but not in skeletal muscles except the masseter.

  4. 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.

  5. Ectopic brown adipose tissue in muscle provides a mechanism for differences in risk of metabolic syndrome in mice

    PubMed Central

    Almind, Katrine; Manieri, Monia; Sivitz, William I.; Cinti, Saverio; Kahn, C. Ronald

    2007-01-01

    C57BL/6 (B6) mice subjected to a high-fat diet develop metabolic syndrome with obesity, hyperglycemia, and insulin resistance, whereas 129S6/SvEvTac (129) mice are relatively protected from this disorder because of differences in higher basal energy expenditure in 129 mice, leading to lower weight gain. At a molecular level, this difference correlates with a marked higher expression of uncoupling protein 1 (UCP1) and a higher degree of uncoupling in vitro in mitochondria isolated from muscle of 129 versus B6 mice. Detailed histological examination, however, reveals that this UCP1 is in mitochondria of brown adipocytes interspersed between muscle bundles. Indeed, the number of UCP1-positive brown fat cells in intermuscular fat in 129 mice is >700-fold higher than in B6 mice. These brown fat cells are subject to further up-regulation of UCP1 after stimulation with a β3-adrenergic receptor agonist. Thus, ectopic deposits of brown adipose tissue in intermuscular depots with regulatable expression of UCP1 provide a genetically based mechanism of protection from weight gain and metabolic syndrome between strains of mice. PMID:17283342

  6. Moderate Exercise Training Attenuates the Severity of Experimental Rodent Colitis: The Importance of Crosstalk between Adipose Tissue and Skeletal Muscles

    PubMed Central

    Mazur-Bialy, Agnieszka I.; Krzysiek-Maczka, Gracjana; Urbanczyk, Katarzyna; Ptak-Belowska, Agata; Mach, Tomasz; Brzozowski, Tomasz

    2015-01-01

    Although progress has been recently made in understanding of inflammatory bowel diseases (IBD), their etiology is unknown apart from several factors from adipose tissue and skeletal muscles such as cytokines, adipokines, and myokines were implicated in the pathogenesis of ulcerative colitis. We studied the effect high-fat diet (HFD; cholesterol up to 70%), low-fat diet (LFD; cholesterol up to 10%), and the normal diet (total fat up to 5%) in rats with TNBS colitis forced to treadmill running exercise (5 days/week) for 6 weeks. In nonexercising HFD rats, the area of colonic damage, colonic tissue weight, the plasma IL-1β, TNF-α, TWEAK, and leptin levels, and the expression of IL-1β-, TNF-α-, and Hif1α mRNAs were significantly increased and a significant fall in plasma adiponectin and irisin levels was observed as compared to LFD rats. In HFD animals, the exercise significantly accelerated the healing of colitis, raised the plasma levels of IL-6 and irisin, downregulated the expression of IL-1β, TNF-α, and Hif1α, and significantly decreased the plasma IL-1β, TNF α, TWEAK, and leptin levels. We conclude that HFD delays the healing of colitis in trained rats via decrease in CBF and plasma IL-1β, TNF-α, TWEAK, and leptin levels and the release of protective irisin. PMID:25684862

  7. 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.

  8. Physical training and weight loss in dogs lead to transcriptional changes in genes involved in the glucose-transport pathway in muscle and adipose tissues.

    PubMed

    Herrera Uribe, Juber; Vitger, Anne D; Ritz, Christian; Fredholm, Merete; Bjørnvad, Charlotte R; Cirera, Susanna

    2016-02-01

    Obesity is a worldwide problem in humans and domestic animals. Interventions, including a combination of dietary management and exercise, have proven to be effective for inducing weight loss in humans. In companion animals, the role of exercise in the management of obesity has received relatively little attention. The aim of the present study was to investigate changes in the transcriptome of key energy metabolism genes in muscle and adipose tissues in response to diet-induced weight loss alone, or combined with exercise in dogs. Overweight pet dogs were enrolled on a weight loss programme, based on calorie restriction and physical training (FD group, n = 5) or calorie restriction alone (DO group, n = 7). mRNA expression of 12 genes and six microRNAs were investigated using quantitative real-time PCR (qPCR). In the FD group, FOXO1 and RAC1 were expressed at lower levels in adipose tissue, whereas ESRRA and AKT2 were more highly expressed in muscle, when compared with the DO group. Comparing expression before and after the intervention, in the DO group, nine genes and three microRNAs showed significant altered expression in adipose tissue (PPARG, ADIPOQ and FOXO1; P < 0.001) and seven genes and two microRNAs were significantly downregulated (NRF2, RAC1, ESRRA, AKT2, PGC1a and mir-23; P < 0.001) in muscle. Thus, calorie restriction causes regulation of several metabolic genes in both tissues. The mild exercise, incorporated into this study design, was sufficient to elicit transcriptional changes in adipose and muscle tissues, suggesting a positive effect on glucose metabolism. The study findings support inclusion of exercise in management of canine obesity.

  9. Physical training and weight loss in dogs lead to transcriptional changes in genes involved in the glucose-transport pathway in muscle and adipose tissues.

    PubMed

    Herrera Uribe, Juber; Vitger, Anne D; Ritz, Christian; Fredholm, Merete; Bjørnvad, Charlotte R; Cirera, Susanna

    2016-02-01

    Obesity is a worldwide problem in humans and domestic animals. Interventions, including a combination of dietary management and exercise, have proven to be effective for inducing weight loss in humans. In companion animals, the role of exercise in the management of obesity has received relatively little attention. The aim of the present study was to investigate changes in the transcriptome of key energy metabolism genes in muscle and adipose tissues in response to diet-induced weight loss alone, or combined with exercise in dogs. Overweight pet dogs were enrolled on a weight loss programme, based on calorie restriction and physical training (FD group, n = 5) or calorie restriction alone (DO group, n = 7). mRNA expression of 12 genes and six microRNAs were investigated using quantitative real-time PCR (qPCR). In the FD group, FOXO1 and RAC1 were expressed at lower levels in adipose tissue, whereas ESRRA and AKT2 were more highly expressed in muscle, when compared with the DO group. Comparing expression before and after the intervention, in the DO group, nine genes and three microRNAs showed significant altered expression in adipose tissue (PPARG, ADIPOQ and FOXO1; P < 0.001) and seven genes and two microRNAs were significantly downregulated (NRF2, RAC1, ESRRA, AKT2, PGC1a and mir-23; P < 0.001) in muscle. Thus, calorie restriction causes regulation of several metabolic genes in both tissues. The mild exercise, incorporated into this study design, was sufficient to elicit transcriptional changes in adipose and muscle tissues, suggesting a positive effect on glucose metabolism. The study findings support inclusion of exercise in management of canine obesity. PMID:26701817

  10. 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

  11. 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

  12. 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

  13. Role of the Adipose Tissue in Determining Muscle Mass in Patients with Chronic Kidney Disease

    PubMed Central

    Castaneda-Sceppa, Carmen; Sarnak, Mark J.; Wang, Xuelei; Greene, Tom; Madero, Magdalena; Kusek, John W.; Beck, Gerald; Collins, Allan J.; Kopple, Joel D.; Levey, Andrew S.; Menon, Vandana

    2009-01-01

    Objective Malnutrition is a powerful predictor of mortality in chronic kidney disease (CKD); however, its etiology is unclear. We hypothesized that adipocyte-derived proteins leptin and adiponectin, inflammation (C-reactive protein –CRP), and insulin resistance (Homeostasis Model Assessment –HOMA); implicated in the malnutrition-inflammation complex syndrome commonly seen in maintenance dialysis patients, would be associated with the loss of muscle mass in earlier stages of CKD. Arm muscle area was used as an indicator of muscle mass. Setting The Modification of Diet in Renal Disease (MDRD) Study cohort of people with CKD stages 3 and 4 was used for analysis. Main Outcome Measures Regression models were carried out to examine the relationships of leptin, adiponectin, CRP, and HOMA with arm muscle area (the main study outcome). Results Arm muscle area was 39 ± 15 cm2 (mean ± standard deviation, SD) and adiponectin levels were 13 ± 7 μg/mL. Median and (inerquartile range, IQR) concentrations were: 9.0 (13.6) ng/mL for leptin, 2.3 (4.9) mg/L for CRP, and 2.4 (2.0) form HOMA. Higher leptin [beta coefficient and (95% confidence interval): −6.9 (−8.7, −5.1), P<0.001] and higher CRP [−2.7 (−3.9, −1.4), P<0.001] were associated with lower arm muscle area. There was a trend toward lower arm muscle area with higher adiponectin (P=0.07) but no association with HOMA (P=0.80). Conclusion Leptin and CRP were associated with lower muscle mass in subjects with CKD stages 3–4. Further studies are needed to understand the mechanisms underlying these associations and to develop targeted interventions for this patient population. PMID:17720100

  14. Molecular mechanisms underlying the effects of cyclosporin A and sirolimus on glucose and lipid metabolism in liver, skeletal muscle and adipose tissue in an in vivo rat model.

    PubMed

    Fuhrmann, A; Lopes, Pc; Sereno, J; Pedro, J; Espinoza, D O; Pereira, M J; Reis, F; Eriksson, J W; Carvalho, E

    2014-03-15

    Cyclosporin A (CsA) and sirolimus (SRL) are immunosuppressive agents (IAs) associated with dyslipidemia, insulin resistance and new onset diabetes after transplantation (NODAT). However, the molecular mechanisms involved are not fully understood. We investigated the effects of six-week treatment of either CsA or SRL on glucose and lipid metabolism in Wistar rats. The results show that, compared with vehicle-treated rats, SRL-treated rats were significantly lighter starting at week 5. CsA or SRL caused glucose intolerance, increased storage of lipids in the liver and skeletal muscle, and decreased the insulin-stimulated glucose uptake in isolated adipocytes. Furthermore, these agents significantly decreased genes involved in insulin action and glucose uptake, such as, IRS-1, Glut4 and Glut1, and increased genes and/or proteins involved in hepatic lipogenesis and gluconeogenesis, while decreasing them in adipose tissue. After either treatment PGC1α gene expression was down regulated in skeletal muscle, an important player in fatty acid oxidation. Moreover, there was an increase in IL-6 gene expression in adipose tissue in the SRL-treated rats, suggesting stimulation of lipolysis. The results of the present study suggest that CsA and SRL lead to metabolic alterations in liver, muscle and adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy. PMID:24462915

  15. Seasonal changes in the expression of energy metabolism-related genes in white adipose tissue and skeletal muscle in female Japanese black bears.

    PubMed

    Shimozuru, Michito; Nagashima, Akiko; Tanaka, Jun; Tsubota, Toshio

    2016-01-01

    Bears undergo annual cycles in body mass: rapid fattening in autumn (i.e., hyperphagia), and mass loss in winter (i.e., hibernation). To investigate how Japanese black bears (Ursus thibetanus japonicus) adapt to such extreme physiological conditions, we analyzed changes in the mRNA expression of energy metabolism-related genes in white adipose tissues and skeletal muscle throughout three physiological stages: normal activity (June), hyperphagia (November), and hibernation (March). During hyperphagia, quantitative real-time polymerase chain reaction analysis revealed the upregulation of de novo lipogenesis-related genes (e.g., fatty acid synthase and diacylglycerol O-acyltransferase 2) in white adipose tissue, although the bears had been maintained with a constant amount of food. In contrast, during the hibernation period, we observed a downregulation of genes involved in glycolysis (e.g., glucose transporter 4) and lipogenesis (e.g., acetyl-CoA carboxylase 1) and an upregulation of genes in fatty acid catabolism (e.g., carnitine palmitoyltransferase 1A) in both tissue types. In white adipose tissues, we observed upregulation of genes involved in glyceroneogenesis, including pyruvate carboxylase and phosphoenolpyruvate carboxykinase 1, suggesting that white adipose tissue plays a role in the recycling of circulating free fatty acids via re-esterification. In addition, the downregulation of genes involved in amino acid catabolism (e.g., alanine aminotransferase) and the TCA cycle (e.g., pyruvate carboxylase) indicated a role of skeletal muscle in muscle protein sparing and pyruvate recycling via the Cori cycle. These examples of coordinated transcriptional regulation would contribute to rapid mass gain during the pre-hibernation period and to energy preservation and efficient energy production during the hibernation period.

  16. Seasonal changes in the expression of energy metabolism-related genes in white adipose tissue and skeletal muscle in female Japanese black bears.

    PubMed

    Shimozuru, Michito; Nagashima, Akiko; Tanaka, Jun; Tsubota, Toshio

    2016-01-01

    Bears undergo annual cycles in body mass: rapid fattening in autumn (i.e., hyperphagia), and mass loss in winter (i.e., hibernation). To investigate how Japanese black bears (Ursus thibetanus japonicus) adapt to such extreme physiological conditions, we analyzed changes in the mRNA expression of energy metabolism-related genes in white adipose tissues and skeletal muscle throughout three physiological stages: normal activity (June), hyperphagia (November), and hibernation (March). During hyperphagia, quantitative real-time polymerase chain reaction analysis revealed the upregulation of de novo lipogenesis-related genes (e.g., fatty acid synthase and diacylglycerol O-acyltransferase 2) in white adipose tissue, although the bears had been maintained with a constant amount of food. In contrast, during the hibernation period, we observed a downregulation of genes involved in glycolysis (e.g., glucose transporter 4) and lipogenesis (e.g., acetyl-CoA carboxylase 1) and an upregulation of genes in fatty acid catabolism (e.g., carnitine palmitoyltransferase 1A) in both tissue types. In white adipose tissues, we observed upregulation of genes involved in glyceroneogenesis, including pyruvate carboxylase and phosphoenolpyruvate carboxykinase 1, suggesting that white adipose tissue plays a role in the recycling of circulating free fatty acids via re-esterification. In addition, the downregulation of genes involved in amino acid catabolism (e.g., alanine aminotransferase) and the TCA cycle (e.g., pyruvate carboxylase) indicated a role of skeletal muscle in muscle protein sparing and pyruvate recycling via the Cori cycle. These examples of coordinated transcriptional regulation would contribute to rapid mass gain during the pre-hibernation period and to energy preservation and efficient energy production during the hibernation period. PMID:26880364

  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. Circulating ghrelin and leptin concentrations and growth hormone secretagogue receptor abundance in liver, muscle, and adipose tissue of beef cattle exhibiting differences in composition of gain.

    PubMed

    Jennings, J S; Wertz-Lutz, A E; Pritchard, R H; Weaver, A D; Keisler, D H; Bruns, K

    2011-12-01

    Data from species other than cattle indicate that ghrelin and GH secretagogue receptor (GHS-R) could play a key role in fat deposition, energy homeostasis, or glucose metabolism by directly affecting liver and adipose tissue metabolism. Beef steers (n = 72) were used to test the hypothesis that plasma ghrelin and leptin concentrations and abundance of the GHS-R in liver, muscle, and adipose tissues differ in steers exhibiting differences in composition of gain. At trial initiation (d 0), 8 steers were slaughtered for initial carcass composition. The remaining 64 steers were stratified by BW, allotted to pen, and treatment was assigned randomly to pen. Steers were not implanted with anabolic steroids. Treatments were 1) a low-energy (LE) diet fed during the growing period (0 to 111 d) followed by a high-energy (HE) diet during the finishing period (112 to 209 d; LE-HE) or 2) the HE diet for the duration of the trial (1 to 209 d; HE-HE). Eight steers per treatment were slaughtered on d 88, 111, 160, and 209. Carcass ninth, tenth, and eleventh rib sections were dissected for chemical composition and regression equations were developed to predict compositional gain. Liver, muscle, and subcutaneous adipose tissues were frozen in liquid nitrogen for subsequent Western blotting for GHS-R. Replicate blood samples collected before each slaughter were assayed for ghrelin and leptin concentrations. When compared at a common compositional fat end-point, the rate of carcass fat accretion (g·kg of shrunk BW(-1)) was greater (P < 0.001) in HE-HE steers whereas the rate of carcass protein accretion (g·kg of shrunk BW(-1)) was less (P < 0.001) compared with LE-HE steers. When compared at a common compositional fat end-point, plasma leptin, ghrelin, and insulin concentrations were greater (P < 0.05) for HE-HE compared with LE-HE steers. Abundance of the GHS-R, to which ghrelin binds, increased over time in liver and adipose tissue but did not differ as a result of treatment

  19. Adipose, bone and muscle tissues as new endocrine organs: role of reciprocal regulation for osteoporosis and obesity development.

    PubMed

    Migliaccio, Silvia; Greco, Emanuela A; Wannenes, Francesca; Donini, Lorenzo M; Lenzi, Andrea

    2014-01-01

    The belief that obesity is protective against osteoporosis has recently been revised. In fact, the latest epidemiologic and clinical studies show that a high level of fat mass, but also reduced muscle mass, might be a risk factor for osteoporosis and fragility fractures. Furthermore, increasing evidence seems to indicate that different components such as myokines, adipokines and growth factors, released by both fat and muscle tissues, could play a key role in the regulation of skeletal health and in low bone mineral density and, thus, in osteoporosis development. This review considers old and recent data in the literature to further evaluate the relationship between fat, bone and muscle tissue.

  20. Effects of nutrient restriction of bovine dams during early gestation on postnatal growth, carcass and organ characteristics, and gene expression in adipose tissue and muscle.

    PubMed

    Long, N M; Prado-Cooper, M J; Krehbiel, C R; DeSilva, U; Wettemann, R P

    2010-10-01

    Angus x Hereford heifers (15 mo and artificially inseminated to a single sire) were used to evaluate the effect of prenatal nutritional restriction on postnatal growth and development. At d 32 of gestation, dams were stratified by BW and BCS and allotted to a low-nutrition [55% of NRC (1996) requirements, n = 10] or moderate-nutrition [100% of NRC (1996) requirements, n = 10] diet. After 83 d of feeding, dams were commingled and received a diet in excess of requirements. Dams were allowed to calve naturally, and birth weights and growth of calves were recorded. Bulls were castrated at birth. Steers (16 mo of age, 5 per treatment) received a high-concentrate diet ad libitum to a constant age (88 ± 1 wk). Steers were slaughtered and weights of the empty body and organs were recorded. Samples of organs, muscle (complexus), and perirenal and subcutaneous adipose tissue were stored at -80 degrees C, and then DNA and protein concentrations were quantified and expression of genes associated with fatty acid metabolism and glucose uptake were measured in adipose and muscle tissue. Dams had similar (P > 0.33) BW and BCS at the beginning of the experiment. At the end of restriction, dams on the low-nutrition diet weighed less (P ≤ 0.01) and had less BCS (P < 0.001) than those on the moderate-nutrition diet. Length of gestation was 274 ± 2 d for dams in the low-nutrition treatment and 278 ± 2 d (P = 0.05) for dams in the moderate-nutrition treatment. Nutrient restriction during gestation did not influence birth weight or postnatal growth of calves. Lungs and trachea of steers whose dams were fed the low-nutrition diet weighed less (P = 0.05) at slaughter than those of steers whose dams were fed the moderate-nutrition diet; weights of other organs were not influenced by treatment. Complexus muscle from steers whose dams were fed the low-nutrition diet had a greater (P = 0.04) concentration of DNA and larger muscle fiber area compared with steers whose dams were fed the

  1. 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

  2. Fatty acid profile of plasma, muscle and adipose tissues in Chilota lambs grazing on two different low quality pasture types in Chiloé Archipelago (Chile).

    PubMed

    Gallardo, Maria A; Dannenberger, Dirk; Rivero, Jordana; Pulido, Ruben; Nuernberg, Karin

    2014-11-01

    There is no information about the effect of different pasture types on tissue fatty acid profiles of a native rustic lamb breed of the Chiloe Archipelago, the Chilota. Eight Chilota lambs were grazed on a 'Calafatal' pasture (CP), a typical secondary succession of Chiloé Archipelago (Chile) and eight Chilota lambs were located to graze on naturalized pasture (NP) of Chiloé. Botanical, chemical and lipid composition of the two types of pastures and of different lamb tissues (muscle, subcutaneous - and tail adipose tissues) and plasma were performed. Both pasture types induced high n-3 polyunsaturated fatty acids (PUFA) and CLAcis-9,trans-11 proportions in Chilota meat. Thus, in muscle, Chilota lambs grazing CP showed higher sum PUFA, sum n-6 PUFA proportion and n-6/n-3 PUFA ratio compared with Chilota lambs grazing NP. In tail fats of Chilota lambs grazing CP significantly higher proportions of 18:3n-3, sum saturated fatty acids, sum PUFA, n-3 and n-6 PUFA were detected compared with Chilota lambs grazing NP. Feeding of different pasture types (CP vs. NP) caused significant differences in fatty acid composition of muscle and the two fat depots in Chilota lambs, but also point to tissue-specific responses of de novo synthesized fatty acid deposition in the tissues.

  3. Crosstalk between intestinal microbiota, adipose tissue and skeletal muscle as an early event in systemic low-grade inflammation and the development of obesity and diabetes.

    PubMed

    Bleau, Christian; Karelis, Antony D; St-Pierre, David H; Lamontagne, Lucie

    2015-09-01

    Obesity is associated with a systemic chronic low-grade inflammation that contributes to the development of metabolic disorders such as cardiovascular diseases and type 2 diabetes. However, the etiology of this obesity-related pro-inflammatory process remains unclear. Most studies have focused on adipose tissue dysfunctions and/or insulin resistance in skeletal muscle cells as well as changes in adipokine profile and macrophage recruitment as potential sources of inflammation. However, low-grade systemic inflammation probably involves a complex network of signals interconnecting several organs. Recent evidences have suggested that disturbances in the composition of the gut microbial flora and alterations in levels of gut peptides following the ingestion of a high-fat diet may be a cause of low-grade systemic inflammation that may even precede and predispose to obesity, metabolic disorders or type 2 diabetes. This hypothesis is appealing because the gastrointestinal system is first exposed to nutrients and may thereby represent the first link in the chain of events leading to the development of obesity-associated systemic inflammation. Therefore, the present review will summarize the latest advances interconnecting intestinal mucosal bacteria-mediated inflammation, adipose tissue and skeletal muscle in a coordinated circuitry favouring the onset of a high-fat diet-related systemic low-grade inflammation preceding obesity and predisposing to metabolic disorders and/or type 2 diabetes. A particular emphasis will be given to high-fat diet-induced alterations of gut homeostasis as an early initiator event of mucosal inflammation and adverse consequences contributing to the promotion of extended systemic inflammation, especially in adipose and muscular tissues.

  4. Nutritional status induces divergent variations of GLUT4 protein content, but not lipoprotein lipase activity, between adipose tissues and muscles in adult cattle.

    PubMed

    Bonnet, Muriel; Faulconnier, Yannick; Hocquette, Jean-François; Bocquier, François; Leroux, Christine; Martin, Patrice; Chilliard, Yves

    2004-10-01

    Metabolic adaptations to variations in food supply are incompletely understood in ruminant animal adipose tissue (AT) and muscle. To explore this, we studied lipid metabolism and glucose transport potential in one internal and one external AT, as well as in one oxidative and one glycolytic muscle from control, 7 d underfed and 21 d refed adult cows. Refeeding increased (+79 to +307 %) the activities of enzymes involved in de novo lipogenesis (fatty acid synthase, malic enzyme, glucose-6-phosphate dehydrogenase) in perirenal and subcutaneous AT; underfeeding did not modify these variables. Underfeeding decreased the activities of lipoprotein lipase (LPL) in perirenal AT (-70 %) and cardiac muscle (-67 %), but did not modify the activities in subcutaneous AT and longissimus thoracis. Refeeding increased LPL activities in all tissues (+40 to +553 %) to levels comparable with (cardiac muscle) or greater than (AT, longissimus thoracis) those observed in control cows. Such variations in perirenal and cardiac muscle LPL activities did not result from variations in LPL mRNA levels, but suggest a post-transcriptional regulation of LPL in these nutritional conditions. Underfeeding did not modify GLUT4 contents in perirenal AT and muscles, while refeeding increased it only in perirenal AT (+250 %). Our present results contrast with previous results in rats, where LPL is regulated in opposite directions in AT and muscles, and GLUT4 is generally increased by fasting and decreased by refeeding in skeletal muscles. The present results highlight the bovine specificity of the response, which probably arises in part from peculiarities of ruminant animals for nutrient digestion and absorption.

  5. 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

  6. 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

  7. 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.

  8. Effects of dietary n-3 polyunsaturated fatty acids, breed and dietary vitamin E on the fatty acids of lamb muscle, liver and adipose tissue.

    PubMed

    Demirel, G; Wachira, A M; Sinclair, L A; Wilkinson, R G; Wood, J D; Enser, M

    2004-04-01

    The effect of feeding n-3 PUFA on the fatty acid composition of muscle, adipose tissue and liver of lambs was investigated. Groups of eight ram lambs per breed, SuffolkxLleyn (24 kg live weight) and Scottish Blackface (18 kg live weight), were each fed one of six diets containing one of three fat sources (50 g fatty acids/kg DM; Megalac((R)) (calcium soap of palm fatty acid distillate; Volac Ltd, Royston, Herts., UK) and formaldehyde-treated whole linseed (Trouw Nutrition UK, Northwich, Ches., UK) either alone or with fish oil (1:1, w/w) and either 100 or 500 mg alpha-tocopheryl acetate/kg DM. Feed was offered ad libitum until slaughter at approximately half breed mature live weight. The type of dietary fat had no effect on intake, growth rate or feed conversion ratio. The 3.0-fold higher concentration of 18 : 3n-3 in the linseed compared with the Megalac((R)) diet approximately doubled (P<0.001) the concentration in the neutral and polar lipid fractions of musculus semimembranosus and liver, and in adipose tissue it increased 2.5-fold. Feeding protected linseed also increased (P<0.001) concentrations of 20 : 5n-3 and 22 : 5n-3 in muscle polar lipids and both lipid fractions of liver. The linseed-fish oil raised the 20 : 5n-3 concentrations above those for the linseed diet and also increased 22 : 6n-3. Scottish Blackface lambs had lower concentrations of 18 : 3n-3 in all lipids compared with Suffolk x Lleyn lambs, but more 20 : 5n-3 in the polar lipids of muscle and liver. High levels of dietary vitamin E were associated with small decreases in the concentration of monounsaturated fatty acids and increases in PUFA. Linseed raised the PUFA : saturated fatty acid ratios in liver and adipose tissue but not in muscle, and improved the n-6 : n-3 fatty acid ratio, as did the linseed-fish oil. Different combinations of dietary fatty acids and better protection against rumen biohydrogenation are required to improve muscle PUFA : saturated fatty acids ratios.

  9. Differentiate into urothelium and smooth muscle cells from adipose tissue-derived stem cells for ureter reconstruction in a rabbit model

    PubMed Central

    Zhao, Zhankui; Yu, Honglian; Fan, Chengjuan; Kong, Qingsheng; Liu, Deqian; Meng, Lin

    2016-01-01

    Ureter reconstruction is still a tough task for urologist. Cell-based tissue engineering serves a better technique for patients with long segments of ureter defect who need ureter reconstruction. In this study, we sought to evaluate the differentiation potential of adipose derived stem cells (ADSCs) into urothelial lineage and smooth muscle lineage and to assess the possibility of ureter reconstruction using differentiated cells seeded vessel extracellular matrix (VECM) in a rabbit model. ADSCs were isolated from adipose tissue and identified in vitro. Subsequently, they were cultured with induction medium for urothelium and smooth muscle phenotypes differentiation. After 14 days inducing, differentiation was evaluated by Quantitative PCR and western blot studies. After fluorescent protein labeling, the differentiated cells were seeded onto VECM and cultured under dynamic conditions in vitro. After 7 days culturing, the cell-seeded graft was tubularized and wrapped by two layers of the omentum in a rabbit. Three weeks later, the maturated graft was used for ureter reconstruction in vivo. The ADSCs were isolated and cultured in vitro. Flow cytometry demonstrated that the ADSCs expressed CD29 and CD90, but did not express CD34. After induction, urothelium phenotypes gene (cytokeratin 7) and smooth muscle expression gene (a-SMA and SM-MHC) was confirmed in mRNA and protein level. After cells seeding onto VECM, the induced urothelium cells formed a single epithelial layer, and the induced smooth muscle cells formed a few cell layers during dynamic culture. After 3 weeks of omental maturation, tubular graft was vascularized and comprised epithelial layer positively with cytokeratin 7, cytokeratin 20 on the luminal aspect. At 8 weeks post ureter reconstruction, histological evaluation showed a clearly layered structure of ureter with terminally differentiated multilayered urothelium positively with cytokeratin 20 and uroplakin III over connective smooth muscle tissue

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.

    PubMed

    Sajuthi, Satria P; Sharma, Neeraj K; Chou, Jeff W; Palmer, Nicholette D; McWilliams, David R; Beal, John; Comeau, Mary E; Ma, Lijun; Calles-Escandon, Jorge; Demons, Jamehl; Rogers, Samantha; Cherry, Kristina; Menon, Lata; Kouba, Ethel; Davis, Donna; Burris, Marcie; Byerly, Sara J; Ng, Maggie C Y; Maruthur, Nisa M; Patel, Sanjay R; Bielak, Lawrence F; Lange, Leslie A; Guo, Xiuqing; Sale, Michèle M; Chan, Kei Hang K; Monda, Keri L; Chen, Gary K; Taylor, Kira; Palmer, Cameron; Edwards, Todd L; North, Kari E; Haiman, Christopher A; Bowden, Donald W; Freedman, Barry I; Langefeld, Carl D; Das, Swapan K

    2016-08-01

    Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes.

  15. Mapping adipose and muscle tissue expression quantitative trait loci in African Americans to identify genes for type 2 diabetes and obesity.

    PubMed

    Sajuthi, Satria P; Sharma, Neeraj K; Chou, Jeff W; Palmer, Nicholette D; McWilliams, David R; Beal, John; Comeau, Mary E; Ma, Lijun; Calles-Escandon, Jorge; Demons, Jamehl; Rogers, Samantha; Cherry, Kristina; Menon, Lata; Kouba, Ethel; Davis, Donna; Burris, Marcie; Byerly, Sara J; Ng, Maggie C Y; Maruthur, Nisa M; Patel, Sanjay R; Bielak, Lawrence F; Lange, Leslie A; Guo, Xiuqing; Sale, Michèle M; Chan, Kei Hang K; Monda, Keri L; Chen, Gary K; Taylor, Kira; Palmer, Cameron; Edwards, Todd L; North, Kari E; Haiman, Christopher A; Bowden, Donald W; Freedman, Barry I; Langefeld, Carl D; Das, Swapan K

    2016-08-01

    Relative to European Americans, type 2 diabetes (T2D) is more prevalent in African Americans (AAs). Genetic variation may modulate transcript abundance in insulin-responsive tissues and contribute to risk; yet, published studies identifying expression quantitative trait loci (eQTLs) in African ancestry populations are restricted to blood cells. This study aims to develop a map of genetically regulated transcripts expressed in tissues important for glucose homeostasis in AAs, critical for identifying the genetic etiology of T2D and related traits. Quantitative measures of adipose and muscle gene expression, and genotypic data were integrated in 260 non-diabetic AAs to identify expression regulatory variants. Their roles in genetic susceptibility to T2D, and related metabolic phenotypes, were evaluated by mining GWAS datasets. eQTL analysis identified 1971 and 2078 cis-eGenes in adipose and muscle, respectively. Cis-eQTLs for 885 transcripts including top cis-eGenes CHURC1, USMG5, and ERAP2 were identified in both tissues. 62.1 % of top cis-eSNPs were within ±50 kb of transcription start sites and cis-eGenes were enriched for mitochondrial transcripts. Mining GWAS databases revealed association of cis-eSNPs for more than 50 genes with T2D (e.g. PIK3C2A, RBMS1, UFSP1), gluco-metabolic phenotypes (e.g. INPP5E, SNX17, ERAP2, FN3KRP), and obesity (e.g. POMC, CPEB4). Integration of GWAS meta-analysis data from AA cohorts revealed the most significant association for cis-eSNPs of ATP5SL and MCCC1 genes, with T2D and BMI, respectively. This study developed the first comprehensive map of adipose and muscle tissue eQTLs in AAs (publically accessible at https://mdsetaa.phs.wakehealth.edu ) and identified genetically regulated transcripts for delineating genetic causes of T2D, and related metabolic phenotypes. PMID:27193597

  16. Analysis of porcine adipose tissue transcriptome reveals differences in de novo fatty acid synthesis in pigs with divergent muscle fatty acid composition

    PubMed Central

    2013-01-01

    Background In pigs, adipose tissue is one of the principal organs involved in the regulation of lipid metabolism. It is particularly involved in the overall fatty acid synthesis with consequences in other lipid-target organs such as muscles and the liver. With this in mind, we have used massive, parallel high-throughput sequencing technologies to characterize the porcine adipose tissue transcriptome architecture in six Iberian x Landrace crossbred pigs showing extreme phenotypes for intramuscular fatty acid composition (three per group). Results High-throughput RNA sequencing was used to generate a whole characterization of adipose tissue (backfat) transcriptome. A total of 4,130 putative unannotated protein-coding sequences were identified in the 20% of reads which mapped in intergenic regions. Furthermore, 36% of the unmapped reads were represented by interspersed repeats, SINEs being the most abundant elements. Differential expression analyses identified 396 candidate genes among divergent animals for intramuscular fatty acid composition. Sixty-two percent of these genes (247/396) presented higher expression in the group of pigs with higher content of intramuscular SFA and MUFA, while the remaining 149 showed higher expression in the group with higher content of PUFA. Pathway analysis related these genes to biological functions and canonical pathways controlling lipid and fatty acid metabolisms. In concordance with the phenotypic classification of animals, the major metabolic pathway differentially modulated between groups was de novo lipogenesis, the group with more PUFA being the one that showed lower expression of lipogenic genes. Conclusions These results will help in the identification of genetic variants at loci that affect fatty acid composition traits. The implications of these results range from the improvement of porcine meat quality traits to the application of the pig as an animal model of human metabolic diseases. PMID:24289474

  17. The fatty acid composition of muscle and adipose tissue of steers offered unwilted or wilted grass silage supplemented with sunflower oil and fishoil.

    PubMed

    Noci, F; Monahan, F J; Scollan, N D; Moloney, A P

    2007-03-01

    The effects of the type of grass silage and dietary inclusion of fish oil (FO) on the fatty acid profile of bovine intramuscular and subcutaneous adipose tissue were investigated. Eighty Friesian steers were assigned (n 10) to unwilted or wilted silage, and to one of four rations which contained, per kg, 80 g of sunflower oil and either 0, 10, 20 or 40 g of FO replacing lard. Animals were slaughtered after 108 d and the fatty acid profile of the neutral, polar and total lipid fractions of the M. longissimus dorsi, and the total lipid fraction of the subcutaneous adipose tissue were determined. Wilting of grass prior to ensiling increased the concentration of conjugated linoleic acid (CLA) in intramuscular total lipid (P<0 x 01), but did not affect the n-6:n-3 PUFA ratio. Increasing FO supply linearly increased (P<0 x 05) the concentration of the cis-9, trans-11 and trans-10, cis-12 isomers of CLA and trans-11 18 : 1 predominantly in the neutral lipid fraction of intramuscular total lipid, and linearly decreased the n-6:n-3 PUFA ratio. Wilting of grass prior to ensiling increased the concentration of CLA in subcutaneous adipose tissue (P<0 x 001), while increasing FO supply linearly increased the concentration of cis-9, trans-11 CLA. From a human nutrition perspective, increasing the level of FO in the ration or wilting of grass prior to ensiling appear to modify the fatty acid composition of beef muscle favourably. However, the health implications of associated increases in trans fatty acids remain to be elucidated.

  18. Perfluoroalkyl Sulfonates and Carboxylic Acids in Liver, Muscle and Adipose Tissues of Black-Footed Albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean

    PubMed Central

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J.; Li, Qing X.

    2015-01-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g-1 wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g-1 ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and C16 PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties. PMID:26037817

  19. Perfluoroalkyl sulfonates and carboxylic acids in liver, muscle and adipose tissues of black-footed albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean.

    PubMed

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J; Li, Qing X

    2015-11-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g(-1) wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g(-1) ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties. PMID:26037817

  20. Perfluoroalkyl sulfonates and carboxylic acids in liver, muscle and adipose tissues of black-footed albatross (Phoebastria nigripes) from Midway Island, North Pacific Ocean.

    PubMed

    Chu, Shaogang; Wang, Jun; Leong, Gladys; Woodward, Lee Ann; Letcher, Robert J; Li, Qing X

    2015-11-01

    The Great Pacific Garbage Patch (GPGP) is a gyre of marine plastic debris in the North Pacific Ocean, and nearby is Midway Atoll which is a focal point for ecological damage. This study investigated 13 C4-C16 perfluorinated carboxylic acids (PFCAs), four (C4, C6, C8 and C10) perfluorinated sulfonates and perfluoro-4-ethylcyclohexane sulfonate [collectively perfluoroalkyl acids (PFAAs)] in black-footed albatross tissues (collected in 2011) from Midway Atoll. Of the 18 PFCAs and PFSAs monitored, most were detectable in the liver, muscle and adipose tissues. The concentrations of PFCAs and PFSAs were higher than those in most seabirds from the arctic environment, but lower than those in most of fish-eating water birds collected in the U.S. mainland. The concentrations of the PFAAs in the albatross livers were 7-fold higher than those in Laysan albatross liver samples from the same location reported in 1994. The concentration ranges of PFOS were 22.91-70.48, 3.01-6.59 and 0.53-8.35 ng g(-1) wet weight (ww), respectively, in the liver, muscle and adipose. In the liver samples PFOS was dominant, followed by longer chain PFUdA (8.04-18.70 ng g(-1) ww), PFTrDA, and then PFNA, PFDA and PFDoA. Short chain PFBA, PFPeA, PFBS and PFODA were below limit of quantification. C8-C13 PFCAs showed much higher composition compared to those found in other wildlife where PFOS typically predominated. The concentrations of PFUdA in all 8 individual albatross muscle samples were even higher than those of PFOS. This phenomenon may be attributable to GPGP as a pollution source as well as PFAA physicochemical properties.

  1. [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.

  2. 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.

  3. Microcalorimetric determination of energy expenditure due to active sodium-potassium transport in the soleus muscle and brown adipose tissue of the rat.

    PubMed

    Chinet, A; Clausen, T; Girardier, L

    1977-02-01

    1. The resting heat production rate (E) of soleus muscles from young rats and brown adipose tissue from adult rats was measured by means of a perfusable heat flux microcalorimeter in the absence and presence of ouabain. In the soleus muscle, the acute response of E to ouabain was compared with the ouabain-suppressible components of 22Na-efflux and 42K-influx. 2. In standard Krebs-Ringer bicarbonate buffer, ouabain (10(-3)M) induced an immediate but transient decrease in E of around 5%. Both in muscle and adipose tissue this was followed by a progressive rise in heat production rate. 3. When the medium was enriched with Mg (10 mM), ouabain produced a sustained decrease in E of the same magnitude as in the standard medium and the secondary rise was less marked or abolished. Under these conditions, in the soleus muscle, ouabain inhibited E by 5% (i.e. by 1-76 +/- 0-22 mcal.g wet wt.-1.min-1), 22Na-efflux by 58% (0-187 +/- 0-013 micronmole. g wet wt.-1.min-1) and 42K-influx by 34% (0-132 +/- 0-028 micronmole. g wet wt.-1.min-1). 4. When the muscles were loaded with Na by pre-incubation in K-free Mg-enriched medium, the addition of K (3mM) induced an immediate ouabain-suppressible increase in E of 2-98 +/- 0-33 mcal. g wet wt.-1.min-1 and a concomitant stimulation of 22Na-efflux of 0-388 +/- 0-136 micronmole. g wet wt.-1.min-1. 5. Maximum Na/ATP ratios for the active Na-K transport process were computed, with no assumption as to the in vivo free energy of ATP hydrolysis. These were 2-1, 1-9 and 2-3 under the conditions described in paragraphs (2), (3) and (4) respectively. 6. The calculated reversible thermodynamic work associated with active Na-K transport corresponded to 34% of the measured ouabain-induced decrease in E. On the premise that the maximum efficiency of the cellular energy conservation processes is 65%, this estimate indicates that the minimum energetic efficiency of ATP utilization by the active Na-K transport process in mammalian muscle is 52%.

  4. 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.

  5. A high omega 3 fatty acid diet alters fatty acid composition of heart, liver, kidney, adipose tissue and skeletal muscle in swine.

    PubMed

    Otten, W; Wirth, C; Iaizzo, P A; Eichinger, H M

    1993-01-01

    The fatty acid profiles and total lipid contents of two skeletal muscles, adipose tissue, heart, liver and kidney of swine fed a diet rich in omega 3 (n-3) fatty acids (i.e., 5% fish oil) was investigated. These values were compared to those determined for animals which were fed an equal caloric diet low in n-3 fatty acids (i.e., 5% coconut oil). All supplementations were given over a 13-week period. The lipids were extracted with chloroform-methanol, trans-esterified and the relative fatty acid methyl-esters concentrations were determined using capillary gas chromatography. The fish oil diet significantly enhanced the relative amounts of n-3 fatty acids (i.e., eicosapentaenoic acid and docosahexaenoic acid) in all tissues examined. In the heart, liver and kidney, the increases in n-3 fatty acids were compensated by decreases primarily in arachidonic acid, but in the other tissues the contents of lauric and myristic acids were also reduced. In general, the n-3 fatty acid contents were 40-165% higher in the animals fed the fish oil. Supplementation of n-3 fatty acids in swine induced a significant incorporation of these fatty acids throughout the body, however the extent of this incorporation differed between tissues perhaps due to tissue-specific metabolic pathways. PMID:8373137

  6. Responsiveness to Thyroid Hormone and to Ambient Temperature Underlies Differences Between Brown Adipose Tissue and Skeletal Muscle Thermogenesis in a Mouse Model of Diet-Induced Obesity

    PubMed Central

    Ueta, Cintia B.; Olivares, Emerson L.

    2011-01-01

    Thyroid hormone accelerates energy expenditure (EE) and is critical for cold-induced thermogenesis. To define the metabolic role played by thyroid hormone in the dissipation of calories from diet, hypothyroid mice were studied for 60 d in a comprehensive lab animal monitoring system. Hypothyroidism decreased caloric intake and body fat while down-regulating genes in the skeletal muscle but not brown adipose tissue thermogenic programs, without affecting daily EE. Only at thermoneutrality (30 C) did hypothyroid mice exhibit slower rate of EE, indicating a metabolic response to hypothyroidism that depends on ambient temperature. A byproduct of this mechanism is that at room temperature (22 C), hypothyroid mice are protected against diet-induced obesity, i.e. only at thermoneutrality did hypothyroid mice become obese when placed on a high-fat diet (HFD). This is in contrast to euthyroid controls, which on a HFD gained more body weight and fat at any temperature while activating the brown adipose tissue and accelerating daily EE but not the skeletal muscle thermogenic program. In the liver of euthyroid controls, HFD caused an approximately 5-fold increase in triglyceride content and expression of key metabolic genes, whereas acclimatization to 30 C cut triglyceride content by half and normalized gene expression. However, in hypothyroid mice, HFD-induced changes in liver persisted at 30 C, resulting in marked liver steatosis. Acclimatization to thermoneutrality dramatically improves glucose homeostasis, but this was not affected by hypothyroidism. In conclusion, hypothyroid mice are metabolically sensitive to environmental temperature, constituting a mechanism that defines resistance to diet-induced obesity and hepatic lipid metabolism. PMID:21771890

  7. 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

  8. Chronic subordination stress selectively downregulates the insulin signaling pathway in liver and skeletal muscle but not in adipose tissue of male mice

    PubMed Central

    Sanghez, Valentina; Cubuk, Cankut; Sebastián-Leon, Patricia; Carobbio, Stefania; Dopazo, Joaquin; Vidal-Puig, Antonio; Bartolomucci, Alessandro

    2016-01-01

    Abstract Chronic stress has been associated with obesity, glucose intolerance, and insulin resistance. We developed a model of chronic psychosocial stress (CPS) in which subordinate mice are vulnerable to obesity and the metabolic-like syndrome while dominant mice exhibit a healthy metabolic phenotype. Here we tested the hypothesis that the metabolic difference between subordinate and dominant mice is associated with changes in functional pathways relevant for insulin sensitivity, glucose and lipid homeostasis. Male mice were exposed to CPS for four weeks and fed either a standard diet or a high-fat diet (HFD). We first measured, by real-time PCR candidate genes, in the liver, skeletal muscle, and the perigonadal white adipose tissue (pWAT). Subsequently, we used a probabilistic analysis approach to analyze different ways in which signals can be transmitted across the pathways in each tissue. Results showed that subordinate mice displayed a drastic downregulation of the insulin pathway in liver and muscle, indicative of insulin resistance, already on standard diet. Conversely, pWAT showed molecular changes suggestive of facilitated fat deposition in an otherwise insulin-sensitive tissue. The molecular changes in subordinate mice fed a standard diet were greater compared to HFD-fed controls. Finally, dominant mice maintained a substantially normal metabolic and molecular phenotype even when fed a HFD. Overall, our data demonstrate that subordination stress is a potent stimulus for the downregulation of the insulin signaling pathway in liver and muscle and a major risk factor for the development of obesity, insulin resistance, and type 2 diabetes mellitus. PMID:26946982

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. Molecular Heterogeneities of Adipose Depots - Potential Effects on Adipose-Muscle Cross-Talk in Humans, Mice and Farm Animals

    PubMed Central

    Komolka, Katrin; Albrecht, Elke; Wimmers, Klaus; Michal, Jennifer J.; Maak, Steffen

    2014-01-01

    Adipose tissue is considered as a major endocrine organ that secretes numerous proteins called adipokines. The heterogeneous nature of adipose tissue in different parts of the body suggests respective heterogeneity of proteomes and secretomes. This review consolidates knowledge from recent studies targeting the diversity of different adipose depots affecting the pattern of secreted adipokines and discusses potential consequences for the cross-talk between adipose and skeletal muscle in humans, rodent models and farm animals. Special attention is paid to muscle-associated fat depots like inter- and intramuscular fat that become focus of attention in the context of the rather new notion of skeletal muscle as a major endocrine organ. Understanding the complexity of communication between adipocytes and skeletal muscle cells will allow developing strategies for improvement of human health and for sustainable production of high quality meat. PMID:25057322

  14. Lipid profiles of adipose and muscle tissues in mouse models of juvenile onset of obesity without high fat diet induction: a Fourier transform infrared (FT-IR) spectroscopic study.

    PubMed

    Sen, Ilke; Bozkurt, Ozlem; Aras, Ebru; Heise, Sebastian; Brockmann, Gudrun Anni; Severcan, Feride

    2015-06-01

    The current study aims to determine lipid profiles in terms of the content and structure of skeletal muscle and adipose tissues to better understand the characteristics of juvenile-onset spontaneous obesity without high fat diet induction. For the purposes of this study, muscle (longissimus, quadriceps) and adipose (inguinal, gonadal) tissues of 10-week-old male DBA/2J and Berlin fat mouse inbred (BFMI) lines (BFMI856, BFMI860, BFMI861) fed with a standard breeding diet were used. Biomolecular structure and composition was determined using attenuated total reflection Fourier transform (ATR FT-IR) spectroscopy, and muscle triglyceride content was further quantified using high-performance liquid chromatography (HPLC) coupled with an evaporative light scattering detector (ELSD). The results revealed a loss of unsaturation in BFMI860 and BFMI861 lines in both muscles and inguinal adipose tissue, together with a decrease in the hydrocarbon chain length of lipids, especially in the BFMI860 line in muscles, suggesting an increased lipid peroxidation. There was an increase in saturated lipid and triglyceride content in all tissues of BFMI lines, more profoundly in longissimus muscle, where the increased triglyceride content was quantitatively confirmed by HPLC-ELSD. Moreover, an increase in the metabolic turnover of carbohydrates in muscles of the BFMI860 line was observed. The results demonstrated that subcutaneous (inguinal) fat also displayed considerable obesity-induced alterations. Taken together, the results revealed differences in lipid structure and content of BFMI lines, which may originate from different insulin sensitivity levels of the lines, making them promising animal models for spontaneous obesity. The results will contribute to the understanding of the generation of insulin resistance in obesity without high fat diet induction.

  15. Effect of rate of weight gain of steers during the stocker phase. III. Gene expression of adipose tissues and skeletal muscle in growing-finishing beef cattle.

    PubMed

    Lancaster, P A; Sharman, E D; Horn, G W; Krehbiel, C R; Starkey, J D

    2014-04-01

    The objective of this study was to determine the impact of stocker production systems differing in growth rate on differential adipogenic and lipogenic gene expression of intramuscular (IM), subcutaneous (SC), and perirenal (PR) adipose tissues. Angus steers were assigned to 4 stocker cattle production systems in 2 consecutive years: 1) cottonseed meal-based supplement while grazing dormant native range (CON), 2) ground corn/soybean meal-based supplement while grazing dormant native range (CORN), 3) grazing wheat pasture at a high stocking rate for a low rate of BW gain (LGWP), and 4) grazing wheat pasture at a low stocking rate for a high rate of BW gain (HGWP). Steers were harvested during the stocker phase at similar age (different carcass weight) in Exp. 1 (3 steers/treatment) or at similar carcass weight in Exp. 2 (4 steers/treatment). Adipose tissues were analyzed for mRNA expression of adipogenic (peroxisome proliferator activated receptor γ [PPARγ], sterol regulatory element binding factor 1 [SREBF1], CAATT/enhancer binding protein β, and delta-like homolog 1) and lipogenic (glycerol-3-phosphate dehydrogenase [GPDH], fatty acid synthase [FASN], and diacylglycerol acyltransferase 2 [DGAT2]) genes. Multivariate analysis was used to evaluate the expression of adipogenic or lipogenic genes collectively. There was not a treatment × adipose tissue interaction (F-test, P > 0.15) when steers were harvested at similar age, but a treatment × adipose tissue interaction (F-test, P < 0.05) was evident when steers were harvested at similar carcass weight. At similar carcass weight, treatment had no effect (P > 0.10) on the canonical variate of adipogenic or lipogenic mRNA expression in IM adipose tissue, but faster rates of gain of LGWP and HGWP steers increased (P < 0.10) the canonical variate of adipogenic and lipogenic mRNA expression in SC and PR adipose tissue compared with CON and CORN steers. Strong positive correlations (P < 0.05) of PPARγ, SREBF1, GPDH

  16. Effects of limited and excess protein intakes of pregnant gilts on carcass quality and cellular properties of skeletal muscle and subcutaneous adipose tissue in fattening pigs.

    PubMed

    Rehfeldt, C; Stabenow, B; Pfuhl, R; Block, J; Nürnberg, G; Otten, W; Metges, C C; Kalbe, C

    2012-01-01

    The aim of this study was to investigate whether dietary protein intake of gilts during gestation below (50%) or above (250%) recommendations affects body composition, carcass and meat quality, and properties of skeletal muscle and subcutaneous adipose tissue (SCAT) in offspring at d 83 and 188 of age. German Landrace gilts were fed isoenergetic gestation diets (~13.7 MJ of ME/kg) containing a low (LP, 6.5%; n = 18), an adequate (AP, 12.1%; n = 20), or a high (HP, 30%; n = 16) protein content from mating until farrowing. Within 48 h of birth, offspring were cross-fostered to sows fed a standard diet. On d 83 of age, no effects of the LP diet on BW and body composition were detected, whereas HP pigs showed a slight growth delay (P = 0.06) associated with increased relative weights of small intestine (P < 0.01) and brain (P = 0.08), and reduced relative thymus weight (P < 0.01). On d 188 of age, BW was not different among the dietary groups. However, the carcass of LP pigs contained less (P = 0.01) lean and more (P = 0.07) fat compared with AP and HP pigs, which was only pronounced in pigs originating from large litters (P < 0.05). Like skeletal muscles (P = 0.06), the heart muscle weighed less (P = 0.02) in LP than AP pigs. Compared with AP pigs, LP pigs exhibited a fewer (P = 0.09) total number of myofibers in semitendinosus muscle plus LM both at d 83 and 188 of age, whereas total muscular DNA was less (P = 0.02) at d 188 only. The mRNA abundance of IGF2 measured on d 188 was reduced in SCAT (P = 0.03) and LM (P = 0.07) of LP compared with AP pigs. No changes in muscular fiber type frequency, capillary density, or creatine kinase activity, as well as SCAT adipocyte size and number, were observed at either stages of age. Meat quality characteristics remained unchanged at d 83, whereas Warner-Bratzler shear force value in LM was decreased (P = 0.03) in LP compared with AP pigs on d 188 of age. The results suggest that the maternal LP diet impairs prenatal myofiber

  17. 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

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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

  3. Negative Energy Balance Induced by Paradoxical Sleep Deprivation Causes Multicompartmental Changes in Adipose Tissue and Skeletal Muscle

    PubMed Central

    Mônico-Neto, Marcos; Giampá, Sara Quaglia de Campos; Lee, Kil Sun; de Melo, Camila Maria; Dáttilo, Murilo; Minali, Paulo Alexandre; Santos Prado, Pedro Henrique; Tufik, Sergio; de Mello, Marco Túlio; Antunes, Hanna Karen Moreira

    2015-01-01

    Objective. Describe multicompartmental changes in the fat and various muscle fiber types, as well as the hormonal profile and metabolic rate induced by SD in rats. Methods. Twenty adult male Wistar rats were equally distributed into two groups: experimental group (EG) and control group (CG). The EG was submitted to SD for 96 h. Blood levels of corticosterone (CORT), total testosterone (TESTO), insulin like growth factor-1 (IGF-1), and thyroid hormones (T3 and T4) were used to assess the catabolic environment. Muscle trophism was measured using a cross-sectional area of various muscles (glycolytic, mixed, and oxidative), and lipolysis was inferred by the weight of fat depots from various locations, such as subcutaneous, retroperitoneal, and epididymal. The metabolic rate was measured using oxygen consumption (V˙O2) measurement. Results. SD increased CORT levels and decreased TESTO, IGF-1, and T4. All fat depots were reduced in weight after SD. Glycolytic and mixed muscles showed atrophy, whereas atrophy was not observed in oxidative muscle. Conclusion. Our data suggest that glycolytic muscle fibers are more sensitive to atrophy than oxidative fibers during SD and that fat depots are reduced regardless of their location. PMID:25821467

  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. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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

  10. Hyperglycemic Challenge and Distribution of Adipose Tissue in Obese Baboons

    PubMed Central

    Kulkarni, Tanmay; Slaughter, Gymama; Ego-Osuala, Chimdi; Kochunov, Peter; Bastarrachea, Raul A.; Mattern, Vicki; Andrade, Marcia; Higgins, Paul B.; Comuzzie, Anthony G.; Voruganti, V. Saroja

    2014-01-01

    Background Blood glucose levels regulate the rate of insulin secretion, which is the body’s mechanism for preventing excessive elevation in blood glucose. Impaired glucose metabolism and insulin resistance have been linked to excess body fat composition. Here, we quantify abdominal muscle and abdominal adipose tissue compartments in a large nonhuman primate, the baboon, and investigate their relationship with serum glucose response to a hyperglycemic challenge. Methods Five female baboons were fasted for 16 hours prior to 90 minute body imaging experiment that consisted of a 20-min baseline, followed by a bolus infusion of glucose (500mg/kg). The blood glucose was sampled at regular intervals. The total volumes of the muscle, visceral and subcutaneous adipose tissue were measured. Results and discussion We found that adipose tissue composition predicted fluctuations in glucose responses to a hyperglycemic challenge of a non-human primate. Animals with higher visceral adiposity showed significantly reduced glucose elimination. The glucose responses were positively correlated with body weight, visceral and muscle fat (p < 0.005). Polynomial regression analysis showed that body weight, visceral and muscle were significant Conclusions These results reveal the similarity between humans and baboons with respect to glucose metabolism and strengthen the utility of baboon for biomedical research. PMID:25429366

  11. The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders.

    PubMed

    Mesnier, Aurélia; Champion, Serge; Louis, Laurence; Sauzet, Christophe; May, Phealay; Portugal, Henri; Benbrahim, Karim; Abraldes, Joelle; Alessi, Marie-Christine; Amiot-Carlin, Marie-Josephe; Peiretti, Franck; Piccerelle, Philippe; Nalbone, Gilles; Villard, Pierre-Henri

    2015-01-01

    Epidemiological studies have associated environmental exposure to polychlorinated biphenyls (PCBs) with an increased risk of type 2 diabetes; however, little is known about the underlying mechanisms involved in the metabolic side-effects of PCB. Our study evaluated the transcriptional effects of a subchronic exposure (gavage at Day 0 and Day 15 with 10 or 100 μmol/Kg bw) to PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), or an equimolar mixture of PCB118 and PCB153 on various tissues (liver, visceral adipose tissue, muscle, and colon) in mice. Our results showed that a short-term exposure to PCB118 and/or PCB153 enhanced circulating triglyceride levels but did not affect glycemia. Among the studied tissues, we did not observe any modification of the expression of inflammation-related genes, such as cytokines or chemokines. The main transcriptional effects were observed in visceral adipose and liver tissues. We found a downregulation of lipin1 and glut4 expression in these two target organs. In adipose tissue, we also showed a downregulation of Agpat2, Slc25a1, and Fasn. All of these genes are involved in lipid metabolism and insulin resistance. In muscles, we observed an induction of CnR1 and Foxo3 expression, which may be partly involved in PCB metabolic effects. In summary, our results suggest that lipin1 and glut4, notably in adipose tissue, are the main targeted genes in PCB-induced metabolic disorders, however, further studies are required to fully elucidate the mechanisms involved.

  12. The Transcriptional Effects of PCB118 and PCB153 on the Liver, Adipose Tissue, Muscle and Colon of Mice: Highlighting of Glut4 and Lipin1 as Main Target Genes for PCB Induced Metabolic Disorders

    PubMed Central

    Mesnier, Aurélia; Champion, Serge; Louis, Laurence; Sauzet, Christophe; May, Phealay; Portugal, Henri; Benbrahim, Karim; Abraldes, Joelle; Alessi, Marie-Christine; Amiot-Carlin, Marie-Josephe; Peiretti, Franck; Piccerelle, Philippe; Nalbone, Gilles; Villard, Pierre-Henri

    2015-01-01

    Epidemiological studies have associated environmental exposure to polychlorinated biphenyls (PCBs) with an increased risk of type 2 diabetes; however, little is known about the underlying mechanisms involved in the metabolic side-effects of PCB. Our study evaluated the transcriptional effects of a subchronic exposure (gavage at Day 0 and Day 15 with 10 or 100 μmol/Kg bw) to PCB118 (dioxin-like PCB), PCB153 (non-dioxin-like PCB), or an equimolar mixture of PCB118 and PCB153 on various tissues (liver, visceral adipose tissue, muscle, and colon) in mice. Our results showed that a short-term exposure to PCB118 and/or PCB153 enhanced circulating triglyceride levels but did not affect glycemia. Among the studied tissues, we did not observe any modification of the expression of inflammation-related genes, such as cytokines or chemokines. The main transcriptional effects were observed in visceral adipose and liver tissues. We found a downregulation of lipin1 and glut4 expression in these two target organs. In adipose tissue, we also showed a downregulation of Agpat2, Slc25a1, and Fasn. All of these genes are involved in lipid metabolism and insulin resistance. In muscles, we observed an induction of CnR1 and Foxo3 expression, which may be partly involved in PCB metabolic effects. In summary, our results suggest that lipin1 and glut4, notably in adipose tissue, are the main targeted genes in PCB-induced metabolic disorders, however, further studies are required to fully elucidate the mechanisms involved. PMID:26086818

  13. Perivascular adipose tissue-derived leptin promotes vascular smooth muscle cell phenotypic switching via p38 mitogen-activated protein kinase in metabolic syndrome rats.

    PubMed

    Li, Hao; Wang, Ya-Ping; Zhang, Li-Na; Tian, Gang

    2014-04-01

    Perivascular adipose tissue (PVAT)-derived leptin is a detrimental adipocytokine and plays a critical role in the development of cardiovascular diseases in metabolic syndrome (MetS). During vascular remodeling, vascular smooth muscle cells (VSMCs) undergo phenotypic switching into a synthetic phenotype characterized by decreased expression of differentiation markers (smooth muscle myosin heavy chain, α-smooth muscle actin, and calponin) and increased proliferation. We aimed to determine whether PVAT-derived leptin influences VSMC phenotypic switching and to explore the underlying mechanisms in MetS rats. In vivo, 32 Wistar rats were divided into two groups that received either a normal diet (control rat) or a high-fat diet (MetS rats). After 16 weeks, rat aortas were stained using hematoxylin-eosin and imaged. VSMC differentiation markers and proliferating cell nuclear antigen (PCNA), PVAT-derived leptin, aortic leptin receptor (ObR), and p38 mitogen-activated protein kinase (MAPK) expression were detected. In vitro, aortic VSMCs were incubated with MetS rat PVAT conditioned medium (PVAT-CM) to mimic in vivo conditions and were pretreated with a p38 MAPK inhibitor (SB 203580) or leptin antagonist. Differentiation marker expression, including PCNA and p38 MAPK, was detected. MetS rats exhibited pronounced insulin resistance, hyperglycemia, hyperlipidemia, hypertension, obesity, and an associated increase in PVAT weight. VSMCs underwent phenotypic switching in MetS rat aorta and contributed to vascular remodeling. PVAT-derived leptin expression was higher in MetS rats than in control rats (P < 0.01). ObRa expression and p38 MAPK phosphorylation were upregulated in MetS rat aorta. In vitro, VSMCs incubated with MetS rat PVAT-CM underwent phenotypic switching, associated with increased p38 MAPK phosphorylation. This VSMC phenotypic switching was inhibited by pretreatment with SB 203580 or a leptin antagonist. These results suggest that in MetS rats, PVAT

  14. ProteINSIDE to Easily Investigate Proteomics Data from Ruminants: Application to Mine Proteome of Adipose and Muscle Tissues in Bovine Foetuses

    PubMed Central

    Kaspric, Nicolas; Picard, Brigitte; Reichstadt, Matthieu; Tournayre, Jérémy; Bonnet, Muriel

    2015-01-01

    Genomics experiments are widely acknowledged to produce a huge amount of data to be analysed. The challenge is to extract meaningful biological context for proteins or genes which is currently difficult because of the lack of an integrative workflow that hinders the efficiency and the robustness of data mining performed by biologists working on ruminants. Thus, we designed ProteINSIDE, a free web service (www.proteinside.org) that (I) provides an overview of the biological information stored in public databases or provided by annotations according to the Gene Ontology, (II) predicts proteins that are secreted to search for proteins that mediate signalisation between cells or tissues, and (III) analyses protein-protein interactions to identify proteins contributing to a process or to visualize functional pathways. Using lists of proteins or genes as a unique input, ProteINSIDE is an original all-in-one tool that merges data from these searches to present a fast overview and integrative analysis of genomic and proteomic data from Bovine, Ovine, Caprine, Human, Rat, and Murine species. ProteINSIDE was bench tested with 1000 proteins identifiers from each species by comparison with DAVID, BioMyn, AgBase, PrediSi, and Phobius. Compared to DAVID or BioMyn, identifications and annotations provided by ProteINSIDE were similar from monogastric proteins but more numerous and relevant for ruminants proteins. ProteINSIDE, thanks to SignalP, listed less proteins potentially secreted with a signal peptide than PrediSi and Phobius, in agreement with the low false positive rate of SignalP. In addition ProteINSIDE is the only resource that predicts proteins secreted by cellular processes that do not involve a signal peptide. Lastly, we reported the usefulness of ProteINSIDE to bring new biological hypotheses of research from proteomics data: the biological meaning of the uptake of adiponectin by the foetal muscle and a role for autophagy during ontogenesis of adipose and muscle

  15. 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.

  16. 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.

  17. Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects.

    PubMed

    Bruun, Jens M; Helge, Jørn W; Richelsen, Bjørn; Stallknecht, Bente

    2006-05-01

    Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight (P < 0.001) and increased insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin (P < 0.001) increased, and C-reactive protein (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.05), and monocyte chemoattractant protein-1 (P < 0.01) decreased. AT inflammation was reduced, determined from an increased mRNA expression of adiponectin (P < 0.001) and a decreased expression of macrophage-specific markers (CD14, CD68), IL-6, IL-8, and tumor necrosis factor-alpha (P < 0.01). After adjusting for macrophage infiltration in AT, only IL-6 mRNA was decreased (P < 0.05). Only very low levels of inflammatory markers were found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to this attenuation of whole body inflammation.

  18. 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.

  19. Insulin Sensitivity in Adipose and Skeletal Muscle Tissue of Dairy Cows in Response to Dietary Energy Level and 2,4-Thiazolidinedione (TZD).

    PubMed

    Hosseini, Afshin; Tariq, Muhammad Rizwan; Trindade da Rosa, Fernanda; Kesser, Julia; Iqbal, Zeeshan; Mora, Ofelia; Sauerwein, Helga; Drackley, James K; Trevisi, Erminio; Loor, Juan J

    2015-01-01

    The effects of dietary energy level and 2,4-thiazolidinedione (TZD) injection on feed intake, body fatness, blood biomarkers and TZD concentrations, genes related to insulin sensitivity in adipose tissue (AT) and skeletal muscle, and peroxisome proliferator-activated receptor gamma (PPARG) protein in subcutaneous AT (SAT) were evaluated in Holstein cows. Fourteen nonpregnant nonlactating cows were fed a control low-energy (CON, 1.30 Mcal/kg) diet to meet 100% of estimated nutrient requirements for 3 weeks, after which half of the cows were assigned to a higher-energy diet (OVE, 1.60 Mcal/kg) and half of the cows continued on CON for 6 weeks. All cows received an intravenous injection of TZD starting 2 weeks after initiation of dietary treatments and for an additional 2 weeks, which served as the washout period. Cows fed OVE had greater energy intake and body mass than CON, and TZD had no effect during the administration period. The OVE cows had greater TZD clearance rate than CON cows. The lower concentration of nonesterified fatty acids (NEFA) and greater concentration of insulin in blood of OVE cows before TZD injection indicated positive energy balance and higher insulin sensitivity. Administration of TZD increased blood concentrations of glucose, insulin, and beta-hydroxybutyrate (BHBA) at 2 to 4 weeks after diet initiation, while the concentration of NEFA and adiponectin (ADIPOQ) remained unchanged during TZD. The TZD upregulated the mRNA expression of PPARG and its targets FASN and SREBF1 in SAT, but also SUMO1 and UBC9 which encode sumoylation proteins known to down-regulate PPARG expression and curtail adipogenesis. Therefore, a post-translational response to control PPARG gene expression in SAT could be a counteregulatory mechanism to restrain adipogenesis. The OVE cows had greater expression of the insulin sensitivity-related genes IRS1, SLC2A4, INSR, SCD, INSIG1, DGAT2, and ADIPOQ in SAT. In skeletal muscle, where PPARA and its targets orchestrate

  20. Insulin Sensitivity in Adipose and Skeletal Muscle Tissue of Dairy Cows in Response to Dietary Energy Level and 2,4-Thiazolidinedione (TZD)

    PubMed Central

    Hosseini, Afshin; Tariq, Muhammad Rizwan; Trindade da Rosa, Fernanda; Kesser, Julia; Iqbal, Zeeshan; Mora, Ofelia; Sauerwein, Helga; Drackley, James K.; Trevisi, Erminio; Loor, Juan J.

    2015-01-01

    The effects of dietary energy level and 2,4-thiazolidinedione (TZD) injection on feed intake, body fatness, blood biomarkers and TZD concentrations, genes related to insulin sensitivity in adipose tissue (AT) and skeletal muscle, and peroxisome proliferator-activated receptor gamma (PPARG) protein in subcutaneous AT (SAT) were evaluated in Holstein cows. Fourteen nonpregnant nonlactating cows were fed a control low-energy (CON, 1.30 Mcal/kg) diet to meet 100% of estimated nutrient requirements for 3 weeks, after which half of the cows were assigned to a higher-energy diet (OVE, 1.60 Mcal/kg) and half of the cows continued on CON for 6 weeks. All cows received an intravenous injection of TZD starting 2 weeks after initiation of dietary treatments and for an additional 2 weeks, which served as the washout period. Cows fed OVE had greater energy intake and body mass than CON, and TZD had no effect during the administration period. The OVE cows had greater TZD clearance rate than CON cows. The lower concentration of nonesterified fatty acids (NEFA) and greater concentration of insulin in blood of OVE cows before TZD injection indicated positive energy balance and higher insulin sensitivity. Administration of TZD increased blood concentrations of glucose, insulin, and beta-hydroxybutyrate (BHBA) at 2 to 4 weeks after diet initiation, while the concentration of NEFA and adiponectin (ADIPOQ) remained unchanged during TZD. The TZD upregulated the mRNA expression of PPARG and its targets FASN and SREBF1 in SAT, but also SUMO1 and UBC9 which encode sumoylation proteins known to down-regulate PPARG expression and curtail adipogenesis. Therefore, a post-translational response to control PPARG gene expression in SAT could be a counteregulatory mechanism to restrain adipogenesis. The OVE cows had greater expression of the insulin sensitivity-related genes IRS1, SLC2A4, INSR, SCD, INSIG1, DGAT2, and ADIPOQ in SAT. In skeletal muscle, where PPARA and its targets orchestrate

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. Hydrogenated fat intake during pregnancy and lactation caused increase in TRAF-6 and reduced AdipoR1 in white adipose tissue, but not in muscle of 21 days old offspring rats

    PubMed Central

    2011-01-01

    Background Although lipids transfer through placenta is very limited, modification in dietary fatty acids can lead to implications in fetal and postnatal development. Trans fatty acid (TFA) intake during gestation and lactation have been reported to promote dyslipidemia and increase in pro- inflammatory adipokines in offspring. The aim of this study was to evaluate whether the alterations on pro-inflammatory cytokines and dyslipidemia observed previously in 21-d-old offspring of rats fed a diet containing hydrogenated vegetable fat during gestation and lactation were related to alterations in TLR-4, TRAF-6 and adipo-R1 receptor in white adipose tissue and muscle. On the first day of gestation, rats were randomly divided into two groups: (C) received a control diet, and (T) received a diet enriched with hydrogenated vegetable fat, rich in trans fatty acids. The diets were maintained throughout gestation and lactation. Each mother was given eight male pups. On the 21st day of life the offspring were killed. Blood, soleus and extensor digital longus (EDL) muscles, and retroperitoneal (RET) white adipose tissue were collected. Results 21-d-old of T rats had higher serum triacylglycerols, cholesterol, and insulin. The Adipo R1 protein expression was lower in RET and higher in EDL of T group than C. TLR-4 protein content in all studied tissues were similar between groups, the same was verified in TRAF-6 protein expression in soleus and EDL. However, TRAF-6 protein expression in RET was higher in T than C. Conclusion These results demonstrated that maternal ingestion of hydrogenated vegetable fat rich in TFAs during gestation and lactation decrease in Adipo R1 protein expression and increase in TRAF-6 protein expression in retroperitoneal adipose tissue, but not in skeletal muscle, which could contributed for hyperinsulinemia and dyslipidemia observed in their 21-d-old offspring. PMID:21266050

  6. Functions of AMP-activated protein kinase in adipose tissue

    PubMed Central

    Daval, Marie; Foufelle, Fabienne; Ferré, Pascal

    2006-01-01

    AMP-activated protein kinase (AMPK) is involved in cellular energy homeostasis. Its functions have been extensively studied in muscles and liver. AMPK stimulates pathways which increase energy production (glucose transport, fatty acid oxidation) and switches off pathways which consume energy (lipogenesis, protein synthesis, gluconeogenesis). This has led to the concept that AMPK has an interesting pharmaceutical potential in situations of insulin resistance and it is indeed the target of existing drugs and hormones which improve insulin sensitivity. Adipose tissue is a key player in energy metabolism through the release of substrates and hormones involved in metabolism and insulin sensitivity. Activation of AMPK in adipose tissue can be achieved through situations such as fasting and exercise. Leptin and adiponectin as well as hypoglycaemic drugs are activators of adipose tissue AMPK. This activation probably involves changes in the AMP/ATP ratio and the upstream kinase LKB1. When activated, AMPK limits fatty acid efflux from adipocytes and favours local fatty acid oxidation. Since fatty acids have a key role in insulin resistance, especially in muscles, activating AMPK in adipose tissue might be found to be beneficial in insulin-resistant states, particularly as AMPK activation also reduces cytokine secretion in adipocytes. PMID:16709632

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. [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.

  12. 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...

  13. 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.

  14. 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

  15. Dietary Salba (Salvia hispanica L) seed rich in α-linolenic acid improves adipose tissue dysfunction and the altered skeletal muscle glucose and lipid metabolism in dyslipidemic insulin-resistant rats.

    PubMed

    Oliva, M E; Ferreira, M R; Chicco, A; Lombardo, Y B

    2013-10-01

    This work reports the effect of dietary Salba (chia) seed rich in n-3 α-linolenic acid on the morphological and metabolic aspects involved in adipose tissue dysfunction and the mechanisms underlying the impaired glucose and lipid metabolism in the skeletal muscle of rats fed a sucrose-rich diet (SRD). Rats were fed a SRD for 3 months. Thereafter, half the rats continued with SRD while in the other half, corn oil (CO) was replaced by chia seed for 3 months (SRD+chia). In control group, corn starch replaced sucrose. The replacement of CO by chia seed in the SRD reduced adipocyte hypertrophy, cell volume and size distribution, improved lipogenic enzyme activities, lipolysis and the anti-lipolytic action of insulin. In the skeletal muscle lipid storage, glucose phosphorylation and oxidation were normalized. Chia seed reversed the impaired insulin stimulated glycogen synthase activity, glycogen, glucose-6-phosphate and GLUT-4 protein levels as well as insulin resistance and dyslipidemia.

  16. 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

  17. Types of muscle tissue (image)

    MedlinePlus

    The 3 types of muscle tissue are cardiac, smooth, and skeletal. Cardiac muscle cells are located in ... heart, appear striated, and are under involuntary control. Smooth muscle fibers are located in walls of hollow ...

  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.

  19. 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.

  20. [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

  1. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice.

    PubMed

    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

  2. Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations.

    PubMed

    Stanford, Kristin I; Middelbeek, Roeland J W; Goodyear, Laurie J

    2015-07-01

    Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health.

  3. Sustainable three-dimensional tissue model of human adipose tissue.

    PubMed

    Bellas, Evangelia; Marra, Kacey G; Kaplan, David L

    2013-10-01

    The need for physiologically relevant sustainable human adipose tissue models is crucial for understanding tissue development, disease progression, in vitro drug development and soft tissue regeneration. The coculture of adipocytes differentiated from human adipose-derived stem cells, with endothelial cells, on porous silk protein matrices for at least 6 months is reported, while maintaining adipose-like outcomes. Cultures were assessed for structure and morphology (Oil Red O content and CD31 expression), metabolic functions (leptin, glycerol production, gene expression for GLUT4, and PPARγ) and cell replication (DNA content). The cocultures maintained size and shape over this extended period in static cultures, while increasing in diameter by 12.5% in spinner flask culture. Spinner flask cultures yielded improved adipose tissue outcomes overall, based on structure and function, when compared to the static cultures. This work establishes a tissue model system that can be applied to the development of chronic metabolic dysfunction systems associated with human adipose tissue, such as obesity and diabetes, due to the long term sustainable functions demonstrated here.

  4. Adipose tissue monomethyl branched chain fatty acids and insulin sensitivity: effects of obesity and weight loss

    PubMed Central

    Su, Xiong; Magkos, Faidon; Zhou, Dequan; Eagon, J. Christopher; Fabbrini, Elisa; Okunade, Adewole L.; Klein, Samuel

    2014-01-01

    Objective An increase in circulating branched-chain amino acids (BCAA) is associated with insulin resistance. Adipose tissue is a potentially important site for BCAA metabolism. We evaluated whether monomethyl branched chain fatty acids (mmBCFA) in adipose tissue, which are likely derived from BCAA catabolism, are associated with insulin sensitivity. Design and Methods Insulin-stimulated glucose disposal was determined by using the hyperinsulinemic-euglycemic clamp procedure with stable isotope glucose tracer infusion, in 9 lean and 9 obese subjects, and in a separate group of 9 obese subjects before and 1 year after Roux-en-Y gastric bypass (RYGB) surgery (38% weight loss). Adipose tissue mmBCFA content was measured in tissue biopsies taken in the basal state. Results Total adipose tissue mmBCFA content was ~30% lower in obese than lean subjects (P = 0.02), and increased by ~65% after weight loss in the RYGB group (P = 0.01). Adipose tissue mmBCFA content correlated positively with skeletal muscle insulin sensitivity (R2 = 35%, P = 0.01, n = 18). Conclusions These results demonstrate a novel association between adipose tissue mmBCFA content and obesity-related insulin resistance. Additional studies are needed to determine whether the association between adipose tissue mmBCFA and muscle insulin sensitivity is causal or a simple association. PMID:25328153

  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. HIV Infection and Antiretroviral Therapy Have Divergent Effects on Mitochondria in Adipose Tissue

    PubMed Central

    Morse, Caryn G.; Voss, Joachim G.; Rakocevic, Goran; McLaughlin, Mary; Vinton, Carol L.; Huber, Charles; Hu, Xiaojun; Yang, Jun; Huang, Da Wei; Logun, Carolea; Danner, Robert L.; Rangel, Zoila G.; Munson, Peter J.; Orenstein, Jan M.; Rushing, Elisabeth J.; Lempicki, Richard A.; Dalakas, Marinos C.; Kovacs, Joseph A.

    2012-01-01

    Background. Although human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) affect mitochondrial DNA (mtDNA) content and function, comprehensive evaluations of their effects on mitochondria in muscle, adipose tissue, and blood cells are limited. Methods. Mitochondrial DNA quantification, mitochondrial genome sequencing, and gene expression analysis were performed on muscle, adipose tissue, and peripheral blood mononuclear cell (PBMC) samples from untreated HIV-positive patients, HIV-positive patients receiving nucleoside reverse transcriptase inhibitor (NRTI)–based ART, and HIV-negative controls. Results. The adipose tissue mtDNA/nuclear DNA (nDNA) ratio was increased in untreated HIV-infected patients (ratio, 353) and decreased in those receiving ART (ratio, 162) compared with controls (ratio, 255; P < .05 for both comparisons); the difference between the 2 HIV-infected groups was also significant (P = .002). In HIV-infected participants, mtDNA/nDNA in adipose tissue correlated with the level of activation (CD38+/HLA-DR+) for CD4+ and CD8+ lymphocytes. No significant differences in mtDNA content were noted in muscle or PMBCs among groups. Exploratory DNA microarray analysis identified differential gene expression between patient groups, including a subset of adipose tissue genes. Conclusions. HIV infection and ART have opposing effects on mtDNA content in adipose tissue; immune activation may mediate the effects of HIV, whereas NRTIs likely mediate the effects of ART. PMID:22476717

  7. Developmental, hormonal, and nutritional regulation of expression of porcine adipose tissue triglyceride lipase (pATGL) gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose triglyceride lipase (ATGL) is a newly identified lipase. We report for the first time the porcine ATGL sequence and characterize ATGL gene and protein expression in vitro and in vivo. Adult pig tissue expresses ATGL at high levels in the white adipose and muscle tissue relative to other te...

  8. [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

  9. 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.

  10. Ablation of the ID2 gene results in altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue.

    PubMed

    Mathew, Deepa; Zhou, Peng; Pywell, Cameron M; van der Veen, Daan R; Shao, Jinping; Xi, Yang; Bonar, Nicolle A; Hummel, Alyssa D; Chapman, Sarah; Leevy, W Matthew; Duffield, Giles E

    2013-01-01

    Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our earlier studies have demonstrated a role for ID2 in the input pathway, core clock function and output pathways of the mouse circadian system. We have also reported that Id2 null (Id2-/-) mice are lean with low gonadal white adipose tissue deposits and lower lipid content in the liver. These results coincided with altered or disrupted circadian expression profiles of liver genes including those involved in lipid metabolism. In the present phenotypic study we intended to decipher, on a sex-specific basis, the role of ID2 in glucose metabolism and in the circadian regulation of activity, important components of energy balance. We find that Id2-/- mice exhibited altered daily and circadian rhythms of feeding and locomotor activity; activity profiles extended further into the late night/dark phase of the 24-hr cycle, despite mice showing reduced total locomotor activity. Also, male Id2-/- mice consumed a greater amount of food relative to body mass, and displayed less weight gain. Id2-/- females had smaller adipocytes, suggesting sexual-dimorphic programing of adipogenesis. We observed increased glucose tolerance and insulin sensitivity in male Id2-/- mice, which was exacerbated in older animals. FDG-PET analysis revealed increased glucose uptake by skeletal muscle and brown adipose tissue of male Id2-/- mice, suggesting increased glucose metabolism and thermogenesis in these tissues. Reductions in intramuscular triacylglycerol and diacylglycerol were detected in male Id2-/- mice, highlighting its possible mechanistic role in enhanced insulin sensitivity in these mice. Our findings indicate a role for ID2 as a regulator of glucose and lipid metabolism, and in the circadian control of feeding/locomotor behavior; and contribute to the understanding of the development of obesity and diabetes, particularly in shift work personnel among whom

  11. Urinary Bladder Smooth Muscle Engineered from Adipose Stem Cells and a Three Dimensional Synthetic Composite

    PubMed Central

    Jack, Gregory S.; Zhang, Rong; Lee, Min; Xu, Yuhan; Wu, Ben; Rodríguez, Larissa V.

    2009-01-01

    Human adipose stem cells were cultured in smooth muscle inductive media and seeded into synthetic bladder composites to tissue engineer bladder smooth muscle. 85:15 poly-lactic-glycolic acid bladder dome composites were cast using an electropulled microfiber luminal surface combined with an outer porous sponge. Cell seeded bladders expressed smooth muscle actin, myosin heavy chain, calponinin, and caldesmon via RT-PCR and immunoflourescence. Nude rats (n=45) underwent removal of half their bladder and repair using: (i) augmentation with the adipose stem cell seeded composites, (ii) augmentation with a matched acellular composite, or (iii) suture closure. Animals were followed for 12 weeks post-implantation and bladders were explanted serially. Results showed that bladder capacity and compliance were maintained in the cell seeded group throughout the 12 weeks, but deteriorated in the acellular scaffold group sequentially with time. Control animals repaired with sutures regained their baseline bladder capacities by week 12, demonstrating a long term limitation of this model. Histological analysis of explanted materials demonstrated viable adipose stem cells and increasing smooth muscle mass in the cell seeded scaffolds with time. Tissue bath stimulation demonstrated smooth muscle contraction of the seeded implants but not the acellular implants after 12 weeks in vivo. Our study demonstrates the feasibility and short term physical properties of bladder tissue engineered from adipose stem cells. PMID:19345408

  12. Influence of betaine and arginine supplementation of reduced protein diets on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of cross-bred pigs.

    PubMed

    Madeira, Marta S; Rolo, Eva S; Alfaia, Cristina M; Pires, Virgínia R; Luxton, Richard; Doran, Olena; Bessa, Rui J B; Prates, José A M

    2016-03-28

    The isolated or combined effects of betaine and arginine supplementation of reduced protein diets (RPD) on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig m. longissimus lumborum and subcutaneous adipose tissue (SAT) were assessed. The experiment was performed on forty intact male pigs (Duroc×Large White×Landrace cross-breed) with initial and final live weights of 60 and 93 kg, respectively. Pigs were randomly assigned to one of the following five diets (n 8): 16·0 % of crude protein (control), 13·0 % of crude protein (RPD), RPD supplemented with 0·33 % of betaine, RPD supplemented with 1·5 % of arginine and RPD supplemented with 0·33 % of betaine and 1·5 % of arginine. Data confirmed that RPD increase intramuscular fat (IMF) content and total fat content in SAT. The increased total fat content in SAT was accompanied by higher GLUT type 4, lipoprotein lipase and stearoyl-CoA desaturase mRNA expression levels. In addition, the supplementation of RPD with betaine and/or arginine did not affect either IMF or total fat in SAT. However, dietary betaine supplementation slightly affected fatty acid composition in both muscle and SAT. This effect was associated with an increase of carnitine O-acetyltransferase mRNA levels in SAT but not in muscle, which suggests that betaine might be involved in the differential regulation of some key genes of lipid metabolism in pig muscle and SAT. Although the arginine-supplemented diet decreased the mRNA expression level of PPARG in muscle and SAT, it did not influence fat content or fatty acid composition in any of these pig tissues.

  13. High intensity interval training improves liver and adipose tissue insulin sensitivity

    PubMed Central

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

  14. 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.

  15. Zilpaterol hydrochloride alters abundance of β-adrenergic receptors in bovine muscle cells but has little effect on de novo fatty acid biosynthesis in bovine subcutaneous adipose tissue explants.

    PubMed

    Miller, E K; Chung, K Y; Hutcheson, J P; Yates, D A; Smith, S B; Johnson, B J

    2012-04-01

    We predicted that zilpaterol hydrochloride (ZH), a β-adrenergic receptor (AR) agonist, would depress mRNA and protein abundance of β-AR in bovine satellite cells. We also predicted that ZH would decrease total lipid synthesis in bovine adipose tissue. Bovine satellite cells isolated from the semimembranosus muscle were plated on tissue culture plates coated with reduced growth factor matrigel or collagen. Real-time quantitative PCR was used to measure specific gene expression after 48 h of ZH exposure in proliferating satellite cells and fused myoblasts. There was no effect of ZH dose on [(3)H]thymidine incorporation into DNA in proliferating myoblasts. Zilpaterol hydrochloride at 1 µM decreased (P < 0.05) β1-AR mRNA, and 0.01 and 1 µM ZH decreased (P < 0.05) β2-AR and β3-AR mRNA in myoblasts. The expression of IGF-I mRNA tended to increase (P = 0.07) with 1 µM ZH. There was no effect (P > 0.10) of ZH on the β-AR or IGF-I gene expression in fused myotube cultures at 192 h or on fusion percentage. The β2-AR antagonist ICI-118, 551 at 0.1 µM attenuated (P < 0.05) the effect of 0.1 µM ZH to reduce expression of β1- and β2-AR mRNA. The combination of 0.01 µM ZH and 0.1 µM ICI-118, 551 caused an increase (P < 0.05) in β1-AR gene expression. There was no effect (P > 0.10) of ICI-118, 551 or ZH on β3-AR or IGF-I. Western blot analysis revealed that the protein content of β2-AR in ZH-treated myotube cultures decreased (P < 0.05) relative to control. Total lipid synthesis from acetate was increased by ZH in bovine subcutaneous adipose tissue explants in the absence of theophylline but was decreased by ZH when theophylline was included in the incubation medium. These data indicate that ZH alters mRNA and protein concentrations of β-AR in satellite cell cultures, which in turn could affect responsiveness of cells to prolonged ZH exposure in vivo. Similar to other β-adrenergic agonists, ZH had only modest effects on lipid metabolism in adipose tissue

  16. Magnetic Resonance Imaging of Human Tissue-Engineered Adipose Substitutes.

    PubMed

    Proulx, Maryse; Aubin, Kim; Lagueux, Jean; Audet, Pierre; Auger, Michèle; Fortin, Marc-André; Fradette, Julie

    2015-07-01

    Adipose tissue (AT) substitutes are being developed to answer the strong demand in reconstructive surgery. To facilitate the validation of their functional performance in vivo, and to avoid resorting to excessive number of animals, it is crucial at this stage to develop biomedical imaging methodologies, enabling the follow-up of reconstructed AT substitutes. Until now, biomedical imaging of AT substitutes has scarcely been reported in the literature. Therefore, the optimal parameters enabling good resolution, appropriate contrast, and graft delineation, as well as blood perfusion validation, must be studied and reported. In this study, human adipose substitutes produced from adipose-derived stem/stromal cells using the self-assembly approach of tissue engineering were implanted into athymic mice. The fate of the reconstructed AT substitutes implanted in vivo was successfully followed by magnetic resonance imaging (MRI), which is the imaging modality of choice for visualizing soft ATs. T1-weighted images allowed clear delineation of the grafts, followed by volume integration. The magnetic resonance (MR) signal of reconstructed AT was studied in vitro by proton nuclear magnetic resonance ((1)H-NMR). This confirmed the presence of a strong triglyceride peak of short longitudinal proton relaxation time (T1) values (200 ± 53 ms) in reconstructed AT substitutes (total T1=813 ± 76 ms), which establishes a clear signal difference between adjacent muscle, connective tissue, and native fat (total T1 ~300 ms). Graft volume retention was followed up to 6 weeks after implantation, revealing a gradual resorption rate averaging at 44% of initial substitute's volume. In addition, vascular perfusion measured by dynamic contrast-enhanced-MRI confirmed the graft's vascularization postimplantation (14 and 21 days after grafting). Histological analysis of the grafted tissues revealed the persistence of numerous adipocytes without evidence of cysts or tissue necrosis. This study

  17. 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

  18. A muscle-liver-fat signalling axis is essential for central control of adaptive adipose remodelling

    PubMed Central

    Shimizu, Noriaki; Maruyama, Takako; Yoshikawa, Noritada; Matsumiya, Ryo; Ma, Yanxia; Ito, Naoki; Tasaka, Yuki; Kuribara-Souta, Akiko; Miyata, Keishi; Oike, Yuichi; Berger, Stefan; Schütz, Günther; Takeda, Shin’ichi; Tanaka, Hirotoshi

    2015-01-01

    Skeletal muscle has a pleiotropic role in organismal energy metabolism, for example, by storing protein as an energy source, or by excreting endocrine hormones. Muscle proteolysis is tightly controlled by the hypothalamus-pituitary-adrenal signalling axis via a glucocorticoid-driven transcriptional programme. Here we unravel the physiological significance of this catabolic process using skeletal muscle-specific glucocorticoid receptor (GR) knockout (GRmKO) mice. These mice have increased muscle mass but smaller adipose tissues. Metabolically, GRmKO mice show a drastic shift of energy utilization and storage in muscle, liver and adipose tissues. We demonstrate that the resulting depletion of plasma alanine serves as a cue to increase plasma levels of fibroblast growth factor 21 (FGF21) and activates liver-fat communication, leading to the activation of lipolytic genes in adipose tissues. We propose that this skeletal muscle-liver-fat signalling axis may serve as a target for the development of therapies against various metabolic diseases, including obesity. PMID:25827749

  19. 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

  20. 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

  1. 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

  2. Brown Adipose Tissue in Cetacean Blubber

    PubMed Central

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall’s and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  3. Brown adipose tissue in cetacean blubber.

    PubMed

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  4. Brown adipose tissue in cetacean blubber.

    PubMed

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  5. 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.

  6. 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.

  7. 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

  8. Hepatic ANGPTL3 regulates adipose tissue energy homeostasis

    PubMed Central

    Wang, Yan; McNutt, Markey C.; Banfi, Serena; Levin, Michael G.; Holland, William L.; Gusarova, Viktoria; Gromada, Jesper; Cohen, Jonathan C.; Hobbs, Helen H.

    2015-01-01

    Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3−/− mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3−/− animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3−/− mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target. PMID:26305978

  9. Hepatic ANGPTL3 regulates adipose tissue energy homeostasis.

    PubMed

    Wang, Yan; McNutt, Markey C; Banfi, Serena; Levin, Michael G; Holland, William L; Gusarova, Viktoria; Gromada, Jesper; Cohen, Jonathan C; Hobbs, Helen H

    2015-09-15

    Angiopoietin-like protein 3 (ANGPTL3) is a circulating inhibitor of lipoprotein and endothelial lipase whose physiological function has remained obscure. Here we show that ANGPTL3 plays a major role in promoting uptake of circulating very low density lipoprotein-triglycerides (VLDL-TGs) into white adipose tissue (WAT) rather than oxidative tissues (skeletal muscle, heart brown adipose tissue) in the fed state. This conclusion emerged from studies of Angptl3(-/-) mice. Whereas feeding increased VLDL-TG uptake into WAT eightfold in wild-type mice, no increase occurred in fed Angptl3(-/-) animals. Despite the reduction in delivery to and retention of TG in WAT, fat mass was largely preserved by a compensatory increase in de novo lipogenesis in Angptl3(-/-) mice. Glucose uptake into WAT was increased 10-fold in KO mice, and tracer studies revealed increased conversion of glucose to fatty acids in WAT but not liver. It is likely that the increased uptake of glucose into WAT explains the increased insulin sensitivity associated with inactivation of ANGPTL3. The beneficial effects of ANGPTL3 deficiency on both glucose and lipoprotein metabolism make it an attractive therapeutic target. PMID:26305978

  10. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  11. [Muscles and connective tissue: histology].

    PubMed

    Delage, J-P

    2012-10-01

    Here, we give some comments about the DVD movies "Muscle Attitudes" from Endovivo productions, the movies up lighting some loss in the attention given to studies on the connective tissue, and especially them into muscles. The main characteristics of the different components in the intra-muscular connective tissue (perimysium, endomysium, epimysium) are shown here with special references to their ordered architecture and special references to their spatial distributions. This connective tissue is abundant into the muscles and is in continuity with the muscles in vicinity, with their tendons and their sheath, sticking the whole on skin. This connective tissue has also very abundant connections on the muscles fibres. It is then assumed that the connective tissue sticks every organs or cells of the locomotion system. Considering the elastic properties of the collagen fibres which are the most abundant component of connective tissue, it is possible to up light a panel of connective tissue associated functions such as the transmission of muscle contractions or the regulation of protein and energetic muscles metabolism.

  12. 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.

  13. Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD

    PubMed Central

    Maddocks, Matthew; Shrikrishna, Dinesh; Vitoriano, Simone; Natanek, Samantha A.; Tanner, Rebecca J.; Hart, Nicholas; Kemp, Paul R.; Moxham, John; Polkey, Michael I.; Hopkinson, Nicholas S.

    2014-01-01

    Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population. In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190– -30 HU; skeletal muscle -29–150 HU. Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72–0.95). Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes. PMID:24993908

  14. Skeletal muscle adiposity is associated with physical activity, exercise capacity and fibre shift in COPD.

    PubMed

    Maddocks, Matthew; Shrikrishna, Dinesh; Vitoriano, Simone; Natanek, Samantha A; Tanner, Rebecca J; Hart, Nicholas; Kemp, Paul R; Moxham, John; Polkey, Michael I; Hopkinson, Nicholas S

    2014-11-01

    Quadriceps muscle phenotype varies widely between patients with chronic obstructive pulmonary disease (COPD) and cannot be determined without muscle biopsy. We hypothesised that measures of skeletal muscle adiposity could provide noninvasive biomarkers of muscle quality in this population. In 101 patients and 10 age-matched healthy controls, mid-thigh cross-sectional area, percentage intramuscular fat and skeletal muscle attenuation were calculated using computed tomography images and standard tissue attenuation ranges: fat -190- -30 HU; skeletal muscle -29-150 HU. Mean±sd percentage intramuscular fat was higher in the patient group (6.7±3.5% versus 4.3±1.2%, p = 0.03). Both percentage intramuscular fat and skeletal muscle attenuation were associated with physical activity level, exercise capacity and type I fibre proportion, independent of age, mid-thigh cross-sectional area and quadriceps strength. Combined with transfer factor of the lung for carbon monoxide, these variables could identify >80% of patients with fibre type shift with >65% specificity (area under the curve 0.83, 95% CI 0.72-0.95). Skeletal muscle adiposity assessed by computed tomography reflects multiple aspects of COPD related muscle dysfunction and may help to identify patients for trials of interventions targeted at specific muscle phenotypes.

  15. 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

  16. Differential effects of reduced protein diets on fatty acid composition and gene expression in muscle and subcutaneous adipose tissue of Alentejana purebred and Large White × Landrace × Pietrain crossbred pigs.

    PubMed

    Madeira, Marta S; Pires, Virgínia M R; Alfaia, Cristina M; Costa, Ana S H; Luxton, Richard; Doran, Olena; Bessa, Rui J B; Prates, José A M

    2013-07-28

    The present study assessed the effect of pig genotype (fatty v. lean) and dietary protein and lysine (Lys) levels (normal v. reduced) on intramuscular fat (IMF) content, subcutaneous adipose tissue (SAT) deposition, fatty acid composition and mRNA levels of genes controlling lipid metabolism. The experiment was conducted on sixty intact male pigs (thirty Alentejana purebred and thirty Large White × Landrace × Pietrain crossbred), from 60 to 93 kg of live weight. Animals were divided into three groups fed with the following diets: control diet equilibrated for Lys (17·5 % crude protein (CP) and 0·7 % Lys), reduced protein diet (RPD) equilibrated for Lys (13·2 % CP and 0·6 % Lys) and RPD not equilibrated for Lys (13·1 % CP and 0·4 % Lys). It was shown that the RPD increased fat deposition in the longissimus lumborum muscle in the lean but not in the fatty pig genotype. It is strongly suggested that the effect of RPD on the longissimus lumborum muscle of crossbred pigs is mediated via Lys restriction. The increase in IMF content under the RPD was accompanied by increased stearoyl-CoA desaturase (SCD) and PPARG mRNA levels. RPD did not alter backfat thickness, but increased the total fatty acid content in both lean and fatty pig genotype. The higher amount of SAT in fatty pigs, when compared with the lean ones, was associated with the higher expression levels of ACACA, CEBPA, FASN and SCD genes. Taken together, the data indicate that the mechanisms regulating fat deposition in pigs are genotype and tissue specific, and are associated with the expression regulation of the key lipogenic genes. PMID:23286604

  17. 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...

  18. 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.

  19. 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 ...

  20. 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

  1. 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.

  2. Cell-autonomous activation of Hedgehog signaling inhibits brown adipose tissue development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Although recent studies have shown that brown adipose tissue (BAT) arises from progenitor cells that also give rise to skeletal muscle, the developmental signals that control the formation of BAT remain largely unknown. Here, we show that brown preadipocytes possess primary cilia and can respond to ...

  3. Non-invasive Assessments of Adipose Tissue Metabolism In Vitro.

    PubMed

    Abbott, Rosalyn D; Borowsky, Francis E; Quinn, Kyle P; Bernstein, David L; Georgakoudi, Irene; Kaplan, David L

    2016-03-01

    Adipose tissue engineering is a diverse area of research where the developed tissues can be used to study normal adipose tissue functions, create disease models in vitro, and replace soft tissue defects in vivo. Increasing attention has been focused on the highly specialized metabolic pathways that regulate energy storage and release in adipose tissues which affect local and systemic outcomes. Non-invasive, dynamic measurement systems are useful to track these metabolic pathways in the same tissue model over time to evaluate long term cell growth, differentiation, and development within tissue engineering constructs. This approach reduces costs and time in comparison to more traditional destructive methods such as biochemical and immunochemistry assays and proteomics assessments. Towards this goal, this review will focus on important metabolic functions of adipose tissues and strategies to evaluate them with non-invasive in vitro methods. Current non-invasive methods, such as measuring key metabolic markers and endogenous contrast imaging will be explored.

  4. Insulin resistance is associated with altered amino acid metabolism and adipose tissue dysfunction in normoglycemic women

    PubMed Central

    Wiklund, Petri; Zhang, Xiaobo; Pekkala, Satu; Autio, Reija; Kong, Lingjia; Yang, Yifan; Keinänen-Kiukaanniemi, Sirkka; Alen, Markku; Cheng, Sulin

    2016-01-01

    Insulin resistance is associated adiposity, but the mechanisms are not fully understood. In this study, we aimed to identify early metabolic alterations associated with insulin resistance in normoglycemic women with varying degree of adiposity. One-hundred and ten young and middle-aged women were divided into low and high IR groups based on their median HOMA-IR (0.9 ± 0.4 vs. 2.8 ± 1.2). Body composition was assessed using DXA, skeletal muscle and liver fat by proton magnetic resonance spectroscopy, serum metabolites by nuclear magnetic resonance spectroscopy and adipose tissue and skeletal muscle gene expression by microarrays. High HOMA-IR subjects had higher serum branched-chain amino acid concentrations (BCAA) (p < 0.05 for both). Gene expression analysis of subcutaneous adipose tissue revealed significant down-regulation of genes related to BCAA catabolism and mitochondrial energy metabolism and up-regulation of several inflammation-related pathways in high HOMA-IR subjects (p < 0.05 for all), but no differentially expressed genes in skeletal muscle were found. In conclusion, in normoglycemic women insulin resistance was associated with increased serum BCAA concentrations, down-regulation of mitochondrial energy metabolism and increased expression of inflammation-related genes in the adipose tissue. PMID:27080554

  5. The Ontogeny of Brown Adipose Tissue.

    PubMed

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2015-01-01

    There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible.

  6. The Ontogeny of Brown Adipose Tissue.

    PubMed

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2015-01-01

    There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible. PMID:26076904

  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. Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m6A Modifications in Adipose and Skeletal Muscle Tissues in Offspring

    PubMed Central

    Li, Xiao; Yang, Jing; Zhu, Youbo; Liu, Yuan; Shi, Xin’e; Yang, Gongshe

    2016-01-01

    Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m6A methylation—an old epigenetic marker receiving increased attention recently—is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee’s index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N6-methyladenosine (m6A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m6A modifications at three weeks, and lowered m6A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m6A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m6A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m6A system during the transmission from maternal nutrition to subsequent generations. PMID:27548155

  9. Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m⁶A Modifications in Adipose and Skeletal Muscle Tissues in Offspring.

    PubMed

    Li, Xiao; Yang, Jing; Zhu, Youbo; Liu, Yuan; Shi, Xin'e; Yang, Gongshe

    2016-08-19

    Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m⁶A methylation-an old epigenetic marker receiving increased attention recently-is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee's index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N⁶-methyladenosine (m⁶A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m⁶A modifications at three weeks, and lowered m⁶A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m⁶A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m⁶A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m⁶A system during the transmission from maternal nutrition to subsequent generations.

  10. Mouse Maternal High-Fat Intake Dynamically Programmed mRNA m⁶A Modifications in Adipose and Skeletal Muscle Tissues in Offspring.

    PubMed

    Li, Xiao; Yang, Jing; Zhu, Youbo; Liu, Yuan; Shi, Xin'e; Yang, Gongshe

    2016-01-01

    Epigenetic mechanisms have an important role in the pre- and peri-conceptional programming by maternal nutrition. Yet, whether or not RNA m⁶A methylation-an old epigenetic marker receiving increased attention recently-is involved remains an unknown question. In this study, mouse high-fat feeding prior to conception was shown to induce overweight and glucose intolerant dams, which then continued to be exposed to a high-fat diet during gestation and lactation. The dams on a standard diet throughout the whole experiment were used as a control. Results showed that maternal high-fat intake impaired postnatal growth in male offspring, indicated by decreased body weight and Lee's index at 3, 8 and 15 weeks old, but the percentages of visceral fat and tibialis anterior relative to the whole body weights were significantly increased at eight weeks of age. The maternal high-fat exposure significantly increased mRNA N⁶-methyladenosine (m⁶A) levels in visceral fat at three weeks old, combined with downregulated Fat mass and obesity-associated gene (FTO) and upregulated Methyltransferase like 3 (METTL3) transcription, and these changes were reversed at eight weeks of age. In the tibialis anterior muscle, the maternal high-fat diet significantly enhanced m⁶A modifications at three weeks, and lowered m⁶A levels at 15 weeks of age. Accordingly, FTO transcription was significantly inhibited at three weeks and stimulated at 15 weeks of age, and METTL3 transcripts were significantly improved at three weeks. Interestingly, both FTO and METTL3 transcription was significantly elevated at eight weeks of age, and yet the m⁶A modifications remained unchanged. Our study showed that maternal high-fat intake could affect mRNA m⁶A modifications and its related genes in offspring in a tissue-specific and development-dependent way, and provided an interesting indication of the working of the m⁶A system during the transmission from maternal nutrition to subsequent generations

  11. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue.

    PubMed

    Šram, Miroslav; Vrselja, Zvonimir; Lekšan, Igor; Ćurić, Goran; Selthofer-Relatić, Kristina; Radić, Radivoje

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. PMID:26124828

  12. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue

    PubMed Central

    Šram, Miroslav; Vrselja, Zvonimir; Lekšan, Igor; Ćurić, Goran; Selthofer-Relatić, Kristina; Radić, Radivoje

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value. PMID:26124828

  13. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue.

    PubMed

    Šram, Miroslav; Vrselja, Zvonimir; Lekšan, Igor; Ćurić, Goran; Selthofer-Relatić, Kristina; Radić, Radivoje

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.

  14. 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.

  15. Synovial fluid of patients with rheumatoid arthritis induces α-smooth muscle actin in human adipose tissue-derived mesenchymal stem cells through a TGF-β1-dependent mechanism

    PubMed Central

    Song, Hae Young; Kim, Min Young; Kim, Kyung Hye; Lee, Il Hwan; Shin, Sang Hun; Lee, Jung Sub

    2010-01-01

    Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-β1 (TGF-β1) is a secreted protein that promotes differentiation of synovial fibroblasts to α-smooth muscle actin (α-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of α-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced α-SMA expression was abrogated by immunodepletion of TGF-β1 from RA-SF with anti-TGF-β1 antibody. Furthermore, pretreatment of hASCs with the TGF-β type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-β type I receptor expression in hASCs blocked RA-SF-induced α-SMA expression. Small interfering RNA-mediated silencing of Smad2 or adenoviral overexpression of Smad7 (an inhibitory Smad isoform) completely inhibited RA-SF-stimulated α-SMA expression. These results suggest that TGF-β1 plays a pivotal role in RA-SF-induced differentiation of hASCs to α-SMA-positive cells. PMID:20628268

  16. 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.

  17. 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

  18. Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake

    PubMed Central

    Zeve, Daniel; Seo, Jin; Suh, Jae Myoung; Stenesen, Drew; Tang, Wei; Berglund, Eric D.; Wan, Yihong; Williams, Linda J.; Lim, Ajin; Martinez, Myrna J.; McKay, Renée M.; Millay, Douglas P.; Olson, Eric N.; Graff, Jonathan M.

    2012-01-01

    SUMMARY Adipose tissues provide circulating nutrients and hormones. We present in vivo mouse studies highlighting roles for Wnt signals in both aspects of metabolism. β-catenin activation in PPARγ–expressing fat progenitors (PBCA) decreased fat mass and induced fibrotic replacement of subcutaneous fat specifically. In spite of lipodystrophy, PBCA mice did not develop the expected diabetes and hepatosteatosis, but rather exhibited improved glucose metabolism and normal insulin sensitivity. Glucose uptake was increased in muscle independently of insulin, associated with cell surface translocation of glucose transporters and AMPK activation. Ex vivo assays showed these effects were likely secondary to blood-borne signals since PBCA sera or conditioned media from PBCA fat progenitors enhanced glucose uptake and activated AMPK in muscle cultures. Thus, adipose progenitor Wnt activation dissociates lipodystrophy from dysfunctional metabolism and highlights a fat-muscle endocrine axis, which may represent a potential therapy to lower blood glucose and improve metabolism. PMID:22482731

  19. Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake.

    PubMed

    Zeve, Daniel; Seo, Jin; Suh, Jae Myoung; Stenesen, Drew; Tang, Wei; Berglund, Eric D; Wan, Yihong; Williams, Linda J; Lim, Ajin; Martinez, Myrna J; McKay, Renée M; Millay, Douglas P; Olson, Eric N; Graff, Jonathan M

    2012-04-01

    Adipose tissues provide circulating nutrients and hormones. We present in vivo mouse studies highlighting roles for Wnt signals in both aspects of metabolism. β-catenin activation in PPARγ-expressing fat progenitors (PBCA) decreased fat mass and induced fibrotic replacement of subcutaneous fat specifically. In spite of lipodystrophy, PBCA mice did not develop the expected diabetes and hepatosteatosis, but rather exhibited improved glucose metabolism and normal insulin sensitivity. Glucose uptake was increased in muscle independently of insulin, associated with cell-surface translocation of glucose transporters and AMPK activation. Ex vivo assays showed these effects were likely secondary to blood-borne signals since PBCA sera or conditioned media from PBCA fat progenitors enhanced glucose uptake and activated AMPK in muscle cultures. Thus, adipose progenitor Wnt activation dissociates lipodystrophy from dysfunctional metabolism and highlights a fat-muscle endocrine axis, which may represent a potential therapy to lower blood glucose and improve metabolism.

  20. 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

  1. 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

  2. Cell Supermarket: Adipose Tissue as a Source of Stem Cells

    PubMed Central

    Dodson, M.V.; Wei, S.; Duarte, M.; Du, M.; Jiang, Z.; Hausman, G.J.; Bergen, W.G.

    2013-01-01

    Adipose tissue is derived from numerous sources, and in recent years this tissue 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 and scientific applications. The focus of this paper is to reflect on this area of research and to provide a list of potential (future) research areas. PMID:25031654

  3. 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

  4. 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.

  5. 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.

  6. Total DDT and dieldrin content of human adipose tissue

    SciTech Connect

    Ahmad, N.; Harsas, W.; Marolt, R.S.; Morton, M.; Pollack, J.K.

    1988-12-01

    As far as the authors could ascertain only 4 well-documented analytical studies have been carried out in Australia determining the total DDT and dieldrin content of human adipose tissue. The latest of these studies was published over 16 years ago. Therefore it is timely and important to re-examine the total DDT and dieldrin concentration within the adipose tissue of the Australian population. The present investigation has analyzed 290 samples of human adipose tissue obtained from Westmead Hospital situated in an outer suburb of Sydney, New South Wales for their content of total DDT and dieldrin.

  7. 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.

  8. Isoliquiritigenin Attenuates Adipose Tissue Inflammation in vitro and Adipose Tissue Fibrosis through Inhibition of Innate Immune Responses in Mice

    PubMed Central

    Watanabe, Yasuharu; Nagai, Yoshinori; Honda, Hiroe; Okamoto, Naoki; Yamamoto, Seiji; Hamashima, Takeru; Ishii, Yoko; Tanaka, Miyako; Suganami, Takayoshi; Sasahara, Masakiyo; Miyake, Kensuke; Takatsu, Kiyoshi

    2016-01-01

    Isoliquiritigenin (ILG) is a flavonoid derived from Glycyrrhiza uralensis and potently suppresses NLRP3 inflammasome activation resulting in the improvement of diet-induced adipose tissue inflammation. However, whether ILG affects other pathways besides the inflammasome in adipose tissue inflammation is unknown. We here show that ILG suppresses adipose tissue inflammation by affecting the paracrine loop containing saturated fatty acids and TNF-α by using a co-culture composed of adipocytes and macrophages. ILG suppressed inflammatory changes induced by the co-culture through inhibition of NF-κB activation. This effect was independent of either inhibition of inflammasome activation or activation of peroxisome proliferator-activated receptor-γ. Moreover, ILG suppressed TNF-α-induced activation of adipocytes, coincident with inhibition of IκBα phosphorylation. Additionally, TNF-α-mediated inhibition of Akt phosphorylation under insulin signaling was alleviated by ILG in adipocytes. ILG suppressed palmitic acid-induced activation of macrophages, with decreasing the level of phosphorylated Jnk expression. Intriguingly, ILG improved high fat diet-induced fibrosis in adipose tissue in vivo. Finally, ILG inhibited TLR4- or Mincle-stimulated expression of fibrosis-related genes in stromal vascular fraction from obese adipose tissue and macrophages in vitro. Thus, ILG can suppress adipose tissue inflammation by both inflammasome-dependent and -independent manners and attenuate adipose tissue fibrosis by targeting innate immune sensors. PMID:26975571

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity

    PubMed Central

    Hamrick, Mark W.; McGee-Lawrence, Meghan E.; Frechette, Danielle M.

    2016-01-01

    Skeletal muscle and bone share common embryological origins from mesodermal cell populations and also display common growth trajectories early in life. Moreover, muscle and bone are both mechanoresponsive tissues, and the mass and strength of both tissues decline with age. The decline in muscle and bone strength that occurs with aging is accompanied in both cases by an accumulation of adipose tissue. In bone, adipocyte (AC) accumulation occurs in the marrow cavities of long bones and is known to increase with estrogen deficiency, mechanical unloading, and exposure to glucocorticoids. The factors leading to accumulation of intra- and intermuscular fat (myosteatosis) are less well understood, but recent evidence indicates that increases in intramuscular fat are associated with disuse, altered leptin signaling, sex steroid deficiency, and glucocorticoid treatment, factors that are also implicated in bone marrow adipogenesis. Importantly, accumulation of ACs in skeletal muscle and accumulation of intramyocellular lipid are linked to loss of muscle strength, reduced insulin sensitivity, and increased mortality among the elderly. Resistance exercise and whole body vibration can prevent fatty infiltration in skeletal muscle and also improve muscle strength. Therapeutic strategies to prevent myosteatosis may improve muscle function and reduce fall risk in the elderly, potentially impacting the incidence of bone fracture. PMID:27379021

  16. Fatty Infiltration of Skeletal Muscle: Mechanisms and Comparisons with Bone Marrow Adiposity.

    PubMed

    Hamrick, Mark W; McGee-Lawrence, Meghan E; Frechette, Danielle M

    2016-01-01

    Skeletal muscle and bone share common embryological origins from mesodermal cell populations and also display common growth trajectories early in life. Moreover, muscle and bone are both mechanoresponsive tissues, and the mass and strength of both tissues decline with age. The decline in muscle and bone strength that occurs with aging is accompanied in both cases by an accumulation of adipose tissue. In bone, adipocyte (AC) accumulation occurs in the marrow cavities of long bones and is known to increase with estrogen deficiency, mechanical unloading, and exposure to glucocorticoids. The factors leading to accumulation of intra- and intermuscular fat (myosteatosis) are less well understood, but recent evidence indicates that increases in intramuscular fat are associated with disuse, altered leptin signaling, sex steroid deficiency, and glucocorticoid treatment, factors that are also implicated in bone marrow adipogenesis. Importantly, accumulation of ACs in skeletal muscle and accumulation of intramyocellular lipid are linked to loss of muscle strength, reduced insulin sensitivity, and increased mortality among the elderly. Resistance exercise and whole body vibration can prevent fatty infiltration in skeletal muscle and also improve muscle strength. Therapeutic strategies to prevent myosteatosis may improve muscle function and reduce fall risk in the elderly, potentially impacting the incidence of bone fracture. PMID:27379021

  17. 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.

  18. The adipose tissue in farm animals: a proteomic approach.

    PubMed

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura; Ceciliani, Fabrizio

    2014-03-01

    Adipose tissue is not only a tissue where energy is stored but is also involved in regulating several body functions such as appetite and energy expenditure via its endocrine activity. Moreover, it thereby modulates complex processes like reproduction, inflammation and immune response. The products secreted from adipose tissue comprise hormones and cytokines that are collectively termed as adipocytokines or "adipokines"; the discovery and characterization of new proteins secreted by adipose tissue is still ongoing and their number is thus increasing. Adipokines act in both endocrine manner as well as locally, as autocrine or paracrine effectors. Proteomics has emerged as a valuable technique to characterize both cellular and secreted proteomes from adipose tissues, including those of main cellular fractions, i.e. the adipocytes or the stromal vascular fraction containing mainly adipocyte precursors and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal structure for the mammary gland and on its role in participating in and regulating of energy metabolism and other functions. Moreover, as pig has recently become an important model organism to study human diseases, the knowledge of adipose tissue metabolism in pig is relevant for the study of obesity and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in

  19. 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

  20. Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

    PubMed

    Hochberg, Irit; Tran, Quynh T; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.

  1. Gene Expression Signature in Adipose Tissue of Acromegaly Patients

    PubMed Central

    Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

  2. 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.

  3. 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

  4. Contrasting effects of cold acclimation versus obesogenic diets on chemerin gene expression in brown and brite adipose tissues.

    PubMed

    Hansen, Ida R; Jansson, Kim M; Cannon, Barbara; Nedergaard, Jan

    2014-12-01

    Based on results from a signal sequence trap, we investigated chemerin gene expression in brown adipose tissue. Male NMRI mice were exposed to 30, 22 or 4 °C for 3 weeks, or were fed control (chow) diet, cafeteria diet or high-fat diet at thermoneutrality for the same time. In brown adipose tissue, cold acclimation strongly diminished chemerin gene expression, whereas obesogenic diets augmented expression. Qualitatively, changes in expression were paralleled in brite/beige adipose tissues (e.g. inguinal), whereas white adipose tissue (epididymal) and muscle did not react to these cues. Changes in tissue expression were not directly paralleled by alterations in plasma levels. Both these intact animal studies and brown adipocyte cell culture studies indicated that the gene expression regulation was not congruent with a sympathetic/adrenergic control. The data are discussed in relation to suggested endocrine, paracrine and autocrine effects of chemerin.

  5. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome

    PubMed Central

    Yuan, Xiaoxue; Hu, Tao; Zhao, Han; Huang, Yuanyuan; Ye, Rongcai; Lin, Jun; Zhang, Chuanhai; Zhang, Hanlin; Wei, Gang; Zhou, Huiqiao; Dong, Meng; Zhao, Jun; Wang, Haibin; Liu, Qingsong; Lee, Hyuek Jong; Jin, Wanzhu; Chen, Zi-Jiang

    2016-01-01

    Polycystic ovary syndrome (PCOS), which is characterized by anovulation, hyperandrogenism, and polycystic ovaries, is a complex endocrinopathy. Because the cause of PCOS at the molecular level is largely unknown, there is no cure or specific treatment for PCOS. Here, we show that transplantation of brown adipose tissue (BAT) reversed anovulation, hyperandrogenism, and polycystic ovaries in a dehydroepiandrosterone (DHEA)-induced PCOS rat. BAT transplantation into a PCOS rat significantly stabilized menstrual irregularity and improved systemic insulin sensitivity up to a normal level, which was not shown in a sham-operated or muscle-transplanted PCOS rat. Moreover, BAT transplantation, not sham operation or muscle transplantation, surprisingly improved fertility in PCOS rats. Interestingly, BAT transplantation activated endogenous BAT and thereby increased the circulating level of adiponectin, which plays a prominent role in whole-body energy metabolism and ovarian physiology. Consistent with BAT transplantation, administration of adiponectin protein dramatically rescued DHEA-induced PCOS phenotypes. These results highlight that endogenous BAT activity is closely related to the development of PCOS phenotypes and that BAT activation might be a promising therapeutic option for the treatment of PCOS. PMID:26903641

  6. 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.

  7. Erythropoietin administration partially prevents adipose tissue loss in experimental cancer cachexia models

    PubMed Central

    Penna, Fabio; Busquets, Silvia; Toledo, Miriam; Pin, Fabrizio; Massa, David; López-Soriano, Francisco J.; Costelli, Paola; Argilés, Josep M.

    2013-01-01

    Cancer-associated cachexia is characterized, among other symptoms, by a dramatic loss of both muscle and fat. In addition, the cachectic syndrome is often associated with anemia. The object of the present investigation was to assess the effects of erythropoietin (EPO) treatment on experimental cancer cachexia models. The results clearly show that, in addition to the improvement of the hematocrit, EPO treatment promoted a partial preservation of adipose tissue while exerting negligible effects on muscle loss. Administration of EPO to tumor-bearing animals resulted in a significant increase of lipoprotein lipase (LPL) activity in adipose tissue, suggesting that the treatment favored triacylglycerol (TAG) accumulation in the adipose tissue. In vitro experiments using both adipose tissue slices and 3T3-L1 adipocytes suggests that EPO is able to increase the lipogenic rate through the activation of its specific receptor (EPOR). This metabolic pathway, in addition to TAG uptake by LPL, may contribute to the beneficial effects of EPO on fat preservation in cancer cachexia. PMID:23966665

  8. Adipose tissue macrophages, low grade inflammation and insulin resistance in human obesity.

    PubMed

    Heilbronn, Leonie K; Campbell, Lesley V

    2008-01-01

    Obesity was first described as a low-grade inflammatory condition more than a decade ago. However, it is only relatively recently that obese individuals have been described with increased macrophage infiltration of adipose tissue, as well as an increase in the number of "M1" or "classically activated" macrophages. Furthermore, macrophages have been identified as the primary source of many of the circulating inflammatory molecules that are detected in the obese state and are postulated to be causal both in the development of insulin resistance and in the progression to type 2 diabetes. There is also novel evidence to suggest that macrophages inhibit adipocyte differentiation, potentially leading to adipocyte hypertrophy, altered secretion of adipokines and ectopic storage of lipid within liver, muscle and other non-adipose tissues. Currently, it is not clear what causes increased macrophage infiltration of adipose tissue in obese individuals. Theories include altered signalling by adipocytes, nutritional induction of metabolic endotoxemia or reduced angiogenesis and local adipose cell hypoxia. Importantly, PPAR-gamma agonists have been shown to alter macrophage phenotype to "M2" or an "alternatively activated" anti-inflammatory phenotype and may induce macrophage specific cell death. Consequently, excitement surrounds the potential for specific inhibition of macrophage infiltration of adipose tissue via pharmacotherapy for obese patients and more particularly as adjunct therapy to improve insulin sensitivity in obese individuals with insulin resistance and overt type 2 diabetes.

  9. 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

  10. 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.

  11. From neutrophils to macrophages: differences in regional adipose tissue depots.

    PubMed

    Dam, V; Sikder, T; Santosa, S

    2016-01-01

    Currently, we do not fully understand the underlying mechanisms of how regional adiposity promotes metabolic dysregulation. As adipose tissue expands, there is an increase in chronic systemic low-grade inflammation due to greater infiltration of immune cells and production of cytokines. This chronic inflammation is thought to play a major role in the development of metabolic complications and disease such as insulin resistance and diabetes. We know that different adipose tissue depots contribute differently to the risk of metabolic disease. People who have an upper body fat distribution around the abdomen are at greater risk of disease than those who tend to store fat in their lower body around the hips and thighs. Thus, it is conceivable that adipose tissue depots contribute differently to the inflammatory milieu as a result of varied infiltration of immune cell types. In this review, we describe the role and function of major resident immune cells in the development of adipose tissue inflammation and discuss their regional differences in the context of metabolic disease risk. We find that although initial studies have found regional differences, a more comprehensive understanding of how immune cells interrupt adipose tissue homeostasis is needed.

  12. Ghrelin receptor regulates adipose tissue inflammation in aging

    PubMed Central

    Buras, Eric D.; Yu, Kaijiang; Wang, Ruitao; Smith, C. Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr−/− mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsr−/− mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsr−/− mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance. PMID:26837433

  13. 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

  14. INVITED REVIEW: Evolution of meat animal growth research during the past 50 years: Adipose and muscle stem cells.

    PubMed

    Dodson, M V; Allen, R E; Du, M; Bergen, W G; Velleman, S G; Poulos, S P; Fernyhough-Culver, M; Wheeler, M B; Duckett, S K; Young, M R I; Voy, B H; Jiang, Z; Hausman, G J

    2015-02-01

    If one were to compare today's animal growth research to research from a mere 50 yr ago, one would see programs with few similarities. The evolution of this research from whole-animal through cell-based and finally molecular and genomic studies has been enhanced by the identification, isolation, and in vitro evaluation of adipose- and muscle-derived stem cells. This paper will highlight the struggles and the milestones that make this evolving area of research what it is today. The contribution of adipose and muscle stem cell research to development and growth, tissue regeneration, and final carcass composition are reviewed.

  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. Inflammation and adipose tissue macrophages in lipodystrophic mice.

    PubMed

    Herrero, Laura; Shapiro, Hagit; Nayer, Ali; Lee, Jongsoon; Shoelson, Steven E

    2010-01-01

    Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-kappaB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance.

  17. Inflammation and adipose tissue macrophages in lipodystrophic mice

    PubMed Central

    Herrero, Laura; Shapiro, Hagit; Nayer, Ali; Lee, Jongsoon; Shoelson, Steven E.

    2009-01-01

    Lipodystrophy and obesity are opposites in terms of a deficiency versus excess of adipose tissue mass, yet these conditions are accompanied by similar metabolic consequences, including insulin resistance, dyslipidemia, hepatic steatosis, and increased risk for diabetes and atherosclerosis. Hepatic and myocellular steatosis likely contribute to metabolic dysregulation in both states. Inflammation and macrophage infiltration into adipose tissue also appear to participate in the pathogenesis of obesity-induced insulin resistance, but their contributions to lipodystrophy-induced insulin resistance have not been evaluated. We used aP2-nSREBP-1c transgenic (Tg) mice, an established model of lipodystrophy, to ask this question. Circulating cytokine elevations suggested systemic inflammation but even more dramatic was the number of infiltrating macrophages in all white and brown adipose tissue depots of the Tg mice; in contrast, there was no evidence of inflammatory infiltrates or responses in any other tissue including liver. Despite there being overt evidence of adipose tissue inflammation, antiinflammatory strategies including salicylate treatment and genetic suppression of myeloid NF-κB signaling that correct insulin resistance in obesity were ineffective in the lipodystrophic mice. We further showed that adipose tissue macrophages (ATMs) in lipodystrophy and obesity are very different in terms of activation state, gene expression patterns, and response to lipopolysaccharide. Although ATMs are even more abundant in lipodystrophy than in obesity, they have distinct phenotypes and likely roles in tissue remodeling, but do not appear to be involved in the pathogenesis of insulin resistance. PMID:20007767

  18. Exercise Regulation of Marrow Adipose Tissue

    PubMed Central

    Pagnotti, Gabriel M.; Styner, Maya

    2016-01-01

    Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally supportive tissues, inhibits bone resorption, and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high-fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone – a PPARγ-agonist known to increase MAT and fracture risk – mice demonstrate a fivefold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  19. Exercise Regulation of Marrow Adipose Tissue.

    PubMed

    Pagnotti, Gabriel M; Styner, Maya

    2016-01-01

    Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally supportive tissues, inhibits bone resorption, and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high-fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a fivefold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise significantly

  20. White Adipose Tissue Resilience to Insulin Deprivation and Replacement

    PubMed Central

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Introduction Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues. PMID:25170835

  1. Control of adipose tissue lipolysis in ectotherm vertebrates.

    PubMed

    Migliorini, R H; Lima-Verde, J S; Machado, C R; Cardona, G M; Garofalo, M A; Kettelhut, I C

    1992-10-01

    Lipolytic activity of fish (Hoplias malabaricus), toad (Bufo paracnemis), and snake (Philodryas patagoniensis) adipose tissue was investigated in vivo and in vitro. Catecholamines or glucagon did not affect the release of free fatty acids (FFA) by incubated fish and toad adipose tissue. Catecholamines also failed to activate snake adipose tissue lipolysis, which even decreased in the presence of epinephrine. However, glucagon stimulated both the lipolytic activity of reptilian tissue in vitro and the mobilization of FFA to plasma when administered to snakes in vivo. The release of FFA from incubated fish, amphibian, and reptilian adipose tissue increased markedly in the presence of cAMP or xanthine derivatives, inhibitors of phosphodiesterase. Forskolin or fluoride, activators of specific components of the adenylate cyclase system, strongly stimulated toad adipose tissue lipolysis. The data suggest that adipocyte triacylglycerol lipase of ectotherm vertebrates is activated by a cAMP-mediated phosphorylation and that the organization of the membrane-bound adenylate cyclase system is similar to that of mammals.

  2. 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

  3. 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

  4. 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

  5. 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

  6. Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue.

    PubMed

    Mori, Shinobu; Kiuchi, Satomi; Ouchi, Atsushi; Hase, Tadashi; Murase, Takatoshi

    2014-01-01

    Adipose tissue is a connective tissue specified for energy metabolism and endocrines, but functional differences between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have not been fully elucidated. To reveal the physiological role of SAT, we characterized in vivo tissue development and in vitro adipocyte differentiation. In a DNA microarray analysis of SAT and VAT in Wistar rats, functional annotation clusters of extracellular matrix (ECM)-related genes were found in SAT, and major ECM molecules expressed in adipose tissues were profiled. In a histological analysis and quantitative expression analysis, ECM expression patterns could be classified into two types: (i) a histogenesis-correlated type such as type IV and XV collagen, and laminin subunits, (ii) a high-SAT expression type such as type I, III, and V collagen and minor characteristic collagens. Type (i) was related to basal membrane and up-regulated in differentiated 3T3-L1 cells and in histogenesis at depot-specific timings. In contrast, type (ii) was related to fibrous forming and highly expressed in 3T3-L1 preadipocytes. Exceptionally, fibronectin was abundant in developed adipose tissue, although it was highly expressed in 3T3-L1 preadipocytes. The present study showed that adipose tissues site-specifically regulate molecular type and timing of ECM expression, and suggests that these characteristic ECM molecules provide a critical microenvironment, which may affect bioactivity of adipocyte itself and interacts with other tissues. It must be important to consider the depot-specific property for the treatment of obesity-related disorders, dermal dysfunction and for the tissue regeneration.

  7. Adipose tissue-liver axis in alcoholic liver disease.

    PubMed

    Wang, Zhi-Gang; Dou, Xiao-Bing; Zhou, Zhan-Xiang; Song, Zhen-Yuan

    2016-02-15

    Alcoholic liver disease (ALD) remains an important health problem worldwide. The disease spectrum is featured by early steatosis, steatohepatitis (steatosis with inflammatory cells infiltration and necrosis), with some individuals ultimately progressing to fibrosis/cirrhosis. Although the disease progression is well characterized, no effective therapies are currently available for the treatment in humans. The mechanisms underlying the initiation and progression of ALD are multifactorial and complex. Emerging evidence supports that adipose tissue dysfunction contributes to the pathogenesis of ALD. In the first part of this review, we discuss the mechanisms whereby chronic alcohol exposure contributed to adipose tissue dysfunction, including cell death, inflammation and insulin resistance. It has been long known that aberrant hepatic methionine metabolism is a major metabolic abnormality induced by chronic alcohol exposure and plays an etiological role in the pathogenesis of ALD. The recent studies in our group documented the similar metabolic effect of chronic alcohol drinking on methionine in adipose tissue. In the second part of this review, we also briefly discuss the recent research progress in the field with a focus on how abnormal methionine metabolism in adipose tissue contributes to adipose tissue dysfunction and liver damage. PMID:26909225

  8. A stringent validation of mouse adipose tissue identity markers.

    PubMed

    de Jong, Jasper M A; Larsson, Ola; Cannon, Barbara; Nedergaard, Jan

    2015-06-15

    The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification (Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.

  9. 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.

  10. 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.

  11. 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

  12. Recent Advances in Proteomic Studies of Adipose Tissues and Adipocytes

    PubMed Central

    Kim, Eun Young; Kim, Won Kon; Oh, Kyoung-Jin; Han, Baek Soo; Lee, Sang Chul; Bae, Kwang-Hee

    2015-01-01

    Obesity is a chronic disease that is associated with significantly increased levels of risk of a number of metabolic disorders. Despite these enhanced health risks, the worldwide prevalence of obesity has increased dramatically over the past few decades. Obesity is caused by the accumulation of an abnormal amount of body fat in adipose tissue, which is composed mostly of adipocytes. Thus, a deeper understanding of the regulation mechanism of adipose tissue and/or adipocytes can provide a clue for overcoming obesity-related metabolic diseases. In this review, we describe recent advances in the study of adipose tissue and/or adipocytes, focusing on proteomic approaches. In addition, we suggest future research directions for proteomic studies which may lead to novel treatments of obesity and obesity-related diseases. PMID:25734986

  13. 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

  14. 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

  15. Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan.

    PubMed

    Friesen, Max; Hudak, Carolyn S; Warren, Curtis R; Xia, Fang; Cowan, Chad A

    2016-08-01

    Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. PMID:27246738

  16. The formation of brown adipose tissue induced by transgenic over-expression of PPARγ2.

    PubMed

    Zhou, Ying; Yang, Jinzeng; Huang, Jinliang; Li, Ting; Xu, Dequan; Zuo, Bo; Hou, Liming; Wu, Wangjun; Zhang, Lin; Xia, Xiaoliang; Ma, Zhiyuan; Ren, Zhuqing; Xiong, Yuanzhu

    2014-04-18

    Brown adipose tissue (BAT) is specialized to dissipate energy as heat, therefore reducing fat deposition and counteracting obesity. Brown adipocytes arise from myoblastic progenitors during embryonic development by the action of transcription regulator PRDM16 binding to PPARγ, which promotes BAT-like phenotype in white adipose tissue. To investigate the capability of converting white adipose tissue to BAT or browning by PPARγ in vivo, we generated transgenic mice with over-expressed PPARγ2. The transgenic mice showed strong brown fat features in subcutaneous fat in morphology and histology. To provide molecular evidences on browning characteristics of the adipose tissue, we employed quantitative real-time PCR to determine BAT-specific gene expressions. The transgenic mice had remarkably elevated mRNA level of UCP1, Elovl3, PGC1α and Cebpα in subcutaneous fat. Compared with wild-type mice, UCP1 protein levels were increased significantly in transgenic mice. ATP concentration was slightly decreased in the subcutaneous fat of transgenic mice. Western blotting analysis also confirmed that phosphorylated AMPK and ACC proteins were significantly (P<0.01) increased in the transgenic mice. Therefore, this study demonstrated that over-expression of PPARγ2 in skeletal muscle can promote conversion of subcutaneous fat to brown fat formation, which can have beneficial effects on increasing energy metabolisms and combating obesity.

  17. Adipose- and muscle-derived Wnts trigger pancreatic β-cell adaptation to systemic insulin resistance

    PubMed Central

    Kozinski, Kamil; Jazurek, Magdalena; Dobrzyn, Pawel; Janikiewicz, Justyna; Kolczynska, Katarzyna; Gajda, Anna; Dobrzyn, Agnieszka

    2016-01-01

    Wnt signaling molecules are associated with obesity, hyperlipidemia, and type 2 diabetes (T2D). Here, we show that two Wnt proteins, WNT3a and WNT4, are specifically secreted by skeletal muscle and adipose tissue during the development of insulin resistance and play an important role in cross-talk between insulin-resistant tissues and pancreatic beta cells. The activation of Frizzled receptor and Wnt signaling in pancreatic islets via circulating WNT3a in blood resulted in higher insulin secretion and an increase in beta cell proliferation, thus leading to islet adaptation in a pre-diabetic state. Interestingly, in fully developed T2D, the expression profiles of Wnt3a and Wnt4 in adipose tissue and muscle cells and blood plasma levels of these proteins were opposite to the pre-diabetic state, thus favoring the downregulation of Wnt signaling in beta cells and resulting in dysfunctional pancreatic islets. These results demonstrate that alterations in the secretion profile of a canonical Wnt activator (WNT3a) and inhibitor (WNT4) from insulin-resistant tissues during the development of T2D are responsible for triggering progression from a pre-diabetic to a diabetic state. We also show here that WNT3a and WNT4 are potent myokines, and their expression and secretion are regulated in response to nutritional and metabolic changes. PMID:27527335

  18. Natural killer T cells in adipose tissue are activated in lean mice.

    PubMed

    Kondo, Taisuke; Toyoshima, Yujiro; Ishii, Yoshiyuki; Kyuwa, Shigeru

    2013-01-01

    Adipose tissues are closely connected with the immune system. It has been suggested that metabolic syndromes such as type 2 diabetes, arteriosclerosis and liver steatosis can be attributed to adipose tissue inflammation characterized by macrophage infiltration. To understand a physiological and pathological role of natural killer T (NKT) cells on inflammation in adipose tissue, we characterized a subset of NKT cells in abdominal and subcutaneous adipose tissues in C57BL/6J mice fed normal or high-fat diets. NKT cells comprised a larger portion of lymphocytes in adipose tissues compared with the spleen and peripheral blood, with epididymal adipose tissue having the highest number of NKT cells. Furthermore, some NKT cells in adipose tissues expressed higher levels of CD69 and intracellular interferon-γ, whereas the Vβ repertoires of NKT cells in adipose tissues were similar to other cells. In obese mice fed a high-fat diet, adipose tissue inflammation had little effect on the Vβ repertoire of NKT cells in epididymal adipose tissues. We speculate that the NKT cells in adipose tissues may form an equivalent subset in other tissues and that these subsets are likely to participate in adipose tissue inflammation. Additionally, the high expression level of CD69 and intracellular IFN-γ raises the possibility that NKT cells in adipose tissue may be stimulated by some physiological mechanism.

  19. The browning of white adipose tissue: some burning issues.

    PubMed

    Nedergaard, Jan; Cannon, Barbara

    2014-09-01

    Igniting thermogenesis within white adipose tissue (i.e., promoting expression and activity of the uncoupling protein UCP1) has attracted much interest. Numerous "browning agents" have now been described (gene ablations, transgenes, food components, drugs, environments, etc.). The implied action of browning agents is that they increase UCP1 through this heat production, leading to slimming. Here, we particularly point to the possibility that cause and effect may on occasion be the reverse: browning agents may disrupt, for example, the fur, leading to increased heat loss, increased thermogenic demand to counteract this heat loss, and thus, through sympathetic nervous system activation, to enhanced UCP1 expression in white (and brown) adipose tissues.

  20. Transplantation of human adipose tissue to nude mice.

    PubMed

    Bach-Mortensen, N; Romert, P; Ballegaard, S

    1976-08-01

    Human adipose tissue was transplanted to the mouse mutant nude (nu/nu). All the grafts were accepted and contained fat cells easily distinguishable from those of the mouse. No detectable relation between the histological pictures before and after grafting was found. In some transplants nerve tissue, and in others macrophages containing fat droplets, were found. The fat tissue graft might be useful for investigation of the influence of various hormones on human fat cells.

  1. [Transplantation of adipose tissue multipotent stromal cells in the treatment of chronic ischemia of the lower extremities].

    PubMed

    Saliutin, R V; Palianytsia, S S; Sirman, V M; Panchenko, L A; Komarova, L S

    2014-07-01

    The expediency of the stromal cells application, obtained from adipose tissue, was determined in a frame of preclinical investigations conduction, concerning experimental works on laboratory rats, in whom the extremity ischemia was simulated. Histologic and immunohistochemical changes were studied in muscular tissue after transplantation of multipotent stromal cells of own adipose tissue in patients, suffering ischemia of the lower extremity. Reduction of severity of the myofibrills ischemic damage, rapid activation of the muscles regenerative power, accurate stimulation of the angiogenesis processes in 3 mo after transplantation of the cells were demonstrated. PMID:25252413

  2. Vitamin D and adipose tissue-more than storage.

    PubMed

    Mutt, Shivaprakash J; Hyppönen, Elina; Saarnio, Juha; Järvelin, Marjo-Riitta; Herzig, Karl-Heinz

    2014-01-01

    The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OH)D), no evidence was obtained for a BMI lowering effect by higher 25(OH)D. Some of the physiological functions of 1,25(OH)2D3 (1,25-dihydroxycholecalciferol or calcitriol) via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine, and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g., in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH)2D3, vitamin D binding proteins (VDBPs) and nuclear vitamin D receptor (VDR) after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH)2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH)2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR(-/-)) and CYP27B1 knock out (CYP27B1 (-/-)) mouse models: Both VDR(-/-) and CYP27B1(-/-) models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH)2D3. Experimental studies demonstrate that 1,25(OH)2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases. PMID:25009502

  3. Impact of holmium fibre laser radiation (λ = 2.1 μm) on the spinal cord dura mater and adipose tissue

    NASA Astrophysics Data System (ADS)

    Filatova, S. A.; Kamynin, V. A.; Ryabova, A. V.; Loshchenov, V. B.; Zelenkov, P. V.; Zolotovskii, I. O.; Tsvetkov, V. B.; Kurkov, A. S.

    2015-08-01

    The impact of holmium fibre laser radiation on the samples of biologic tissues (dura mater of spinal cord and adipose tissue with interlayers of muscle) is studied. The experimental results are evaluated by the size of carbonisation and coagulation necrosis zones. The experiment shows that in the case of irradiation of the spinal cord dura mater samples the size of carbonisation and coagulation necrosis zones is insignificant. In the adipose tissue the carbonisation zone is also insignificant, but the region of cellular structure disturbance is large. In the muscle tissue the situation is opposite. The cw laser operation provides clinically acceptable degree of destruction in tissue samples with a minimal carbonisation zone.

  4. 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

  5. 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

  6. Browning of white adipose tissue: role of hypothalamic signaling.

    PubMed

    Bi, Sheng; Li, Lin

    2013-10-01

    Two types of fat, white adipose tissue (WAT) and brown adipose tissue (BAT), exist in mammals including adult humans. While WAT stores excess calories and an excessive accumulation of fat causes obesity, BAT dissipates energy to produce heat through nonshivering thermogenesis for protection against cold environments and provides the potential for the development of novel anti-obesity treatments. The hypothalamus plays a central role in the control of energy balance. Specifically, recent observations indicate the importance of the dorsomedial hypothalamus (DMH) in thermoregulation. We have found that the orexigenic neuropeptide Y (NPY) in the DMH has distinct actions in modulating adiposity and BAT thermogenesis. Knockdown of NPY in the DMH elevates the thermogenic activity of classic BAT and promotes the development of brown adipocytes in WAT, leading to increased thermogenesis. These findings identify a novel potential target for combating obesity.

  7. 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.

  8. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    PubMed

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  9. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders

    PubMed Central

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  10. [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.

  11. Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue.

    PubMed

    Fu, Jianfei; Li, Zhen; Zhang, Huiqin; Mao, Yushan; Wang, Anshi; Wang, Xin; Zou, Zuquan; Zhang, Xiaohong

    2015-07-01

    Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue.

  12. Deficiency of Interleukin-15 Confers Resistance to Obesity by Diminishing Inflammation and Enhancing the Thermogenic Function of Adipose Tissues

    PubMed Central

    Lacraz, Gregory; Rakotoarivelo, Volatiana; Labbé, Sebastien M.; Vernier, Mathieu; Noll, Christophe; Mayhue, Marian; Stankova, Jana; Schwertani, Adel; Grenier, Guillaume; Carpentier, André; Richard, Denis; Ferbeyre, Gerardo; Fradette, Julie; Rola-Pleszczynski, Marek; Menendez, Alfredo; Langlois, Marie-France; Ilangumaran, Subburaj; Ramanathan, Sheela

    2016-01-01

    Objective IL-15 is an inflammatory cytokine secreted by many cell types. IL-15 is also produced during physical exercise by skeletal muscle and has been reported to reduce weight gain in mice. Contrarily, our findings on IL-15 knockout (KO) mice indicate that IL-15 promotes obesity. The aim of this study is to investigate the mechanisms underlying the pro-obesity role of IL-15 in adipose tissues. Methods Control and IL-15 KO mice were maintained on high fat diet (HFD) or normal control diet. After 16 weeks, body weight, adipose tissue and skeletal mass, serum lipid levels and gene/protein expression in the adipose tissues were evaluated. The effect of IL-15 on thermogenesis and oxygen consumption was also studied in primary cultures of adipocytes differentiated from mouse preadipocyte and human stem cells. Results Our results show that IL-15 deficiency prevents diet-induced weight gain and accumulation of lipids in visceral and subcutaneous white and brown adipose tissues. Gene expression analysis also revealed elevated expression of genes associated with adaptive thermogenesis in the brown and subcutaneous adipose tissues of IL-15 KO mice. Accordingly, oxygen consumption was increased in the brown adipocytes from IL-15 KO mice. In addition, IL-15 KO mice showed decreased expression of pro-inflammatory mediators in their adipose tissues. Conclusions Absence of IL-15 results in decreased accumulation of fat in the white adipose tissues and increased lipid utilization via adaptive thermogenesis. IL-15 also promotes inflammation in adipose tissues that could sustain chronic inflammation leading to obesity-associated metabolic syndrome. PMID:27684068

  13. Colonic Macrophages "Remote Control" Adipose Tissue Inflammation and Insulin Resistance.

    PubMed

    Biswas, Subhra K; Bonecchi, Raffaella

    2016-08-01

    The early events linking diet-induced adipose tissue inflammation and insulin resistance remain poorly understood. In this issue of Cell Metabolism, Kawano et al. (2016) show that infiltration of colonic pro-inflammatory macrophages orchestrated by the intestinal CCL2/CCR2 axis kick-starts this process during high-fat-diet feeding. PMID:27508866

  14. Browning attenuates murine white adipose tissue expansion during postnatal development.

    PubMed

    Lasar, D; Julius, A; Fromme, T; Klingenspor, M

    2013-05-01

    During postnatal development of mice distinct white adipose tissue depots display a transient appearance of brown-like adipocytes. These brite (brown in white) adipocytes share characteristics with classical brown adipocytes including a multilocular appearance and the expression of the thermogenic protein uncoupling protein 1. In this study, we compared two inbred mouse strains 129S6sv/ev and C57BL6/N known for their different propensity to diet-induced obesity. We observed transient browning in retroperitoneal and inguinal adipose tissue depots of these two strains. From postnatal day 10 to 20 the increase in the abundance of multilocular adipocytes and uncoupling protein 1 expression was higher in 129S6sv/ev than in C57BL6/N pups. The parallel increase in the mass of the two fat depots was attenuated during this browning period. Conversely, epididymal white and interscapular brown adipose tissue displayed a steady increase in mass during the first 30 days of life. In this period, 129S6sv/ev mice developed a significantly higher total body fat mass than C57BL6/N. Thus, while on a local depot level a high number of brite cells is associated with the attenuation of adipose tissue expansion the strain comparison reveals no support for a systemic impact on energy balance. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  15. Endocrine modulators of mouse subcutaneous adipose tissue beige adipocyte markers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The stromal vascular fraction (SVF) of subcutaneous adipose tissue contains precursors that can give rise to beige adipocytes. Beige adipocytes are characterized by the expression of specific markers, but it is not clear which markers best evaluate beige adipocyte differentiation. Both regulators of...

  16. Human omental and subcutaneous adipose tissue exhibit specific lipidomic signatures.

    PubMed

    Jové, Mariona; Moreno-Navarrete, José María; Pamplona, Reinald; Ricart, Wifredo; Portero-Otín, Manuel; Fernández-Real, José Manuel

    2014-03-01

    Despite their differential effects on human metabolic pathophysiology, the differences in omental and subcutaneous lipidomes are largely unknown. To explore this field, liquid chromatography coupled with mass spectrometry was used for lipidome analyses of adipose tissue samples (visceral and subcutaneous) selected from a group of obese subjects (n=38). Transcriptomics and in vitro studies in adipocytes were used to confirm the pathways affected by location. The analyses revealed the existence of obesity-related specific lipidome signatures in each of these locations, attributed to selective enrichment of specific triglycerides, glycerophospholipids, and sphingolipids, because these were not observed in adipose tissues from nonobese individuals. The changes were compatible with subcutaneous enrichment in pathways involved in adipogenesis, triacylglyceride synthesis, and lipid droplet formation, as well as increased α-oxidation. Marked differences between omental and subcutaneous depots in obese individuals were seen in the association of lipid species with metabolic traits (body mass index and insulin sensitivity). Targeted studies also revealed increased cholesterol (Δ56%) and cholesterol epoxide (Δ34%) concentrations in omental adipose tissue. In view of the effects of cholesterol epoxide, which induced enhanced expression of adipocyte differentiation and α-oxidation genes in human omental adipocytes, a novel role for cholesterol epoxide as a signaling molecule for differentiation is proposed. In summary, in obesity, adipose tissue exhibits a location-specific differential lipid profile that may contribute to explaining part of its distinct pathogenic role.

  17. Spice Up Your Life: Adipose Tissue and Inflammation

    PubMed Central

    Agarwal, Anil K.

    2014-01-01

    Cells of the immune system are now recognized in the adipose tissue which, in obesity, produces proinflammatory chemokines and cytokines. Several herbs and spices have been in use since ancient times which possess anti-inflammatory properties. In this perspective, I discuss and propose the usage of these culinary delights for the benefit of human health. PMID:24701352

  18. 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.

  19. 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

  20. 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

  1. The influence of thiazolidinediones on adipogenesis in vitro and in vivo: potential modifiers of intramuscular adipose tissue deposition in meat animals.

    PubMed

    Hausman, G J; Poulos, S P; Pringle, T D; Azain, M J

    2008-04-01

    Thiazolidinediones (TZD) are insulin sensitizing agents currently used for the treatment of type 2 diabetes and are widely used as adipogenic agents because they are ligands of peroxisome proliferator-activated receptor gamma (PPARgamma), a key adipogenic transcription factor. In vivo and in vitro studies of TZD as potential modifiers of intramuscular or marbling adipogenesis are reviewed. Thiazolidinedione-induced adipogenesis has been reported in numerous cell culture systems, including rodent, human, bovine, and porcine adipose tissue stromal-vascular (S-V) cell cultures. Studies of porcine S-V cell cultures derived from semitendinosus muscle show that TZD can potentially modify intramuscular or marbling adipogenesis. Preadipocyte recruitment was TZD-dependent in muscle S-V cultures but TZD-independent in adipose S-V cultures. There appear to be differences between adipocytes in muscle and subcutaneous adipose tissue, reminiscent of differences observed in adipocytes from different adipose tissue depots. Troglitazone, a TZD, induces marbling adipogenesis without inhibiting myogenesis when cells are grown on laminin precoated culture dishes. Additionally, troglitazone treatment does not increase lipid content in porcine adipose tissue or muscle S-V cell cultures. Thiazolidinedione treatment increases lipid content of muscle in rodents and humans; however, rosiglitazone treatment for 49 d in pigs did not influence muscle lipid content and meat quality, but several significant changes in muscle fatty acid composition were observed. Although timing of treatment with TZD needs to be optimized, evidence suggests these compounds may enhance marbling deposition in swine.

  2. 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

  3. Pharmacological and nutritional agents promoting browning of white adipose tissue.

    PubMed

    Bonet, M Luisa; Oliver, Paula; Palou, Andreu

    2013-05-01

    The role of brown adipose tissue in the regulation of energy balance and maintenance of body weight is well known in rodents. Recently, interest in this tissue has re-emerged due to the realization of active brown-like adipose tissue in adult humans and inducible brown-like adipocytes in white adipose tissue depots in response to appropriate stimuli ("browning process"). Brown-like adipocytes that appear in white fat depots have been called "brite" (from brown-in-white) or "beige" adipocytes and have characteristics similar to brown adipocytes, in particular the capacity for uncoupled respiration. There is controversy as to the origin of these brite/beige adipocytes, but regardless of this, induction of the browning of white fat represents an attractive potential strategy for the management and treatment of obesity and related complications. Here, the different physiological, pharmacological and dietary determinants that have been linked to white-to-brown fat remodeling and the molecular mechanisms involved are reviewed in detail. In the light of available data, interesting therapeutic perspectives can be expected from the use of specific drugs or food compounds able to induce a program of brown fat differentiation including uncoupling protein 1 expression and enhancing oxidative metabolism in white adipose cells. However, additional research is needed, mainly focused on the physiological relevance of browning and its dietary control, where the use of ferrets and other non-rodent animal models with a more similar adipose tissue organization and metabolism to humans could be of much help. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  4. Caspase Induction and BCL2 Inhibition in Human Adipose Tissue

    PubMed Central

    Tinahones, Francisco José; Coín Aragüez, Leticia; Murri, Mora; Oliva Olivera, Wilfredo; Mayas Torres, María Dolores; Barbarroja, Nuria; Gomez Huelgas, Ricardo; Malagón, Maria M.; El Bekay, Rajaa

    2013-01-01

    OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance. PMID:23193206

  5. Flow cytometry on the stromal-vascular fraction of white adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adipose tissue contains cell types other than adipocytes that may contribute to complications linked to obesity. For example, macrophages have been shown to infiltrate adipose tissue in response to a high-fat diet. Isolation of the stromal-vascular fraction of adipose tissue allows one to use flow c...

  6. Association between subcutaneous white adipose tissue and serum 25-hydroxyvitamin D in overweight and obese adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Cholecalciferol is known to be deposited in human adipose tissue, but the distribution of 25-hydroxyvitamin D (25(OH)D) in adipose tissue is not known. Objectives: To determine whether 25(OH)D is detectable in subcutaneous white adipose tissue (SWAT) in overweight and obese persons an...

  7. 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...

  8. The effect of insulin on porcine adipose tissue lipogenesis.

    PubMed

    Mersmann, H J

    1989-01-01

    1. This laboratory and others have not been able to demonstrate consistent insulin stimulation of glucose incorporation into lipid by porcine adipose tissue in vitro. 2. A multiplicity of tissue handling procedures, additions to the incubation medium, and pig size (age) did not allow the expression of a consistent and substantial insulin stimulation. 3. It is suggested that the twofold or greater stimulation of glucose metabolism observed occasionally in this laboratory results from pig genetics, husbandry, or seasonal effects. PMID:2514071

  9. The effect of insulin on porcine adipose tissue lipogenesis.

    PubMed

    Mersmann, H J

    1989-01-01

    1. This laboratory and others have not been able to demonstrate consistent insulin stimulation of glucose incorporation into lipid by porcine adipose tissue in vitro. 2. A multiplicity of tissue handling procedures, additions to the incubation medium, and pig size (age) did not allow the expression of a consistent and substantial insulin stimulation. 3. It is suggested that the twofold or greater stimulation of glucose metabolism observed occasionally in this laboratory results from pig genetics, husbandry, or seasonal effects.

  10. 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...

  11. Circadian Regulation of Lipid Mobilization in White Adipose Tissues

    PubMed Central

    Shostak, Anton; Meyer-Kovac, Judit; Oster, Henrik

    2013-01-01

    In mammals, a network of circadian clocks regulates 24-h rhythms of behavior and physiology. Circadian disruption promotes obesity and the development of obesity-associated disorders, but it remains unclear to which extent peripheral tissue clocks contribute to this effect. To reveal the impact of the circadian timing system on lipid metabolism, blood and adipose tissue samples from wild-type, ClockΔ19, and Bmal1−/− circadian mutant mice were subjected to biochemical assays and gene expression profiling. We show diurnal variations in lipolysis rates and release of free fatty acids (FFAs) and glycerol into the blood correlating with rhythmic regulation of two genes encoding the lipolysis pacemaker enzymes, adipose triglyceride (TG) lipase and hormone-sensitive lipase, by self-sustained adipocyte clocks. Circadian clock mutant mice show low and nonrhythmic FFA and glycerol blood content together with decreased lipolysis rates and increased sensitivity to fasting. Instead circadian clock disruption promotes the accumulation of TGs in white adipose tissue (WAT), leading to increased adiposity and adipocyte hypertrophy. In summary, circadian modulation of lipolysis rates regulates the availability of lipid-derived energy during the day, suggesting a role for WAT clocks in the regulation of energy homeostasis. PMID:23434933

  12. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes

    PubMed Central

    Kovacova, Zuzana; Tharp, William G.; Liu, Dianxin; Wei, Wan; Xie, Hui

    2016-01-01

    Objective Cardiac natriuretic peptides (NPs) bind to two receptors (NPRA‐mediator of signaling; NPRC‐clearance receptor) whose ratio, NPRR (NPRA/NPRC), determines the NP bioactivity. This study investigated the relationship of NP receptor gene expression in adipose tissue and muscle with obesity and glucose intolerance. Prospectively, the study also assessed whether changes in NP receptor expression and thermogenic gene markers accompanied improvements of insulin sensitivity. Methods A cross‐sectional study of subjects with a wide range of BMI and glucose tolerance (n = 50) was conducted, as well as a randomized 12‐week trial of subjects with type 2 diabetes mellitus (T2DM) treated with pioglitazone (n = 9) or placebo (n = 10). Results NPRR mRNA was significantly lower in adipose tissue of subjects with obesity when compared with lean subjects (P ≤ 0.001). NPRR decreased with progression from normal glucose tolerance to T2DM (P < 0.01) independently of obesity. Treatment of subjects with T2DM with pioglitazone increased NPRR in adipose tissue (P ≤ 0.01) in conjunction with improvements in insulin sensitivity and increases of the thermogenic markers PPARγ coactivator‐1α and uncoupling protein 1 (P ≤ 0.01). Conclusions Decreased adipose tissue NPRR was associated with obesity, glucose intolerance, and insulin resistance. This relationship was not observed for skeletal muscle NPRR. Pharmacological improvement of insulin sensitivity in subjects with T2DM was tied to improvement in NPRR and increased expression of genes involved in thermogenic processes. PMID:26887289

  13. Influence of hatch time and access to feed on intramuscular adipose tissue deposition in broilers.

    PubMed

    Powell, D J; Velleman, S G; Cowieson, A J; Singh, M; Muir, W I

    2016-06-01

    The effect of hatch time and subsequent access to feed on intramuscular adipose tissue deposition was studied in the pectoralis major muscle of male Ross 308 broiler chickens. Based on their hatch time chicks were classified as early (EH), midterm (MH), or late (LH) hatchers, with an average incubation duration of 497.7 h for EH, 508.8 h for MH, and 514.5 h for LH birds. Chicks were provided access to feed either immediately at hatch, or 24 h after the conclusion of the hatch window. Expression of the adipogenic regulatory genes peroxisome proliferator-activated receptor gamma (PPARγ), and stearoyl-CoA desaturase (SCD), were measured at the time of hatch, and zero, one, 4, 7, 28, and 40 d. Intramuscular adipocyte cell width and visualization of adipose tissue deposition was observed at 28 and 40 d. Expression of PPARγ was increased in the pectoralis major of LH birds at the time of hatch, zero, and one d. The expression of PPARγ at one and 7 d, and SCD at 7 d were increased in all birds that received delayed access to feed. At 28 d, adipocyte cell width was increased in LH birds with delayed access to feed, compared to EH and MH birds with delayed access to feed and LH birds with immediate access to feed. At 40 d, adipocyte cell width was increased in all birds that received delayed access to feed. Also at 40 d, there was a trend (P = 0.078) for more extensive intramuscular adipose tissue deposition in LH than EH birds, and in birds with delayed access to feed (P = 0.075). These data indicate delayed access to feed increases intramuscular adipose tissue deposition in the pectoralis major muscle, and suggest that hatch time influences this regulation. PMID:26976909

  14. 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

  15. Effect of sex and age on bovine muscle and adipose fatty acid composition and stearoyl-CoA desaturase mRNA expression.

    PubMed

    Bartoň, L; Bureš, D; Kott, T; Rehák, D

    2011-12-01

    The objective of the study was to investigate the effects of sex and slaughter age on the fatty acid (FA) composition and stearoyl-CoA desaturase gene expression in muscle and adipose tissue. Twenty-four Charolais × Simmental crossbred bulls and heifers were raised under similar conditions and slaughtered at 14 or 18 months of age. The total amount of FA in muscle increased markedly in older animals with higher contents of monounsaturated FA (MUFA) in heifers than bulls. The proportions of MUFA and desaturation indices were higher in heifers, whereas polyunsaturated FA were higher in bulls in both muscle and subcutaneous adipose tissue. The results of this study demonstrated sex-dependent differences in the FA composition of muscle and subcutaneous adipose tissue from cattle slaughtered at different ages. The expression of the stearoyl-CoA desaturase gene was higher in the adipose tissue of heifers compared to bulls, and its variation partly contributed to sex- and age-differences in the FA composition of bovine adipose tissue.

  16. Metabolic remodeling of white adipose tissue in obesity

    PubMed Central

    Cummins, Timothy D.; Holden, Candice R.; Sansbury, Brian E.; Gibb, Andrew A.; Shah, Jasmit; Zafar, Nagma; Tang, Yunan; Hellmann, Jason; Rai, Shesh N.; Spite, Matthew; Bhatnagar, Aruni

    2014-01-01

    Adipose tissue metabolism is a critical regulator of adiposity and whole body energy expenditure; however, metabolic changes that occur in white adipose tissue (WAT) with obesity remain unclear. The purpose of this study was to understand the metabolic and bioenergetic changes occurring in WAT with obesity. Wild-type (C57BL/6J) mice fed a high-fat diet (HFD) showed significant increases in whole body adiposity, had significantly lower V̇o2, V̇co2, and respiratory exchange ratios, and demonstrated worsened glucose and insulin tolerance compared with low-fat-fed mice. Metabolomic analysis of WAT showed marked changes in lipid, amino acid, carbohydrate, nucleotide, and energy metabolism. Tissue levels of succinate and malate were elevated, and metabolites that could enter the Krebs cycle via anaplerosis were mostly diminished in high-fat-fed mice, suggesting altered mitochondrial metabolism. Despite no change in basal oxygen consumption or mitochondrial DNA abundance, citrate synthase activity was decreased by more than 50%, and responses to FCCP were increased in WAT from mice fed a high-fat diet. Moreover, Pgc1a was downregulated and Cox7a1 upregulated after 6 wk of HFD. After 12 wk of high-fat diet, the abundance of several proteins in the mitochondrial respiratory chain or matrix was diminished. These changes were accompanied by increased Parkin and Pink1, decreased p62 and LC3-I, and ultrastructural changes suggestive of autophagy and mitochondrial remodeling. These studies demonstrate coordinated restructuring of metabolism and autophagy that could contribute to the hypertrophy and whitening of adipose tissue in obesity. PMID:24918202

  17. Mouse adipose tissue stromal cells give rise to skeletal and cardiomyogenic cell sub-populations.

    PubMed

    Dromard, Cécile; Barreau, Corinne; André, Mireille; Berger-Müller, Sandra; Casteilla, Louis; Planat-Benard, Valerie

    2014-01-01

    We previously reported that adipose tissue could generate cardiomyocyte-like cells from crude stromal vascular fraction (SVF) in vitro that improved cardiac function in a myocardial infarction context. However, it is not clear whether these adipose-derived cardiomyogenic cells (AD-CMG) constitute a homogenous population and if AD-CMG progenitors could be isolated as a pure population from the SVF of adipose tissue. This study aims to characterize the different cell types that constitute myogenic clusters and identify the earliest AD-CMG progenitors in vitro for establishing a complete phenotype and use it to sort AD-CMG progenitors from crude SVF. Here, we report cell heterogeneity among adipose-derived clusters during their course of maturation and highlighted sub-populations that exhibit original mixed cardiac/skeletal muscle phenotypes with a progressive loss of cardiac phenotype with time in liquid culture conditions. Moreover, we completed the phenotype of AD-CMG progenitors but we failed to sort them from the SVF. We demonstrated that micro-environment is required for the maturation of myogenic phenotype by co-culture experiments. These findings bring complementary data on AD-CMG and suggest that their emergence results from in vitro events.

  18. Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness

    PubMed Central

    Arpaci, Dilek; Gurkan Tocoglu, Aysel; Yilmaz, Sabiye; Korkmaz, Sumeyye; Ergenc, Hasan; Gunduz, Huseyin; Keser, Nurgul; Tamer, Ali

    2016-01-01

    Background Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. Methods Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. Results The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values < 0.01). However, both groups had similar EAT thickness (P = 0.532), which was positively correlated with BMI, fat mass, WC, HC, VAAT thickness, abdominal subcutaneous adipose tissue thickness, and serum triglyceride (TG) level (all P values < 0.01). We found no correlation between EAT thickness and thyroid-stimulating hormone (TSH) level, free thyroxine (FT4) level, or low-density lipoprotein-cholesterol (LDL-C) level, and anti-TPO level (all P values > 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). Conclusion Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to

  19. 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

  20. Foraging at wastewater treatment works affects brown adipose tissue fatty acid profiles in banana bats

    PubMed Central

    Hill, Kate; van Aswegen, Sunet; Schoeman, M. Corrie; Claassens, Sarina; Jansen van Rensburg, Peet; Naidoo, Samantha; Vosloo, Dalene

    2016-01-01

    ABSTRACT In this study we tested the hypothesis that the decrease in habitat quality at wastewater treatment works (WWTW), such as limited prey diversity and exposure to the toxic cocktail of pollutants, affect fatty acid profiles of interscapular brown adipose tissue (iBrAT) in bats. Further, the antioxidant capacity of oxidative tissues such as pectoral and cardiac muscle may not be adequate to protect those tissues against reactive molecules resulting from polyunsaturated fatty acid auto-oxidation in the WWTW bats. Bats were sampled at two urban WWTW, and two unpolluted reference sites in KwaZulu-Natal, South Africa. Brown adipose tissue (BrAT) mass was lower in WWTW bats than in reference site bats. We found lower levels of saturated phospholipid fatty acids and higher levels of mono- and polyunsaturated fatty acids in WWTW bats than in reference site bats, while C18 desaturation and n-6 to n-3 ratios were higher in the WWTW bats. This was not associated with high lipid peroxidation levels in pectoral and cardiac muscle. Combined, these results indicate that WWTW bats rely on iBrAT as an energy source, and opportunistic foraging on abundant, pollutant-tolerant prey may change fatty acid profiles in their tissue, with possible effects on mitochondrial functioning, torpor and energy usage. PMID:26740572

  1. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.

    PubMed

    Biondo, Luana Amorim; Lima Junior, Edson Alves; Souza, Camila Oliveira; Cruz, Maysa Mariana; Cunha, Roberta D C; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M Oller; Pimentel, Gustavo Duarte; Dos Santos, Ronaldo V T; Lira, Fabio Santos; Rosa Neto, José Cesar

    2016-01-01

    White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. PMID:27015538

  2. [Epicardial adipose tissue and its role in cardiac physiology and disease].

    PubMed

    Toczyłowski, Kacper; Gruca, Michał; Baranowski, Marcin

    2013-06-20

    Adipose tissue secretes a number of cytokines, referred to as adipokines. Intensive studies conducted over the last two decades showed that adipokines exert broad effects on cardiac metabolism and function. In addition, the available data strongly suggests that these cytokines play an important role in development of cardiovascular diseases. Epicardial adipose tissue (EAT) has special properties that distinguish it from other deposits of visceral fat. Overall, there appears to be a close functional and anatomic relationship between the EAT and the cardiac muscle. They share the same coronary blood supply, and there is no structure separating the adipose tissue from the myocardium or coronary arteries. The role of EAT in osierdziocardiac physiology remains unclear. Its putative functions include buffering coronary arteries against the torsion induced by the arterial pulse wave and cardiac contraction, regulating fatty acid homeostasis in the coronary microcirculation, thermogenesis, and neuroprotection of the cardiac autonomic ganglia and nerves. Obesity (particularly the abdominal phenotype) leads to elevated EAT content, and the available data suggests that high amount of this fat depot is associated with increased risk of ischemic heart disease, cardiac hypertrophy and diastolic dysfunction. The mass of EAT is small compared to other fat deposits in the body. Nevertheless, its close anatomic relationship to the heart suggests that this organ is highly exposed to EAT-derived adipokines which makes this tissue a very promising area of research. In this paper we review the current knowledge on the role of EAT in cardiac physiology and development of heart disease.

  3. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.

    PubMed

    Biondo, Luana Amorim; Lima Junior, Edson Alves; Souza, Camila Oliveira; Cruz, Maysa Mariana; Cunha, Roberta D C; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M Oller; Pimentel, Gustavo Duarte; Dos Santos, Ronaldo V T; Lira, Fabio Santos; Rosa Neto, José Cesar

    2016-01-01

    White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects.

  4. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue

    PubMed Central

    Cruz, Maysa Mariana; Cunha, Roberta D. C.; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M. Oller; Pimentel, Gustavo Duarte; dos Santos, Ronaldo V. T.; Lira, Fabio Santos

    2016-01-01

    White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. PMID:27015538

  5. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues.

    PubMed

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-12-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

  6. Brown adipose tissue development and metabolism in ruminants.

    PubMed

    Smith, S B; Carstens, G E; Randel, R D; Mersmann, H J; Lunt, D K

    2004-03-01

    We conducted several experiments to better understand the relationship between brown adipose tissue (BAT) metabolism and thermogenesis. In Exp. 1, we examined perirenal (brown) and sternum s.c. adipose tissue in 14 Wagyu x Angus neonates infused with norepinephrine (NE). Perirenal adipocytes contained numerous large mitochondria with well-differentiated cristae; sternum s.c. adipocytes contained a few, small mitochondria, with poorly developed cristae. Lipogenesis from acetate was high in BAT but barely detectable in sternum s.c. adipose tissue. In Exp. 2, we compared perirenal and tailhead adipose tissues between NE-infused Angus (n = 6) and Brahman (n = 7) newborn calves. Brahman BAT contained two-to-three times as many total beta-receptors as Angus BAT. The mitochondrial UCP1:28S rRNA ratio was greater in Brahman BAT than in BAT from Angus calves. Lipogenesis from acetate and glucose again was high, but lipogenesis from palmitate was barely detectable. Tail-head s.c. adipose tissue from both breed types contained adipocytes with distinct brown adipocyte morphology. In Exp. 3, three fetuses of each breed type were taken at 96, 48, 24, 14, and 6 d before expected parturition, and at parturition. Lipogenesis from acetate and glucose in vitro decreased 97% during the last 96 d of gestation in both breed types, whereas the UCP1 gene expression tripled during gestation in both breed types. At birth, palmitate esterification was twice as high in Angus than in Brahman BAT and was at least 100-fold higher than in BAT from NE-infused calves from Exp. 2. Uncoupling protein-1 mRNA was readily detectable in tailhead s.c. adipose tissue in all fetal samples. In Exp. 4, male Brahman and Angus calves (n = 5 to 7 per group) were assigned to 1) newborn treatment (15 h of age), 2) 48 h of warm exposure (22 degrees C) starting at 15 h of age, or 3) 48 h of cold exposure (4 degrees C) starting at 15 h of age. Brahman BAT adipocytes shrank with cold exposure, whereas Angus BAT

  7. Adiposity-Dependent Regulatory Effects on Multi-tissue Transcriptomes.

    PubMed

    Glastonbury, Craig A; Viñuela, Ana; Buil, Alfonso; Halldorsson, Gisli H; Thorleifsson, Gudmar; Helgason, Hannes; Thorsteinsdottir, Unnur; Stefansson, Kari; Dermitzakis, Emmanouil T; Spector, Tim D; Small, Kerrin S

    2016-09-01

    Obesity is a global epidemic that is causally associated with a range of diseases, including type 2 diabetes and cardiovascular disease, at the population-level. However, there is marked heterogeneity in obesity-related outcomes among individuals. This might reflect genotype-dependent responses to adiposity. Given that adiposity, measured by BMI, is associated with widespread changes in gene expression and regulatory variants mediate the majority of known complex trait loci, we sought to identify gene-by-BMI (G × BMI) interactions on the regulation of gene expression in a multi-tissue RNA-sequencing (RNA-seq) dataset from the TwinsUK cohort (n = 856). At a false discovery rate of 5%, we identified 16 cis G × BMI interactions (top cis interaction: CHURC1, rs7143432, p = 2.0 × 10(-12)) and one variant regulating 53 genes in trans (top trans interaction: ZNF423, rs3851570, p = 8.2 × 10(-13)), all in adipose tissue. The interactions were adipose-specific and enriched for variants overlapping adipocyte enhancers, and regulated genes were enriched for metabolic and inflammatory processes. We replicated a subset of the interactions in an independent adipose RNA-seq dataset (deCODE genetics, n = 754). We also confirmed the interactions with an alternate measure of obesity, dual-energy X-ray absorptiometry (DXA)-derived visceral-fat-volume measurements, in a subset of TwinsUK individuals (n = 682). The identified G × BMI regulatory effects demonstrate the dynamic nature of gene regulation and reveal a functional mechanism underlying the heterogeneous response to obesity. Additionally, we have provided a web browser allowing interactive exploration of the dataset, including of association between expression, BMI, and G × BMI regulatory effects in four tissues. PMID:27588447

  8. 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 ...

  9. Breast muscle tissue characteristics in growing broilers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Muscle cell development in broilers influences growth rate, breast meat yield, and meat quality. The objective of this study was to characterize muscle tissue changes in breast muscles from two commercial lines of broilers from 21 to 56 days of age. The experiment was designed as a 2×2×6 factorial...

  10. Ontogenetic development of adipose tissue in grass carp (Ctenopharyngodon idellus).

    PubMed

    Liu, Pin; Ji, Hong; Li, Chao; Tian, Jingjing; Wang, Yifei; Yu, Ping

    2015-08-01

    To investigate the adipose tissue development process during the early stages of grass carp (Ctenopharyngodon idellus) development, samples were collected from fertilized eggs to 30 days post-fertilization (dpf) of fish. Paraffin and frozen sections were taken to observe the characteristics of adipocytes in vivo by different staining methods, including hematoxylin and eosin (H&E), Oil red O, and BODIPY. The expression of lipogenesis-related genes of the samples at different time points was detected by real-time qPCR. In addition, protein expression level of peroxisome proliferator-activated receptors γ (PPAR γ) was detected by immunohistochemistry. The results showed that the neutral lipid droplets accumulated first in the hepatocytes of 14-dpf fish larvae, and visceral adipocytes appeared around the hepatopancreas on 16 dpf. As grass carp grew, the adipocytes increased in number and spread to other tissues. In 20-dpf fish larvae, the intestine was observed to be covered by adipose tissue. However, there was no significant change in the average size (30.40-40.01 μm) of adipocytes during this period. Accordingly, the gene expression level of PPAR γ and CCAAT/enhancer-binding proteins α (C/EBP α) was significantly elevated after fertilization for 12 days (p < 0.05), but C/EBP α declined at 20 dpf. Expression of lipoprotein lipase (LPL) increased from 2 to 16 dpf and then declined. In addition, immunoreaction of PPAR γ was positive on hepatocytes after fertilization for 15 days. These results implied that the early developmental stage of adipose tissue is caused by active recruitment of adipocytes as opposed to hypertrophy of the cell. In addition, our study indicated that lipogenesis-related genes might regulate the ongoing development of adipose tissue.

  11. [The adipose tissue as a regulatory center of the metabolism].

    PubMed

    Fonseca-Alaniz, Miriam H; Takada, Julie; Alonso-Vale, Maria Isabel C; Lima, Fabio Bessa

    2006-04-01

    The recent progress in the research about the metabolic properties of the adipose tissue and the discovery of its ability to produce hormones that are very active in pathophysiologic as well as physiologic processes is rebuilding the concepts about its biology. Its involvement in conditions like obesity, type 2 diabetes mellitus, arterial hypertension, arteriosclerosis, dislipidemias and chronic and acute inflammatory processes indicate that the understanding of its functional capacities may contribute to improve the prognosis of those diseases whose prevalence increased in a preoccupying manner. Here we review some functional aspects of adipocytes, such as the metabolism, its influence on energy homeostasis, its endocrine ability and the adipogenesis, i.e., the potential of pre-adipocytes present in adipose tissue stroma to differentiate into new adipocytes and regenerate the tissue. In addition, we are including some studies on the relationship between the adipose tissue and the pineal gland, a new and poorly known, although, as will be seen, very promising aspect of adipocyte physiology together with its possible favorable repercussions to the therapy of the obesity related diseases.

  12. 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

  13. The Expression of Adipogenic Genes in Adipose Tissues of Feedlot Steers Fed Supplementary Palm Oil or Soybean Oil

    PubMed Central

    Choi, Seong Ho; Park, Sung Kwon; Choi, Chang Weon; Li, Xiang Zi; Kim, Kyoung Hoon; Kim, Won Young; Jeong, Joon; Johnson, Bradley J.; Zan, Linsen; Smith, Stephen B.

    2016-01-01

    We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression and stearoyl-CoA desaturase (SCD) gene expression in subcutaneous (s.c.) and intramuscular (i.m.) adipose tissues of feedlot steers. Eighteen Angus and Angus crossbred steers were assigned to three groups of 6 steers and fed a basal diet (control), with 3% palm oil, or with 3% soybean oil, for 70 d, top-dressed daily. Tailhead s.c. adipose tissue was obtained by biopsy at 14 d before the initiation of dietary treatments and at 35 d of dietary treatments. At slaughter, after 70 d of dietary treatment, tailhead s.c. adipose tissue and i.m. adipose tissue were obtained from the longissimus thoracis muscle. Palm oil increased plasma palmitic acid and soybean oil increased plasma linoleic acid and α-linolenic acid relative to the initial sampling time. Expression of AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor gamma (PPARγ) increased between the initial and intermediate biopsies and declined thereafter (p<0.03). SCD gene expression did not change between the initial and intermediate biopsies but declined by over 75% by the final period (p = 0.04), and G-coupled protein receptor 43 (GPR43) gene expression was unaffected by diet or time on trial. Soybean oil decreased (p = 0.01) PPARγ gene expression at the intermediate sample time. At the terminal sample time, PPARγ and SCD gene expression was less in i.m. adipose tissue than in s.c. adipose tissue (p<0.05). AMPKα gene expression was less in s.c. adipose tissue of palm oil-fed steers than in control steers (p = 0.04) and CCAAT enhancer binding protein-beta (CEBPβ) gene expression was less in s.c. and i.m. adipose tissues of palm oil-fed steers than in soybean oil-fed steers (p<0.03). Soybean oil decreased SCD gene expression in s.c. adipose tissue (p = 0.05); SCD gene expression in palm oil-fed steers was intermediate between control and soybean oil-fed steers

  14. The Expression of Adipogenic Genes in Adipose Tissues of Feedlot Steers Fed Supplementary Palm Oil or Soybean Oil.

    PubMed

    Choi, Seong Ho; Park, Sung Kwon; Choi, Chang Weon; Li, Xiang Zi; Kim, Kyoung Hoon; Kim, Won Young; Jeong, Joon; Johnson, Bradley J; Zan, Linsen; Smith, Stephen B

    2016-03-01

    We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression and stearoyl-CoA desaturase (SCD) gene expression in subcutaneous (s.c.) and intramuscular (i.m.) adipose tissues of feedlot steers. Eighteen Angus and Angus crossbred steers were assigned to three groups of 6 steers and fed a basal diet (control), with 3% palm oil, or with 3% soybean oil, for 70 d, top-dressed daily. Tailhead s.c. adipose tissue was obtained by biopsy at 14 d before the initiation of dietary treatments and at 35 d of dietary treatments. At slaughter, after 70 d of dietary treatment, tailhead s.c. adipose tissue and i.m. adipose tissue were obtained from the longissimus thoracis muscle. Palm oil increased plasma palmitic acid and soybean oil increased plasma linoleic acid and α-linolenic acid relative to the initial sampling time. Expression of AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor gamma (PPARγ) increased between the initial and intermediate biopsies and declined thereafter (p<0.03). SCD gene expression did not change between the initial and intermediate biopsies but declined by over 75% by the final period (p = 0.04), and G-coupled protein receptor 43 (GPR43) gene expression was unaffected by diet or time on trial. Soybean oil decreased (p = 0.01) PPARγ gene expression at the intermediate sample time. At the terminal sample time, PPARγ and SCD gene expression was less in i.m. adipose tissue than in s.c. adipose tissue (p<0.05). AMPKα gene expression was less in s.c. adipose tissue of palm oil-fed steers than in control steers (p = 0.04) and CCAAT enhancer binding protein-beta (CEBPβ) gene expression was less in s.c. and i.m. adipose tissues of palm oil-fed steers than in soybean oil-fed steers (p<0.03). Soybean oil decreased SCD gene expression in s.c. adipose tissue (p = 0.05); SCD gene expression in palm oil-fed steers was intermediate between control and soybean oil-fed steers

  15. The Expression of Adipogenic Genes in Adipose Tissues of Feedlot Steers Fed Supplementary Palm Oil or Soybean Oil.

    PubMed

    Choi, Seong Ho; Park, Sung Kwon; Choi, Chang Weon; Li, Xiang Zi; Kim, Kyoung Hoon; Kim, Won Young; Jeong, Joon; Johnson, Bradley J; Zan, Linsen; Smith, Stephen B

    2016-03-01

    We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression and stearoyl-CoA desaturase (SCD) gene expression in subcutaneous (s.c.) and intramuscular (i.m.) adipose tissues of feedlot steers. Eighteen Angus and Angus crossbred steers were assigned to three groups of 6 steers and fed a basal diet (control), with 3% palm oil, or with 3% soybean oil, for 70 d, top-dressed daily. Tailhead s.c. adipose tissue was obtained by biopsy at 14 d before the initiation of dietary treatments and at 35 d of dietary treatments. At slaughter, after 70 d of dietary treatment, tailhead s.c. adipose tissue and i.m. adipose tissue were obtained from the longissimus thoracis muscle. Palm oil increased plasma palmitic acid and soybean oil increased plasma linoleic acid and α-linolenic acid relative to the initial sampling time. Expression of AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor gamma (PPARγ) increased between the initial and intermediate biopsies and declined thereafter (p<0.03). SCD gene expression did not change between the initial and intermediate biopsies but declined by over 75% by the final period (p = 0.04), and G-coupled protein receptor 43 (GPR43) gene expression was unaffected by diet or time on trial. Soybean oil decreased (p = 0.01) PPARγ gene expression at the intermediate sample time. At the terminal sample time, PPARγ and SCD gene expression was less in i.m. adipose tissue than in s.c. adipose tissue (p<0.05). AMPKα gene expression was less in s.c. adipose tissue of palm oil-fed steers than in control steers (p = 0.04) and CCAAT enhancer binding protein-beta (CEBPβ) gene expression was less in s.c. and i.m. adipose tissues of palm oil-fed steers than in soybean oil-fed steers (p<0.03). Soybean oil decreased SCD gene expression in s.c. adipose tissue (p = 0.05); SCD gene expression in palm oil-fed steers was intermediate between control and soybean oil-fed steers

  16. Adipose tissue development in extramuscular and intramuscular depots in meat animals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The cellular and metabolic aspects of developing intramuscular adipose tissue and other adipose tissue depots have been studied including examination of the expression of a number of genes. Depot dependent or depot “marker” genes such as stearoyl-CoA desaturase and leptin for subcutaneous adipose ti...

  17. 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

  18. Brown adipose tissue: physiological function and evolutionary significance.

    PubMed

    Oelkrug, R; Polymeropoulos, E T; Jastroch, M

    2015-08-01

    In modern eutherian (placental) mammals, brown adipose tissue (BAT) evolved as a specialized thermogenic organ that is responsible for adaptive non-shivering thermogenesis (NST). For NST, energy metabolism of BAT mitochondria is increased by activation of uncoupling protein 1 (UCP1), which dissipates the proton motive force as heat. Despite the presence of UCP1 orthologues prior to the divergence of teleost fish and mammalian lineages, UCP1's significance for thermogenic adipose tissue emerged at later evolutionary stages. Recent studies on the presence of BAT in metatherians (marsupials) and eutherians of the afrotherian clade provide novel insights into the evolution of adaptive NST in mammals. In particular studies on the 'protoendothermic' lesser hedgehog tenrec (Afrotheria) suggest an evolutionary scenario linking BAT to the onset of eutherian endothermy. Here, we review the physiological function and distribution of BAT in an evolutionary context by focusing on the latest research on phylogenetically distinct species.

  19. 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

  20. Levels of chlordane, oxychlordane, and nonachlor in human adipose tissues

    SciTech Connect

    Hirai, Yukio; Tomokuni, Katsumaro )

    1991-08-01

    Chlordane was used as a termiticide for more than twenty years in Japan. Chlordane is stable in the environment such as sediment and its bioaccumulation in some species of bacteria, freshwater invertebrates, and marine fish is large. Many researches were done to elucidate the levels of chlordane and/or its metabolite oxychlordane in human adipose tissues. A comprehensive review concerning chlordane was recently provided by USEPA. On the other hand, Japan authorities banned the use of chlordane in September 1986. In the last paper, the authors reported that both water and sediment of the rivers around Saga city were slightly contaminated with chlordane. In the present study, they investigated the levels of chlordane, oxychlordane and nonachlor in human adipose tissues.

  1. 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.

  2. 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.

  3. 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.

  4. Inhibition of Sam68 triggers adipose tissue browning

    PubMed Central

    Zhou, Junlan; Cheng, Min; Boriboun, Chan; Ardehali, Mariam Mina; Jiang, Changfei; Liu, Qinghua; Han, Shuling; Goukassian, David A.; Tang, Yao-Liang; Zhao, Ting C.; Zhao, Ming; Cai, Lu; Richard, Stéphane; Kishore, Raj; Qin, Gangjian

    2015-01-01

    Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms promoting energy expenditure may be utilized for effective therapy. Src-associated-in-mitosis-of-68kDa (Sam68) is potentially significant because knockout (KO) of Sam68 leads to markedly-reduced adiposity. Here we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We firstly found in Sam68-KO mice a significantly-reduced body weight with the difference explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake, but rather associated with enhanced physical activity. When fed high-fat diet, Sam68-KO mice gained much lesser body weight and fat mass as compared to wild-type (WT) littermates and displayed an improved glucose and insulin tolerance. The brown adipose tissue (BAT), inguinal and epididymal depots are smaller and their adipocytes less hypertrophy in Sam68-KO mice than in WT littermates. The BAT of Sam68-KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty-acid-oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68-KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16 and Ppargc1a genes was greater as compared to WT controls, suggesting that loss of Sam68 also promotes WAT browning. Furthermore, in all fat depots of Sam68-KO mice, the expression of M2 macrophage markers were upregulated and M1 markers downregulated. Thus Sam68 plays a crucial role in the control of thermogenesis and may be targeted to combat obesity and associated disorders. PMID:25934704

  5. Inhibition of Sam68 triggers adipose tissue browning.

    PubMed

    Zhou, Junlan; Cheng, Min; Boriboun, Chan; Ardehali, Mariam M; Jiang, Changfei; Liu, Qinghua; Han, Shuling; Goukassian, David A; Tang, Yao-Liang; Zhao, Ting C; Zhao, Ming; Cai, Lu; Richard, Stéphane; Kishore, Raj; Qin, Gangjian

    2015-06-01

    Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders.

  6. Association of Rev-erbα in adipose tissues with Type 2 diabetes mellitus amelioration after gastric bypass surgery in Goto-Kakizaki rats.

    PubMed

    Zhang, Rui; Yan, Caifeng; Zhou, Xinrong; Qian, Bangguo; Li, Fuqiang; Sun, Yidan; Shi, Chen; Li, Bing; Saito, Shigeru; Horimoto, Katsuhisa; Zhou, Huarong

    2013-07-15

    We estimated the key molecules related to Type 2 diabetes mellitus (T2DM) in adipose, liver, and muscle tissues, from nonobese diabetic Goto-Kakizaki (GK) rats and their Wistar controls, by computationally analyzing the expression profiles in open source data. With the aid of information from previous reports, Rev-erbα in adipose tissue emerged as one of the most plausible candidates. Here, in animal models, including GK rats surgically treated to ameliorate T2DM, we examined the association of Rev-erbα in adipose tissue with T2DM progression. After analyses of the Rev-erbα mRNA expression in the adipose tissue of our animal models, we compared the Rev-erbα protein expression levels in the adipose, liver, and muscle tissues of GK and Wistar controls at the ages of 1 mo (M), 3M, and 6M. The Rev-erbα protein levels in adipose tissue showed a distinctive pattern, with the negative correlation of an increasing trend in GK rats, and a decreasing trend in Wistar rats during aging, from those in liver and muscle tissues. Moreover, dysregulation of the circadian Rev-erbα expression in the adipose tissue of 6-mo-old GK rats was also observed. In particular, we ameliorated T2DM in GK rats by gastric bypass surgery, and revealed that T2DM amelioration in diabetic GK rats was associated with improved circadian Rev-erbα expression, in a comparison between the surgically treated and untreated GK rats. The roles of Rev-erbα in adipose tissue were further investigated by observations of Rev-erbα-related molecules, with reference to previous reports.

  7. NAMPT-Mediated NAD(+) Biosynthesis in Adipocytes Regulates Adipose Tissue Function and Multi-organ Insulin Sensitivity in Mice.

    PubMed

    Stromsdorfer, Kelly L; Yamaguchi, Shintaro; Yoon, Myeong Jin; Moseley, Anna C; Franczyk, Michael P; Kelly, Shannon C; Qi, Nathan; Imai, Shin-Ichiro; Yoshino, Jun

    2016-08-16

    Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD(+) biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people. We found that adipocyte-specific Nampt knockout mice had severe insulin resistance in adipose tissue, liver, and skeletal muscle and adipose tissue dysfunction, manifested by increased plasma free fatty acid concentrations and decreased plasma concentrations of a major insulin-sensitizing adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and PPARγ (serine-273) and decreased gene expression of obesity-linked phosphorylated PPARγ targets in adipose tissue. These deleterious alterations were normalized by administering rosiglitazone or a key NAD(+) intermediate, nicotinamide mononucleotide (NMN). Collectively, our results provide important mechanistic and therapeutic insights into obesity-associated systemic metabolic derangements, particularly multi-organ insulin resistance.

  8. NAMPT-mediated NAD+ biosynthesis in adipocytes regulates adipose tissue function and multi-organ insulin sensitivity in mice

    PubMed Central

    Stromsdorfer, Kelly L.; Yamaguchi, Shintaro; Yoon, Myeong Jin; Moseley, Anna C.; Franczyk, Michael P.; Kelly, Shannon C.; Qi, Nathan; Imai, Shin-ichiro; Yoshino, Jun

    2016-01-01

    SUMMARY Obesity is associated with adipose tissue dysfunction and multi-organ insulin resistance. However, the mechanisms of such obesity-associated systemic metabolic complications are not clear. Here, we characterized mice with adipocyte-specific deletion of nicotinamide phosphoribosyltransferase (NAMPT), a rate-limiting NAD+ biosynthetic enzyme known to decrease in adipose tissue of obese and aged rodents and people. We found that adipocyte-specific Nampt knockout mice had severe insulin resistance in adipose tissue, liver, and skeletal muscle, and adipose tissue dysfunction, manifested by increased plasma free fatty acids concentrations and decreased plasma concentrations of a major insulin-sensitizing adipokine, adiponectin. Loss of Nampt increased phosphorylation of CDK5 and PPARγ (serine-273) and decreased gene expression of obesity-linked phosphorylated PPARγ targets in adipose tissue. Remarkably, these deleterious alterations were normalized by administering rosiglitazone or a key NAD+ intermediate, nicotinamide mononucleotide (NMN). Collectively, our results provide important mechanistic and therapeutic insights into obesity-associated systemic metabolic derangements, particularly multi-organ insulin resistance. PMID:27498863

  9. Developmental androgen excess programs sympathetic tone and adipose tissue dysfunction and predisposes to a cardiometabolic syndrome in female mice.

    PubMed

    Nohara, Kazunari; Waraich, Rizwana S; Liu, Suhuan; Ferron, Mathieu; Waget, Aurélie; Meyers, Matthew S; Karsenty, Gérard; Burcelin, Rémy; Mauvais-Jarvis, Franck

    2013-06-15

    Among women, the polycystic ovarian syndrome (PCOS) is considered a form of metabolic syndrome with reproductive abnormalities. Women with PCOS show increased sympathetic tone, visceral adiposity with enlarged adipocytes, hypoadiponectinemia, insulin resistance, glucose intolerance, increased inactive osteocalcin, and hypertension. Excess fetal exposure to androgens has been hypothesized to play a role in the pathogenesis of PCOS. Previously, we showed that neonatal exposure to the androgen testosterone (NT) programs leptin resistance in adult female mice. Here, we studied the impact of NT on lean and adipose tissues, sympathetic tone in cardiometabolic tissues, and the development of metabolic dysfunction in mice. Neonatally androgenized adult female mice (NTF) displayed masculinization of lean tissues with increased cardiac and skeletal muscle as well as kidney masses. NTF mice showed increased and dysfunctional white adipose tissue with increased sympathetic tone in both visceral and subcutaneous fat as well as increased number of enlarged and insulin-resistant adipocytes that displayed altered expression of developmental genes and hypoadiponectinemia. NTF exhibited dysfunctional brown adipose tissue with increased mass and decreased energy expenditure. They also displayed decreased undercarboxylated and active osteocalcin and were predisposed to obesity during chronic androgen excess. NTF showed increased renal sympathetic tone associated with increased blood pressure, and they developed glucose intolerance and insulin resistance. Thus, developmental exposure to testosterone in female mice programs features of cardiometabolic dysfunction, as can be observed in women with PCOS, including increased sympathetic tone, visceral adiposity, insulin resistance, prediabetes, and hypertension.

  10. Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function.

    PubMed

    Boucher, Jeremie; Softic, Samir; El Ouaamari, Abdelfattah; Krumpoch, Megan T; Kleinridders, Andre; Kulkarni, Rohit N; O'Neill, Brian T; Kahn, C Ronald

    2016-08-01

    To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets. Both F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold and developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. Leptin treatment normalized blood glucose levels in both groups. Glucose levels also improved spontaneously by 1 year of age, despite sustained lipodystrophy and insulin resistance. Thus, loss of IR is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal BAT function and temperature homeostasis. IGF1R has only a modest contribution to both WAT and BAT formation and function.

  11. Differential Roles of Insulin and IGF-1 Receptors in Adipose Tissue Development and Function.

    PubMed

    Boucher, Jeremie; Softic, Samir; El Ouaamari, Abdelfattah; Krumpoch, Megan T; Kleinridders, Andre; Kulkarni, Rohit N; O'Neill, Brian T; Kahn, C Ronald

    2016-08-01

    To determine the roles of insulin and insulin-like growth factor 1 (IGF-1) action in adipose tissue, we created mice lacking the insulin receptor (IR), IGF-1 receptor (IGF1R), or both using Cre-recombinase driven by the adiponectin promoter. Mice lacking IGF1R only (F-IGFRKO) had a ∼25% reduction in white adipose tissue (WAT) and brown adipose tissue (BAT), whereas mice lacking both IR and IGF1R (F-IR/IGFRKO) showed an almost complete absence of WAT and BAT. Interestingly, mice lacking only the IR (F-IRKO) had a 95% reduction in WAT, but a paradoxical 50% increase in BAT with accumulation of large unilocular lipid droplets. Both F-IRKO and F-IR/IGFRKO mice were unable to maintain body temperature in the cold and developed severe diabetes, ectopic lipid accumulation in liver and muscle, and pancreatic islet hyperplasia. Leptin treatment normalized blood glucose levels in both groups. Glucose levels also improved spontaneously by 1 year of age, despite sustained lipodystrophy and insulin resistance. Thus, loss of IR is sufficient to disrupt white fat formation, but not brown fat formation and/or maintenance, although it is required for normal BAT function and temperature homeostasis. IGF1R has only a modest contribution to both WAT and BAT formation and function. PMID:27207537

  12. 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

  13. Positive Association Between Adipose Tissue and Bone Stiffness.

    PubMed

    Berg, R M; Wallaschofski, H; Nauck, M; Rettig, R; Markus, M R P; Laqua, R; Friedrich, N; Hannemann, A

    2015-07-01

    Obesity is often considered to have a protective effect against osteoporosis. On the other hand, several recent studies suggest that adipose tissue may have detrimental effects on bone quality. We therefore aimed to investigate the associations between body mass index (BMI), waist circumference (WC), visceral adipose tissue (VAT) or abdominal subcutaneous adipose tissue (SAT), and bone stiffness. The study involved 2685 German adults aged 20-79 years, who participated in either the second follow-up of the population-based Study of Health in Pomerania (SHIP-2) or the baseline examination of the SHIP-Trend cohort. VAT and abdominal SAT were quantified by magnetic resonance imaging. Bone stiffness was assessed by quantitative ultrasound (QUS) at the heel (Achilles InSight, GE Healthcare). The individual risk for osteoporotic fractures was determined based on the QUS-derived stiffness index and classified in low, medium, and high risk. Linear regression models, adjusted for sex, age, physical activity, smoking status, risky alcohol consumption, diabetes, and height (in models with VAT or abdominal SAT as exposure), revealed positive associations between BMI, WC, VAT or abdominal SAT, and the QUS variables broadband-ultrasound attenuation or stiffness index. Moreover, BMI was positively associated with speed of sound. Our study shows that all anthropometric measures including BMI and, WC as well as abdominal fat volume are positively associated with bone stiffness in the general population. As potential predictors of bone stiffness, VAT and abdominal SAT are not superior to easily available measures like BMI or WC.

  14. Deep sequencing of the transcriptome reveals inflammatory features of porcine visceral adipose tissue.

    PubMed

    Wang, Tao; Jiang, Anan; Guo, Yanqin; Tan, Ya; Tang, Guoqing; Mai, Miaomiao; Liu, Haifeng; Xiao, Jian; Li, Mingzhou; Li, Xuewei

    2013-01-01

    Functional differences in the different types of adipose tissue and the impact of their dysfunction on metabolism are associated with the regional distribution of adipose depots. Here we show a genome-wide comparison between the transcriptomes of one source of subcutaneous and two sources of visceral adipose tissue in the pig using an RNA-seq approach. We obtained ~32.3 million unique mapped reads which covered ~80.2% of the current annotated transcripts across these three sources of adipose tissue. We identified various genes differentially expressed between subcutaneous and visceral adipose tissue, which are potentially associated with the inflammatory features of visceral adipose tissue. These results are of benefit for understanding the phenotypic, metabolic and functional differences between different types of adipose tissue that are deposited in different body sites.

  15. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism.

    PubMed

    Zhang, Wei; Cline, Mark A; Gilbert, Elizabeth R

    2014-01-01

    Neuropeptide Y (NPY) is an orexigenic neuropeptide that plays a role in regulating adiposity by promoting energy storage in white adipose tissue and inhibiting brown adipose tissue activation in mammals. This review describes mechanisms underlying NPY's effects on adipose tissue energy metabolism, with an emphasis on cellular proliferation, adipogenesis, lipid deposition, and lipolysis in white adipose tissue, and brown fat activation and thermogenesis. In general, NPY promotes adipocyte differentiation and lipid accumulation, leading to energy storage in adipose tissue, with effects mediated mainly through NPY receptor sub-types 1 and 2. This review highlights hypothalamus-sympathetic nervous system-adipose tissue innervation and adipose tissue-hypothalamus feedback loops as pathways underlying these effects. Potential sources of NPY that mediate adipose effects include the bloodstream, sympathetic nerve terminals that innervate the adipose tissue, as well as adipose tissue-derived cells. Understanding the role of central vs. peripherally-derived NPY in whole-body energy balance could shed light on mechanisms underlying the pathogenesis of obesity. This information may provide some insight into searching for alternative therapeutic strategies for the treatment of obesity and associated diseases.

  16. Laser light propagation in adipose tissue and laser effects on adipose cell membranes

    NASA Astrophysics Data System (ADS)

    Solarte, Efraín; Rebolledo, Aldo; Gutierrez, Oscar; Criollo, William; Neira, Rodrigo; Arroyave, José; Ramírez, Hugo

    2006-01-01

    Recently Neira et al. have presented a new liposuction technique that demonstrated the movement of fat from inside to outside of the cell, using a low-level laser device during a liposuction procedure with Ultrawet solution. The clinical observations, allowed this new surgical development, started a set of physical, histological and pharmacological studies aimed to determine the mechanisms involved in the observed fat mobilization concomitant to external laser application in liposuction procedures. Scanning and Transmission Electron Microscopy, studies show that the cellular arrangement of normal adipose tissue changes when laser light from a diode laser: 10 mW, 635 nm is applied. Laser exposures longer than 6 minutes cause the total destruction of the adipocyte panicles. Detailed observation of the adipose cells show that by short irradiation times (less than four minutes) the cell membrane exhibits dark zones, that collapse by longer laser exposures. Optical measurements show that effective penetration length depends on the laser intensity. Moreover, the light scattering is enhanced by diffraction and subsequent interference effects, and the tumescent solution produces a clearing of the tissue optical medium. Finally, isolate adipose cell observation show that fat release from adipocytes is a concomitant effect between the tumescent solution (adrenaline) and laser light, revealing a synergism which conduces to the aperture, and maybe the disruption, of the cell membrane. All these studies were consistent with a laser induced cellular process, which causes fat release from inside the adipocytes into the intercellular space, besides a strong modification of the cellular membranes.

  17. Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds.

    PubMed

    Han, Tim Tian Y; Toutounji, Sandra; Amsden, Brian G; Flynn, Lauren E

    2015-12-01

    Decellularized adipose tissue (DAT) has shown promise as an adipogenic bioscaffold for soft tissue augmentation and reconstruction. The objective of the current study was to investigate the effects of allogeneic adipose-derived stem/stromal cells (ASCs) on in vivo fat regeneration in DAT bioscaffolds using an immunocompetent rat model. ASC seeding significantly enhanced angiogenesis and adipogenesis, with cell tracking studies indicating that the newly-forming tissues were host-derived. Incorporating ASCs also mediated the inflammatory response and promoted a more constructive macrophage phenotype. A fraction of the CD163(+) macrophages in the implants expressed adipogenic markers, with higher levels of this "adipocyte-like" phenotype in proximity to the developing adipose tissues. Our results indicate that the combination of ASCs and adipose extracellular matrix (ECM) provides an inductive microenvironment for adipose regeneration mediated by infiltrating host cell populations. The DAT scaffolds are a useful tissue-specific model system for investigating the mechanisms of in vivo adipogenesis that may help to develop a better understanding of this complex process in the context of both regeneration and disease. Overall, combining adipose-derived matrices with ASCs is a highly promising approach for the in situ regeneration of host-derived adipose tissue.

  18. Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds.

    PubMed

    Han, Tim Tian Y; Toutounji, Sandra; Amsden, Brian G; Flynn, Lauren E

    2015-12-01

    Decellularized adipose tissue (DAT) has shown promise as an adipogenic bioscaffold for soft tissue augmentation and reconstruction. The objective of the current study was to investigate the effects of allogeneic adipose-derived stem/stromal cells (ASCs) on in vivo fat regeneration in DAT bioscaffolds using an immunocompetent rat model. ASC seeding significantly enhanced angiogenesis and adipogenesis, with cell tracking studies indicating that the newly-forming tissues were host-derived. Incorporating ASCs also mediated the inflammatory response and promoted a more constructive macrophage phenotype. A fraction of the CD163(+) macrophages in the implants expressed adipogenic markers, with higher levels of this "adipocyte-like" phenotype in proximity to the developing adipose tissues. Our results indicate that the combination of ASCs and adipose extracellular matrix (ECM) provides an inductive microenvironment for adipose regeneration mediated by infiltrating host cell populations. The DAT scaffolds are a useful tissue-specific model system for investigating the mechanisms of in vivo adipogenesis that may help to develop a better understanding of this complex process in the context of both regeneration and disease. Overall, combining adipose-derived matrices with ASCs is a highly promising approach for the in situ regeneration of host-derived adipose tissue. PMID:26360790

  19. Increased peroxisome proliferator-activated receptor γ expression levels in visceral adipose tissue, and serum CCL2 and interleukin-6 levels during visceral adipose tissue accumulation.

    PubMed

    Yogarajah, Thaneswary; Bee, Yvonne-Tee Get; Noordin, Rahmah; Yin, Khoo Boon

    2015-01-01

    This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPARγ mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPARγ expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPARγ in accumulated visceral adipose tissues.

  20. Adipose tissue n-3 fatty acids and metabolic syndrome

    PubMed Central

    Cespedes, Elizabeth; Baylin, Ana; Campos, Hannia

    2014-01-01

    Background Evidence regarding the relationship of n-3 fatty acids (FA) to type 2 diabetes (T2D) and metabolic syndrome components (MetS) is inconsistent. Objective To examine associations of adipose tissue n-3 FA with MetS. Design We studied 1611 participants without prior history of diabetes or heart disease who were participants in a population-based case-control study of diet and heart disease (The Costa Rica Heart Study). We calculated prevalence ratios (PR) and 95% confidence intervals (CI) for MetS by quartile of n-3 FA in adipose tissue derived mainly from plants [α-Linolenic acid (ALA)], fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], or metabolism [docosapentaenoic acid (DPA), as well as the EPA:ALA ratio, a surrogate marker of delta-6 desaturase activity]. Results N-3 FA levels in adipose tissue were associated with MetS prevalence in opposite directions. The PR (95% CI) for the highest compared to the lowest quartile adjusted for age, sex, BMI, residence, lifestyle, diet and other fatty acids were 0.60 (0.44, 0.81) for ALA, 1.43 (1.12, 1.82) for EPA, 1.63 (1.22, 2.18) for DPA, and 1.47 (1.14, 1.88) for EPA:ALA, all p for trend <0.05. Although these associations were no longer significant (except DPA) after adjustment for BMI, ALA and DPA were associated with lower glucose and higher triglyceride levels, p<0.05 (respectively). Conclusions These results suggest that ALA could exert a modest protective benefit, while EPA and DHA are not implicated in MetS. The positive associations for DPA and MetS could reflect higher delta-6 desaturase activity caused by increased adiposity. PMID:25097001

  1. Regulation of glucose homoeostasis by brown adipose tissue.

    PubMed

    Peirce, Vivian; Vidal-Puig, Antonio

    2013-12-01

    Brown adipose tissue (BAT) has emerged as a therapeutic target for the treatment of obesity. Activation of BAT in human beings could also have beneficial metabolic effects that might resolve common complications of obesity, such as type 2 diabetes, by ameliorating the glucolipotoxic pathological changes that underlie the development of peripheral insulin resistance and impaired insulin secretion due to pancreatic β-cell failure. Evidence from rodent models suggests that BAT activation improves glucose homoeostasis through several mechanisms, which could point to new strategies to optimise stimulation of BAT in human beings and reverse insulin resistance in peripheral tissues.

  2. Chronic treatment with myo-inositol reduces white adipose tissue accretion and improves insulin sensitivity in female mice.

    PubMed

    Croze, Marine L; Vella, Roxane E; Pillon, Nicolas J; Soula, Hédi A; Hadji, Lilas; Guichardant, Michel; Soulage, Christophe O

    2013-02-01

    Type 2 diabetes is a complex disease characterized by a state of insulin resistance in peripheral tissues such as skeletal muscle, adipose tissue or liver. Some inositol isomers have been reported to possess insulin-mimetic activity and to be efficient in lowering blood glucose level. The aim of the present study was to assess in mice the metabolic effects of a chronic treatment with myo-inositol, the most common stereoisomer of inositol. Mice given myo-inositol treatment (0.9 or 1.2 mg g(-1) day(-1), 15 days, orally or intraperitoneally) exhibited an improved glucose tolerance due to a greater insulin sensitivity. Mice treated with myo-inositol exhibited a decreased white adipose tissue accretion (-33%, P<.005) compared with controls. The decrease in white adipose tissue deposition was due to a decrease in adipose cell volume (-33%, P<.05), while no change was noticed in total adipocyte number. In skeletal muscle, in vivo as well as ex vivo myo-inositol treatment increased protein kinase B/Akt phosphorylation under baseline and insulin-stimulated conditions, suggesting a synergistic action of myo-inositol treatment and insulin on proteins of the insulin signalling pathway. Myo-inositol could therefore constitute a viable nutritional strategy for the prevention and/or treatment of insulin resistance and type 2 diabetes.

  3. Adjustment of directly measured adipose tissue volume in infants

    PubMed Central

    Gale, C; Santhakumaran, S; Wells, J C K; Modi, N

    2014-01-01

    Background: Direct measurement of adipose tissue (AT) using magnetic resonance imaging is increasingly used to characterise infant body composition. Optimal techniques for adjusting direct measures of infant AT remain to be determined. Objectives: To explore the relationships between body size and direct measures of total and regional AT, the relationship between AT depots representing the metabolic load of adiposity and to determine optimal methods of adjusting adiposity in early life. Design: Analysis of regional AT volume (ATV) measured using magnetic resonance imaging in longitudinal and cross-sectional studies. Subjects: Healthy term infants; 244 in the first month (1–31 days), 72 in early infancy (42–91 days). Methods: The statistical validity of commonly used indices adjusting adiposity for body size was examined. Valid indices, defined as mathematical independence of the index from its denominator, to adjust ATV for body size and metabolic load of adiposity were determined using log-log regression analysis. Results: Indices commonly used to adjust ATV are significantly correlated with body size. Most regional AT depots are optimally adjusted using the index ATV/(height)3 in the first month and ATV/(height)2 in early infancy. Using these indices, height accounts for<2% of the variation in the index for almost all AT depots. Internal abdominal (IA) ATV was optimally adjusted for subcutaneous abdominal (SCA) ATV by calculating IA/SCA0.6. Conclusions: Statistically optimal indices for adjusting directly measured ATV for body size are ATV/height3 in the neonatal period and ATV/height2 in early infancy. The ratio IA/SCA ATV remains significantly correlated with SCA in both the neonatal period and early infancy; the index IA/SCA0.6 is statistically optimal at both of these ages. PMID:24662695

  4. Expression of ceramide-metabolising enzymes in subcutaneous and intra-abdominal human adipose tissue

    PubMed Central

    2012-01-01

    Background Inflammation and increased ceramide concentrations characterise adipose tissue of obese women with high liver fat content compared to equally obese women with normal liver fat content. The present study characterises enzymes involved in ceramide metabolism in subcutaneous and intra-abdominal adipose tissue. Methods Pathways leading to increased ceramide concentrations in inflamed versus non-inflamed adipose tissue were investigated by quantifying expression levels of key enzymes involved in ceramide metabolism. Sphingomyelinases (sphingomyelin phosphodiesterases SMPD1-3) were investigated further using immunohistochemistry to establish their location within adipose tissue, and their mRNA expression levels were determined in subcutaneous and intra-abdominal adipose tissue from both non-obese and obese subject. Results Gene expression levels of sphingomyelinases, enzymes that hydrolyse sphingomyelin to ceramide, rather than enzymes involved in de novo ceramide synthesis, were higher in inflamed compared to non-inflamed adipose tissue of obese women (with high and normal liver fat contents respectively). Sphingomyelinases were localised to both macrophages and adipocytes, but also to blood vessels and to extracellular regions surrounding vessels within adipose tissue. Expression levels of SMPD3 mRNA correlated significantly with concentrations of different ceramides and sphingomyelins. In both non-obese and obese subjects SMPD3 mRNA levels were higher in the more inflamed intra-abdominal compared to the subcutaneous adipose tissue depot. Conclusions Generation of ceramides within adipose tissue as a result of sphingomyelinase action may contribute to inflammation in human adipose tissue. PMID:22974251

  5. 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

  6. Central Nervous System Regulation of Brown Adipose Tissue

    PubMed Central

    Morrison, Shaun F.; Madden, Christopher J.

    2015-01-01

    Thermogenesis, the production of heat energy, in brown adipose tissue is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man and plays a key role in elevating body temperature during the febrile response to infection. The sympathetic neural outflow determining brown adipose tissue (BAT) thermogenesis is regulated by neural networks in the CNS which increase BAT sympathetic nerve activity in response to cutaneous and deep body thermoreceptor signals. Many behavioral states, including wakefulness, immunologic responses, and stress, are characterized by elevations in core body temperature to which central command-driven BAT activation makes a significant contribution. Since energy consumption during BAT thermogenesis involves oxidation of lipid and glucose fuel molecules, the CNS network driving cold-defensive and behavioral state-related BAT activation is strongly influenced by signals reflecting the short and long-term availability of the fuel molecules essential for BAT metabolism and, in turn, the regulation of BAT thermogenesis in response to metabolic signals can contribute to energy balance, regulation of body adipose stores and glucose utilization. This review summarizes our understanding of the functional organization and neurochemical influences within the CNS networks that modulate the level of BAT sympathetic nerve activity to produce the thermoregulatory and metabolic alterations in BAT thermogenesis and BAT energy expenditure that contribute to overall energy homeostasis and the autonomic support of behavior. PMID:25428857

  7. Mechanobiology and Mechanotherapy of Adipose Tissue-Effect of Mechanical Force on Fat Tissue Engineering

    PubMed Central

    Yuan, Yi

    2015-01-01

    Summary: Our bodies are subjected to various mechanical forces, which in turn affect both the structure and function of our bodies. In particular, these mechanical forces play an important role in tissue growth and regeneration. Adipocytes and adipose-derived stem cells are both mechanosensitive and mechanoresponsive. The aim of this review is to summarize the relationship between mechanobiology and adipogenesis. PubMed was used to search for articles using the following keywords: mechanobiology, adipogenesis, adipose-derived stem cells, and cytoskeleton. In vitro and in vivo experiments have shown that adipogenesis is strongly promoted/inhibited by various internal and external mechanical forces, and that these effects are mediated by changes in the cytoskeleton of adipose-derived stem cells and/or various signaling pathways. Thus, adipose tissue engineering could be enhanced by the careful application of mechanical forces. It was shown recently that mature adipose tissue regenerates in an adipose tissue-engineering chamber. This observation has great potential for the reconstruction of soft tissue deficiencies, but the mechanisms behind it remain to be elucidated. On the basis of our understanding of mechanobiology, we hypothesize that the chamber removes mechanical force on the fat that normally impose high cytoskeletal tension. The reduction in tension in adipose stem cells triggers their differentiation into adipocytes. The improvement in our understanding of the relationship between mechanobiology and adipogenesis means that in the near future, we may be able to increase or decrease body fat, as needed in the clinic, by controlling the tension that is loaded onto fat. PMID:26894003

  8. Mechanobiology and Mechanotherapy of Adipose Tissue-Effect of Mechanical Force on Fat Tissue Engineering.

    PubMed

    Yuan, Yi; Gao, Jianhua; Ogawa, Rei

    2015-12-01

    Our bodies are subjected to various mechanical forces, which in turn affect both the structure and function of our bodies. In particular, these mechanical forces play an important role in tissue growth and regeneration. Adipocytes and adipose-derived stem cells are both mechanosensitive and mechanoresponsive. The aim of this review is to summarize the relationship between mechanobiology and adipogenesis. PubMed was used to search for articles using the following keywords: mechanobiology, adipogenesis, adipose-derived stem cells, and cytoskeleton. In vitro and in vivo experiments have shown that adipogenesis is strongly promoted/inhibited by various internal and external mechanical forces, and that these effects are mediated by changes in the cytoskeleton of adipose-derived stem cells and/or various signaling pathways. Thus, adipose tissue engineering could be enhanced by the careful application of mechanical forces. It was shown recently that mature adipose tissue regenerates in an adipose tissue-engineering chamber. This observation has great potential for the reconstruction of soft tissue deficiencies, but the mechanisms behind it remain to be elucidated. On the basis of our understanding of mechanobiology, we hypothesize that the chamber removes mechanical force on the fat that normally impose high cytoskeletal tension. The reduction in tension in adipose stem cells triggers their differentiation into adipocytes. The improvement in our understanding of the relationship between mechanobiology and adipogenesis means that in the near future, we may be able to increase or decrease body fat, as needed in the clinic, by controlling the tension that is loaded onto fat.

  9. 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.

  10. Estradiol effects on subcutaneous adipose tissue lipolysis in premenopausal women are adipose tissue depot specific and treatment dependent.

    PubMed

    Gavin, Kathleen M; Cooper, Elizabeth E; Raymer, Dustin K; Hickner, Robert C

    2013-06-01

    Estrogen has direct effects within adipose tissue and has been implicated in regional adiposity; however, the influence of estrogen on in vivo lipolysis is unclear. The purpose of this study was to investigate the effect of local 17β-estradiol (E(2)) on subcutaneous adipose tissue (SAT) lipolysis in premenopausal women. In vivo lipolysis (dialysate glycerol) was measured in 17 women (age 27.4 ± 2.0 yr, BMI 29.7 ± 0.5 kg/m(2)) via microdialysis of abdominal (AB) and gluteal (GL) SAT. Glycerol was measured at baseline and during acute interventions to increase lipolysis including local perfusion of isoproterenol (ISO, β-adrenergic agonist, 1.0 μmol/l), phentolamine (PHEN, α-adrenergic antagonist, 0.1 mmol/l), and submaximal exercise (60% Vo(2peak), 30 min); all with and without coperfusion of E(2) (500 nmol/l). E(2) coperfusion blunted the lipolytic response to ISO in AB (E(2) 196 ± 31%, control 258 ± 26%, P = 0.003) but not in GL (E(2) 113 ± 14%, control 111 ± 12%, P = 0.43) adipose tissue. At rest, perfusion of PHEN with ISO did not change dialysate glycerol. Submaximal exercise during ISO + PHEN increased dialysate glycerol in the AB (56 ± 9%) and GL (62 ± 12%) regions. Probes perfused with E(2) during exercise and ISO + PHEN had an increased lipolytic response in AB (90 ± 9%, P = 0.007) but a lower response in GL (35 ± 7%, P = 0.05) SAT compared with no-E(2) conditions. E(2) effects on lipolysis are region specific and may work through both adrenergic and adrenergic-independent mechanisms to potentiate and/or blunt SAT lipolysis in premenopausal women. PMID:23531620

  11. Muscle tissue changes with aging.

    PubMed

    Pereira, Ana Fátima; Silva, António José; Matos Costa, Aldo; Monteiro, António Miguel; Bastos, Estela Maria; Cardoso Marques, Mário

    2013-01-01

    Sarcopenia is characterized by a progressive generalized decrease of skeletal muscle mass, strength and function with aging. Recently, the genetic determination has been associated with muscle mass and muscle strength in elderly. These two phenotypes of risk are the most commonly recognized and studied for sarcopenia, with heritability ranging from 30 to 85% for muscle strength and 45-90% for muscle mass. It is well known that the development and maintenance of muscle mass in early adulthood reduces the risk of developing sarcopenia and leads to a healthy aging. For that reason it seems important to identify which genetic factors interact with aging and in particular with the musculoskeletal response to exercise in such individuals. This review is designed to summarize the most important and representative studies about the possible association between certain genetic polymorphisms and muscle phenotypes in older populations. Also we will focuses on nutrition and some concerns associated with aging, including the role that exercise can have on reducing the negative effects of this phenomenon. Some results are inconsistent between studies and more replication studies underlying sarcopenia are needed, with larger samples and with different life cycles, particularly in the type and level of physical activity throughout life. In future we believe that further progress in understanding the genetic etiology and the metabolic pathways will provide valuable information on important biological mechanisms underlying the muscle physiology. This will enable better recognition of individuals at higher risk and the ability to more adequately address this debilitating condition.

  12. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs

    PubMed Central

    Castellano, Rosa; Perruchot, Marie-Hélène; Conde-Aguilera, José Alberto; van Milgen, Jaap; Collin, Anne; Tesseraud, Sophie; Mercier, Yves; Gondret, Florence

    2015-01-01

    Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight) were restrictively-fed diets providing either an adequate (CTRL) or a deficient methionine supply (MD) during 10 days (n=6 per group). At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently adapts tissue

  13. A Methionine Deficient Diet Enhances Adipose Tissue Lipid Metabolism and Alters Anti-Oxidant Pathways in Young Growing Pigs.

    PubMed

    Castellano, Rosa; Perruchot, Marie-Hélène; Conde-Aguilera, José Alberto; van Milgen, Jaap; Collin, Anne; Tesseraud, Sophie; Mercier, Yves; Gondret, Florence

    2015-01-01

    Methionine is a rate-limiting amino-acid for protein synthesis but non-proteinogenic roles on lipid metabolism and oxidative stress have been demonstrated. Contrary to rodents where a dietary methionine deficiency led to a lower adiposity, an increased lipid accretion rate has been reported in growing pigs fed a methionine deficient diet. This study aimed to clarify the effects of a dietary methionine deficiency on different aspects of tissue lipid metabolism and anti-oxidant pathways in young pigs. Post-weaned pigs (9.8 kg initial body weight) were restrictively-fed diets providing either an adequate (CTRL) or a deficient methionine supply (MD) during 10 days (n=6 per group). At the end of the feeding trial, pigs fed the MD diet had higher lipid content in subcutaneous adipose tissue. Expression levels of genes involved in glucose uptake, lipogenesis but also lipolysis, and activities of NADPH enzyme suppliers were generally higher in subcutaneous and perirenal adipose tissues of MD pigs, suggesting an increased lipid turnover in those pigs. Activities of the anti-oxidant enzymes superoxide dismutase, catalase and glutathione reductase were increased in adipose tissues and muscle of MD pigs. Expression level and activity of the glutathione peroxidase were also higher in liver of MD pigs, but hepatic contents in the reduced and oxidized forms of glutathione and glutathione reductase activity were lower compared with control pigs. In plasma, superoxide dismutase activity was higher but total anti-oxidant power was lower in MD pigs. These results show that a dietary methionine deficiency resulted in increased levels of lipogenesis and lipolytic indicators in porcine adipose tissues. Decreased glutathione content in the liver and coordinated increase of enzymatic antioxidant activities in adipose tissues altered the cellular redox status of young pigs fed a methionine-deficient diet. These findings illustrate that a rapidly growing animal differently adapts tissue

  14. Diversity of lipid mediators in human adipose tissue depots

    PubMed Central

    Clària, Joan; Nguyen, Binh T.; Madenci, Arin L.; Ozaki, C. Keith

    2013-01-01

    Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The “classic” eicosanoids prostaglandin (PG) E2, PGD2, PGF2α, leukotriene (LT) B4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2α differed significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE2. In this tissue, proresolving mediators RvD2 and LXA4 were identified in lower levels than the proinflammatory LTB4. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD. PMID:23364264

  15. The effect of diabetes on the wound healing potential of adipose-tissue derived stem cells.

    PubMed

    Kim, Sue Min; Kim, Yun Ho; Jun, Young Joon; Yoo, Gyeol; Rhie, Jong Won

    2016-03-01

    To investigate whether diabetes mellitus affects the wound-healing-promoting potential of adipose tissue-derived stem cells, we designed a wound-healing model using diabetic mice. We compared the degree of wound healing between wounds treated with normal adipose tissue-derived stem cells and wounds treated with diabetic adipose tissue-derived stem cells. We evaluated the wound-healing rate, the epithelial tongue distance, the area of granulation tissue, the number of capillary and the number of Ki-67-stained cells. The wound-healing rate was significantly higher in the normal adipose tissue-derived stem cells group than in the diabetic adipose tissue-derived stem cells group; it was also significantly higher in the normal adipose tissue-derived stem cells group than in the control group. Although the diabetic adipose tissue-derived stem cells group showed a better wound-healing rate than the control group, the difference was not statistically significant. Similar trends were observed for the other parameters examined: re-epithelisation and keratinocyte proliferation; granulation tissue formation; and dermal regeneration. However, with regard to the number of capillary, diabetic adipose tissue-derived stem cells retained their ability to promote neovasculisation and angiogenesis. These results reflect the general impairment of the therapeutic potential of diabetic adipose tissue-derived stem cells in vivo.

  16. Two types of brown adipose tissue in humans.

    PubMed

    Lidell, Martin E; Betz, Matthias J; Enerbäck, Sven

    2014-01-01

    During the last years the existence of metabolically active brown adipose tissue in adult humans has been widely accepted by the research community. Its unique ability to dissipate chemical energy stored in triglycerides as heat makes it an attractive target for new drugs against obesity and its related diseases. Hence the tissue is now subject to intense research, the hypothesis being that an expansion and/or activation of the tissue is associated with a healthy metabolic phenotype. Animal studies provide evidence for the existence of at least two types of brown adipocytes. Apart from the classical brown adipocyte that is found primarily in the interscapular region where it constitutes a thermogenic organ, a second type of brown adipocyte, the so-called beige adipocyte, can appear within white adipose tissue depots. The fact that the two cell types develop from different precursors suggests that they might be recruited and stimulated by different cues and therefore represent two distinct targets for therapeutic intervention. The aim of this commentary is to discuss recent work addressing the question whether also humans possess two types of brown adipocytes and to highlight some issues when looking for molecular markers for such cells.

  17. The contribution of arachidonate 15-lipoxygenase in tissue macrophages to adipose tissue remodeling.

    PubMed

    Kwon, H-J; Kim, S-N; Kim, Y-A; Lee, Y-H

    2016-01-01

    Cellular plasticity in adipose tissue involves adipocyte death, its clearance, and de novo adipogenesis, enabling homeostatic turnover and adaptation to metabolic challenges; however, mechanisms regulating these serial events are not fully understood. The present study investigated the roles of arachidonate 15-lipoxygenase (Alox15) in the clearance of dying adipocytes by adipose tissue macrophages. First, upregulation of Alox15 expression and apoptotic adipocyte death in gonadal white adipose tissue (gWAT) were characterized during adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Next, an in vitro reconstruction of adipose tissue macrophages and apoptotic adipocytes recapitulated adipocyte clearance by macrophages and demonstrated that macrophages co-cultured with apoptotic adipocytes increased the expression of efferocytosis-related genes. Genetic deletion and pharmacological inhibition of Alox15 diminished the levels of adipocyte clearance by macrophages in a co-culture system. Gene expression profiling of macrophages isolated from gWAT of Alox15 knockout (KO) mice demonstrated distinct phenotypes, especially downregulation of genes involved in lipid uptake and metabolism compared to wild-type mice. Finally, in vivo β3-adrenergic stimulation in Alox15 KO mice failed to recruit crown-like structures, a macrophage network clearing dying adipocytes in gWAT. Consequently, in Alox15 KO mice, proliferation/differentiation of adipocyte progenitors and β3-adrenergic remodeling of gWAT were impaired compared to wild-type control mice. Collectively, our data established a pivotal role of Alox15 in the resolution of adipocyte death and in adipose tissue remodeling. PMID:27362803

  18. Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.

    PubMed

    Vaicik, Marcella K; Thyboll Kortesmaa, Jill; Movérare-Skrtic, Sofia; Kortesmaa, Jarkko; Soininen, Raija; Bergström, Göran; Ohlsson, Claes; Chong, Li Yen; Rozell, Björn; Emont, Margo; Cohen, Ronald N; Brey, Eric M; Tryggvason, Karl

    2014-01-01

    Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/-) and compared to wild-type (Lama4+/+) control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.

  19. [12 hours running results in a decrease of the subcutaneous adipose tissue].

    PubMed

    Knechtle, B; Zimmermann, K; Wirth, A; Knechtle, P; Kohler, G

    2007-09-19

    A runner has completed 80 km in a 12-hour run. Prior and shortly after the run, fat and skeletal muscle mass were determined non invasively both by the bioelectrical impedance analysis and the classic skin fold method. In addition, blood and urine samples were taken in order to assess fluid balance. By applying the bioelectrical impedance analysis, the runner has increased body mass by 1.5 kg, fat-free body mass by 4.2 kg and muscle mass by 1.0 kg, whereas fat mass decreased by 4.4 kg. Since body water increased by 4.9 l, the determination of haematocrit, haemoglobin and sodium showed a haemodilution and the specific gravity of urine indicated no dehydration, we assume a substantial decrease of subcutaneous adipose tissue for energy production and intracellular oedemas. The difference between determining fat mass with the skin fold method or with the bioelectrical impedance analysis is discussed. PMID:17933286

  20. Adipose tissue-derived stem cells as a therapeutic tool for cardiovascular disease.

    PubMed

    Suzuki, Etsu; Fujita, Daishi; Takahashi, Masao; Oba, Shigeyoshi; Nishimatsu, Hiroaki

    2015-08-26

    Adipose tissue-derived stem cells (ADSCs) are adult stem cells that can be easily harvested from subcutaneous adipose tissue. Many studies have demonstrated that ADSCs differentiate into vascular endothelial cells (VECs), vascular smooth muscle cells (VSMCs), and cardiomyocytes in vitro and in vivo. However, ADSCs may fuse with tissue-resident cells and obtain the corresponding characteristics of those cells. If fusion occurs, ADSCs may express markers of VECs, VSMCs, and cardiomyocytes without direct differentiation into these cell types. ADSCs also produce a variety of paracrine factors such as vascular endothelial growth factor, hepatocyte growth factor, and insulin-like growth factor-1 that have proangiogenic and/or antiapoptotic activities. Thus, ADSCs have the potential to regenerate the cardiovascular system via direct differentiation into VECs, VSMCs, and cardiomyocytes, fusion with tissue-resident cells, and the production of paracrine factors. Numerous animal studies have demonstrated the efficacy of ADSC implantation in the treatment of acute myocardial infarction (AMI), ischemic cardiomyopathy (ICM), dilated cardiomyopathy, hindlimb ischemia, and stroke. Clinical studies regarding the use of autologous ADSCs for treating patients with AMI and ICM have recently been initiated. ADSC implantation has been reported as safe and effective so far. Therefore, ADSCs appear to be useful for the treatment of cardiovascular disease. However, the tumorigenic potential of ADSCs requires careful evaluation before their safe clinical application.

  1. 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.

  2. 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

  3. Exercise Prevents Diet-Induced Cellular Senescence in Adipose Tissue.

    PubMed

    Schafer, Marissa J; White, Thomas A; Evans, Glenda; Tonne, Jason M; Verzosa, Grace C; Stout, Michael B; Mazula, Daniel L; Palmer, Allyson K; Baker, Darren J; Jensen, Michael D; Torbenson, Michael S; Miller, Jordan D; Ikeda, Yasuhiro; Tchkonia, Tamara; van Deursen, Jan M; Kirkland, James L; LeBrasseur, Nathan K

    2016-06-01

    Considerable evidence implicates cellular senescence in the biology of aging and chronic disease. Diet and exercise are determinants of healthy aging; however, the extent to which they affect the behavior and accretion of senescent cells within distinct tissues is not clear. Here we tested the hypothesis that exercise prevents premature senescent cell accumulation and systemic metabolic dysfunction induced by a fast-food diet (FFD). Using transgenic mice that express EGFP in response to activation of the senescence-associated p16(INK4a) promoter, we demonstrate that FFD consumption causes deleterious changes in body weight and composition as well as in measures of physical, cardiac, and metabolic health. The harmful effects of the FFD were associated with dramatic increases in several markers of senescence, including p16, EGFP, senescence-associated β-galactosidase, and the senescence-associated secretory phenotype (SASP) specifically in visceral adipose tissue. We show that exercise prevents the accumulation of senescent cells and the expression of the SASP while nullifying the damaging effects of the FFD on parameters of health. We also demonstrate that exercise initiated after long-term FFD feeding reduces senescent phenotype markers in visceral adipose tissue while attenuating physical impairments, suggesting that exercise may provide restorative benefit by mitigating accrued senescent burden. These findings highlight a novel mechanism by which exercise mediates its beneficial effects and reinforces the effect of modifiable lifestyle choices on health span. PMID:26983960

  4. Characterization of microRNA expression in bovine adipose tissues: a potential regulatory mechanism of subcutaneous adipose tissue development

    PubMed Central

    2010-01-01

    Background MicroRNAs (miRNAs), a family of small non-coding RNA molecules, appear to regulate animal lipid metabolism and preadipocyte conversion to form lipid-assimilating adipocytes (i.e. adipogenesis). However, no miRNA to date has been reported to modulate adipogenesis and lipid deposition in beef cattle. Results The expression patterns of 89 miRNAs including four bovine specific miRNAs in subcutaneous adipose tissues from three groups of crossbred steers differing in backfat thickness were compared using qRT-PCR analysis. Eighty-six miRNAs were detectable in all samples, with 42 miRNAs differing among crossbreds (P < 0.05) and 15 miRNAs differentially expressed between tissues with high and low backfat thickness (P < 0.05). The expression levels of 18 miRNAs were correlated with backfat thickness (P < 0.05). The miRNA most differentially expressed and the most strongly associated with backfat thickness was miR-378, with a 1.99-fold increase in high backfat thickness tissues (r = 0.72). Conclusions MiRNA expression patterns differed significantly in response to host genetic components. Approximately 20% of the miRNAs in this study were identified as being correlated with backfat thickness. This result suggests that miRNAs may play a regulatory role in white adipose tissue development in beef animals. PMID:20423511

  5. A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue.

    PubMed

    Haim, Yulia; Tarnovscki, Tanya; Bashari, Dana; Rudich, Assaf

    2013-11-01

    Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture "authentic" interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes.

  6. 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...

  7. Modal response of a computational vocal fold model with a substrate layer of adipose tissue.

    PubMed

    Jones, Cameron L; Achuthan, Ajit; Erath, Byron D

    2015-02-01

    This study demonstrates the effect of a substrate layer of adipose tissue on the modal response of the vocal folds, and hence, on the mechanics of voice production. Modal analysis is performed on the vocal fold structure with a lateral layer of adipose tissue. A finite element model is employed, and the first six mode shapes and modal frequencies are studied. The results show significant changes in modal frequencies and substantial variation in mode shapes depending on the strain rate of the adipose tissue. These findings highlight the importance of considering adipose tissue in computational vocal fold modeling.

  8. Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.

    PubMed

    Ramseyer, Vanesa D; Granneman, James G

    2016-01-01

    The discovery of brown adipose tissue in adult humans along with the recognition of adipocyte heterogeneity and plasticity of white fat depots has renewed the interest in targeting adipose tissue for therapeutic benefit. Adrenergic activation is a well-established means of recruiting catabolic adipocyte phenotypes in brown and white adipose tissues. In this article, we review mechanisms of brown adipocyte recruitment by the sympathetic nervous system and by direct β-adrenergic receptor activation. We highlight the distinct modes of brown adipocyte recruitment in brown, beige/brite, and white adipose tissues, UCP1-independent thermogenesis, and potential non-thermogenic, metabolically beneficial effects of brown adipocytes.

  9. Targeting adipose tissue in the treatment of obesity-associated diabetes.

    PubMed

    Kusminski, Christine M; Bickel, Perry E; Scherer, Philipp E

    2016-09-01

    Adipose tissue regulates numerous physiological processes, and its dysfunction in obese humans is associated with disrupted metabolic homeostasis, insulin resistance and type 2 diabetes mellitus (T2DM). Although several US-approved treatments for obesity and T2DM exist, these are limited by adverse effects and a lack of effective long-term glucose control. In this Review, we provide an overview of the role of adipose tissue in metabolic homeostasis and assess emerging novel therapeutic strategies targeting adipose tissue, including adipokine-based strategies, promotion of white adipose tissue beiging as well as reduction of inflammation and fibrosis. PMID:27256476

  10. Adipose tissue chromium and vanadium disbalance in high-fat fed Wistar rats.

    PubMed

    Tinkov, Alexey A; Popova, Elizaveta V; Polyakova, Valentina S; Kwan, Olga V; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-01-01

    The primary objective of the current study is to investigate the relationship between adipose tissue chromium and vanadium content and adipose tissue dysfunction in a model of diet-induced obesity. A total of 26 female Wistar rats were fed either standard or high-fat diet (31.6% of fat from total caloric content) for 3 months. High-fat-feeding resulted in 21 and 33% decrease in adipose tissue chromium and vanadium content, respectively. No change was seen in hair chromium or vanadium levels. Statistical analysis revealed a significant inverse correlation of adipose tissue Cr and V with animal morphometric parameters and adipocyte size. Significant inverse dependence was observed between adipose tissue Cr and V and serum leptin and proinflammatory cytokines' levels. At the same time, adipose tissue Cr and V levels were characterized by positive correlation between serum adiponectin and adiponectin/leptin ratio. Adipose tissue Cr and V were inversely correlated (p<0.05) with insulin and homeostatic model assessment insulin resistance index (HOMA-IR) levels. Cr and V concentrations were not correlated with serum glucose in either high-fat fed or control rats; however, both serum glucose and HOMA-IR levels were significantly higher in high-fat fed, compared to control, rats. The results allow to hypothesize that impairment of adipose tissue Cr and V content plays a certain role in the development of adipose tissue endocrine dysfunction in obesity.

  11. Sugar-sweetened and diet beverages in relation to visceral adipose tissue.

    PubMed

    Odegaard, Andrew O; Choh, Audrey C; Czerwinski, Stefan A; Towne, Bradford; Demerath, Ellen W

    2012-03-01

    Frequent sugar-sweetened beverage (SSB) intake has been consistently associated with increased adiposity and cardio-metabolic risk, whereas the association with diet beverages is more mixed. We examined how these beverages associate with regional abdominal adiposity measures, specifically visceral adipose tissue (VAT). In a cross-sectional analysis of 791 non-Hispanic white men and women aged 18-70 we examined how beverage consumption habits obtained from a food frequency questionnaire associate with overall and abdominal adiposity measures from MRI. With increasing frequency of SSB intake, we observed increases in waist circumference (WC) and the proportion of visceral to subcutaneous abdominal adipose tissue (VAT%), with no change in total body fat (TBF%) or BMI. Greater frequency of diet beverage intake was associated with greater WC, BMI, and TBF%, but was not associated with variation in visceral adiposity We conclude that increased frequency of SSB consumption is associated with a more adverse abdominal adipose tissue deposition pattern.

  12. Cloning of porcine GPIHBP1 gene and its tissue expression pattern and genetic effect on adipose traits.

    PubMed

    Xu, Huaming; Tao, Xuelian; Wei, Yingying; Chen, Jianning; Xing, Shuhua; Cen, Wangmin; Wen, Anxiang; Zhu, Li; Tang, Guoqing; Li, Mingzhou; Jiang, Anan; Jiang, Yanzhi; Li, Xuewei

    2015-02-25

    Lipoprotein lipase (LPL) is a key enzyme in lipid metabolism and is transported by glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1) from the interstitial spaces to the capillary lumen. Here, we cloned a cDNA and the genomic locus of the porcine GPIHBP1 gene, and investigated its tissue expression pattern and its genetic effects on adipose traits. Porcine GPIHBP1 exhibits a four-exon/three-intron structure, including a 543bp open reading frame that encodes 180 amino acids. The porcine GPIHBP1 protein shows 49%-65% homology and shares the major conserved structural domains of GPIHBP1 proteins in other mammals. Porcine GPIHBP1 mRNA levels were high in the adipose tissue, muscle and lung, and higher mRNA levels were observed in sows compared to boars in adipose tissues of the inner and outer layers of subcutaneous fat, abdominal fat, and suet fat. The mRNA expression pattern of porcine GPIHBP1 and LPL genes was similar in most tissues except for the lung. Thirty six single nucleotide polymorphisms (SNPs) were found in the porcine GPIHBP1 gene. Association analyses showed that the g.-255G>C and g.-626T>G SNPs are associated with intramuscular fat content, and that the g.-1557T>C and g.-1948G>A SNPs are associated with back fat thickness. In conclusion, porcine GPIHBP1 mRNA is abundantly expressed in the adipose tissue, muscle and lung, and gender affects GPIHBP1 mRNA expression levels; furthermore, four GPIHBP1 SNPs are genetic factors affecting adipose traits.

  13. High-affinity glutamate transporter and glutamine synthetase content in longissimus dorsi and adipose tissues of growing Angus steers differs among suckling, weanling, backgrounding, and finishing production stages.

    PubMed

    Matthews, J C; Huang, J; Rentfrow, G

    2016-03-01

    Skeletal muscle and adipose tissues play important roles in maintaining whole-body Glu and N homeostasis by the uptake of Glu and release of Gln. To test the hypothesis that expression of high-affinity Glu transporters (GLAST1, EAAT4, EAAC1, GLT-1) and glutamine synthetase (GS) would increase in longissimus dorsi and adipose tissue of newborn Angus steers randomly assigned ( = 6) to develop through suckling (S; 32 d) and/or weanling (W; 184 d), backgrounding (B; 248 d), and finishing (F; 423 d) production stages. Carcass quality was determined at slaughter to verify shifts in adipose and lean deposition with development. Expression of mRNA (RT-PCR/Southern) and relative protein abundance (Western analysis) were determined in tissue homogenates isolated from longissimus dorsi, and kidney and subcutaneous adipose. The effect of production stage or tissue type on carcass and protein abundance was assessed by 1-way ANOVA using the GLM procedure of SAS, and Fisher's protected LSD procedure was used to separate data means. Neither GLAST1 nor EAAT4 mRNA or protein was detected. EAAC1, GLT-1, and GS mRNA were identified in all tissues, but GLT-1 and GS protein were not detected in kidney or subcutaneous adipose, and GS protein was not detected in longissimus dorsi. The EAAC1 content of subcutaneous ( = 0.06) and kidney ( = 0.02) adipose was 2 times greater in B and F than W steers, whereas GS was 5 times greater ( < 0.07) in B than F steers (B = W > F). For longissimus dorsi, EAAC1 ( < 0.01) and GLT-1 ( < 0.04) content decreased with development (S > W > B = F, S = W > B = F, respectively). Within F steers, EAAC1 and GLT-1 mRNA was expressed by subcutaneous, kidney, omental, mesenchymal, and intramuscular adipose tissues, whereas GS mRNA was expressed by all except for intramuscular. Only EAAC1 protein was detected in any adipose tissue, with EAAC1 content being 104% and 112% greater ( < 0.01) in intramuscular than in kidney or subcutaneous adipose, respectively, and not

  14. High-affinity glutamate transporter and glutamine synthetase content in longissimus dorsi and adipose tissues of growing Angus steers differs among suckling, weanling, backgrounding, and finishing production stages.

    PubMed

    Matthews, J C; Huang, J; Rentfrow, G

    2016-03-01

    Skeletal muscle and adipose tissues play important roles in maintaining whole-body Glu and N homeostasis by the uptake of Glu and release of Gln. To test the hypothesis that expression of high-affinity Glu transporters (GLAST1, EAAT4, EAAC1, GLT-1) and glutamine synthetase (GS) would increase in longissimus dorsi and adipose tissue of newborn Angus steers randomly assigned ( = 6) to develop through suckling (S; 32 d) and/or weanling (W; 184 d), backgrounding (B; 248 d), and finishing (F; 423 d) production stages. Carcass quality was determined at slaughter to verify shifts in adipose and lean deposition with development. Expression of mRNA (RT-PCR/Southern) and relative protein abundance (Western analysis) were determined in tissue homogenates isolated from longissimus dorsi, and kidney and subcutaneous adipose. The effect of production stage or tissue type on carcass and protein abundance was assessed by 1-way ANOVA using the GLM procedure of SAS, and Fisher's protected LSD procedure was used to separate data means. Neither GLAST1 nor EAAT4 mRNA or protein was detected. EAAC1, GLT-1, and GS mRNA were identified in all tissues, but GLT-1 and GS protein were not detected in kidney or subcutaneous adipose, and GS protein was not detected in longissimus dorsi. The EAAC1 content of subcutaneous ( = 0.06) and kidney ( = 0.02) adipose was 2 times greater in B and F than W steers, whereas GS was 5 times greater ( < 0.07) in B than F steers (B = W > F). For longissimus dorsi, EAAC1 ( < 0.01) and GLT-1 ( < 0.04) content decreased with development (S > W > B = F, S = W > B = F, respectively). Within F steers, EAAC1 and GLT-1 mRNA was expressed by subcutaneous, kidney, omental, mesenchymal, and intramuscular adipose tissues, whereas GS mRNA was expressed by all except for intramuscular. Only EAAC1 protein was detected in any adipose tissue, with EAAC1 content being 104% and 112% greater ( < 0.01) in intramuscular than in kidney or subcutaneous adipose, respectively, and not

  15. Composite hydrogel scaffolds incorporating decellularized adipose tissue for soft tissue engineering with adipose-derived stem cells.

    PubMed

    Cheung, Hoi Ki; Han, Tim Tian Y; Marecak, Dale M; Watkins, John F; Amsden, Brian G; Flynn, Lauren E

    2014-02-01

    An injectable tissue-engineered adipose substitute that could be used to deliver adipose-derived stem cells (ASCs), filling irregular defects and stimulating natural soft tissue regeneration, would have significant value in plastic and reconstructive surgery. With this focus, the primary aim of the current study was to characterize the response of human ASCs encapsulated within three-dimensional bioscaffolds incorporating decellularized adipose tissue (DAT) as a bioactive matrix within photo-cross-linkable methacrylated glycol chitosan (MGC) or methacrylated chondroitin sulphate (MCS) delivery vehicles. Stable MGC- and MCS-based composite scaffolds were fabricated containing up to 5 wt% cryomilled DAT through initiation with long-wavelength ultraviolet light. The encapsulation strategy allows for tuning of the 3-D microenvironment and provides an effective method of cell delivery with high seeding efficiency and uniformity, which could be adapted as a minimally-invasive in situ approach. Through in vitro cell culture studies, human ASCs were assessed over 14 days in terms of viability, glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, adipogenic gene expression and intracellular lipid accumulation. In all of the composites, the DAT functioned as a cell-supportive matrix that enhanced ASC viability, retention and adipogenesis within the gels. The choice of hydrogel also influenced the cell response, with significantly higher viability and adipogenic differentiation observed in the MCS composites containing 5 wt% DAT. In vivo analysis in a subcutaneous Wistar rat model at 1, 4 and 12 weeks showed superior implant integration and adipogenesis in the MCS-based composites, with allogenic ASCs promoting cell infiltration, angiogenesis and ultimately, fat formation. PMID:24331712

  16. 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

  17. 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

  18. Lipid metabolism during lactation: a review of adipose tissue-liver interactions and the development of fatty liver.

    PubMed

    Vernon, Richard G

    2005-11-01

    Fatty acids are the major source of energy for most tissues during periods of negative energy balance; however, fatty acids can, in some circumstances, have pathological effects. Fatty acids are stored as triacylglycerols (TAG), mostly in the various adipose tissue depots of the body. However, if blood unesterified fatty acid (NEFA) levels are elevated for prolonged periods, as may occur during lactation or obesity, TAG can accumulate in other tissues including liver and muscle cells (myocytes), and this can have pathological consequences such as the development of ketosis (Grummer, 1993; Drackley et al. 2001) or type 2 diabetes (Boden & Shulman, 2002; McGarry, 2002).

  19. 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.

  20. 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

  1. Local proliferation initiates macrophage accumulation in adipose tissue during obesity.

    PubMed

    Zheng, C; Yang, Q; Cao, J; Xie, N; Liu, K; Shou, P; Qian, F; Wang, Y; Shi, Y

    2016-01-01

    Obesity-associated chronic inflammation is characterized by an accumulation of adipose tissue macrophages (ATMs). It is generally believed that those macrophages are derived from peripheral blood monocytes. However, recent studies suggest that local proliferation of macrophages is responsible for ATM accumulation. In the present study, we revealed that both migration and proliferation contribute to ATM accumulation during obesity development. We show that there is a significant increase in ATMs at the early stage of obesity, which is largely due to an enhanced in situ macrophage proliferation. This result was obtained by employing fat-shielded irradiation and bone marrow reconstitution. Additionally, the production of CCL2, a pivotal chemoattractant of monocytes, was not found to be increased at this stage, corroborating with a critical role of proliferation. Nonetheless, as obesity proceeds, the role of monocyte migration into adipose tissue becomes more significant and those new immigrants further proliferate locally. These proliferating ATMs mainly reside in crown-like structures formed by macrophages surrounding dead adipocytes. We further showed that IL-4/STAT6 is a driving force for ATM proliferation. Therefore, we demonstrated that local proliferation of resident macrophages contributes to ATM accumulation during obesity development and has a key role in obesity-associated inflammation. PMID:27031964

  2. Ultrastructure of the adipose tissue matrix in children with malnutrition.

    PubMed

    Alexa, A; Drăgan, M; Popa, I; Raica, M; Dema, E

    1995-01-01

    Bioptic fragments of adipose white tissue taken from trochanterian area from children of 2-22 months old were ultrastructurally investigated. Children were of both sexes, 5 normal and 22 with clinical diagnosis of malnutrition. There were studied many interadipocyte spaces signalling out in cases with malnutrition modifications of different components, some of them related with the degree of malnutrition. There were noted: disorganisation and disappearance of basal membranes of capillaries and glycolema; modifications of endothelial cells with lesions of the capillary wall and free degraded red blood cells; disorganization of the ground substance in small areas or sometimes extended to all matrix of the space; collagen fibres reduced in number and size, and in two cases the presence of collagen fibrils with severe lesions, realeasing an electrondense material, fibrinoid-like; matrix infiltration, in some cases with lipids. In only one interadipocyte space a synaptic button was noted in contact with capillary. In malnutrition lesions of cellular elements of the white adipose tissue the following were observed: adipocytes, fibroblasts, fibrocytes, endothelial cells, mast cells--which in their turn are responsible for modifications of macromolecular structures of the extracellular matrix--glycosaminoglycans, proteoglycans, components of which biosyntheses are cell-dependent. PMID:8772367

  3. 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

  4. 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.

  5. The Gq signalling pathway inhibits brown and beige adipose tissue

    PubMed Central

    Klepac, Katarina; Kilić, Ana; Gnad, Thorsten; Brown, Loren M.; Herrmann, Beate; Wilderman, Andrea; Balkow, Aileen; Glöde, Anja; Simon, Katharina; Lidell, Martin E.; Betz, Matthias J.; Enerbäck, Sven; Wess, Jürgen; Freichel, Marc; Blüher, Matthias; König, Gabi; Kostenis, Evi; Insel, Paul A.; Pfeifer, Alexander

    2016-01-01

    Brown adipose tissue (BAT) dissipates nutritional energy as heat via the uncoupling protein-1 (UCP1) and BAT activity correlates with leanness in human adults. Here we profile G protein-coupled receptors (GPCRs) in brown adipocytes to identify druggable regulators of BAT. Twenty-one per cent of the GPCRs link to the Gq family, and inhibition of Gq signalling enhances differentiation of human and murine brown adipocytes. In contrast, activation of Gq signalling abrogates brown adipogenesis. We further identify the endothelin/Ednra pathway as an autocrine activator of Gq signalling in brown adipocytes. Expression of a constitutively active Gq protein in mice reduces UCP1 expression in BAT, whole-body energy expenditure and the number of brown-like/beige cells in white adipose tissue (WAT). Furthermore, expression of Gq in human WAT inversely correlates with UCP1 expression. Thus, our data indicate that Gq signalling regulates brown/beige adipocytes and inhibition of Gq signalling may be a novel therapeutic approach to combat obesity. PMID:26955961

  6. Hypothalamic Regulation of Brown Adipose Tissue Thermogenesis and Energy Homeostasis

    PubMed Central

    Zhang, Wei; Bi, Sheng

    2015-01-01

    Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT) is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT) or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis. PMID:26379628

  7. Tissue/blood partition coefficients for xenon in various adipose tissue depots in man.

    PubMed

    Bülow, J; Jelnes, R; Astrup, A; Madsen, J; Vilmann, P

    1987-02-01

    Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates of the adipose tissue blood flow measured with the 133Xe wash-out method.

  8. Adipose Tissue-Derived Stem Cells for the Treatment of Erectile Dysfunction.

    PubMed

    Gokce, Ahmet; Peak, Taylor C; Abdel-Mageed, Asim B; Hellstrom, Wayne J

    2016-02-01

    Although a spectrum of options is available for erectile dysfunction (ED) treatment, ED in diabetics, post-prostatectomy patients, and those with Peyronie's disease (PD) may be more severe in degree and less likely to respond to conventional medical therapies. Unfortunately, there have been limited breakthroughs in therapeutic options for severe ED during the past decade. However, one of the more fascinating strategies in preclinical development to treat ED is stem cell transplantation. Depending on the cell type, recent research has demonstrated that with transplantation, these stem cells can exert a paracrine effect on surrounding penile tissues and differentiate into smooth muscle, endothelium, and neurons. Adipose tissue-derived stem cells (ADSCs) have become a valuable resource because of their abundance and ease of isolation. It is evident that ADSCs may provide a realistic, therapeutic modality for the treatment of ED. In this review, we will cover the literature that has evaluated ADSCs in the treatment of ED.

  9. Encapsulation Thermogenic Preadipocytes for Transplantation into Adipose Tissue Depots

    PubMed Central

    Xu, Lu; Shen, Qiwen; Mao, Zhongqi; Lee, L. James; Ziouzenkova, Ouliana

    2015-01-01

    Cell encapsulation was developed to entrap viable cells within semi-permeable membranes. The engrafted encapsulated cells can exchange low molecular weight metabolites in tissues of the treated host to achieve long-term survival. The semipermeable membrane allows engrafted encapsulated cells to avoid rejection by the immune system. The encapsulation procedure was designed to enable a controlled release of bioactive compounds, such as insulin, other hormones, and cytokines. Here we describe a method for encapsulation of catabolic cells, which consume lipids for heat production and energy dissipation (thermogenesis) in the intra-abdominal adipose tissue of obese mice. Encapsulation of thermogenic catabolic cells may be potentially applicable to the prevention and treatment of obesity and type 2 diabetes. Another potential application of catabolic cells may include detoxification from alcohols or other toxic metabolites and environmental pollutants. PMID:26066392

  10. Retention of sedentary obese visceral white adipose tissue phenotype with intermittent physical activity despite reduced adiposity.

    PubMed

    Wainright, Katherine S; Fleming, Nicholas J; Rowles, Joe L; Welly, Rebecca J; Zidon, Terese M; Park, Young-Min; Gaines, T'Keaya L; Scroggins, Rebecca J; Anderson-Baucum, Emily K; Hasty, Alyssa H; Vieira-Potter, Victoria J; Padilla, Jaume

    2015-09-01

    Regular physical activity is effective in reducing visceral white adipose tissue (AT) inflammation and oxidative stress, and these changes are commonly associated with reduced adiposity. However, the impact of multiple periods of physical activity, intercalated by periods of inactivity, i.e., intermittent physical activity, on markers of AT inflammation and oxidative stress is unknown. In the present study, 5-wk-old male C57BL/6 mice were randomized into three groups (n = 10/group): sedentary, regular physical activity, and intermittent physical activity, for 24 wk. All animals were singly housed and fed a diet containing 45% kcal from fat. Regularly active mice had access to voluntary running wheels throughout the study period, whereas intermittently active mice had access to running wheels for 3-wk intervals (i.e., 3 wk on/3 wk off) throughout the study. At death, regular and intermittent physical activity was associated with similar reductions in visceral AT mass (approximately -24%, P < 0.05) relative to sedentary. However, regularly, but not intermittently, active mice exhibited decreased expression of visceral AT genes related to inflammation (e.g., monocyte chemoattractant protein 1), immune cell infiltration (e.g., CD68, CD11c, F4/80, CD11b/CD18), oxidative stress (e.g., p47 phagocyte oxidase), and endoplasmic reticulum stress (e.g., CCAAT enhancer-binding protein homologous protein; all P < 0.05). Furthermore, regular, but not intermittent, physical activity was associated with a trend toward improvement in glucose tolerance (P = 0.059). Collectively, these findings suggest that intermittent physical activity over a prolonged period of time may lead to a reduction in adiposity but with retention of a sedentary obese white AT and metabolic phenotype. PMID:26180183

  11. Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

    PubMed

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

    2016-09-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc.

  12. Paracrine and intracrine contributions of androgens and estrogens to adipose tissue biology: physiopathological aspects.

    PubMed

    Waraich, Rizwana S; Mauvais-Jarvis, Franck

    2013-08-01

    In mammals, the male and female hormones androgen and estrogen act as endocrine regulators of energy metabolism. However, adipose tissue is also a site of androgen and estrogen synthesis; androgens convert to estrogens in these tissues, and adipose tissue is also a reservoir of steroids that act locally in a paracrine and intracrine manner. Thus, in adipose tissue, the local output of sex hormones is more complex than would be suggested by routine measurement of serum hormone concentrations. This review integrates studies on the effects of androgens and estrogens in the developmental programming of adipose tissue function in early life and addresses the contributions of local androgen and estrogen metabolism on adipose tissue function in adults.

  13. Decellularized Extracellular Matrix Derived from Porcine Adipose Tissue as a Xenogeneic Biomaterial for Tissue Engineering

    PubMed Central

    Choi, Young Chan; Choi, Ji Suk; Kim, Beob Soo; Kim, Jae Dong; Yoon, Hwa In

    2012-01-01

    Cells in tissues are surrounded by the extracellular matrix (ECM), a gel-like material of proteins and polysaccharides that are synthesized and secreted by cells. Here we propose that the ECM can be isolated from porcine adipose tissue and holds great promise as a xenogeneic biomaterial for tissue engineering and regenerative medicine. Porcine adipose tissue is easily obtained in large quantities from commonly discarded food waste. Decellularization protocols have been developed for extracting an intact ECM while effectively eliminating xenogeneic epitopes and minimally disrupting the ECM composition. Porcine adipose tissue was defatted by homogenization and centrifugation. It was then decellularized via chemical (1.5 M sodium chloride and 0.5% sodium dodecyl sulfate) and enzymatic treatments (DNase and RNase) with temperature control. After decellularization, immunogenic components such as nucleic acids and α-Gal were significantly reduced. However, abundant ECM components, such as collagen (332.9±12.1 μg/mg ECM dry weight), sulfated glycosaminoglycan (GAG, 85±0.7 μg/mg ECM dry weight), and elastin (152.6±4.5 μg/mg ECM dry weight), were well preserved in the decellularized material. The biochemical and mechanical features of a decellularized ECM supported the adhesion and growth of human cells in vitro. Moreover, the decellularized ECM exhibited biocompatibility, long-term stability, and bioinductivity in vivo. The overall results suggest that the decellularized ECM derived from porcine adipose tissue could be useful as an alternative biomaterial for xenograft tissue engineering. PMID:22559904

  14. Adipose tissue development during early life: novel insights into energy balance from small and large mammals.

    PubMed

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2012-08-01

    Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.

  15. Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment

    PubMed Central

    Reyes-Vidal, Carlos M.; Mojahed, Hamed; Shen, Wei; Jin, Zhezhen; Arias-Mendoza, Fernando; Fernandez, Jean Carlos; Gallagher, Dympna; Bruce, Jeffrey N.; Post, Kalmon D.

    2015-01-01

    Context: GH and IGF-I have important roles in the maintenance of substrate metabolism and body composition. However, when in excess in acromegaly, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) deposition. Objectives: The purpose of this study was to examine the effect of surgery for acromegaly on AT distribution and ectopic lipid deposition in liver and muscle. Design: This was a prospective study before and up to 2 years after pituitary surgery. Setting: The setting was an academic pituitary center. Patients: Participants were 23 patients with newly diagnosed, untreated acromegaly. Main Outcome Measures: We determined visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue (IMAT), and skeletal muscle compartments by total-body magnetic resonance imaging, intrahepatic and intramyocellular lipid by proton magnetic resonance spectroscopy, and serum endocrine, metabolic, and cardiovascular risk markers. Results: VAT and SAT masses were lower than predicted in active acromegaly, but increased after surgery in male and female subjects along with lowering of GH, IGF-I, and insulin resistance. VAT and SAT increased to a greater extent in men than in women. Skeletal muscle mass decreased in men. IMAT was higher in active acromegaly and decreased in women after surgery. Intrahepatic lipid increased, but intramyocellular lipid did not change after surgery. Conclusions: Acromegaly may present a unique type of lipodystrophy characterized by reduced storage of AT in central depots and a shift of excess lipid to IMAT. After surgery, this pattern partially reverses, but differentially in men and women. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use. PMID:26037515

  16. Methyl-ß-cyclodextrin alters adipokine gene expression and glucose metabolism in swine adipose tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study was designed to determine if metabolic stress as induced by methyl-ß-cyclodextrin (MCD) can alter cytokine expression in neonatal swine adipose tissue explants. Subcutaneous adipose tissue explants (100 ± 10 mg) were prepared from 21 day old pigs. Explants were incubated in medium 199 s...

  17. 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.

  18. 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.

  19. Metabolic inflammation in inflammatory bowel disease: crosstalk between adipose tissue and bowel.

    PubMed

    Gonçalves, Pedro; Magro, Fernando; Martel, Fátima

    2015-02-01

    Epidemiological studies show that both the incidence of inflammatory bowel disease (IBD) and the proportion of people with obesity and/or obesity-associated metabolic syndrome increased markedly in developed countries during the past half century. Obesity is also associated with the development of more active IBD and requirement for hospitalization and with a decrease in the time span between diagnosis and surgery. Patients with IBD, especially Crohn's disease, present fat-wrapping or "creeping fat," which corresponds to ectopic adipose tissue extending from the mesenteric attachment and covering the majority of the small and large intestinal surface. Mesenteric adipose tissue in patients with IBD presents several morphological and functional alterations, e.g., it is more infiltrated with immune cells such as macrophages and T cells. All these lines of evidence clearly show an association between obesity, adipose tissue, and functional bowel disorders. In this review, we will show that the mesenteric adipose tissue and creeping fat are not innocent by standers but actively contribute to the intestinal and systemic inflammatory responses in patients with IBD. More specifically, we will review evidence showing that adipose tissue in IBD is associated with major alterations in the secretion of cytokines and adipokines involved in inflammatory process, in adipose tissue mesenchymal stem cells and adipogenesis, and in the interaction between adipose tissue and other intestinal components (immune, lymphatic, neuroendocrine, and intestinal epithelial systems). Collectively, these studies underline the importance of adipose tissue for the identification of novel therapeutic approaches for IBD.

  20. 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

  1. Adipogenesis: new insights into brown adipose tissue differentiation.

    PubMed

    Carobbio, Stefania; Rosen, Barry; Vidal-Puig, Antonio

    2013-12-01

    Confirmation of the presence of functional brown adipose tissue (BAT) in humans has renewed interest in investigating the potential therapeutic use of this tissue. The finding that its activity positively correlates with decreased BMI, decreased fat content, and augmented energy expenditure suggests that increasing BAT mass/activity or browning of white adipose tissue (WAT) could be a strategy to prevent or treat obesity and its associated morbidities. The challenge now is to find a safe and efficient way to develop this idea. Whereas BAT has being widely studied in murine models both in vivo and in vitro, there is an urgent need for human cellular models to investigate BAT physiology and functionality from a molecular point of view. In this review, we focus on the latest insights surrounding BAT development and activation in rodents and humans. Then, we discuss how the availability of murine models has been essential to identify BAT progenitors and trace their lineage. Finally, we address how this information can be exploited to develop human cellular models for BAT differentiation/activation. In this context, human embryonic stem and induced pluripotent stem cells-based cellular models represent a resource of great potential value, as they can provide a virtually inexhaustible supply of starting material for functional genetic studies, -omics based analysis and validation of therapeutic approaches. Moreover, these cells can be readily genetically engineered, opening the possibility of generating patient-specific cellular models, allowing the investigation of the influence of different genetic backgrounds on BAT differentiation in pathological or in physiological states.

  2. 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.

  3. Identification of cyclopropaneoctanoic acid 2-hexyl in human adipose tissue and serum.

    PubMed

    Sledzinski, Tomasz; Mika, Adriana; Stepnowski, Piotr; Proczko-Markuszewska, Monika; Kaska, Lukasz; Stefaniak, Tomasz; Swierczynski, Julian

    2013-08-01

    Fatty acids containing a cyclopropane ring in their structure (cyclopropane FA) have been found in a wide variety of bacteria, a number of protozoa, and Myriapoda. Little is known about cyclopropane FA in mammal, especially in human tissues. The present study deals with the identification of cyclopropane FA in adipose tissue and serum of humans and rats. Fatty acids extracted from the adipose tissue and serum obtained from obese women during bariatric surgery were methylated and analyzed on GC-MS. We have identified: cyclopropaneoctanoic acid 2-hexyl, cyclopropaneoctanoic acid 2-octyl, cyclopropanenonanoic acid, and 2-[[2-[(2-ethylcyclopropyl)methyl]cyclopropyl]methyl] acid in human adipose tissue. We confirmed the presence of cyclopropaneoctanoic acid 2-hexyl by derivatization of FA extracted from human adipose tissue to picolinyl esters. Cyclopropaneoctanoic acid 2-hexyl was the main cyclopropane FA (approximately 0.4 % of total fatty acids in human adipose tissue, and about 0.2 % of total fatty acids in the serum). In adipose tissue cyclopropaneoctanoic acid 2-hexyl was found mainly in triacylglycerols, whereas in serum in phospholipids and triacylglycerols. The cyclopropaneoctanoic acid 2-hexyl has also been found in serum, and adipose tissue of rats in amounts comparable to humans. The content of cyclopropaneoctanoic acid 2-hexyl decreased in adipose tissue of rats maintained on a restricted diet for 1 month. In conclusion, we demonstrated that cyclopropaneoctanoic acid 2-hexyl is present in human adipose tissue and serum. Adipose tissue cyclopropaneoctanoic acid 2-hexyl is stored mainly in triacylglycerols and the storage of this cyclopropane FA is affected by food restriction.

  4. Optical measurement of adipose tissue thickness and comparison with ultrasound, magnetic resonance imging, and callipers

    NASA Astrophysics Data System (ADS)

    Geraskin, Dmitri; Boeth, Heide; Kohl-Bareis, Matthias

    2009-07-01

    Near-infrared spectroscopy is used to quantify the subcutaneous adipose tissue thickness (ATT) over five muscle groups (vastus medialis, vastus lateralis, gastrocnemius, ventral forearm and biceps brachii muscle) of healthy volunteers (n=20). The optical lipid signal (OLS) was obtained from the second derivative of broad band attenuation spectra and the lipid absorption peak (λ=930 nm). Ultrasound and MR imaging as well as mechanical calliper readings were taken as reference methods. The data show that the OLS is a good predictor for ATT (<16 mm) with absolute and relative errors of <0.8 mm and <24%, respectively. The optical method compares favourably with calliper reading. The finding of a non-linear relationship of optical signal vs. ultrasound is explained by a theoretical two-layer model based on the diffusion approximation for the transport of photons. The crosstalk between the OLS and tissue hemoglobin concentration changes during an incremental cycling exercise was found to be small, indicating the robustness of OLS. Furthermore, the effect of ATT on spatially-resolved spectroscopy measurements is shown to decrease the calculated muscle hemoglobin concentration and to increase oxygen saturation.

  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. Adipose tissue engineering: state of the art, recent advances and innovative approaches.

    PubMed

    Tanzi, Maria Cristina; Farè, Silvia

    2009-09-01

    Adipose tissue is a highly specialized connective tissue found either in white or brown forms, the white form being the most abundant in adult humans. Loss or damage of white adipose tissue due to aging or pathological conditions needs reconstructive approaches. To date, two main strategies are being investigated for generating functional adipose tissue: autologous tissue/cell transplantation and adipose tissue engineering. Free-fat transplantation rarely achieves sufficient tissue augmentation owing to delayed neovascularization, with subsequent cell necrosis and graft volume shrinkage. Tissue engineering approaches represent, instead, a more suitable alternative for adipose tissue regeneration; they can be performed either with in situ or de novo adipogenesis. In situ adipogenesis or transplantation of encapsulated cells can be useful in healing small-volume defects, whereas restoration of large defects, where vascularization and a rapid volumetric gain are strict requirements, needs de novo strategies with 3D scaffold/filling matrix combinations. For adipose tissue engineering, the use of adult mesenchymal stem cells (both adipose- and bone marrow-derived stem cells) or of preadipocytes is preferred to the use of mature adipocytes, which have low expandability and poor ability for volume retention. This review intends to assemble and describe recent work on this topic, critically presenting successes obtained and drawbacks faced to date.

  7. The role of brown adipose tissue in temperature regulation. [of hibernating and hypothermic mammals

    NASA Technical Reports Server (NTRS)

    Smith, R. E.

    1973-01-01

    The thermogenetic capacities of brown adipose tissue were studied on marmots, rats and monkeys in response to cold exposure. All experiments indicated that the brown fat produced heat and slowed the cooling of tissues.

  8. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    ERIC Educational Resources Information Center

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)</