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Kristy L. Meadows – One of the best experts on this subject based on the ideXlab platform.

  • Ischemic stroke and select Adipose-Derived and sex Hormones: a review
    Hormones, 2018
    Co-Authors: Kristy L. Meadows
    Abstract:

    Ischemic stroke is the fifth leading cause of death in the USA and is the leading cause of serious, long-term disability worldwide. The principle sex Hormones (estrogen, progesterone, and testosterone), both endogenous and exogenous, have profound effects on various stroke outcomes and have become the focus of a number of studies evaluating risk factors and treatment options for ischemic stroke. In addition, the expression of other Hormones that may influence stroke outcome, including select Adipose-Derived Hormones (adiponectin, leptin, and ghrelin), can be regulated by sex Hormones and are also the focus of several ischemic stroke studies. This review aims to summarize some of the preclinical and clinical studies investigating the principle sex Hormones, as well as select Adipose-Derived Hormones, as risk factors or potential treatments for ischemic stroke. In addition, the potential for relaxin, a lesser studied sex hormone, as a novel treatment option for ischemic stroke is explored.

Mykola Ya Spivak – One of the best experts on this subject based on the ideXlab platform.

  • The efficacy of probiotics for monosodium glutamate-induced obesity: dietology concerns and opportunities for prevention
    EPMA Journal, 2014
    Co-Authors: Oleksandr A Savcheniuk, Oleksandr V Virchenko, Tetyana M Falalyeyeva, Tetyana V Beregova, Lidia P Babenko, Liudmyla M Lazarenko, Olga M Demchenko, Rostyslav V Bubnov, Mykola Ya Spivak
    Abstract:

    Introduction Obesity becomes endemic today. Monosodium glutglutamate was proved as obesogenic food additive. Probiotics are discussed to impact on obesity development. Aims and objectives The aim was to study the effects of probiotics on the development of monosodium glutglutamate (MSG)-induced obesity in rats. Material and methods We included 45 Wistar male rats and divided into three groups ( n  = 15). Newborn rats of group 1 (control) received subcutaneously 8 μl/g saline. Group 2 received 3 to 4 mg/g MSG subcutaneously on the second, fourth, sixth, eighth and tenth day of life. Within 4 months after birth, rats were on a standard diet. Group 3 received an aqueous solution of probiotics mixture (2:1:1 Lactobacillus casei IMVB-7280, Bifidobacterium animalis VKL, B. animalis VKB) at the dose of 5 × 10^9 CFU/kg (50 mg/kg) intragastrically. Administration of probiotics was started at the age of 4 weeks just after weaning and continued for 3 months during 2-week courses. Group 2 received intragastrically 2.5 ml/kg water. Organometric and biochemical parameters in all groups of rats were analyzed over 4 months. The concentration of adiponectin was determined in serum, and leptin – in adipose tissue. Results Administration of MSG led to the development of obesity in rats; body weight had increased by 7.9% vs controls ( p < 0.05); body length had increased by 5.4% ( p < 0.05). Body mass index and Lee index and visceral fat mass had increased ( p < 0.001). Under the neonatal injection of MSG, the concentration of total cholesterol, triglycerides, VLDL cholesterol and LDL cholesterol significantly increased ( p < 0.001), in comparison with controls. Adipose-Derived Hormones changed in MSG obesity rats: adiponectin decreased by 58.8% ( p < 0.01), and leptin concentration in adipose tissue had increased by 74.7% ( p < 0.01). The probiotic therapy of rats from group 3 prevented obesity development. Parameters of rats treated with probiotic mixture did not differ from that in the control. Conclusions The introduction of MSG to newborn rats caused the obesity in adulthood. Periodic administration of probiotic mixture to rat injected with MSG neonatally resulted in recovery of lipid metabolism and prevention of the obesity development.

Cereijo Téllez Rubén – One of the best experts on this subject based on the ideXlab platform.

  • Nous actors moleculars en la fisiologia del teixit adipós i patologies associades
    'Edicions de la Universitat de Barcelona', 2016
    Co-Authors: Cereijo Téllez Rubén
    Abstract:

    [cat] El teixit adipós ha passat d’ésser considerat un mer reservori d’energia a un òrgan complex, implicat de forma activa en l’homeòstasi energètica i amb funcions endocrines de rellevància. Les malalties en què hi està involucrat per excés (obesitat) o manca (lipodistròfies) provoquen, coherentment, alteracions metabòliques greus que suposen un risc per a la salut. A nivell de balanç energètic, dos tipus de teixit adipós disposen de funcions diametralment oposades dins l’organisme: El teixit adipós blanc (TAB) té com a objectiu emmagatzemar reserves lipídiques en condicions d’excés de nutrients i mobilitzar-les per a garantir el funcionament dels diversos òrgans, mentre que el teixit adipós marró (TAM) pot dissipar energia en forma de calor per tal de regular la temperatura corporal. Tot i que se n’hi creia absent, el recent descobriment de la presència de TAM i de la capacitat d’inducció del mateix (“browning”) en individus humans adults ha despertat un creixent interès en aquest teixit, donada la potencial aplicació del seu reclutament com a teràpia contra l’obesitat. Les cèl·lules majoritàries del teixit adipós i que realitzen les seves funcions principals són els adipòcits, blancs en el cas del TAB o marrons clàssics i beix/brite en el del TAM. No obstant, aquests estan en estreta comunicació amb altres tipus cel·lulars, especialment amb les cèl·lules del sistema immunitari, les quals produeixen diversos factors bioactius. La producció de mediadors inflamatoris en situacions patològiques i d’estrès altera la biologia dels adipòcits i la secreció de llurs Hormones (adipocines), afectant l’organisme a nivell global, mentre que en condicions de salut mediadors antiinflamatoris milloren la funció adipocitària. A la present tesi doctoral s’analitzà el patró d’expressió gènica als fenòmens de lipomatosi associats a una lipodistròfia d’origen genètic (FPLD2) i a l’associada a la infecció pel virus de la immunodeficiència humana i a la teràpia antiretroviral d’alta activitat (HALS). També s’identifiquen noves proteïnes secretables produïdes preferentment pel TAM respecte al TAB a partir d’aproximacions in silico amb la seva posterior validació funcional in vitro i in vivo. Els lipomes són insults patofisiològics ocasionals en les lipodistròfies, però estan menys caracteritzats que d’altres de concomitants. En general, presentaren alteracions heterogènies, especialment a nivell de cicle cel·lular i senescència, tant en el cas de l’FPLD2 com en la HALS. En aquesta darrera, la comparació entre els lipomes pertanyents a ubicacions anatòmiques diverses i a la zona dorsocervical va permetre detectar diferències entre tots dos tipus d’insults quant a l’existència d’un fenotip de TAM clàssic aberrant, ZIC1+, als segons, tot posant de manifest la complexitat de les alteracions en la biologia del teixit adipós en aquestes malalties. Emprant aproximacions bioinformàtiques s’identificaren diverses proteïnes secretades sobreexpressades al TAM, de les quals es procedí a la caracterització d’una en concret. CXCL14 és una quimiocina pleiotròpica amb funcions metabòliques descrites a nivell de TAB, si bé el seu paper al TAM era, fins el moment, desconegut. Com es demostrà, CXCL14 és produïda pels adipòcits marrons i la seva expressió i secreció són induïdes per estímuls simpàtics. Els animals deficients per a aquest gen mostraven alteracions en transcrits de termogènesi, de metabolisme lipídic i d’infiltració immunitària, les quals es traduïen en una disminució de la funció termogènica del TAM. Anàlisis de quimiotaxi i d’expressió gènica revelaren que la CXCL14 produïda pels adipòcits marrons realitza accions de tipus paracrí, actuant sobre macròfags activats alternativament. D’altra banda, l’administració continuada de CXCL14 exògena activà el browning als dipòsits de TAB, quelcom que suggereix accions també endocrines. En conjunt, aquests resultats destaquen el paper de l’adipocina marró CXCL14 en les interaccions teixit adipós-sistema immunitari i en la comunicació intra i intertissular que requereix la coordinació de tota maquinària termogènica.[eng] Adipose tissue was hitherto considered just an energy storage site, but it is currently widely recognized as a dynamic homeostatic organ with relevant endocrine properties. The main function of white adipadipose tissue (WAT) is to store and release lipids on demand, whereas brown adipose tissue (BAT) dissipates energy as heat. The discovery of thermally-inducible BAT in human adult subjects has revamped research on it since this ability could be harnessed to improve obesity. Adipocytes, white in BAT and classic brown or beige/brite in BAT, are the main functional actors in adipose tissue, but a close cross-talk with other cell types, especially those of the immune system, is present. Accordingly, stress and production of inflammatory cytokines in pathological conditions alters the biology of adipocytes and the secretion of Adipose-Derived Hormones (adipokines), while in healthy adipose tissue immune cell-derived anti-inflammatory cytokines improve adipose functions. The current doctoral thesis aims to assess alterations in the transcriptional signature of lipomas in lipodystrophies and to identify novel secretable proteins preferentially produced by BAT. Lipomas are a recurring symptom in lipodystrophies, but they have been poorly characterized to date. In general, lipomas exhibited heterogenic alterations in respect to healthy and lipoatrophic adipose tissue, mostly related to cell cycle control. In the case of HIV-1- and HAART-associated lipodystrophy, a differential expression pattern between dorso-cervical lipomas and those arising at different anatomical sites revealed the existence of a brown-like molecular signature in the former. Several proteins were identified in silico as potential brown adipokines. Among them, chemokine CXCL14 was considered to be a promising candidate, since validation studies revealed differential expression between WAT and BAT, transcriptional induction in the presence of thermogenic stimuli and release by brown adipocytes. Brown adipocyte-derived CXCL14 was able to blunt proinflammatory, classical macrophage activation and to recruit alternatively activated macrophages, which are known to be involved in BAT activation. Coherently, continuous external administration of CXCL14 increased browning and alternatively activated macrmacrophage abundance of WAT depots, whereas CXCL14 knock-out mice exhibited compromised expression of transcripts related to BAT function and immune infiltration. These results indicate an instrumental role for CXCL14 in coordinating adaptive thermogenesis

  • Nous actors moleculars en la fisiologia del teixit adipós i patologies associades
    'Edicions de la Universitat de Barcelona', 2015
    Co-Authors: Cereijo Téllez Rubén
    Abstract:

    El teixit adipós ha passat d’ésser considerat un mer reservori d’energia a un òrgan complex, implicat de forma activa en l’homeòstasi energètica i amb funcions endocrines de rellevància. Les malalties en què hi està involucrat per excés (obesitat) o manca (lipodistròfies) provoquen, coherentment, alteracions metabòliques greus que suposen un risc per a la salut. A nivell de balanç energètic, dos tipus de teixit adipós disposen de funcions diametralment oposades dins l’organisme: El teixit adipós blanc (TAB) té com a objectiu emmagatzemar reserves lipídiques en condicions d’excés de nutrients i mobilitzar-les per a garantir el funcionament dels diversos òrgans, mentre que el teixit adipós marró (TAM) pot dissipar energia en forma de calor per tal de regular la temperatura corporal. Tot i que se n’hi creia absent, el recent descobriment de la presència de TAM i de la capacitat d’inducció del mateix (“browning”) en individus humans adults ha despertat un creixent interès en aquest teixit, donada la potencial aplicació del seu reclutament com a teràpia contra l’obesitat. Les cèl·lules majoritàries del teixit adipós i que realitzen les seves funcions principals són els adipòcits, blancs en el cas del TAB o marrons clàssics i beix/brite en el del TAM. No obstant, aquests estan en estreta comunicació amb altres tipus cel·lulars, especialment amb les cèl·lules del sistema immunitari, les quals produeixen diversos factors bioactius. La producció de mediadors inflamatoris en situacions patològiques i d’estrès altera la biologia dels adipòcits i la secreció de llurs Hormones (adipocines), afectant l’organisme a nivell global, mentre que en condicions de salut mediadors antiinflamatoris milloren la funció adipocitària. A la present tesi doctoral s’analitzà el patró d’expressió gènica als fenòmens de lipomatosi associats a una lipodistròfia d’origen genètic (FPLD2) i a l’associada a la infecció pel virus de la immunodeficiència humana i a la teràpia antiretroviral d’alta activitat (HALS). També s’identifiquen noves proteïnes secretables produïdes preferentment pel TAM respecte al TAB a partir d’aproximacions in silico amb la seva posterior validació funcional in vitro i in vivo. Els lipomes són insults patofisiològics ocasionals en les lipodistròfies, però estan menys caracteritzats que d’altres de concomitants. En general, presentaren alteracions heterogènies, especialment a nivell de cicle cel·lular i senescència, tant en el cas de l’FPLD2 com en la HALS. En aquesta darrera, la comparació entre els lipomes pertanyents a ubicacions anatòmiques diverses i a la zona dorsocervical va permetre detectar diferències entre tots dos tipus d’insults quant a l’existència d’un fenotip de TAM clàssic aberrant, ZIC1+, als segons, tot posant de manifest la complexitat de les alteracions en la biologia del teixit adipós en aquestes malalties. Emprant aproximacions bioinformàtiques s’identificaren diverses proteïnes secretades sobreexpressades al TAM, de les quals es procedí a la caracterització d’una en concret. CXCL14 és una quimiocina pleiotròpica amb funcions metabòliques descrites a nivell de TAB, si bé el seu paper al TAM era, fins el moment, desconegut. Com es demostrà, CXCL14 és produïda pels adipòcits marrons i la seva expressió i secreció són induïdes per estímuls simpàtics. Els animals deficients per a aquest gen mostraven alteracions en transcrits de termogènesi, de metabolisme lipídic i d’infiltració immunitària, les quals es traduïen en una disminució de la funció termogènica del TAM. Anàlisis de quimiotaxi i d’expressió gènica revelaren que la CXCL14 produïda pels adipòcits marrons realitza accions de tipus paracrí, actuant sobre macròfags activats alternativament. D’altra banda, l’administració continuada de CXCL14 exògena activà el browning als dipòsits de TAB, quelcom que suggereix accions també endocrines. En conjunt, aquests resultats destaquen el paper de l’adipocina marró CXCL14 en les interaccions teixit adipós-sistema immunitari i en la comunicació intra i intertissular que requereix la coordinació de tota maquinària termogènica.Adipose tissue was hitherto considered just an energy storage site, but it is currently widely recognized as a dynamic homeostatic organ with relevant endocrine properties. The main function of white adipadipose tissue (WAT) is to store and release lipids on demand, whereas brown adipose tissue (BAT) dissipates energy as heat. The discovery of thermally-inducible BAT in human adult subjects has revamped research on it since this ability could be harnessed to improve obesity. Adipocytes, white in BAT and classic brown or beige/brite in BAT, are the main functional actors in adipose tissue, but a close cross-talk with other cell types, especially those of the immune system, is present. Accordingly, stress and production of inflammatory cytokines in pathological conditions alters the biology of adipocytes and the secretion of Adipose-Derived Hormones (adipokines), while in healthy adipose tissue immune cell-derived anti-inflammatory cytokines improve adipose functions. The current doctoral thesis aims to assess alterations in the transcriptional signature of lipomas in lipodystrophies and to identify novel secretable proteins preferentially produced by BAT. Lipomas are a recurring symptom in lipodystrophies, but they have been poorly characterized to date. In general, lipomas exhibited heterogenic alterations in respect to healthy and lipoatrophic adipose tissue, mostly related to cell cycle control. In the case of HIV-1- and HAART-associated lipodystrophy, a differential expression pattern between dorso-cervical lipomas and those arising at different anatomical sites revealed the existence of a brown-like molecular signature in the former. Several proteins were identified in silico as potential brown adipokines. Among them, chemokine CXCL14 was considered to be a promising candidate, since validation studies revealed differential expression between WAT and BAT, transcriptional induction in the presence of thermogenic stimuli and release by brown adipocytes. Brown adipocyte-derived CXCL14 was able to blunt proinflammatory, classical macrophage activation and to recruit alternatively activated macrophages, which are known to be involved in BAT activation. Coherently, continuous external administration of CXCL14 increased browning and alternatively activated macrmacrophage abundance of WAT depots, whereas CXCL14 knock-out mice exhibited compromised expression of transcripts related to BAT function and immune infiltration. These results indicate an instrumental role for CXCL14 in coordinating adaptive thermogenesis

Hyeong Rok Kim – One of the best experts on this subject based on the ideXlab platform.

  • Obesity-Related Colorectal Cancer: The Role of Leptin
    Annals of coloproctology, 2015
    Co-Authors: Hyeong Rok Kim
    Abstract:

    Obesity is linked to increased risk of colon cancer. Consequently, rising levels of obesity worldwide are likely to have a significant impact on obesity-related colon cancers in the decades to come. Understanding the molecular mechanisms whereby obesity increases the risk of colon cancer is, thus, a focus for research on strategies to prevent the increasing trend in obesity-related cancers. The epidemiological evidence clearly indicates common factors linking obesity and colon cancer. Both are associated with consumption of high-energy diets, a sedentary lifestyle, increased age and reduced consumption of fruit, vegetables and fiber [1-3]. All these factors influence adipose tissue, now firmly established as the body’s largest endocrine organ [4]. These factors have the potential to influence the production of Adipose-Derived Hormones and cytokines from the adipose organ [5-8]. Leptin and adiponectin are two of the most abundant and most investigated Adipose-Derived Hormones. Friedman and Halaas [9] positionally cloned the ob gene and demonstrated that it was encoded for a hormone that they called leptin (after the Greek ‘leptos’ for thin). The proposed role of leptin was as a growth factor in the colon, stimulating proliferation of the colon epithelium and inhibiting apoptosis. That leptin increased colon tumor growth in obese patients subsequent to the initiation of colon cancer. Leptin is important for colorectal cancer (CRC) growth in obese patients and acts as a growth factor for CRC at stages subsequent to tumor initiation in colorectal carcinogenesis [10]. However, leptin failed to promote the growth of colon cancer xenografts in nude mice and did not increase intestinal tumorigenesis in ApcMin/ + mice [11]. The present study also failed to demonstrate the impact of leptin for increasing tumorigenesis and improving the prognosis. Moreover, an inverse association of nodal stage with high leptin expression was found. Therefore, the authors concluded that a higher leptin expression level was a predictor of a better oncologic outcome and that high leptin expression in colorectal-cancer tissue might be a good prognostic factor. Assessment of leptin signaling in tumor tissue needs further investigation to determine its possible impact on prognosis [12]. The complexity of this issue is confounded by various aspects associated with leptin production and signaling in human coloncancer patients. Leptin receptors are expressed by normal colon epithelial cells in human subjects [13, 14]. High expression of the long-form signaling receptor, ObRb, has been associated with increased age, proximally-located tumors, and high levels of microsatellite instability and lymphocyte infiltration [13]. The impact of plasma leptin is confounded by inconsistent and conflicting data reported from studies on patients with colon cancer [15-20]. A more recent report failed to determine significant differences in serum leptin between patients with colon cancer and controls [15]. The conflicting reports may be due, in part, to cachexia and anorexia, which are common in patients with CRC [21]. Leptin expression in colon tissue may be positively correlated with tumor features that are associated with improved survival of patients with CRC [22]. At present, the significant relationship between leptin expression and clinicopathological details, such as tumor stage and prognosis, suggests a possible role for leptin as a novel growth factor driving the development and the progression of CRC. Large clinical studies are needed to determine the mechanisms underlying the effects of leptin on the development and the progression of CRC.

Jianhua Shao – One of the best experts on this subject based on the ideXlab platform.