We aimed to elucidate the role of vitamin D supplementation on adipokines through a systematic review and a meta-analysis of randomized placebo-controlled trials (RCTs). The search included PUBMED, Scopus, Web of Science and Google Scholar through July 1st, 2015. Finally we identified 9 RCTs and 484 participants. Meta-analysis of data from 7 studies did not find a significant change in plasma adiponectin concentrations following vitamin D supplementation (mean difference [MD]: 4.45%, 95%CI: -3.04, 11.93, p=0.244; Q=2.18, I(2)=0%). In meta-regression, changes in plasma adiponectin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: 0.25; 95%CI: -0.69, 1.19; p=0.603) and changes in serum 25-hydroxy vitamin D [25(OH)D] levels (slope: -0.02; 95%CI: -0.15, 0.12; p=0.780). Meta-analysis of data from 6 studies did not find a significant change in plasma leptin concentrations following vitamin D supplementation (MD: -4.51%, 95%CI: -25.13, 16.11, p=0.668; Q=6.41, I(2)=21.97%). Sensitivity analysis showed that this effect size is sensitive to one of the studies; removing it resulted in a significant reduction in plasma leptin levels (MD: -12.81%, 95%CI: -24.33, -1.30, p=0.029). In meta-regression, changes in plasma leptin concentrations following vitamin D supplementation were found to be independent of treatment duration (slope: -1.93; 95%CI: -4.08, 0.23; p=0.080). However, changes in serum 25(OH)D were found to be significantly associated with changes in plasma leptin levels following vitamin D supplementation (slope: 1.05; 95%CI: 0.08, 2.02; p=0.033). In conclusion, current data did not indicate a significant effect of vitamin D supplementation on adiponectin and leptin levels. / Revisión por pares

Submitted by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T18:24:07Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) VANESSA RETAMOSO.pdf: 592024 bytes, checksum: c46345bdfcf46ad95175002ba7a6262e (MD5) / Approved for entry into archive by Marcos Anselmo (marcos.anselmo@unipampa.edu.br) on 2016-09-22T18:24:24Z (GMT) No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) VANESSA RETAMOSO.pdf: 592024 bytes, checksum: c46345bdfcf46ad95175002ba7a6262e (MD5) / Made available in DSpace on 2016-09-22T18:24:24Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) VANESSA RETAMOSO.pdf: 592024 bytes, checksum: c46345bdfcf46ad95175002ba7a6262e (MD5) Previous issue date: 2016-05-05 / A prevalência da síndrome metabólica (SM) vem crescendo com o passar dos anos, juntamente com a epidemia da obesidade na população de idosos. O atual processo de transição nutricional contribui para acelerar ainda mais o aparecimento de alterações metabólicas que levam ao diagnóstico da SM, e uma série de fatores ambientais se relacionam com o aparecimento desta doença. Hábitos alimentares inadequados os quais se destacam o consumo excessivo de alimentos refinados, ricos em gordura e uma ingestão reduzida de alimentos integrais, frutas, legumes e verduras, torna a dieta pobre em valor nutricional, possivelmente relacionado à incidência de SM. Além dos fatores mencionados a SM também pode estar relacionada a fatores genéticos, onde os níveis de adiponectina ao contrário das outras substâncias liberadas pelo tecido adiposo agem como fator de proteção para doenças cardiovasculares. Desta forma o presente estudo visou analisar uma possível associação entre o polimorfismo da ADIPOQ 45 T>G, dieta usual e SM em idosos. Foram avaliados marcadores inflamatórios e bioquímicos comparados com grupos de idosos (idade ≥60anos) com e sem SM, além das medidas antropométricas de peso, altura e circunferência da cintura, o polimorfismo ADIPOQ 45 T>G foi determinado através de PCR-RFLP e o consumo alimentar investigado através de questionário de frequência alimentar. Participaram do estudo 111 idosos, onde 53,2% sem SM e 46,8% com SM. Nossos principais resultados mostram que houve relação significativa entre o consumo habitual de leite para o grupo que possuía SM (p<0,05), os níveis de HDL-c, glicose, triglicerídeos e as medidas de peso, altura, circunferência da cintura e pressão arterial diastólica apresentaram-se alteradas no grupo com SM. Houve associação entre o consumo alimentar habitual de carnes brancas e legumes com os haplótipos TG e GG. Conclui-se que não há associação entre o polimorfismo ADIPOQ 45 T>G e SM no grupo de idosos estudados, contudo a relação entre consumo habitual de determinados grupos alimentares e ADIPOQ indicam a necessidade de estudos complementares melhor elucidação desta relação. / The prevalence of metabolic syndrome (MS) has been growing over the years, along with an epidemic obesity in the elderly population. The current nutritional transition contributes accelerate the beginning of metabolic alterations that leads to the diagnosis of MS, and a variety of environmental factors relate to the onset of this disease. Poor eating habits which stand out excessive consumption of refined foods, high in fat and low intake of whole foods, fruits and vegetables, makes the diet low in nutritional value, possibly related to the incidence of MS. In addition to the factors mentioned MS may also be related to genetic factors, which adiponectin levels unlike other substances released by adipose tissue act as a protective factor for cardiovascular disease. Thus, the present study aims to examine a possible association between the polymorphism ADIPOQ 45 T> G, usual diet and MS in the elderly. Inflammatory and biochemical markers compared with older age groups were analyzed (age ≥60 anos) with and without the MS. Also in addition to the anthropometric measurements of weight, height and waist circumference, the ADIPOQ polymorphism 45 T> G was determined by PCR-RFLP and investigated dietary intake through food frequency questionnaire. The study included 111 elderly people, where 53.2% had not the MS and 46.8% had such decease. Our main results show that there was significant relationship between habitual consumption of milk for the group had MS (p <0.05), HDL-C levels, glucose, triglycerides and weight, height, waist circumference and diastolic blood pressure had to be altered in patients with the MS. There was an association between habitual dietary intake of white meat and vegetables with the haplotype TG and GG. We conclude that there is no association between the polymorphism ADIPOQ 45 T> G and MS in the group of elderly studied, however the relationship between habitual consumption of certain food groups and ADIPOQ indicate the need for further studies elucidate this relationship.

Le tissu adipeux, outre son rôle de réserve énergétique, joue un rôle essentiel dans le contrôle de l'homéostasie du métabolisme ainsi que dans la physiopathologie de différentes affections, telles que diabète de type 2, dyslipidémies ou athérosclérose. Ce rôle est en partie assuré par des substances sécrétées par le tissu adipeux dans le plasma et regroupées sous le terme d'adipokines. Il s'agit notamment du tumor necrosis factor (TNF)-α, de la leptine, résistine ou encore de l'adiponectine (ApN). L'ApN se distingue des autres adipokines car, contrairement à l'augmentation des concentrations plasmatiques de leptine, de résistine ou de TNF-α observée dans l'obésité, ses taux sont corrélés de façon négative à l'indice de masse corporelle et de façon positive à la sensibilité à l'insuline. L'ApN joue donc un rôle très important dans la modulation du métabolisme lipidique et glucidique et/ou dans la régulation de l'insulinosensibilité. Afin d'étudier les répercussions in vivo d'une expression précoce et chronique d'ApN spécifiquement dans le tissu adipeux, nous avons créé des souris transgéniques où l'ADNc de l'ApN (forme complète) a été placé sous contrôle d'un promoteur adipocytaire. Selon le nombre de copies du transgène intégré dans le génome, nous obtenons des phénotypes forts différents, voire opposés. Dans notre étude réalisée chez des souris ayant intégré un nombre modeste de copies du transgène (6 copies), nous observons une diminution de l'expression (ARNm) et du contenu protéique en ApN du tissu adipeux. Ce rétrocontrôle négatif de la production d'ApN est associé à un phénotype d'intolérance au glucose et d'insulinorésistance, à une adiposité accrue probablement suite à la faible expression des molécules impliquées dans la dissipation d'énergie et à l'accroissement de la lipogenèse. Nous assistons également à une faible expression d'AdipoR2, l'isoforme du récepteur responsable de l'action de l'ApN sous sa forme complète. A l'inverse, les souris ayant intégré un grand nombre (100) de copies du transgène présentent une augmentation de l'expression et du contenu en ApN dans différents sites du tissu adipeux blanc (le phénomène de rétrocontrôle de l'ApN endogène étant masqué par une surexpression plus prononcée de l'ApN exogène). Cette surexpression d'ApN est associée à une amélioration attendue de l'homéostasie glucidique et du profil lipidique. De plus, ces souris présentent une nette réduction de leur adiposité secondaire à une augmentation de la dépense énergétique et, fait original, à une diminution de la différenciation adipocytaire. Le remaniement du tissu adipeux résulte en de petits adipocytes, caractérisés par une diminution d'expression des enzymes lipogéniques et de marqueurs adipocytaires, ainsi que par une augmentation d'expression de protéines découplantes et d'un marqueur préadipocytaire (Pref-1). Chez ces souris, l'expression d'AdipoR2 est accrue, peut-être suite à une réduction locale de TNFα. / Adipose tissue regulates fuel homeostasis and is implicated in the pathophysiology of several components of the metabolic syndrome, such as diabetes of type 2, dyslipidemia or atherosclerosis. The secretion of regulatory peptides, often referred to as adipocytokines, mediates in part these adipose functions. The best-known adipokines include tumor necrosis factor α (TNFα), leptin, resistin and adiponectin (ApN). Unlike the other adipokines, which are elevated in obesity, plasma ApN levels are negatively correlated to body mass index and positively to insulin sensitivity. Thus, ApN plays a fundamental role in regulating lipid and glucose metabolism, and insulin action. To study in vivo the chronic effects of ApN specifically on adipose tissue, we generated transgenic mouse lines allowing persistent and moderate expression of native full-length ApN targeted to white adipose tissue. We have obtained two different phenotypes according to the number of transgene copies integrated into the genome In our mouse lines with a modest copy number (6), we observed a decrease of expression (ARNm) and protein content of ApN in adipose tissue. This negative feedback on ApN production was associated with a phenotype of the glucose intolerance and insulin resistance, and with an increased adiposity due to low expression of molecules involved in energy expenditure, and to increased lipogenesis. We also observed a weak expression of AdipoR2, the receptor isoform responsible for the action of full-length ApN. On the contrary, mice with a high copy number (100), clearly overexpressed ApN in various sites of white fat (the downregulation of endogenous ApN being masked by the marked overexpression of exogenous ApN). This overexpression of ApN was associated with an expected improvement of glucose homeostasis and lipid profile. Furthermore, these mice showed reduced adiposity, due to increased energy expenditure and decreased adipocyte differentiation. Adipose tissue remodelling resulted in smaller (younger) adipocytes, characterized by a decrease of lipogenic enzymes and of adipocyte markers, as well as by an increased expression of uncoupling proteins and a preadipocyte marker (Pref-1). In this group of mice, the expression of AdipoR2 was enhanced possibly because of a local reduction of TNFα.

The purpose of this biobehavioral study was to explore relationships between psychosocial stressors of acculturation, acculturative stress, and metabolic markers of leptin and adiponectin in Mexican American women with and without gestational diabetes mellitus (GDM). A case control design was used for this secondary analysis which included a sample of 38 pregnant women with GDM and 38 healthy controls without GDM, who were matched on age and BMI status. Subjects completed two surveys—the Multidimensional Acculturation Scale II (MASII) and the Multidimensional Acculturative Stress Inventory (MASI)—which measured acculturation and acculturative stress. Descriptive statistics, Pearson r correlations, and independent sample t-tests were used to analyze the data. The results from this study indicated that significant relationships do exist between some of the variables of interest; however, there were no overall significant differences found between women with and without gestational diabetes. These mixed results may be an indicator of a need to further explore these concepts. / text

Background: It has been reported that the ratio of limb fat to trunk fat (LF/TF) is associated with markers of cardiometabolic risk in elderly men and women. However, it is unknown if LF/TF is associated with cardiometabolic risk beyond that explained by LF and TF independently. Objective: To determine if LF/TF is associated with markers of cardiometabolic risk in elderly men and women after control for LF and TF. A secondary objective was to examine the independent associations of LF and TF with markers of cardiometabolic risk. Methods: Subjects included abdominally obese men (n=58) and women (n=78) between 60 and 80 years of age. Regional adiposity was quantified using magnetic resonance imaging. Insulin resistance, fasting glucose, HDL-cholesterol, plasma triglycerides and adiponectin were determined. Regression analyses and partial correlations were used to assess the independent associations between variables. Results: After control for potential confounders, TF was positively associated with fasting glucose, insulin resistance and plasma triglycerides, and negatively associated with HDL-cholesterol (p<0.05). These associations were strengthened after further control for LF (p<0.05). LF was not associated with any marker of cardiometabolic risk after control for potential confounders (p>0.05). However, after further control for TF, LF was positively associated with HDL-cholesterol and negatively associated with plasma triglycerides (p<0.05). Plasma adiponectin was independently associated with both LF and TF in elderly women (p<0.05) but was not independently associated with either depot in elderly men (p>0.05). LF/TF was not associated with any marker of cardiometabolic risk after control for LF and TF. Conclusions: These results suggest that it is the absolute, rather than relative amounts of LF and TF which have the greatest influence on cardiometabolic risk in elderly men and women. Further, these results suggest that the associations between plasma adiponectin and regional adiposity are significantly influenced by sex in elderly men and women. / Thesis (Master, Kinesiology & Health Studies) -- Queen's University, 2008-12-05 16:08:10.868

Adiponectin (ADP) is an adipokine, which acts as an insulin sensitizing hormone. Recent studies have shown that adiponectin receptors (AdipoR1, AdipoR2) are present in the CNS; however, there is some debate as to whether or not ADP crosses the blood brain barrier (BBB). Circumventricular organs (CVO) are CNS sites outside the BBB, and thus represent sites at which circulating adiponectin may act to influence the CNS without having to cross the BBB. The subfornical organ (SFO) is a CVO that is responsive to a number of different circulating satiety signals including amylin, CCK, and ghrelin. We report here that the SFO also shows a high density of mRNA for both adiponectin receptors. These observations support the concept that the SFO may be a key player in sensing circulating ADP. To test the hypothesis that ADP influences the excitability of SFO neurons, we used current-clamp electrophysiology on dissociated SFO neurons to observe changes in membrane potential. ADP (10 nM) application effected the excitability of SFO neurons, where the cells either depolarized (8.9±0.9 mV, 21 of 97 cells) or hyperpolarized (-8.0±0.5 mV, 34 of 97 cells). Using single-cell RT-PCR we found that the majority of the responsive neurons expressed AdipoR1 or R2 and the non-responsive neurons expressed neither. In view of the recognized role of ADP in the regulation of energy balance, we next examined the effects of food deprivation for 48 hours on ADP signaling in the SFO. Our previous microarray analysis of SFO showed increases in AdipoR2 mRNA, with no significant change in AdipoR1 mRNA. We have also assessed the effects of such changes in receptor expression on ADP signaling in SFO neurons using calcium imaging and patch clamp techniques. In SFO neurons obtained from control animals, ADP induced increases in intracellular Ca2+ were observed in 25% of cells, while following food deprivation 0% of cells showed this response. Furthermore, 77% of neurons from starved animals showed clear depolarization, while no hyperpolarizing responses were observed. The results presented in this study suggest that adiponectin modulates the excitability of SFO neurons and that the response to ADP changes during starvation. / Thesis (Master, Neuroscience Studies) -- Queen's University, 2008-09-17 18:07:35.099

Adiponectin regulates feeding behavior, energy expenditure and autonomic function through the activation of two receptors present in nuclei throughout the central nervous system, however much remains unknown about the mechanisms mediating these effects. Here I investigate the actions of adiponectin in autonomic centers of the hypothalamus (the paraventricular nucleus) and brainstem (the nucleus of the solitary tract) through examining molecular, electrical, hormonal and physiological consequences of peptidergic signalling. RT-PCR and in situ hybridization experiments demonstrate the presence of AdipoR1 and AdipoR2 mRNA in the paraventricular nucleus. Investigation of the electrical consequences following receptor activation in the paraventricular nucleus indicates that magnocellular-oxytocin cells are homogeneously inhibited while magnocellular-vasopressin neurons display mixed responses. Single cell RT-PCR analysis shows oxytocin neurons express both receptors while vasopressin neurons express either both receptors or one receptor. Co-expressing oxytocin and vasopressin neurons express neither receptor and are not affected by adiponectin. Median eminence projecting corticotropin releasing hormone neurons, brainstem projecting oxytocin neurons, and thyrotropin releasing hormone neurons are all depolarized by adiponectin. Plasma adrenocorticotropin hormone concentration is increased following intracerebroventricular injections of adiponectin. I demonstrate that the nucleus of the solitary tract, the primary cardiovascular regulation site of the medulla, expresses mRNA for AdipoR1 and AdipoR2 and mediates adiponectin induced hypotension. Adiponectin has electrical effects on a majority of medial solitary tract neurons and depolarizes those expressing mRNA for the hypotensive neuropeptide Y, revealing a central mechanism to modulate blood pressure. Finally, I show that adiponectin controls paraventricular nucleus neuron excitability by either inhibiting a tetraethyl ammonium-sensitive potassium current thereby depolarizing neurons or activating a glibenclamide-sensitive voltage independent potassium current hyperpolarizing neurons. Therefore, adiponectin differentially modulates potassium current to confer its central effects. These results are the first to show the physiological and electrical actions of adiponectin on individual neurons in blood brain barrier protected central autonomic nuclei. This thesis provides a framework for how adiponectin acts centrally to coordinate whole body energy homeostasis and feeding behavior in the rat. / Thesis (Ph.D, Physiology) -- Queen's University, 2009-09-15 16:50:13.933

Background.  Sepsis is a syndrome associated with high mortality rates, substantial morbidity and high costs of care. The incidents of sepsis is reported to be high and controversy exists whether gender affect severity or outcome. Little is known about factors determining suscepti­bility for developing the syndrome and severity of the syndrome once developed. Early detection and adequate antibiotic administration are the mainstay of treatment and means to identify patients with particular high risk of adverse outcome are desirable. There are data to suggest that the course of sepsis and outcome from the syndrome may be influenced by inherited differences in the immunological response among humans Aims: Paper I: Assess incidence and outcome for ICU-treated sepsis patients in this region; Paper II: Assess if there are gender differences related to characteristics, aspects of treatment or out­come in sepsis in this region. Paper III: Assess the association of baseline levels of leptin and adiponectin and future sepsis event, and association of these adipokines in the cute phase and sepsis severity and outcome. Paper IV: Assess association of baseline levels of mannose-binding lectin (MBL) and future sepsis event, and MBL levels in the acute phase in relation to sepsis severity and outcome. Results. Paper I:  Overall ICU mortality rate was 25%, while the ICU mortality for patients with septic shock was 58% in this retrospective single university hospital cohort analysis. Cardio­vascular disease and diabetes were the most prevalent comorbidities among patients who died during hospital stay.  Paper II:  No gender-related differences in mortality or length of stay was found in this prospective single center observational study. Differences in aspects of treatment were related to differences in site of infection. Men had more often infections in skin and skin-structures, whereas women more often had abdominal infections. Early organ dysfunction asses­sed as SOFA score at admission was a stronger predictor for hospital mortality for women than for men. The discrepancy was related to the SOFA coagulation-sub score.  Paper III: In this nes­ted case-referent study hyperleptinemia at baseline predicted a first-ever sepsis event, even after adjustment for BMI and other cardiovascular risk factors. Hyperleptinemia in the acute sepsis phase was associated with reduced risk of in-hospital death in men, but associated with increased risk of in-hospital   death in women.  Paper IV: In the same matched cohort as in Paper III high baseline levels of MBL predicted a first ever sepsis event. High MBL levels in the acute phase or an increase from baseline to the acute phase associate with increased in-hospital death in women but not in men. Low MBL levels was not identified as a risk for acute sepsis or in-hospital death. Conclusions. Mortality from severe sepsis is high, equally affecting men and women. There are differences in patient characteristics and inflammatory markers, which associate with in-hospital mortality differentially in men and women. Aspects of gender should be mandatory, and genetic analysis are desired in future sepsis research.

Thesis (M.Sc.). / Written for the Dept. of Biochemistry. Title from title page of PDF (viewed 2008/05/13). Includes bibliographical references.

Thesis (Ph. D.)--University of Washington, 2007. / Vita. Includes bibliographical references (leaves 49-56).