Leptin, adiponectin, leptin to adiponectin ratio and insulin resistance in depressive women.

PubMed

Zeman, Miroslav; Jirak, Roman; Jachymova, Marie; Vecka, Marek; Tvrzicka, Eva; Zak, Ales

2009-01-01

Depressive disorder (DD) is associated with an increased risk of type 2 diabetes mellitus (DM2) and cardiovascular disease (CVD). It was suggested, that metabolic syndrome (MetS), cluster of metabolic and hormonal changes, such as insulin resistence (IR), abdominal obesity, dyslipidemia, arterial hypertension and elevated fasting glycaemia, could stand behind the connection. Recent findings have shown, that adipocytokines leptin and adiponectin might play a role in both depression and MetS. The aim of this pilot study was to observe the plasma concentrations of leptin, adiponectin, leptin-to-adiponectin ratio and indices of IR in women with depressive disorder. The plasma leptin, adiponectin, parameters of lipid and glucose homeostasis and indices of IR were investigated in a group of 38 women with DD. The results were compared with those of 38 healthy women of the control group, matched for age. Depressive women differed significantly from the controls in higher concentrations of plasma leptin (p <0.05), insulin (p <0.01), C-peptide (p <0.01), value of HOMA-IR (p <0.01), and the leptin-to-adiponectin ratio (p <0.05).The QUICKI index of insulin sensitivity was lower (p <0.01). HAM-D score of DD cases correlated negatively with adiponectin (r = - 0.3505; p < 0.05), independently of HOMA-IR. We have not found in DD group any differences between the drug free patients and those treated either with escitaloprame alone or in the combination with mirtazapine. The results of the pilot study presented support the hypothesis that at least part of DD cases has increased leptin serum levels and certain features of MetS. It could be the factor connecting depression with an increased risk of either DM2 or CVD.

Adiponectin, Leptin, and Yoga Practice

PubMed Central

Kiecolt-Glaser, Janice K.; Christian, Lisa M.; Andridge, Rebecca; Hwang, Beom Seuk; Malarkey, William B.; Belury, Martha A.; Emery, Charles F.; Glaser, Ronald

2012-01-01

To address the mechanisms underlying hatha yoga’s potential stress-reduction benefits, we compared adiponectin and leptin data from well-matched novice and expert yoga practitioners. These adipocytokines have counter-regulatory functions in inflammation; leptin plays a proinflammatory role, while adiponectin has anti-inflammatory properties. Fifty healthy women (mean age=41.32, range=30-65), 25 novices and 25 experts, provided fasting blood samples during three separate visits. Leptin was 36% higher among novices compared to experts, P = .008. Analysis of adiponectin revealed a borderline effect of yoga expertise, P = .08; experts’ average adiponectin levels were 28% higher than novices across the three visits. In contrast, experts’ average adiponectin to leptin ratio was nearly twice that of novices, P = .009. Frequency of self-reported yoga practice showed significant negative relationships with leptin; more weeks of yoga practice over the last year, more lifetime yoga sessions, and more years of yoga practice were all significantly associated with lower leptin, with similar findings for the adiponectin to leptin ratio. Novices and experts did not show even marginal differences on behavioral and physiological dimensions that might represent potential confounds, including BMI, central adiposity, cardiorespiratory fitness, and diet. Prospective studies addressing increased risk for type II diabetes, hypertension, and cardiovascular disease have highlighted the importance of these adipocytokines in modulating inflammation. Although these health risks are clearly related to more extreme values then we found in our healthy sample, our data raise the possibility that longer-term and/or more intensive yoga practice could have beneficial health consequences by altering leptin and adiponectin production. PMID:22306535

Association study of the HTR2C, leptin and adiponectin genes and serum marker analyses in clozapine treated long-term patients with schizophrenia.

PubMed

Klemettilä, J-P; Kampman, O; Seppälä, N; Viikki, M; Hämäläinen, M; Moilanen, E; Mononen, N; Lehtimäki, T; Leinonen, E

2015-02-01

Clozapine treatment is associated with weight gain and cardio-metabolic consequences among patients with schizophrenia. Polymorphisms of leptin, serotonin receptor HTR2C and adiponectin genes have been associated with antipsychotic-induced weight gain and metabolic comorbidity. However, the results of the studies so far are inconclusive. The aim of the present study was first to test for a possible role of serum leptin and adiponectin levels as a marker of weight gain in association with inflammatory cytokines/adipokines (IL-6, IL-1Ra, hs-CRP and adipsin), and second to study associations between SNPs LEP rs7799039 (-2548 A/G), ADIPOQ rs1501299 and HTR2C rs1414334 and weight gain and levels of leptin and adiponectin, in 190 patients with schizophrenia on clozapine treatment, with retrospectively assessed weight change and cross-sectionally measured cytokine levels. A strong association was found between serum levels of leptin and weight gain and cytokines/adipokines related to metabolic comorbidity, especially among female patients (in women leptin vs. weight gain, IL-6 and IL-1Ra, P<0.001; in men leptin vs. weight gain, P=0.026, leptin vs. IL-1Ra, P<0.001). In male patients low adiponectin level was a more specific marker of clozapine-induced weight gain (P=0.037). The results of the present study do not support a major role of SNPs LEP rs7799039, ADIPOQ rs1501299 and HTR2C rs1414334 in the regulation of weight gain or association of serum levels of leptin and adiponectin and corresponding studied SNPs in patients with schizophrenia on clozapine treatment. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Short communication: The association of adiponectin and leptin concentrations with prepartum dietary energy supply, parity, body condition, and postpartum hyperketonemia in transition dairy cows.

PubMed

Mann, S; Urh, C; Sauerwein, H; Wakshlag, J J; Yepes, F A Leal; Overton, T R; Nydam, D V

2018-01-01

Adipokines-hormones produced by adipose tissue-have important regulatory functions, and their concentrations can change around the time of calving when energy balance rapidly decreases. Hence, energy balance may be an important factor in determining the circulating concentrations of adipokines, particularly adiponectin and leptin. The objective of our study was to investigate the association between the level of energy fed to prepartum Holstein cows and circulating concentrations of adiponectin and leptin before and after calving. Holstein dairy cows entering second or greater lactation were fed either a controlled-energy diet formulated to supply approximately 100% of energy requirements (n = 28) or a high-energy diet formulated to supply approximately 150% of energy requirements throughout the entire dry period (n = 28). Serum samples were analyzed for adiponectin and leptin concentrations at 56, 28, 10, and 1 d prepartum as well as on d 1, 10, 21, and 42 postpartum using ELISA. Parity was dichotomized into cows entering second versus higher parity. Average peripartum body condition score (BCS) was computed from weekly measurements and dichotomized into animals with an average BCS of ≤3.25 and >3.25. In addition, cows were classified according to the occurrence of hyperketonemia (β-hydroxybutyrate concentrations ≥1.2 mmol/L at any time between 3 and 21 d in milk). Data were analyzed using repeated-measures ANOVA. Serum leptin but not adiponectin concentrations were associated with prepartum feeding level such that leptin concentrations increased transiently during the dry period in cows overfed energy, but concentrations were not different postpartum. Cows entering second parity had higher adiponectin and lower leptin concentrations compared with cows in higher parities. Cows that developed hyperketonemia postpartum had consistently lower adiponectin concentrations during the study period. Cows with average BCS >3.25 had higher leptin concentrations during

Adipokines in human reproduction.

PubMed

Dupont, Joëlle; Pollet-Villard, Xavier; Reverchon, Maxime; Mellouk, Namya; Levy, Rachel

2015-10-01

Adipose tissue communicates with other central and peripheral organs by the synthesis and release of substances called adipokines. The most studied adipokine is leptin but others have been recently identified including resistin, adiponectin, chemerin, omentin and visfatin. These adipokines have a critical role in the development of obesity-related complications and inflammatory conditions. However, they are also involved in other functions in the organism including reproductive functions. Indeed, many groups have demonstrated that adipokine receptors, such as adiponectin and chemerin, but also adipokines themselves (adiponectin, chemerin, resistin, visfatin and omentin) are expressed in human peripheral reproductive tissues and that these adipokines are likely to exert direct effects on these tissues. After a brief description of these new adipokines, an overview of their actions in different human reproductive organs (hypothalamus, pituitary, ovary, testis, uterus and placenta) will be presented. Finally, comments will be made on the eventual alterations of these adipokines in reproductive disorders, with special attention to polycystic ovary syndrome, a disease characterized by dysfunction of gonadal axis and systemic nerve endocrine metabolic network with a prevalence of up to 10% in women of reproductive age.

Differential adipokine receptor expression on circulating leukocyte subsets in lean and obese children.

PubMed

Keustermans, Genoveva; van der Heijden, Laila B; Boer, Berlinda; Scholman, Rianne; Nuboer, Roos; Pasterkamp, Gerard; Prakken, Berent; de Jager, Wilco; Kalkhoven, Eric; Janse, Arieke J; Schipper, Henk S

2017-01-01

Childhood obesity prevalence has increased worldwide and is an important risk factor for type 2 diabetes (T2D) and cardiovascular disease (CVD). The production of inflammatory adipokines by obese adipose tissue contributes to the development of T2D and CVD. While levels of circulating adipokines such as adiponectin and leptin have been established in obese children and adults, the expression of adiponectin and leptin receptors on circulating immune cells can modulate adipokine signalling, but has not been studied so far. Here, we aim to establish the expression of adiponectin and leptin receptors on circulating immune cells in obese children pre and post-lifestyle intervention compared to normal weight control children. 13 obese children before and after a 1-year lifestyle intervention were compared with an age and sex-matched normal weight control group of 15 children. Next to routine clinical and biochemical parameters, circulating adipokines were measured, and flow cytometric analysis of adiponectin receptor 1 and 2 (AdipoR1, AdipoR2) and leptin receptor expression on peripheral blood mononuclear cell subsets was performed. Obese children exhibited typical clinical and biochemical characteristics compared to controls, including a higher BMI-SD, blood pressure and circulating leptin levels, combined with a lower insulin sensitivity index (QUICKI). The 1-year lifestyle intervention resulted in stabilization of their BMI-SD. Overall, circulating leukocyte subsets showed distinct adipokine receptor expression profiles. While monocytes expressed high levels of all adipokine receptors, NK and iNKT cells predominantly expressed AdipoR2, and B-lymphocytes and CD4+ and CD8+ T-lymphocyte subsets expressed AdipoR2 as well as leptin receptor. Strikingly though, leukocyte subset numbers and adipokine receptor expression profiles were largely similar in obese children and controls. Obese children showed higher naïve B-cell numbers, and pre-intervention also higher numbers of

From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century.

PubMed

Blüher, Matthias; Mantzoros, Christos S

2015-01-01

This year marks the 20th anniversary of the discovery of leptin, which has tremendously stimulated translational obesity research. The discovery of leptin has led to realizations that have established adipose tissue as an endocrine organ, secreting bioactive molecules including hormones now termed adipokines. Through adipokines, the adipose tissue influences the regulation of several important physiological functions including but not limited to appetite, satiety, energy expenditure, activity, insulin sensitivity and secretion, glucose and lipid metabolism, fat distribution, endothelial function, hemostasis, blood pressure, neuroendocrine regulation, and function of the immune system. Adipokines have a great potential for clinical use as potential therapeutics for obesity, obesity related metabolic, cardiovascular and other diseases. After 20 years of intense research efforts, recombinant leptin and the leptin analog metreleptin are already available for the treatment of congenital leptin deficiency and lipodystrophy. Other adipokines are also emerging as promising candidates for urgently needed novel pharmacological treatment strategies not only in obesity but also other disease states associated with and influenced by adipose tissue size and activity. In addition, prediction of reduced type 2 diabetes risk by high circulating adiponectin concentrations suggests that adipokines have the potential to be used as biomarkers for individual treatment success and disease progression, to monitor clinical responses and to identify non-responders to anti-obesity interventions. With the growing number of adipokines there is an increasing need to define their function, molecular targets and translational potential for the treatment of obesity and other diseases. In this review we present research data on adipose tissue secreted hormones, the discovery of which followed the discovery of leptin 20 years ago pointing to future research directions to unravel mechanisms of action

Obesity-related adipokines predict patient-reported shoulder pain.

PubMed

Gandhi, Rajiv; Perruccio, Anthony V; Rizek, Randy; Dessouki, Omar; Evans, Heather M K; Mahomed, Nizar N

2013-01-01

Increasingly, an inflammatory modulating effect of adipokines within synovial joints is being recognized. To date, there has been no work examining a potential association between the presence of adipokines in the shoulder and patient-reported outcomes. This study undertakes an investigation assessing these potential links. 50 osteoarthritis patients scheduled for shoulder surgery completed a pre-surgery questionnaire capturing demographic information including validated, patient-reported function (Disabilities of the Arm, Shoulder, and Hand questionnaire) and pain (Short Form McGill Pain Questionnaire) measures. Synovial fluid (SF) samples were analyzed for leptin, adiponectin, and resistin levels using Milliplex MAP assays. Linear regression modeling was used to assess the association between adipokine levels and patient-reported outcomes, adjusted for age, sex, BMI, and disease severity. 54% of the cohort was female (n = 27). The mean age (SD) of the sample was 62.9 (9.9) years and the mean BMI (SD) was 28.1 (5.4) kg/m(2). From regression analyses, greater SF leptin and adiponectin levels, but not regarding resistin, were found to be associated with greater pain (p < 0.05). Adipokine levels were not associated with functional outcome scores. The identified association between shoulder-derived SF leptin and adiponectin and shoulder pain is likely explained by the pro-inflammatory characteristics of the adipokines and represents potentially important therapeutic targets. © 2013 S. Karger GmbH, Freiburg.

Ghrelin, leptin and adiponectin as possible predictors of the hedonic value of odors.

PubMed

Trellakis, Sokratis; Tagay, Sefik; Fischer, Cornelia; Rydleuskaya, Alena; Scherag, André; Bruderek, Kirsten; Schlegl, Sandra; Greve, Jens; Canbay, Ali E; Lang, Stephan; Brandau, Sven

2011-02-25

Several lines of evidence point to a close relationship between the hormones of energy homeostasis and the olfactory system. Examples are the localization of leptin and adiponectin receptors in the olfactory system or increased activation of brain regions related to the palatability and the hedonic value of food in response to food pictures after application of ghrelin. In this preliminary study, we tested in 31 subjects (17 male and 14 female) if and to what extent the peripheral blood concentrations of "satiety" hormones, such as leptin, adiponectin, and ghrelin (acyl and total), are correlated with the self-ratings of odor pleasantness and with the objective olfactory and gustatory ability. The hedonic values of some odors were found to be differently rated between donors depending on gender and body weight. The concentrations of leptin, adiponectin and total ghrelin were significantly associated with the hedonic value of pepper black oil, but failed to show significant correlations for 5 other odors tested. Except for a significant association between leptin and odor identification, hormone concentrations were not linked to the abilities of smell and taste. Peripheral adipokines and gut hormones may alter the perception and pleasantness of specific odors, presumably either directly through their receptors in the olfactory system or indirectly through central interfaces between the regulation systems of olfaction, appetite control, memory and motivation. Copyright © 2010 Elsevier B.V. All rights reserved.

Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, A; Ceballos-Ceballos, R J M; Poblete-Aro, C E; Hackney, A C; Mota, J; Ramírez-Vélez, R

2017-04-01

Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. Exercise was associated with a significant increase in adiponectin (WMD=0.882 μg ml -1 , 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.

UV-induced inhibition of adipokine production in subcutaneous fat aggravates dermal matrix degradation in human skin.

PubMed

Kim, Eun Ju; Kim, Yeon Kyung; Kim, Min-Kyoung; Kim, Sungsoo; Kim, Jin Yong; Lee, Dong Hun; Chung, Jin Ho

2016-05-10

Ultraviolet (UV) exposure to the human skin reduces triglycerides contents and lipid synthesis in the subcutaneous (SC) fat. Because adiponectin and leptin are the most abundant adipokines from the SC fat, we aim to investigate how they interact with UV exposure and skin aging. The expressions of adiponectin and leptin were significantly decreased in SC fat of sun-exposed forearm skin, in comparison with that of sun-protected buttock skin of the same elderly individuals, indicating that chronic UV exposure decreases both adipokines. Acute UV irradiation also decreased the expressions of adiponectin and leptin in SC fat. The expressions of adiponectin receptor 1/2 and leptin receptor were significantly decreased in the dermis as well as in SC fat. Moreover, while exogenous adiponectin and leptin administration prevented UV- and TNF-α induced matrix metalloproteinase (MMP)-1 expression, they also increased UV- and TNF-α induced reduction of type 1 procollagen production. Silencing of adiponectin, leptin or their receptors led to an increased MMP-1 and a decreased type 1 procollagen expression, which was reversed by treatment with recombinant human adiponectin or leptin. In conclusion, UV exposure decreases the expression of adiponectin and leptin, leading to the exacerbation of photoaging by stimulating MMP-1 expression and inhibiting procollagen synthesis.

No association of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin gene with food preferences in the Czech population.

PubMed

Bienertova-Vasku, Julie; Bienert, Petr; Tomandl, Josef; Forejt, Martin; Vavrina, Martin; Kudelkova, Jana; Vasku, Anna

2008-02-01

Previously, it has been reported that mutations in the genes encoding for adipokines may be associated with impaired food intake and may serve as potential obesity biomarkers. The aim of this study was to investigate the possible associations of defined variability in leptin, leptin receptor, adiponectin, proopiomelanocortin and ghrelin genes with food preferences in the obese and non-obese Czech population and evaluate their potential as the obesity susceptibility genes. Using PCR followed by restriction analysis, we studied 185 volunteers. Basic anthropometrical characteristics associated to obesity were measured and the food intake was monitored using a 7-day record method. In the group of obese individuals, a subset of 34 morbidly obese patients was studied for plasma leptin and soluble leptin receptor levels. None of the examined polymorphisms was associated to anthropometrical or demographic characteristics of the study subjects. The Gln223Arg polymorphism within the leptin receptor gene was significantly associated with lower plasma leptin levels (the RR genotype being more frequent in patients with lower plasma leptin levels; P = 0.001). No associations of the examined polymorphisms with food preferences was observed. Based on our results, the examined polymorphisms in the adipokine genes do not seem to be the major risk factor for obesity development in the Czech population nor significantly affect food preferences.

Fatty acids derived from a food frequency questionnaire and measured in the erythrocyte membrane in relation to adiponectin and leptin concentrations.

PubMed

Santos, S; Oliveira, A; Pinho, C; Casal, S; Lopes, C

2014-05-01

Evidence on the association between fatty acids and adiponectin and leptin concentrations is scarce and inconsistent, which may in part be due to limitations of dietary reporting methods. We aimed to estimate the association of fatty acids, derived from a food frequency questionnaire (FFQ) and measured in the erythrocyte membrane, with adiponectin and leptin concentrations. We studied 330 non-institutionalized inhabitants of Porto (52.4% women; age range: 26-64 years) evaluated in 2010-2011, as part of the EPIPorto cohort study. Fatty acids were derived from a validated semiquantitative FFQ and measured in the erythrocyte membrane by gas chromatography. Serum concentrations of adiponectin and leptin were determined through radioimmunoassay. Regression coefficients (β) and 95% confidence intervals (95% CI) were obtained from linear regression models, after controlling for gender, age, education, leisure time physical activity and total body fat percentage (obtained from dual energy X-ray absorptiometry). Fatty acids measured by FFQ showed no significant associations with both adipokines. Lauric and linoleic acids, measured in the erythrocyte membrane, were significantly and positively associated with adiponectin (β=0.292, 95% CI: 0.168-0.416; β=0.150, 95% CI: 0.020-0.280) and leptin (β=0.071, 95% CI: 0.003-0.138; β=0.071, 95% CI: 0.002-0.140), whereas total n-3, eicosapentaenoic and docosahexaenoic acids were significantly but negatively associated with adiponectin (β=-0.289, 95% CI: -0.420 to -0.159; β=-0.174, 95% CI -0.307 to -0.040; β=-0.253, 95% CI -0.383 to -0.124) and leptin (β=-0.151, 95% CI: -0.220 to -0.083; β=-0.080, 95% CI: -0.151 to -0.009; β=-0.146, 95% CI: -0.214 to -0.078). Positive significant associations of palmitic and trans-fatty acids with adiponectin were also observed. A positive association of lauric and linoleic acids and a negative association of total n-3 fatty acids with both adipokines were observed only with fatty acids

The concentrations of adipokines in goat milk: relation to plasma levels, inflammatory status, milk quality and composition.

PubMed

Guzel, Saime; Yibar, Artun; Belenli, Deniz; Cetin, Ismail; Tanriverdi, Meltem

2017-03-23

The main objectives of our study were to measure the major adipokines adiponectin, leptin and resistin in goat milk, to assess their interrelationships and to assess their relationships with the plasma and serum concentrations of total protein, cholesterol, total lipids, plasma C-reactive protein (CRP), milk somatic cell count (SCC), milk total aerobic colony and lactobacillus count, and milk components in lactating Saanen goats. The study was performed on eighteen lactating Saanen goats. Milk and blood samples were collected on days 20, 35, 50, 65 and 80 of lactation postpartum. The milk and plasma adiponectin levels on days 50, 65 and 80 postpartum were significantly higher than those on day 20. The milk and plasma leptin levels were lower on day 20 than on days 35, 50, 65 and 80. The milk concentrations of these major adipokines were positively intercorrelated. The milk and plasma concentrations of these three adipokines were also positively correlated. The plasma CRP concentrations correlated positively with milk leptin and resistin concentrations and inversely with milk adiponectin concentration. Milk adiponectin concentration was inversely related with its SCC. These data confirm that adiponectin, leptin and resistin are present in goat milk. The milk concentrations of these three adipokines were interrelated and interacted with the general inflammatory marker, CRP. The inverse relationship between milk adiponectin concentrations and its SCC suggests that variations in milk adiponectin might be involved in the udder health of lactating goats, but clinical trials are needed to support this hypothesis.

The relationship between breast milk leptin and adiponectin with child body composition from 3 to 5 years: a follow-up study.

PubMed

Meyer, D M; Brei, C; Stecher, L; Much, D; Brunner, S; Hauner, H

2017-08-01

Research indicates that breast milk contains bioactive components that influence metabolism in infancy and may play a role in the prevention of obesity in early childhood. In our initial study, 147 breastfeeding mother/child pairs were followed from birth to 2 years of age to examine the relationship between breast milk leptin and total adiponectin (collected at 6 weeks and 4 months postpartum) and infant body composition. Higher breast milk total adiponectin was related to greater fat mass and weight gain in children at 1 and 2 years of age, whereas leptin showed no association. In this follow-up, we examined the relationship between both adipokines and children's body weight, body mass index percentiles, sum of four skin-folds, percentage of body fat, fat mass and lean body mass at 3, 4 and 5 years of age. Breast milk adipokines were largely unrelated to child anthropometric measures. Our results do not provide significant evidence that breast milk adipokines can predict adiposity in preschool children. © 2016 World Obesity Federation.

Adiposity trajectory and its associations with plasma adipokine levels in children and adolescents-A prospective cohort study.

PubMed

Li, Shenghui; Liu, Rong; Arguelles, Lester; Wang, Guoying; Zhang, Jun; Shen, Xiaoming; Wang, Xiaobin

2016-02-01

This study aimed to examine the associations of longitudinal adiposity measures with two adipokines, leptin and adiponectin, and their ratio in children and adolescents. A total of 953 children and adolescents participated in a 6-year longitudinal study. Body mass index (BMI), percentage body fat (%BF), and fat mass index (FMI) were used to assess adiposity status. After adjusting for possible confounders, our regression models revealed that BMI, %BF, and FMI, in both the baseline and follow-up surveys were independently associated with a higher level of leptin and the leptin/adiponectin ratio at the follow-up survey, whereas the significant association with adiponectin only partly existed in adiposity measures at the follow-up visit. Moreover, the longitudinal change in adiposity measures was found to be a significant predictor for follow-up plasma adipokine levels. Compared with the low→low group, the medium→medium group, up-trend group, and high→high group all showed a significantly increased level of leptin and leptin/adiponectin ratio. The up-trend group and high→high group also had significantly decreased adiponectin levels. These findings highlight the importance of adiposity surveillance and the utility of adipokines as biomarkers for adverse metabolic consequences of childhood adiposity. © 2015 The Obesity Society.

Association of prenatal antibiotics with foetal size and cord blood leptin and adiponectin.

PubMed

Mueller, N T; Rifas-Shiman, S L; Blaser, M J; Gillman, M W; Hivert, M-F

2017-04-01

Early postnatal antibiotic use has been shown to promote excess weight gain, but it is unclear whether intrauterine exposure to antibiotics is associated with foetal growth and adiposity. The objective of this study was to examine associations of antibiotic prescription in each trimester of pregnancy with foetal size and adipokine levels at birth. In 2128 pregnant women from the pre-birth Project Viva cohort, from electronic medical records, we estimated antibiotic prescribing by timing during pregnancy. Outcomes were sex-specific birth weight-for-gestational-age z-score (BW/GA-z) and levels of umbilical cord leptin and adiponectin. We used linear regression models adjusted for maternal age, pre-pregnancy body mass index, parity, race/ethnicity, education, smoking during pregnancy, household income and child sex and additionally adjusted cord blood leptin and adiponectin models for gestation length. Of the 2128 women in our sample, 643 (30.2%) were prescribed with oral antibiotics during pregnancy. Mean (standard deviation) BW/GA-z was 0.17 (0.97), cord blood leptin was 9.0 ng mL -1 (6.6) and cord blood adiponectin was 28.8 ng mL -1 (6.8). Overall, antibiotic prescription in pregnancy was associated with lower BW/GA-z [multivariable adjusted β -0.11; 95% confidence interval {CI} -0.20, -0.01]. In trimester-specific analyses, only second trimester antibiotic prescription was associated with lower BW/GA-z (β -0.23; 95% CI -0.37, -0.08). Overall, antibiotic prescription in pregnancy was not associated with cord blood leptin or adiponectin levels. However, in trimester-specific analyses, third trimester antibiotic prescription was associated with higher cord blood leptin (β 2.28 ng mL -1 ; 95% CI 0.38, 4.17). Antibiotics in mid-pregnancy were associated with lower birth weight for gestational age, whereas third trimester antibiotics were associated with higher cord blood leptin. © 2016 World Obesity Federation.

Higher Leptin and Adiponectin Concentrations Predict Poorer Performance-based Physical Functioning in Midlife Women: the Michigan Study of Women’s Health Across the Nation

PubMed Central

Zheng, Huiyong; Mancuso, Peter; Harlow, Siobán D.

2016-01-01

Background. Excess fat mass is a greater contributor to functional limitations than is reduced lean mass or the presence of obesity-related conditions. The impact of fat mass on physical functioning may be due to adipokines, adipose-derived proteins that have pro- or anti-inflammatory properties. Methods. Serum samples from 1996 to 2003 that were assayed for leptin, adiponectin, and resistin were provided by 511 participants from the Michigan site of the Study of Women’s Health Across the Nation. Physical functioning performance was assessed annually during study visits from 1996 to 2003. Results. Among this population of Black and White women (mean baseline age = 45.6 years, SD = 2.7 years), all of whom were premenopausal at baseline, higher baseline leptin concentrations predicted longer stair climb, sit-to-rise, and 2-pound lift times and shorter forward reach distance (all p < .01). This relationship persisted after adjustment for age, BMI, percent skeletal muscle mass, race/ethnicity, economic strain, bodily pain, diabetes, knee osteoarthritis, and C-reactive protein. Baseline total adiponectin concentrations did not predict any mobility measures but did predict quadriceps strength; a 1 µg/mL higher adiponectin concentration was associated with 0.64 Nm lower quadriceps strength (p = .02). Resistin was not associated with any of the physical functioning performance measures. Change in the adipokines was not associated with physical functioning. Conclusion. In this population of middle-aged women, higher baseline leptin concentrations predicted poorer mobility-based functioning, whereas higher adiponectin concentrations predicted reduced quadriceps strength. These findings suggest that the relationship between the adipokines and physical functioning performance is independent of other known correlates of poor functioning. PMID:26302979

Adipokines in human breast milk.

PubMed

Kratzsch, Juergen; Bae, Yoon Ju; Kiess, Wieland

2018-01-01

The review describes the molecular characteristics of so far detected breast milk adipokines and ranks their breast milk level compared to the respective levels in maternal and infant blood. Moreover, analytical knowledge for measurements of breast milk adipokines will be delineated. Next, we summarized data about two main potential influencing factors on adipokine concentration in breast milk, maternal weight and pasteurization of milk. Finally, associations between adipokines in breast milk and weight gain in infants as well as the putative mechanisms for effects of breast milk adipokines on food intake and weight gain in later life will debated. Our findings suggest that a source of adipokines in human breast milk cannot be uniformly defined. In dependence on the ratio between serum and breast milk levels the major quantity of these proteins may be derived from peripheral tissues, from the breast tissue itself or from both. Thus, leptin and in part adiponectin levels in breast milk are dependent on a plenty of influencing factors with an important relevance of maternal anthropometric characteristics There is some evidence that leptin, adiponectin and ghrelin levels in breast milk may be associated with growth gain of infants and even with increased risk for being overweight during infancy or childhood. We hypothesize that a dysregulation in adipokine homeostasis in early life could promote obesity and metabolic disturbance in later life. Copyright © 2018 Elsevier Ltd. All rights reserved.

Elevated total plasma-adiponectin is stable over time in young women with bulimia nervosa.

PubMed

Syk, M; Ramklint, M; Fredriksson, R; Ekselius, L; Cunningham, J L

2017-03-01

Bulimia nervosa (BN) is characterized by dysregulated eating behaviour and present data suggest adipokines may regulate food intake. We investigated a possible association between BN and adipokine levels and hypothesized that plasma (P)-adiponectin would be elevated and P-leptin and P-leptin-adiponectin-ratio would be reduced in women with BN. The study was designed as a cross-sectional study with a longitudinal arm for patients with BN. Plasma-adiponectin and leptin was measured in 148 female patients seeking psychiatric ambulatory care and 45 female controls. Fifteen patients were diagnosed with BN and the remaining with other affective and anxiety disorders. P-adiponectin and P-leptin levels were compared between patients with BN, patients without BN and controls. At follow-up 1-2years later, adipokines were reassessed in patients with BN and the Eating Disorder Examination Questionnaire was used to assess symptom severity. P-adiponectin was elevated in patients with BN at baseline and at follow-up when compared to patients without BN and controls (P<0.004 and <0.008 respectively). The difference remained significant after controlling for body mass index. P-adiponectin was correlated to symptom severity at follow-up in patients with BN without morbid obesity (ρ=0.72, P<0.04). P-leptin-adiponectin-ratio was significantly lower in patients with BN compared to controls (P<0.04) and P-leptin non-significantly lower. Findings indicate a stable elevation of P-adiponectin in women with BN. P-adiponectin at follow-up correlates to eating disorder symptom severity in patients without morbid obesity, indicating that P-adiponectin should be further investigated as a possible potential prognostic biomarker for BN. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Airway and serum adipokines after allergen and diesel exposure in a controlled human crossover study of atopic adults.

PubMed

Kramer, Marabeth M; Hirota, Jeremy A; Sood, Akshay; Teschke, Kay; Carlsten, Christopher

2017-04-01

Adipokines are mediators released from adipose tissue. These proteins are regarded as active elements of systemic and pulmonary inflammation, whose dysregulation can alter an individual's risk of developing allergic lung diseases. Despite this knowledge, adipokine responses to inhaled stimuli are poorly understood. We sought to measure serum and lung adiponectin, leptin, and resistin in an atopic adult study population following exposure to allergen and diesel exhaust (DE). Two types of lung samples including bronchoalveolar lavage (BAL) and bronchial wash (BW), and a time course of serum samples, were collected from the 18 subjects who participated in the randomized, double-blinded controlled human study. The two crossover exposure triads in this study were inhaled DE and filtered air each followed by instilled allergen or saline. Serum and lung adipokine responses to these exposures were quantified using enzyme-linked immunosorbent assay. Allergen significantly increased adiponectin and leptin in BAL, and adiponectin in the BW 48 hours after exposure. Serum leptin and resistin responses were not differentially affected by exposure, but varied over time. Coexposure with DE and allergen revealed significant correlations between the adiponectin/leptin ratio and FEV 1 changes and airway responsiveness measures. Changes in lung and serum adipokines in response to allergen exposure were identified in the context of a controlled exposure study. Coexposure identified a potentially protective role of adiponectin in the lung. This response was not observed in those with baseline airway hyper-responsiveness, or after allergen exposure alone. The clinical relevance of this potentially adaptive adipokine pattern warrants further study. Copyright © 2016 Elsevier Inc. All rights reserved.

Alterations in adipokines in feline hepatic lipidosis.

PubMed

Mazaki-Tovi, M; Abood, S K; Segev, G; Schenck, P A

2013-01-01

Feline hepatic lipidosis (HL) is associated with alterations in lipid and carbohydrate metabolism. The adipokines, adiponectin, and leptin have lipid-lowering and insulin-sensitizing effects. Serum concentrations of adiponectin and leptin are altered in feline HL. Client-owned cats: 55 healthy and 45 with liver disease. Cats with liver disease were categorized as having HL (n = 20), HL and concurrent disease (n = 19), or other liver disease (n = 6), based on clinical signs, laboratory findings, abdominal ultrasound examination as well as liver cytopathology, histopathology, or both. Serum samples were collected and body condition score determined. Mean serum concentrations of adiponectin were higher in overweight cats with HL (4.5 μg/mL), HL and concurrent disease (4.4 μg/mL), or other liver disease (6.1 μg/mL), as compared with healthy cats (1.5 μg/mL; P < .001, P < .001, and P = .04, respectively). Mean serum concentration of leptin was higher in cats with HL (9.8 ng/mL) or HL and concurrent disease (10.7 ng/mL) than healthy cats (4.9 ng/mL, P < .001 and P < .001, respectively). Cats with other liver disease had leptin concentration (4.9 ng/mL) similar to healthy cats. Concentrations of adiponectin were correlated with alanine aminotransferase activity (r = 0.40, P = .0069), and concentrations of leptin were correlated with alkaline phosphatase activity (r = 0.42, P = .0051) in cats with liver disease. Adipokine concentrations are altered in feline HL. Increased concentrations of adiponectin are related to liver disease, whereas increased concentrations of leptin are specifically related to HL. Copyright © 2013 by the American College of Veterinary Internal Medicine.

Leptin but not adiponectin is related to type 2 diabetes mellitus in obese adolescents.

PubMed

Reinehr, Thomas; Woelfle, Joachim; Wiegand, Susanna; Karges, Beate; Meissner, Thomas; Nagl, Katrin; Holl, Reinhard W

2016-06-01

Adipokines have been suggested to be involved in the development of type 2 diabetes mellitus (T2DM). However, studies in humans are controversial and analyzes at the onset of disease are scarce. We compared adiponectin and leptin levels between 74 predominately Caucasian adolescents with T2DM and 74 body mass index (BMI)-, age-, and gender-matched controls without T2DM. Adiponectin and leptin were correlated to age, BMI, hemoglobin A1c (HbA1c), blood pressure, and lipids. Adolescents with T2DM showed significant lower leptin levels as compared with controls (18 ± 12 vs. 37 ± 23 ng/mL, p < 0.001), whereas the adiponectin levels did not differ between the adolescents with and without T2DM (5.0 ± 2.5 vs. 4.9 ± 2.5 µg/mL, p = 0.833). The associations between adiponectin and high-density lipoprotein (HDL) cholesterol (r = 0.42), systolic (r = -0.15), and diastolic blood pressure (r = -0.20) were stronger as the associations of leptin to these parameters (all r < 0.07). In multiple linear regression analysis, leptin was significantly and positively associated with BMI [β-coefficient: 1.3 (95% confidence interval (95% CI): ±0.5), p < 0.001] and female sex [β-coefficient: 9.7 (95% CI: ±6.7), p = 0.005], and negatively with age [β-coefficient: -2.3 (95% CI: ±2.1), p < 0.001] and HbA1c [β-coefficient -3.1 (95% CI: ±2.1), p = 0.011]. Adiponectin was not significantly associated with BMI, HbA1c, age, or gender in multiple linear regression analysis. Because adiponectin levels did not differ between obese adolescents with and without T2DM, hypoadiponectinemia as observed in obesity seems not to be involved in the genesis of T2DM. The relative hypoleptinemia in obese adolescents with T2DM as compared with obese adolescents without T2DM may contribute to the development of T2DM. Future longitudinal studies in humans are necessary to prove this hypothesis. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Branched Chain Amino Acids Are Associated with Insulin Resistance Independent of Leptin and Adiponectin in Subjects with Varying Degrees of Glucose Tolerance.

PubMed

Connelly, Margery A; Wolak-Dinsmore, Justyna; Dullaart, Robin P F

2017-05-01

Branched chain amino acids (BCAA) may be involved in the pathogenesis of insulin resistance and are associated with type 2 diabetes mellitus (T2DM) development. Adipokines such as leptin and adiponectin influence insulin resistance and reflect adipocyte dysfunction. We examined the extent to which the association of BCAA with insulin resistance is attributable to altered leptin and adiponectin levels in individuals with varying degrees of glucose tolerance. BCAA were measured by nuclear magnetic resonance, whereas leptin and adiponectin were measured by immunoassay, in subjects with normal fasting glucose (n = 30), impaired fasting glucose (n = 25), and T2DM (n = 15). Insulin resistance was estimated by homeostasis model assessment (HOMAir). BCAA were higher in men than in women (P < 0.001) and tended to be higher in T2DM subjects (P = 0.10) compared to subjects with normal or impaired fasting glucose. In univariate regression analysis, BCAA were correlated with HOMAir (r = 0.46; P < 0.001) and inversely with adiponectin (r = -0.53; P < 0.001) but not with leptin (r = -0.08; P > 0.05). Multivariable linear regression analysis, adjusting for age, sex, T2DM, and body mass index (BMI), demonstrated that BCAA were positively associated with HOMAir (β = 0.242, P = 0.023). When BCAA, leptin, and adiponectin were included together, the positive relationship of HOMAir with BCAA (β = 0.275, P = 0.012) remained significant. Insulin resistance was associated with BCAA. This association remained after adjusting for age, sex, T2DM, BMI, as well as leptin and adiponectin. It is unlikely that the relationship of insulin resistance with BCAA is to a major extent attributable to effects of leptin and adiponectin.

Association between Several Persistent Organic Pollutants in Serum and Adipokine Levels in Breast Milk among Lactating Women of Korea.

PubMed

Kim, Sunmi; Park, Jeongim; Kim, Hai-Joong; Lee, Jeong Jae; Choi, Gyuyeon; Choi, Sooran; Kim, Sungjoo; Kim, Su Young; Lee, Duk Hee; Moon, Hyo-Bang; Kim, Sungkyoon; Choi, Kyungho

2015-07-07

Exposure to several persistent organic pollutants (POPs) has been linked to alteration of lipid metabolism. Adipokines, such as leptin and adiponectin, are hormones that play roles in lipid metabolism, and have been suggested as markers of health effects that may lead to obesity. To date, only serum adipokines have been associated with POPs exposure. In the present study, for the first time, the associations between leptin and adiponectin in breast milk, and several POPs in serum were investigated among 82 lactating Korean women between 25 and 46 years of age. Breast milk adipokines are important because adipokine intake of infant through breastfeeding may influence the growth of infants. The median concentrations of leptin and adiponectin in skimmed milk of the Korean lactating women were 17.9 ng/L and 16.5 μg/L, respectively. Leptin concentrations in breast milk were negatively associated with ∑hexachlorohexane (HCH), oxychlordane, ∑chlordane, or 2,2',4,4',5,5'-hexachlorobiphenyl (CB 153) levels in maternal serum. Linear relationships between adiponectin and POPs concentrations were not observed, however, nonmonotonic relationship which showed generally positive associations was suggested for p,p'-dichlorodiphenyltrichloroethane (DDT) and ∑chlordane in quartile analysis. Our observations show that POPs at the current level of exposure may be associated with the alteration of lipid metabolism among lactating women. Implication of adipokine transfer to breastfed infants is of concern and deserves further investigation.

The effect of n-3 PUFAs on circulating adiponectin and leptin in patients with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.

PubMed

Farimani, Azam Rezaei; Hariri, Mitra; Azimi-Nezhad, Mohsen; Borji, Abasalt; Zarei, Sadegh; Hooshmand, Elham

2018-02-16

N-3 PUFAs can potentially influence levels of inflammatory and non-inflammatory adipokines. Given the contradictory effects of n-3 PUFAs on serum levels of adipokines in type 2 diabetes, we conducted a systematic review and meta-analysis study of randomized placebo-controlled clinical trials that examined the effects of n-3 PUFAs on serum levels of leptin and adiponectin in patients with type 2 diabetes. The electronic databases, without regard to language restrictions including PubMed/Medline, Google Scholar, SCOPUS and ISI Web of Science until August 2017, were used to identify randomized controlled trials that assessed the effect of n-3 PUFAs on serum leptin and adiponectin concentrations in type 2 diabetes. Outcomes were extracted based on the mean ± SD as effect size at baseline and end of the intervention. Between-study heterogeneity was evaluated by the I 2 estimates and their 95% CIs. Funnel plot asymmetry was used to investigate the existence of publication bias. Stata software and Review Manager were used for statistical data analysis. Data from 10 eligible articles involved 494 subjects with type 2 diabetes mellitus (intervention groups = 254 and control groups = 240), with age between 44 and 70 years, treated with doses of 0.52-7.4 g/day n-3 PUFAs. Adiponectin concentration nonsignificantly increased by a MD = 0.17 µg/mL (95% CI - 0.11, 0.44). Also, leptin concentration nonsignificantly reduced by a MD = - 0.31 ng/mL (95% CI - 0.69, 0.07). Plant and marine sources of n-3 PUFAs can modify serum leptin and adiponectin levels by increasing adiponectin and decreasing leptin levels in patients with type 2 diabetes. Due to some limitations in this study, further studies are needed to reach a definitive conclusion about the effect of n-3 PUFAs on the levels of leptin and adiponectin in T2DM.

Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin.

PubMed

Zhang, Zhi; Wang, Fang; Wang, Bing-Jian; Chu, Guang; Cao, Qunan; Sun, Bao-Gui; Dai, Qiu-Yan

2014-10-01

Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling in vascular smooth muscle cells, thus preventing excess ECM production, in our already established 3D co-culture vessel models. Our 3D co-culture vessel model, which mimics true blood vessels, is composed of vascular endothelial cells, vascular smooth muscle cells and collagen type I. We validated the profibrogenic effects of leptin and analysed matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase 1 (TIMP1) and collagen types II/IV secretion in 3D vessel models. The protective/inhibitory effects of adiponectin were re-analysed by inhibiting adiponectin receptor 1 (AdipoR) and AdipoR2 expression in endothelial cells using RNAi technology. In the 3D vessel models, adiponectin blocked the leptin-stimulated secretion of collagen types II/IV and TIMP1 while significantly increasing MMP2/9 activity. In endothelial cells, adiponectin induced phosphorylation of AMPK, thereby suppressing leptin-mediated STAT3 phosphorylation through induction of SOCS3 in smooth muscle cells. Our findings indicate that adiponectin disrupted the leptin-induced vascular ECM remodelling via AdipoR1 and enhanced AMPK signalling in endothelial cells, which, in turn, promoted SOCS3 up-regulation in smooth muscle cells to repress leptin-stimulated phosphorylation of STAT3. © 2014 The authors.

Inhibition of leptin-induced vascular extracellular matrix remodelling by adiponectin

PubMed Central

Zhang, Zhi; Wang, Fang; Wang, Bing-jian; Chu, Guang; Cao, Qunan; Sun, Bao-Gui; Dai, Qiu-Yan

2014-01-01

Vascular extracellular matrix (ECM) remodelling, which is the result of disruption in the balance of ECM synthesis and degradation, induces vessel fibrosis and thereby leads to hypertension. Leptin is known to promote tissue fibrosis, while adiponectin has recently been demonstrated to be anti-fibrogenic in tissue fibrosis. In this study, we aimed to evaluate the leptin-antagonist function of adiponectin and to further elucidate the mechanisms through which adiponectin dampens leptin signalling in vascular smooth muscle cells, thus preventing excess ECM production, in our already established 3D co-culture vessel models. Our 3D co-culture vessel model, which mimics true blood vessels, is composed of vascular endothelial cells, vascular smooth muscle cells and collagen type I. We validated the profibrogenic effects of leptin and analysed matrix metalloproteinase 2 (MMP2), MMP9, tissue inhibitor of metalloproteinase 1 (TIMP1) and collagen types II/IV secretion in 3D vessel models. The protective/inhibitory effects of adiponectin were re-analysed by inhibiting adiponectin receptor 1 (AdipoR) and AdipoR2 expression in endothelial cells using RNAi technology. In the 3D vessel models, adiponectin blocked the leptin-stimulated secretion of collagen types II/IV and TIMP1 while significantly increasing MMP2/9 activity. In endothelial cells, adiponectin induced phosphorylation of AMPK, thereby suppressing leptin-mediated STAT3 phosphorylation through induction of SOCS3 in smooth muscle cells. Our findings indicate that adiponectin disrupted the leptin-induced vascular ECM remodelling via AdipoR1 and enhanced AMPK signalling in endothelial cells, which, in turn, promoted SOCS3 up-regulation in smooth muscle cells to repress leptin-stimulated phosphorylation of STAT3. PMID:24982243

Analysis of the association of leptin and adiponectin concentrations with metabolic syndrome in children: Results from the IDEFICS study.

PubMed

Nappo, A; González-Gil, E M; Ahrens, W; Bammann, K; Michels, N; Moreno, L A; Kourides, Y; Iacoviello, L; Mårild, S; Fraterman, A; Molnàr, D; Veidebaum, T; Siani, A; Russo, P

2017-06-01

Adipokines may play a role in the pathogenesis of the metabolic syndrome (MetS) in children. We aimed to evaluate the association of leptin, adiponectin, and its ratio (L/A ratio) with the metabolic syndrome (MetS) in a subsample of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS) cohort. Leptin, adiponectin and MetS parameters were measured in a subsample of 1253 children (3-9.9 years) participating to the IDEFICS study, grouped as: Non-OW (underweight/normal weight) and OW/Ob (overweight/obese). MetS was defined using the sex- and age-specific cut-offs based on the distribution of MetS components in the IDEFICS cohort. The prevalence of the MetS among OW/Ob was 24.8% and 27.1% in boys and girls respectively, whereas ≤2% among Non-OW. OW/Ob had significantly higher leptin and L/A ratio as compared to Non-OW. Significantly higher leptin was found in OW/Ob with MetS as compared with OW/Ob without MetS. Significantly lower adiponectin was observed only in OW/Ob girls as compared to Non-OW. A 1SD increase in leptin and L/A ratio z-scores or a 1SD decrease in adiponectin z-score were significantly associated with higher risk of MetS. After adjustment for BMI or body fat mass (BFM) the association remained significant only for leptin. We showed that in European children, higher leptin concentration is associated with MetS, even after adjusting for BMI or BFM, confirming an early role of leptin in MetS, while the association of adiponectin with MetS seems be mediated by body fat in this age range. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Chemotherapy and plasma adipokines level in patients with colorectal cancer.

PubMed

Słomian, Grzegorz; Świętochowska, Elżbieta; Nowak, Grzegorz; Pawlas, Krystyna; Żelazko, Aleksandra; Nowak, Przemysław

2017-04-12

Adipokines are molecules produced and secreted by adipose tissue and are linked to multiple malignancies. Adipokines can suppress or promote particular cell behaviors in different types of cancer. The aim of this study was to investigate the impact of chemotherapy on select adipokines in patients with colorectal cancer (CRC). Blood samples were collected from 42 patients with pathologically documented advanced CRC, who required palliative chemotherapy. Leptin, adiponectin, resistin and visfatin levels were measured by ELISA before and 3 months after the administration of chemotherapy. Among the 42 patients evaluated, 18 achieved a partial response (PR), 16 achieved stable disease (SD) and 8 patients experienced disease progression (PD). We found that 5-fluorouracil-based chemotherapy regimens significantly increased plasma levels of leptin and adiponectin and decreased plasma levels of resistin and visfatin in PR and SD patients, whereas the plasma levels of these molecules were not affected in PD patients. Furthermore, the mean plasma levels of leptin were significantly lower, and the mean plasma levels of resistin and visfatin were significantly greater in patients with PD compared with PR and SD both before and after chemotherapy treatment. We conclude that palliative chemotherapy in CRC patients, in addition to providing clinical benefits, positively affects cytokine production and secretion in PR and SD patients. Specifically, we found that palliative chemotherapy increased plasma levels of the anti-inflammatory adipokine adiponectin and decreased the plasma levels of visfatin and resistin, molecules known to promote angiogenesis and cancer cell proliferation in PR and SD patients. Moreover, the baseline values of leptin, visfatin and resistin might serve as prognostic indicators of a poor response to chemotherapy.

Adipokines in Liver Cirrhosis.

PubMed

Buechler, Christa; Haberl, Elisabeth M; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-06-29

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively.

Adipokines in Liver Cirrhosis

PubMed Central

Haberl, Elisabeth M.; Rein-Fischboeck, Lisa; Aslanidis, Charalampos

2017-01-01

Liver fibrosis can progress to cirrhosis, which is considered a serious disease. The Child-Pugh score and the model of end-stage liver disease score have been established to assess residual liver function in patients with liver cirrhosis. The development of portal hypertension contributes to ascites, variceal bleeding and further complications in these patients. A transjugular intrahepatic portosystemic shunt (TIPS) is used to lower portal pressure, which represents a major improvement in the treatment of patients. Adipokines are proteins released from adipose tissue and modulate hepatic fibrogenesis. These proteins affect various biological processes that are involved in liver function, including angiogenesis, vasodilation, inflammation and deposition of extracellular matrix proteins. The best studied adipokines are adiponectin and leptin. Adiponectin protects against hepatic inflammation and fibrogenesis, and leptin functions as a profibrogenic factor. These and other adipokines are supposed to modulate disease severity in patients with liver cirrhosis. Consequently, circulating levels of these proteins have been analyzed to identify associations with parameters of hepatic function, portal hypertension and its associated complications in patients with liver cirrhosis. This review article briefly addresses the role of adipokines in hepatitis and liver fibrosis. Here, studies having analyzed these proteins in systemic blood in cirrhotic patients are listed to identify adipokines that are comparably changed in the different cohorts of patients with liver cirrhosis. Some studies measured these proteins in systemic, hepatic and portal vein blood or after TIPS to specify the tissues contributing to circulating levels of these proteins and the effect of portal hypertension, respectively. PMID:28661458

Circulating Adipokines and Vascular Function: Cross-Sectional Associations in a Community-Based Cohort.

PubMed

Zachariah, Justin P; Hwang, Susan; Hamburg, Naomi M; Benjamin, Emelia J; Larson, Martin G; Levy, Daniel; Vita, Joseph A; Sullivan, Lisa M; Mitchell, Gary F; Vasan, Ramachandran S

2016-02-01

Adipokines may be potential mediators of the association between excess adiposity and vascular dysfunction. We assessed the cross-sectional associations of circulating adipokines with vascular stiffness in a community-based cohort of younger adults. We related circulating concentrations of leptin and leptin receptor, adiponectin, retinol-binding protein 4, and fatty acid-binding protein 4 to vascular stiffness measured by arterial tonometry in 3505 Framingham Third Generation cohort participants free of cardiovascular disease (mean age 40 years, 53% women). Separate regression models estimated the relations of each adipokine to mean arterial pressure and aortic stiffness, as carotid femoral pulse wave velocity, adjusting for age, sex, smoking, heart rate, height, antihypertensive treatment, total and high-density lipoprotein cholesterol, diabetes mellitus, alcohol consumption, estimated glomerular filtration rate, glucose, and C-reactive protein. Models evaluating aortic stiffness also were adjusted for mean arterial pressure. Mean arterial pressure was positively associated with blood retinol-binding protein 4, fatty acid-binding protein 4, and leptin concentrations (all P<0.001) and inversely with adiponectin (P=0.002). In fully adjusted models, mean arterial pressure was positively associated with retinol-binding protein 4 and leptin receptor levels (P<0.002 both). In fully adjusted models, aortic stiffness was positively associated with fatty acid-binding protein 4 concentrations (P=0.02), but inversely with leptin and leptin receptor levels (P≤0.03 both). In our large community-based sample, circulating concentrations of select adipokines were associated with vascular stiffness measures, consistent with the hypothesis that adipokines may influence vascular function and may contribute to the relation between obesity and hypertension. © 2015 American Heart Association, Inc.

Serum leptin and adiponectin levels in children with type 1 diabetes mellitus - Relation to body fat mass and disease course.

PubMed

Majewska, Katarzyna Anna; Majewski, Dominik; Skowrońska, Bogda; Stankiewicz, Witold; Fichna, Piotr

2016-03-01

Leptin and adiponectin are adipokines presenting a wide range of impacts, including glycemic balance regulations. Insulin is one of the main regulators of adipose tissue function. In type 1 diabetes mellitus (T1DM) endogenous insulin secretion is replaced by the exogenous supply, which is not regulated naturally. The aim of the study was to establish serum leptin and adiponectin levels, and their relations to body fat mass and disease course in children with T1DM. The study included 75 children with T1DM and the control group of 20 healthy coevals. All children had estimated serum leptin and adiponectin concentrations, lipid profile, and bioelectrical impedance analysis. Serum leptin concentrations in children with T1DM were not significantly different from the control group (p=0.067, mean values±SD: 3.11±2.98 vs. 5.29±5.06μg/l, respectively), and related positively to body fat mass in both groups. Adiponectin serum concentrations were significantly higher in children with T1DM than in the control group (p<0.001; mean values: 18.82±9.31 vs. 12.10±5.53μg/ml, respectively), and were not related to the body fat content in the study group. Both, leptin and adiponectin, showed no relation to any of the analyzed parameters of the disease course. Differences observed between children with T1DM and their healthy coevals, when similar in terms of age, body weight, and body fat mass, seem not to depend directly on the disease duration, its metabolic control or insulin supply. Copyright © 2015 Medical University of Bialystok. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Serum adipokine levels in chronic liver diseases: association of resistin levels with fibrosis severity.

PubMed

Tsochatzis, Emmanuel; Papatheodoridis, George V; Hadziyannis, Emilia; Georgiou, Anastasia; Kafiri, Georgia; Tiniakos, Dina G; Manesis, Emanuel K; Archimandritis, Athanasios J

2008-01-01

Leptin and adiponectin have been implicated in the pathogenesis and progression of non-alcoholic steatohepatitis (NASH) and chronic hepatitis C (CHC), but little is known about the role of resistin in chronic liver diseases. The objective of this study was to investigate serum levels of the above three adipokines in relation to the etiology of liver disease and to determine their associations with histological severity. We prospectively evaluated 146 patients (HBeAg-negative chronic hepatitis B (CHB): 52, CHC: 70, NASH: 24) who consecutively underwent liver biopsy. Detailed epidemiological, anthropometric and laboratory data were recorded. Histological lesions were evaluated blindly according to the Ishak and the Brunt classifications for CHB/CHC and NASH, respectively. Serum adipokine levels were similar between CHB and CHC patients, while CHB/CHC patients had significantly lower leptin levels compared with NASH patients (8.3+/-7.3 versus 17.6+/-16.6 ng/ml, p=0.012) and higher adiponectin (10.2+/-5.1 versus 7.5+/-4 microg/ml, p=0.018) and resistin levels (7.1+/-2.5 versus 5.7+/-2.8 ng/ml, p=0.016). In CHB/CHC, there was no significant association between steatosis or necroinflammation and levels of adipokines, while the presence of moderate/severe fibrosis (stages 4-6) was associated with higher leptin and adiponectin levels in male but not in female patients and with lower resistin levels irrespective of gender or other factors (adjusted odds ratio=0.788, p=0.035). Serum adipokine levels depend on the etiology of liver disease differing between chronic viral hepatitis and NASH, but not between CHB and CHC. In CHB/CHC, resistin levels are independently associated with fibrosis severity, whereas in the association of leptin and adiponectin levels with fibrosis, it seems to be a gender effect.

Serum Adiponectin and Leptin Concentrations in Relation to Body Fat Distribution, Hematological Indices and Lipid Profile in Humans.

PubMed

Lubkowska, Anna; Radecka, Aleksandra; Bryczkowska, Iwona; Rotter, Iwona; Laszczyńska, Maria; Dudzińska, Wioleta

2015-09-14

The purpose of the study was to evaluate the relationship between serum adiponectin and leptin concentrations and body composition, hematological indices and lipid profile parameters in adults. The study involved 95 volunteers (BMI from 23.3 to 53 kg/m²). Anthropometric parameters were measured: body weight and height, waist and hip circumference, waist-to-hip ratio, body fat mass (BMF), subcutaneous and visceral fat mass (SFM, VFM), lean body mass (LBM), skeletal muscle mass (SMM). In serum we determined adiponectin and leptin concentrations, extracellular hemoglobin, total bilirubin, as well as lipid metabolism (TCh, HDL-Ch, LDL-Ch, TG). Mean adipokine levels were significantly higher in women (p ≤ 0.01), adiponectin significantly negatively correlated with body height and weight, systolic blood pressure and absolute LBM and SMM values. The same relation was observed for erythroid system indicators and lipid indicators. A positive correlation was exceptionally found between adiponectin and HDL-Ch. LEP negatively correlated with some percentage rates (%LBM, %SMM). Only in women, we observed a positive correlation between LEP and body weight, BMI and WHR. Studies on ADPN and the ADPN/LEP ratio as a valuable complementary diagnostic element in the prediction and prevention of cardiovascular diseases need to be continued.

[Serum adipokines and their receptors in endometrial and colon cancer patients: relationship with tumor invasion and metastasis].

PubMed

Yunusova, N V; Kondakova, I V; Kolomiets, L A; S G Afanasiev; Chernyshova, A L; Shatokhina, O V; Frolova, A E; Zhou, Zhiwei; Wang, Wei

2015-01-01

The aim of the study was to investigate the serum adipokine levels and expression of adipokine receptors (AdipoR1, AdipoR2) in patients with endometrial and colon cancer in relation with the main clinical morphological parameters (tumor invasion, lymph node involvement). The study included 60 endometrial cancer patients with I-II Stage and 31 patients with colon cancer (T2-4N0-2M0). Serum adipokine levels, the level of soluble form of the leptin receptor (sOb-R) and AdipoR1 and AdipoR2 expression were evaluated with ELISA. In endometrial cancer serum leptin and adiponectin levels were associated not only with metabolic disorders but also with cervical invasion. In colon cancer serum leptin level was associated with lymph node involvement. The data obtained showed the potential implication of serum adipokines into tumor invasion and metastasis. In both sites intratumoral levels of AdipoR1 H AdipoR2 were not associated with the presence of metabolic syndrome. The AdipoR1 level was related with myometrial invasion. In colon cancer patients, AdipoR1 and AdipoR2 expressions were associated with lymph node involvement, and AdipoR1 expression was correlated with tumor size. The obtained results demonstrated involvement of adipose tissue hormones (leptin and adiponectin) and adiponectin receptors (AdipoR1 and AdipoR2) in tumor growth, invasion and lymphogenic metastasis.

Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity

PubMed Central

Kocot, Joanna; Dziemidok, Piotr; Kiełczykowska, Małgorzata; Hordyjewska, Anna; Szcześniak, Grzegorz; Musik, Irena

2017-01-01

Background The fast pace of life, promoting fast food consumption and low physical activity, has resulted in obesity and/or diabetes as being serious social problems. The aim of the present study was to evaluate concentrations of selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in relation to degree of obesity. Material/Methods The study comprised 92 T2D subjects divided into 4 groups according to BMI value – I (normal body weight), II (overweight), III (obesity), and IV (severe obesity) – and 20 healthy volunteers (control group). Each group was divided into male and female subgroups. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. Results In women, leptin concentration was significantly higher in group IV, whereas in men it was higher in groups III and IV than in the control group and groups I and II. Irrespective of sex, a significant decrease in adiponectin level was observed in group III vs. control. There was no significant difference in resistin levels. In women visfatin was markedly enhanced in group III, whereas in men in groups II, III and IV vs. control. Leptin/adiponectin ratio was increased in groups III and IV vs. control in women, whereas in men vs. both control and group I. Conclusions The obese type 2 diabetic patients presented a disturbed adipokine profile, which seems to be an important link between obesity and T2D. The future studies concerning the question if regulating of adipokines’ concentrations could be a promising approach for managing metabolic disorders seem to be well-grounded. PMID:29049270

Effect of telmisartan on selected adipokines, insulin sensitivity, and substrate utilization during insulin-stimulated conditions in patients with metabolic syndrome and impaired fasting glucose.

PubMed

Wohl, Petr; Krusinová, Eva; Hill, Martin; Kratochvílová, Simona; Zídková, Katerina; Kopecký, Jan; Neskudla, Tomás; Pravenec, Michal; Klementová, Marta; Vrbíková, Jana; Wohl, Pavel; Mlejnek, Petr; Pelikánová, Terezie

2010-10-01

Telmisartan improves glucose and lipid metabolism in rodents. This study evaluated the effect of telmisartan on insulin sensitivity, substrate utilization, selected plasma adipokines and their expressions in subcutaneous adipose tissue (SAT) in metabolic syndrome. Twelve patients with impaired fasting glucose completed the double-blind, randomized, crossover trial. Patients received telmisartan (160 mg/day) or placebo for 3 weeks and vice versa with a 2-week washout period. At the end of each period, a hyperinsulinemic euglycemic clamp (HEC) combined with indirect calorimetry was performed. During HEC (0, 30, and 120 min), plasma levels of adipokines were measured and a needle biopsy (0 and 30 min) of SAT was performed. Fasting plasma glucose was lower after telmisartan compared with placebo (P<0.05). There were no differences in insulin sensitivity and substrate utilization. We found no differences in basal plasma adiponectin, resistin and tumour necrosis factor α (TNFα), but an increase was found in basal leptin, after telmisartan treatment. Insulin-stimulated plasma adiponectin (P<0.05), leptin and resistin (P<0.001) were increased, whereas TNFα was decreased (P<0.05) after telmisartan treatment. Expression of resistin, but not adiponectin, TNFα and leptin was increased after telmisartan treatment. Despite the decrease in fasting plasma glucose, telmisartan does not improve insulin sensitivity and substrate utilization. Telmisartan increases plasma leptin as well as insulin-stimulated plasma adiponectin, leptin and resistin, and decreases plasma TNFα during HEC. Changes in plasma adipokines cannot be explained by their expressions in SAT. The changes in plasma adipokines might be involved in the metabolic effects of telmisartan in metabolic syndrome.

ASSOCIATIONS OF ADIPONECTIN, LEPTIN LEVELS, AND THE CHANGE OF BODY COMPOSITION IN PATIENTS ON PERITONEAL DIALYSIS: A PROSPECTIVE COHORT STUDY.

PubMed

Xu, Xiao; Tian, Xue; Chen, Yuan; Yang, Zhi-Kai; Qu, Zhen; Dong, Jie

2018-04-19

Although the association between adipokines such as adiponectin, leptin, and body composition has been noted, whether they could predict the change of fat mass and lean body mass is unknown. We aimed to examine these associations in patients on peritoneal dialysis (PD) through a prospective cohort study. Body composition (by dual-energy x-ray absorptiometry) including fat mass and lean body mass were examined at baseline and then at year 3. Serum leptin and adiponectin levels were measured. Demographic data, comorbidity, biochemical data, inflammation (high-sensitive C-reactive protein [hs-CRP]) and insulin resistance (homeostatic model assessment [HOMA-IR]) were also examined. At baseline, serum adiponectin levels were significantly inversely correlated with weight, lean body mass index (LBMI), fat mass index (FMI), lean body mass (LBM), and fat mass (FM) in 213 prevalent patients. At year 3, FMI, LBMI, FM, and the percentage of FM (FM%) increased while the percentage of LBM (LBM%) significantly decreased despite unchanged weight and LBM among the remaining 112 patients. After adjustment for demographic data, comorbidities, hs-CRP, HOMA-IR, and daily energy intake (DEI), serum adiponectin at baseline was not associated with increases in LBMI, FMI, and FM, but independently associated with an increase in FM% and a decrease in LBM%. The predictive effect of high-serum adiponectin level on mortality disappeared after adjusting for diabetes and cardiovascular disease. Serum leptin was not associated with any changes in body composition during the follow-up, nor with the mortality in this cohort. A high adiponectin level could predict an increase in FM% and a decrease in LBM% during a 3-year follow-up in PD patients. Serum adiponectin could not independently predict mortality in PD patients.

Adiponectin stimulates IL-8 production by rheumatoid synovial fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kitahara, Kanako; Department of Immunology, Toho University School of Medicine, Tokyo; Kusunoki, Natsuko

The adipokines are linked not only to metabolic regulation, but also to immune responses. Adiponectin, but not leptin or resistin induced interleukin-8 production from rheumatoid synovial fibroblasts (RSF). The culture supernatant of RSF treated with adiponectin induced chemotaxis, although adiponectin itself had no such effect. Addition of antibody against adiponectin, and inhibition of adiponectin receptor gene decreased adiponectin-induced IL-8 production. Nuclear translocation of nuclear factor-kappa B was increased by adiponectin. The induction of interleukin-8 was inhibited by mitogen-activated protein kinase inhibitors. These findings suggest that adiponectin contributes to the pathogenesis of rheumatoid arthritis.

Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size.

PubMed

Ahlsson, Fredrik; Diderholm, Barbro; Ewald, Uwe; Jonsson, Björn; Forslund, Anders; Stridsberg, Mats; Gustafsson, Jan

2013-05-01

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation. Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique. Median (range) rate of glucose production was 805 (653-1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5mg/L and median level of leptin was 47.1 (9.9-58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure. The inverse

Association between plasma concentrations of branched-chain amino acids and adipokines in Japanese adults without diabetes.

PubMed

Katagiri, Ryoko; Goto, Atsushi; Budhathoki, Sanjeev; Yamaji, Taiki; Yamamoto, Hiroshi; Kato, Yumiko; Iwasaki, Motoki; Tsugane, Shoichiro

2018-01-18

Previous studies have consistently reported an association between circulating levels of branched-chain amino acids (BCAAs) or adipokines and insulin resistance; however, the association between BCAA and adipokine levels remains to be clarified. In this cross-sectional study involving 678 participants (435 men) without diabetes, plasma BCAA (valine, leucine, and isoleucine), adipokine (total and high molecular weight [HMW] adiponectin, leptin, and tumor necrosis factor-α [TNF-α]) concentrations, and an updated homeostasis model assessment of insulin resistance (HOMA2-IR) were measured. The association between the concentrations of total BCAAs and adipokines was adjusted for confounding factors, including body mass index. For the lowest and highest BCAA quartiles, the adjusted geometric mean levels of HMW adiponectin were, respectively, 1.51 and 0.91 μg/mL, in men (P for trend < 0.0001); 3.61 and 2.29 μg/mL, in women (P = 0.0005). The corresponding geometric mean levels for leptin were 1681 and 2620 pg/mL, in men (P = 0.003), and 4270 and 6510 pg/mL, in women (P = 0.003). Those for HOMA2-IR were 0.89 and 1.11, in men (P < 0.0001), and 0.79 and 0.96, in women (P < 0.0001); no significant association was found with TNF-α. These results suggest significant associations between BCAA concentrations and those for adiponectin, leptin and HOMA2-IR in individuals without diabetes.

Adipokine profile in celiac patients: differences in comparison with patients suffering from diarrhea-predominant IBS and healthy subjects.

PubMed

Russo, Francesco; Chimienti, Guglielmina; Clemente, Caterina; D'Attoma, Benedetta; Linsalata, Michele; Orlando, Antonella; De Carne, Massimo; Cariola, Filomena; Semeraro, Francesco P; Pepe, Gabriella; Riezzo, Giuseppe

2013-12-01

OBJECTIVE. The role of adipokines such as resistin, leptin, and adiponectin could be pivotal in the molecular crosstalk between the inflamed intestine and the surrounding mesenteric adipose tissue. Our aims were to a) evaluate their circulating concentrations in patients with active celiac disease (ACD) and compare them to those in patients with diarrhea-predominant irritable bowel syndrome (IBS-d) and healthy subjects; b) establish the impact of genetic variability in resistin; and c) evaluate whether a 1-year gluten-free diet (GFD) modifies circulating concentrations of resistin, leptin, and adiponectin in celiac patients. MATERIAL AND METHODS. The study included 34 ACD patients, 29 IBS-d patients, and 27 healthy controls. Circulating concentrations of resistin, leptin, adiponectin, IL-6, and IL-8 were evaluated at the time of enrollment. Resistin +299 G/A polymorphism was also analysed. In CD patients, biochemical measurements were repeated after a 1-year GFD. RESULTS. Along with higher IL-6 and IL-8 plasma levels, higher resistin and adiponectin concentrations were found in ACD and IBS-d patients compared with controls (p: 0.0351 and p: 0.0020, respectively). Resistin values proved to be predictable from a linear combination of IL-8 and +299 polymorphism. GFD affected resistin (p: 0.0009), but not leptin and adiponectin concentrations. CONCLUSIONS. Our data suggest that these adipokines are involved in modulating inflammatory processes in both CD and IBS-d patients. Alterations in the adipokine profile as well as the higher prevalence of the resistin +299 G/A SNP A allele compared to controls support the hypothesis that, at least in well-defined cases of IBS, a genetic component may also be supposed.

Relationship between adiponectin, leptin, IGF-1 and total lipid peroxides plasma concentrations in patients with systemic sclerosis: possible role in disease development.

PubMed

Winsz-Szczotka, Katarzyna; Kuźnik-Trocha, Kornelia; Komosińska-Vassev, Katarzyna; Kucharz, Eugeniusz; Kotulska, Anna; Olczyk, Krystyna

2016-07-01

The relationship between adiponectin, leptin, insulin-like growth factor-1 (IGF-1) and total lipid peroxide (TLP) concentrations, and its possible role in the development of diffuse cutaneous systemic sclerosis (dcSSc), were evaluated in this study. Plasma adipokines and IGF-1 levels were determined using the enzyme-linked immunosorbent assay method, whereas TLP levels were determined using a photometric test, in 36 dcSSc patients and 40 healthy controls matched by age, sex and body mass index (BMI). Plasma levels of adipokines were significantly lowered, while TLP and IGF-1 were increased in dcSSc patients compared to controls. Adiponectin correlated significantly with leptin (r = 0.44), TLP (r = -0.54), CRP (r = -0.47), erythrocyte sedimentation rate (ESR) (r = -0.40) and duration of disease (r = -0.44). A significant relationship was found between leptinemia and IGF-1 (r = -0.40), TLP (r = 0.44), duration of disease (r = -0.38) and BMI (r = 0.65). TLP correlated with IGF-1 (r = -0.43), C-reactive protein (r = 0.47), ESR (r = 0.49) and duration of disease (r = 0.46), while IGF-1 correlated with ESR (r = -0.40). Adipose tissue may play a complex role in the development of dcSSc, affecting both the metabolic state of the organism, as well as free radical-induced connective tissue degradation. Although, leptin seems to exert a pro-oxidative effect and both adiponectin and IGF-1 appear to prevent free radical damage, confirmation of the above effects requires further research. © 2014 Asia Pacific League of Associations for Rheumatology and Wiley Publishing Asia Pty Ltd.

Association of Circulating Adipokines With Echocardiographic Measures of Cardiac Structure and Function in a Community-Based Cohort.

PubMed

von Jeinsen, Beatrice; Short, Meghan I; Xanthakis, Vanessa; Carneiro, Herman; Cheng, Susan; Mitchell, Gary F; Vasan, Ramachandran S

2018-06-21

Adipokines mediate cardiometabolic risk associated with obesity but their role in the pathogenesis of obesity-associated heart failure remains uncertain. We investigated the associations between circulating adipokine concentrations and echocardiographic measures in a community-based sample. We evaluated 3514 Framingham Heart Study participants (mean age 40 years, 53.8% women) who underwent routine echocardiography and had select circulating adipokines measured, ie, leptin, soluble leptin receptor, fatty acid-binding protein 4, retinol-binding protein 4, fetuin-A, and adiponectin. We used multivariable linear regression, adjusting for known correlates (including weight), to relate adipokine concentrations (independent variables) to the following echocardiographic measures (dependent variables): left ventricular mass index, left atrial diameter in end systole, fractional shortening, and E/e'. In multivariable-adjusted analysis, left ventricular mass index was inversely related to circulating leptin and fatty acid-binding protein 4 concentrations but positively related to retinol-binding protein 4 and leptin receptor levels ( P ≤0.002 for all). Left atrial end-systolic dimension was inversely related to leptin but positively related to retinol-binding protein 4 concentrations ( P ≤0.0001). E/e' was inversely related to leptin receptor levels ( P =0.0002). We observed effect modification by body weight for select associations (leptin receptor and fatty acid-binding protein 4 with left ventricular mass index, and leptin with left atrial diameter in end systole; P <0.05 for interactions). Fractional shortening was not associated with any of the adipokines. No echocardiographic trait was associated with fetuin-A or adiponectin concentrations. In our cross-sectional study of a large, young to middle-aged, relatively healthy community-based sample, key indices of subclinical cardiac remodeling were associated with higher or lower circulating concentrations of

Adiponectin inhibits leptin signalling via multiple mechanisms to exert protective effects against hepatic fibrosis.

PubMed

Handy, Jeffrey A; Fu, Ping P; Kumar, Pradeep; Mells, Jamie E; Sharma, Shvetank; Saxena, Neeraj K; Anania, Frank A

2011-12-15

Adiponectin is protective against hepatic fibrosis, whereas leptin promotes fibrosis. In HSCs (hepatic stellate cells), leptin signals via a JAK2 (Janus kinase 2)/STAT3 (signal transducer and activator of transcription 3) pathway, producing effects that enhance ECM (extracellular matrix) deposition. SOCS-3 (suppressor of cytokine signalling-3) and PTP1B (protein tyrosine phosphatase 1B) are both negative regulators of JAK/STAT signalling, and recent studies have demonstrated a role for adiponectin in regulating SOCS-3 expression. In the present study we investigate mechanisms whereby adiponectin dampens leptin signalling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad-/-) and wild-type mice with leptin and/or carbon tetrachloride (CCl4) or saline. We analyse JAK2 and Ob-Rb (long form of the leptin receptor) phosphorylation, and PTP1B expression and activity. We also explore potential mechanisms through which adiponectin regulates SOCS-3-Ob-Rb association. Adiponectin inhibits leptin-stimulated JAK2 activation and Ob-Rb phosphorylation in HSCs, whereas both were increased in Ad-/- mice. Adiponectin stimulates PTP1B expression and activity in vitro, whereas PTP1B expression was lower in Ad-/-mice than in wild-type mice. Adiponectin also promotes SOCS-3-Ob-R association and blocks leptin-stimulated formation of extracellular TIMP-1 (tissue inhibitor of metalloproteinases-1)-MMP-1 (matrix metalloproteinase-1) complexes in vitro. These results suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: (i) by promoting binding of SOCS-3 to Ob-Rb, and (ii) by stimulating PTP1B expression and activity, thus inhibiting JAK2/STAT3 signalling at multiple points.

Leptin and adiponectin in patients with systemic lupus erythematosus: clinical and laboratory correlations.

PubMed

Barbosa, Vitalina de Souza; Francescantônio, Paulo Luiz; Silva, Nílzio Antônio da

2015-01-01

To evaluate the serum levels of leptin and adiponectin in patients with systemic lupus erythematosus (SLE) and correlate their levels with disease activity, presence of autoantibodies and clinical manifestations. 52 women with SLE and 33 healthy women were evaluated. The patients were divided into two groups, the first with active SLE and the second with inactive SLE. Patients with SLEDAI ≥3 were considered active. Serum levels of leptin (ng/ml) and adiponectin (μg/ml) were measured by enzyme immunoassay. There was a significant difference in leptin levels between SLE and controls (20.7 ± 17.1 vs. 8.0 ± 5.0 ng/mL, P <0.001), but no significant difference in adiponectin levels (87.5 ± 69.7 vs. 118.1 ± 70.6 pg/ml, P = 0.053). No significant difference in levels of leptin and adiponectin was noted between inactive and active SLE groups. There was a significant association between low levels of leptin and positivity for anticardiolipin (aCL) (P = 0.025) and lupus anticoagulant (LA) (p = 0.003) and a significant association between high levels of leptin and the presence of renal disease (p <0.001). However, there was no association between adiponectin levels with autoantibodies and clinical features in SLE patients. Patients with SLE had elevated leptin levels, with association with renal involvement. Leptin and adiponectin were not correlated with disease activity. Low levels of leptin have been associated with the presence of LA and aCL. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Adiponectin inhibits leptin signaling via multiple mechanisms to exert protective effects against hepatic fibrosis

PubMed Central

HANDY, Jeffrey A.; FU, Ping P.; KUMAR, Pradeep; MELLS, Jamie E.; SHARMA, Shvetank; SAXENA, Neeraj K.; ANANIA, Frank A.

2011-01-01

SYNOPSIS Adiponectin is protective against hepatic fibrosis, while leptin promotes fibrosis. In hepatic stellate cells (HSCs), leptin signals via a Janus Kinase 2/Signal Transducers and Activators of Transcription 3 (Jak2/Stat3) pathway, producing effects that enhance extracellular matrix deposition. Suppressors of Cytokine Signaling-3 (SOCS-3) and Protein Tyrosine Phosphatase-1B (PTP1B) are both negative regulators of Jak/Stat signaling, and recent studies demonstrated a role for adiponectin in regulating SOCS-3 expression. In this study we investigated mechanisms whereby adiponectin dampens leptin signaling and prevents excess ECM production. We treated culture-activated rat HSCs with recombinant adiponectin, leptin, both or neither, and also treated adiponectin knockout (Ad−/−) and wild-type mice with leptin and/or carbon tetrachloride (CCl4), or saline. We analyzed Jak2 and Ob-Rb phosphorylation, and PTP1B expression and activity. We also explored potential mechanisms through which adiponectin regulates SOCS-3/Ob-Rb association. Adiponectin inhibited leptin-stimulated Jak2 activation and Ob-Rb phosphorylation in HSCs, while both were increased in Ad−/− mice. Adiponectin stimulated PTP1B expression and activity, in vitro, while PTP1B expression was lower in Ad−/−mice than in wild-type mice. Adiponectin also promoted SOCS-3/Ob-R association, and blocked leptin-stimulated formation of extracellular TIMP-1/MMP-1 complexes, in vitro. These data suggest two novel mechanisms whereby adiponectin inhibits hepatic fibrosis: by promoting binding of SOCS-3 to Ob-Rb, and stimulating PTP1B expression and activity, thus inhibiting Jak2-Stat3 signaling at multiple points. PMID:21846328

Adiponectin, Leptin and Objectively Measured Physical Activity in Adults: A Narrative Review

PubMed Central

Nurnazahiah, Ali; Lua, Pei Lin; Shahril, Mohd Razif

2016-01-01

The objective of this study was to compile and analyse existing scientific evidences reporting the effects of objectively measured physical activity on the levels of adiponectin and leptin. Articles related to the effects of objectively measured physical activity on the levels of adiponectin and leptin were searched from the Medline and PubMed databases. The search was limited to ‘objectively measured’ physical activity, and studies that did not objectively measure the physical activity were excluded. Only English articles were included in the search and review. A total of 18 articles encompassing 2,026 respondents met the inclusion criteria. The eligible articles included all forms of evidence (e.g., cross-sectional and intervention). Seventeen and 11 studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Five and four cross-sectional studies showed the effects of objectively measured physical activity on adiponectin and leptin, respectively. Two out of five studies showed a weak to moderate positive association between adiponectin and objectively measured physical activity, while three out of four studies showed a weak to moderate inverse association between leptin and objectively measured physical activity. For intervention studies, six out of 12 studies involving adiponectin and five out of seven studies involving leptin showed a significant effect between the proteins and objectively measured physical activity. However, a definitive conclusion could not be drawn due to several methodological flaws in the existing articles and the acute lack of additional research in this area. In conclusion, the existing evidences are encouraging but yet not compelling. Hence, further well-designed large trials are needed before the effectiveness of objectively measured physical activity in elevating adiponectin levels and in decreasing leptin levels could be strongly confirmed. PMID:28090175

The efficacy of adipokines and indices of metabolic syndrome as predictors of severe obesity-related hepatic steatosis.

PubMed

Méndez-Sánchez, Nahum; Chávez-Tapia, Norberto C; Medina-Santillán, Roberto; Villa, Antonio R; Sánchez-Lara, Karla; Ponciano-Rodríguez, Guadalupe; Ramos, Martha H; Uribe, Misael

2006-10-01

The aim of this study was to investigate adiponectin, leptin, and metabolic syndrome as predictors of the severity of obesity-related steatosis. By ultrasonography steatosis-positive (cases) subjects (n = 141) were compared with controls (n = 111). Demographic and anthropometric data and serum concentrations of adiponectin, leptin, and insulin were measured. The impact of several criteria of metabolic syndrome, serum adiponectin concentrations, and serum leptin concentrations were tested using a multivariate logistic regression analysis. The frequency of metabolic syndrome was higher in cases (44.0% versus 9.2%; P < .0001). Cases were older and had higher insulin resistance, waist circumference, and lower concentrations of adiponectin (all P < .001). The upper adiponectin quartile was associated with a lesser grade of steatosis. Metabolic syndrome and adiponectin concentrations were independently associated with the probability of steatosis. In conclusion, adipokines and metabolic syndrome are useful indices for the prediction of the severity of obesity-related steatosis.

Adiponectin and leptin in overweight/obese and lean women with polycystic ovary syndrome.

PubMed

Chen, Chin-I; Hsu, Ming-I; Lin, Shyh-Hsiang; Chang, Yuan-Chin I; Hsu, Chun-Sen; Tzeng, Chii-Ruey

2015-04-01

The objective of this study was to evaluate the adiponectin and leptin levels in overweight/obese and lean women with polycystic ovary syndrome (PCOS). This was a retrospective study. Of the 422 studied patients, 224 women with PCOS and 198 women without PCOS were evaluated. Insulin resistance and the metabolic components were assessed. The adiponectin and leptin levels were also evaluated. Adiponectin was negatively correlated with insulin resistance, body mass index (BMI), and total testosterone, triglyceride, and low-density lipoprotein (LDL) levels; conversely, leptin reversed the aforementioned reaction and was negatively correlated with adiponectin levels. The adiponectin to leptin ratios were significantly lower in PCOS women than in those without PCOS. Compared to women with non-PCOS, overweight/obese women with PCOS had lower serum adiponectin levels than women without PCOS, which was not the case for lean women. Conversely, lean women with PCOS had higher serum leptin levels than those without PCOS, which was not the case for overweight/obese women. Adipose tissue might play an important role in the metabolic complications in women with PCOS. To study the impact of obesity biomarkers in women with PCOS, overweight/obese and lean women should be considered separately.

Changes in profile of lipids and adipokines in patients with newly diagnosed hypothyroidism and hyperthyroidism

PubMed Central

Chen, Yanyan; Wu, Xiafang; Wu, Ruirui; Sun, Xiance; Yang, Boyi; Wang, Yi; Xu, Yuanyuan

2016-01-01

Changes in profile of lipids and adipokines have been reported in patients with thyroid dysfunction. But the evidence is controversial. The present study aimed to explore the relationships between thyroid function and the profile of lipids and adipokines. A cross-sectional study was conducted in 197 newly diagnosed hypothyroid patients, 230 newly diagnosed hyperthyroid patients and 355 control subjects. Hypothyroid patients presented with significantly higher serum levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDLC), fasting insulin, resistin and leptin than control (p < 0.05). Hyperthyroid patients presented with significantly lower serum levels of high-density lipoprotein cholesterol, LDLC and leptin, as well as higher levels of fasting insulin, resistin, adiponectin and homeostasis model insulin resistance index (HOMA-IR) than control (p < 0.05). Nonlinear regression and multivariable linear regression models all showed significant associations of resistin or adiponectin with free thyroxine and association of leptin with thyroid-stimulating hormone (p < 0.001). Furthermore, significant correlation between resistin and HOMA-IR was observed in the patients (p < 0.001). Thus, thyroid dysfunction affects the profile of lipids and adipokines. Resistin may serve as a link between thyroid dysfunction and insulin resistance. PMID:27193069

Adipokines and insulin action

PubMed Central

Knights, Alexander J; Funnell, Alister PW; Pearson, Richard CM; Crossley, Merlin; Bell-Anderson, Kim S

2014-01-01

Obesity is a major public health concern and a strong risk factor for insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The last two decades have seen a reconsideration of the role of white adipose tissue (WAT) in whole body metabolism and insulin action. Adipose tissue-derived cytokines and hormones, or adipokines, are likely mediators of metabolic function and dysfunction. While several adipokines have been associated with obese and insulin-resistant phenotypes, a select group has been linked with insulin sensitivity, namely leptin, adiponectin, and more recently, adipolin. What is known about these insulin-sensitizing molecules and their effects in healthy and insulin resistant states is the subject of this review. There remains a significant amount of research to do to fully elucidate the mechanisms of action of these adipokines for development of therapeutics in metabolic disease. PMID:24719781

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs.

PubMed

Abu-Farha, Mohamed; Behbehani, Kazem; Elkum, Naser

2014-04-09

Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47-6.19) and (OR = 2.52, 95% CI = 1.45-4.35), (OR = 4.26, 95% CI = 2.39-7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0.22, 95% CI = 0.12-0.40). Leptin, PAI-1 and

Comprehensive analysis of circulating adipokines and hsCRP association with cardiovascular disease risk factors and metabolic syndrome in Arabs

PubMed Central

2014-01-01

Background Cardiovascular diseases (CVD) are a leading cause of death worldwide including the Middle East. This is caused in part by the dysregulation of adipose tissue leading to increased production of pro-inflammatory adipokines and reduction in cardio-protective adipokines such as adiponectin. Ethnicity has been recognized as a major factor in the association between CVD risk factors and the different circulating adipokines. In this study, for the first time, the relationship between traditional cardiovascular risk factors, Metabolic Syndrome (MetS) and circulating level of adipokines in Arab ethnicity was investigated. Methods We conducted a population-based cross-sectional survey on 379 adult Arab participants living in Kuwait. Traditional cardiovascular risk factors such as blood pressure (BP), low density lipoprotein (LDL) and triglyceride (TG) were measured. Plasma levels of circulating Leptin, Plasminogen Activator Inhibitor (PAI-1) visfatin, adiponectin, resistin and adipsin were assessed using the multiplexing immunobead-based assay. Results Circulating levels of High sensitivity C-Reactive Protein (hsCRP), Leptin, PAI-1 and adiponectin were significantly higher in Arab women than men (p < 0.0001). In multi-variate analysis, the homeostasis model assessment-insulin resistance (HOMA-IR) and body mass index (BMI) showed strong association with most of the biomarkers (p < 0.05). HsCRP showed significant association with all risk factors (p < 0.05). Leptin, PAI-1 and adipsin showed significant positive correlation with BMI, unlike adiponectin which showed inverse correlation (p < 0.05). Subjects in the highest tertile of leptin, PAI-1 and hsCRP had higher odds of having Metabolic Syndrome (MetS) (odd ratio [OR] = 3.02, 95% confidence interval [CI] = 1.47 – 6.19) and (OR = 2.52, 95% CI = 1.45 – 4.35), (OR = 4.26, 95% CI = 2.39 – 7.59) respectively. On the other hand subjects with highest tertile of adiponectin had lower odds of having MetS (OR = 0

Effects of a walking intervention using mobile technology and interactive voice response on serum adipokines among postmenopausal women at increased breast cancer risk.

PubMed

Llanos, Adana A M; Krok, Jessica L; Peng, Juan; Pennell, Michael L; Vitolins, Mara Z; Degraffinreid, Cecilia R; Paskett, Electra D

2014-04-01

Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin, and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m(2) or >30 kg/m(2)) and randomized to a 12-week, two-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were IVR + coach and IVR + no-coach condition. Pre-post changes in serum adiponectin, leptin, and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95 % confidence intervals [CI]) corresponding to postintervention adipokine concentrations relative to preintervention concentrations. While postintervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (ratio = 0.86, 95 % CI 0.74-1.01, and ratio = 0.94, 95 % CI 0.87-1.01, respectively) and increase in A/L ratio = 1.09, 95 % CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention.

Effects of a walking intervention using mobile technology and interactive voice response on serum adipokines among postmenopausal women at increased breast cancer risk

PubMed Central

Llanos, Adana A.M.; Krok, Jessica L.; Peng, Juan; Pennell, Michael L.; Vitolins, Mara Z.; Degraffinreid, Cecilia R.; Paskett, Electra D.

2014-01-01

Practical methods to reduce the risk of obesity-related breast cancer among high-risk subgroups are lacking. Few studies have investigated the effects of exercise on circulating adipokines, which have been shown to be associated with obesity and breast cancer. The aim of this study was to examine the effects of a walking intervention on serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L). Seventy-one overweight and obese postmenopausal women at increased risk of developing breast cancer were stratified by BMI (25-30 kg/m2 or >30 kg/m2) and randomized to a 12-week, 2-arm walking intervention administered through interactive voice response (IVR) and mobile devices. The intervention arms were: IVR + coach and IVR + no coach condition. Pre-post changes in serum adiponectin, leptin and the A/L ratio were examined using mixed regression models, with ratio estimates (and 95% confidence intervals [CI]) corresponding to post-intervention adipokine concentrations relative to pre-intervention concentrations. While post-intervention effects included statistically significant improvements in anthropometric measures, the observed decreases in adiponectin and leptin (Ratio=0.86, 95% CI 0.74-1.01 and Ratio=0.94, 95% CI 0.87-1.01, respectively) and increase in A/L (Ratio=1.09, 95% CI 0.94-1.26) were not significant. Thus, these findings do not support significant effects of the walking intervention on circulating adipokines among overweight and obese postmenopausal women. Additional studies are essential to determine the most effective and practical lifestyle interventions that can promote beneficial modification of serum adipokine concentrations, which may prove useful for obesity-related breast cancer prevention. PMID:24435584

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis.

PubMed

Diaz-Rizo, Valeria; Bonilla-Lara, David; Gonzalez-Lopez, Laura; Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S; Perez-Guerrero, Edsaul E; Rodriguez-Jimenez, N Alejandra; Saldaña-Cruz, A Miriam; Vazquez-Villegas, M Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario; Gamez-Nava, Jorge I

2017-01-01

There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01-1.12; p = 0.02). Instead, leptin was not associated with LN. These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse.

Analysis of the associations among Helicobacter pylori infection, adiponectin, leptin, and 10-year fracture risk using the fracture risk assessment tool: A cross-sectional community-based study

PubMed Central

Chen, Fang-Ping; Hsieh, Chia-Wen; Kuo, Sheng-Fong; Chien, Rong-Nan

2017-01-01

Helicobacter pylori (H. pylori) infection may induce inflammatory cytokines or adipokines that influence bone turnover and bone fracture risk. This study aimed to evaluate the association among H. pylori infection, adipokines, and 10-year fracture risk using the Fracture Risk Assessment Tool scale. From August 2013 to February 2016, a community-based cohort was surveyed by Keelung Chang-Gung Memorial Hospital. Subjects were included if they were older than 40 years and not pregnant. All participants underwent a standardized questionnaire survey, physical examination, urea breath test, and blood tests. A total of 2,689 participants (1,792 women) were included in this cross-sectional study. In both sexes, participants with a high fracture risk were older and had higher adiponectin values than participants without a high fracture risk (mean age, female: 72.9 ± 5.6 vs. 55.8 ± 7.3 years, P < 0.0001; male: 78.9 ± 4.7 vs. 58.1 ± 8.9 years, P < 0.001) (adiponectin, female: 10.8 ± 6.3 vs. 8.7 ± 5.2 ng/ml, P < 0.001; male: 9.7 ± 6.1 vs. 5.5 ± 3.8 ng/ml, P < 0.001). Adiponectin was correlated with high fracture risk in both sexes, but H. pylori infection and leptin was not. In logistic regression analysis, adiponectin could not predict high fracture risk when adjusting the factor of body mass index (BMI) in men group. In conclusion, H. pylori infection and leptin could not predict 10-year fracture risk in either sex. Adiponectin was correlated with bone fracture risk in both sexes and the correlation might be from the influence of BMI. PMID:28388631

Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B.

PubMed

Beales, Ian L P; Garcia-Morales, Carla; Ogunwobi, Olorunseun O; Mutungi, Gabriel

2014-01-25

Obesity is characterised by hyperleptinaemia and hypoadiponectinaemia and these metabolic abnormalities may contribute to the progression of several obesity-associated cancers including oesophageal adenocarcinoma (OAC). We have examined the effects of leptin and adiponectin on OE33 OAC cells. Leptin stimulated proliferation, invasion and migration and inhibited apoptosis in a STAT3-dependant manner. Leptin-stimulated MMP-2 secretion in a partly STAT3-dependent manner and MMP-9 secretion via a STAT3-independent pathway. Adiponectin inhibited leptin-induced proliferation, migration, invasion, MMP secretion and reduced the anti-apoptotic effects: these effects of adiponectin were ameliorated by both a non-specific tyrosine phosphatase inhibitor and a specific PTP1B inhibitor. Adiponectin reduced leptin-stimulated JAK2 activation and STAT3 transcriptional activity in a PTP1B-sensitive manner and adiponectin increased both PTP1B protein and activity. We conclude that adiponectin restrains leptin-induced signalling and pro-carcinogenic behaviour by inhibiting the early events in leptin-induced signal transduction by activating PTP1B. Relative adiponectin deficiency in obesity may contribute to the promotion of OAC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Serum levels of adiponectin and leptin as biomarkers of proteinuria in lupus nephritis

PubMed Central

Sanchez-Mosco, Dalia; Fajardo-Robledo, Nicte S.; Perez-Guerrero, Edsaul E.; Rodriguez-Jimenez, N. Alejandra; Saldaña-Cruz, A. Miriam; Vazquez-Villegas, M. Luisa; Gomez-Bañuelos, Eduardo; Vazquez-Del Mercado, Monica; Cardona-Muñoz, E. German; Cardona-Muller, David; Trujillo, Xochitl; Huerta, Miguel; Salazar-Paramo, Mario

2017-01-01

Introduction There are controversial results about the role of serum leptin and adiponectin levels as biomarkers of the severity of proteinuria in lupus nephritis. Objective The aim of this study was to evaluate the relationship between serum leptin and adiponectin levels with severity of proteinuria secondary to lupus nephritis (LN). Methods In a cross-sectional study, 103 women with systemic lupus erythematosus (SLE) were evaluated for kidney involvement. We compared 30 SLE patients with LN, all of them with proteinuria, versus 73 SLE patients without renal involvement (no LN). A comprehensive set of clinical and laboratory variables was assessed, including serum levels of leptin and adiponectin by ELISA. Multivariate analyses were used to adjust for potential confounders associated with proteinuria in LN. Results We found higher adiponectin levels in the LN group compared with the no LN group (20.4 ± 10.3 vs 15.6 ± 7.8 μg/mL; p = 0.02), whereas no differences were observed in leptin levels (33.3 ± 31.4 vs 22.5 ± 25.5 ng/mL; p = 0.07). Severity of proteinuria correlated with an increase in adiponectin levels (r = 0.31; p = 0.001), but no correlation was observed with leptin. Adiponectin levels were not related to anti-dsDNA or anti-nucleosome antibodies. In the logistic regression, adiponectin levels were associated with a high risk of proteinuria in SLE (OR = 1.06; 95% CI 1.01–1.12; p = 0.02). Instead, leptin was not associated with LN. Conclusion These findings indicate that adiponectin levels are useful markers associated with proteinuria in LN. Further longitudinal studies are required to identify if these levels are predictive of renal relapse. PMID:28898254

Adipokines and Hepatic Insulin Resistance

PubMed Central

Hassan, Waseem

2013-01-01

Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

Is There Any Relationship between Plasma 25-Hydroxyvitamin D3, Adipokine Profiles and Excessive Body Weight in Type 2 Diabetic Patients?

PubMed Central

Dziemidok, Piotr; Kiełczykowska, Małgorzata; Kurzepa, Jacek; Szcześniak, Grzegorz; Musik, Irena

2017-01-01

A growing interest in the role of vitamin D in metabolic diseases led us to study the relationships between 25-hydroxyvitamin D3 (25(OH)D3) and the profiles of selected adipokines in type 2 diabetic (T2DM) patients. The study comprised 92 type 2 diabetics divided into quartiles regarding 25(OH)D3 concentration. Each group was divided into male and female subgroups. All the studied patients had their anthropometric and biochemical parameters determined. Plasma 25-hydroxyvitamin D3 concentration was determined by HPLC, while the selected adipokines (leptin, adiponectin, resistin and visfatin) by ELISA methods. The ratio of leptin to adiponectin (L/A) was calculated for all the patients. In 85.3% of diabetics a full (<20 ng/mL) or moderate (20–30 ng/mL) vitamin D deficit was found. Irrespective of sex, plasma leptin concentration decreased across increasing quartiles of 25(OH)D3 level. In women, 25(OH)D3 was negatively correlated with BMI, leptin level as well as L/A ratio, and positively with adiponectin concentration. In men, 25(OH)D3 was positively correlated with HDL and negatively with systolic blood pressure (SBP), leptin level and L/A ratio. Considering all the patients, there ocurred a significant negative correlation between 25(OH)D3 and SBP, BMI, WHR, TG, leptin and L/A ratio and positive ones between 25(OH)D3 and both adiponectin and HDL. The results of the study support the existence of the relationship among vitamin D, obesity and leptin in type 2 diabetic patients. PMID:29295491

Association Between Coffee Consumption and Circulating Levels of Adiponectin and Leptin.

PubMed

Lee, Chang Beom; Yu, Sung Hoon; Kim, Na Yeon; Kim, Seon Mee; Kim, Sung Rae; Oh, Seung Joon; Jee, Sun Ha; Lee, Jung Eun

2017-11-01

Coffee has been proposed to have benefits for chronic diseases; however, the relevant mechanism remains to be elucidated. We conducted a cross-sectional study and evaluated the levels of adiponectin and leptin in relation to coffee consumption. We included a total of 4406 individuals (men = 2587 and women = 1819) for adiponectin analysis and 2922 individuals (men = 1731 and women = 1191) for leptin analysis. Participants answered number of cups of coffee per week and types of coffee they consumed and their serum levels of adiponectin and leptin were measured using an enzyme-linked immunosorbent assay. We found that increasing coffee consumption was associated with increased levels of adiponectin among women; geometric means of adiponectin were 8.0 (95% CI: 7.2-8.9 μg/mL) among women who regularly consumed 15 or greater cups/week, but 7.5 (95% CI: 6.8-8.4 μg/mL) among women who did not consume coffee (P for trend = .009). Leptin levels were inversely associated with coffee consumption among both men and women (P for trend = .04 for men and 0.04 for women); geometric means of 15 or greater cups of coffee per week were 2.6 (95% CI: 2.4-2.8 ng/mL) among men and 5.1 (95% CI: 4.5-5.8 ng/mL) among women, but for noncoffee drinkers, geometric means were 3.0 (95% CI: 2.7-3.3 ng/mL) for men and 5.8 (95% CI: 5.1-6.6 ng/mL) for women. Coffee consumption was associated with higher circulating levels of adiponectin and lower circulating levels of leptin. Our study may suggest that improvement in adipocyte function contributes to the beneficial metabolic effects of coffee consumption.

Effects of 17β-estradiol and progesterone on the production of adipokines in differentiating 3T3-L1 adipocytes: Role of Rho-kinase.

PubMed

Pektaş, Mehtap; Kurt, Akif Hakan; Ün, İsmail; Tiftik, Rukiye Nalan; Büyükafşar, Kansu

2015-04-01

Effect of female sex hormones on the production/release of adipocyte-derived cytokines has been debatable. Furthermore, whether the cellular signaling triggered by these hormones involve Rho-kinase has not been investigated yet. Therefore, in this study, effects of 17β-estradiol and progesterone as well as the Rho-kinase inhibitor, Y-27632 on the level of adipokines such as resistin, adiponectin, leptin, TNF-α and IL-6 were investigated in 3T3-L1-derived adipocytes. Differentiation was induced in the post-confluent preadipocytes by the standard differentiation medium (Dulbecco's modified Eagle's medium with 10% fetal bovine serum together with the mixture of isobutylmethylxanthine, dexamethasone and insulin) in the presence of 17β-estradiol (10(-8)-10(-7)M), progesterone (10(-6)-10(-5)M), the Rho-kinase inhibitor, Y-27632 (10(-5)M) and their combination for 8days. Measurements of the adipokines were performed in the culturing medium by ELISA kits using specific monoclonal antibodies. 17β-estradiol elevated resistin but decreased adiponectin and IL-6 levels; however, it did not alter the concentration of leptin and TNF-α. Y-27632 pretreatment inhibited the rise of resistin and the fall of adiponectin by 17β-estradiol without any effects by its own. Progesterone did not change resistin, leptin and TNF-α level; however, it elevated adiponectin and decreased IL-6 production. Neither 17β-estradiol nor Y-27632 was able to antagonize the increase of adiponectin and the reduction of IL-6 levels by progesterone. While Y-27632 alone lowered IL-6 level, it increased leptin and TNF-α concentration without altering resistin and adiponectin. In conclusion, 17β-estradiol could modify adipokine production in 3T3-L1 adipocytes with the actions some of which involve Rho-kinase mediation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Association of serum leptin and adiponectin with anthropomorphic indices of obesity, blood lipids and insulin resistance in a Sub-Saharan African population.

PubMed

Ayina, Clarisse Noël A; Noubiap, Jean Jacques N; Etoundi Ngoa, Laurent Serge; Boudou, Philippe; Gautier, Jean François; Mengnjo, Michel Karngong; Mbanya, Jean Claude; Sobngwi, Eugene

2016-05-17

There is little data on the metabolic effects of adipokines in sub-Saharan African populations. This study aimed to explore the potential relationship of leptin and adiponectin, with obesity, plasma lipids and insulin resistance in a Cameroonian population. We enrolled 167 men and 309 women aged ≥18 years from the general population in Cameroon. Data were collected on waist circumference (WC), body mass index (BMI), waist-to-hip ratio (WHR), body fat (BF%), fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). Pearson's correlation and multiple stepwise linear regression analyses were used to determine correlates of leptin and adiponectin serum levels. The prevalence of obesity was higher in women compared to men (p < 0.0001), and Central obesity which is more prevalent particularly in women (WC = 42.4%, WHR = 42.3%), is almost for 90% comparable to %BF (42.7%). Adiponectin negatively with BMI (r = -0.294, p < 0.0001), WC (r = -0.294, p < 0.0001), %BF (r = -0.122, p = 0.028), WHR (r = -0.143, p = 0.009), triglycerides (r = -0.141, p = 0.011), HOMA-IR (r = -0.145, p = 0.027) and insulin (r = -0.130, p = 0.048). Leptin positively correlated with BMI (r = 0.628), WC (r = 0.530), BF% (r = 0.720), (all p < 0.0001); with DBP (r = 0.112, p = 0.043), total cholesterol (r = 0.324, p < 0.0001), LDL-cholesterol (r = 0.298, p < 0.0001), insulin (r = 0.320, p < 0.001 and HOMA-IR (r = 0.272, p < 0.0001). In multiple stepwise regression analysis, adiponectin was negatively associated with WC (β = -0.38, p = 0.001) and BF% (β = 0.33, p < 0.0001), while leptin was positively associated with BF% (β = 0.60, p < 0.0001), total cholesterol (β = 0.11, p = 0.02) and HOMA-IR (β = 0.11, p = 0.02). When controlled for gender, HOMA-IR was found significantly associated to adiponectin (β = 0.13, p = 0.046), but not BF%, while the association previously found between leptin and HOMA

Effects of Body Fat on the Associations of High-Molecular-Weight Adiponectin, Leptin and Soluble Leptin Receptor with Metabolic Syndrome in Chinese

PubMed Central

Yu, Danxia; Yu, Zhijie; Sun, Qi; Sun, Liang; Li, Huaixing; Song, Jun; Mi, Ming; Wu, Hongyu; Lu, Ling; Liu, Chen; Zhang, Geng; Hu, Frank B.; Lin, Xu

2011-01-01

Background Little is known regarding the associations between high-molecular-weight (HMW-) adiponectin, leptin and soluble leptin receptor (sOB-R) and metabolic syndrome (MetS) in Chinese. Also few studies elucidate the effects of inflammation and body fat mass on the relations. Methods Plasma HMW-adiponectin, leptin and sOB-R were measured among 1055 Chinese men and women (35∼54 yrs). Whole body and trunk fat mass were determined by Dual-energy X-ray absorptiometry. MetS was defined by the updated NCEP/ATPIII criterion for Asian-Americans. Results HMW-adiponectin was inversely associated with MetS in multivariate model including fat mass index (FMI), inflammatory markers, leptin and sOB-R (OR in the highest quartile  = 0.30, 95%CI 0.18∼0.50, P<.0001). Plasma sOB-R was also inversely associated with MetS independent of body fatness and inflammatory markers, whereas the association was somewhat attenuated after adjusting HMW-adiponectin (OR for the highest quartile  = 0.78, 95%CI 0.47∼1.32, P = 0.15). In contrast, leptin was associated with increased odds of MetS independent of inflammatory markers, HMW-adiponectin, and sOB-R (OR for the highest quartile  = 2.64, 95%CI 1.35∼5.18, P = 0.006), although further adjustment for FMI abolished this association. Conclusions HMW-adiponectin exhibited strong inverse associations with MetS independent of body composition, inflammation, leptin and sOB-R; while the associations of leptin and sOB-R were largely explained by fat mass or HMW-adiponectin, respectively. PMID:21347230

The Role of Adipokines in Intervertebral Disc Degeneration.

PubMed

Sharma, Anirudh

2018-04-24

Intervertebral disc degeneration (IDD) is an important cause of low back pain. Recent evidence suggests that in addition to abnormal and excessive mechanical loading, inflammation may be a key driver for both IDD and low back pain. Obesity, a known mechanical risk factor of IDD, is now increasingly being recognized as a systemic inflammatory state with adipokines being postulated as likely inflammatory mediators. The aim of this review was to summarize the current literature regarding the inflammatory role of adipokines in the pathophysiology of IDD. A systematic literature search was performed using the OVID Medline, EMBASE and PubMed databases to identify all studies assessing IDD and adipokines. Fifteen studies were included in the present review. Leptin was the most commonly assessed adipokine. Ten of 15 studies were conducted in humans; three in rats and two in both humans and rats. Studies focused on a variety of topics ranging from receptor identification, pathway analysis, genetic associations, and proteonomics. Currently, data from both human and animal experiments demonstrate significant effects of leptin and adiponectin on the internal milieu of intervertebral discs. However, future studies are needed to determine the molecular pathway relationships between adipokines in the pathophysiology of IDD as avenues for future therapeutic targets.

Adiponectin activation of AMPK disrupts leptin-mediated hepatic fibrosis via suppressors of cytokine signaling (SOCS-3).

PubMed

Handy, Jeffrey A; Saxena, Neeraj K; Fu, Pingping; Lin, Songbai; Mells, Jamie E; Gupta, Nitika A; Anania, Frank A

2010-08-01

Adiponectin is an adipocytokine that was recently shown to be anti-fibrogenic in hepatic fibrosis. Leptin, on the other hand, promotes hepatic fibrosis. The purpose of the present study was to elucidate a mechanism (or mechanisms) whereby adiponectin dampens leptin signaling in activated hepatic stellate cells (HSCs), and prevents excess extracellular matrix production. Activated HSCs, between passages 2 and 5, were cultured and exposed to recombinant human adiponectin and recombinant leptin. Immunoblot analysis for SOCS-3, TIMP-1, and the phosphorylated species of Stat3 and adenosine monophosphate-activated protein kinase (AMPK) were conducted. We also examined MMP-1 activity by immunosorbant fluorimetric analysis. In HSCs, adiponectin-induced phosphorylation of AMPK, and subsequently suppressed leptin-mediated Stat3 phosphorylation and SOCS-3 induction. Adiponectin also blocked leptin-stimulated secretion of TIMP-1, and significantly increased MMP-1 activity, in vitro. To extend this study, we treated adiponectin knockout mice (Ad-/-) daily with 5 mg/kg recombinant leptin and/or carbon tetrachloride (2 ml/kg) for 6 weeks. Post-necropsy analysis was performed to examine for inflammation, and histological changes in the Ad-/- and wild-type mice. There was no significant difference in inflammation, or aminotransferases, between mice receiving carbon tetrachloride and leptin versus carbon tetrachloride alone. As anticipated, the combination of leptin and CCl(4) enhanced hepatic fibrosis in both wild-type and Ad-/- mice, as estimated by amount of collagen in injured livers, but wild-type mice had significantly higher levels of SOCS-3 and significantly lower levels of TIMP-1 mRNA and protein than did adiponectin KO mice exposed to both CCl(4) and leptin. We therefore conclude that the protective effects of adiponectin against liver fibrosis require AMPK activation, and may occur through inhibition of the Jak-Stat signal transduction pathway. Published 2010 Wiley

Influence of Weight Loss, Body Composition, and Lifestyle Behaviors on Plasma Adipokines: A Randomized Weight Loss Trial in Older Men and Women with Symptomatic Knee Osteoarthritis

PubMed Central

Miller, Gary D.; Jenks, Monica Z.; Vendela, Mandolyn; Norris, James L.; Muday, Gloria K.

2012-01-01

Objective. To investigate effects of weight loss on adipokines and health measures in obese older adults with symptomatic knee osteoarthritis. Methods. Participants were randomly assigned to either weight loss (WL) (men: 12, women: 14) or weight stable (WS) group (men: 12, women: 13). WL intervention included meal replacements and structured exercise training. Measurements of leptin, adiponectin, soluble leptin receptor, lifestyle behaviors, and body composition were collected at baseline and 6 months. Univariate analysis of covariance was performed on 6 month variables, and Spearman and partial correlations were made between variables. Results. Weight loss was 13.0% and 6.7% in WL for men and women, respectively. Women in WL had lower whole body and trunk fat than WS. The leptin : adiponectin ratio was lower for women in WL than WS at 6 months, with no group differences in adipokines for men. Leptin and free leptin index correlated with body fat in both genders at baseline. Interestingly, only women showed reductions in leptin (P < 0.100) and correlations between the percentage change leptin and trunk fat and the percentage changes in free leptin index with total fat and trunk fat. Partial correlations between 6 month adipokines after adjustments for covariates and group/time period show potential multivariate influences. Conclusions. In the presence of an effective weight loss intervention in older obese adults, there are significant relationships between weight and fat loss and leptin in women, but not men, suggesting gender-specific features of adipokine metabolism in this age group. PMID:23326650

Dichotomous roles of leptin and adiponectin as enforcers against lipotoxicity during feast and famine.

PubMed

Unger, Roger H; Scherer, Philipp E; Holland, William L

2013-10-01

Science is marked by the death of dogmas; the discovery that adipocytes are more than just lipid-storing cells but rather produce potent hormones is one such example that caught physiologists by surprise and reshaped our views of metabolism. While we once considered the adipocyte as a passive storage organ for efficient storage of long-term energy reserves in the form of triglyceride, we now appreciate the general idea (once a radical one) that adipocytes are sophisticated enough to have potent endocrine functions. Over the past two decades, the discoveries of these adipose-derived factors ("adipokines") and their mechanistic actions have left us marveling at and struggling to understand the role these factors serve in physiology and the pathophysiology of obesity and diabetes. These hormones may serve an integral role in protecting nonadipose tissues from lipid-induced damage during nutrient-deprived or replete states. As such, adipocytes deliver not only potentially cytotoxic free fatty acids but, along with these lipids, antilipotoxic adipokines such as leptin, adiponectin, and fibroblast growth factor 21 that potently eliminate excessive local accumulation of these lipids or their conversion to unfavorable sphingolipid intermediates.

Evaluation of leptin, adiponectin, and ghrelin levels in patients with acne vulgaris.

PubMed

Ozuguz, P; Kacar, S D; Asik, G; Ozuguz, U; Karatas, S

2016-02-09

The research evaluating adipokines are very few in patients with acne vulgaris. The hypothesis that hyperinsulinemic and high glycemic index diet plays a role in the pathogenesis of acne is still controversial. In this study, we aimed to evaluate adipokines such as leptin (L), adiponectin (A), ghrelin and A levels, and A/L rates that indicate insulin resistance in nonobese patients with severe acne vulgaris. Thirty patients who are nonobese with moderate acne vulgaris, aged 18 to 25 years, and 15 age-sex compatible controls were included in our study. The acne lesions were assessed using the Global Acne Grading Scale (GAGS). All participants were evaluated for the parameters that may affect the metabolism of serum L, A, and ghrelin levels in blood, and their body mass index were calculated. The significance level was determined as p ≤ 0.05. Of the 30 patients, 17 were women and 13 were men. The mean age was 20.60 years and the mean duration of the disease were 2.8 years. All of patients had moderate acne vulgaris (GAGS 19-30). Of the 15 controls, 11 were women and 4 were men. The mean age was 21.20 years. There were not a statistically significant difference in L, ghrelin, A levels, and A/L ratio between the two groups. Adipokines may have a role in the pathogenesis of acne vulgaris. L, A, ghrelin, and insulin resistance may not participate in the responsible mechanisms in nonobese patients with moderate acne vulgaris. © The Author(s) 2016.

Exercise effects on adipokines and the IGF axis in men with prostate cancer treated with androgen deprivation: A randomized study

PubMed Central

Mina, Daniel Santa; Connor, Michael K.; Alibhai, Shabbir M.H.; Toren, Paul; Guglietti, Crissa; Matthew, Andrew G.; Trachtenberg, John; Ritvo, Paul

2013-01-01

Background Androgen deprivation therapy (ADT) has significant deleterious effects on body composition that may be accompanied by unfavourable changes in adipokine levels. While exercise has been shown to improve a number of side effects associated with ADT for prostate cancer, no studies have assessed the effect of exercise on adiponectin and leptin levels, which have been shown to alter the mitogenic environment. Methods: Twenty-six men with prostate cancer treated with ADT were randomized to home-based aerobic exercise training or resistance exercise training for 24 weeks. Adiponectin, leptin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) were analyzed by ELISA (enzyme-linked immunosorbent assay), in addition to physical activity volume, peak aerobic capacity, and anthropometric measurements, at baseline, 3 months and 6 months. Results: Resistance exercise significantly reduced IGF-1 after 3 months (p = 0.019); however, this change was not maintained at 6 months. At 6 months, IGFBP-3 was significantly increased compared to baseline for the resistance training group (p = 0.044). In an exploratory analysis of all exercisers, favourable changes in body composition and aerobic fitness were correlated with favourable levels of leptin, and favourable leptin:adiponectin and IGF-1:IGFBP-3 ratios at 3 and 6 months. Conclusions: Home-based exercise is correlated with positive changes in adipokine levels and the IGF-axis that may be related to healthy changes in physical fitness and body composition. While the improvements of adipokine markers appear to be more apparent with resistance training compared to aerobic exercise, these findings must be considered cautiously and require replication from larger randomized controlled trials to clarify the role of exercise on adipokines and IGF-axis proteins for men with prostate cancer. PMID:24282459

Impact of Atypical Antipsychotic Therapy on Leptin, Ghrelin, and Adiponectin

PubMed Central

Jin, Hua; Meyer, Jonathan M.; Mudaliar, Sunder; Jeste, Dilip V.

2009-01-01

Background Many adverse effects of atypical antipsychotic treatment are associated with antagonism of monoamine receptors; however, data indicate that important metabolic effects, such as hypertriglyceridemia and impairment in glucose/insulin homeostasis, may not be related to these mechanisms, leading investigators to explore alternative hypotheses. Promising candidates include a possible impact of antipsychotics on peptide hormonal regulators of metabolic control such as leptin, ghrelin, and adiponectin. The purpose of this review is to summarize recent data on changes in these hormones during atypical antipsychotic treatment. Methods A Medline search was performed for papers published from January 1999 to January 2007 using key words antipsychotic, atypical antipsychotic, and individual atypical antipsychotic drug names cross-referenced with leptin, ghrelin, and adiponectin. Results The bulk of the published work focused on changes in body weight and serum leptin, with far less data on ghrelin, and adiponectin, and non-weight metabolic changes. Leptin changes were directly related to a medication’s weight gain liability, with no added antipsychotic effects on leptin signaling. Conflicting results emerged for the other markers, but all three long-term studies on ghrelin showed increased levels in patients on atypical antipsychotics with weight gain liabilities. Conclusions Leptin increases during antipsychotic treatment are a result of weight gain rather than a direct impact of atypical antipsychotics on leptin physiology. Preliminary long-term data show increased ghrelin levels, but this finding must be replicated. The association with antipsychotic effects on glucose and lipid metabolism and these hormones remains virtually unstudied. Future research should indicate whether ghrelin and other peptide hormones may be useful predictors of weight gain or metabolic changes in patients on antipsychotics. PMID:18206351

Experimental hyperthyroidism decreases gene expression and serum levels of adipokines in obesity.

PubMed

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Male Wistar rats were randomly divided into two groups: control (C)-fed with commercial chow ad libitum-and obese (OB)-fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T(3))/100 BW (OT). The T(3) dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. T(3) treatment was effective, increasing fT(3) levels and decreasing fT(4) and TSH serum concentration. Administration of T(3) promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Our results suggest that T(3) modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T(3) and adipokines in obesity.

Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

PubMed Central

Luvizotto, Renata de Azevedo Melo; do Nascimento, André Ferreira; de Síbio, Maria Teresa; Olímpio, Regiane Marques Castro; Conde, Sandro José; Lima-Leopoldo, Ana Paula; Leopoldo, André Soares; Cicogna, Antonio Carlos; Nogueira, Célia Regina

2012-01-01

Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity. PMID:22645452

Serum levels of leptin and high molecular weight adiponectin are inversely associated with radiographic spinal progression in patients with ankylosing spondylitis: results from the ENRADAS trial.

PubMed

Hartl, Agnes; Sieper, Joachim; Syrbe, Uta; Listing, Joachim; Hermann, Kay-Geert; Rudwaleit, Martin; Poddubnyy, Denis

2017-06-15

Previous research indicates a role of adipokines in inflammation and osteogenesis. Hence adipokines might also have a pathophysiological role in inflammation and new bone formation in patients with ankylosing spondylitis (AS). The aim of this study was to investigate the role of adipokine serum levels as predictors of radiographic spinal progression in patients with AS. A total of 120 patients with definite AS who completed a 2-year follow up in the ENRADAS trial were included in the current study. Radiographic spinal progression was defined as: (1) worsening of the modified Stoke Ankylosing Spondylitis spine (mSASSS) score by ≥2 points and/or (2) new syndesmophyte formation or progression of existing syndesmophytes after 2 years. Serum levels of adipokines (adiponectin (APN) and its high molecular weight form (HMW-APN), chemerin, leptin, lipocalin-2, omentin, resistin, visfatin) were measured using enzyme-linked immunosorbent assays. There was a significant association between radiographic spinal progression and both leptin and HMW-APN. Baseline serum levels of both adipokines were lower in patients who showed radiographic spinal progression after 2 years. This association was especially evident in men; they had generally lower leptin and HMW-APN serum levels as compared to women. The inverse association between adipokines and radiographic spinal progression was confirmed in the logistic regression analysis: the odds ratios (OR) for the outcome "no mSASSS progression ≥2 points" were 1.16 (95% CI 1.03 to 1.29) and 1.17 (95% CI 0.99 to 1.38), for leptin and HMW-APN, respectively; for "no syndesmophyte formation/progression" the respective OR were 1.29 (95% CI 1.11 to 1.50) and 1.18 (95% CI 0.98 to 1.42), adjusted for the presence of syndesmophytes at baseline, C-reactive protein at baseline, sex, body mass index (BMI), non-steroidal anti-inflammatory drugs intake score over 2 years, and smoking status at baseline. Serum leptin and HMW-APN predict

Leptin, adiponectin and serotonin levels in lean and obese dogs.

PubMed

Park, Hyung-Jin; Lee, Sang-Eun; Oh, Jung-Hyun; Seo, Kyoung-Won; Song, Kun-Ho

2014-05-13

Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity.

Leptin, adiponectin and serotonin levels in lean and obese dogs

PubMed Central

2014-01-01

Background Serotonin (5-hydroytryptamine or 5HT) is associated with numerous behavioral and psychological factors and is a biochemical marker of mood. 5HT is involved in the hypothalamic regulation of energy consumption. 5HT controls appetite in the central nerve system (CNS) and stimulates intestinal mobility. There are few studies looking at the role of 5HT and the relationship between peripheral circulating serotonin and obesity. The aim of this study was to find any differences in leptin, adiponectin, and 5HT between lean and obese dogs and to identify correlations among these factors. Results Leptin, triglyceride (TG) and cholesterol levels were higher in the obese group (all p < 0.01). Adiponectin and 5HT levels were higher in the lean group compared to the obese group (p < 0.01). Leptin (r = 0.628, p < 0.01), TG (r = 0.491, p < 0.01) and cholesterol (r = 0.419, p < 0.01) were positively correlated with body condition score (BCS), and adiponectin (r = -0.446, p < 0.01) and 5HT (r = -0.490, p < 0.01) were negatively correlated with BCS. Leptin was negatively correlated with adiponectin (r = -0.294, p < 0.01) and 5HT (r = -0.343, p < 0.01). 5HT was negatively correlated with leptin (r = -0.343, p < 0.01), TG (r = -0.268, p < 0.05) and cholesterol (r = -0.357, p < 0.05). Conclusions 5HT is an important appetite control neurotransmitter, but there are limited studies for 5HT levels related to obesity in dogs. To the best of our knowledge, this is the first study to evaluate peripheral 5HT levels in obese dogs. From this research, we can assume that 5HT may be correlated with canine obesity. Further studies will be needed to further elucidate the role of low serum 5HT levels in canine obesity. PMID:24886049

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis.

PubMed

González-Reimers, Emilio; López-Prieto, Javier; Quintero-Platt, Geraldine; Pelazas-González, Ricardo; Alemán-Valls, M Remedios; Pérez-Hernández, Onán; de-la-Vega-Prieto, M José; Gómez-Rodríguez, M Angeles; Martín-González, Candelaria; Santolaria-Fernández, Francisco

2016-01-08

To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines.

Adipokines in human milk and risk of overweight in early childhood: a prospective cohort study.

PubMed

Weyermann, Maria; Brenner, Hermann; Rothenbacher, Dietrich

2007-11-01

Multiple studies have suggested that breast-feeding can prevent obesity, but the evidence remains inconclusive. The concentrations of specific constituents of human milk, such as adipokines, may play a role in this relationship, and these have rarely been considered. We assessed the role of adiponectin and leptin in human milk in childhood overweight. Between November 2000 and November 2001 all women delivering at the Department of Gynecology and Obstetrics at the University of Ulm, Germany were invited to participate in the study together with their healthy newborns. Milk samples were collected 6 weeks postpartum. Adiponectin and leptin levels were determined by commercially available ELISA. Active follow-up was performed at age 12 and 24 months. Of the 674 breast-fed children, 56 (8%) were overweight at the age of 2 years. Median adiponectin and leptin levels in milk were 10.9 ng/mL and 174.5 pg/mL, respectively. Adjusted odds ratio for overweight at the age of 2 was 1.6 (95% confidence interval = 1.0-2.6) per unit increase of log adiponectin and 1.1 (0.8-1.5) per unit increase of log leptin. Among children who were breast-fed for at least 6 months, adjusted odds ratios were 2.1 (1.1-4.2) per unit increase of log adiponectin, and 1.1 (0.7-1.6) per unit increase of log leptin. High levels of adiponectin in maternal milk may be a risk factor for childhood overweight.

Adipokines and insulin action: A sensitive issue.

PubMed

Knights, Alexander J; Funnell, Alister Pw; Pearson, Richard Cm; Crossley, Merlin; Bell-Anderson, Kim S

2014-04-01

Obesity is a major public health concern and a strong risk factor for insulin resistance, type 2 diabetes mellitus (T2DM), and cardiovascular disease. The last two decades have seen a reconsideration of the role of white adipose tissue (WAT) in whole body metabolism and insulin action. Adipose tissue-derived cytokines and hormones, or adipokines, are likely mediators of metabolic function and dysfunction. While several adipokines have been associated with obese and insulin-resistant phenotypes, a select group has been linked with insulin sensitivity, namely leptin, adiponectin, and more recently, adipolin. What is known about these insulin-sensitizing molecules and their effects in healthy and insulin resistant states is the subject of this review. There remains a significant amount of research to do to fully elucidate the mechanisms of action of these adipokines for development of therapeutics in metabolic disease.

Protein kinase CK2 interacts with adiponectin receptor 1 and participates in adiponectin signaling.

PubMed

Heiker, John T; Wottawah, Cornelia M; Juhl, Cathleen; Kosel, David; Mörl, Karin; Beck-Sickinger, Annette G

2009-06-01

Adiponectin is an adipokine with anti-atherogenic, anti-diabetic and insulin sensitizing properties. Its effects on energy homeostasis, glucose and lipid metabolism are mediated by two ubiquitously expressed seven-transmembrane receptors, AdipoR1 and -R2. With the exception of APPL1 and RACK1, no intracellular binding partners of adiponectin receptors are reported and thus signaling pathways downstream of these receptors remain largely unknown. To incorporate adiponectins protective potential in drug development it is essential to understand adiponectin signaling cascades in detail. A yeast two-hybrid approach employing AdipoR1s cytoplasmatic N-terminus led to the identification of the regulatory subunit of protein kinase CK2. We confirmed the interaction in co-immunoprecipitation, ELISA experiments and co-localization analysis in mammalian cells. Furthermore we could localize the interaction site in an N-terminal basic region close to the transmembrane domain. In adiponectin stimulation experiments of C2C12 mouse myotubes and MCF7 cells incorporating CK2 inhibitor 2-dimethylamino-4,5,6,7-tetrabromo-1H-benz-imidazole (DMAT) we found a modulator role of CK2 in adiponectin signaling. Accordingly we identified the regulatory subunit of protein kinase CK2 as a novel intracellular partner of AdipoR1 and have strong evidence of CK2 as an effector molecule in adiponectin signaling. Since CK2 is involved in signaling cascades of other adipokines and hormones, e.g. leptin and insulin, our findings suggest a possible key function in crosstalk between adiponectin and insulin signaling pathways and could provide further insight into the anti-diabetic effects of adiponectin.

Possible implications of leptin, adiponectin and ghrelin in the regulation of energy homeostasis by thyroid hormone.

PubMed

Kokkinos, Alexander; Mourouzis, Iordanis; Kyriaki, Despoina; Pantos, Constantinos; Katsilambros, Nicholas; Cokkinos, Dennis V

2007-08-01

Thyroid hormone plays a critical role in energy homeostasis through mechanisms, which are not fully understood. In the present study, we investigated possible alterations of important energy regulators such as leptin, adiponectin, and ghrelin in relation to changes in thyroid hormones. Thyroid hormone (250 microg/kg) was administered in male Wistar rats for 2 weeks (THYR), while hypothyroidism (HYPO) was induced by propylthiouracil administration (0.05% in drinking water) for 3 weeks. Untreated animals served as controls (NORM). Leptin and adiponectin were measured in plasma by ELISA, while total ghrelin was measured with RIA. Body weight was significantly reduced both in THYR and HYPO rats, while food intake was significantly increased in THYR and decreased in HYPO. This response was associated with various changes in leptin, adiponectin, and ghrelin in plasma. In fact, in THYR rats, leptin levels (mean +/- SEM) were 240 +/- 55 pg/ml as compared to 819 +/- 70 pg/ml in untreated rats (P < 0.05), while no changes were observed in ghrelin and adiponectin. In HYPO rats, leptin levels were 1400 +/- 200 pg/ml vs. 819 +/- 70 pg/ml in untreated rats (P < 0.05), while ghrelin and adiponectin were significantly increased in HYPO rats as compared to untreated rats (P < 0.05). Furthermore, T(3) and T(4) levels were inversely correlated to leptin (P = 0.014), while ghrelin and adiponectin were inversely correlated to weight changes (P = 0.05 and P = 0.03, respectively). In conclusion, leptin seems mainly to be involved in the thyroid hormone effects on energy homeostasis. Ghrelin and adiponectin may serve a compensatory physiological role in hypothyroidism.

Gene expression of leptin, resistin, and adiponectin in the white adipose tissue of obese patients with non-alcoholic fatty liver disease and insulin resistance.

PubMed

Baranova, Ancha; Gowder, Shobha J; Schlauch, Karen; Elariny, Hazem; Collantes, Rochelle; Afendy, Arian; Ong, Janus P; Goodman, Zachary; Chandhoke, Vikas; Younossi, Zobair M

2006-09-01

Adipose tissue is an active endocrine organ that secretes a variety of metabolically important substances including adipokines. These factors affect insulin sensitivity and may represent a link between obesity, insulin resistance, type 2 diabetes (DM), and nonalcoholic fatty liver disease (NAFLD). This study uses real-time polymerase chain reaction (PCR) quantification of mRNAs encoding adiponectin, leptin, and resistin on snap-frozen samples of intra-abdominal adipose tissue of morbidly obese patients undergoing bariatric surgery. Morbidly obese patients undergoing bariatric surgery were studied. Patients were classified into two groups: Group A (with insulin resistance) (N=11; glucose 149.84 +/- 40.56 mg/dL; serum insulin 8.28 +/- 3.52 microU/mL), and Group B (without insulin resistance) (N=10; glucose 102.2 +/- 8.43 mg/dL; serum insulin 3.431 +/- 1.162 microU/mL). Adiponectin mRNA in intra-abdominal adipose tissue and serum adiponectin levels were significantly lower in Group A compared to Group B patients (P<0.016 and P<0.03, respectively). Although serum resistin was higher in Group A than in Group B patients (P<0.005), resistin gene expression was not different between the two groups. Finally, for leptin, neither serum level nor gene expression was different between the two groups. Serum adiponectin level was the only predictor of nonalcoholic steatohepatitis (NASH) in this study (P=0.024). Obese patients with insulin resistance have decreased serum adiponectin and increased serum resistin. Additionally, adiponectin gene expression is also decreased in the adipose tissue of these patients. This low level of adiponectin expression may predispose patients to the progressive form of NAFLD or NASH.

Genetic Determination of Serum Levels of Diabetes-Associated Adipokines

PubMed Central

Schleinitz, Dorit

2015-01-01

Adipose tissue secretes an abundance of proteins. Some of these proteins are known as adipokines and adipose-derived hormones which have been linked with metabolic disorders, including type 2 diabetes, and even with cancer. Variance in serum adipokine concentration is often closely associated with an increase (obesity) or decrease (lipodystrophy) in fat tissue mass, and it is affected by age, gender, and localization of the adipose tissue. However, there may be genetic variants which, in consequence, influence the serum concentration of a certain adipokine, and thereby promote metabolic disturbances or, with regard to the “protective” allele, exert beneficial effects. This review focuses on the genetic determination of serum levels of the following adipokines: adiponectin, chemerin, leptin, progranulin, resistin, retinol binding protein 4, vaspin, adipsin, apelin, and omentin. The article reports on the latest findings from genome-wide association studies (GWAS) and candidate gene studies, showing variants located in/nearby the adipokine genes and other (non-receptor) genes. An extra chapter highlights adipokine-receptor variants. Epigenetic studies on adipokines are also addressed. PMID:26859657

Prognostic Value of Adipokines in Predicting Cardiovascular Outcome: Explaining the Obesity Paradox.

PubMed

Wolk, Robert; Bertolet, Marnie; Singh, Prachi; Brooks, Maria M; Pratley, Richard E; Frye, Robert L; Mooradian, Arshag D; Rutter, Martin K; Calvin, Andrew D; Chaitman, Bernard R; Somers, Virend K

2016-07-01

To evaluate the cardiovascular (CV) prognostic value of adipokines in a large prospective cohort of patients participating in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial. The effects of the adipokine levels at baseline and change from baseline on the composite outcome (CV death, myocardial infarction, and stroke) were analyzed using unadjusted and fully adjusted Cox models in 2330 patients with type 2 diabetes and coronary artery disease who had participated in the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial (from January 1, 2001, through December 1, 2008). In a fully adjusted model, baseline leptin and change from baseline leptin were protective for CV events, whereas baseline adiponectin, baseline tumor necrosis factor α (TNF-α), change from baseline TNF-α, baseline C-reactive protein (CRP), and change from baseline CRP were harmful. The effect of baseline leptin on CV events depended on the body mass index (BMI), such that the hazard ratios (HRs) varied between 0.6 and 1.4 across the BMI quintiles (interaction P=.03). The same was true for baseline adiponectin (HR varied from 0.7 to 1.7; interaction P=.01), change from baseline monocyte chemoattractant protein-1 (HR varied from 0.8 to 1.8; interaction P=.03), change from baseline TNF-α (HR varied from 0.9 to 1.4; interaction P=.02), and change from baseline IL-6 (HR varied from 0.7 to 1.8; interaction P=.005). Adipokines are independent predictors of CV events in patients with type 2 diabetes and coronary artery disease. The association between the specific adipokines and CV outcome varies depending on BMI. This reflects the complex pathophysiology of CV disease in obesity and may help explain the "obesity paradox." clinicaltrials.gov Identifier: NCT00006305. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Leptin Is Associated With Persistence of Hyperglycemia in Acute Pancreatitis

PubMed Central

Kennedy, James I.C.; Askelund, Kathryn J.; Premkumar, Rakesh; Phillips, Anthony R.J.; Murphy, Rinki; Windsor, John A.; Petrov, Maxim S.

2016-01-01

Abstract Adipokines have many homeostatic roles, including modulation of glucose metabolism, but their role in the pathophysiology of hyperglycemia associated with acute and critical illnesses in general, and acute pancreatitis (AP) in particular, is largely unknown. This study aimed to investigate the relationship between a panel of adipokines and hyperglycemia in the early course of AP, as well as the role of adipokines as predictors of AP severity. Adiponectin, leptin, omentin, resistin, and visfatin were measured on a daily basis in the first 72 hours after hospital admission. A first set of analyses was undertaken with admission glycemia stratified by severity, and a second set of analyses was undertaken based on persistence of early hyperglycemia. All of the analyses were adjusted for confounders. A total of 32 patients with AP were included in this study. None of the studied adipokines was significantly associated with glucose level on admission. Leptin was significantly (P = 0.003) increased in patients with persistent hyperglycemia. Adiponectin was significantly associated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) score in patients with persistent hyperglycemia (P = 0.015), visfatin with APACHE II score in patients with persistent hyperglycemia (P = 0.014), and omentin with APACHE II score in all of the patients regardless of the presence or absence of hyperglycemia (P = 0.021). Leptin is significantly associated with persistent hyperglycemia in the early course of AP. Omentin has a potential to become an accurate predictor of AP severity. PMID:26871770

Effect of heat stress on adipokines and some blood metabolites in goats from Jordan.

PubMed

Al-Dawood, Amani

2017-02-01

To date and to the best of our knowledge, there have been no available data on the interaction between heat stress (HS) and secretion of adipokines and some blood metabolites in Baladi goats from Jordan. Therefore, this study aimed at evaluating the changes in leptin, adiponectin, non-ester fatty acid (NEFA) and beta-hydroxybutyrate (BHB) concentrations in Baladi goats under HS conditions in Jordan. Six goats were exposed to direct solar radiation versus six goats exposed to shade regimen. Blood samples were collected and serum concentrations of leptin, adiponectin, NEFA and BHB were measured. Ambient temperature, relative humidity (RH) and body weight (BW) were recorded. Results indicated that leptin and adiponectin concentrations were significantly increased under HS. The concentration of NEFA was significantly increased under HS at the 7th and 14th days of the experiment, while mean total concentration of NEFA was not significantly affected by HS. Neither weekly nor mean total concentrations of BHB were significantly affected by HS during the experimental period. In conclusion, HS is associated with changes in leptin and adiponectin concentrations in Baladi goats. Heat-stressed goats were able to keep their blood NEFA and BHB concentrations similar to those of thermo-neutral goats. © 2016 Japanese Society of Animal Science.

High-intensity interval training acutely alters plasma adipokine levels in young overweight/obese women.

PubMed

Vardar, Selma Arzu; Karaca, Aziz; Güldiken, Sibel; Palabıyık, Orkide; Süt, Necdet; Demir, Ahmet Muzaffer

2018-05-01

The aim of this study was to investigate the plasma adipokine responses to high-intensity interval training (HIT) in overweight/obese women. Twelve women (age 21.7 ± 3.8 years) completed a 19 days of HIT comprising six session of 4-6 repeats of a Wingate test (0.065 kg load/kg). Plasma adipokine levels were measured before exercise, and at 5 and 90 min after exercise on the first and the last training days. Adiponectin was higher at 5 min than 90 min post-exercise (11.7 ± 7.3 and 10.5 ± 5.8 ng/ml; p = .01) in the first exercise day. Leptin decreased 5 min after exercise (23.6 ± 13.2 vs. baseline 27.8 ± 14.4 ng/ml; p < .01) and remained depressed following 90 min (p < .01). The changes in adiponectin and leptin concentrations were similar on the first and last exercise days. No consistent effect was found on resistin concentration. Future studies are required to disclose the functional consequences of these alterations in plasma adipokine levels.

Adipokines, insulin resistance, and adiposity as a predictors of metabolic syndrome in child survivors of lymphoma and acute lymphoblastic leukemia of a developing country.

PubMed

Barbosa-Cortés, Lourdes; López-Alarcón, Mardia; Mejía-Aranguré, Juan Manuel; Klünder-Klünder, Miguel; Del Carmen Rodríguez-Zepeda, María; Rivera-Márquez, Hugo; de la Vega-Martínez, Alan; Martin-Trejo, Jorge; Shum-Luis, Juan; Solis-Labastida, Karina; López-Aguilar, Enrique; Matute-González, Guadalupe; Bernaldez-Rios, Roberto

2017-02-13

There is a growing body of evidence indicating that pediatric survivors of cancer are at a greater risk of developing metabolic syndrome. This study evaluated some probable predictors of metabolic syndrome (MS), such as leptin and adiponectin concentrations, the leptin/adiponectin ratio, insulin resistance, and adiposity, in a sample of child survivors of lymphoma and leukemia in Mexico City. Fifty two children (leukemia n = 26, lymphoma n = 26), who were within the first 5 years after cessation of therapy, were considered as eligible to participate in the study. Testing included fasting insulin, glucose, adipokines and lipids; body fat mass was measured by DXA. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. Comparisons between continuous variables were performed according to the data distribution. The MS components were analyzed according to tertiles of adipokines, insulin resistance, and adiposity. With the purpose of assessing the risk of a present MS diagnosis, odds ratios (OR) with a 95% confidence interval (95% IC) were obtained using logistic regression analysis according to the various metabolic markers. The median children age was 12.1 years, and the interval time from the completion of therapy to study enrollment was 4 years. Among the MS components, the prevalence of HDL-C low was most common (42%), followed by central obesity (29%). The HOMA-IR (OR 9.0, 95% CI 2.0; 41.1), body fat (OR 5.5, 95% CI 1.6; 19.3), leptin level (OR 5.7, 95% CI 1.6; 20.2) and leptin/adiponectin ratio (OR 9.4, 95% CI 2.0; 49.8) in the highest tertile, were predictive factors of developing MS; whereas the lowest tertile of adiponectin was associated with a protective effect but not significant. Biomarkers such as HOMA-IR, leptin and leptin/adiponectin are associated with each of the components of the MS and with a heightened risk of suffering MS among children survivors of cancer. Given the close relationship

Serum level of orexin-A, leptin, adiponectin and insulin in north Indian obese women.

PubMed

Mishra, Sameeksha; Gupta, Vani; Mishra, Supriya; Sachan, Rekha; Asthana, Akash

2017-12-01

Obesity is regulated by different metabolic factors like leptin, adiponectin insulin and neuropeptide orexin-A. The aim of this study is to assess the role of these hormones and their interrelationship with obesity in north Indian women. A total of 168 obese women with Body Mass Index (BMI)>30kg/m 2 and 150 lean women (BMI<25kg/m 2 ) as control were recruited in this study. Women with obesity were further subdivided into two groups according to their BMI, 71 overweight women with the BMI 25-29.9kg/m 2 (mean±S.D: 27.87±0.71) and the 97 obese women with BMI>30kg/m 2 (34.68±1.90). Orexin -A, leptin and adiponectin were estimated using quantitative sandwich enzyme linked immunoassay and insulin was estimated by using an immuno-radiometric assay. Orexin -A and adiponectin level were significantly lower however, leptin and inulin level were significantly higher in obese women as compared with control group. Further, the one- way group analysis showed that the orexin -A and adiponectin level were significantly lower but leptin and insulin level was significantly higher in obese women as compared to overweight and control group respectively. Result showed that the level of adiponectin, leptin, orexin-A and insulin play an important role in the regulation of energy expenditure. In obesity, the activity of these peptides is disturbed. Copyright © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Serum adipokine concentrations in dogs with diabetes mellitus: a pilot study

PubMed Central

Kim, Ah Young; Kim, Hye-Sun; Yang, Mhan-Pyo

2015-01-01

This study was conducted to determine whether serum adipokine concentrations differed between healthy dogs and dogs with diabetes mellitus (DM). To accomplish this, 19 dogs with newly diagnosed DM were compared to 20 otherwise healthy dogs. The serum concentrations of visfatin, leptin, IL-1β, IL-6, IL-18, and TNF-α were significantly higher in diabetic dogs than in healthy dogs, whereas the serum adiponectin concentrations were lower in diabetic dogs. However, there were no significant differences in the IL-10 and resistin levels between groups. The serum leptin concentrations in diabetic dogs with and without concurrent disorders differed significantly. Treatment with insulin induced a significant decrease in IL-6 in diabetic dogs without concurrent disorders. These results show that the clinical diabetic state of dogs could modulate the circulating visfatin and adiponectin concentrations directly, while upregulation of leptin was probably a result of concurrent disorders rather than an effect of persistent hyperglycemia as a result of DM. PMID:25643799

Serum adipokines and HIV viral replication in patients undergoing antiretroviral therapy

PubMed Central

Aramă, Victoria; Tilişcan, Cătălin; Ion, Daniela Adriana; Mihăilescu, Raluca; Munteanu, Daniela; Streinu-Cercel, Anca; Tudor, Ana Maria; Hristea, Adriana; Leoveanu, Viorica; Olaru, Ioana; Aramă, Ştefan Sorin

2012-01-01

Introduction Several studies have reported that cytokines secreted by adipose tissue (adipokines) may be linked to HIV replication. The aim of the study was to evaluate the relationship between HIV replication and serum levels of adipokines, in a Caucasian HIV-infected population of men and women undergoing complex antiretroviral therapy. Methods A cross-sectional study was conducted in an unselected sample of 77 HIV-1-positive patients. Serum adipokines levels were measured including circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6). Patients were divided into two groups: Group 1 - with undetectable viral load and Group 2 - with persistent HIV viral replication. Differences between groups ? were tested using independent-sample t-test for Gaussian variables and Mann–Whitney–Wilcoxon test for non-parametric variables. Pearson's chi-squared test was used for correlation analysis. Results A total of 77 patients (age range: 17-65, mean: 32.5 years) including 44 men (57.1% men, age range: 17–63 years, mean: 34.1 years) and 33 women (42.9% women age range: 19–65 years, mean: 30.3 years) were included in the study. TNF-alpha had significantly higher serum levels in patients with detectable viral load (16.89 vs. 9.35 pg/mL), (p=0.043), but correlation analysis lacked statistical significance. Adiponectin had median serum levels of 9.22 ìg/mL in Group 1 vs. 16.50 ìg/mL in Group 2 but the results lacked statistical significance (p=0.059). Higher leptin, IL-6 and resistin serum levels were noted in patients with undetectable HIV viral load, without statistical significance. Conclusions The present study reported higher TNF-alpha serum levels in patients with persistent HIV viral load. We found no statistically significant correlations between adiponectin, leptin, resistin and IL-6 and HIV viral load in our Caucasian HIV-positive study population, undergoing antiretroviral therapy. PMID:24432258

Adipokines and the cardiovascular system: mechanisms mediating health and disease.

PubMed

Northcott, Josette M; Yeganeh, Azadeh; Taylor, Carla G; Zahradka, Peter; Wigle, Jeffrey T

2012-08-01

This review focuses on the role of adipokines in the maintenance of a healthy cardiovascular system, and the mechanisms by which these factors mediate the development of cardiovascular disease in obesity. Adipocytes are the major cell type comprising the adipose tissue. These cells secrete numerous factors, termed adipokines, into the blood, including adiponectin, leptin, resistin, chemerin, omentin, vaspin, and visfatin. Adipose tissue is a highly vascularised endocrine organ, and different adipose depots have distinct adipokine secretion profiles, which are altered with obesity. The ability of many adipokines to stimulate angiogenesis is crucial for adipose tissue expansion; however, excessive blood vessel growth is deleterious. As well, some adipokines induce inflammation, which promotes cardiovascular disease progression. We discuss how these 7 aforementioned adipokines act upon the various cardiovascular cell types (endothelial progenitor cells, endothelial cells, vascular smooth muscle cells, pericytes, cardiomyocytes, and cardiac fibroblasts), the direct effects of these actions, and their overall impact on the cardiovascular system. These were chosen, as these adipokines are secreted predominantly from adipocytes and have known effects on cardiovascular cells.

Acute effects of a single warm-water bath on serum adiponectin and leptin levels in healthy men: A pilot study

NASA Astrophysics Data System (ADS)

Shimodozono, Megumi; Matsumoto, Shuji; Ninomiya, Koji; Miyata, Ryuji; Ogata, Atsuko; Etoh, Seiji; Watanabe, Satoshi; Kawahira, Kazumi

2012-09-01

To preliminarily assess the acute effects of a single warm -water bath (WWB) on serum adipokine activity, we measured serum adiponectin, leptin and other metabolic profiles before, immediately after and 30 minutes after WWB in seven healthy male volunteers (mean age, 39.7 ± 6.0 years; mean body mass index, 21.6 ± 1.8 kg/m2). The subjects were immersed in tap water at 41°C for 10 minutes. Two weeks later, the same subjects underwent a single WWB with a bath additive that included inorganic salts and carbon dioxide (WWB with ISCO2) by the same protocol as for the first WWB. Leptin levels significantly increased immediately after WWB with tap water and ISCO2 (both P < 0.05), and remained significantly higher than those at baseline even 30 minutes after WWB with tap water ( P < 0.05). Adiponectin levels showed a slight, but not significant, increase both immediately after and 30 minutes after WWB with tap water or ISCO2. Some parameters, such as serum total cholesterol, red blood cell count, hemoglobin and hematocrit significantly increased immediately after WWB with tap water or ISCO2 (all P < 0.05), but they all returned to the baseline levels 30 minutes after bathing under both conditions. The sublingual temperature rose significantly after 10 minutes of WWB with tap water (0.96 ± 0.16°C relative to baseline, P < 0.01) and after the same duration of WWB with ISCO2 (1.24 ± 0.34°C relative to baseline, P < 0.01). These findings suggest that a single WWB at 41°C for 10 minutes may modulate leptin and adiponectin profiles in healthy men.

Favorable effects of low-fat and low-carbohydrate dietary patterns on serum leptin, but not adiponectin, among overweight and obese premenopausal women: a randomized trial.

PubMed

Llanos, Adana Am; Krok, Jessica L; Peng, Juan; Pennell, Michael L; Olivo-Marston, Susan; Vitolins, Mara Z; Degraffinreid, Cecilia R; Paskett, Electra D

2014-01-01

The most effective dietary pattern for breast cancer prevention has been greatly debated in recent years. Studies have examined hypocaloric diets, with particular emphasis on macronutrient composition, yielding inconclusive data. The objective of this study was to examine the effects of calorie-restricted low-fat and low-carbohydrate diets (LFD and LCD, respectively) on circulating adipokines among overweight and obese premenopausal women. Seventy-nine overweight and obese premenopausal women were randomized to either LFD or LCD, with increased physical activity, for 52 weeks. Serum adiponectin, leptin and the adiponectin-to-leptin ratio (A/L) were measured at baseline, and at weeks 34 and 52 to assess intervention effects. While there were no significant changes in serum adiponectin concentrations following the LCD and LFD interventions, leptin concentrations significantly decreased by week 34 of the intervention period (LCD: 35.3%, P = 0.004; LFD: 30.0%, P = 0.01), with no difference by intervention arm. At week 52, these reductions were statistically non-significant, indicating a return to baseline levels by the end of the intervention. While there were non-significant increases in the A/L ratio following the LCD and LFD intervention arms, the overall trend, across groups, was marginally significant (P = 0.05) with increases of 16.2% and 35.1% at weeks 34 and 52, respectively. These findings suggest that caloric-restricted LCD and LFD dietary patterns favorably modify leptin and possibly the A/L ratio, and lend support to the hypothesis that these interventions may be effective for obesity-related breast cancer prevention through their effects on biomarkers involved in metabolic pathways. NCT01559194.

The levels of the adipokines adipsin and leptin are associated with knee osteoarthritis progression as assessed by MRI and incidence of total knee replacement in symptomatic osteoarthritis patients: a post hoc analysis.

PubMed

Martel-Pelletier, Johanne; Raynauld, Jean-Pierre; Dorais, Marc; Abram, François; Pelletier, Jean-Pierre

2016-04-01

Limited studies have explored the association between adipokines and knee OA structural progression using quantitative MRI (qMRI), and very few have included total knee replacement (TKR) as a disease outcome. The objective of this study was to compare serum levels of five adipokines to cartilage volume loss (CVL) and investigate their predictive value for TKR. The according-to-protocol population (n = 138) of a knee OA trial was used. Serum levels of adipsin (complement factor D), leptin, adiponectin, resistin and serpin E1, and cartilage volume were determined at baseline and 24 months with specific ELISAs and qMRI, respectively. Study knee TKR incidence up to 4 years post-trial was also assessed. Greater baseline values of adipsin and leptin correlated with increased CVL in the global knee and medial femur (P ⩽ 0.032) and of adipsin in the lateral compartment and femur (P ⩽ 0.028). Adiponectin showed an inverse correlation in the medial compartment and femur (P ⩽ 0.027). Resistin and serpin E1 were not associated with CVL. Multivariate analyses revealed that patients in the highest tertile at baseline of adipsin presented a greater odds ratio of CVL in the lateral compartment and femur (⩾2.87; P ⩽ 0.011), and those in the highest tertile of leptin in the medial compartment (2.78; P = 0.038). Most clinically relevant, patients in the highest tertile of adipsin or leptin at baseline had significantly greater incidence of TKR (P = 0.027). Data demonstrate that both adipsin and leptin predict greater CVL over time in the lateral and medial compartment, respectively. Importantly, this study also demonstrates that higher baseline levels of adipsin or leptin are associated with higher incidence of TKR. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Adipokines, cytokines and body fat stores in hepatitis C virus liver steatosis

PubMed Central

González-Reimers, Emilio; López-Prieto, Javier; Quintero-Platt, Geraldine; Pelazas-González, Ricardo; Alemán-Valls, M Remedios; Pérez-Hernández, Onán; de-la-Vega-Prieto, M José; Gómez-Rodríguez, M Angeles; Martín-González, Candelaria; Santolaria-Fernández, Francisco

2016-01-01

AIM: To identify patients with or without liver steatosis and its severity in treatment-naïve patients affected by hepatitis C virus (HCV) infection. METHODS: We included 56 HCV infected patients, and assessed the amount of liver fat by histomorphometry, and its relationships with fat and lean mass at different parts of the body (by densitometry), hormones [insulin, homeostatic model assessment (HOMA)], adipokines (resistin, adiponectin, leptin), and cytokines (tumor necrosis factor α, interleukin-6). RESULTS: Although the intensity of liver steatosis is related to trunk fat mass and HOMA, 33% of patients showed no liver steatosis, and this finding was not related to body mass index or genotype. Besides trunk fat mass, no other factor was related to the presence or not of liver steatosis, or to the intensity of it, by multivariate analysis. Lean mass was not related to liver steatosis. Adiponectin levels were lower among patients. No differences were observed in leptin and resistin. CONCLUSION: Steatosis in HCV infection is common (67.2%), and closely related to trunk fat, and insulin resistance, but not with leg fat mass or adipokines. PMID:26783423

Exercise induced adipokine changes and the metabolic syndrome.

PubMed

Golbidi, Saeid; Laher, Ismail

2014-01-01

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

Sleep Duration and Cardiometabolic Risk Among Chinese School-aged Children: Do Adipokines Play a Mediating Role?

PubMed

Li, Lujiao; Fu, Junling; Yu, Xin Ting; Li, Ge; Xu, Lu; Yin, Jinghua; Cheng, Hong; Hou, Dongqing; Zhao, Xiaoyuan; Gao, Shan; Li, Wenhui; Li, Changhong; Grant, Struan F A; Li, Mingyao; Xiao, Yi; Mi, Jie; Li, Ming

2017-05-01

To assess the associations between sleep duration and cardiometabolic risk factors in Chinese school-aged children and to explore the possible mediating role of adipokines. Sleep duration was collected in 3166 children from the Beijing Child and Adolescent Metabolic Syndrome study. Glucose homeostasis and other cardiometabolic risk factors were assessed. Serum adipokines including leptin, total and high-molecular-weight (HMW) adiponectin, resistin, fibroblast growth factor 21 (FGF21), and retinol binding protein 4 (RBP4) were determined. Among the 6- to 12-year-old children, after adjusting for covariates including puberty, short sleep duration was associated with increased body mass index (BMI), waist circumference, fasting glucose, insulin and homeostasis model assessment of insulin resistance (all p < .0001), higher triglyceride and lower high-density lipoprotein cholesterol (p < .05), along with increased leptin (p < .0001), FGF21 (p < .05) and decreased HMW-adiponectin (p ≤ .01); the association with leptin remained significant after further adjustment for BMI. However, these associations, except for glucose (p < .0001), disappeared after further adjusted for leptin. For the 13-18 years old group, short sleep duration was associated with higher BMI, waist circumference, and RBP4 (all p < .05), but the association with RBP4 was attenuated after adjusting for BMI (p = .067). Short sleep duration is strongly associated with obesity and hyperglycemia (in 6-12 years old), along with adverse adipokine secretion patterns among Chinese children. The associations with cardiometabolic risk factors appear to be more pronounced in younger children, and could be explained, at least partially, by leptin levels. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Relationship of postprandial nonesterified fatty acids, adipokines, and insulin across gender in human immunodeficiency virus-positive patients undergoing highly active antiretroviral therapy.

PubMed

Lu, Guijing; Thomas-Geevarghese, Asha; Anuurad, Erdembileg; Raghavan, Subhashree; Minolfo, Robert; Ormsby, Bernard; Karmally, Wahida; El-Sadr, Wafaa M; Albu, Jeanine; Berglund, Lars

2009-06-01

Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART). For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r(2) = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r(2) = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed. In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase.

Effects of Tomato and Soy on Serum Adipokine Concentrations in Postmenopausal Women at Increased Breast Cancer Risk: A Cross-Over Dietary Intervention Trial

PubMed Central

Llanos, Adana A.; Peng, Juan; Pennell, Michael L.; Krok, Jessica L.; Vitolins, Mara Z.; Degraffinreid, Cecilia R.

2014-01-01

Context: Breast cancer risk among postmenopausal women increases as body mass index increases. Practical preventive methods to reduce risk of breast cancer are lacking. Few studies have investigated the effects of carotenoids and isoflavones on circulating adipokines in postmenopausal women. Objective: The aim was to examine the effects of lycopene- and isoflavone-rich diets on serum adipokines. Design: This was a 26-week, two-arm, longitudinal crossover trial. Setting: Participants were recruited from clinics at The Ohio State University Comprehensive Cancer Center. Participants: Seventy postmenopausal women at increased breast cancer risk participated in the study. The mean age and body mass index of participants was 57.2 years and 30.0 kg/m2, respectively; the study was comprised of 81.4% whites. Interventions: The interventions included 10 weeks of consumption of a tomato-based diet (≥25 mg lycopene daily) and 10 weeks of consumption of a soy-based diet (≥40 g of soy protein daily), with a 2-week washout in between. Main Outcome Measures: Changes in serum adiponectin, leptin, and the adiponectin to leptin ratio were examined for each intervention through linear mixed models, with ratio estimates corresponding to postintervention adipokine concentrations relative to preintervention concentrations. Results: After the tomato intervention, among all women, adiponectin concentration increased (ratio 1.09, 95% confidence interval (CI) 1.00–1.18), with a stronger effect observed among nonobese women (ratio 1.13, 95% CI 1.02–1.25). After the soy intervention, adiponectin decreased overall (ratio 0.91, 95% CI 0.84–0.97), with a larger reduction observed among nonobese women (ratio 0.89, 95% CI 0.81–0.98). Overall, no significant changes in leptin or the adiponectin to leptin ratio were observed after either intervention. Conclusions: Increasing dietary consumption of tomato-based foods may beneficially increase serum adiponectin concentrations among

Independent Circadian and Sleep/Wake Regulation of Adipokines and Glucose in Humans

PubMed Central

Shea, Steven A.; Hilton, Michael F.; Orlova, Christine; Ayers, R. Timothy; Mantzoros, Christos S.

2010-01-01

Leptin and adiponectin play important physiological roles in regulating appetite, food intake, and energy balance and have pathophysiological roles in obesity and anorexia nervosa. To assess the relative contributions of day/night patterns in behaviors (sleep/wake cycle and food intake) and of the endogenous circadian pacemaker on observed day/night patterns of adipokines, in six healthy subjects we measured circulating leptin, soluble leptin receptor, adiponectin, glucose, and insulin levels throughout a constant routine protocol (38 h of wakefulness with constant posture, temperature, and dim light, as well as identical snacks every 2 h) and throughout sleep and fasting periods before and after the constant routine. There were significant endogenous circadian rhythms in leptin, glucose, and insulin, with peaks around the usual time of awakening. Sleep/fasting resulted in additional systematic decreases in leptin, glucose, and insulin, whereas wakefulness/food intake resulted in a systematic increase in leptin. Thus, the day/night pattern in leptin is likely caused by combined effects from the endogenous circadian pacemaker and day/night patterns in behaviors. Our data imply that alterations in the sleep/wake schedule would lead to an increased daily range in circulating leptin, with lowest leptin upon awakening, which, by influencing food intake and energy balance, could be implicated in the increased prevalence of obesity in the shift work population. PMID:15687326

Clinical characteristics of high plasma adiponectin and high plasma leptin as risk factors for arterial stiffness and related end-organ damage.

PubMed

Kohara, Katsuhiko; Ochi, Masayuki; Okada, Yoko; Yamashita, Taiji; Ohara, Maya; Kato, Takeaki; Nagai, Tokihisa; Tabara, Yasuharu; Igase, Michiya; Miki, Tetsuro

2014-08-01

The relationship between plasma levels of adiponectin and cardiovascular events is inconclusive. We evaluated the clinical characteristics of people with high plasma adiponectin and high plasma leptin levels. Thousand seven hundred participants recruited from visitors to the Anti-Aging Doc were divided into four groups by combining the bipartiles of plasma adiponectin and leptin levels in men and women separately: AL, high adiponectin and high leptin; Al, high adiponectin and low leptin; al, low adiponectin and low leptin; aL, low adiponectin and high leptin. Body composition, including visceral fat area and thigh muscle cross-sectional area (CSA), brachial-ankle pulse wave velocity (baPWV), periventricular hyperintensity, and urinary albumin excretion, were determined. Twenty percent of the studied population fell within the AL group. This group had a significantly higher visceral fat area than the Al group. Thigh muscle CSA was lowest in the AL group among groups. baPWV, brain white matter lesions, and albuminuria findings in the AL group were significantly higher than those of the Al group. Multiple and logistic regression analyses with confounding parameters further confirmed that plasma adiponectin was not an independent determinant for brain and renal small vessel-related disease. These findings suggest that the plasma level of adiponectin alone is not enough for the risk stratification of cardiovascular disease. Leptin resistance associated with skeletal muscle loss in addition to obesity may need to be addressed to identify high risk people with high plasma adiponectin levels. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Increased Adipocyte Size, Macrophage Infiltration, and Adverse Local Adipokine Profile in Perirenal Fat in Cushing's Syndrome.

PubMed

Roerink, Sean H P P; Wagenmakers, Margreet A E M; Langenhuijsen, Johan F; Ballak, Dov B; Rooijackers, Hanne M M; d'Ancona, Frank C; van Dielen, François M; Smit, Jan W A; Plantinga, Theo S; Netea-Maier, Romana T; Hermus, Ad R M M

2017-08-01

To analyze changes in fat cell size, macrophage infiltration, and local adipose tissue adipokine profiles in different fat depots in patients with active Cushing's syndrome. Subcutaneous (SC) and perirenal (PR) adipose tissue of 10 patients with Cushing's syndrome was compared to adipose tissue of 10 gender-, age-, and BMI-matched controls with regard to adipocyte size determined by digital image analysis on hematoxylin and eosin stainings, macrophage infiltration determined by digital image analysis on CD68 stainings, and adipose tissue leptin and adiponectin levels using fluorescent bead immunoassays and ELISA techniques. Compared to the controls, mean adipocyte size was larger in PR adipose tissue in patients. The percentage of macrophage infiltration of the PR adipose tissue and PR adipose tissue lysate leptin levels were higher and adiponectin levels were lower in SC and PR adipose tissue lysates in patients. The adiponectin levels were also lower in the SC adipose tissue supernatants of patients. Associations were found between the severity of hypercortisolism and PR adipocyte size. Cushing's syndrome is associated with hypertrophy of PR adipocytes and a higher percentage of macrophage infiltration in PR adipose tissue. These changes are associated with an adverse local adipokine profile. © 2017 The Obesity Society.

Association of Parental Obesity and Diabetes Mellitus With Circulating Adipokines in Nonobese Nondiabetic Offspring.

PubMed

Zachariah, Justin P; Quiroz, Rene; Enserro, Danielle; Andersson, Charlotte; Keaney, John F; Sullivan, Lisa M; Vasan, Ramachandran S

2017-07-16

Adipokines are implicated in the development of obesity-related traits. We hypothesized that nonobese participants without diabetes mellitus (DM) whose parents were obese or had DM would have altered circulating adipokines compared with those without parental history of these conditions. Participants in the community-based Framingham Third Generation cohort who were not obese (body mass index <30) and not diabetic with both parents in the Framingham Offspring cohort were included in this analysis (n=2034, mean age 40 years, 54% women). Circulating concentrations of fetuin A, RBP4 (retinol binding protein 4), FABP4 (fatty acid binding protein 4), leptin, LEP-R (leptin receptor), and adiponectin were assayed. Parental DM was defined as occurring before age 60 years, and obesity was defined as body mass index ≥30 before age 60 years. General estimating equations were used to compare concentrations of adipokines among participants with 0, 1, or 2 parents affected by obesity or DM (separate analyses for each), adjusting for known correlates of adipokines. Overall, 44% had at least 1 parent who was obese and 15% had parents with DM. Parental obesity was associated with higher serum levels of FABP4 and LEP-R in their offspring ( P =0.02 for both). Parental DM was associated with lower adiponectin but higher RBP4 concentrations in offspring ( P ≤0.02 for both). In our community-based sample, a parental history of DM or obesity was associated with an altered adipokine profile in nonobese nondiabetic offspring. Additional studies are warranted to evaluate whether such preclinical biomarker alterations presage future risk of disease. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Abnormality of adipokines and endothelial dysfunction in Mexican obese adolescents with insulin resistance.

PubMed

Ortiz Segura, Maria Del Carmen; Del Río Navarro, Blanca Estela; Rodríguez Espino, Benjamín Antonio; Marchat, Laurence A; Sánchez Muñoz, Fausto; Villafaña, Santiago; Hong, Enrique; Meza-Cuenca, Fabián; Mailloux Salinas, Patrick; Bolaños-Jiménez, Francisco; Zambrano, Elena; Arredondo-López, Abel Armando; Bravo, Guadalupe; Huang, Fengyang

2017-08-01

The aim of this study was to investigate the possible relationship among insulin resistance (IR), endothelial dysfunction, and alteration of adipokines in Mexican obese adolescents and their association with metabolic syndrome (MetS). Two hundred and twenty-seven adolescents were classified according to the body mass index (BMI) (control: N=104; obese: N=123) and homeostasis model of the assessment-insulin resistance index (HOMA-IR) (obese with IR: N=65). The circulating concentrations of leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), and IR were determined by standard methods. The obese adolescents with IR presented increased presence of MetS and higher circulating concentrations in sICAM-1 in comparison with the obese subjects without IR. The lowest concentrations of adiponectin were observed in the obese with IR. In multivariate linear regression models, sICAM-1 along with triglycerides, total cholesterol, and waist circumference was strongly associated with HOMA-IR (R 2 =0.457, P=0.008). Similarly, after adjustment for age, BMI-SDS, lipids, and adipokines, HOMA-IR remained associated with sICAM-1 (R 2 =0.372, P=0.008). BMI-SDS was mildly associated with leptin (R 2 =0.176, P=0.002) and the waist circumference was mild and independent determinant of adiponectin (R 2 =0.136, P=0.007). Our findings demonstrated that the obese adolescents, particularly the obese subjects with IR exhibited increased presence of MetS, abnormality of adipokines, and endothelial dysfunction. The significant interaction between IR and endothelial dysfunction may suggest a novel therapeutic approach to prevent or delay systemic IR and the genesis of cardiovascular diseases in obese patients.

Ethnic differences in serum adipokine and C-reactive protein levels: the multiethnic cohort.

PubMed

Morimoto, Y; Conroy, S M; Ollberding, N J; Kim, Y; Lim, U; Cooney, R V; Franke, A A; Wilkens, L R; Hernandez, B Y; Goodman, M T; Henderson, B E; Kolonel, L N; Le Marchand, L; Maskarinec, G

2014-11-01

Ethnic disparities in metabolic disease risk may be the result of differences in circulating adipokines and inflammatory markers related to ethnic variations in obesity and body fat distribution. In a cross-sectional design, we compared serum levels of leptin, adiponectin, C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in control subjects (321 men and 930 women) from two nested case-control studies conducted within the Multiethnic Cohort Study consisting of whites, Japanese Americans (JA), Latinos, African Americans (AA) and Native Hawaiians (NH). General linear models were applied to evaluate ethnic differences in log-transformed serum biomarker levels before and after adjusting for body mass index (BMI) at cohort entry. In comparison to whites, significant ethnic differences were observed for all biomarkers except TNF-α. JA men and women had significantly lower leptin and CRP levels than whites, and JA women also had lower adiponectin levels. Leptin was significantly higher in AA women (P < 0.01), adiponectin was significantly lower in AA men and women (P = 0.02 and P < 0.001), and CRP and IL-6 were significantly higher in AA men and women. Lower adiponectin (P < 0.0001) and CRP (P = 0.03) levels were the only biomarkers in NH women that differed from whites; no statistically significant differences were seen for NH men and for Latino men and women. When adjusted for BMI at cohort entry, the differences between the lowest and the highest values across ethnic groups decreased for all biomarkers except adiponectin in men indicating that ethnic differences were partially due to weight status. These findings demonstrate the ethnic variations in circulating adipokine and CRP levels before and after adjustment for BMI. Given the limitation of BMI as a general measure of obesity, further investigation with visceral and subcutaneous adiposity measures are warranted to elucidate ethnicity-related differences in adiposity in relation

Serum adipokines (adiponectin and resistin) correlation in developing gestational diabetes mellitus: pilot study.

PubMed

Siddiqui, Khalid; George, Teena P; Nawaz, Shaik Sarfaraz; Shehata, Nevene; El-Sayed, Amel Ahmed; Khanam, Latifa

2018-06-01

Adiponectin and resistin are adipose tissue-derived proteins with antagonistic actions; adiponectin has insulin sensitive properties while resistin is involved in the development of insulin resistance. We analyzed adiponectin and resistin levels in gestational diabetes mellitus (GDM) women to evaluate the association of these adipokines in a very high diabetes prevalence population. An age-matched case-control study of GDM and normal pregnant women in Saudi population. We recruited 90 pregnant women at 24-32 weeks of gestation. Glucose levels (fasting, 1, 2, and 3 h) and lipid parameters (cholesterol, triglyceride, HDL cholesterol, LDL cholesterol) were measured. Serum adiponectin and resistin levels were analyzed using Randox evidence biochip analyzer. Pearson's correlation coefficient was used to determine the association of adiponectin and resistin with GDM risk factors. GDM women showed significantly low adiponectin and high resistin levels when compared with control group. Pearson's correlation analysis of adiponectin and resistin in all the subjects with various GDM risk factors showed a negative association of adiponectin (r = -0.32, p = .05) and a positive correlation of resistin (r = 0.41, p = .01) with LDL cholesterol. This study analyzes adiponectin and resistin levels together, as accumulating evidences shows that these are involved in the pathophysiology of GDM. This is going to help to determine in conjunction with traditional risk factors the incremental value of circulating adiponectin and resistin in developing GDM.

Resveratrol supplementation and plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Mohammadi-Sartang, Mohsen; Mazloom, Zohreh; Sohrabi, Zahra; Sherafatmanesh, Saeed; Barati-Boldaji, Reza

2017-03-01

The results of human clinical trials have revealed that the effects of resveratrol on adipokines are inconsistent. Our objective was to elucidate the role of resveratrol supplementation on adipokines through a systematic review and a meta-analysis of available randomized placebo-controlled trials (RCTs). 1 The search included PubMed-MEDLINE, SCOPUS and ISI web of sciences database till up to 6th November 2016. Weight mean differences (WMD) 2 were calculated for net changes in adipokines using fixed-effects or random-effects models; meta-regression analysis and publication bias were conducted in accordance with standard methods. Nine RCTs with 11 treatment arms were eligible for inclusion in this systematic review and meta-analysis. Meta-analysis of data from 10 treatment arms showed a significant change in plasma adiponectin concentrations following resveratrol supplementation (WMD: 1.10μg/ml, 95%CI: 0.88, 1.33, p<0.001); Q=11.43, I 2 =21.29%, p=0.247). There was a significant greater adiponectin-reducing effect in trials with higher than or equal to 100mg/day (WMD: 1.11μg/ml, 95%CI: 0.88, 1.34, p<0.001), versus those with less than 100 mg/day dosage (WMD: 0.84μg/ml, 95%CI: -0.62, 2.31, p=0.260). Meta-analysis of data from 5 treatment arms did not find any significant change in plasma leptin concentrations following resveratrol supplementation (WMD: 3.77ng/ml, 95% CI: -2.28, 9.83, p=0.222; Q=8.00, I 2 =50.01%). Resveratrol significantly improves adiponectin but does not affect leptin concentrations. Additional studies are required to further evaluate the potential benefits of resveratrol on adipokines in humans. Copyright © 2017. Published by Elsevier Ltd.

Adipokines, insulin resistance and hyperandrogenemia in obese patients with polycystic ovary syndrome: cross-sectional correlations and the effects of weight loss.

PubMed

Spanos, Nikolaos; Tziomalos, Konstantinos; Macut, Djuro; Koiou, Ekaterini; Kandaraki, Eleni A; Delkos, Dimitrios; Tsourdi, Elena; Panidis, Dimitrios

2012-01-01

To assess the effects of weight loss on serum adipokine levels in polycystic ovary syndrome (PCOS). We determined serum leptin, adiponectin, resistin, and visfatin levels in 60 overweight/obese women with PCOS and 48 BMI-matched female volunteers. Measurements were repeated after 24 weeks of treatment with orlistat 120 mg 3 times per day along with an energy-restricted diet. At baseline, serum visfatin concentration was higher in patients with PCOS than in controls (p = 0.036); serum levels of leptin, adiponectin, and resistin did not differ between the two groups. After 24 weeks, a significant reduction in BMI and waist circumference was observed in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). Also serum leptin levels decreased in both patients with PCOS and controls (p < 0.001 vs. baseline in both groups). The reduction in serum leptin levels did not differ between groups. Serum adiponectin, resistin, and visfatin levels did not change in either group. Leptin, adiponectin, and resistin do not appear to play major pathogenetic roles in overweight/obese patients with PCOS. In contrast, visfatin emerges as a potentially important mediator of the endocrine abnormalities of these patients. However, serum visfatin levels are not substantially affected by weight loss.

Polyunsaturated fatty acids of marine origin induce adiponectin in mice fed a high-fat diet.

PubMed

Flachs, P; Mohamed-Ali, V; Horakova, O; Rossmeisl, M; Hosseinzadeh-Attar, M J; Hensler, M; Ruzickova, J; Kopecky, J

2006-02-01

Diets rich in n-3 polyunsaturated fatty acids, namely eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), protect against insulin resistance and obesity in rodents and increase insulin sensitivity in healthy humans. We tested whether the anti-diabetic effects of EPA and DHA involve enhanced production of the endogenous insulin sensitiser, adiponectin. We studied the effects, in an obesity-promoting high-fat diet, of partial replacement of vegetable oils by EPA/DHA concentrate (6% EPA, 51% DHA) over a 5-week period in adult male C57BL/6J mice that either had free access to food or had their food intake restricted by 30%. At the end of the treatment, systemic markers of lipid and glucose metabolism and full-length adiponectin and leptin were measured. Adiponectin (Adipoq) and leptin (Lep) gene expression in dorsolumbar and epididymal white adipose tissue (WAT) and isolated adipocytes was quantified and adipokine production from WAT explants evaluated. In mice with free access to food, plasma triacylglycerols, NEFA, and insulin levels were lower in the presence of EPA/DHA, while glucose and leptin levels were not significantly altered. Food restriction decreased plasma triacylglycerols, glucose, insulin and leptin, but not adiponectin. EPA/DHA increased plasma adiponectin levels, independent of food intake, reflecting the stimulation of Adipoq expression in adipocytes and the release of adiponectin from WAT, particularly from epididymal fat. Expression of Lep and the release of leptin from WAT, while being extremely sensitive to caloric restriction, was unaltered by EPA/DHA. Intake of diets rich in EPA and DHA leads to elevated systemic concentrations of adiponectin, largely independent of food intake or adiposity and explain, to some extent, their anti-diabetic effects.

Relationship among serum taurine, serum adipokines, and body composition during 8-week human body weight control program.

PubMed

You, Jeong Soon; Park, Ji Yeon; Zhao, Xu; Jeong, Jin Seok; Choi, Mi Ja; Chang, Kyung Ja

2013-01-01

Human adipose tissue is not only a storage organ but also an active endocrine organ to release adipokines. This study was conducted to investigate the relationship among serum taurine and adipokine levels, and body composition during 8-week human body weight control program in obese female college students. The program consisted of diet therapy, exercise, and behavior modification. After the program, body weight, body fat mass, percent body fat, and body mass index (BMI) were significantly decreased. Serum triglyceride (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly decreased. Also serum adiponectin level was significantly increased and serum leptin level was significantly decreased. There were no differences in serum taurine and homocysteine levels. The change of serum adiponectin level was positively correlated with change of body fat mass and percent body fat. These results may suggest that body fat loss by human body weight control program is associated with an increase in serum adiponectin in obese female college students. Therefore, further study such as taurine intervention study is needed to know more exact correlation between dietary taurine intake and serum adipokines or body composition.

Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus–Positive Patients Undergoing Highly Active Antiretroviral Therapy

PubMed Central

Lu, Guijing; Thomas-Geevarghese, Asha; Anuurad, Erdembileg; Raghavan, Subhashree; Minolfo, Robert; Ormsby, Bernard; Karmally, Wahida; El-Sadr, Wafaa M.; Albu, Jeanine

2009-01-01

Abstract Background Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. Methods We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART). Results For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r2 = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r2 = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed. Conclusions In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase. PMID:19320559

Adipokines and nutritional status for patients on maintenance hemodialysis.

PubMed

Małgorzewicz, S; Aleksandrowicz-Wrona, E; Owczarzak, A; Debska-Slizień, A; Rutkowski, B; Łysiak-Szydłowska, W

2010-09-01

The aim of this study was to investigate the serum concentration of adipokines, such as leptin, adiponectin, and resistin, and assess its relation to nutritional and inflammatory parameters in both overweight and normal weight patients on maintenance hemodialysis. A total of 36 hemodialysis patients (27 M, 9 F; mean age 55.3 +/- 12 yr.) were examined and 23 additional healthy volunteers were recruited as the control group. The concentrations of leptin, leptin receptor, adiponectin, resistin, IL-6, TNFa and CRP were measured by ELISA. Assessment of nutritional status was determined by the levels of albumin, BMI, percentage of body fat (%F), lean body mass (LBM), and Subjective Global Assessment Score (SGA). According to the SGA 7-points score and the albumin level, 20 patients were of good nutritional status (6-7 points), while 16 patients were mildly malnourished (4-5 points). The concentrations of CRP, resistin, adiponectin, and TNFa were statistically higher in hemodialysis patients than in the control group (p pound 0.05). The adiponectin level was inversely correlated with %F (R Spearman=-0.3; p pound 0.05). The level of leptin was positively correlated with %F as well as with BMI and SGA scores (R Spearman=0.4; p pound 0.05). Although there was no significant difference in the nutritional status between the nonoverweight (BMI 18.5-24.99) and overweight (BMI (3)25.0) groups of patients, in the nonoverweight group there were 12 patients (54.5%) with signs of mild malnutrition compared to 4 malnourished patients (28.5%) in the overweight group. Nonoverweight patients presented significantly lower leptin concentration (12.7 vs 27.8 ug/l) and higher adiponectin level (38.9 vs 32.5 ng/ml) when compared to overweight patients. The levels of IL-6 and TNFa were higher in the nonoverweight group of patients. Overweight patients also had shorter durations of stay in the hemodialysis program (30.5 vs. 87.6 months). The results of our study indicate that lean hemodialysis

Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

PubMed Central

Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

2015-01-01

Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

Alterations in Mouse Hypothalamic Adipokine Gene Expression and Leptin Signaling following Chronic Spinal Cord Injury and with Advanced Age

PubMed Central

Bigford, Gregory E.; Bracchi-Ricard, Valerie C.; Nash, Mark S.; Bethea, John R.

2012-01-01

Chronic spinal cord injury (SCI) results in an accelerated trajectory of several cardiovascular disease (CVD) risk factors and related aging characteristics, however the molecular mechanisms that are activated have not been explored. Adipokines and leptin signaling are known to play a critical role in neuro-endocrine regulation of energy metabolism, and are now implicated in central inflammatory processes associated with CVD. Here, we examine hypothalamic adipokine gene expression and leptin signaling in response to chronic spinal cord injury and with advanced age. We demonstrate significant changes in fasting-induced adipose factor (FIAF), resistin (Rstn), long-form leptin receptor (LepRb) and suppressor of cytokine-3 (SOCS3) gene expression following chronic SCI and with advanced age. LepRb and Jak2/stat3 signaling is significantly decreased and the leptin signaling inhibitor SOCS3 is significantly elevated with chronic SCI and advanced age. In addition, we investigate endoplasmic reticulum (ER) stress and activation of the uncoupled protein response (UPR) as a biological hallmark of leptin resistance. We observe the activation of the ER stress/UPR proteins IRE1, PERK, and eIF2alpha, demonstrating leptin resistance in chronic SCI and with advanced age. These findings provide evidence for adipokine-mediated inflammatory responses and leptin resistance as contributing to neuro-endocrine dysfunction and CVD risk following SCI and with advanced age. Understanding the underlying mechanisms contributing to SCI and age related CVD may provide insight that will help direct specific therapeutic interventions. PMID:22815920

Obesity and adipokines: effects on sympathetic overactivity

PubMed Central

Smith, Michael M; Minson, Christopher T

2012-01-01

Excess body weight is a major risk factor for cardiovascular disease, increasing the risk of hypertension, hyperglycaemia and dyslipidaemia, recognized as the metabolic syndrome. Adipose tissue acts as an endocrine organ by producing various signalling cytokines called adipokines (including leptin, free fatty acids, tumour necrosis factor-α, interleukin-6, C-reactive protein, angiotensinogen and adiponectin). A chronic dysregulation of certain adipokines can have deleterious effects on insulin signalling. Chronic sympathetic overactivity is also known to be present in central obesity, and recent findings demonstrate the consequence of an elevated sympathetic outflow to organs such as the heart, kidneys and blood vessels. Chronic sympathetic nervous system overactivity can also contribute to a further decline of insulin sensitivity, creating a vicious cycle that may contribute to the development of the metabolic syndrome and hypertension. The cause of this overactivity is not clear, but may be driven by certain adipokines. The purpose of this review is to summarize how obesity, notably central or visceral as observed in the metabolic syndrome, leads to adipokine expression contributing to changes in insulin sensitivity and overactivity of the sympathetic nervous system. PMID:22351630

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes.

PubMed

Huang, Wan-Yu; Chang, Chia-Chu; Chen, Dar-Ren; Kor, Chew-Teng; Chen, Ting-Yu; Wu, Hung-Ming

2017-01-01

Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women. In this cross-sectional study, a total of 151 women aged 45-60 years were stratified into one of three groups according to hot-flash status over the past three months: never experienced hot flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, fasting levels of circulating glucose, lipid profiles, plasma insulin, and adipocyte-derived hormones. Multiple linear regression analysis was used to evaluate the associations of hot flashes with adipocyte-derived hormones, and with insulin resistance. The study was performed in a hospital medical center. The mean (standard deviation) of body-mass index was 22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S, respectively. Women in Group S displayed statistically significantly higher levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin than those in Groups M and N. Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with higher leptin levels, lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate linear regression analysis revealed that hot-flash severity was strongly associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence interval, 31.00-90.64; p < 0.001). The association between hot flashes and HOMA-IR index was attenuated after adjusting for leptin or adiponectin and was no longer significant after simultaneously adjusting for leptin and adiponectin. The present study provides evidence that hot flashes are associated with insulin resistance in postmenopausal women. It further suggests that hot flash association with

Association of the leptin-to-adiponectin ratio with metabolic syndrome in a sub-Saharan African population.

PubMed

Ayina, Clarisse Noël A; Endomba, Francky Teddy A; Mandengue, Samuel Honoré; Noubiap, Jean Jacques N; Ngoa, Laurent Serge Etoundi; Boudou, Philippe; Gautier, Jean-François; Mbanya, Jean Claude; Sobngwi, Eugene

2017-01-01

Worldwide there is an increased prevalence of metabolic syndrome mainly due to life-style modifications, and Africans are not saved of this situation. Many markers have been studied to predict the risk of this syndrome but the most used are leptin and adiponectin. Data on these metabolic markers are scare in Africa and this study aimed to assess the association between the leptin-to-adiponectin ratio (LAR) with metabolic syndrome in a Cameroonian population. This was a cross-sectional study that included 476 adults among a general population of Cameroon. Data collected concerned the body mass index, waist circumference, systolic blood pressure, diastolic blood pressure, fasting blood glucose, plasma lipids, adiponectin, leptin, insulin and homeostasis model for assessment of insulin resistance (HOMA-IR). To assess correlations we used Spearman's analyses and association of the studied variables with metabolic syndrome were done using binary logistic regression analysis. The leptin to adiponectin ratio was significantly and positively correlated with the body mass index (r = 0.669, p < 0.0001), waist circumference (r = 0.595, p < 0.0001), triglycerides (r = 0.190, p = 0.001), insulin levels (r = 0.333, p < 0.0001) and HOMA-IR (r = 0.306, p < 0.0001). Binary logistic regression analysis revealed that leptin, adiponectin and LAR were significantly associated with metabolic syndrome with respective unadjusted OR of 1.429, 0.468 and 1.502. After adjustment, for age and sex, the associations remained significative; LAR was also found to be significantly associated with metabolic syndrome (OR = 1.573, p value =0.000) as well as lower levels of adiponectin (OR = 0.359, p value =0.000) and higher levels of leptin (OR = 1.469, p value =0.001). This study revealed that LAR is significantly associated with metabolic syndrome in sub-Saharan African population, independently to age and sex.

Circulating leptin and adiponectin are associated with insulin resistance in healthy postmenopausal women with hot flashes

PubMed Central

Huang, Wan-Yu; Chang, Chia-Chu; Chen, Dar-Ren; Kor, Chew-Teng; Chen, Ting-Yu; Wu, Hung-Ming

2017-01-01

Introduction Hot flashes have been postulated to be linked to the development of metabolic disorders. This study aimed to evaluate the relationship between hot flashes, adipocyte-derived hormones, and insulin resistance in healthy, non-obese postmenopausal women. Participants and design In this cross-sectional study, a total of 151 women aged 45–60 years were stratified into one of three groups according to hot-flash status over the past three months: never experienced hot flashes (Group N), mild-to-moderate hot flashes (Group M), and severe hot flashes (Group S). Variables measured in this study included clinical parameters, hot flash experience, fasting levels of circulating glucose, lipid profiles, plasma insulin, and adipocyte-derived hormones. Multiple linear regression analysis was used to evaluate the associations of hot flashes with adipocyte-derived hormones, and with insulin resistance. Settings The study was performed in a hospital medical center. Results The mean (standard deviation) of body-mass index was 22.8(2.7) for Group N, 22.6(2.6) for Group M, and 23.5(2.4) for Group S, respectively. Women in Group S displayed statistically significantly higher levels of leptin, fasting glucose, and insulin, and lower levels of adiponectin than those in Groups M and N. Multivariate linear regression analysis revealed that hot-flash severity was significantly associated with higher leptin levels, lower adiponectin levels, and higher leptin-to-adiponectin ratio. Univariate linear regression analysis revealed that hot-flash severity was strongly associated with a higher HOMA-IR index (% difference, 58.03%; 95% confidence interval, 31.00–90.64; p < 0.001). The association between hot flashes and HOMA-IR index was attenuated after adjusting for leptin or adiponectin and was no longer significant after simultaneously adjusting for leptin and adiponectin. Conclusion The present study provides evidence that hot flashes are associated with insulin resistance in

Resistin is linked to inflammation, and leptin to metabolic syndrome, in women with inflammatory arthritis.

PubMed

Kontunen, P; Vuolteenaho, K; Nieminen, R; Lehtimäki, L; Kautiainen, H; Kesäniemi, Ya; Ukkola, O; Kauppi, M; Hakala, M; Moilanen, E

2011-01-01

To investigate how inflammation and metabolic syndrome (MetS) are associated with adipokine levels in patients with inflammatory arthritis. Fifty-four female patients with arthritis were enrolled in the study. Twenty (37%) of these patients had MetS, which was diagnosed according to the definition of the International Diabetes Federation (IDF). Interleukin (IL)-6 and four adipokines (resistin, leptin, adiponectin, and adipsin) were determined by immunoassay. Healthy women with body mass index (BMI) between 22 and 25 kg/m(2) served as controls. The patients with arthritis had higher levels of resistin than the healthy controls. This difference was clear in patients without MetS (17.4 in patients vs. 10.8 ng/mL in controls, p < 0.001), and even higher resistin levels were found in the patients with MetS (20.7 ng/mL; p < 0.001 vs. healthy controls; and p = 0.095 vs. patients without MetS). In the patients with arthritis and MetS, resistin correlated positively with IL-6 (Pearson's r = 0.5, p = 0.03). Leptin levels were increased in arthritis patients with MetS as compared to healthy controls, but not in patients without MetS. The statistically significant difference between patients with MetS and controls remained when leptin was adjusted with BMI. Accordingly, adiponectin levels were lower in patients with MetS than in healthy controls (p < 0.05). Leptin, adiponectin, and adipsin did not correlate with the inflammatory cytokine IL-6 or with C-reactive protein (CRP). The results show that high resistin levels are associated with arthritis independently of MetS, whereas leptin is increased only in arthritis patients with MetS.

Effects of adrenomedullin on tumour necrosis factor alpha, interleukins, endothelin-1, leptin, and adiponectin in the epididymal fat and soleus muscle of the rat.

PubMed

Liao, S B; Wong, P F; Cheung, B M Y; Tang, F

2013-01-01

Adrenomedullin (ADM) is a peptide hormone, which participates in the development of metabolic syndrome. In this study, we have investigated the interaction of ADM and cytokines, endothelin-1 (EDN-1) and adipokines in the epididymal fat and the soleus muscle. Epididymal fat and soleus muscles from adult male Sprague-Dawley rat were incubated with ADM at concentration of 100 nM for the study of the gene expression and secretion of tumour necrosis factor (TNF-α), EDN-1, leptin, adiponectin, interleukin 1β (IL-1β), and IL-6. The effects of TNF-α and EDN-1 on ADM gene expression and secretion were also investigated. The results showed that ADM decreased the gene expression and protein secretion of TNF-α in both the epididymal fat and the soleus muscle and decreased IL-1β gene expression and secretion in the soleus muscle. It also decreased endothelin gene expression and adiponectin gene expression and release and increased IL-6 and leptin gene expression and secretion in the epididymal fat. These effects were effectively blocked by the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP8-37, but not by the ADM receptor antagonist, hADM22-52. The reduction of inflammatory cytokines and EDN-1 may help to decrease insulin resistance and increase glucose uptake. As TNF-α also increases ADM levels in the epididymal fat and the soleus muscle and EDN-1 also increases ADM levels in the epididymal fat, they may form a feedback loop with ADM in these tissues. The increase in leptin and the decrease in adiponectin by ADM in the epididymal fat may have opposite effects on metabolism. © Georg Thieme Verlag KG Stuttgart · New York.

The role of adipokines in the rapid antidepressant effects of ketamine.

PubMed

Machado-Vieira, R; Gold, P W; Luckenbaugh, D A; Ballard, E D; Richards, E M; Henter, I D; De Sousa, R T; Niciu, M J; Yuan, P; Zarate, C A

2017-01-01

We previously found that body mass index (BMI) strongly predicted response to ketamine. Adipokines have a key role in metabolism (including BMI). They directly regulate inflammation and neuroplasticity pathways and also influence insulin sensitivity, bone metabolism and sympathetic outflow; all of these have been implicated in mood disorders. Here, we sought to examine the role of three key adipokines-adiponectin, resistin and leptin-as potential predictors of response to ketamine or as possible transducers of its therapeutic effects. Eighty treatment-resistant subjects who met DSM-IV criteria for either major depressive disorder (MDD) or bipolar disorder I/II and who were currently experiencing a major depressive episode received a single ketamine infusion (0.5 mg kg -1 for 40 min). Plasma adipokine levels were measured at three time points (pre-infusion baseline, 230 min post infusion and day 1 post infusion). Overall improvement and response were assessed using percent change from baseline on the Montgomery-Asberg Depression Rating Scale and the Hamilton Depression Rating Scale. Lower baseline levels of adiponectin significantly predicted ketamine's antidepressant efficacy, suggesting an adverse metabolic state. Because adiponectin significantly improves insulin sensitivity and has potent anti-inflammatory effects, this finding suggests that specific systemic abnormalities might predict positive response to ketamine. A ketamine-induced decrease in resistin was also observed; because resistin is a potent pro-inflammatory compound, this decrease suggests that ketamine's anti-inflammatory effects may be transduced, in part, by its impact on resistin. Overall, the findings suggest that adipokines may either predict response to ketamine or have a role in its possible therapeutic effects.

New insights into adipokines as potential biomarkers for type-2 diabetes mellitus.

PubMed

Olivera Santa-Catalina, Marta; Redondo, Pedro C; Cantonero, C; Granados, Maria P; Sanchez-Collado, Jose; Albarran, Letizia; Lopez, Jose Javier

2017-12-05

A large number of studies have been focused on investigating serum biomarkers associated with risk or diagnosis of type-2 diabetes mellitus. In the last decade, promising studies have shown that circulating levels of adipokines could be used as a relevant biomarker for diabetes mellitus progression as well as therapeutic future targets. Here we discuss the possible use of recent described adipokines, including apelin, omentin-1, resistin, FGF-21, neuregulin-4 and visfatin, as early biomarkers for diabetes. In addition, we also include recent findings of other well know adipokines such as leptin and adiponectin. In conclusion, further studies are needed to clarify the pathophysiological significance and clinical value of these biological factors as potential biomarkers in type-2 diabetes and related dysfunctions. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels

PubMed Central

Abbenhardt, Clare; McTiernan, Anne; Alfano, Catherine M.; Wener, Mark H.; Campbell, Kristin L.; Duggan, Catherine; Foster-Schubert, Karen E.; Kong, Angela; Toriola, Adetunji T; Potter, John D.; Mason, Caitlin; Xiao, Liren; Blackburn, George L.; Bain, Carolyn; Ulrich, Cornelia M.

2013-01-01

Background Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes, and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Methods Overweight/obese postmenopausal women (n=439) were randomized as follows: 1) a reduced calorie, weight loss diet (diet; N=118); 2) moderate-to-vigorous intensity aerobic exercise (exercise; N=117); 3) a combination of a reduced calorie, weight loss diet and moderate-to-vigorous intensity aerobic exercise (diet+exercise; N=117); or 4) control (N=87). The reduced calorie diet had a 10% weight loss goal. The exercise intervention consisted of 45 minutes of moderate-to-vigorous aerobic activity 5 days/week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Results Adiponectin increased by 9.5 % in the diet group and 6.6 % in the diet+exercise group (both p≤0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet+exercise, −40.1%, p<0.0001; diet, −27.1%, p<0.0001; exercise, −12.7%, p=0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, p-trend=0.0002; diet+exercise, p-trend=0.0005) and directly associated with leptin (diet, p-trend<0.0001; diet+exercise, p-trend<0.0001). Conclusion Weight loss through diet or diet+exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet+exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via effects on adiponectin and leptin. PMID

Combined association of maternal and paternal family history of diabetes with plasma leptin and adiponectin in overweight Hispanic children.

PubMed

Koebnick, C; Kelly, L A; Lane, C J; Roberts, C K; Shaibi, G Q; Toledo-Corral, C M; Davis, J N; Weigensberg, M J; Goran, M I

2008-09-01

To investigate the importance of a maternal and paternal family history of Type 2 diabetes and their combined association with plasma leptin and adiponectin levels in overweight Latino children with a family history of Type 2 diabetes (T2DM). This cross-sectional study investigated the combined association of a maternal and paternal family history of T2DM with leptin and adiponectin in 175 overweight Latino children (age 11.1 +/- 1.7 years). All subjects had a family history of T2DM. Plasma adiponectin and leptin levels, body fat measured by dual-energy X-ray absorptiometry, Tanner stage, age and insulin sensitivity were assessed. After adjustment for age, gestational diabetes, insulin sensitivity and body fat, a combined maternal and paternal family history of T2DM was associated with higher leptin concentrations (P = 0.004) compared with a maternal or paternal family history alone. This association was most pronounced at Tanner stage 1 (P for interaction family history x tanner stage = 0.022). The presence of a combined maternal and paternal family history of T2DM accounted for 4% (P = 0.003) of the variation in leptin concentrations. No such combined association was observed for adiponectin levels. Maternal and paternal family history of T2DM may have an additive impact on leptin, but not on adiponectin levels independent of adiposity and insulin sensitivity in overweight Latino children. This may contribute to a further clinically relevant deterioration of metabolic health in this population.

Reference values for leptin and adiponectin in children below the age of 10 based on the IDEFICS cohort.

PubMed

Erhardt, E; Foraita, R; Pigeot, I; Barba, G; Veidebaum, T; Tornaritis, M; Michels, N; Eiben, G; Ahrens, W; Moreno, L A; Kovács, E; Molnár, D

2014-09-01

To establish age- and sex-specific reference values for serum leptin and adiponectin in normal-weight 3.0-8.9-year old European children. Blood samples for hormone analysis were taken from 1338 children of the IDEFICS (Identification and prevention of Dietary- and lifestyle-induced health Effects in Children and infantS) study cohort. Only normal-weight children aged 3.0-8.9 years were included (n=539) in our analysis. Using the General Additive Model for Location Scale and Shape, age- and sex-specific percentiles were derived. The influence of under/overweight and obesity on the proposed reference curves based on normal-weight children was investigated in several sensitivity analyses using the sample without obese children (n=1015) and the whole study sample (n=1338). There was a negative age trend of adiponectin blood levels and a positive trend of leptin levels in boys and girls. Percentiles derived for girls were generally higher than those obtained for boys. The corresponding age-specific differences of the 97th percentile ranged from -2.2 to 4.6 μg ml(-1) and from 2.2 to 4.8 ng ml(-1) for adiponectin and leptin, respectively. According to our knowledge, these are the first reference values of leptin and adiponectin in prepubertal, normal-weight children. The presented adiponectin and leptin reference curves may allow for a more differentiated interpretation of children's hormone levels in epidemiological and clinical studies.

The role of adiponectin and adipolin as anti-inflammatory adipokines in the formation of macrophage foam cells and their association with cardiovascular diseases.

PubMed

Sargolzaei, Javad; Chamani, Elham; Kazemi, Tooba; Fallah, Soudabeh; Soori, Hosna

2018-04-01

Obesity is one of the major public health concerns that is closely associated with obesity-related disorders such as type 2 diabetes mellitus (T2DM), hypertension, and atherosclerosis. Atherosclerosis is a chronic disease characterized by excess cholesterol deposition in the arterial intima and the formation of foam cells. Adipocytokines or adipokines are secreted by the adipose tissue as endocrine glands; adiponectin and adipolin are among these adipokines that are associated with obese and insulin-resistant phenotypes. Adipolin and adiponectin are cytokines that exert substantial impact on obesity, progression of atherosclerosis, insulin resistance, and glucose metabolism. In this paper, we review the formation of macrophage foam cells, which are associated with atherosclerosis, and the macrophage mechanism, which includes uptake, esterification, and release. We also summarize current information on adipose tissue-derived hormone and energy homeostasis in obesity. Finally, the role of adipokines, e.g., adipoline and adiponectin, in regulating metabolic, cardiovascular diseases is discussed. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Relationship between adiponectin and leptin on osteocalcin in obese adolescents during weight loss therapy.

PubMed

Campos, Raquel Munhoz da Silveira; Masquio, Deborah Cristina Landi; Corgosinho, Flávia Campos; Carvalho-Ferreira, Joana Pereira de; Molin Netto, Bárbara Dal; Clemente, Ana Paula Grotti; Tock, Lian; Tufik, Sergio; Mello, Marco Túlio de; Dâmaso, Ana Raimunda

2018-05-17

Obesity is a multifactorial disease characterized by the presence of the pro-inflammatory state associated with the development of many comorbidities, including bone turnover marker alterations. This study aimed to investigate the role of the inflammatory state on bone turnover markers in obese adolescents undergoing interdisciplinary weight loss treatment for one year. Thirty four post-pubescent obese adolescents with primary obesity, a body mass index (BMI) greater than > 95th percentile of the CDC reference growth charts, participated in the present investigation. Measurements of body composition, bone turnover markers, inflammatory biomarkers and visceral and subcutaneous fat were taken. Adolescents were submitted to one year of interdisciplinary treatment (clinical approach, physical exercise, physiotherapy intervention, nutritional and psychological counseling). Reduction in body mass, body fat mass, visceral and subcutaneous fat, as well as, an increase in the body lean mass and bone mineral content was observed. An improvement in inflammatory markers was seen with an increase in adiponectin, adiponectin/leptin ratio and inteleukin-15. Moreover, a positive correlation between the adiponectin/leptin ratio and osteocalcin was demonstrated. Further, both lean and body fat mass were predictors of osteocalcin. Negative associations between leptin with osteocalcin, adiponectin with Beta CTX-collagen, and visceral fat with adiponectin were observed. It is possible to conclude that the inflammatory state can negatively influence the bone turnover markers in obese adolescents. In addition, the interdisciplinary weight loss treatment improved the inflammatory state and body composition in obese adolescents. Therefore, the present findings should be considered in clinical practice.

Long-Term Dietary Sodium Restriction Increases Adiponectin Expression and Ameliorates the Proinflammatory Adipokine Profile in Obesity

PubMed Central

Baudrand, R; Lian, CG; Lian, BQ; Ricchiuti, V; Yao, TM; Li, J; Williams, GH; Adler, GK

2015-01-01

Background/Aim Obesity is associated with changes in adiponectin and pro-inflammatory adipokines. Sodium intake can affect adipokine secretion suggesting a role in cardiovascular dysfunction. We tested if long-term dietary sodium restriction modifies the expression of adiponectin and ameliorates the pro-inflammatory profile of obese, diabetic Methods/Results Db/db mice were randomized to high sodium (HS 1.6% Na+, n=6) or low sodium (LS 0.03% Na+, n=8) diet for 16 weeks and compared with lean, db/+ mice on HS diet (n=8). Insulin levels were 50% lower in the db/db mice on LS diet when compared with HS db/db (p <0.05). LS diet increased cardiac adiponectin mRNA levels in db/db mice by 5-fold when compared with db/db mice on HS diet and by 2-fold when compared with HS lean mice (both p < 0.01). LS diet increased adiponectin in adipose tissue compared with db/db mice on HS diet, achieving levels similar to those of lean mice. MCP-1, IL-6 and TNF-α expression were reduced more than 50% in adipose tissue of db/db mice on LS diet when compared with HS db/db mice (all p < 0.05), to levels observed in the HS lean mice. Further, LS db/db mice had significantly reduced circulating MCP-1 and IL-6 levels when compared with HS db/db mice (both p < 0.01). Conclusion In obese-diabetic mice, long-term LS diet increases adiponectin in heart and adipose tissue and reduces pro-inflammatory factors in adipose tissue and plasma. These additive mechanisms may contribute to the potential cardioprotective benefits of LS diet in obesity-related metabolic disorders. PMID:24418377

Effects of Sugar-sweetened Beverages on plasma Acylation Stimulating Protein, Leptin & Adiponectin and Metabolic Parameters

PubMed Central

Rezvani, Reza; Cianflone, Katherine; McGahan, John P.; Berglund, Lars; Bremer, Andrew A.; Keim, Nancy L.; Griffen, Steven C.; Havel, Peter J.; Stanhope, Kimber L.

2013-01-01

Objective We determined the effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity. Design and Methods 32 overweight/obese adults consumed glucose- or fructose-sweetened beverages (25% energy requirement) with their ad libitum diets for 8 weeks, followed by sweetened beverage consumption for 2 weeks with a standardized, energy-balanced diet. Plasma variables were measured at baseline, 2, 8 and 10 weeks, and body adiposity and insulin sensitivity at baseline and 10 weeks. Results Fasting and postprandial ASP concentrations increased at 2 and/or 8 weeks. ASP increases correlated with changes in late-evening triglyceride concentrations. At 10 weeks, fasting adiponectin levels decreased in both groups, and decreases were inversely associated with baseline intra-abdominal fat volume. Sugar consumption increased fasting leptin concentrations; increases were associated with body weight changes. 24-h leptin profiles increased during glucose consumption and decreased during fructose consumption. These changes correlated with changes of 24-h insulin levels. Conclusions The consumption of fructose and glucose beverages induced changes in plasma concentrations of ASP, adiponectin and leptin. Further study is required to determine if these changes contribute to the metabolic dysfunction observed during fructose consumption. PMID:23512943

Effects of individual and combined dietary weight loss and exercise interventions in postmenopausal women on adiponectin and leptin levels.

PubMed

Abbenhardt, C; McTiernan, A; Alfano, C M; Wener, M H; Campbell, K L; Duggan, C; Foster-Schubert, K E; Kong, A; Toriola, A T; Potter, J D; Mason, C; Xiao, L; Blackburn, G L; Bain, C; Ulrich, C M

2013-08-01

Excess body weight and a sedentary lifestyle are associated with the development of several diseases, including cardiovascular disease, diabetes and cancer in women. One proposed mechanism linking obesity to chronic diseases is an alteration in adipose-derived adiponectin and leptin levels. We investigated the effects of 12-month reduced calorie, weight loss and exercise interventions on adiponectin and leptin concentrations. Overweight/obese postmenopausal women (n = 439) were randomized as follows: (i) a reduced calorie, weight-loss diet (diet; N = 118), (ii) moderate-to-vigorous intensity aerobic exercise (exercise; N = 117), (iii) a combination of a reduced calorie, weight-loss diet and moderate-to-vigorous intensity aerobic exercise (diet + exercise; N = 117), and (iv) control (N = 87). The reduced calorie diet had a 10% weight-loss goal. The exercise intervention consisted of 45 min of moderate-to-vigorous aerobic activity 5 days per week. Adiponectin and leptin levels were measured at baseline and after 12 months of intervention using a radioimmunoassay. Adiponectin increased by 9.5% in the diet group and 6.6% in the diet + exercise group (both P ≤ 0.0001 vs. control). Compared with controls, leptin decreased with all interventions (diet + exercise, -40.1%, P < 0.0001; diet, -27.1%, P < 0.0001; exercise, -12.7%, P = 0.005). The results were not influenced by the baseline body mass index (BMI). The degree of weight loss was inversely associated with concentrations of adiponectin (diet, P-trend = 0.0002; diet + exercise, P-trend = 0.0005) and directly associated with leptin (diet, P-trend < 0.0001; diet + exercise, P-trend < 0.0001). Weight loss through diet or diet + exercise increased adiponectin concentrations. Leptin concentrations decreased in all of the intervention groups, but the greatest reduction occurred with diet + exercise. Weight loss and exercise exerted some beneficial effects on chronic diseases via

Association of polymorphism in adiponectin (+45 T/G) and leptin (–2548 G/A) genes with type 2 diabetes mellitus in male Egyptians

PubMed Central

Motawi, Tarek; Salman, Tarek; Shaker, Olfat

2015-01-01

Introduction Adiponectin is an adipose tissue-specific protein with insulin-sensitizing properties. Many investigators have explored the association between adiponectin single nucleotide polymorphisms (SNPs) and type 2 diabetes mellitus (T2DM) in different ethnic populations from different regions. Leptin is a protein hormone constituting an important signal in the regulation of adipose tissue mass and body weight. The aim of this study was to explore potential associations between SNP +45 T>G of the adiponectin gene and SNP 2548G/A of leptin with T2DM and the effect of SNPs on serum adiponectin and leptin levels. Material and methods From the Egyptian population, we enrolled 110 T2DM patients and 90 non-diabetic controls. Serum lipid profile, blood glucose, serum adiponectin, and leptin were measured. Genotyping for two common SNPs of the adiponectin and leptin genes was performed by polymerase chain reaction–restriction fragment length polymorphism. Results The G allele and TG/GG genotype of SNP 45 occurred more frequently than the T allele and TT genotype in T2DM patients compares to the controls. Subjects with the GG + TG genotype of SNP 45 were at increased risk for T2DM (OR = 6.476; 95% CI: 3.401–12.33) and associated with a low serum adiponectin level compared with the TT genotype. The serum leptin concentration of GA + AA genotype carriers was not significantly different from that of the GG genotype in the diabetic group. Conclusions The G allele carriers who have reduced plasma concentrations of adiponectin may have an association with T2DM, while leptin SNP 2548 G/A is not associated with the risk of development of T2DM in the Egyptian population. PMID:26528333

Breast-feeding, Leptin:Adiponectin Ratio, and Metabolic Dysfunction in Adolescents with Obesity.

PubMed

Mihalopoulos, Nicole L; Urban, Brittney M; Metos, Julie M; Balch, Alfred H; Young, Paul C; Jordan, Kristine C

2017-05-01

Increased adiposity increases leptin and decreases adiponectin concentrations, resulting in an increased leptin:adiponectin ratio (LAR). In adults, components of the metabolic syndrome and other cardiometabolic risk factors, what we classify here as "metabolic dysfunction," are associated with both a high LAR and a history of being breast-fed. The relation among breast-feeding, LAR, and degree of metabolic dysfunction in obese youth is unknown. The purpose of our pilot study was to explore this relation and estimate the effect size of the relations to determine the sample size needed to power future prospective studies. We obtained fasting levels of leptin, adiponectin, lipids, insulin, and glucose from obese youth (aged 8-17 years). Weight, height, waist circumference, blood pressure, and breast-feeding history also were assessed. Of 96 participants, 78 were breast-fed as infants, 54% of whom were breast-fed for >6 months. Wide variation was observed in LARs among children who were and were not breast-fed (>100% coefficient of variation). Overall, prevalence of metabolic dysfunction in the cohort was 94% and was not proven to be associated with higher LAR. In this cohort of obese youth, we found a high prevalence of breast-feeding, metabolic dysfunction, and wide variation in the LARs. Based on the effect size estimated, future studies would need to enroll >1500 patients or identify, stratify, and selectively enroll obese patients without metabolic dysfunction to accurately determine whether breast-feeding in infancy influences LARs or metabolic dysfunction among obese youth.

Ghrelin, leptin, adiponectin, and insulin levels and concurrent and future weight change in overweight, postmenopausal women.

PubMed

Soni, Amy C; Conroy, Molly B; Mackey, Rachel H; Kuller, Lewis H

2011-03-01

Weight loss and maintenance can be particularly challenging for postmenopausal women given the changes in body composition, metabolism, and lifestyle that can accompany the menopausal transition. Peptides mediating energy homeostasis (ghrelin, leptin, adiponectin, and insulin) may play an important role in the weight and body composition changes of postmenopausal women and may in turn be affected by hormone therapy (HT) use. This study examines how success with weight loss may be related to peptides mediating energy homeostasis and HT use. The present analysis involves 200 women from a lifestyle intervention trial in overweight, postmenopausal women for whom data on the peptides ghrelin, leptin, adiponectin, and insulin were collected at 0 and 18 months. Peptide levels were compared with changes in weight from 0 to 18 and from 18 to 30 months. Baseline peptide levels were not significantly related to future weight change. From 0 to 18 months, ghrelin (P = 0.0005) and adiponectin (P ≤ 0.0001) levels increased, whereas leptin (P ≤ 0.0001) and insulin (P = 0.0003) levels decreased with increasing amount of weight loss. However, only leptin change was related to 18-30-month weight change. Women who were on HT at 0 months but discontinued by 18 months had a greater increase in ghrelin level from 0 to 18 months compared with women with continuous HT use or nonuse. In overweight, postmenopausal women, changes in energy homeostasis peptides relate to both concurrent and future weight change. Future studies should continue to address how ghrelin, leptin, insulin, and adiponectin contribute to body composition changes and weight loss maintenance after menopause.

Ghrelin, Leptin, Adiponectin, and Insulin Levels and Concurrent and Future Weight Change in Overweight Postmenopausal Women

PubMed Central

Soni, Amy C.; Conroy, Molly B.; Mackey, Rachel H.; Kuller, Lewis H.

2010-01-01

Objective Weight loss and maintenance can be particularly challenging for postmenopausal women given the changes in body composition, metabolism, and lifestyle that can accompany the menopausal transition. Peptides mediating energy homeostasis (i.e., ghrelin, leptin, adiponectin, and insulin) may play an important role in the weight and body composition changes of postmenopausal women, and may in turn be affected by hormone therapy (HT) use. This study examines how success with weight loss may be related to peptides mediating energy homeostasis and HT use. Methods The present analysis involves 200 women from a lifestyle intervention trial in overweight, postmenopausal women for whom data on the peptides ghrelin, leptin, adiponectin, and insulin were collected at 0 and 18 months. Peptide levels were compared to changes in weight from 0-18 and18-30 months. Results Baseline peptide levels were not significantly related to future weight change. From 0-18 months, ghrelin (p=0.0005) and adiponectin (p=<0.0001) levels increased, while leptin (p=<0.0001), and insulin (p=0.0003) decreased with increasing amount of weight loss. However, only leptin change was related to 18-30 month weight change. Women who were on HT at 0 months but discontinued by 18 months had a greater increase in ghrelin from 0-18 months compared to women with continuous HT use or non-use. Conclusions In overweight, postmenopausal women, changes in energy homeostasis peptides relate to both concurrent and future weight change. Future studies should continue to address the how ghrelin, leptin, insulin, and adiponectin contribute to body composition changes and weight loss maintenance after menopause. PMID:21449093

A prospective 4-year study of insulin resistance and adipokines in morbidly obese diabetic and non-diabetic patients after gastric banding.

PubMed

Urbanavicius, Vaidotas; Juodeikis, Zygimantas; Dzenkeviciute, Vilma; Galkine, Aiste; Petrulioniene, Zaneta; Sapoka, Virginijus; Brimiene, Vilma; Vitkus, Dalius; Brimas, Gintautas

2017-06-01

There are insufficient data regarding the changes in adipokine levels after laparoscopic adjustable gastric banding (LAGB) in diabetic and non-diabetic patients and their effects on insulin resistance and type 2 diabetes remission. To assess leptin, adiponectin, and insulin resistance changes after LAGB in diabetic and non-diabetic morbidly obese patients. One hundred and three patients (37 with and 66 without type 2 diabetes) underwent LAGB from January 2009 to January 2010. Glycated hemoglobin, insulin, adipokine levels and insulin resistance were evaluated preoperatively, and 1 and 4 years after LAGB. The mean patient age was 45.9 ±11.7 years and mean preoperative body mass index was 47.5 ±7.3 kg/m 2 . A total of 80 of 103 patients (77.6%) completed the 4-year follow-up. After 4 years the mean excess weight loss was 38.8% and 39.5% in diabetic and non-diabetic patients respectively. Leptin levels decreased significantly in both groups at 1 year, but after 4 years this was noted only in non-diabetic patients. After 1 year adiponectin levels increased significantly only in non-diabetic patients (p = 0.003) and remained almost the same at 4 years. A significant decrease in insulin resistance was noted in both groups 1 year after LAGB and diabetes remission was observed in 23 (62.1%) patients. There was a negative correlation between preoperative insulin resistance and adiponectin levels throughout the follow-up period. Leptin levels positively correlated with BMI throughout the study period (baseline r = 0.45; p < 0.001; after 1 year r = 0.71; p < 0.001; after 4 years r = 0.68; p < 0.001). There was no significant correlation between leptin and adiponectin concentrations preoperatively or after 1 year; however, at 4 years it was significant (r = 0.27; p < 0.02). The most significant metabolic changes occurred within 1 year after LAGB. The 4-year follow-up revealed stabilization in metabolic indices rather than significant improvement.

The role of pro-inflammatory and anti-inflammatory adipokines on exercise-induced bronchospasm in obese adolescents undergoing treatment.

PubMed

da Silva, Patrícia Leão; de Mello, Marco Túlio; Cheik, Nadia Carla; Sanches, Priscila Lima; Piano, Aline; Corgosinho, Flávia Campos; Campos, Raquel Munhoz da Silveira; Carnier, June; Inoue, Daniela; do Nascimento, Claudia Mo; Oyama, Lila M; Tock, Lian; Tufik, Sérgio; Dâmaso, Ana R

2012-04-01

Recent studies have demonstrated a greater prevalence in exercise-induced bronchospasm (EIB) in obese adolescents. However, the role of pro-/anti-inflammatory adipokines and the repercussions of obesity treatment on EIB need to be explored further. Therefore, the objective of this study was to evaluate the role of pro-/anti-inflammatory adipokines on EIB in obese adolescents evaluated after long-term interdisciplinary therapy. Thirty-five post-pubertal obese adolescents, including 20 non-EIB (body mass index [BMI] 36 ± 5 kg/m(2)) and 15 EIB (BMI 36 ± 5 kg/m(2)), were enrolled in this study. Body composition was measured by plethysmography, using the BOD POD body composition system, and visceral fat was analyzed by ultrasound. Serum levels of adiponectin and leptin were analyzed. EIB and lung function were evaluated according to the American Thoracic Society criteria. Patients were recruited to a 1-year interdisciplinary intervention of weight loss, consisting of medical, nutritional, exercise, and psychological components. Anthropometrics and lung function variables improved significantly after the therapy in both groups. Furthermore we observed a reduction in EIB occurrence in obese adolescents after treatment. There was an increase in adiponectin levels and a reduction in leptin levels after the therapy. In addition, a low FEV(1) value was a risk factor associated with EIB occurrence at baseline, and was correlated after treatment with changes in anthropometric and maximal O(2) consumption values as well as the adipokines profile. In the present study it was demonstrated that 1 year of interdisciplinary therapy decreased EIB frequency in obese adolescents, paralleled by an increase in lung function and improvement in pro-/anti-inflammatory adipokines.

Association of obesity with serum leptin, adiponectin, and serotonin and gut microflora in beagle dogs.

PubMed

Park, H-J; Lee, S-E; Kim, H-B; Isaacson, R E; Seo, K-W; Song, K-H

2015-01-01

Serotonin (5-hydroxytryptamine, 5HT) is involved in hypothalamic regulation of energy consumption. Also, the gut microbiome can influence neuronal signaling to the brain through vagal afferent neurons. Therefore, serotonin concentrations in the central nervous system and the composition of the microbiota can be related to obesity. To examine adipokine, and, serotonin concentrations, and the gut microbiota in lean dogs and dogs with experimentally induced obesity. Fourteen healthy Beagle dogs were used in this study. Seven Beagle dogs in the obese group were fed commercial food ad libitum, over a period of 6 months to increase their weight and seven Beagle dogs in lean group were fed a restricted amount of the same diet to maintain optimal body condition over a period of 6 months. Peripheral leptin, adiponectin, 5HT, and cerebrospinal fluid (CSF-5HT) levels were measured by ELISA. Fecal samples were collected in lean and obese groups 6 months after obesity was induced. Targeted pyrosequencing of the 16S rRNA gene was performed using a Genome Sequencer FLX plus system. Leptin concentrations were higher in the obese group (1.98 ± 1.00) compared to those of the lean group (1.12 ± 0.07, P = .025). Adiponectin and 5-hydroytryptamine of cerebrospinal fluid (CSF-5HT) concentrations were higher in the lean group (27.1 ± 7.28) than in the obese group (14.4 ± 5.40, P = .018). Analysis of the microbiome revealed that the diversity of the microbial community was lower in the obese group. Microbes from the phylum Firmicutes (85%) were predominant group in the gut microbiota of lean dogs. However, bacteria from the phylum Proteobacteria (76%) were the predominant group in the gut microbiota of dogs in the obese group. Decreased 5HT levels in obese group might increase the risk of obesity because of increased appetite. Microflora enriched with gram-negative might be related with chronic inflammation status in obese dogs. Copyright © 2014 by the American College of Veterinary

The adipokine adiponectin has potent anti-fibrotic effects mediated via adenosine monophosphate-activated protein kinase: novel target for fibrosis therapy

PubMed Central

2012-01-01

Introduction Fibrosis in scleroderma is associated with collagen deposition and myofibroblast accumulation. Peroxisome proliferator activated receptor gamma (PPAR-γ), a master regulator of adipogenesis, inhibits profibrotic responses induced by transforming growth factor-ß (TGF-β), and its expression is impaired in scleroderma. The roles of adiponectin, a PPAR-γ regulated pleiotropic adipokine, in regulating the response of fibroblasts and in mediating the effects of PPAR-γ are unknown. Methods Regulation of fibrotic gene expression and TGF-ß signaling by adiponectin and adenosine monophosphate protein-activated (AMP) kinase agonists were examined in normal fibroblasts in monolayer cultures and in three-dimensional skin equivalents. AdipoR1/2 expression on skin fibroblasts was determined by real-time quantitative PCR. Results Adiponectin, an adipokine directly regulated by PPAR-γ, acts as a potent anti-fibrotic signal in normal and scleroderma fibroblasts that abrogates the stimulatory effects of diverse fibrotic stimuli and reduces elevated collagen gene expression in scleroderma fibroblasts. Adiponectin responses are mediated via AMP kinase, a fuel-sensing cellular enzyme that is necessary and sufficient for down-regulation of fibrotic genes by blocking canonical Smad signaling. Moreover, we demonstrate that endogenous adiponectin accounts, at least in part, for the anti-fibrotic effects exerted by ligands of PPAR-γ. Conclusions These findings reveal a novel link between cellular energy metabolism and extracellular matrix homeostasis converging on AMP kinase. Since the levels of adiponectin as well as its receptor are impaired in scleroderma patients with progressive fibrosis, the present results suggest a potential role for defective adiponectin expression or function in progressive fibrogenesis in scleroderma and other chronic fibrosing conditions. Restoring the adiponectin signaling axis in fibroblasts might, therefore, represent a novel

Ethnic differences in leptin and adiponectin levels between Greenlandic Inuit and Danish children

PubMed Central

Munch-Andersen, Thor; Sorensen, Kaspar; Aachmann-Andersen, Niels-Jacob; Aksglaede, Lise; Juul, Anders; Helge, Jørn W.

2013-01-01

Objective In a recent study, we found that Greenlandic Inuit children had a more adverse metabolic profile than Danish children. Aerobic fitness and adiposity could only partly account for the differences. Therefore, we set out to evaluate and compare plasma leptin and adiponectin levels in Danish and Inuit children. Methods In total, 187 Inuit and 132 Danish children (5.7–17.1 years) had examinations of anthropometrics, body fat content, pubertal staging, fasting blood and aerobic fitness. Results Plasma leptin was higher in Danish boys [3,774 (4,741–3,005)] [pg/mL unadjusted geometric mean (95% CI)] compared to both northern [2,076 (2,525–1,706)] (p<0.001) and southern (2,515 (3,137–2,016)) (p<0.001) living Inuit boys and higher in Danish girls [6,988 (8,353–5,847)] compared to southern living Inuit girls [4,910 (6,370–3,785)] (p=0.021) and tended to be higher compared to northern living Inuit girls [5,131 (6,444–4,085)] (p=0.052). Plasma adiponectin was higher for both Danish boys [22,359 (2,573–19,428)] [ng/mL unadjusted geometric mean (95% CI)] and girls [26,609 (28,994–24,420)] compared to southern living Inuit boys [15,306 (18,406–12,728)] and girls [18,864 (22,640–15,717)] (both p<0.001), respectively. All differences remained after adjustment for body fat percentage (BF%), aerobic fitness, age and puberty. The leptin/adiponectin ratio was higher in Danish boys and tended to be higher in Danish girls compared to northern living Inuit boys and girls, respectively. These differences were eliminated after adjustment for BF%, aerobic fitness, age and puberty. Conclusions In contrast to our hypothesis, plasma leptin was higher in Danish children despite a more healthy metabolic profile compared to Inuit children. As expected, plasma adiponectin was lowest in Inuit children with the most adverse metabolic profile. PMID:23940841

Ethnic differences in leptin and adiponectin levels between Greenlandic Inuit and Danish children.

PubMed

Munch-Andersen, Thor; Sorensen, Kaspar; Aachmann-Andersen, Niels-Jacob; Aksglaede, Lise; Juul, Anders; Helge, Jørn W

2013-01-01

In a recent study, we found that Greenlandic Inuit children had a more adverse metabolic profile than Danish children. Aerobic fitness and adiposity could only partly account for the differences. Therefore, we set out to evaluate and compare plasma leptin and adiponectin levels in Danish and Inuit children. In total, 187 Inuit and 132 Danish children (5.7-17.1 years) had examinations of anthropometrics, body fat content, pubertal staging, fasting blood and aerobic fitness. Plasma leptin was higher in Danish boys [3,774 (4,741-3,005)] [pg/mL unadjusted geometric mean (95% CI)] compared to both northern [2,076 (2,525-1,706)] (p < 0.001) and southern (2,515 (3,137-2,016)) (p < 0.001) living Inuit boys and higher in Danish girls [6,988 (8,353-5,847)] compared to southern living Inuit girls [4,910 (6,370-3,785)] (p = 0.021) and tended to be higher compared to northern living Inuit girls [5,131 (6,444-4,085)] (p = 0.052). Plasma adiponectin was higher for both Danish boys [22,359 (2,573-19,428)] [ng/mL unadjusted geometric mean (95% CI)] and girls [26,609 (28,994-24,420)] compared to southern living Inuit boys [15,306 (18,406-12,728)] and girls [18,864 (22,640-15,717)] (both p < 0.001), respectively. All differences remained after adjustment for body fat percentage (BF%), aerobic fitness, age and puberty. The leptin/adiponectin ratio was higher in Danish boys and tended to be higher in Danish girls compared to northern living Inuit boys and girls, respectively. These differences were eliminated after adjustment for BF%, aerobic fitness, age and puberty. In contrast to our hypothesis, plasma leptin was higher in Danish children despite a more healthy metabolic profile compared to Inuit children. As expected, plasma adiponectin was lowest in Inuit children with the most adverse metabolic profile.

Breast-feeding, Leptin:Adiponectin Ratio, and Metabolic Dysfunction in Adolescents with Obesity

PubMed Central

Mihalopoulos, Nicole L.; Urban, Brittney M.; Metos, Julie M.; Balch, Alfred H.; Young, Paul C.; Jordan, Kristine C.

2017-01-01

Objectives Increased adiposity increases leptin and decreases adiponectin concentrations, resulting in an increased leptin:adiponectin ratio (LAR). In adults, components of the metabolic syndrome and other cardiometabolic risk factors, what we classify here as “metabolic dysfunction,” are associated with both a high LAR and a history of being breast-fed. The relation among breast-feeding, LAR, and degree of metabolic dysfunction in obese youth is unknown. The purpose of our pilot study was to explore this relation and estimate the effect size of the relations to determine the sample size needed to power future prospective studies. Methods We obtained fasting levels of leptin, adiponectin, lipids, insulin, and glucose from obese youth (aged 8–17 years). Weight, height, waist circumference, blood pressure, and breast-feeding history also were assessed. Results Of 96 participants, 78 were breast-fed as infants, 54% of whom were breast-fed for >6 months. Wide variation was observed in LARs among children who were and were not breast-fed (>100% coefficient of variation). Overall, prevalence of metabolic dysfunction in the cohort was 94% and was not proven to be associated with higher LAR. Conclusions In this cohort of obese youth, we found a high prevalence of breast-feeding, metabolic dysfunction, and wide variation in the LARs. Based on the effect size estimated, future studies would need to enroll >1500 patients or identify, stratify, and selectively enroll obese patients without metabolic dysfunction to accurately determine whether breast-feeding in infancy influences LARs or metabolic dysfunction among obese youth. PMID:28464176

Expression of adipokines in osteoarthritis osteophytes and their effect on osteoblasts.

PubMed

Junker, Susann; Frommer, Klaus W; Krumbholz, Grit; Tsiklauri, Lali; Gerstberger, Rüdiger; Rehart, Stefan; Steinmeyer, Jürgen; Rickert, Markus; Wenisch, Sabine; Schett, Georg; Müller-Ladner, Ulf; Neumann, Elena

2017-10-01

Osteophyte formation in osteoarthritis (OA) is mediated by increased osteoblast activity, which is -in turn- regulated by the Wnt signaling pathway. Obesity is regarded a risk factor in OA, yet little is known about the interaction between adipose tissue-derived factors, the adipokines, and bone formation, although adipokines are associated with the pathogenesis of OA. Therefore, the effect of adipokines on bone and cartilage forming cells and osteophyte development was analyzed. Human OA osteophytes were histologically characterized and adipokine expression was evaluated by immunohistochemistry. Osteoblasts and chondrocytes were isolated from OA tissue and stimulated with adiponectin, resistin, or visfatin. Cytokine and osteoblast/chondrocyte markers were quantified and activation of Wnt and p38 MAPK signaling was analyzed. Adiponectin, resistin, and visfatin were expressed in OA osteophytes by various articular cell types. Stimulation of OA osteoblasts with adiponectin and of OA chondrocytes with visfatin led to an increased release of proinflammatory mediators but not to osteoblast differentiation or activation. Additionally, visfatin increased matrix degrading factors in chondrocytes. Wnt signaling was not altered by adipokines, but adiponectin induced p38 MAPK signaling in osteoblasts. Adipokines are present in OA osteophytes, and adiponectin and visfatin increase the release of proinflammatory mediators by osteoblasts and chondrocytes. The effects of adiponectin were mediated by p38 MAPK but not Wnt signaling in osteoblasts. Therefore, the results support the idea that adipokines do not directly influence osteophyte development but the proinflammatory conditions in OA. Copyright © 2016 Elsevier B.V. All rights reserved.

Association of adiponectin/leptin ratio with carbohydrate and lipid metabolism parameters in HIV-infected patients during antiretroviral therapy.

PubMed

Tiliscan, Catalin; Arama, Victoria; Mihailescu, Raluca; Munteanu, Daniela; Iacob, Diana Gabriela; Popescu, Cristina; Catana, Remulus; Negru, Anca; Lobodan, Alina; Arama, Stefan Sorin

2018-02-16

Adiponectin and leptin are adipose tissue hormones that regulate important lipid and glucose metabolic pathways. Our objective was to evaluate the interplay of these hormones described by the adiponectin/leptin ratio (ALR) in correlation to lipid and carbohydrate metabolism parameters in nondiabetic HIV-infected patients during antiretroviral therapy (ART). We enrolled consecutive nondiabetic patients with confirmed HIV infection, undergoing stable ART regimens for at least six months. Blood samples were collected and tested for immunological and virological parameters, adiponectin and leptin, fasting insulin, fasting plasma glucose, fasting triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol. ALR was computed for each patient. Resistance to insulin was assessed by calculating the Quantitative Insulin Sensitivity Check Index (QUICKI). We enrolled 87 HIV-infected persons, with a mean age of 31.7 years (range: 18-65), including 47 men (mean age = 32.8 years) and 40 women (mean age = 30.5 years). The median value of ALR was 6.8 (interquartile range - IQR = 17.1). In male patients, ALR was inversely associated with the serum level of triglycerides (R = 0.285, p = 0.05), total cholesterol (R = 0.326, p = 0.02), and LDL cholesterol (R = 0.298, p = 0.04). Also for the male cohort, an increase in ALR seemed to improve insulin sensitivity (R = 0.323, p = 0.02) and serum HDL cholesterol (R = 0.597, p = 0.01). None of these correlations were observed in HIV-infected women. Adiponectin and leptin seem to play important but different gender-specific roles in the pathogenesis of lipid and glucose metabolism of HIV-infected patients undergoing antiretroviral therapy. ALR, adiponectin/leptin ratio; BMI, body mass index; LDL, low-density lipoprotein; HDL, high-density lipoprotein; QUICKI, Quantitative Insulin Sensitivity Check Index.

Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.

PubMed

Roumaud, Pauline; Martin, Luc J

2015-10-01

The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

Early Life Adversity Is Associated With Elevated Levels of Circulating Leptin, Irisin, and Decreased Levels of Adiponectin in Midlife Adults

PubMed Central

Joung, Kyoung Eun; Park, Kyung-Hee; Zaichenko, Lesya; Sahin-Efe, Ayse; Thakkar, Bindiya; Brinkoetter, Mary; Usher, Nicole; Warner, Dorothy; Davis, Cynthia R.; Crowell, Judith A.

2014-01-01

Context: Early-life adversity, defined as physical, emotional, or sexual abuse and neglect before 18 years of age, is associated with metabolic syndrome, obesity, and type 2 diabetes mellitus in adult life. However, the underlying mechanism is not fully understood, and whether adipomyokines are associated with early-life adversity independent of other factors such as body mass index, psychosocial risks, and health behaviors is not known. Objectives: The objective of the study was to evaluate the association between early-life adversity and circulating the levels of the adipomyokines such as leptin, adiponectin, and irisin and the inflammatory marker, C-reactive protein (CRP). Design/Subjects/Setting: This study was a cross-sectional study of 95 adults at a university-based research center. We collected venous blood from participants and analyzed serum for leptin, adiponectin, irisin, and CRP. Results: Circulating leptin, irisin, and CRP levels were significantly higher in the highest adversity tertile group compared with low and middle tertile groups (P < .001 for leptin, P = .01 for irisin, and P = .02 for CRP). Adiponectin levels were lower in the highest tertile group compared with the low and middle tertile groups (P = .03). After adjusting for demographic variables, physical activity, diet, current mental health, and body mass index, the associations between early-life adversity leptin, irisin, and did not change. However, adiponectin and CRP levels were no longer significantly related to early life adversity. Conclusion: Early-life adversity is directly associated with elevated circulating leptin and irisin, and indirectly associated with elevated CRP and decreased adiponectin. These findings suggest that these adipomyokines may play a role in the pathogenesis of metabolic abnormality in a population with significant early life adversity. PMID:24650014

Higher fetuin-A, lower adiponectin and free leptin levels mediate effects of excess body weight on insulin resistance and risk for myelodysplastic syndrome.

PubMed

Dalamaga, Maria; Karmaniolas, Konstantinos; Chamberland, John; Nikolaidou, Athina; Lekka, Antigoni; Dionyssiou-Asteriou, Amalia; Mantzoros, Christos S

2013-12-01

Excess body weight has been implicated in the pathogenesis of myelodysplastic syndrome (MDS). We thus explored the role of serum fetuin-A reflecting ectopic hepatic fat deposition when storage capacity of adipocytes has been exceeded, free leptin reflecting overall fat mass and adiponectin reflecting visceral fat mass, all potential mediators of the effects of obesity on insulin resistance and, consequently, to MDS risk. In a hospital-based case-control study, we studied 101 cases with incident, histologically confirmed primary MDS and 101 controls matched on gender, age and date of diagnosis, between 2004 and 2007. Serum fetuin-A, adiponectin, leptin, leptin receptor, free leptin and insulin were determined. Higher serum fetuin-A, lower adiponectin and lower free leptin were all individually and independently associated with higher risk of MDS before and after controlling for matching and risk factors, such as age, gender, date of diagnosis, body mass index (BMI), family history of lymphohematopoietic cancer, smoking history and serum insulin. Interestingly, we have shown that these associations were prominent among overweight/obese individuals and persisted after controlling for BMI and serum insulin indicating that their effects are above and beyond insulinemia only. Elevated serum fetuin-A but lower adiponectin and free leptin are associated with higher risk of MDS particularly among overweight/obese individuals. These findings suggest that the association between excessive weight gain and the risk of MDS could be mediated by fetuin-A, adiponectin and free leptin, which may have potential clinical and preventive implications. © 2013.

Circulating Adipokines in Healthy versus Unhealthy Overweight and Obese Subjects

PubMed Central

Alfadda, Assim A.

2014-01-01

It is now well established that not all obese subjects are at increased risk of cardiometabolic complications; such patients are termed the metabolically healthy obese. Despite their higher-than-normal body fat mass, they are still insulin sensitive, with a favorable inflammatory and lipid profile and no signs of hypertension. It remains unclear which factors determine an individual's metabolic health. Adipose tissue is known to secrete multiple bioactive substances, called adipokines, that can contribute to the development of obesity-associated complications. The goal of this study was to determine whether the circulating adipokine profiles differs between metabolically healthy and metabolically unhealthy overweight and obese subjects, thereby obtaining data that could help to explain the link between obesity and its related cardiometabolic complications. We defined metabolic health in terms of several metabolic and inflammatory risk factors. The serum adiponectin levels were higher in the healthy group and showed a positive correlation with HDL cholesterol levels in the unhealthy group. There were no differences between the two groups in the levels of serum leptin, chemerin and orosomucoid. Accordingly, adiponectin might play a role in protecting against obesity-associated cardiometabolic derangements. More studies are needed to clarify the role of different chemerin isoforms in this system. PMID:24550983

Adiponectin, in contrast to leptin, is not associated with body mass index, waist circumference and HOMA-IR in subjects of a west-African population.

PubMed

Awede, Bonaventure; Adovoekpe, Diane; Adehan, Grace; MacFarlane, Niall G; Azonbakin, Simon; Dossou, Emmanuel; Amoussou-Guenou, Marcellin; Djrolo, François

2018-06-01

Factors associated with plasma levels of adiponectin and leptin were studied in adult subjects without diabetes from Cotonou in Benin (West-Africa). Seventy (70) men and 45 women were included in the study. Anthropometric variables were measured and a venous blood sample was drawn from each subject, after an overnight fasting period, for measurement of plasma glucose, insulin, leptin, and adiponectin levels. HOMA-IR was determined to assess insulin resistance. Adiponectin and leptin levels were higher in women than in men (with adiponectin 18.48 ± 12.77 vs.7.8 ± 10.39 μg/mL, P < 0.0001, and leptin 30.77 ± 19.16 vs. 8.66 ± 8.24 ng/mL, P < 0.0001). Fasting insulin level and HOMA-IR were also higher in the females. Hyperleptinemia was observed in 66,96% of subjects and hypoadiponectinemia was present in 44.35% of subjects. In both men and women, leptin correlated with age (r = 0.2; P = 0.02), BMI (r = 0.572; P < 0.0001), waist circumference (r = 0.534; P < 0.0001), fasting insulin (r = 0.461; P < 0.001), and HOMA-IR (r = 0.430; P < 0.0001). No significant correlation was observed for adiponectin levels with these variables. Only in women, adiponectin was inversely correlated with fasting glucose (r = -0.423; P < 0.004). These data confirm previous descriptions of leptin but suggest that variations in factors determining serum adiponectin levels observed between ethnicities could also been seen between populations from the same ethnicity. © 2018 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.

Key Clinical Factors Predicting Adipokine and Oxidative Stress Marker Concentrations among Normal, Overweight and Obese Pregnant Women Using Artificial Neural Networks.

PubMed

Solis-Paredes, Mario; Estrada-Gutierrez, Guadalupe; Perichart-Perera, Otilia; Montoya-Estrada, Araceli; Guzmán-Huerta, Mario; Borboa-Olivares, Héctor; Bravo-Flores, Eyerahi; Cardona-Pérez, Arturo; Zaga-Clavellina, Veronica; Garcia-Latorre, Ethel; Gonzalez-Perez, Gabriela; Hernández-Pérez, José Alfredo; Irles, Claudine

2017-12-28

Maternal obesity has been related to adverse neonatal outcomes and fetal programming. Oxidative stress and adipokines are potential biomarkers in such pregnancies; thus, the measurement of these molecules has been considered critical. Therefore, we developed artificial neural network (ANN) models based on maternal weight status and clinical data to predict reliable maternal blood concentrations of these biomarkers at the end of pregnancy. Adipokines (adiponectin, leptin, and resistin), and DNA, lipid and protein oxidative markers (8-oxo-2'-deoxyguanosine, malondialdehyde and carbonylated proteins, respectively) were assessed in blood of normal weight, overweight and obese women in the third trimester of pregnancy. A Back-propagation algorithm was used to train ANN models with four input variables (age, pre-gestational body mass index (p-BMI), weight status and gestational age). ANN models were able to accurately predict all biomarkers with regression coefficients greater than R² = 0.945. P-BMI was the most significant variable for estimating adiponectin and carbonylated proteins concentrations (37%), while gestational age was the most relevant variable to predict resistin and malondialdehyde (34%). Age, gestational age and p-BMI had the same significance for leptin values. Finally, for 8-oxo-2'-deoxyguanosine prediction, the most significant variable was age (37%). These models become relevant to improve clinical and nutrition interventions in prenatal care.

Insulin use, adipokine profiles and breast cancer prognosis.

PubMed

Wintrob, Zachary A P; Hammel, Jeffrey P; Khoury, Thaer; Nimako, George K; Fu, Hsin-Wei; Fayazi, Zahra S; Gaile, Dan P; Forrest, Alan; Ceacareanu, Alice C

2017-01-01

Type-2 diabetes mellitus (T2DM) and breast cancer (BC) share common cytokine signaling changes resultant from adipose tissue dysfunction. This modified adipokine signaling was shown to be directly associated with changes in the body mass index (BMI) and diet and it is expected to also be influenced by T2DM pharmacotherapy. We evaluated the relationship between pre-existing diabetes treatment, circulating adipokine levels at cancer diagnosis, and long-term outcomes. All incident BC cases were reviewed (01/01/2003-12/31/2009, N=2194). Each of the subjects with baseline T2DM (cases) was matched with two other subjects without T2DM (controls) based on the following criteria: age, BMI, ethnicity, menopausal status and tumor stage. All cases and controls with available baseline plasma and tumor biopsies, and being surgery and BC treatment naïve, were included (N 1 =97, N 2 =194). Clinical history and vital status were documented. Adipokine levels (adiponectin, leptin, TNF-α, CRP, IL-1β, IL-1Ra, IL-6, and C-peptide) were assessed by either ELISA or Luminex® assays. Cancer outcomes were assessed by Kaplan-Meier analysis; associations between categorical variables were assessed by Fisher's exact test, categorical and continuous variables by Kruskal-Wallis or Wilcoxon Rank-Sum test, where appropriate. Multivariate adjustments (MVP, multivariate p-value) were performed accounting for age, tumor stage, BMI, estrogen receptor (ER) status and cumulative comorbidity. All biomarker correlations were assessed by the Pearson method. Utilization of insulin and insulin secretagogues was associated with ER (-) phenotype (p=0.008, p=0.043) and poorer BC outcomes (p=0.012, p=0.033). Insulin users were found to have lower C-peptide and higher IL-6, TNF-α and CRP levels, of which elevated CRP and TNF-α were associated with poorer BC outcomes (p=0.003, MVP=0.210). Insulin remarked by higher leptin levels as compared to controls (p=0.052), but did not differ significantly from non

Body and liver fat content and adipokines in schizophrenia: a magnetic resonance imaging and spectroscopy study.

PubMed

Kim, Jong-Hoon; Kim, Jung-Hyun; Park, Pil-Whan; Machann, Jürgen; Roden, Michael; Lee, Sheen-Woo; Hwang, Jong-Hee

2017-06-01

Although antipsychotic treatment often causes weight gain and lipid abnormalities, quantitative analyses of tissue-specific body fat content and its distribution along with adipokines have not been reported for antipsychotic-treated patients. The purposes of the present study were to quantitatively assess abdominal and liver fat in patients with schizophrenia on antipsychotic treatment and age- and body mass index (BMI)-matched healthy controls and to evaluate their associations with plasma leptin and adiponectin levels. In 13 schizophrenia patients on antipsychotic treatment and 11 age- and BMI-matched controls, we simultaneously quantified visceral and subcutaneous fat content using T1-weighted magnetic resonance imaging and liver fat content by 1 H magnetic resonance spectroscopy. Associations of tissue-specific fat content with plasma levels of leptin and adiponectin were evaluated. Plasma adiponectin level (μg/mL) was not statistically different between groups (7.02 ± 2.67 vs. 7.59 ± 2.92), whereas plasma leptin level (ng/mL) trended to be higher in patients than in controls (11.82 ± 7.89 vs. 7.93 ± 5.25). The values of liver fat (%), visceral fat (L), and subcutaneous fat (L) were 9.64 ± 8.03 vs. 7.07 ± 7.35, 4.41 ± 1.64 vs. 3.31 ± 1.97, and 8.37 ± 3.34 vs. 7.16 ± 2.99 in patients vs. controls, respectively. Liver fat content was inversely correlated with adiponectin in controls (r =  - 0.87, p < 0.001) but not in patients (r =  - 0.26, p = 0.39). In both groups, visceral fat was inversely associated with adiponectin (controls : r =  - 0.66, p = 0.03; patients : r =  - 0.65, p = 0.02), while subcutaneous fat was positively correlated with leptin (controls : r = 0.90, p < 0.001; patients : r = 0.67, p = 0.01). These findings suggest that antipsychotic treatment may disrupt the physiological relationship between liver fat content and

The Effects of Exercise Training on Obesity-Induced Dysregulated Expression of Adipokines in White Adipose Tissue

PubMed Central

Sakurai, Takuya; Ogasawara, Junetsu; Kizaki, Takako; Ishibashi, Yoshinaga; Takahashi, Motoko; Kobayashi, Osamu; Nagasawa, Junichi; Takahashi, Kazuto; Ishida, Hitoshi; Ohno, Hideki

2013-01-01

Obesity is recognized as a risk factor for lifestyle-related diseases such as type 2 diabetes and cardiovascular disease. White adipose tissue (WAT) is not only a static storage site for energy; it is also a dynamic tissue that is actively involved in metabolic reactions and produces humoral factors, such as leptin and adiponectin, which are collectively referred to as adipokines. Additionally, because there is much evidence that obesity-induced inflammatory changes in WAT, which is caused by dysregulated expression of inflammation-related adipokines involving tumor necrosis factor-α and monocyte chemoattractant protein 1, contribute to the development of insulin resistance, WAT has attracted special attention as an organ that causes diabetes and other lifestyle-related diseases. Exercise training (TR) not only leads to a decrease in WAT mass but also attenuates obesity-induced dysregulated expression of the inflammation-related adipokines in WAT. Therefore, TR is widely used as a tool for preventing and improving lifestyle-related diseases. This review outlines the impact of TR on the expression and secretory response of adipokines in WAT. PMID:24369466

Early Whole Blood for Patients Requiring Massive Transfusion after Major Trauma. Addendum

DTIC Science & Technology

2013-10-01

process of determining which of the 45 patients had an abdominal CT. Measure serum (adipokines, leptin, adiponectin, and ghrelin ). We obtained serial...samples thru 24 hours on 60 patients and samples thru five days on 23 patients. We measured serum adiponectin, leptin, ghrelin , and resistin, and...adiponectin, leptin, and ghrelin were all lower in injured patients than in healthy volunteers at all timepoints. Adiponectin slowly decreased over time

Adipokine Profiling in Adult Women With Central Obesity and Hypertension

PubMed Central

Supriya, Rashmi; Yung, Benjamin Y.; Yu, Angus P.; Lee, Paul H.; Lai, Christopher W.; Cheng, Kenneth K.; Yau, Suk Y.; Chan, Lawrence W. C.; Sheridan, Sinead; Siu, Parco M.

2018-01-01

Central obesity and hypertension are common risk factors for the metabolic syndrome, cardiovascular and renal diseases. Studies have shown that it is more difficult to control blood pressure and prevent end-organ damage in obese individuals with hypertension compared to their non-obese counterparts, especially among women. Obese females have a 6 times higher risk of developing hypertension than non-obese females while obese males are at a 1.5 times higher risk of developing hypertension, compared to their non-obese counterparts. Indeed, the inter-relationship between obesity and hypertension is unclear. Adipokines have been proposed to play a mediating role in the relationship between obesity and hypertension and are involved in the pathogenesis of metabolic diseases. Therefore, this study sought to determine the role of adipokines (adiponectin, plasminogen activator inhibitor-1, leptin, and tumor necrosis factor-α) in hypertensive Hong Kong Chinese women with central obesity. A total of 387 women aged 58 ± 11 years who were examined with a 2 × 2 factorial design for central obesity (waist circumference ≥ 80 cm) and hypertension (blood pressure ≥ 140/90 mmHg), were recruited from a pool of 1,492 Hong Kong Chinese adults who were previously screened for metabolic syndrome. Subjects with hyperglycemia, hypertriglyceridemia, and dyslipidemia were excluded to eliminate confounding effects. Our findings revealed that hypertensive women with central obesity had a lower anti-inflammatory status (adiponectin) and a higher pro-inflammatory status (TNF-α) than obese alone or hypertensive alone women. Also, women with central obesity had higher circulatory PAI-1 and leptin concentrations than their non-obese counterparts. We conclude that obesity may shift toward a more pro-inflammatory state and may become more severe in the presence of hypertension or vice versa. PMID:29636702

[Cardiovascular exercise on obese women: effects on adiponectine, leptine, and tumour necrosis factor-alpha].

PubMed

Landeros-Olvera, Erick; López-Alvarenga, Juan Carlos; Nava-González, Edna J; Gallegos-Cabriales, Esther; Lavalle-González, Fernando; Bastarrachea, Raúl A; Salazar González, Bertha Cecilia

2014-01-01

The relationship of hormones adiponectin, leptin and tumor necrosis factor-alpha in adipose tissue on the atherogenic process is one of the most promising models in preventive medicine. The numerous tests performed to identify the effect of exercise on these hormones have not been clear on the type of exercise routine and physical effort calculated to contribute to changing plasma concentrations in obese women. Analyze controlledcardiovascular exercise effect on serum level of adiponectin, leptin, and tumournecrosis factor-alpha in obese young women. A simple blind clinical essay. The intervention covered a 10-week controlled, cardiovascular exercise program by 34 women (cases n=17, controls n=17) with a body mass index>27kg/m(2). Molecular analysis was performed by immune-fluorescence. Following the intervention, cases and controls means were as follows: adiponectin 19.0 vs. 12.2μ/ml (P=.008); leptin 20.0 vs. 28.0μ/L (P=.02); and tumour necrosis factor-alpha 4.7 vs. 5.1pg/ml (P=.05). The established exercise (5 sessions a week of exercise of 40min each for 10 weeks with a heart rate reserve of 40 to 80%) improved plasma concentrations of these hormones in the expected direction. This finding highlights an unpublished amount of exercise, controlled by the reserve cardiac frequency that might contribute the cardiovascular and metabolic protection to obese women. Copyright © 2013 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.

[Association of leptin, adiponectin, and ghrelin in breast milk with the growth of infants with exclusive breastfeeding].

PubMed

Huang, Li-Li; Yang, Fan; Xiong, Fei

2018-02-01

To investigate the association of leptin, adiponectin, and ghrelin in breast milk with the weight growth velocity of infants with exclusive breastfeeding. A total of 67 full-term singleton infants who received regular child care and exclusive breastfeeding and their mothers were enrolled. The nutritional status was evaluated based on the measurements of body weight and body length (underweight, growth retardation, emaciation, overweight, and obesity). Z score was used to calculate growth velocity, and according to the ΔZ score, the infants were divided into poor growth group, low growth velocity group, and normal growth velocity group. Mature breast milk samples were collected from their mothers, and ELISA was used to measure the levels of leptin, adiponectin, and ghrelin. The emaciation group had a significantly lower level of leptin in breast milk than the non-emaciation group (P<0.05), and the overweight/obesity group had a significantly lower level of adiponectin than the non-overweight/obesity group (P<0.05). The correlation analysis showed that the level of ghrelin in breast milk was positively correlated with Z score of current body weight and ΔZ score compared with birth weight (r s =0.280 and 0.290 respectively; P<0.05). The regression analysis showed that the level of ghrelin in breast milk was an important influencing factor for the Z score of body weight (β=0.161, P<0.05). Various active constituents in breast milk, including leptin, adiponectin, and ghrelin, may regulate the growth and development of infants to a certain degree, but long-term studies and observation are needed to investigate their association with offspring growth and development and the health-promoting effect of breast milk on offspring.

Effect of aerobic interval training on serum IL-10, TNFα, and adipokines levels in women with multiple sclerosis: possible relations with fatigue and quality of life.

PubMed

Mokhtarzade, Motahare; Ranjbar, Rouholah; Majdinasab, Nastaran; Patel, Darpan; Molanouri Shamsi, Mehdieh

2017-08-01

Multiple sclerosis is associated with immune system dysfunction and chronic inflammation; however, possible relations between immunologic and metabolic factors and some psychological indexes such as fatigue and quality of life, especially in relation to exercise training, have not yet been investigated. The present study was designed to investigate the effect of aerobic interval training on interleukin-10/tumor necrosis factor ratio and adipokine (leptin and adiponectin) concentrations in women with multiple sclerosis. Furthermore, the relationship between these factors with fatigue and quality of life were assessed. Forty women with multiple sclerosis (Expanded Disability Status Scale ≤3) were randomized into either a non-exercising control or training group. The training group performed 8-weeks of upper and lower limb aerobic interval training. Serum concentrations of tumor necrosis factorα, interleukin-10, leptin, and adiponectin were measured before and after the 8-week intervention. Moreover, antropometric measures and measures for fatigue and quality of life were determined at the onset of and after exercise training. The results revealed that leptin and tumor necrosis factorα levels significantly decreased subsequent to the aerobic interval training. Although blood adiponectin levels considerably increased in the training group, interleukin-10 and interleukin-10/tumor necrosis factorα ratio underwent no substantial change after the exercise training. In addition, the aerobic interval training was associated with improvement in fatigue, quality of life, and maximal oxygen consumption. Our findings suggested that aerobic interval training can be an effective strategy for managing the immune system at least by its significant impact on inflammatory cytokines and adipokines levels in women with multiple sclerosis. Additionally, this positive impact improved fatigue and adipose tissue indicators.

Influence of endurance and sprinting exercise on plasma adiponectin, leptin and irisin concentrations in racing Greyhounds and sled dogs.

PubMed

Bell, M A; Levine, C B; Downey, R L; Griffitts, C; Mann, S; Frye, C W; Wakshlag, J J

2016-05-01

The objective of this study was to assess the effects of both short-term anaerobic exercise and long-term aerobic exercise on leptin, adiponectin and irisin concentrations in both sprint and endurance canine athletes. Prospective field trial repeated measures. The 25 racing Greyhounds were run over 400 m, with blood samples collected prior to exercise and at 10 min and 120 min after exercise. The 16 sled dogs were run an average of 3.5-5 h/day on 5 out of 8 days of stage stop racing competition, with assessment on days 0, 2 and 8. Baseline leptin concentrations were found to be lower than previously recorded values of domestic dogs, possibly because of a lower body fat content in athletes, with concentrations in sled dogs being slightly higher than those in Greyhounds. Baseline adiponectin concentrations in both groups of dogs, on average, were lower than most previously recorded values in domestic dogs; although unexpected, these findings may be attributed to differences in body fat content of the study population. Endurance exercise in sled dogs resulted in a persistent decrease in leptin that appears to be independent of race-associated weight loss, with no appreciable changes in adiponectin or irisin concentrations. The anaerobic exercise of Greyhounds produced no detectable changes in leptin and adiponectin concentrations; however, a significant rise in irisin 10 min post-exercise may be a compensatory mechanism for restoration of ATP homeostasis in skeletal muscle. © 2016 Australian Veterinary Association.

Compensation for obesity-induced insulin resistance in dogs: assessment of the effects of leptin, adiponectin, and glucagon-like peptide-1 using path analysis.

PubMed

Verkest, K R; Fleeman, L M; Morton, J M; Ishioka, K; Rand, J S

2011-07-01

The hormonal mediators of obesity-induced insulin resistance and compensatory hyperinsulinemia in dogs have not been identified. Plasma samples were obtained after a 24-h fast from 104 client-owned lean, overweight, and obese dogs. Plasma glucose and insulin concentrations were used to calculate insulin sensitivity and β-cell function with the use of the homeostasis model assessment (HOMA(insulin sensitivity) and HOMA(β-cell function), respectively). Path analysis with multivariable linear regression was used to identify whether fasting plasma leptin, adiponectin, or glucagon-like peptide-1 concentrations were associated with adiposity, insulin sensitivity, and basal insulin secretion. None of the dogs were hyperglycemic. In the final path model, adiposity was positively associated with leptin (P < 0.01) and glucagon-like peptide-1 (P = 0.04) concentrations. No significant total effect of adiposity on adiponectin in dogs (P = 0.24) was observed. If there is a direct effect of leptin on adiponectin, then our results indicate that this is a positive relationship, which at least partly counters a negative direct relationship between adiposity and adiponectin. Fasting plasma leptin concentration was directly negatively associated with fasting insulin sensitivity (P = 0.01) and positively associated with β-cell function (P < 0.01), but no direct association was observed between adiponectin concentration and either insulin sensitivity or β-cell function (P = 0.42 and 0.11, respectively). We conclude that dogs compensate effectively for obesity-induced insulin resistance. Fasting plasma leptin concentrations appear to be associated with obesity-associated changes in insulin sensitivity and compensatory hyperinsulinemia in naturally occurring obese dogs. Adiponectin does not appear to be involved in the pathophysiology of obesity-associated changes in insulin sensitivity. Copyright © 2011 Elsevier Inc. All rights reserved.

Adipokines, oxidized low-density lipoprotein, and C-reactive protein levels in lean, overweight, and obese portuguese patients with type 2 diabetes.

PubMed

Neuparth, Maria João; Proença, Jorge Brandão; Santos-Silva, Alice; Coimbra, Susana

2013-01-01

Aim. Our aim was to study how different BMI scores may influence the levels of inflammation, oxidative stress, adipogenesis, glucose, and lipid metabolism, in lean, overweight, and obese Portuguese patients with type 2 diabetes mellitus (T2DM). Methods. We studied 28 lean, 38 overweight, and 17 obese patients with T2DM and 20 controls (gender and age matched). The circulating levels of oxLDL, CRP, and some adipokines-adiponectin, leptin, and chemerin-and the lipid profile were evaluated. Results. Obese patients presented significantly lower levels of adiponectin and higher leptin, oxLDL, and chemerin levels, as compared to the overweight, lean, and control groups. Overweight, compared to lean and control, subjects showed significantly lower adiponectin and higher leptin and chemerin levels; oxLDL values were significantly higher in overweight than in lean patients. Lean patients presented significantly higher chemerin values than the control. Obese patients presented significantly higher CRP values, as compared to lean patients and the control group. Obese and overweight patients presented significantly higher triglycerides values than lean patients. Except for CRP, all the observed significant changes between control and patients remained significant after statistical adjustment for the body mass index (BMI). Conclusion. The levels of leptin, adiponectin, oxLDL, CRP, and triglycerides in patients with T2DM seem to be more associated with obesity and less with diabetes. Chemerin levels were raised in lean, overweight, and obese patients, suggesting that, independently of BMI, an adipocyte dysfunction occurs. Moreover, chemerin may provide an important early biomarker of adipocyte dysfunction and a link between obesity and type 2 diabetes mellitus.

Adiponectin, Leptin, IGF-1, and Tumor Necrosis Factor Alpha As Potential Serum Biomarkers for Non-Invasive Diagnosis of Colorectal Adenoma in African Americans.

PubMed

Ashktorab, Hassan; Soleimani, Akbar; Nichols, Alexandra; Sodhi, Komal; Laiyemo, Adeyinka O; Nunlee-Bland, Gail; Nouraie, Seyed Mehdi; Brim, Hassan

2018-01-01

The potential role of adiponectin, leptin, IGF-1, and tumor necrosis factor alpha (TNF-α) as biomarkers in colorectal adenoma is not clear. Therefore, we aimed to investigate the blood serum levels of these biomarkers in colorectal adenoma. The case-control study consisted of serum from 180 African American patients with colon adenoma (cases) and 198 healthy African Americans (controls) at Howard University Hospital. We used ELISA for adiponectin, leptin, IGF-1, and TNF-α detection and quantification. Statistical analysis was performed by t -test and multivariate logistic regression. The respective differences in median leptin, adiponectin, IGF-1, and TNF-α levels between control and case groups (13.9 vs. 16.4), (11.3 vs. 46.0), (4.5 vs. 12.9), and (71.4 vs. 130.8) were statistically significant ( P  < 0.05). In a multivariate model, the odds ratio for adiponectin, TNF-α, and IGF-1 were 2.0 (95% CI = 1.6-2.5; P  < 0.001), 1.5 (95% CI = 1.5(1.1-2.0); P  = 0.004), and 1.6 (95% CI = 1.3-2.0; P  < 0.001), respectively. There was a positive correlation between serum adiponectin and IGF-1 concentrations with age ( r  = 0.17, P  < 0.001 and r  = 0.13, P  = 0.009), TNF-α, IGF-1, and leptin concentration with body mass index (BMI) ( r  = 0.44, P  < 0.001; r  = 0.11, P  = 0.03; and r  = 0.48, P  < 0.001), respectively. Also, there was a negative correlation between adiponectin and leptin concentrations with BMI ( r  = -0.40, P  < 0.001), respectively. These data support the hypothesis that adiponectin, IGF-1, and TNF-α high levels correlate with higher risk of colon adenoma and can thus be used for colorectal adenomas risk assessment.

Alterations in markers of bone metabolism and adipokines following a 3-month lifestyle intervention induced weight loss in obese prepubertal children.

PubMed

Gajewska, J; Weker, H; Ambroszkiewicz, J; Szamotulska, K; Chełchowska, M; Franek, E; Laskowska-Klita, T

2013-08-01

Adipokines may influence bone metabolism in children, but this phenomenon is not well understood. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children. We determined serum leptin, soluble leptin receptor (sOB-R), adiponectin, BALP (bone alkaline phosphatase), CTX-I (C-terminal telopeptide of type I collagen), body composition and bone mineral density (by dual-energy X-ray absorptiometry) in 100 obese prepubertal children before and after 3 months of lifestyle intervention (low-energy diet, physical activity). The control group consisted of 70 non-obese children. Obese children had higher BALP activity by about 20% (p<0.001) and similar value of CTX-I compared with non-obese children. After weight loss (-0.96 BMI-SDS mean change), the BALP value in obese patients decreased (p<0.001), whereas CTX-I concentration was unchanged. Changes in BALP were positively correlated with changes in BMI (Body Mass Index) (r=0.352, p<0.001), but not associated with adipokine levels. Trend analysis using SDS-BMI subgroups showed that greater reduction of body mass was associated with a greater decrease of BALP (p=0.035) and leptin values (p<0.001), as well as a greater increase of sOB-R (p<0.003). Obesity during the prepubertal period is associated with an alteration in the adipokines profile and greater whole-body bone mass as a result of increased bone formation rather than reduced bone resorption. Changes in bone metabolism during lifestyle intervention seem to be related to weight loss but not to changes in adipokines. Further studies should elucidate the influence of long-term therapy on bone mass in childhood. © Georg Thieme Verlag KG Stuttgart · New York.

Running a marathon induces changes in adipokine levels and in markers of cartilage degradation--novel role for resistin.

PubMed

Vuolteenaho, Katriina; Leppänen, Tiina; Kekkonen, Riina; Korpela, Riitta; Moilanen, Eeva

2014-01-01

Running a marathon causes strenuous joint loading and increased energy expenditure. Adipokines regulate energy metabolism, but recent studies have indicated that they also exert a role in cartilage degradation in arthritis. Our aim was to investigate the effects of running a marathon on the levels of adipokines and indices of cartilage metabolism. Blood samples were obtained from 46 male marathoners before and after a marathon run. We measured levels of matrix metalloproteinase-3 (MMP-3), cartilage oligomeric protein (COMP) and chitinase 3-like protein 1 (YKL-40) as biomarkers of cartilage turnover and/or damage and plasma concentrations of adipokines adiponectin, leptin and resistin. Mean marathon time was 3:30:46±0:02:46 (h:min:sec). The exertion more than doubled MMP-3 levels and this change correlated negatively with the marathon time (r = -0.448, p = 0.002). YKL-40 levels increased by 56% and the effect on COMP release was variable. Running a marathon increased the levels of resistin and adiponectin, while leptin levels remained unchanged. The marathon-induced changes in resistin levels were positively associated with the changes in MMP-3 (r = 0.382, p = 0.009) and YKL-40 (r = 0.588, p<0.001) and the pre-marathon resistin levels correlated positively with the marathon induced change in YKL-40 (r = 0.386, p = 0.008). The present results show the impact of running a marathon, and possible load frequency, on cartilage metabolism: the faster the marathon was run, the greater was the increase in MMP-3 levels. Further, the results introduce pro-inflammatory adipocytokine resistin as a novel factor, which enhances during marathon race and associates with markers of cartilage degradation.

Adipokines induce catabolism of newly synthesized matrix in cartilage and meniscus tissues.

PubMed

Nishimuta, James F; Levenston, Marc E

Altered synovial levels of various adipokines (factors secreted by fat as well as other tissues) have been associated with osteoarthritis (OA) onset and progression. However, the metabolic effects of adipokines on joint tissues, in particular the fibrocartilaginous menisci, are not well understood. This study investigated effects of several adipokines on release of recently synthesized extracellular matrix in bovine cartilage and meniscus tissue explants. After labeling newly synthesized proteins and sulfated glycosaminoglycans (sGAGs) with 3 H-proline and 35 S-sulfate, respectively; bovine cartilage and meniscus tissue explants were cultured for 6 days in basal medium (control) or media supplemented with adipokines (1 µg/ml of leptin, visfatin, adiponectin, or resistin) or 20 ng/ml interleukin-1 (IL-1). Release of radiolabel and sGAG to the media during culture and the final explant water, DNA, sGAG, and retained radiolabel were measured. Matrix metalloproteinase (MMP-2) and MMP-3 activities were assessed using gelatin and casein zymography, respectively. Water and DNA contents were not significantly altered by any treatment. Visfatin, adiponectin, resistin, and IL-1 stimulated sGAG release from meniscus, whereas only IL-1 stimulated sGAG release from cartilage. Release of 3 H and 35 S was stimulated not only by resistin and IL-1 in meniscus but also by IL-1 in cartilage. Retained 3 H was unaltered by any treatment, while retained 35 S was reduced by visfatin, resistin, and IL-1 in meniscus and by only IL-1 in cartilage. Resistin and IL-1 elevated active MMP-2 and total MMP-3 in meniscus, whereas cartilage MMP-3 activity was elevated by only IL-1. Resistin stimulated rapid and extensive catabolism of meniscus tissue, similar to IL-1, whereas adipokines minimally affected cartilage. Release of newly synthesized matrix was similar to overall release in both tissues. These observations provide further indications that meniscal tissue is more sensitive to pro

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile

PubMed Central

Swisher, Anne K.; Abraham, Jame; Bonner, Daniel; Gilleland, Diana; Hobbs, Gerald; Kurian, Sobha; Yanosik, Mary Anne; Vona-Davis, Linda

2015-01-01

Purpose Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been testing specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. Methods Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy—Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). Results Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p<0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p<0.05). Conclusions Exercise and dietary counseling led

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

PubMed

Swisher, Anne K; Abraham, Jame; Bonner, Daniel; Gilleland, Diana; Hobbs, Gerald; Kurian, Sobha; Yanosik, Mary Anne; Vona-Davis, Linda

2015-10-01

Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p < 0.05) than the control group. The intervention group also improved quality of life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p < 0.05). Exercise and dietary counseling led to loss of body fat and improved

Serum adipokines, adipose tissue measurements and metabolic parameters in patients with advanced radiographic knee osteoarthritis.

PubMed

Toussirot, Eric; Michel, Fabrice; Béreau, Matthieu; Dehecq, Barbara; Gaugler, Béatrice; Wendling, Daniel; Grandclément, Emilie; Saas, Philippe; Dumoulin, Gilles

2017-11-01

We conducted the present study to evaluate the serum levels of adipokines (leptin, total and high molecular adiponectin, resistin), a marker of cartilage breakdown (C2C), and ghrelin together with body composition in patients with knee osteoarthritis (OA). Fifty patients and 50 sex-matched healthy subjects (HS) were evaluated. Knee OA was scored according to the Kellgren-Lawrence (KL) grade. Body composition parameters including lean mass and measurements of fat mass (total fat, adiposity, fat in the android and gynoid regions, visceral fat and trunk/legs fat ratio) were obtained using dual energy X-ray absorptiometry. Most of the recruited patients (88%) had advanced knee OA with KL grade 3 or 4. The patients had higher body mass index than HS (p < 0.0001). Serum leptin, high molecular adiponectin, resistin and ghrelin levels did not differ between patients and HS. Total adiponectin was higher in women with OA compared to women from the HS group (p = 0.004). Total fat mass, adiposity and measurements of central adiposity (fat in the android region, trunk/lower limbs fat ratio and visceral fat) were increased in patients with knee OA (all p < 0.05). Total adiponectin was borderline associated with the severity of OA. Our results show that total adiponectin is significantly increased in women with advanced knee OA. Independently of gender, patients with severe knee OA were characterized by a significant excess of fat with a distribution toward the visceral region. This abnormal body composition may contribute to the cardiometabolic profile that is described in patients with knee OA.

Running a Marathon Induces Changes in Adipokine Levels and in Markers of Cartilage Degradation – Novel Role for Resistin

PubMed Central

Vuolteenaho, Katriina; Leppänen, Tiina; Kekkonen, Riina; Korpela, Riitta; Moilanen, Eeva

2014-01-01

Running a marathon causes strenuous joint loading and increased energy expenditure. Adipokines regulate energy metabolism, but recent studies have indicated that they also exert a role in cartilage degradation in arthritis. Our aim was to investigate the effects of running a marathon on the levels of adipokines and indices of cartilage metabolism. Blood samples were obtained from 46 male marathoners before and after a marathon run. We measured levels of matrix metalloproteinase-3 (MMP-3), cartilage oligomeric protein (COMP) and chitinase 3-like protein 1 (YKL-40) as biomarkers of cartilage turnover and/or damage and plasma concentrations of adipokines adiponectin, leptin and resistin. Mean marathon time was 3∶30∶46±0∶02∶46 (h:min:sec). The exertion more than doubled MMP-3 levels and this change correlated negatively with the marathon time (r = –0.448, p = 0.002). YKL-40 levels increased by 56% and the effect on COMP release was variable. Running a marathon increased the levels of resistin and adiponectin, while leptin levels remained unchanged. The marathon-induced changes in resistin levels were positively associated with the changes in MMP-3 (r = 0.382, p = 0.009) and YKL-40 (r = 0.588, p<0.001) and the pre-marathon resistin levels correlated positively with the marathon induced change in YKL-40 (r = 0.386, p = 0.008). The present results show the impact of running a marathon, and possible load frequency, on cartilage metabolism: the faster the marathon was run, the greater was the increase in MMP-3 levels. Further, the results introduce pro-inflammatory adipocytokine resistin as a novel factor, which enhances during marathon race and associates with markers of cartilage degradation. PMID:25333960

Effects of Alpha-Lipoic Acid Supplementation on Plasma Adiponectin Levels and Some Metabolic Risk Factors in Patients with Schizophrenia.

PubMed

Vidović, Bojana; Milovanović, Srđan; Stefanović, Aleksandra; Kotur-Stevuljević, Jelena; Takić, Marija; Debeljak-Martačić, Jasmina; Pantović, Maja; Đorđević, Brižita

2017-01-01

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and anti-inflammatory properties and is suggested to be a biomarker of metabolic disturbances. The aim of this study was to investigate the effects of alpha-lipoic acid (ALA) on plasma adiponectin and some metabolic risk factors in patients with schizophrenia. The plasma adipokine levels (adiponectin and leptin), routine biochemical and anthropometric parameters, markers of oxidative stress, and the serum phospholipid fatty acid profile in eighteen schizophrenic patients at baseline, in the middle, and at the end of a 3-month long supplementation period with ALA (500 mg daily) were determined. A significant increase in the plasma adiponectin concentrations, as well as a decrease in fasting glucose and aspartate aminotransferase activity (AST), was found. Baseline AST activity was independently correlated with the adiponectin concentrations. Our data show that ALA can improve plasma adiponectin levels and may play a potential role in the treatment of metabolic risk factor in patients with schizophrenia. Future randomized controlled trials are needed to confirm these preliminary investigations.

Effects of Varying Degrees of Intermittent Hypoxia on Proinflammatory Cytokines and Adipokines in Rats and 3T3-L1 Adipocytes

PubMed Central

Zhou, Qin; Zhu, Hui; Niu, Wen-yan; Feng, Jing; Wang, Yan; Cao, Jie; Chen, Bao-yuan

2014-01-01

Objectives Intermittent hypoxia (IH), resulted from recurring episodes of upper airway obstruction, is the hallmark feature and the most important pathophysiologic pathway of obstructive sleep apnea (OSA). IH is believed to be the most important factor causing systemic inflammation. Studies suggest that insulin resistance (IR) is positively associated with OSA. In this study, we hypothesized that the recurrence of IH might result in cellular and systemic inflammation, which was manifested through the levels of proinflammatory cytokines and adipokines after IH exposure, and because IR is linked with inflammation tightly, this inflammatory situation may implicate an IR status. Methods We developed an IH 3T3-L1 adipocyte and rat model respectively, recapitulating the nocturnal oxygen profile in OSA. In IH cells, nuclear factor kappa B (NF-κB) DNA binding reactions, hypoxia-inducible factor-1α (HIF-1α), glucose transporter-1 (Glut-1), necrosis factor alpha (TNF-α), interleukin (IL) -6, leptin, adiponectin mRNA transcriptional activities and protein expressions were measured. In IH rats, blood glucose, insulin, TNF-α, IL-6, leptin and adiponectin levels were analyzed. Results The insulin and blood glucose levels in rats and NF-κB DNA binding activities in cells had significantly statistical results described as severe IH>moderate IH>mild IH>sustained hypoxia>control. The mRNA and protein levels of HIF-1α and Glut-1 in severe IH group were the highest. In cellular and animal models, both the mRNA and protein levels of TNF-α, IL-6 and leptin were the highest in severe IH group, when the lowest in severe IH group for adiponectin. Conclusions Oxidative stress and the release of pro-inflammatory cytokines/adipokines, which are the systemic inflammatory markers, are associated with IH closely and are proportional to the severity of IH. Because IR and glucose intolerance are linked with inflammation tightly, our results may implicate the clinical relationships between

RELATIONSHIP OF ADIPOKINES AND PROINFLAMMATORY CYTOKINES AMONG ASIAN INDIANS WITH OBESITY AND YOUTH ONSET TYPE 2 DIABETES.

PubMed

Gokulakrishnan, Kuppan; Amutha, Anandakumar; Ranjani, Harish; Bibin, Subramanian Y; Balakumar, Mahalingam; Pandey, Gautam Kumar; Anjana, Ranjit Mohan; Ali, Mohammed K; Narayan, K M Venkat; Mohan, Viswanathan

2015-10-01

It is well known that inflammation is associated with diabetes, but it is unclear whether obesity mediates this association in individuals with youth-onset type 2 diabetes mellitus (T2DM-Y). We recruited individuals with T2DM-Y (age at onset <25 years) and age-matched normal glucose tolerance (NGT) subjects. Participants were further classified using Asia-Pacific body mass index cut-points for obesity and categorized as: nonobese NGT (n = 100), Obese NGT (n = 50), nonobese T2DM-Y (n = 50), and obese T2DM-Y (n = 50). We compared adipokines (adiponectin and leptin) and proinflammatory cytokines (tumor necrosis factor alpha [TNF-α] and monocyte chemotactic protein-1 [MCP-1]) across groups. Compared to nonobese NGT, the other 3 groups (obese NGT, nonobese T2DM-Y, and obese T2DM-Y) were found to have lower adiponectin (7.7 vs. 5.7, 4.2, 3.8 μg/mL, P<.01), and higher leptin (3.6 vs. 5.4, 5.7, 7.9 μg/mL, P<.001) and MCP 1 (186 vs. 272, 340, 473 pg/mL, P<.001) respectively. However, TNF-α levels were higher only among nonobese T2DM-Y (112 pg/mL) and obese T2DM-Y (141 pg/mL, P<.01 for each). After adjusting for age, sex, waist, hypertension, homeostatic model assessment of insulin resistance (HOMA-IR), serum cholesterol, triglycerides, and family history of diabetes, adiponectin was associated with 33% and 41% lower odds of being nonobese T2DM and obese T2DM, respectively. However, adjusted for same factors, leptin, TNF-α, and MCP-1 were associated with markedly higher odds (5- to 14-fold) of nonobese and obese T2DM. In young Asian Indians, leptin and proinflammatory cytokines are positively, and adiponectin negatively, associated with both nonobese and obese T2DM-Y compared to nonobese NGT individuals.

Effects of sugar-sweetened beverages on plasma acylation stimulating protein, leptin, and adiponectin: Relationships with metabolic outcomes

USDA-ARS?s Scientific Manuscript database

OBJECTIVE: The effects of fructose and glucose consumption on plasma acylation stimulating protein (ASP), adiponectin, and leptin concentrations relative to energy intake, body weight, adiposity, circulating triglycerides, and insulin sensitivity were determined. DESIGN AND METHODS: Thirty two over...

Adipokines in peritoneal dialysis: relevant clinical impact according to body composition.

PubMed

Bernardo, Ana Paula; Fonseca, Isabel; Oliveira, José Carlos; Santos, Olivia; Carvalho, Maria João; Cabrita, António; Rodrigues, Anabela

2015-04-01

Adipokines impact on clinical outcomes is not adequately addressed in peritoneal dialysis (PD). We investigated the impact of leptin/adiponectin ratio (L/A) as a predictor of cardiovascular events (CVE) in PD, taking into consideration patient's body composition and the potential role of glucose load. We prospectively followed 66 prevalent PD patients for 47.0 ± 28.2 months. New CVE were evaluated. Lean tissue index (LTI), relative fat mass (relFM) and relative overhydration (relOH) using multifrequency bioimpedance (BCM) were assessed; serum lipids, interleukin-6 (IL-6), leptin and adiponectin were measured. We established the determinants of L/A using multiple linear regression and the impact of L/A on CVE. Obesity was present in 47 (73.4%) patients according to relFM, and in seven (10.6%) according to body mass index (BMI). Leptin and L/A exhibited a stronger correlation with relFM (both r = 0.62, P < 0.0001) than with BMI (r = 0.46 and r = 0.51, respectively, both P < 0.0001). L/A showed a significant correlation with triglycerides (r = 0.41, P = 0.001) and HDL-cholesterol (r = -0.358, P = 0.003), better than isolated leptin or adiponectin. RelFM (RR = 0.130, 95%confidence interval [CI]:0.086-0.174, P < 0.0001) and LTI (RR = 0.194, 95%CI:0.037-0.351, P = 0.016) were independent predictors of L/A (R(2) = 0.67). Patients who suffered new CVE were older (59.12 ± 12.41 vs. 47.52 ± 13.84years, P = 0.003) and had a higher relOH (11.28 ± 7.29 vs. 6.60 ± 8.16%, P = 0.028). L/A was significantly higher in patients with CVE[2.29 (1.79) vs. 0.65 (1.73), P = 0.028] but this association was only put on evidence after excluding patients with wasting. BMI is an inaccurate method to classify obesity in PD since it underestimates its prevalence compared with body composition assessment using BCM. High adiponectin and low leptin are associated with a more favorable metabolic risk profile

Circulating ghrelin, leptin, and soluble leptin receptor concentrations and cardiometabolic risk factors in a community-based sample.

PubMed

Ingelsson, Erik; Larson, Martin G; Yin, Xiaoyan; Wang, Thomas J; Meigs, James B; Lipinska, Izabella; Benjamin, Emelia J; Keaney, John F; Vasan, Ramachandran S

2008-08-01

The conjoint effects and relative importance of ghrelin, leptin, and soluble leptin receptor (sOB-R), adipokines involved in appetite control and energy expenditure in mediating cardiometabolic risk, is unknown. The objective of the study was to study the cross-sectional relations of these adipokines to cardiometabolic risk factors in a community-based sample. We measured circulating ghrelin, leptin, and sOB-R in 362 participants (mean age 45 yr; 54% women) of the Framingham Third Generation Cohort. Body mass index, waist circumference (WC), blood pressure, lipid measures, fasting glucose, smoking, and metabolic syndrome (MetS) were measured. Ghrelin and leptin concentrations were significantly higher in women (P < 0.0001). In multivariable models, ghrelin was inversely associated with age and systolic blood pressure, and leptin was positively related to body mass index and WC. sOB-R was positively associated with age, total cholesterol, and fasting glucose and inversely with WC and high-density lipoprotein cholesterol. Ghrelin and sOB-R concentrations were significantly lower with number of MetS components (P for trend = 0.022 and < 0.0001, respectively), whereas leptin concentrations were higher (P for trend = 0.0001). Relating all adipokines to MetS conjointly, higher ghrelin and leptin concentrations were associated with decreased and increased odds of MetS (odds ratio 0.55, P < 0.0001; odds ratio 4.44, P = 0.0002, per 1 sd increase of respective log adipokine). In our community-based sample, we observed a sexual dimorphism in circulating ghrelin and leptin concentrations. Ghrelin, leptin, and sOB-R were associated with number of MetS components cross-sectionally, consistent with the hypothesis that these adipokines may have a central role in cardiometabolic risk.

Resistin, visfatin, leptin and omentin are differently related to hormonal and metabolic parameters in growth hormone-deficient children.

PubMed

Ciresi, A; Pizzolanti, G; Leotta, M; Guarnotta, V; Teresi, G; Giordano, C

2016-09-01

The effect of growth hormone (GH) on adipose tissue and the role of adipokines in modulating metabolism are documented, but with discordant data. Our aim was to evaluate the impact of GH treatment on a series of selected adipokines known to have a metabolic role and poorly investigated in this setting. This is a prospective study. Thirty-one prepubertal children (25 M, 6 F; aged 8.5 ± 1.6 years) with isolated GH deficiency treated with GH for at least 12 months and 30 matched controls were evaluated. Auxological and metabolic parameters, insulin sensitivity indexes, leptin, soluble leptin receptor, adiponectin, visfatin, resistin, omentin, adipocyte fatty acid-binding protein and retinol-binding protein-4 were evaluated before and after 12 months of treatment. At baseline, no significant difference in metabolic parameters was found between GHD children and controls, except for higher LDL cholesterol (p = 0.004) in the first group. At multivariate analysis, LDL cholesterol was independently associated with resistin (B 0.531; p = 0.002), while IGF-I was the only variable independently associated with visfatin (B 0.688; p < 0.001). After 12 months, a significant increase in fasting insulin (p = 0.008), Homa-IR (p = 0.007) and visfatin (p < 0.001) was found, with a concomitant decrease in LDL cholesterol (p = 0.015), QUICKI (p = 0.001), ISI Matsuda (p = 0.006), leptin (p = 0.015) and omentin (p = 0.003)]. At multivariate analysis, BMI was the only variable independently associated with leptin (B 0.485; p = 0.040). GH treatment modifies adipokine secretion and the perturbation of some adipokine levels could contribute to the clinical and metabolic changes observed during the follow-up.

Insulin resistance, adipokine profile and hepatic expression of SOCS-3 gene in chronic hepatitis C.

PubMed

Wójcik, Kamila; Jabłonowska, Elżbieta; Omulecka, Aleksandra; Piekarska, Anna

2014-08-14

To analyze adipokine concentrations, insulin resistance and hepatic expression of suppressor of cytokine signaling 3 (SOCS-3) in patients with chronic hepatitis C genotype 1 with normal body weight, glucose and lipid profile. The study group consisted of 31 patients with chronic hepatitis C and 9 healthy subjects. Total levels of adiponectin, leptin, resistin, visfatin, omentin, osteopontin and insulin were measured using an ELISA kit. The hepatic expression of SOCS-3 was determined by the use of the reverse transcription polymerase chain reaction method. Homeostasis model assessment for insulin resistance (HOMA-IR) values were significantly higher in hepatitis C virus (HCV) infected patients without metabolic disorders compared to healthy controls (2.24 vs 0.59, P = 0.0003). Hepatic steatosis was observed in 32.2% of patients with HCV infection and was found in patients with increased HOMA-IR index (2.81 vs 1.99, P = 0.05) and reduced adiponectin level (5.96 vs 8.37, P = 0.04). Inflammatory activity (G ≥ 2) was related to increased osteopontin concentration (34.04 vs 23.35, P = 0.03). Advanced liver fibrosis (S ≥ 2) was associated with increased levels of omentin and osteopontin (436.94 vs 360.09, P = 0.03 and 32.84 vs 20.29, P = 0.03) and reduced resistin concentration (1.40 vs 1.74, P = 0.047). No correlations were reported between adipokine profile, HOMA-IR values and hepatic expression of the SOCS-3 gene. We speculated that no relationship between adipokines and HOMA-IR values may indicate that HCV can induce insulin resistance itself. Some adipokines appear to be biochemical markers of steatosis, inflammation and fibrosis in patients with chronic HCV infection. © 2014 Baishideng Publishing Group Inc. All rights reserved.

Type 2 diabetes and metabolic syndrome - adipokine levels and effect of drugs.

PubMed

Farooq, Rabia; Amin, Shajrul; Hayat Bhat, M; Malik, Rawoof; Wani, Hilal Ahmad; Majid, Sabhiya

2017-01-01

Type 2 diabetes mellitus (T2DM) is a consequence of complex interactions among multiple genetic variants and environmental risk factors. This complex disorder is also characterized by changes in various adipokines. In this study, our objective was to estimate the levels of adiponectin, leptin, and resistin (ALR) in T2DM patients, besides studying the effect of various drugs on their levels. Study participants included 400 diabetic and 300 normal patients from the Department of Endocrinology and Department of Biochemistry, Govt Medical College Srinagar. Subjects were categorized under various groups, i.e., Group 1 (metformin treated) and Group 2 (glimepiride treated), and cases were also categorized as obese with T2DM (Group A), obese without T2DM (Group B), and T2DM only (Group C). The serum ALR levels were estimated by ELISA (Alere), and biochemical parameters were also evaluated before and after treatment. Adiponectin levels were found to be significantly lower in T2DM cases as compared to controls (12 ± 5.5 versus 22.5 ± 7.9 μg/ml), while leptin and resistin levels were found to be significantly higher than controls (14.3 ± 7.4 versus 7.36 ± 3.73 ng/ml) (13.4 ± 1.56 versus 7.236 ± 2.129 pg/ml). Taking the effect of drugs into consideration, the effect on adiponectin and resistin levels was found to be highly significant in Group 2 before and after treatment (11 ± 5 versus 19.2 ± 4.5 μg/ml) (13.6 ± 2.5 versus 7.3 ± 2.9 pg/ml), while more effect was observed in leptin among Group 1 (metformin)-treated cases (27 ± 15 ng/ml versus 15 ± 15 ng/ml). Further the adiponectin levels were found to be significantly lower in Group B, while leptin and resistin levels were found to be significantly higher among obese cases when compared to T2DM cases only. Glimepiride also shows more effect on FBG, HbA1c% levels, while metformin shows more effect on Lipid profile levels. From the study, it can be

In middle-aged and old obese patients, training intervention reduces leptin level: A meta-analysis

PubMed Central

Rostás, Ildikó; Pótó, László; Mátrai, Péter; Hegyi, Péter; Tenk, Judit; Garami, András; Illés, Anita; Solymár, Margit; Pétervári, Erika; Szűcs, Ákos; Párniczky, Andrea; Pécsi, Dániel; Rumbus, Zoltán; Zsiborás, Csaba; Füredi, Nóra; Balaskó, Márta

2017-01-01

Background Leptin is one of the major adipokines in obesity that indicates the severity of fat accumulation. It is also an important etiological factor of consequent cardiometabolic and autoimmune disorders. Aging has been demonstrated to aggravate obesity and to induce leptin resistance and hyperleptinemia. Hyperleptinemia, on the other hand, may promote the development of age-related abnormalities. While major weight loss has been demonstrated to ameliorate hyperleptinemia, obese people show a poor tendency to achieve lasting success in this field. The question arises whether training intervention per se is able to reduce the level of this adipokine. Objectives We aimed to review the literature on the effects of training intervention on peripheral leptin level in obesity during aging, in order to evaluate the independent efficacy of this method. In the studies that were included in our analysis, changes of adiponectin levels (when present) were also evaluated. Data sources 3481 records were identified through searching of PubMed, Embase and Cochrane Library Database. Altogether 19 articles were suitable for analyses. Study eligibility criteria Empirical research papers were eligible provided that they reported data of middle-aged or older (above 45 years of age) overweight or obese (body mass index above 25) individuals and included physical training intervention or at least fitness status of groups together with corresponding blood leptin values. Statistical methods We used random effect models in each of the meta-analyses calculating with the DerSimonian and Laird weighting methods. I-squared indicator and Q test were performed to assess heterogeneity. To assess publication bias Egger’s test was applied. In case of significant publication bias, the Duval and Tweedie's trim and fill algorithm was used. Results Training intervention leads to a decrease in leptin level of middle-aged or older, overweight or obese male and female groups, even without major weight

Acylated and unacylated ghrelin levels in normal weight and obese children: influence of puberty and relationship with insulin, leptin and adiponectin levels.

PubMed

Bellone, S; Prodam, F; Savastio, S; De Rienzo, F; Demarchi, I; Trovato, L; Petri, A; Rapa, A; Aimaretti, G; Bona, G

2012-02-01

Ghrelin circulates in blood as acylated (AG) and unacylated (UAG) ghrelin. The physiological role of the two forms is poorly understood, in particular in childhood. Aim of the study was to evaluate the AG and UAG levels in obese and normal weight (NW) children, pre-pubertal and pubertal, and their relationship with insulin, leptin and adiponectin levels. A population based study in which AG, UAG, leptin, adiponectin, glucose, insulin, testosterone or estradiol levels, insulinemic indexes were evaluated in 82 NW and 58 obese (OB) children. Both ghrelin forms in NW were higher (AG, p<0.02; UAG, p<0.0001) than in OB subjects, with similar ratio AG/UAG . While no differences were observed for gender, puberty AG (p<0.01) and UAG (p<0.0001) levels were higher in pre-pubertal than pubertal NW and OB subjects. Adiponectin levels in NW subjects were higher (p<0.001), while leptin and insulin levels were lower (p<0.0001) than in OB subjects. NW children showed homeostasis model assessment (HOMA) and HOMAβ indices lower than OB children (p<0.0001) with a higher a quantitative insulin sensitivity check index (p<0.0001). AG and UAG levels correlated to each other (p<0.0001), each showing a negative correlation to age, height, weight and body mass index. Both forms, but more strongly UAG, correlated with adiponectin, leptin, and insulin. OB children show lower levels of both AG and UAG when compared to NW subjects, with lower levels during puberty. These results demonstrate a peculiar strong relationship between UAG levels and metabolic parameters in the pediatric population, suggesting a role for UAG in metabolic functions.

Does vitamin D supplementation alter plasma adipokines concentrations? A systematic review and meta-analysis of randomized controlled trials.

PubMed

Dinca, Madalina; Serban, Maria-Corina; Sahebkar, Amirhossein; Mikhailidis, Dimitri P; Toth, Peter P; Martin, Seth S; Blaha, Michael J; Blüher, Matthias; Gurban, Camelia; Penson, Peter; Michos, Erin D; Hernandez, Adrian V; Jones, Steven R; Banach, Maciej

2016-05-01

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. Copyright © 2016 Elsevier Ltd. All rights reserved.

Serum and CSF adiponectin, leptin, and interleukin 6 levels as adipocytokines in Egyptian children with febrile seizures: a cross-sectional study.

PubMed

Azab, Seham F; Abdalhady, Mohamed A; Almalky, Mohamed A A; Amin, Ezzat K; Sarhan, Dina T; Elhindawy, Eman M; Allah, Mayy A N; Elhewala, Ahmed A; Salam, Mohamed M A; Hashem, Mustafa I A; Soliman, Attia A; Akeel, Nagwa E; Abdellatif, Sawsan H; Elsamad, Nahla A; Rass, Anwar A; Arafat, Manal S

2016-04-12

A febrile seizure (FS) is the most common convulsive disorder in children. Activation of cytokine network is involved in FS pathogenesis. Adiponectin, leptin and IL-6 are the major adipocytokines secreted by fat cells. To date, only a few studies concerned the association of adipocytokines with febrile seizures. In this study, we tried to investigate serum and CSF levels of adiponectin, leptin, and interleukin-6 (IL-6); as adipocytokines, for the first time in Egyptian children with febrile seizures. This was a prospective cross-sectional study included one hundred patients with febrile seizure, and matched with age, gender, 100 children with febrile illness without seizures (febrile control, FC) and 100 healthy control group (HC). Serum and cerebrospinal fluid (CSF) levels of adiponectin, leptin, and (IL-6) were measured by enzyme-linked immunosorbent assay (ELISA) method. Serum adiponectin was significantly higher in children with FS (16.8 ± 3.7 ug/ml) and the FC group (18.3 ± 4.3 ug/ml) compared to the HC group (9.5 ± 2.2 ug/ml); P < 0.05, respectively. Serum leptin was significantly lower in children with FS (0.9 ± 0.3 ng/ml) compared to both the FC group (4.7 ± 1.2 ng/ml) and the HC group (1.8 ± 0.4 ng/ml); P < 0.01, respectively. Children with FS had significantly higher serum IL-6 levels (43.7 ± 11.7 ng/ml) than the FC group (21.9 ± 4.5 ng/ml) and the HC group (6.5 ± 1.8 ng/ml); P < 0.01, respectively. Patients with simple febrile seizures (SFS) had serum and CSF adiponectin levels similar to those with complex febrile seizures (CFS); (P > 0.05). Serum and CSF leptin levels were significantly lower in patients with CFS compared to the SFS group (P < 0.05). Serum and CSF IL-6 levels were significantly higher in patients with CFS compared to the SFS group (P < 0.01). On multivariate logistic regression analysis, the high serum IL-6 levels was the most significant risk factor associated with

Repeated electroacupuncture in obese Zucker diabetic fatty rats: adiponectin and leptin in serum and adipose tissue.

PubMed

Peplow, Philip V

2015-04-01

Fasted, male, obese, Zucker, diabetic fatty rats aged 10-16 weeks were anesthetized with 1% halothane in nitrous oxide-oxygen (3:1) on alternate weekdays over 2 weeks. Group 1 (n = 4) did not receive electroacupuncture (controls); Group 2 (n = 4) received electroacupuncture using the Zhongwan and the Guanyuan acupoints; Group 3 (n = 4) received electroacupuncture using the bilateral Zusanli acupoints; Group 4 (n = 6) received neither halothane in nitrous oxide:oxygen nor electroacupuncture. At the end of study, animals were injected with sodium pentobarbitone (60 mg/mL, i.p.), and blood and white adipose tissue were collected. Analysis of variance and Duncan's tests showed that the mean leptin in serum was significantly lower and the adiponectin:leptin ratio was significantly higher in Group 2 than in Group 1 (p < 0.05); for Group 4, the serum leptin was significantly higher than it was for Groups 1-3 (p < 0.05), and the adiponectin:leptin ratio was significantly lower than it was for Group 2 (p < 0.05). Similar changes occurred for the leptin levels in the pelvic adipose tissue. In addition, for Group 2, the mean serum insulin: glucose ratio was significantly higher than it was for Group 1 (p < 0.05); for Group 4 the mean serum insulin and insulin: glucose ratio were significantly higher than they were for Groups 1 and 3 (p < 0.05), but not Group 2 (p > 0.05). No significant differences in the serum or the adipose-tissue measurements between Groups 1 and 3 were observed (p > 0.05). Copyright © 2015. Published by Elsevier B.V.

Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis.

PubMed

Yu, Zhangbin; Han, Shuping; Cao, Xingguo; Zhu, Chun; Wang, Xuejie; Guo, Xirong

2012-02-01

Polymorphisms in adipokine genes, such as leptin (LEP), leptin receptor (LEPR), resistin (RETN), adiponectin (ADIPOQ), interleukin-1β (IL-1β), IL-6 (IL-6), and tumor necrosis factor-α (TNF-α) may be involved in the development of obesity. We conducted a systematic review of published evidence on the association between different adipokine genes and the risk of obesity. Librarian-designed searches of PubMed and HuGeNet, review of reference lists from published reviews and content expert advice identified potentially eligible studies. The genotyping information and polymorphisms of different adipokine genes, numbers of genotyped cases and controls and frequencies of genotypes were extracted from 48 eligible studies included in this review. Twenty-one polymorphisms each associated with obesity in at least one study were identified. Polymorphisms in the adipokine genes, LEP, LEPR, and RETN were not associated with obesity susceptibility, whereas ADIPOQ G276T (T vs. G: odds ratio (OR), 1.59; 95% confidence interval (CI), 1.39-1.81), IL-1β C3953T (CC vs. CT+TT: OR, 1.61; 95% CI, 1.18-2.20), and TNF-α G308A (GG vs. GA+AA: OR, 1.19; 95% CI, 1.02-1.39) polymorphisms were associated with an increased risk of obesity. The IL-6 G174C polymorphism was also associated obesity when using allelic comparisons, the recessive genetic model and the dominant genetic model with OR (95% CI) of 1.95 (1.37-2.77), 1.44 (1.15-1.80), and 1.36 (1.16-1.59), respectively. No significant evidence of publication bias was present. However, these "null" results were underpowered due to a small pooled sample size, and analysis of additional case-control studies with larger sample sizes should provide further clarifications.

Adiponectin gene polymorphisms: Association with childhood obesity

PubMed Central

Fraga, Vanêssa Gomes; Gomes, Karina Braga

2014-01-01

The current childhood obesity epidemic represents a particular challenge for public health. Understanding of the etiological mechanisms of obesity remains integral in treating this complex disorder. In recent years, studies have elucidated the influence of hormones secreted by adipose tissue named adipokines. Adiponectin is a adipokine that exhibits important anti-inflammatory, insulin-sensitizing and anti-atherogenic properties and it is strongly associated to obesity development. It is well known that adiponectin levels decrease with obesity. Furthermore, studies show that some single nucleotide polymorphisms in the gene encoding adiponectin, ADIPOQ, may influence the expression of this protein. The objective of this paper is to provide an up-to-date review of ADIPOQ polymorphisms in the context of childhood obesity. PMID:27625863

Scleroderma Related Lung Disease: Is There a Pathogenic Role for Adipokines?

PubMed Central

Haley, Shannon; Shah, Dilip; Romero, Freddy; Summer, Ross

2013-01-01

Scleroderma is a systemic autoimmune disease of unknown etiology whose hallmark features include endothelial cell dysfunction, fibroblast proliferation and immune dysregulation. Although virtually any organ can be pathologically involved in scleroderma, lung complications including interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH) are the leading cause of death in patients with this condition. Currently, the molecular mechanisms leading to development of scleroderma-related lung disease are poorly understood; however, the systemic nature of this condition has led many to implicate circulating factors in the pathogenesis of some of its organ impairment. In this article, we focus on a new class of circulating factors derived from adipose-tissue called adipokines, which are known to be altered in scleroderma. Recently, the adipokines adiponectin and leptin have been found to regulate biological activities in endothelial, fibroblast and immune cell types in lung and in many other tissues. The pleiotropic nature of these circulating factors and their functional activity on many cell types implicated in the pathogenesis of ILD and PAH suggest these hormones may play a mechanistic role in the onset and/or progression of scleroderma-related lung diseases. PMID:24173692

Adipose Tissue and Adipokines: The Association with and Application of Adipokines in Obesity

PubMed Central

Khan, Muhammad; Joseph, Frank

2014-01-01

2014 marks the 20th anniversary of adipokines. Through the identification of leptin, our perceived understanding of adipose tissue was changed instantaneously. From a simple dormant site of energy storage, adipose tissue is now recognized as an integral hub of various hormones known as adipokines. Although great strides have been made in characterizing these hormones in health, research also shows they are significantly implicated in a series of pathologies. One such condition is obesity. Defined as an excess of adipose tissue, obesity remains one of the greatest healthcare epidemics of the 21st century. With no definitive treatment, attention has shifted to understanding the role of adipokines in obesity. This review provides an introduction to the salient obesity-related adipokines and their possible application as a treatment for obesity. PMID:25309775

Interrelations among the adipocytokines leptin and adiponectin, oxidative stress and aseptic inflammation markers in pre- and early-pubertal normal-weight and obese boys.

PubMed

Paltoglou, George; Schoina, Maria; Valsamakis, George; Salakos, Nicolaos; Avloniti, Alexandra; Chatzinikolaou, Athanasios; Margeli, Alexandra; Skevaki, Chrysanthi; Papagianni, Maria; Kanaka-Gantenbein, Christina; Papassotiriou, Ioannis; Chrousos, George P; Fatouros, Ioannis G; Mastorakos, George

2017-03-01

Presumed interrelationships among deleterious aspects of adipose tissue metabolism, inflammation, and cellular oxidative stress could be influenced by pubertal hormonal changes. They were investigated in pre- and early pubertal normal-weight and obese boys before and after an exercise bout employed as an energy demanding stimulator. Cross-sectional study. Seventy-six healthy pre- (mean ± SD, 10.6 ± 0.2 years old, 28 normal-weight, and 11 obese) and early-(11.4 ± 0.2 years old, 25 normal-weight, and 12 obese) pubertal boys, were blood-sampled before and after a bout of exercise at 70% VO 2 max. Leptin, adiponectin, markers of inflammation (high-sensitivity C-reactive protein, high sensitivity IL-6), pro- (thiobarbitouric acid reactive substances, protein carbonyls) and anti- (glutathione, oxidized glutathione, glutathione peroxidase, catalase, total antioxidant capacity) oxidation were measured. Baseline and post-exercise adiponectin was greater and leptin and high-sensitivity C-reactive protein were lower in normal-weight than in obese pre- and early pubertal boys, while high sensitivity IL-6 was greater in obese than in normal-weight pre-pubertal boys. In pre-pubertal obese boys: at baseline, high-sensitivity C-reactive protein correlated negatively with catalase; high sensitivity IL-6 correlated positively with protein carbonyls; Δ (difference during exercise) adiponectin correlated positively with Δcatalase. In all boys: at baseline, high sensitivity IL-6 correlated positively with leptin and was the best negative and the second best positive predictor for post-exercise glutathione/oxidized glutathione and protein carbonyls, respectively; leptin was the best negative predictor for post-exercise glutathione; waist to height ratio was the best positive predictor for post-exercise thiobarbitouric acid reactive substances; body mass index z-score and adiponectin were, respectively, the best positive predictor for post-exercise protein carbonyls

[Occupational semicircular lipoatrophy associated with serum adipokine abnormalities].

PubMed

Reinoso-Barbero, Luis; Díaz-Garrido, Ramón; González-Gómez, María-Fernanda; Olarrea, José; Gómez-Gallego, Félix; Bandrés, Fernando

2015-10-21

The aim of this study was to examine the relationship between semicircular lipoatrophy (SL), inflammation marker (high sensibility C-reactive protein [hs-CRP]), adipokines (leptine, chemerine and vaspine) and autoimmune markers (rheumatoid factor [RF], C3 and C4 complement fractions, antinuclear antibodies [ANA], HLA DR3, and DR4). Chemerine is an adipokine, but also is an immunity marker. A case-control study was performed in May 2013; 21 cases were included. The closest healthy coworker to each case was used as a control. We calculated Kruskal-Wallis nonparametric test. We found statistical significance (P<.05) between SL and raised hs-CRP, raised leptine and low chemerine. i) There seems to be an underlying inflammatory component (raised hs-CRP) in SL; ii) adipokine alteration (raised leptine and low chemerine) supports the idea that adipocytic differentiation is affected in SL, and iii) we have not found any immune marker associated with SL, except chemerine itself, which could explain a possible association between SL and immunity. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Different protein composition of low-calorie diet differently impacts adipokine profile irrespective of weight loss in overweight and obese women.

PubMed

Mateo-Gallego, R; Lamiquiz-Moneo, I; Perez-Calahorra, S; Marco-Benedí, V; Bea, A M; Baila-Rueda, L; Laclaustra, M; Peñalvo, J L; Civeira, F; Cenarro, A

2018-02-01

High-protein (HP) diets have shown benefits in cardiometabolic markers such as insulin or triglycerides but the responsible mechanisms are not known. We aimed to assess the effect of three energy-restricted diets with different protein contents (20%, 27%, and 35%; ∼80% coming from animal source) on plasma adipokine concentration and its association with changes in cardiometabolic markers. Seventy-six women (BMI 32.8 ± 2.93) were randomized to one of three calorie-reduced diets, with protein, 20%, 27%, or 35%; carbohydrates, 50%, 43%, or 35%; and fat, 30%, for 3 months. Plasma adipokine (leptin, resistin, adiponectin, and retinol-binding protein 4; RBP4) levels were assessed. After 3 months, leptin concentration decreased in all groups without differences among them, while resistin levels remained unchanged. Adiponectin concentration heterogeneously changed in all groups (P for trend = 0.165) and resistin concentration did not significantly change. RPB4 significantly decreased by -17.5% (-31.7, -3.22) in 35%-protein diet (P for trend = 0.024 among diets). Triglycerides improved in women following the 35%-protein diet regardless of weight loss; RBP4 variation significantly influenced triglyceride concentration change by 24.9% and 25.9% when comparing 27%- and 35%- with 20%-protein diet, respectively. A 35%-protein diet induced a decrease in RBP4 regardless of weight loss, which was directly associated with triglyceride concentration improvement. These findings suggest that HP diets improve the cardiometabolic profile, at least in part, through changes in adipokine secretion. Whether this beneficial effect of HP diet is due to improvements in hepatic or adipose tissue functionality should be elucidated. The clinical trial has been registered in ClinicalTrials.gov (Identifier: NCT02160496). Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of

Effects of clozapine on adipokine secretions/productions and lipid droplets in 3T3-L1 adipocytes.

PubMed

Tsubai, Tomomi; Yoshimi, Akira; Hamada, Yoji; Nakao, Makoto; Arima, Hiroshi; Oiso, Yutaka; Noda, Yukihiro

2017-02-01

Clozapine, a second-generation antipsychotic (SGA), is a cause of side effects related to metabolic syndrome. The participation of serotonin 5-HT 2C and histamine H 1 receptors in the central nervous system has been reported as a mechanism of the weight gain caused by clozapine. In the present study, we investigated the direct pharmacological action of clozapine on the 3T3-L1 adipocytes and compared it to that of blonanserin, an SGA with low affinity for both receptors. Short-term exposure to clozapine decreased secretion and mRNA expression of leptin. Long-term exposure decreased leptin as well as adiponectin secretion, and further increased lipid droplets accumulation. However, short- and long-term exposures to blonanserin did not affect these parameters. A selective serotonin 5-HT 2C , but not a histamine H 1 , receptor antagonist enhanced the decreased secretion of leptin induced by short-term exposure to clozapine, but did not affect the increased accumulation of lipid droplets. Our findings indicate that clozapine, but not blonanserin, strongly and directly affected the secretion of adipokines, such as leptin, in adipocytes and caused adipocyte enlargement. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Role of anti-inflammatory adipokines in obesity-related diseases.

PubMed

Ohashi, Koji; Shibata, Rei; Murohara, Toyoaki; Ouchi, Noriyuki

2014-07-01

Obesity results in many health complications. Accumulating evidence indicates that the obese state is characterized by chronic low-grade inflammation, thereby leading to the initiation and progression of obesity-related disorders such as type 2 diabetes, hypertension, cardiovascular disease, and atherosclerosis. Fat tissue releases numerous bioactive molecules, called adipokines, which affect whole-body homeostasis. Most adipokines are proinflammatory, whereas a small number of anti-inflammatory adipokines including adiponectin exert beneficial actions on obese complications. The dysregulated production of adipokines seen in obesity is linked to the pathogenesis of various disease processes. In this review we focus on the role of the anti-inflammatory adipokines that are of current interest in the setting of obesity-linked metabolic and cardiovascular diseases. Copyright © 2014 Elsevier Ltd. All rights reserved.

Exposure to cigarette smoke disturbs adipokines secretion causing intercellular damage and insulin resistance in high fructose diet-induced metabolic disorder mice.

PubMed

Kim, Sanghwa; Lee, Ah Young; Kim, Hyeon-Jeong; Hong, Seong-Ho; Go, Ryeo-Eun; Choi, Kyung-Chul; Kang, Kyung-Sun; Cho, Myung-Haing

2017-12-16

A large amount of fructose intake along with smoking is associated with increased incidence of diseases linked to metabolic syndrome. More research is necessary to understand the complex mechanism that ultimately results in metabolic syndrome and the effect, if any, of high fructose dietary intake and smoking on individual health. In this study, we investigated changes in ER-Golgi network and disturbance to secretion of adipokines induced by cigarette smoking (CS) and excess fructose intake and their contribution to the disruption of metabolic homeostasis. We used high fructose-induced metabolic disorder mice model by feeding them with high fructose diet for 8 weeks. For CS exposure experiment, these mice were exposed to CS for 28 days according to OECD guideline 412. Our results clearly showed that the immune system was suppressed and ER stress was induced in mice with exposure to CS and fed with high fructose. Furthermore, their concentrations of adipokines including leptin and adiponectin were aberrant. Such alteration in secretion of adipokines could cause insulin resistance which may lead to the development of type 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction

PubMed Central

Michalakis, Konstantinos G.; Segars, James H.

2011-01-01

Objective To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system. Design A Medline computer search was performed to identify relevant articles. Setting Research institution. Intervention(s) None. Result(s) Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes. Conclusion(s) Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles. PMID:20561616

Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system.

PubMed

Budak, Erdal; Fernández Sánchez, Manuel; Bellver, José; Cerveró, Ana; Simón, Carlos; Pellicer, Antonio

2006-06-01

To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. A MEDLINE computer search was performed to identify relevant articles. Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.

Leptin increases prostate cancer aggressiveness.

PubMed

López Fontana, Constanza M; Maselli, María E; Pérez Elizalde, Rafael F; Di Milta Mónaco, Nicolás A; Uvilla Recupero, Ana L; López Laur, José D

2011-12-01

Recent studies indicate that adipose tissue and adipocytokines might affect the development of prostate cancer (PCa). Leptin would have a stimulating effect on prostate cancer cells by inducing promotion and progression, whereas adiponectin would have a protective effect. The aim of this study was to determine the relation between body composition, leptin, and adiponectin levels with the prevalence and aggressiveness of PCa in men of Mendoza, Argentina. Seventy volunteers between 50 and 80 years (35 healthy men as control group and 35 with PCa) were selected. The PCa group was subclassified according to the Gleason Score (GS). Digital rectal examination, transrectal ultrasound, and prostatic biopsy were performed; PSA, testosterone, leptin, and adiponectin levels were determined; and a nutritional interview including anthropometric measurements and a food frequency questionnaire was carried out. Statistical analysis was performed by Student t test, ANOVA I, and Bonferroni (p < 0.05). Body mass index and percentage of body fat mass were not statistically different between PCa and control groups. However, body fat mass was higher in subjects with more aggressive tumors (p = 0.032). No differences were observed regarding leptin levels between the groups. Nevertheless, leptin levels were higher in subjects with high GS (p < 0.001). Adiponectin levels showed no statistical differences regarding the presence and aggressiveness of the tumor (p = 0.131). Finally, consumption and nutrient intake did not differ in the studied groups. In conclusion, body composition and leptin are related to the PCa aggressiveness but not with its prevalence.

Infant Body Composition and Adipokine Concentrations in Relation to Maternal Gestational Weight Gain

PubMed Central

Estampador, Angela C.; Pomeroy, Jeremy; Renström, Frida; Nelson, Scott M.; Mogren, Ingrid; Persson, Margareta; Sattar, Naveed; Domellöf, Magnus; Franks, Paul W.

2014-01-01

OBJECTIVE To investigate associations of maternal gestational weight gain and body composition and their impact on offspring body composition and adipocytokine, glucose, and insulin concentrations at age 4 months. RESEARCH DESIGN AND METHODS This was a prospective study including 31 mother-infant pairs (N = 62). Maternal body composition was assessed using doubly labeled water. Infant body composition was assessed at 4 months using air displacement plethysmography, and venous blood was assayed for glucose, insulin, adiponectin, interleukin-6 (IL-6), and leptin concentrations. RESULTS Rate of gestational weight gain in midpregnancy was significantly associated with infant fat mass (r = 0.41, P = 0.03); rate of gestational weight in late pregnancy was significantly associated with infant fat-free mass (r = 0.37, P = 0.04). Infant birth weight was also strongly correlated with infant fat-free mass at 4 months (r = 0.63, P = 0.0002). Maternal BMI and maternal fat mass were strongly inversely associated with infant IL-6 concentrations (r = −0.60, P = 0.002 and r = −0.52, P = 0.01, respectively). Infant fat-free mass was inversely related to infant adiponectin concentrations (r = −0.48, P = 0.008) and positively correlated with infant blood glucose adjusted for insulin concentrations (r = 0.42, P = 0.04). No significant associations for leptin were observed. CONCLUSIONS Timing of maternal weight gain differentially impacts body composition of the 4-month-old infant, which in turn appears to affect the infant’s glucose and adipokine concentrations. PMID:24623025

Maternal bisphenol A alters fetal endocrine system: Thyroid adipokine dysfunction.

PubMed

Ahmed, R G

2016-09-01

Because bisphenol A (BPA) has been detected in animals, the aim of this study was to investigate the possible effects of maternal BPA exposure on the fetal endocrine system (thyroid-adipokine axis). BPA (20 or 40 μg/kg body weight) was orally administered to pregnant rats from gestation day (GD) 1-20. In both treated groups, the dams and their fetuses had lower serum thyroxine (T4) and triiodothyronine (T3) levels, and higher thyrotropin (TSH) level than control dams and fetuses at GD 20. Some histopathological changes in fetal thyroid glands were observed in both maternal BPA groups at embryonic day (ED) 20, including fibroblast proliferation, hyperplasia, luminal obliteration, oedema, and degeneration. These disorders resulted in the suppression of fetal serum growth hormone (GH), insulin growth factor-1 (IGF1) and adiponectin (ADP) levels, and the elevation of fetal serum leptin, insulin and tumor necrosis factor-alpha (TNFα) levels in both treated groups with respect to control. The depraved effects of both treated groups were associated with reduced maternal and fetal body weight compared to the control group. These alterations were dose dependent. Thus, BPA might penetrate the placental barrier and perturb the fetal thyroid adipokine axis to influence fat metabolism and the endocrine system. Copyright © 2016 Elsevier Ltd. All rights reserved.

Apoptosis and Inflammation: Role of Adipokines in Inflammatory Bowel Disease

PubMed Central

Ponemone, Venkatesh; Keshavarzian, Ali; Brand, Marc I; Saclarides, Theodore; Abcarian, Herand; Cabay, Robert J; Fletcher, Emma; Larsen, Bianca; Durstine, Larry J; Fantuzzi, Giamila; Fayad, Raja

2010-01-01

OBJECTIVES: Leptin and adiponectin (APN) are adipokines produced by adipocytes that participate in the modulation of immune and inflammatory responses. In Crohn's disease (CD), fat wrapping surrounding the inflamed intestine produces high levels of leptin and APN. In inflammatory bowel disease (IBD), apoptosis resistance of lamina propria T lymphocytes (LPL-T) is one of the mechanisms that maintains chronic inflammation. We addressed the mechanism by which leptin and APN regulate inflammation and apoptosis in IBD. METHODS: Immune cell infiltration, several factors expressed by adipose tissue (AT), and spontaneous release of cytokines by adipocytes were measured. The presence of APN and leptin in intestinal mucosa was detected and their effect on LPL-T apoptosis, signal transducer and activator of transcription 3 (STAT3), Suppressor of Cytokine Signaling 3 (SOCS3), Bcl-2 and Bcl-xL expression, and cytokine production was studied. In addition, the effects of globular and high-molecular-weight (HMW) APN on LPL-T cytokine production and apoptosis were studied. RESULTS: Higher levels of several chemokines, cytokines, and growth factors were present in AT near active than near inactive disease. A significantly higher amount of inflammatory infiltrate was present in AT near active CD than near ulcerative colitis, controls, and near the inactive area of CD. There were no changes in the ratios of APN molecular weight in control and IBD adipocyte products. Leptin and APN inhibited anti-CD3-stimulated-LPL-T apoptosis and potentiated STAT3 phosphorylation, Bcl-2, and Bcl-xL expression in IBD and control mucosa. However, SOCS3 expression was suppressed only in IBD. Both globular and HMW APN have similar effects on LPL-T cytokine production and apoptosis. Leptin and APN enhanced interleukin (IL)-10 production by anti-CD3-stimulated LPL-T in IBD only. APN, but not leptin, increased anti-CD3-induced IL-6 levels in LPL-T only in IBD patients. IL-10 exerts its anti

Adiponectin, Resistin, and Visfatin in Childhood Obesity and Exercise.

PubMed

Jamurtas, Athanasios Z; Stavropoulos-Kalinoglou, Antonios; Koutsias, Stilianos; Koutedakis, Yiannis; Fatouros, Ioannis

2015-11-01

Childhood obesity is increasing alarmingly, and a strong association with chronic diseases has been established. Specific adipokines are released from the adipose tissue and relate with chronic diseases even in the pediatric population. Adiponectin levels are lower in obesity and increase with decreasing body weight. A few pediatric studies examining a possible relationship between resistin and obesity do not provide a clear picture. Most studies agree that visfatin levels appear elevated in childhood obesity. Exercise seems to increase adiponectin levels whereas resistin levels are reduced. The lack of data on the effects of acute and chronic exercise on visfatin levels precludes us from making safe conclusions as to what the effects of exercise (acute or chronic) would be on visfatin levels in children. Clearly, exercise has an impact on the adipose tissue and the release of adiponectin, resistin, and visfatin. However, other factors affect the secretion rate of these adipokines from the adipose tissue; these factors should also be taken into consideration when examining the effects of exercise on adipokines. Gender, age, body composition, physical activity levels, mode and intensity of exercise are some of the factors that should be looked into in future studies.

Searching for Evidence of an Anti-Inflammatory Diet in Children: A Systematic Review of Randomized Controlled Trials for Pediatric Obesity Interventions With a Focus on Leptin, Ghrelin, and Adiponectin.

PubMed

Lewis, Kimberly A; Brown, Sharon A

2017-10-01

To address the complex phenomenon of pediatric obesity, one must understand the physiological mechanisms regulating energy intake and inflammation. The peptide hormones leptin, ghrelin, and adiponectin are involved in both, but their functions are dysregulated in obesity. The purpose of this systematic review is (1) to characterize studies of nutrition interventions for weight management in children who measure these peptides as outcomes, (2) to assess risk of bias in the studies, and (3) to determine the relationships between these peptides and body mass index (BMI). Eligibility Criteria: Peer-reviewed articles written in English, published in 2001-2016, and describing randomized controlled trials of pediatric interventions involving a nutrition component with the outcome measures leptin, ghrelin, and/or adiponectin were included. Articles were excluded if the intervention involved pharmaceuticals, supplements, infant formula, breastfeeding, or surgery. The 25 international studies represented 2,153 obese children. Ten diets were identified. Successful interventions included both structured exercise and hypocaloric dietary components, with or without counseling, resistance training, or medical components. Direct measures of adiposity were used in 69% of studies. Comparison group designs were disparate. Leptin levels decreased as BMI decreased. Evidence regarding the relationships of ghrelin and adiponectin with BMI was inconclusive. Despite known effects of maturation on hormones, studies did not consistently differentiate findings by maturational stage. Common anti-inflammatory and disease risk modification diets were missing or underrepresented. Studies that include children with comorbidities are needed. BMI and leptin levels have a positive relationship, but evidence on ghrelin and adiponectin was inconclusive.

Physical fitness and activity, metabolic profile, adipokines and endothelial function in children.

PubMed

Penha, Jociene Terra da; Gazolla, Fernanda Mussi; Carvalho, Cecília Noronha de Miranda; Madeira, Isabel Rey; Rodrigues-Júnior, Flávio; Machado, Elisabeth de Amorim; Sicuro, Fernando Lencastre; Farinatti, Paulo; Bouskela, Eliete; Collett-Solberg, Paulo Ferrez

2018-05-30

The prevalence of obesity is increasing. The aim of this study was to investigate if there is endothelial dysfunction in children with normal or excess weight, and whether the metabolic profile, adipokines, and endothelial dysfunction would be more strongly associated with physical fitness or with physical activity levels. Cross-sectional study involving children aged 5-12 years. The evaluation included venous occlusion plethysmography, serum levels of adiponectin, leptin and insulin, lipid profile, physical activity score (PAQ-C questionnaire), and physical fitness evaluation (Yo-Yo test). A total of 62 children participated in this study. Based on the body mass index, 27 were eutrophic, 10 overweight and 25 obese. Triglycerides, LDL cholesterol, HOMA-IR, and leptin were higher in the obese and excess-weight groups compared to the eutrophic group (p<0.01). HDL cholesterol and adiponectin levels were higher in the eutrophic group compared to the obese and excess-weight groups (p<0.01). Flow-mediated vasodilation after hyperemia was higher in the eutrophic group in comparison to obese and excess-weight subjects (p<0.05). There was no difference in the physical activity levels among groups measured by PAQ-C. The Yo-Yo test was significantly associated with HDL cholesterol (rho=-0.41; p=0.01), and this association remained after adjusting for body mass index z-score (rho=0.28; p=0.03). This study showed that endothelial dysfunction is already present in obese children, suggesting a predisposition to atherosclerotic disease. Moreover, HDL cholesterol levels were correlated with physical fitness, regardless of body mass index. Copyright © 2018. Published by Elsevier Editora Ltda.

Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.

PubMed

Suman, Shubhankar; Kumar, Santosh; Fornace, Albert J; Datta, Kamal

2016-08-25

Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as (56)Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of (56)Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of (56)Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.

Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows.

PubMed

Kasimanickam, Ramanathan K; Kasimanickam, Vanmathy R; Olsen, Jesse R; Jeffress, Erin J; Moore, Dale A; Kastelic, John P

2013-11-09

Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions. Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1. Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P < 0.05). Furthermore, serum leptin, TNF-alpha, IL-1beta and IL-6 were higher in cows with subclinical endometritis compared to normal cows (P < 0.05), and insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P < 0.05). Serum concentrations of adipokines, insulin

Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows

PubMed Central

2013-01-01

Background Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions. Methods Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1. Results Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P < 0.05). Furthermore, serum leptin, TNF-alpha, IL-1beta and IL-6 were higher in cows with subclinical endometritis compared to normal cows (P < 0.05), and insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P < 0.05). Conclusions

DNA methylation of leptin and adiponectin promoters in children is reduced by the combined presence of obesity and insulin resistance.

PubMed

García-Cardona, M C; Huang, F; García-Vivas, J M; López-Camarillo, C; Del Río Navarro, B E; Navarro Olivos, E; Hong-Chong, E; Bolaños-Jiménez, F; Marchat, L A

2014-11-01

Epigenetic alterations have been suggested to be associated with obesity and related metabolic disorders. Here we examined the correlation between obesity and insulin resistance with the methylation frequency of the leptin (LEP) and adiponectin (ADIPOQ) promoters in obese adolescents with the aim to identify epigenetic markers that might be used as tools to predict and follow up the physiological alterations associated with the development of the metabolic syndrome. One hundred and six adolescents were recruited and classified according to body mass index and homeostasis model of assessment-insulin resistance index. The circulating concentrations of leptin, adiponectin and of several metabolic markers of obesity and insulin resistance were determined by standard methods. The methylation frequency of the LEP and ADIPOQ promoters was determined by methylation-specific PCR (MS-PCR) in DNA obtained from peripheral blood samples. Obese adolescents without insulin resistance showed higher and lower circulating levels of, respectively, leptin and adiponectin along with increased plasmatic concentrations of insulin and triglycerides. They also exhibited the same methylation frequency than lean subjects of the CpG sites located at -51 and -31 nt relative to the transcription start site of the LEP gene. However, the methylation frequency of these nucleotides dropped markedly in obese adolescents with insulin resistance. We found the same inverse relationship between the combined presence of obesity and insulin resistance and the methylation frequency of the CpG site located at -283 nt relative to the start site of the ADIPOQ promoter. These observations sustain the hypothesis that epigenetic modifications might underpin the development of obesity and related metabolic disorders. They also validate the use of blood leukocytes and MS-PCR as a reliable and affordable methodology for the identification of epigenetic modifications that could be used as molecular markers to

Role of leptin in female reproduction.

PubMed

Pérez-Pérez, Antonio; Sánchez-Jiménez, Flora; Maymó, Julieta; Dueñas, José L; Varone, Cecilia; Sánchez-Margalet, Víctor

2015-01-01

Reproductive function is dependent on energy resources. The role of weight, body composition, fat distribution and the effect of diet have been largely investigated in experimental female animals as well as in women. Any alteration in diet and/or weight may induce abnormalities in timing of sexual maturation and fertility. However, the cellular mechanisms involved in the fine coordination of energy balance and reproduction are largely unknown. The brain and hypothalamic structures receive endocrine and/or metabolic signals providing information on the nutritional status and the degree of fat stores. Adipose tissue acts both as a store of energy and as an active endocrine organ, secreting a large number of biologically important molecules termed adipokines. Adipokines have been shown to be involved in regulation of the reproductive functions. The first adipokine described was leptin. Extensive research over the last 10 years has shown that leptin is not only an adipose tissue-derived messenger of the amount of energy stores to the brain, but also a crucial hormone/cytokine for a number of diverse physiological processes, such as inflammation, angiogenesis, hematopoiesis, immune function, and most importantly, reproduction. Leptin plays an integral role in the normal physiology of the reproductive system with complex interactions at all levels of the hypothalamic-pituitary gonadal (HPG) axis. In addition, leptin is also produced by placenta, where it plays an important autocrine function. Observational studies have demonstrated that states of leptin excess, deficiency, or resistance can be associated with abnormal reproductive function. This review focuses on the leptin action in female reproduction.

Impact of the Adipokine Adiponectin and the Hepatokine Fetuin-A on the Development of Type 2 Diabetes: Prospective Cohort- and Cross-Sectional Phenotyping Studies

PubMed Central

Stefan, Norbert; Sun, Qi; Fritsche, Andreas; Machann, Jürgen; Schick, Fritz; Gerst, Felicia; Jeppesen, Charlotte; Joost, Hans-Georg; Hu, Frank B.; Boeing, Heiner; Ullrich, Susanne; Häring, Hans-Ulrich; Schulze, Matthias B.

2014-01-01

Background Among adipokines and hepatokines, adiponectin and fetuin-A were consistently found to predict the incidence of type 2 diabetes, both by regulating insulin sensitivity. Objective To determine to what extent circulating adiponectin and fetuin-A are independently associated with incident type 2 diabetes in humans, and the major mechanisms involved. Methods Relationships with incident diabetes were tested in two cohort studies: within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study (628 cases) and the Nurses' Health Study (NHS; 470 cases). Relationships with body fat compartments, insulin sensitivity and insulin secretion were studied in the Tübingen Lifestyle Intervention Program (TULIP; N = 358). Results Circulating adiponectin and fetuin-A, independently of several confounders and of each other, associated with risk of diabetes in EPIC-Potsdam (RR for 1 SD: adiponectin: 0.45 [95% CI 0.37–0.54], fetuin-A: 1.18 [1.05–1.32]) and the NHS (0.51 [0.42–0.62], 1.35 [1.16–1.58]). Obesity measures considerably attenuated the association of adiponectin, but not of fetuin-A. Subjects with low adiponectin and concomitantly high fetuin-A had the highest risk. Whereas both proteins were independently (both p<1.8×10−7) associated with insulin sensitivity, circulating fetuin-A (r = −0.37, p = 0.0004), but not adiponectin, associated with insulin secretion in subjects with impaired glucose tolerance. Conclusions We provide novel information that adiponectin and fetuin-A independently of each other associate with the diabetes risk. Furthermore, we suggest that they are involved in the development of type 2 diabetes via different mechanisms, possibly by mediating effects of their source tissues, expanded adipose tissue and nonalcoholic fatty liver. PMID:24643166

Serum Levels of the Adipokine Progranulin Depend on Renal Function

PubMed Central

Richter, Judit; Focke, Denise; Ebert, Thomas; Kovacs, Peter; Bachmann, Anette; Lössner, Ulrike; Kralisch, Susan; Kratzsch, Jürgen; Beige, Joachim; Anders, Matthias; Bast, Ingolf; Blüher, Matthias; Stumvoll, Michael; Fasshauer, Mathias

2013-01-01

OBJECTIVE Progranulin has recently been introduced as a novel adipokine inducing insulin resistance and obesity. In the current study, we investigated renal elimination, as well as association of the adipokine with markers of the metabolic syndrome. RESEARCH DESIGN AND METHODS Progranulin serum levels were quantified by enzyme-linked immunosorbent assay and correlated to anthropometric and biochemical parameters of renal function and glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD). RESULTS Median serum progranulin levels adjusted for age, sex, and BMI were significantly different between CKD stages with highest values detectable in stage 5 (stage 1, 58.3 µg/L; stage 2, 63.0 µg/L; stage 3, 65.4 µg/L; stage 4, 68.8 µg/L; and stage 5, 90.6 µg/L). Furthermore, CKD stage was the strongest independent predictor of circulating progranulin in our cohort. In addition, high-sensitivity interleukin-6 and adiponectin remained significantly and independently correlated with the adipokine. CONCLUSIONS We demonstrate that progranulin serum levels increase with deteriorating renal function. These findings are in accordance with the hypothesis that renal clearance is a major elimination route for circulating progranulin. Furthermore, the adipokine is positively and independently associated with markers of inflammation and adiponectin. PMID:23033238

Adiponectin is partially associated with exosomes in mouse serum.

PubMed

Phoonsawat, Worrawalan; Aoki-Yoshida, Ayako; Tsuruta, Takeshi; Sonoyama, Kei

2014-06-06

Exosomes are membrane vesicles 30-120 nm in diameter that are released by many cell types and carry a cargo of proteins, lipids, mRNA, and microRNA. Cultured adipocytes reportedly release exosomes that may play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, adipocyte-derived exosomes could exist in the circulation and may be associated with adipocyte-specific proteins such as adipocytokines. We isolated exosomes from serum of mice by differential centrifugation and analyzed adiponectin, leptin, and resistin in the exosome fraction. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. Quantitative ELISA showed that the exosome fraction contains considerable amounts of adiponectin, but not leptin or resistin. The concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. We propose adiponectin as a marker of exosomes released from adipocytes in vivo. Copyright © 2014 Elsevier Inc. All rights reserved.

Adiponectin, Leptin and Inflammatory Markers in HIV-associated Metabolic Syndrome in Children and Adolescents.

PubMed

Espiau, María; Yeste, Diego; Noguera-Julian, Antoni; Soler-Palacín, Pere; Fortuny, Clàudia; Ferrer, Roser; Comas, Immaculada; Martín-Nalda, Andrea; Deyà-Martínez, Ángela; Figueras, Concepció; Carrascosa, Antonio

2017-02-01

Metabolic syndrome (MetS) is more common in HIV-infected adults and children than in the general population. Adipocytokines and inflammatory markers may contribute to the pathophysiology of this condition and could be useful indices for monitoring MetS. The objective of this study was to provide information on the prevalence of MetS and investigate the role of adipocytokines and other biomarkers in this syndrome in HIV-infected pediatric patients. A cross-sectional study was conducted between October 2013 and March 2014 in the outpatient clinics of 2 tertiary pediatric referral hospitals. Fifty-four HIV-infected children and adolescents were included. MetS was defined according to the International Diabetes Federation and modified National Cholesterol Education Program Adult Treatment Panel III criteria. Measurements included anthropometry, waist circumference, blood pressure, fasting lipids, glucose and insulin, adiponectin, leptin, interleukin-6, vitamin D and C-reactive protein and clinical lipodystrophy assessment. Among the total, 3.7% of patients met the International Diabetes Federation criteria for MetS and 7.4% met the National Cholesterol Education Program Adult Treatment Panel III criteria. C-reactive protein and leptin levels were significantly higher and adiponectin level significantly lower in patients with MetS, regardless of the criteria used. Insulin resistance was observed in 40.7% of patients; abnormal quantitative insulin sensitivity check index values were found in 88.9%. Eighteen patients (33.3%) had vitamin D deficiency. The prevalence of MetS was similar to that observed in larger cohorts of HIV-infected patients in our setting. Adipocytokine dysregulation seems to be related to MetS in HIV-infected children. A high percentage of patients showed insulin resistance, which should be strictly monitored.

Evidence of a link between resting energy expenditure and bone remodelling, glucose homeostasis and adipokine variations in adolescent girls with anorexia nervosa.

PubMed

Maïmoun, L; Guillaume, S; Lefebvre, P; Philibert, P; Bertet, H; Picot, M-C; Gaspari, L; Paris, F; Seneque, M; Dupuys, A-M; Courtet, P; Thomas, E; Mariano-Goulart, D; Bringer, J; Renard, E; Sultan, C

2016-01-01

Low bone mass is a consequence of anorexia nervosa (AN). This study assessed the effects of energy deficiency on various bone and hormonal parameters. The interrelationships between energy deficiency and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency to limit demineralisation and hormonal alterations in AN patients. Low areal bone mineral density (aBMD) is a well-known consequence of AN. However, the impact of reduced energy expenditure on bone metabolism is unknown. This study assessed the effects of energy deficiency on bone remodelling and its potential interactions with glucose homeostasis and adipose tissue-derived hormones in AN, a clinical model for reduced energy expenditure. Fifty women with AN and 50 age-matched controls (mean age 18.1 ± 2.7 and 18.0 ± 2.1 years, respectively) were enrolled. aBMD was determined with DXA. Resting energy expenditure (REEm), a marker of energy status, was indirectly assessed by calorimetry. Bone turnover markers, undercarboxylated osteocalcin (ucOC), parameters of glucose homeostasis, adipokines and growth factors were concomitantly evaluated. AN patients presented low aBMD at all bone sites. REEm, bone formation markers, ucOC, glucose, insulin, HOMA-IR, leptin and IGF-1 were significantly reduced, whereas the bone resorption marker, leptin receptor (sOB-R) and adiponectin were elevated in AN compared with CON. In AN patients, REEm was positively correlated with weight, BMI, whole body (WB) fat mass, WB fat-free soft tissue, markers of bone formation, glucose, insulin, HOMA-IR, leptin and IGF-1 and negatively correlated with the bone resorption marker and sOB-R. Biological parameters, aBMD excepted, appeared more affected by the weight variation in the last 6 months than by the disease duration. The strong interrelationships between REEm and bone remodelling, glucose homeostasis and adipokines underscore the importance of preventing energy deficiency

Leptin and Hormones: Energy Homeostasis.

PubMed

Triantafyllou, Georgios A; Paschou, Stavroula A; Mantzoros, Christos S

2016-09-01

Leptin, a 167 amino acid adipokine, plays a major role in human energy homeostasis. Its actions are mediated through binding to leptin receptor and activating JAK-STAT3 signal transduction pathway. It is expressed mainly in adipocytes, and its circulating levels reflect the body's energy stores in adipose tissue. Recombinant methionyl human leptin has been FDA approved for patients with generalized non-HIV lipodystrophy and for compassionate use in subjects with congenital leptin deficiency. The purpose of this review is to outline the role of leptin in energy homeostasis, as well as its interaction with other hormones. Copyright © 2016 Elsevier Inc. All rights reserved.

Bone status and adipokine levels in children on vegetarian and omnivorous diets.

PubMed

Ambroszkiewicz, Jadwiga; Chełchowska, Magdalena; Szamotulska, Katarzyna; Rowicka, Grażyna; Klemarczyk, Witold; Strucińska, Małgorzata; Gajewska, Joanna

2018-03-23

Measurements of bone mineral density (BMD) reflect bone status but not the dynamics of bone turnover. Biochemical markers, which show global skeletal activity, were validated for the assessment of bone formation and resorption processes. Adipokines also play a significant role in the regulation of bone metabolism. To assess body composition, bone mineral density, bone turnover markers and adipokine levels in relation to vegetarian and omnivorous diets. The study included 53 vegetarian and 53 omnivorous prepubertal healthy children matched for age and sex (median age 7.0 years). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. 25-hydroxyvitamin D and parathormone levels were measured by chemiluminescence method. Serum carboxy-terminal propeptide of type I collagen (CICP), total osteocalcin (OC) and its forms carboxylated (c-OC) and undercarboxylated (uc-OC), C-terminal cross-linking telopeptide of collagen type I (CTX), leptin and adiponectin levels were determined using immunoenzymatic assays. Both groups of children were comparable in terms of body composition, except for the percentage of fat mass, which was lower (19.24 vs. 21.77%, p = 0.018) in vegetarians. Mean values of total BMD z-score and lumbar spine BMD z-score were lower (-0.583 vs. -0.194, p = 0.009 and -0.877 vs. -0.496, p = 0.019, respectively) in vegetarians compared with omnivores. Serum leptin level was about 2-fold lower (1.39 vs. 2.94 ng/mL, p < 0.001) in vegetarians, however, adiponectin concentration was similar in both groups. Vegetarians had similar concentration of 25-hydroxyvitamin D, but higher parathormone (40.8 vs. 32.1 pg/mL, p = 0.015) and CTX (1.94 vs. 1.76 ng/mL, p = 0.077) levels than omnivores. Total osteocalcin and CICP concentrations were comparable in both groups, however, c-OC/uc-OC ratio was higher (1.43 vs. 1.04 ng/mL, p < 0.05) in vegetarians. We found positive correlation between c-OC and nutritional parameters adjusted for

Adipokines, adiposity, and bone marrow adipocytes: Dangerous accomplices in multiple myeloma.

PubMed

Morris, Emma V; Edwards, Claire M

2018-06-26

Obesity has become a global epidemic influencing the establishment and progression of a wide range of diseases, such as diabetes, cardiovascular disease, and cancer. In 2016, International Agency for Research on Cancer reported that obesity is now associated with 13 different cancers, one of which is multiple myeloma (MM), a destructive cancer of plasma cells that predominantly reside in the bone marrow. Obesity is the accumulation of excess body fat, which causes metabolic, endocrine, immunologic, and inflammatory-like changes. Obesity is usually associated with an increase in visceral and/or subcutaneous fat; however, an additional fat depot that also responds to diet-induced changes is bone marrow adipose tissue (BMAT). There have been several studies over the past few decades that have identified BMAT as a key driver in MM progression. Adipocytes secrete numerous adipokines, such as leptin, adiponectin, resistin, adipsin, and visfatin, which when secreted at normal controlled levels have protective properties. However, in obesity these levels of secretion change, coupled with an increase in adipocyte number and size causing a profound and lasting effect on the bone microenvironment, contributing to MM cell growth, survival, and migration as well as potentially fueling bone destruction. Obesity is a modifiable risk factor making it an attractive option for targeted therapy. This review discusses the link between obesity, monoclonal gammopathy of undetermined significance (a benign condition that precedes MM), and myeloma, and the contribution of key adipokines to disease establishment and progression. © 2018 Wiley Periodicals, Inc.

Effect of Weight Loss with or without Exercise on Inflammatory Markers and Adipokines in Postmenopausal Women: The SHAPE-2 Trial, A Randomized Controlled Trial.

PubMed

van Gemert, Willemijn A; May, Anne M; Schuit, Albertine J; Oosterhof, Blanche Y M; Peeters, Petra H; Monninkhof, Evelyn M

2016-05-01

We investigated the effect of equivalent weight loss, by a hypocaloric diet or mainly exercise, on inflammatory markers and adipokines in overweight postmenopausal women. Women were randomized to a diet (n = 97), mainly exercise (n = 98), or control group (n = 48). Goal of both interventions was to lose 5 to 6 kg bodyweight by a hypocaloric diet or an exercise program (4 hours/week) combined with a small caloric intake restriction. Outcomes after 16 weeks included serum high-sensitive C-reactive protein (hsCRP), IL6, adiponectin, and leptin. Both intervention groups achieved the target weight loss. Controls remained weight stable. Compared with control, hsCRP decreased with mainly exercise [treatment effect ratio (TER) = 0.64] and borderline statistically significant with diet (TER = 0.77). There was a suggestively larger effect of exercise, directly compared with diet (TER = 0.83). Leptin decreased with both interventions: mainly exercise (TER = 0.55) and diet (TER = 0.59), versus control. Effects attenuated and lost significance after adjusting for change in body fat percentage, and to a lesser extent when adjusting for fitness. No effects were seen on IL6 and adiponectin. A 16-week randomized intervention inducing comparable weight loss by a hypocaloric diet or mainly exercise, resulted in favorable effects on serum hsCRP and leptin. We found a possible more beneficial effect on hsCRP with mainly exercise versus diet. These effects of exercise were established by changes in body fat percentage and physical fitness. A modest amount of weight loss in postmenopausal women reduces hsCRP and leptin levels which might be associated with a lower breast cancer risk. Cancer Epidemiol Biomarkers Prev; 25(5); 799-806. ©2016 AACR. ©2016 American Association for Cancer Research.

Effect of Sibutramine on Plasma C-Reactive Protein, Leptin and Adipon ectin Concentrations: A Systematic Review and Meta-Analysis of Randomized Contr olled Trials.

PubMed

De Vincentis, Antonio; Pedone, Claudio; Vespasiani-Gentilucci, Umberto; Picardi, Antonio; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

2017-01-01

Sibutramine is an anti-obesity medication whose effects on weight loss have been widely explored. Moreover, limited number of studies also evidenced its correlates on adipokines and proinflammatory markers; however, their results have not been conclusive. Hence, a systematic review and meta-analysis of available evidence was conducted in order to calculate the effect size of sibutramine therapy on C-reactive protein (CRP), leptin and adiponectin concentrations. Seven randomized clinical trials with a total of 601 subjects met the eligibility criteria. Random effect meta-analysis evidenced a significant decrease in plasma levels of CRP and leptin (weighted mean difference [WMD] -15.58%, 95% confidence interval [95%CI]: -28.84, -2.33, p=0.021 and WMD -9.25, 95%CI: -15.73, -2.78, p=0.005, respectively) and increase of adiponectin (WMD 9.86%, 95%CI: 1.76, 17.96, p=0.017) following sibutramine therapy. Subgroup analysis showed a greater CRP-lowering effect of sibutramine with doses <15 mg/day (WMD -17.26%, 95%CI: -31.02, -3.5, p=0.014) compared with doses .15 mg/day (WMD 6.01%, 95%CI: -43.38, 55.40, p=0.811). In meta-regression analysis, changes in CRP were found to be independent of baseline or percentage change in body mass index. These results suggest a significant improvement of plasma CRP, leptin and adiponectin levels following treatment with sibutramine. Possible impacts and relevance of these alterations on cardiovascular risk profile remain to be clarified, especially in post-hoc analyses of sibutramine outcome trials among people without pre-existing cardiovascular disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Analysis of the relationship of leptin, high-sensitivity C-reactive protein, adiponectin, insulin, and uric acid to metabolic syndrome in lean, overweight, and obese young females.

PubMed

Abdullah, Abdul Ridha; Hasan, Haydar A; Raigangar, Veena L

2009-02-01

Over the last decade there has been a steady rise in obesity and co-morbidity, but little is known about the rate of metabolic dysfunction among young adults in the United Arab Emirates. Various factors have been implicated as biomarkers of metabolic syndrome. The objective of this study was to analyze the relationships of leptin, C-reactive protein (CRP), adiponectin, insulin, and uric acid to the metabolic syndrome components in lean, overweight, and obese young females. This was a cross-sectional study of 69 apparently healthy young females, who were classified according to their body mass index (BMI) (kg/m(2)) into three groups: lean (25 and <30), and obese (>or=30). Estimated biomarkers were: leptin, insulin, adiponectin, high-sensitivity [hs]-CRP, uric acid, blood sugar, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides (TG). Anthropometric measures, blood pressure, and homeostasis model assessment-insulin resistance (HOMA-IR) were also measured. Serum leptin, hs-CRP, insulin, and uric acid increased significantly (p < 0.01) with increased BMI. Only one significant correlation (p < 0.05) between the biomarkers and the metabolic syndrome components was found in lean subjects (leptin vs. waist circumference r = 0.48) as opposed to six in the obese group (hs-CRP vs. waist circumference and systolic blood pressure [SBP], r = 0.45 and r = -0.41, respectively; insulin vs. diastolic blood pressure [DBP], r = 0.47; adiponectin vs. blood sugar, r = -0.44; and uric acid vs. waist circumference and TG, r = 0.5 and r = 0.51, respectively). Estimation of the levels of studied biomarkers could be an important tool for early detection of metabolic syndrome before the appearance of its frank components. Uric acid seems to be the most reliable biomarker to identify obese subjects with metabolic syndrome.

TNFα blockade for inflammatory rheumatic diseases is associated with a significant gain in android fat mass and has varying effects on adipokines: a 2-year prospective study.

PubMed

Toussirot, Éric; Mourot, Laurent; Dehecq, Barbara; Wendling, Daniel; Grandclément, Émilie; Dumoulin, Gilles

2014-04-01

To evaluate the long-term consequences of TNFα inhibitors on body composition and fat distribution, as well as changes in serum adipokines in patients with rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Eight patients with RA and twelve with AS requiring a TNFα inhibitor were prospectively followed for 2 years. Body composition was evaluated by dual X-ray absorptiometry and included measurements of total fat mass, lean mass, fat in the gynoid and android regions, and visceral fat. Serum leptin, total and high molecular weight (HMW) adiponectin, resistin, and ghrelin were also assessed. There was a significant gain in body mass index (p = 0.05) and a tendency for weight (p = 0.07), android fat (p = 0.07), and visceral fat (p = 0.059) increase in patients with RA, while in AS, total fat mass significantly increased (p = 0.02) with a parallel weight gain (p = 0.07). When examining the whole population of patients, we observed after 2 years a significant increase in body weight (+1.9%; p = 0.003), body mass index (+2.5%; p = 0.004), total fat mass (+11.1%; p = 0.007), and fat in the android region (+18.3%; p = 0.02). There was a substantial, albeit nonsignificant gain in visceral fat (+24.3%; p = 0.088). Lean mass and gynoid fat were not modified. No major changes were observed for serum leptin, total adiponectin, and ghrelin, while HMW adiponectin and the HMW/total adiponectin ratio tended to decrease (-15.2%, p = 0.057 and -9.3%, p = 0.067, respectively). Resistin decreased significantly (-22.4%, p = 0.01). Long-term TNFα inhibition in RA and AS is associated with a significant gain in fat mass, with a shift to the android (visceral) region. This fat redistribution raises questions about its influence on the cardiovascular profile of patients receiving these treatments.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuan, Guoyue, E-mail: yuanguoyue@hotmail.com; Jia, Jue; Di, Liangliang

Highlights: Black-Right-Pointing-Pointer CRP increases TNF-{alpha} and IL-6 genes expression in matured 3T3-L1 adipocytes. Black-Right-Pointing-Pointer CRP suppresses adiponectin, leptin and PPAR-{gamma} mRNA levels in matured 3T3-L1 cells. Black-Right-Pointing-Pointer Wortmannin reverses effects of CRP on adiponectin, TNF-{alpha} and leptin mRNA levels. Black-Right-Pointing-Pointer CRP may regulate IR, obesity and metabolic syndrome by this mechanism. -- Abstract: Adipose tissue is now recognized to be an important endocrine organ, secreting a variety of adipokines that are involved in the regulation of energy metabolism, insulin resistance and metabolic syndrome. C-reactive protein (CRP) is considered as one of the most sensitive markers of inflammation. A number ofmore » studies have shown that elevation of CRP concentrations is an independent predictive parameter of type 2 diabetes mellitus, which is also strongly associated with various components of the metabolic syndrome. The aim of the present study is to investigate the effects of CRP on adipokines genes expression in 3T3-L1 adipocytes. Quantitative real-time PCR analysis revealed that CRP inhibited adiponectin, leptin and peroxisome proliferator-activated receptor-gamma (PPAR-{gamma}) genes expression and raised tumor necrosis factor-{alpha} (TNF-{alpha}) and interleukin-6 (IL-6) mRNA levels in matured 3T3-L1 adipocytes in a dose and time-dependent manner. Pharmacological inhibition of phosphatidylinositol (PI)-3 kinase by wortmannin partially reversed the effects of CRP on adiponectin, TNF-{alpha} and leptin genes expression. These results collectively suggest that CRP regulates adiponectin, TNF-{alpha}, leptin, IL-6 and PPAR-{gamma} genes expression, and that might represent a mechanism by which CRP regulates insulin resistance, obesity and metabolic syndrome.« less

Serum Adipokines and Adipose Tissue Distribution in Rheumatoid Arthritis and Ankylosing Spondylitis. A Comparative Study

PubMed Central

Toussirot, Éric; Grandclément, Émilie; Gaugler, Béatrice; Michel, Fabrice; Wendling, Daniel; Saas, Philippe; Dumoulin, Gilles

2013-01-01

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These

Serum adipokines and adipose tissue distribution in rheumatoid arthritis and ankylosing spondylitis. A comparative study.

PubMed

Toussirot, Eric; Grandclément, Emilie; Gaugler, Béatrice; Michel, Fabrice; Wendling, Daniel; Saas, Philippe; Dumoulin, Gilles

2013-01-01

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are inflammatory rheumatic diseases that may modify body composition. Adipose tissue has the ability to release a wide range of products involved in physiologic functions, but also in various pathological processes, including the inflammatory/immune response. RA and AS are both associated with the development of cardiovascular complications. It is has been established that central/abdominal, and particularly intra-abdominal or visceral adiposity is closely linked to cardiovascular events. Thus, in this study, we aimed to evaluate the body composition of patients with RA or AS compared to healthy controls (HC), with a special emphasis on the visceral region. In parallel, we measured adipose products or adipokines, namely leptin, adiponectin and its high molecular weight (HMW) isoform, resistin, and ghrelin, a gastric peptide that plays a role in energetic balance. The homeostasis model assessment for insulin resistance (HOMA-IR) and atherogenic index were used to evaluate cardiovascular risk. One hundred and twelve subjects were enrolled (30 patients with RA, 31 with AS, and 51 HC). Body composition was measured using dual-energy X-ray absorptiometry to determine total fat mass and lean mass, adiposity, fat in the android and gynoid regions, and visceral fat. Patients and HC did not differ in terms of body mass index. On the contrary, adiposity was increased in RA (p = 0.01) while visceral fat was also increased, but only in women (p = 0.01). Patients with AS tended to have lower total fat mass (p = 0.07) and higher lean mass compared to HC (p = 0.07). Leptin and leptin/fat mass were decreased in male patients with AS (p < 0.01), while total adiponectin and the ratio of HMW to total adiponectin were both increased in RA (p < 0.01). There were no changes in serum resistin and ghrelin in any group of patients. HOMA-IR and the atherogenic index were not modified in RA and AS. These

Conventional kinesin KIF5B mediates adiponectin secretion in 3T3-L1 adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cui, Ju, E-mail: juzi.cui@gmail.com; Pang, Jing; Lin, Ya-Jun

2016-08-05

Insulin stimulates adiponectin secretion and glucose transporter type 4 (GLUT4) translocation in adipocyte to regulate metabolism homeostasis. Similar to GLUT4 translocation, intracellular trafficking and release of adiponectin in adipocytes relies on the trans-Golgi network and endosomal system. Recent studies show that the heavy chain of conventional kinesin (KIF5B) mediates GLUT4 translocation in murine 3T3-L1 adipocytes, however, the motor machinery involved in mediating intracellular trafficking and release of adiponectin is unknown. Here, we examined the role of KIF5B in the regulation of adiponectin secretion. The KIF5B level was up-regulated during 3T3-L1 adipogenesis. This increase in cytosolic KIF5B was synchronized with themore » induction of adiponectin. Endogenous KIF5B and adiponectin were partially colocalized at the peri-nuclear and cytosolic regions. In addition, adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. Knockdown of KIF5B resulted in a marked inhibition of adiponectin secretion and overexpression of KIF5B enhanced adiponectin release, whereas leptin secretion was not affected by changes in KIF5B expression. These data suggest that the secretion of adiponectin, but not leptin, is dependent on functional KIF5B. - Highlights: • The KIF5B level was up regulated during 3T3-L1 adipogenesis. • Endogenous KIF5B and adiponectin were partially colicalized. • Adiponectin-containing vesicles were co-immunoprecipitated with KIF5B. • The secretion of adiponectin, but not leptin, is dependent on functional KIF5B.« less

The soluble leptin receptor.

PubMed

Schaab, Michael; Kratzsch, Juergen

2015-10-01

The adipokine leptin realizes signal transduction via four different leptin receptor (OB-R) isoforms. The amount of functionally active OB-R, however, is affected by constitutive shedding of the extracellular domain. The product of the cleavage process, the so-called soluble leptin receptor (sOB-R), is the main binding protein for leptin in human blood and modulates its bioavailability. Concentrations of sOB-R are differentially regulated in metabolic disorders, such as type 1 diabetes mellitus or obesity, and can, therefore, enhance or reduce leptin sensitivity. Lipotoxicity and apoptosis increase OB-R cleavage via ADAM10-dependent mechanisms. In contrast, although increased sOB-R concentrations seem to directly inhibit leptin effects, reduced amounts of sOB-R may reflect decreased membrane expression of OB-R. These findings, in part, explain alterations of leptin sensitivity that are associated with changes in serum sOB-R concentrations seen in metabolic disorders. Copyright © 2015 Elsevier Ltd. All rights reserved.

Gene expression of placental hormones regulating energy balance in small for gestational age neonates.

PubMed

Struwe, Ellen; Berzl, Gabriele M; Schild, Ralf L; Dötsch, Jörg

2009-01-01

Fetal growth restriction is associated with an increased risk for metabolic and cardiovascular disease in later life. To further elucidate mechanisms that might be involved in the process of prenatal programming, we measured the adipokines leptin, resistin, and adiponectin and the GH-releasing hormone ghrelin in the placenta of small for gestational age (SGA) neonates. The control group included 24 placentas of appropriate for gestational age (AGA) newborns, in the study group were 16 placentas of SGA neonates. Gene expression of leptin, resistin, adiponectin, and ghrelin was examined. For hormones showing alterations in gene regulation placental protein expression was measured by Western blot. Placental mRNA expression of leptin was significantly increased in SGA placentas (p=0.0035, related to beta-actin). Protein concentration was increased, as well. There were no differences in placental resistin, adiponectin, or ghrelin gene expressions between SGA neonates and controls. Leptin was the only hormone to demonstrate a significant inverse correlation with birth weight (r=-0.44, p=0.01). Adiponectin correlated significantly with leptin (r=0.53, p=0.0023) and ghrelin (r=0.50, p=0.0045). Placental leptin gene expression and protein concentration showed the expected increase in the SGA group. Leptin was inversely correlated with birth weight. Positive correlation of adiponectin with leptin and ghrelin expression suggests an interaction between these hormones in the placenta. However, the unchanged expression of resistin, adiponectin, and ghrelin in SGA placentas and the absence of correlation with birth weight cast doubt whether these hormones produced in the placenta play a key role in fetal programming.

Measurement of salivary resistin, visfatin and adiponectin levels.

PubMed

Mamali, Irene; Roupas, Nikolaos D; Armeni, Anastasia K; Theodoropoulou, Anastasia; Markou, Kostas B; Georgopoulos, Neoklis A

2012-01-01

Hormonal determination in saliva offers several advantages. Peptides enter the salivary glands either by active transport mechanisms or are expressed and secreted by the salivary glands themselves. The collection of saliva is a noninvasive, easily repeatable and less stressful technique than blood withdrawal. The purpose of the present study was to introduce a method for measuring salivary resistin, visfatin and adiponectin levels and to evaluate their associations with serum levels. Resistin, visfatin and adiponectin levels were measured in serum and saliva of 50 healthy adult volunteers (17 male and 33 female) using commercial enzyme immunoassay kits for serum with minor modifications. The present study documented the determination of resistin and adiponectin levels in saliva and the significant correlation of salivary levels with serum levels (r=0.441, p<0.01 and r=0.347, p<0.05, respectively). Moreover, the identification of visfatin in saliva was achieved, but no significant correlation with serum visfatin levels was observed. To our knowledge, this is the first study to report the determination of resistin and visfatin in saliva and the significant correlation of salivary resistin with serum levels, while it confirmed the significant association between salivary and serum adiponectin. The introduction of salivary determinations of adipokines could contribute to the elucidation of the physiology and the role of the specific adipokines in various clinical conditions (obesity, insulin resistance, inflammation, reproduction, energy imbalance and stress response). Copyright © 2011 Elsevier Inc. All rights reserved.

Maternal blood metal levels and fetal markers of metabolic function

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ashley-Martin, Jillian; Dodds, Linda, E-mail: l.dodds@dal.ca; Arbuckle, Tye E.

Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal–Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers ofmore » fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥90%) and low (≤10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures. - Highlights: • We determined relationships between maternal metal levels and cord blood adipokines. • Cord blood leptin levels were higher among female than male infants. • Maternal cadmium was associated with elevated leptin in male, not female infants. • No significant associations were observed between

Insulin-independent role of adiponectin receptor signaling in Drosophila germline stem cell maintenance.

PubMed

Laws, Kaitlin M; Sampson, Leesa L; Drummond-Barbosa, Daniela

2015-03-15

Adipocytes have key endocrine roles, mediated in large part by secreted protein hormones termed adipokines. The adipokine adiponectin is well known for its role in sensitizing peripheral tissues to insulin, and several lines of evidence suggest that adiponectin might also modulate stem cells/precursors. It remains unclear, however, how adiponectin signaling controls stem cells and whether this role is secondary to its insulin-sensitizing effects or distinct. Drosophila adipocytes also function as an endocrine organ and, although no obvious adiponectin homolog has been identified, Drosophila AdipoR encodes a well-conserved homolog of mammalian adiponectin receptors. Here, we generate a null AdipoR allele and use clonal analysis to demonstrate an intrinsic requirement for AdipoR in germline stem cell (GSC) maintenance in the Drosophila ovary. AdipoR null GSCs are not fully responsive to bone morphogenetic protein ligands from the niche and have a slight reduction in E-cadherin levels at the GSC-niche junction. Conversely, germline-specific overexpression of AdipoR inhibits natural GSC loss, suggesting that reduction in adiponectin signaling might contribute to the normal decline in GSC numbers observed over time in wild-type females. Surprisingly, AdipoR is not required for insulin sensitization of the germline, leading us to speculate that insulin sensitization is a more recently acquired function than stem cell regulation in the evolutionary history of adiponectin signaling. Our findings establish Drosophila female GSCs as a new system for future studies addressing the molecular mechanisms whereby adiponectin receptor signaling modulates stem cell fate. Copyright © 2015 Elsevier Inc. All rights reserved.

Potential role of leptin expression in hepatocellular carcinoma

PubMed Central

Wang, S‐N; Yeh, Y‐T; Yang, S‐F; Chai, C‐Y; Lee, K‐T

2006-01-01

Background Obesity is associated with hepatocellular carcinoma (HCC). The association may result from the aberrant expression of adipokines. Aim To explore the potential biological effect and prognostic value of leptin, one of the adipokines, in HCC. Methods Immunohistochemistry was used to evaluate the expression of leptin in 68 patients with HCC. The expression of Ki‐67 and microvessel density (MVD) of tumorous lesions in HCC were also analysed. The result of leptin expression was further correlated with Ki‐67 expression, intratumour MVD, clinicopathological characteristics, overall survival and the postoperative use of medroxyprogesterone acetate (MPA). Results High leptin expression was seen in 60.3% of patients with HCC and was significantly correlated with intratumour MVD (high v low; 59.2 (standard deviation 3.2) v 44.2 (19.5), p = 0.004), but not with Ki‐67 expression. No marked correlation was seen between leptin expression and clinicopathological characteristics. However, using a multivariate Cox's proportional hazards model, leptin expression was a predictor for improved overall survival of patients with HCC (odds ratio 0.16; 95% confidence interval 0.03 to 0.87; p = 0.033). In addition, the Kaplan–Meier survival curve showed that high leptin expression was associated with a better survival in patients with HCC, treated postoperatively with MPA (p = 0.008, log rank test). Conclusion High leptin expression was associated with an increased intratumour MVD and thus may be associated with HCC development. In addition, high leptin expression was a predictor for improved survival of patients with HCC, treated postoperatively with MPA. PMID:16565221

Cord blood adipokines, neonatal anthropometrics and postnatal growth in offspring of Hispanic and Native American women with diabetes mellitus.

PubMed

Teague, April M; Fields, David A; Aston, Christopher E; Short, Kevin R; Lyons, Timothy J; Chernausek, Steven D

2015-06-26

Offspring of women with diabetes mellitus (DM) during pregnancy have a risk of developing metabolic disease in adulthood greater than that conferred by genetics alone. The mechanisms responsible are unknown, but likely involve fetal exposure to the in utero milieu, including glucose and circulating adipokines. The purpose of this study was to assess the impact of maternal DM on fetal adipokines and anthropometry in infants of Hispanic and Native American women. We conducted a prospective study of offspring of mothers with normoglycemia (Con-O; n = 79) or type 2 or gestational DM (DM-O; n = 45) pregnancies. Infant anthropometrics were measured at birth and 1-month of age. Cord leptin, high-molecular-weight adiponectin (HMWA), pigment epithelium-derived factor (PEDF) and C-peptide were measured by ELISA. Differences between groups were assessed using the Generalized Linear Model framework. Correlations were calculated as standardized regression coefficients and adjusted for significant covariates. DM-O were heavier at birth than Con-O (3.7 ± 0.6 vs. 3.4 ± 0.4 kg, p = 0.024), but sum of skinfolds (SSF) were not different. At 1-month, there was no difference in weight, SSF or % body fat or postnatal growth between groups. Leptin was higher in DM-O (20.1 ± 14.9 vs. 9.5 ± 9.9 ng/ml in Con-O, p < 0.0001). Leptin was positively associated with birth weight (p = 0.0007) and SSF (p = 0.002) in Con-O and with maternal hemoglobin A1c in both groups (Con-O, p = 0.023; DM-O, p = 0.006). PEDF was positively associated with birth weight in all infants (p = 0.004). Leptin was positively associated with PEDF in both groups, with a stronger correlation in DM-O (p = 0.009). At 1-month, HMWA was positively associated with body weight (p = 0.004), SSF (p = 0.025) and % body fat (p = 0.004) across the cohort. Maternal DM results in fetal hyperleptinemia independent of adiposity. HMWA appears to influence postnatal growth. Thus, in

Serum adipokine profile and fatty acid composition of adipose tissues are affected by conjugated linoleic acid and saturated fat diets in obese Zucker rats.

PubMed

Martins, Susana V; Lopes, Paula A; Alfaia, Cristina M; Rodrigues, Pedro O; Alves, Susana P; Pinto, Rui M A; Castro, Matilde F; Bessa, Rui J B; Prates, José A M

2010-03-01

Conjugated linoleic acid (CLA) has been reported as having body fat lowering properties and the ability to modulate the inflammatory system in several models. In the present study, the effects of CLA added to saturated fat diets, from vegetable and animal origins, on the serum adipokine profile of obese Zucker rats were assessed. In addition, the fatty acid composition of epididymal and retroperitoneal adipose tissues was determined and a principal component analysis (PCA) was used to assess possible relationships between fatty acids and serum metabolites. Atherogenic diets (2 % cholesterol) were formulated with palm oil and ovine fat and supplemented or not with 1 % of a mixture (1:1) of cis-9, trans-11 and trans-10, cis-12-CLA isomers. CLA-fed animals exhibited lower daily feed intake, final body and liver weights, and hepatic lipids content. Total and LDL-cholesterol levels were increased in CLA-supplemented groups. CLA also promoted higher adiponectin and lower plasminogen activator inhibitor-1 (PAI-1) serum concentrations. In contrast to palm oil diets, ovine fat increased insulin resistance and serum levels of leptin, TNF-alpha and IL-1beta. Epididymal and retroperitoneal adipose tissues had similar deposition of individual fatty acids. The PCA analysis showed that the trans-10, cis-12-CLA isomer was highly associated with adiponectin and PAI-1 levels. Summing up, CLA added to vegetable saturated enriched diets, relative to those from animal origin, seems to improve the serum profile of adipokines and inflammatory markers in obese Zucker rats due to a more favourable fatty acid composition.

Measurement of salivary adiponectin concentrations in dogs.

PubMed

Tvarijonaviciute, Asta; Carrillo-Sanchez, Juana D; García-Martinez, Juan D; Tecles, Fernando; Martinez-Subiela, Silvia; German, Alexander J; Ceron, Jose J

2014-09-01

Measurement of salivary adiponectin could improve understanding of this adipokine's physiology, and its role in various clinical conditions. The purpose of the study was to evaluate the utility of a human adiponectin ELISA kit for measurement of salivary adiponectin in dogs, to compare serum and salivary adiponectin concentrations in a healthy dog population, and to evaluate possible effects of tooth-cleaning on serum and salivary adiponectin concentrations in dogs. For analytical validation, precision, accuracy, and lower limit of quantification of the assay were determined with saliva samples. In addition, adiponectin concentrations were quantified in serum and saliva samples from 24 healthy dogs, and from 7 dogs with mild gingivitis before and after a tooth-cleaning procedure. The validation assays for salivary adiponectin had all coefficients of variation <15%, and recovery ranged from 85% to 120%. In the linearity test, interference was observed when measuring adiponectin in saliva, but this was solved by diluting samples 1:4. In healthy dogs, salivary and serum adiponectin concentrations were positively correlated (r = .650; P = .009). After the tooth-cleaning procedure, salivary adiponectin concentration increased on day 0 (P = .004), but by day 14, concentrations were less than prior to the procedure (P = .041). The human adiponectin ELISA kit can be used for precise and accurate salivary adiponectin measurement in dogs. Salivary adiponectin increased 24 hours after tooth-cleaning, possibly due to acute inflammation or adiponectin leakage from the blood after gingival trauma. © 2014 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

Globular adiponectin induces a pro-inflammatory response in human astrocytic cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wan, Zhongxiao; Mah, Dorrian; Simtchouk, Svetlana

Highlights: • Adiponectin receptors are expressed in human astrocytes. • Globular adiponectin induces secretion of IL-6 and MCP-1 from cultured astrocytes. • Adiponectin may play a pro-inflammatory role in astrocytes. - Abstract: Neuroinflammation, mediated in part by activated brain astrocytes, plays a critical role in the development of neurodegenerative disorders, including Alzheimer’s disease (AD). Adiponectin is the most abundant adipokine secreted from adipose tissue and has been reported to exert both anti- and pro-inflammatory effects in peripheral tissues; however, the effects of adiponectin on astrocytes remain unknown. Shifts in peripheral concentrations of adipokines, including adiponectin, could contribute to the observedmore » link between midlife adiposity and increased AD risk. The aim of the present study was to characterize the effects of globular adiponectin (gAd) on pro-inflammatory cytokine mRNA expression and secretion in human U373 MG astrocytic cells and to explore the potential involvement of nuclear factor (NF)-κB, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2, c-Jun N-terminal kinase (JNK) and phosphatidylinositide 3-kinases (PI3 K) signaling pathways in these processes. We demonstrated expression of adiponectin receptor 1 (adipoR1) and adipoR2 in U373 MG cells and primary human astrocytes. gAd induced secretion of interleukin (IL)-6 and monocyte chemoattractant protein (MCP)-1, and gene expression of IL-6, MCP-1, IL-1β and IL-8 in U373 MG cells. Using specific inhibitors, we found that NF-κB, p38MAPK and ERK1/2 pathways are involved in gAd-induced induction of cytokines with ERK1/2 contributing the most. These findings provide evidence that gAd may induce a pro-inflammatory phenotype in human astrocytes.« less

Leptin, An Adipokine With Central Importance in the Global Obesity Problem.

PubMed

Mechanick, Jeffrey I; Zhao, Shan; Garvey, W Timothy

2017-12-13

Leptin has central importance in the global obesity and cardiovascular disease problem. Leptin is principally secreted by adipocytes and acts in the hypothalamus to suppress appetite and food intake, increase energy expenditure, and regulate body weight. Based on clinical translation of specific and networked actions, leptin affects the cardiovascular system and may be a marker and driver of cardiometabolic risk factors with interventions that are actionable by cardiologists. Leptin subnetwork analysis demonstrates a statistically significant role for ethnoculturally and socioeconomically appropriate lifestyle intervention in cardiovascular disease. Emergent mechanistic components and potential diagnostic or therapeutic targets include hexokinase 3, urocortins, clusterin, sialic acid-binding immunoglobulin-like lectin 6, C-reactive protein, platelet glycoprotein VI, albumin, pentraxin 3, ghrelin, obestatin prepropeptide, leptin receptor, neuropeptide Y, and corticotropin-releasing factor receptor 1. Emergent associated symptoms include weight change, eating disorders, vascular necrosis, chronic fatigue, and chest pain. Leptin-targeted therapies are reported for lipodystrophy and leptin deficiency, but they are investigational for leptin resistance, obesity, and other chronic diseases. Copyright © 2017 World Heart Federation (Geneva). Published by Elsevier B.V. All rights reserved.

Impact of toll-like-receptor-9 (TLR9) deficiency on visceral adipose tissue adipokine expression during chronic DSS-induced colitis in mice.

PubMed

Karrasch, T; Schmid, A; Kopp, A; Obermeier, F; Hofmann, C; Schäffler, A

2015-02-01

Studies postulate an involvement of adipokines in inflammatory gastrointestinal diseases. Leptin-deficient ob/ob mice as well as TLR9-deficient mice have a more moderate course of chronic DSS-induced colitis (DSS-CC) and adipocytes do express functional TLR9 molecules. Adipokine mRNA expression in visceral adipose tissue of mice before and after the induction of DSS-CC was investigated. Experiments were performed in both TLR9(wt/wt) and TLR9(-/-) mice. In vitro, the effect of TLR9 blocking peptide on leptin and visfatin protein secretion was studied in 3T3-L1 adipocytes. Induction of DSS-CC led to an upregulation of leptin mRNA expression in TLR9(wt/wt) mice, while TLR9(-/-) animals showed a significant reduction of leptin expression even below baseline. While visfatin expression remained unchanged in TLR9(wt/wt) animals, TLR9(-/-) mice exhibited a significant induction during DSS-CC. CTRP-3 expression was reduced after colitis induction only in TLR9(-/-) animals. Of note, IL-6 expression levels remained unchanged, while CXCL1/KC and cyclophilin A expression was reduced in DSS-CC. Inhibition of TLR9 signaling by using TLR9 blocking peptide led to reduced leptin protein secretion into cell culture supernatants in 3T3-L1 adipocytes, while visfatin protein secretion was enhanced. DSS-CC leads to differential adipokine expression profiles in the visceral fat pad in TLR9(wt/wt) vs. TLR9(-/-) mice. In vitro, inhibition of TLR9 signaling induces visfatin secretion while inhibiting leptin secretion in adipocytes. Thus, visceral adipokines are regulated by intact TLR9 signaling pathway and a specific interplay between the leptin- and the TLR9-pathways might be of pathophysiological importance in chronic intestinal inflammation. © Georg Thieme Verlag KG Stuttgart · New York.

Adiponectin and resistin gene polymorphisms in association with their respective adipokine levels.

PubMed

Lau, Cia-Hin; Muniandy, Sekaran

2011-05-01

Single nucleotide polymorphisms (SNPs) at the adiponectin and resistin loci are strongly associated with hypoadiponectinemia and hyperresistinemia, which may eventually increase risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease. Real-time PCR was used to genotype SNPs of the adiponectin (SNP+45T>G, SNP+276G>T, SNP+639T>C, and SNP+1212A>G) and resistin (SNP-420C>G and SNP+299G>A) genes in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40 and 70 years old. The genotyping results for each SNP marker was verified by sequencing. The anthropometric clinical and metabolic parameters of subjects were recorded. None of these SNPs at the adiponectin and resistin loci were associated with T2DM and MS susceptibility in Malaysian men. SNP+45T>G, SNP+276G>T, and SNP+639T>C of the adiponectin gene did not influence circulating levels of adiponectin. However, the G-allele of SNP+1212A>G at the adiponectin locus was marginally associated (P= 0.0227) with reduced circulating adiponectin levels. SNP-420C>G (df = 2; F= 16.026; P= 1.50×10(-7) ) and SNP+299G>A (df = 2; F= 22.944; P= 2.04×10(-10) ) of the resistin gene were strongly associated with serum resistin levels. Thus, SNP-420C>G and SNP+299G>A of the resistin gene are strongly associated with the risk of hyperresistinemia in Malaysian men. © 2011 The Authors Annals of Human Genetics © 2011 Blackwell Publishing Ltd/University College London.

A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4

PubMed Central

Phillips, Amy

2014-01-01

With a more sedentary population comes growing rates of obesity and increased type 2 diabetes mellitus (T2DM) risk. Exercise generally induces positive changes in traditional T2DM risk markers such as lipids, glucose tolerance, and insulin sensitivity; however alterations in concentrations of many circulating cytokines and their respective receptors are also becoming apparent. These cytokines may be early-response health risk factors otherwise overlooked in traditional T2DM risk marker analysis. Plasma levels of two adipocyte-originating cytokines, adiponectin and retinol binding protein 4 (RBP-4), alter following exercise. Adiponectin has anti-inflammatory, anti-atherosclerotic, and anti-insulin resistance roles and its secretion increases with physical activity, whilst elevated RBP-4 leads to increased insulin resistance, and secretion decreases with increasing physical activity; thus these plasma adipokine levels alter favourably following exercise. Although current data are limited, they do suggest that the more intense the exercise, the greater the positive effect on plasma RBP-4 levels, whilst lower intensity aerobic exercise may positively improve adiponectin concentrations. Therefore short-duration, high intensity training may provide a time-efficient alternative to the recommended 150 min moderate aerobic exercise per week in providing positive changes in RBP-4 and other traditional T2DM risk markers and due to increased compliance give greater health benefits over the longer term. PMID:26464853

Circadian aspects of adipokine regulation in rodents.

PubMed

Challet, Etienne

2017-12-01

Most hormones display daily fluctuations of secretion during the 24-h cycle. This is also the case for adipokines, in particular the anorexigenic hormone, leptin. The temporal organization of the endocrine system is principally controlled by a network of circadian clocks. The circadian network comprises a master circadian clock, located in the suprachiasmatic nucleus of the hypothalamus, synchronized to the ambient light, and secondary circadian clocks found in various peripheral organs, such as the adipose tissues. Besides circadian clocks, other factors such as meals and metabolic status impact daily profiles of hormonal levels. In turn, the precise daily pattern of hormonal release provides temporal signaling information. This review will describe the reciprocal links between the circadian clocks and rhythmic secretion of leptin, and discuss the metabolic impact of circadian desynchronization and altered rhythmic leptin. Copyright © 2017 Elsevier Ltd. All rights reserved.

Canine adiponectin: cDNA structure, mRNA expression in adipose tissues and reduced plasma levels in obesity.

PubMed

Ishioka, K; Omachi, A; Sagawa, M; Shibata, H; Honjoh, T; Kimura, K; Saito, M

2006-04-01

Adiponectin is a protein synthesized and secreted by adipocytes. Decreased adiponectin is responsible for insulin resistance and atherosclerosis associated with human obesity. We obtained a cDNA clone corresponding to canine adiponectin, whose nucleotide and deduced amino acid sequences were highly identical to those of other species. Adiponectin mRNA was detected in adipose tissues, but not in other tissues, of dogs. When 22 adult beagles were given a high-energy diet for 14 weeks, they became obese, showing heavier body weights, higher plasma leptin concentrations, but lower plasma adiponectin concentrations. The adiponectin concentrations of plasma samples collected from 71 dogs visiting veterinary practices were negatively correlated to plasma leptin concentrations, being lower in obese than non-obese dogs. These results are compatible with those reported in other species, and suggest that adiponectin is an index of adiposity and a target molecule for studies on diseases associated with obesity in dogs.

Changes in daily leptin, ghrelin and adiponectin profiles following a diet with carbohydrates eaten at dinner in obese subjects.

PubMed

Sofer, S; Eliraz, A; Kaplan, S; Voet, H; Fink, G; Kima, T; Madar, Z

2013-08-01

Our recently published randomised clinical trial evaluated the effect of a low-calorie diet with carbohydrates eaten at dinner. This dietary pattern led to lower hunger scores, and better anthropometric, biochemical and inflammatory outcomes compared to a standard low-calorie diet. In the same study, changes in diurnal secretion patterns of leptin, ghrelin and adiponectin were investigated. Seventy-eight police officers (body mass index (BMI) > 30) were randomly allocated to experimental (carbohydrates at dinner) or control weight loss diets for 6 months. Sixty-three subjects finished the programme. On days 0, 7, 90 and 180 blood samples and hunger scores were collected every 4 h from 8:00 to 20:00. Hormonal profiles were available for 39. The dietary manipulation led to changes in daylight hormonal profiles in the experimental group. Leptin's secretion curve became convex, with a nadir later in the day (significant difference compared to baseline at morning and evening, p = 0.023, p = 0.021, respectively). Ghrelin's secretion curve became concave, peaking only in the evening hours. Adiponectin's curve was elevated only after the experimental diet (significant difference compared to baseline at afternoon, p = 0.044). We propose that a low-calorie diet with carbohydrates eaten at dinner can modulate daytime hormonal profiles. Taken together with our earlier results, we believe this diet regime may prevent mid-day hunger, better support weight loss and improve metabolic outcomes compared to conventional weight loss diets. The trial is registered at controlled-trials.com, ISRCTN37829376, December 2009. Copyright © 2012 Elsevier B.V. All rights reserved.

Leptin enhances the invasive ability of glioma stem-like cells depending on leptin receptor expression.

PubMed

Han, Guosheng; Zhao, Wenyuan; Wang, Laixing; Yue, Zhijian; Zhao, Rui; Li, Yanan; Zhou, Xiaoping; Hu, Xiaowu; Liu, Jianmin

2014-01-16

Glioma stem-like cells have been demonstrated to have highly invasive activity, which is the major cause of glioma recurrence after therapy. Leptin plays a role in glioma invasion, however, whether and how leptin contributes to the biological properties of glioma stem-like cells, such as invasion, remains to be explored. In the current study, we aimed to explore the role of leptin during glioma stem-like cells invasion as well as the signaling pathway. We found that glioma stem-like cells exhibited high invasive potential, especially in the presence of leptin, Ob-R coexpressed with CD133 in glioma stem-like cells was showed to be responsible for leptin mediated invasion of glioma stem-like cells. Our results indicated that leptin served as a key intermediary linking the accumulation of excess adipokine to the invasion of glioma stem-like cells, which may be a novel therapeutic target for suppressing tumor invasion and recurrence. © 2013 Published by Elsevier B.V.

IGFBP-3, hypoxia and TNF-{alpha} inhibit adiponectin transcription

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zappala, Giovanna, E-mail: zappalag@mail.nih.gov; Rechler, Matthew M.; Clinical Endocrinology Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD

2009-05-15

The thiazolidinedione rosiglitazone, an agonist ligand for the nuclear receptor PPAR-{gamma}, improves insulin sensitivity in part by stimulating transcription of the insulin-sensitizing adipokine adiponectin. It activates PPAR-{gamma}-RXR-{alpha} heterodimers bound to PPAR-{gamma} response elements in the adiponectin promoter. Rosiglitazone-stimulated adiponectin protein synthesis in 3T3-L1 mouse adipocytes has been shown to be inhibited by IGFBP-3, which can be induced by hypoxia and the proinflammatory cytokine, TNF-{alpha}, two inhibitors of adiponectin transcription. The present study demonstrates that IGFBP-3, the hypoxia-mimetic agent cobalt chloride, and TNF-{alpha} inhibit rosiglitazone-induced adiponectin transcription in mouse embryo fibroblasts that stably express PPAR-{gamma}2. Native IGFBP-3 can bind RXR-{alpha} andmore » inhibited rosiglitazone stimulated promoter activity, whereas an IGFBP-3 mutant that does not bind RXR-{alpha} did not. These results suggest that IGFBP-3 may mediate the inhibition of adiponectin transcription by hypoxia and TNF-{alpha}, and that IGFBP-3 binding to RXR-{alpha} may be required for the observed inhibition.« less

Psoriasis is associated with decreased plasma adiponectin levels independently of cardiometabolic risk factors

PubMed Central

Li, R. C.; Krishnamoorthy, P.; DerOhannessian, S.; Doveikis, J.; Wilcox, M.; Thomas, P.; Rader, D. J.; Reilly, M. P.; Voorhees, A. Van; Gelfand, J. M.; Mehta, N. N.

2013-01-01

Summary Background Psoriasis is an inflammatory skin disease that may be associated with an adverse cardiometabolic profile including modulated plasma adiponectin and leptin levels. Whether these levels are independent of cardiometabolic risk factors, which are also prevalent in psoriasis, is not known. Methods A consecutive sample of 122 participants with varying degrees of psoriasis severity, and a random sample of 134 participants without psoriasis were recruited for this case–control study. Cardiometabolic risk factors including traditional cardiovascular risk factors, waist circumference, insulin resistance, and total plasma adiponectin and leptin were measured. Total plasma adiponectin and leptin levels were compared in unadjusted and adjusted analyses by psoriasis status. Results Participants with psoriasis had mostly mild disease and were mainly on topical therapies, but still had a more adverse cardiometabolic profile compared with those without psoriasis. Furthermore, plasma adiponectin levels were significantly lower in participants with psoriasis than those without {7.13 µg/mL [interquartile range (IQR) 4.9–11.3) vs. 14.5 µg/mL (IQR 8.4–24.1); P < 0.001]}. Plasma leptin (ng/mL) levels were higher in the psoriasis group but this did not reach statistical significance [11.3 (IQR 6.4–21.8) vs. 9.8 (IQR 4.9–20.5); P = 0.07]. In multivariable modelling, plasma adiponectin levels were still negatively associated with psoriasis status after adjusting for waist size (% difference = −41.2%, P < 0.001), insulin resistance (% difference = −39.5%, P < 0.001) and both waist size and insulin resistance (% difference = −38.5%, P < 0.001) Conclusion Plasma levels of adiponectin were lower in psoriasis, and this relationship persisted after adjusting for cardiometabolic risk factors known to decrease adiponectin levels. These findings suggest that inflammation present in psoriasis may be associated with adipose tissue dysfunction; however, direct

Ghrelin and adipokines as circulating markers of disease activity in patients with Takayasu arteritis

PubMed Central

2012-01-01

Introduction The current markers of disease activity in Takayasu arteritis (TA) are insufficient for proper assessment. We investigated circulating levels of unacylated and acylated ghrelin, leptin and adiponectin and their relationships with disease activity in patients with TA. Methods This study included 31 patients with TA and 32 sex-, age- and body mass index-matched healthy controls. Disease activity was assessed in TA patients using various tools, including Kerr's criteria, disease extent index-Takayasu, physician's global assessment, radiological parameters, and laboratory markers. Plasma unacylated and acylated ghrelin, and serum leptin and adiponectin levels were measured using an enzyme-linked immunosorbent assay. Results Unacylated and acylated ghrelin levels were found to be significantly lower in TA patients than that in healthy controls. Patients with active disease had lower unacylated ghrelin levels than those with inactive disease and had lower acylated ghrelin levels than healthy controls. Ghrelin levels were negatively correlated with various parameters of disease activity. The leptin/ghrelin ratio was significantly higher in TA patients than controls. It was positively correlated with disease activity. There was a positive correlation between unacylated and acylated ghrelin and a negative correlation between leptin and ghrelin. There was no statistical difference in adiponectin levels between TA patients and controls. The radiological activity markers were positively correlated with other parameters of disease activity. Conclusions This study suggests that plasma unacylated and acylated ghrelin levels may be useful in monitoring disease activity and planning treatment strategies for patients with TA. The serum leptin level and leptin/ghrelin ratio may also be used to help assess the disease activity. PMID:23259466

Adiponectin and vitamin D-binding protein are independently associated at birth in both mothers and neonates.

PubMed

Karras, Spyridon N; Polyzos, Stergios A; Newton, Danforth A; Wagner, Carol L; Hollis, Bruce W; Ouweland, Jody van den; Dursun, Erdinc; Gezen-Ak, Duygu; Kotsa, Kalliopi; Annweiler, Cedric; Naughton, Declan P

2018-01-01

Adult body fat is associated with birth anthropometry, suggesting a role for metabolic regulators including vitamin D and the adipokines-adiponectin and irisin-which have been reported to interact but, as yet, data remain controversial. To study (i) the relationship between vitamin D, its binding protein (VDBP) and the adipokines, adiponectin, and irisin in mothers and neonates at birth and (ii) their effects on neonate anthropometric outcomes. Cross-sectional study for healthy mothers with full-term and uncomplicated births. Primary care. Seventy pairs of newly delivered neonates and their mothers. Biochemical markers from maternal and cord: VDBP, adiponectin, irisin, calcium, albumin, parathyroid hormone, 25OHD, 1,25(OH) 2 D. Maternal demographic and social characteristics and neonate anthropometric parameters were recorded. Maternal VDBP levels (364.1 ± 11.9 μg/ml) demonstrated a strong positive correlation with maternal adiponectin (4.4 ± 0.4 μg/ml) and irisin (308.8 ± 50.8 ng/ml) concentrations, which remained significant (p < 0.001 and p < 0.041, respectively) after adjustment with multiple parameters, including weeks of gestation, maternal age, and BMI. The finding of a strong association of VDBP (355.3 ± 29.2 μg/ml) and adiponectin (11.9 ± 2.0 μg/ml) but not irisin (174.4 ± 26.0 ng/ml) was also evident in neonates (p = 0.03 and p = 0.94, respectively). No association was observed in both maternal and neonatal vitamin D, adiponectin, and irisin. The main findings of this study are (i) the perspective of a potential independent interaction of VDBP and adiponectin in both mothers and neonates and (ii) the lack of a causative model effect of both maternal/neonatal vitamin D status and adipokine profile on neonatal anthropometry at birth, as a surrogate marker of future metabolic health of the offspring.

Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers

PubMed Central

Mazur-Bialy, Agnieszka Irena; Bilski, Jan; Wojcik, Dagmara; Brzozowski, Bartosz; Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Chmura, Anna; Magierowski, Marcin; Magierowska, Katarzyna; Mach, Tomasz; Brzozowski, Tomasz

2017-01-01

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn‘s disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 (p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice (p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice (p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can

Beneficial Effect of Voluntary Exercise on Experimental Colitis in Mice Fed a High-Fat Diet: The Role of Irisin, Adiponectin and Proinflammatory Biomarkers.

PubMed

Mazur-Bialy, Agnieszka Irena; Bilski, Jan; Wojcik, Dagmara; Brzozowski, Bartosz; Surmiak, Marcin; Hubalewska-Mazgaj, Magdalena; Chmura, Anna; Magierowski, Marcin; Magierowska, Katarzyna; Mach, Tomasz; Brzozowski, Tomasz

2017-04-20

Inflammatory bowel diseases (IBDs) are a heterogeneous group of disorders exhibited by two major phenotypic forms: Crohn's disease and ulcerative colitis. Although the aetiology of IBD is unknown, several factors coming from the adipose tissue and skeletal muscles, such as cytokines, adipokines and myokines, were suggested in the pathogenesis of ulcerative colitis; however, it has not been extensively studied whether voluntary exercise can ameliorate that disorder. We explored the effect of moderate exercise (i.e., voluntary wheel running) on the disease activity index (DAI), colonic blood flow (CBF), plasma irisin and adiponectin levels and real-time PCR expression of proinflammatory markers in mesenteric fat in mice with 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis fed a high-fat diet (HFD) compared to those on a standard chow diet (SD). Macroscopic and microscopic colitis in sedentary SD mice was accompanied by a significant fall in CBF, some increase in colonic tissue weight and a significant increase in the plasma levels of tumour necrosis factor-alpha (TNF-α), IL-6, monocyte chemotactic protein 1 (MCP-1) and IL-13 ( p < 0.05). In sedentary HFD mice, colonic lesions were aggravated, colonic tissue weight increased and the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels significantly increased. Simultaneously, a significant decrease in the plasma irisin and adiponectin levels was observed in comparison with SD mice ( p < 0.05). Exercise significantly decreased macroscopic and microscopic colitis, substantially increased CBF and attenuated the plasma TNF-α, IL-6, MCP-1, IL-1β and leptin levels while raising the plasma irisin and the plasma and WAT concentrations of adiponectin in HFD mice ( p < 0.05). We conclude that: (1) experimental colitis is exacerbated in HFD mice, possibly due to a fall in colonic microcirculation and an increase in the plasma and mesenteric fat content of proinflammatory biomarkers; and (2) voluntary physical activity can

Adiponectin and Its Receptors in the Ovary: Further Evidence for a Link between Obesity and Hyperandrogenism in Polycystic Ovary Syndrome

PubMed Central

Comim, Fabio V.; Hardy, Kate; Franks, Stephen

2013-01-01

Polycystic ovary syndrome (PCOS), characterized by ovarian androgen excess, is the commonest endocrine disorder in women. Obesity increases androgen synthesis, a phenomenon attributed to the accompanying hyperinsulinemia. Our hypothesis was that adipokines, fat cell-derived hormones, play a direct role in modulating ovarian androgen secretion. Therefore, the aims of this study were to explore the effects of adipokines (in particular, adiponectin) on ovarian steroidogenesis and compare the expression of adiponectin receptors in ovaries from women with and without PCO. Sections of archived human ovaries (nine from women with normal ovaries and 16 with PCOS, classified histologically, with reference to menstrual history and ultrasound) were analysed by quantitative morphometry and the proportion of positive-labelling cells compared. In addition, studies of androgen production in relation to adipokine function in primary bovine theca cell culture were also performed. A significantly lower proportion of theca cells expressed adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) in polycystic ovaries than in normal ovaries. In cultured theca cells, adiponectin suppressed androstenedione production and gene expression of LH receptor and key enzymes in the androgen synthesis pathway. Moreover, knockdown of genes for AdipoR1 and AdipoR2 was associated with increased androstenedione secretion by bovine theca cells. These results provide evidence for a direct link between fat cell metabolism and ovarian steroidogenesis, suggesting that disruption of adiponectin and/or its receptors plays a key role in pathogenesis of hyperandrogenism in PCOS. PMID:24260388

Appetite and energy balance signals from adipocytes

PubMed Central

Trayhurn, Paul; Bing, Chen

2006-01-01

Interest in the biology of white adipose tissue has risen markedly with the recent surge in obesity and its associated disorders. The tissue is no longer viewed simply as a vehicle for lipid storage; instead, it is recognized as a major endocrine and secretory organ. White adipocytes release a multiplicity of protein hormones, signals and factors, termed adipokines, with an extensive range of physiological actions. Foremost among these various adipokines is the cytokine-like hormone, leptin, which is synthesized predominantly in white fat. Leptin plays a critical role in the control of appetite and energy balance, with mutations in the genes encoding the hormone or its receptor leading to profound obesity in both rodents and man. Leptin regulates appetite primarily through an interaction with hypothalamic neuroendocrine pathways, inhibiting orexigenic peptides such as neuropeptide Y and orexin A, and stimulating anorexigenic peptides such as proopiomelanocortin. White fat also secretes several putative appetite-related adipokines, which include interleukin-6 and adiponectin, but whether these are indeed significant signals in the regulation of food intake has not been established. Through leptin and the other adipokines it is evident that adipose tissue communicates extensively with other organs and plays a pervasive role in metabolic homeostasis. PMID:16815801

Serum adiposity-induced biomarkers in obese and lean children with recently diagnosed autoimmune type 1 diabetes.

PubMed

Redondo, M J; Rodriguez, L M; Haymond, M W; Hampe, C S; Smith, E O; Balasubramanyam, A; Devaraj, S

2014-12-01

Obesity increases the risk of cardiovascular disease and diabetic complications in type 1 diabetes. Adipokines, which regulate obesity-induced inflammation, may contribute to this association. We compared serum adipokines and inflammatory cytokines in obese and lean children with new-onset autoimmune type 1 diabetes. We prospectively studied 32 lean and 18 obese children (age range: 2-18 yr) with new-onset autoimmune type 1 diabetes and followed them for up to 2 yr. Serum adipokines [leptin, total and high molecular weight (HMW) adiponectin, omentin, resistin, chemerin, visfatin], cytokines [interferon (IFN)-gamma, interleukin (IL)-10, IL-12, IL-6, IL-8, and tumor necrosis factor (TNF)-alpha] and C-reactive protein (CRP) were measured at a median of 7 wk after diagnosis (range: 3-16 wk). Lean children were 71.9% non-Hispanic White, 21.9% Hispanic, and 6.3% African-American, compared with 27.8, 55.6, and 16.7%, respectively, for obese children (p = 0.01). Compared with lean children, obese children had significantly higher serum leptin, visfatin, chemerin, TNF-alpha and CRP, and lower total adiponectin and omentin after adjustment for race/ethnicity and Tanner stage. African-American race was independently associated with higher leptin among youth ≥10 yr (p = 0.007). Leptin levels at onset positively correlated with hemoglobin A1c after 1-2 yr (p = 0.0001) independently of body mass index, race/ethnicity, and diabetes duration. Higher TNF-alpha was associated with obesity and female gender, after adjustment for race/ethnicity (p = 0.0003). Obese children with new-onset autoimmune type 1 diabetes have a proinflammatory profile of circulating adipokines and cytokines that may contribute to the development of cardiovascular disease and diabetic complications. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of established East Asian obesity-related loci on pediatric leptin levels highlights a neuronal influence on body weight regulation in Chinese children and adolescents: the BCAMS study.

PubMed

Fu, Junling; Li, Ge; Li, Lujiao; Yin, Jinhua; Cheng, Hong; Han, Lanwen; Zhang, Qian; Li, Naishi; Xiao, Xinhua; Grant, Struan F A; Li, Mingyao; Gao, Shan; Mi, Jie; Li, Ming

2017-11-07

Genome-wide association studies have identified multiple variants associated with adult obesity, mostly in European-ancestry populations. We aimed to systematically assess the contribution of key loci, which had been previously shown to be associated in East Asian adults, to childhood obesity, related adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and retinol binding protein 4) were evaluated in 3,506 Chinese children and adolescents aged 6-18. After correction for multiple comparisons, six of these SNPs were robustly associated with childhood obesity: FTO -rs1558902 ( P =5.6×10 -5 ), MC4R -rs2331841 ( P =4.4×10 -4 ), GNPDA2 -rs16858082 ( P = 3.4×10 -4 ), PCSK1 -rs261967 ( P = 0.001), SEC16B -rs516636 ( P = 0.004) and MAP2K5 -rs4776970 ( P = 0.004), with odds ratios ranging from 1.211 to 1.421; while ITIH4 -rs2535633 and BDNF -rs2030323 yielded nominal association with the same trait ( P < 0.05). Moreover, the risk alleles of six SNPs displayed significant ( P < 0.004) or nominal ( P < 0.05) association with leptin levels, namely at in/near PCSK1, MC4R, FTO, MAP2K5, GNPDA2 and BDNF plus their cumulative genetic score yielded stronger association with increased leptin levels ( P = 6.2×10 -11 ). Our results reveal that key obesity-associated loci previously reported in Europeans, but also associated with East Asian adults, are also associated with obesity and/or metabolic quantitative traits in Chinese children. These associations coincide with six brain-expressed loci that correlate with leptin levels, thus may point to an important neuronal influence on body weight regulation in the pediatric setting.

A prospective study of soluble receptor for advanced glycation end products and adipokines in association with pancreatic cancer in postmenopausal women.

PubMed

White, Donna L; Hoogeveen, Ron C; Chen, Liang; Richardson, Peter; Ravishankar, Milan; Shah, Preksha; Tinker, Lesley; Rohan, Thomas; Whitsel, Eric A; El-Serag, Hashem B; Jiao, Li

2018-05-01

Advanced glycation end products (AGEs) dysregulate adipokines and induce inflammation by binding to their adipocyte receptor (RAGE). Soluble RAGE (sRAGE) prevents AGEs/RAGE signaling. We performed a nested case-control study of the association between sRAGE, adipokines, and incident pancreatic cancer risk in the prospective Women's Health Initiative Study. We individually matched controls (n = 802) to cases (n = 472) on age, race, and blood draw date. We evaluated serum concentrations of sRAGE, adiponectin, leptin, monocyte chemotactic protein 1 (MCP1), and plasminogen activator inhibitor-1 (PAI1) using immunoassay. We used conditional logistic regression model to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for pancreatic cancer over biomarker quartiles (Q1-Q4). We used principal component analysis to create two composite biomarkers and performed a confirmatory factor analysis to examine the association between composite biomarker scores (CBS) and pancreatic cancer risk. Baseline serum sRAGE concentrations were inversely associated with pancreatic cancer risk (aOR Q4 vs. Q1  = 0.70, 95% CI: 0.50-0.99). High MCP1 (aOR Q4 vs. Q1  = 2.55, 95% CI: 1.41-4.61) and the higher CBS including MCP1, PAI1, and leptin (aOR Q4 vs. Q1  = 1.82, 95% CI = 1.04-3.18) were also associated with increased pancreatic cancer risk among women with BMI <25 kg/m 2 (P values for interaction <0.05). We found an inverse association between prediagnostic sRAGE concentrations and risk of incident pancreatic cancer in postmenopausal women. A proinflammatory CBS was associated with increased risk only in women with normal BMI. MCP1 was not modulated by sRAGE. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity.

PubMed

Min, Y; Lowy, C; Islam, S; Khan, F S; Swaminathan, R

2011-06-01

Plasma leptin and adiponectin, and membrane phospholipid fatty acid composition are implicated into the mechanism of insulin resistance but no clear pattern has emerged. Hence, this study examined these variables in subjects presenting to the diabetic clinic for a diagnostic glucose tolerance test. Body composition, glucose, glycated hemoglobin, insulin, leptin, adiponectin, and red cell and plasma phospholipid fatty acids were assessed from 42 normal and 28 impaired glucose tolerant subjects. Insulin sensitivity was determined by homeostatic model assessment. The plasma phosphatidylcholine fatty acid composition of the impaired glucose tolerant subjects was similar to that of normal subjects. However, the impaired glucose tolerant subjects had significantly lower linoleic (P<0.05), eicosapentaenoic (P<0.05) and docosahexaenoic (P<0.01) acids in the red cell phosphatidylcholine and phosphatidylethanolamine compared with the normal subjects. Moreover, red cell phosphatidylcholine docosahexaenoic acid correlated positively with adiponectin (r=0.290, P<0.05) but negatively with leptin (r=-0.252, P<0.05), insulin (r=-0.335, P<0.01) and insulin resistance (r=-0.322, P<0.01). Plasma triglycerides, leptin and glucose combined predicted about 60% of variation in insulin level whereas insulin was the only component that predicted the membrane fatty acids. We postulate that membrane phospholipids fatty acids have an indirect role in determining insulin concentration but insulin has a major role in determining membrane fatty acid composition.

The Effects of Leptin Replacement on Neural Plasticity

PubMed Central

Paz-Filho, Gilberto J.

2016-01-01

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function. PMID:26881138

The Effects of Leptin Replacement on Neural Plasticity.

PubMed

Paz-Filho, Gilberto J

2016-01-01

Leptin, an adipokine synthesized and secreted mainly by the adipose tissue, has multiple effects on the regulation of food intake, energy expenditure, and metabolism. Its recently-approved analogue, metreleptin, has been evaluated in clinical trials for the treatment of patients with leptin deficiency due to mutations in the leptin gene, lipodystrophy syndromes, and hypothalamic amenorrhea. In such patients, leptin replacement therapy has led to changes in brain structure and function in intra- and extrahypothalamic areas, including the hippocampus. Furthermore, in one of those patients, improvements in neurocognitive development have been observed. In addition to this evidence linking leptin to neural plasticity and function, observational studies evaluating leptin-sufficient humans have also demonstrated direct correlation between blood leptin levels and brain volume and inverse associations between circulating leptin and risk for the development of dementia. This review summarizes the evidence in the literature on the role of leptin in neural plasticity (in leptin-deficient and in leptin-sufficient individuals) and its effects on synaptic activity, glutamate receptor trafficking, neuronal morphology, neuronal development and survival, and microglial function.

Elevated Adiponectin Serum Levels in Women with Systemic Autoimmune Diseases

PubMed Central

Toussirot, Éric; Gaugler, Béatrice; Bouhaddi, Malika; Nguyen, Nhu Uyen; Saas, Philippe; Dumoulin, Gilles

2010-01-01

Adipose tissue produces a wide range of proteins that may influence the immune system. In this study, we assessed the serum levels of leptin, adiponectin, and ghrelin, in association with the measurements of body composition, in 15 female patients with various autoimmune diseases (systemic lupus erythematosus, primary Sjögren's syndrome, sarcoidosis, mixed connective tissue disease, vasculitis, CREST syndrome, and polymyositis) and in 15 healthy female controls. There were no statistically significant differences between the patients and controls with regard to serum leptin, serum ghrelin, global fat mass, adiposity, and fat mass in the android or gynoid regions, whereas serum adiponectin levels were higher in patients than controls (16.3 ± 1.6 μg/mL versus 9.7 ± 0.6 μg/mL; P = .01). As adiponectin is known to exhibit potent anti-inflammatory properties, a high adiponectinemia in patients with systemic autoimmune disease may mitigate the inflammatory response. However, the precise consequences of these elevated serum adiponectin levels on the metabolic syndrome development and atherosclerotic cardiovascular risk in this patient population still needs to be determined. PMID:21234350

Leptin in joint and bone diseases: new insights.

PubMed

Scotece, M; Conde, J; Lopez, V; Lago, F; Pino, J; Gomez-Reino, J J; Gualillo, O

2013-01-01

Leptin is an adipokine with pleiotropic actions that regulates food intake, energy metabolism, inflammation and immunity, and also participates in the complex mechanism that regulates skeleton biology, both at bone and cartilage level. Leptin is increased in obesity and contributes to the "low-grade inflammatory state" of obese subjects causing a cluster of metabolic aberrations that affects joints and bone. In this review, we report the most recent research advances about the role of leptin in bone and cartilage function and its implication in inflammatory and degenerative joint diseases, such as osteoarthritis, rheumatoid arthritis and osteoporosis.

Increased Body Adiposity and Serum Leptin Concentrations in Very Long-Term Adult Male Survivors of Childhood Acute Lymphoblastic Leukemia.

PubMed

Jahnukainen, Kirsi; Heikkinen, Risto; Henriksson, Markus; Andersson, Sture; Ivaska, Kaisa K; Puukko-Viertomies, Leena-Riitta; Mäkitie, Outi

2015-01-01

We evaluated the body composition and its association with hypogonadism in adult male long-term acute lymphoblastic leukemia (ALL) survivors. The cohort included 49 long-term male ALL survivors and 55 age-matched healthy controls. Fat and lean mass was assessed by dual-energy X-ray absorptiometry; blood biochemistry was obtained for adipokines and testicular endocrine markers. As compared with controls, the ALL survivors (median age 29 years, range 25-38), assessed 10-28 years after ALL diagnosis, had higher percentages of body (p < 0.05) and trunk fat mass (p < 0.05), and a lower body lean mass (p < 0.001). Survivors had significantly higher levels of leptin and adiponectin and lower levels of insulin-like growth factor-binding protein 3. Body fat mass and percent fat mass correlated with serum leptin and sex hormone-binding globulin (SHBG) levels. Altogether, 15% of the ALL survivors and 9% of age-matched controls were obese (BMI ≥ 30). Obese survivors more often had hypogonadism, had received testicular irradiation, and needed testosterone replacement therapy compared to nonobese survivors. At young adulthood, long-term male ALL survivors have significantly increased body adiposity despite normal weight and BMI. Potential indicators of increased adiposity included high leptin and low SHBG levels. Serum testicular endocrine markers did not correlate with body adiposity. © 2015 S. Karger AG, Basel.

Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.

PubMed

Fuggle, N R; Westbury, L D; Syddall, H E; Duggal, N A; Shaw, S C; Maslin, K; Dennison, E M; Lord, J; Cooper, C

2018-05-28

Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1β, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses. In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the

Tomato juice supplementation in young women reduces inflammatory adipokine levels independently of body fat reduction.

PubMed

Li, Yu-Fen; Chang, Ya-Yuan; Huang, Hui-Chi; Wu, Yi-Chen; Yang, Mei-Due; Chao, Pei-Min

2015-05-01

Lycopene is a carotene and phytochemical known to protect against metabolic diseases. It is found in red fruits and vegetables, predominantly tomatoes. This study aimed to show the supplementation effect of tomato juice on indices associated with metabolic health and adipokine profiles in generally healthy people. A total of 30 young females (20- to 30-years-old) with a body mass index (BMI) ≥ 20 were recruited, of whom 25 completed the entire study. The subjects continued with their normal diet and exercise schedule, but were given 280 mL of tomato juice (containing 32.5 mg of lycopene) daily for 2 mo. Metabolic indices, including anthropometric data and serum levels of glucose, lipids, adipokines, lycopene, and antioxidants, were compared pre- and postintervention. Tomato juice supplementation significantly reduced body weight, body fat, waist circumference, BMI, and serum levels of cholesterol, monocyte chemoattractant protein-1 (MCP-1), and thiobarbituric reactive substances, while significantly increasing serum levels of adiponectin, triglyceride, and lycopene. When subjects were stratified by body fat change, i.e., reduction or non-reduction (including increase or no change), the tomato juice-induced reduction in waist circumference, serum cholesterol, and MCP-1 levels and increase in adiponectin and lycopene levels were seen in both subgroups. The changes in waist circumference, cholesterol, MCP-1, and adiponectin levels remained significant after adjusting for each covariable individually, with the exception of lycopene. These results show that daily tomato juice supplementation reduces waist circumference, as well as serum cholesterol and inflammatory adipokine levels in young healthy women and that these effects are unrelated to body fat changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Effect of hormonal and energy-related factors on plasma adiponectin in transition dairy cows.

PubMed

Krumm, C S; Giesy, S L; Caixeta, L S; Butler, W R; Sauerwein, H; Kim, J W; Boisclair, Y R

2017-11-01

In transition dairy cows, plasma levels of the insulin-sensitizing hormone adiponectin fall to a nadir at parturition and recover in early lactation. The transition period is also characterized by rapid changes in metabolic and hormonal factors implicated in other species as positive regulators of adiponectin production (i.e., negative energy balance, lipid mobilization) and others as negative regulators (i.e., reduced leptin and insulin and increased growth hormone and plasma fatty acids). To assess the role of onset of negative energy balance and lipid mobilization after parturition, dairy cows were either milked thrice daily (lactating) or never milked (nonlactating) for up to 4 wk after parturition. Plasma adiponectin was 21% higher across time in nonlactating than lactating cows. Moreover, nonlactating cows recovered plasma adiponectin at similar rates as lactating cows even though they failed to lose body condition. Next, we assessed the ability of individual hormones to alter plasma adiponectin in transition dairy cows. In the first experiment, dairy cows received a constant 96-h intravenous infusion of either saline or recombinant human leptin starting on d 8 of lactation. In the second experiment, dairy cows were studied in late pregnancy (LP, starting on prepartum d -31) and again in early lactation (EL, starting on d 7 postpartum) during a 66-h period of basal sampling followed by 48 h of hyperinsulinemic-euglycemia. In the third experiment, cows were studied either in LP (starting on d -40 prepartum) or EL (starting on d 7 postpartum) during a 3-h period of basal sampling followed by 5 d of bovine somatotropin treatment. Plasma adiponectin was reduced by an average of 21% in EL relative to LP in these experiments, but neither leptin, insulin, or growth hormone treatment affected adiponectin in LP or EL. Finally, the possibility that plasma fatty acids repress plasma adiponectin was evaluated by intravenous infusion of a lipid emulsion in nonpregnant

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients.

PubMed

Jacobo-Cejudo, M Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E; Harbige, Laurence S

2017-06-03

Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n- 3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n- 3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n- 3 PUFA intake was calculated in g/day. Waist circumference and blood glucose showed significant reductions in the FOG group ( p = 0.001 and p = 0.011, respectively). Hb1Ac ( p = 0.009 and p = 0.004), leptin ( p < 0.000 and p < 0.000), and leptin/adiponectin ratio ( p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols ( p = 0.002) and atherogenic index ( p = 0.031); in contrast, the PG group had increased total cholesterol ( p < 0.000), non-HDL cholesterol ( p < 0.000), and atherogenic index ( p = 0.017). We found a beneficial effect of n- 3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups.

Effect of n-3 Polyunsaturated Fatty Acid Supplementation on Metabolic and Inflammatory Biomarkers in Type 2 Diabetes Mellitus Patients

PubMed Central

Jacobo-Cejudo, M. Gorety; Valdés-Ramos, Roxana; Guadarrama-López, Ana L.; Pardo-Morales, Rosa-Virgen; Martínez-Carrillo, Beatriz E.; Harbige, Laurence S.

2017-01-01

Background: Type 2 diabetes mellitus (T2DM) is accompanied by chronic low-grade inflammation, with an imbalance in the secretion of adipokines and, worsening insulin resistance. Supplementation with n-3 PUFA in T2DM decreases inflammatory markers, the purpose of the study was to investigate the effect of n-3 PUFA supplementation on adipokines, metabolic control, and lipid profile in T2DM Mexican adults. Methods: In a randomized, single-blind, placebo-controlled pilot study, 54 patients with T2DM received 520 mg of DHA + EPA-enriched fish-oil (FOG) or a placebo (PG) daily. Baseline and 24-week anthropometric and biochemical measurements included glucose, insulin, glycosylated hemoglobin (Hb1Ac), leptin, adiponectin, resistin, and lipid profile; n-3 PUFA intake was calculated in g/day. Results: Waist circumference and blood glucose showed significant reductions in the FOG group (p = 0.001 and p = 0.011, respectively). Hb1Ac (p = 0.009 and p = 0.004), leptin (p < 0.000 and p < 0.000), and leptin/adiponectin ratio (p < 0.000 and p < 0.000) decreased significantly in both groups after 24 weeks (FOG and PG respectively). Serum resistin (FOG p < 0.000 and PG p = 0.001), insulin (FOG p < 0.000 and PG p < 0.000), and HOMA-IR (FOG p = 0.000 and PG p < 0.000) increased significantly in both groups. FOG had an overall improvement in the lipid profile with a significant decrease in triacylgycerols (p = 0.002) and atherogenic index (p = 0.031); in contrast, the PG group had increased total cholesterol (p < 0.000), non-HDL cholesterol (p < 0.000), and atherogenic index (p = 0.017). Conclusions: We found a beneficial effect of n-3 PUFA supplementation on waist circumference, glucose, Hb1Ac, leptin, leptin/adiponectin ratio, and lipid profile, without significant changes in adiponectin, and increases in resistin, insulin, and HOMA-IR in both groups. PMID:28587203

Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome.

PubMed

Broedl, Uli C; Lehrke, Michael; Fleischer-Brielmaier, Elisabeth; Tietz, Anne B; Nagel, Jutta M; Göke, Burkhard; Lohse, Peter; Parhofer, Klaus G

2006-05-15

Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T) in perfect linkage disequilibrium (r2 = 1) with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.

Effect of ezetimibe on plasma adipokines: a systematic review and meta-analysis.

PubMed

Dolezelova, Eva; Stein, Evan; Derosa, Giuseppe; Maffioli, Pamela; Nachtigal, Petr; Sahebkar, Amirhossein

2017-07-01

Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials. A systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI). Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy. The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect. © 2017 The British Pharmacological Society.

Chemerin and Adiponectin Contribute Reciprocally to Metabolic Syndrome

PubMed Central

Chu, Sang Hui; Lee, Mi Kyung; Ahn, Ki Yong; Im, Jee-Aee; Park, Min Soo; Lee, Duk-Chul; Jeon, Justin Y.; Lee, Ji Won

2012-01-01

Obesity and metabolic syndrome (MetS) are considered chronic inflammatory states. Chemerin, a novel adipokine, may play an important role in linking MetS and inflammation. We investigated the association of chemerin with inflammatory markers and with characteristics of MetS in apparently healthy overweight and obese adults. We studied 92 adults; 59 men and 33 women whose average body mass index (BMI) was 28.15±5.08 kg/m2. Anthropometric parameters, insulin resistance indices, lipid profiles, and inflammatory markers including high sensitivity C-reactive protein (hsCRP), pentraxin 3 (PTX3), adiponectin, and chemerin were measured. Controlling for age, gender, and BMI, serum chemerin level was positively correlated with body fat and serum triglyceride, and negatively correlated with adiponectin and high density lipoprotein cholesterol (HDL- C), and was not correlated with altered hsCRP or PTX3 levels. Among the low, moderate and high chemerin groups, high chemerin individuals are more likely to have lower HDL-C. Conversely, individuals in the low adiponectin group are more likely to have lower HDL-C and show more MetS phenotypic traits than moderate and high adiponectin subjects. To determine the relationships of chemerin and adiponectin to MetS and its components, participants were stratified into four groups based on their chemerin and adiponectin levels (high chemerin/high adiponectin, high chemerin/low adiponectin, low chemerin/high adiponectin, or low chemerin/low adiponectin). Participants who were in the high chemerin/low adiponectin group more likely to have dyslipidemia and MetS (OR: 5.79, 95% CI:1.00–33.70) compared to the other three group. Our findings suggest that chemerin and adiponectin may reciprocally participate in the development of MetS. PMID:22509348

Adipokines and Insulin Resistance According to Characteristics of Pregnant Women with Gestational Diabetes Mellitus.

PubMed

Jeon, Eon Ju; Hong, Seong Yeon; Lee, Ji Hyun

2017-12-01

The aim of this study was to evaluate adipokines concentration and insulin resistance according to maternal age or obesity at pregnancy and weight change at diagnosed gestational diabetes mellitus (GDM) in pregnant women with GDM. This study included 57 pregnant women who were diagnosed with GDM at 24 to 28 weeks of gestation. The subjects were classified into two or three groups according to pre-pregnancy body mass index (BMI, <25 kg/m² vs. ≥25 kg/m²), maternal age at pregnancy (<35 years old vs. ≥35 years old), and weight change during pregnancy at screening for GDM (weight change below, within, and in excess of the recommended range). They were respectively compared in each group. Leptin, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA2-%B were increased in the group with pre-pregnancy BMI ≥25 kg/m². Leptin and HOMA-IR were positively correlated with BMI both before pregnancy and at screening for GDM. There were no significant correlations between HOMA-IR and adipokines. HOMA-IR showed positive correlation with HOMA2-%B and negative correlation with HOMA2-%S. Leptin and HOMA-IR at diagnosed GDM were increased in the GDM patients with obesity before pregnancy. They were positively correlated with BMI both before pregnancy and at screening for GDM. The effect of maternal age at pregnancy and weight change during pregnancy at GDM screening on adipokines and insulin resistance might be less pronounced than the effect of maternal obesity. Copyright © 2017 Korean Diabetes Association

Prolonged fasting and the effects on biomarkers of inflammation and on adipokines in healthy lean men.

PubMed

van Herpen, N A; Sell, H; Eckel, J; Schrauwen, P; Mensink, R P

2013-05-01

Obesity and insulin resistance are associated with low-grade systemic inflammation, which is related to increased concentrations of plasma FFAs, glucose, or insulin. Prolonged fasting induces insulin resistance due to elevated plasma FFAs, but is not accompanied by hyperinsulinemia or hyperglycemia. This makes it possible to study effects of physiologically increased FFA concentrations on inflammatory markers, when insulin and glucose concentrations are not increased. In random order, 10 healthy young lean men (mean BMI: 22.8 kg/m2) were fasted or fed in energy balance for 60 h with a 2-week wash-out period. Subjects stayed in a respiration chamber during the 60-h periods. Blood samples were taken after 12, 36, and 60 h. Then, a hyperinsulinemic-euglycemic clamp was performed.Fasting decreased insulin sensitivity by 45% and increased FFA concentrations 5-fold. Fasting did not change concentrations of the inflammatory cytokines TNF-α, IL-1β, IL-6 and IL-8, or of hs-CRP. Effects on vascular endothelial growth factor (VEGF)--which may positively relate to insulin resistance, and on chemerin and leptin--adipokines related to obesity, and obesity-related pathologies, were also studied. At t=60 h, VEGF concentrations were significantly increased during the fasted period (p<0.05). At the same time point, chemerin (p<0.01) and leptin (p<0.01) were significantly decreased after fasting. For leptin, this decrease was also significant after 36 h (p<0.01). Adiponectin levels remained unchanged. In healthy young lean men, fasting-induced increases in FFAs leading to insulin resistance do not cause changes in concentrations of the inflammatory cytokines. VEGF concentrations increased and those of chemerin decreased. © Georg Thieme Verlag KG Stuttgart · New York.

A prospective study of gynecological cancer risk in relation to adiposity factors: cumulative incidence and association with plasma adipokine levels.

PubMed

Wu, Meei-Maan; Chen, Hui-Chi; Chen, Chi-Ling; You, San-Lin; Cheng, Wen-Fang; Chen, Chi-An; Lee, Te-Chang; Chen, Chien-Jen

2014-01-01

Associations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers. Totally, 11,258 women, aged 30-65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991-1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government's National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels. There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95%  = 4.83-53.00), high triglyceride levels (HR = 2.58, 95% = 1.28-5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95%  = 1.08-3.38) were associated with increased UCC risk. High body mass index (BMI ≥ 27 kg/m(2), HR = 2.90, 95%  = 1.30-6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates. We provided evidence that alcohol intake, high triglyceride levels and long

Leptin Modulates Mitochondrial Function, Dynamics and Biogenesis in MCF-7 Cells.

PubMed

Blanquer-Rosselló, M Mar; Santandreu, Francisca M; Oliver, Jordi; Roca, Pilar; Valle, Adamo

2015-09-01

The adipokine leptin, known for its key role in the control of energy metabolism, has been shown to be involved in both normal and tumoral mammary growth. One of the hallmarks of cancer is an alteration of tumor metabolism since cancerous cells must rewire metabolism to satisfy the demands of growth and proliferation. Considering the sensibility of breast cancer cells to leptin, the objective of this study was to explore the effects of this adipokine on their metabolism. To this aim, we treated the MCF-7 breast cancer cell line with 50 ng/mL leptin and analyzed several features related to cellular and mitochondrial metabolism. As a result, leptin increased cell proliferation, shifted ATP production from glycolysis to mitochondria and decreased the levels of the glycolytic end-product lactate. We observed an improvement in ADP-dependent oxygen consumption and an amelioration of oxidative stress without changes in total mitochondrial mass or specific oxidative phosphorylation (OXPHOS) complexes. Furthermore, RT-PCR and western blot showed an up-regulation for genes and proteins related to biogenesis and mitochondrial dynamics. This expression signature, together with an increased mitophagy observed by confocal microscopy suggests that leptin may improve mitochondrial quality and function. Taken together, our results propose that leptin may improve bioenergetic efficiency by avoiding the production of reactive oxygen species (ROS) and conferring benefits for growth and survival of MCF-7 breast cancer cells. © 2015 Wiley Periodicals, Inc.

Potential beneficial effect of some adipokines positively correlated with the adipose tissue content on the cardiovascular system.

PubMed

Sawicka, Magdalena; Janowska, Joanna; Chudek, Jerzy

2016-11-01

Obesity is a risk factor of cardiovascular diseases. However, in the case of heart failure, obese and overweight patients have a more favourable prognosis compared to patients who have a normal body weight. This phenomenon is referred to as the "obesity paradox," and it is explained by, among others, a positive effect of adipokines produced by adipose tissue, particularly by the tissue located in the direct vicinity of the heart and blood vessels. The favourable effect on the cardiovascular system is mostly associated with adiponectin and omentin, but the levels of these substances are reduced in obese patients. Among the adipokines which levels are positively correlated with the adipose tissue content, favourable activity is demonstrated by apelin, progranulin, chemerin, TNF-α (tumour necrosis factor-)α, CTRP-3 (C1q/tumour necrosis factor (TNF) related protein), leptin, visfatin and vaspin. This activity is associated with the promotion of regeneration processes in the damaged myocardium, formation of new blood vessels, reduction of the afterload, improvement of metabolic processes in cardiomyocytes and myocardial contractile function, inhibition of apoptosis and fibrosis of the myocardium, as well as anti-inflammatory and anti-atheromatous effects. The potential use of these properties in the treatment of heart failure and ischaemic heart disease, as well as in pulmonary hypertension, arterial hypertension and the limitation of the loss of cardiomyocytes during cardioplegia-requiring cardiosurgical procedures, is studied. The most advanced studies focus on analogues of apelin and progranulin. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Association of ADIPOQ, leptin, LEPR, and resistin polymorphisms with obesity parameters in Hammam Sousse Sahloul Heart Study.

PubMed

Zayani, Nesrine; Omezzine, Asma; Boumaiza, Imen; Achour, Ons; Rebhi, Lamia; Rejeb, Jihen; Ben Rejeb, Nabila; Ben Abdelaziz, Ahmed; Bouslama, Ali

2017-11-01

Adipose tissue is an important endocrine organ that secretes a number of adipokines, such as adiponectin (ADIPOQ), leptin (LEP), leptin receptor (LEPR), and resistin (RETN) which may be implicated in obesity. Some adipokines' polymorphisms of genes might influence their concentrations and/or activities. Our aim was to study the relationship between seven SNPs in ADIPOQ (+45T

Attenuated improvements in adiponectin and fat loss characterize type 2 diabetes non-remission status after bariatric surgery.

PubMed

Malin, S K; Bena, J; Abood, B; Pothier, C E; Bhatt, D L; Nissen, S; Brethauer, S A; Schauer, P R; Kirwan, J P; Kashyap, S R

2014-12-01

To identify the metabolic determinants of type 2 diabetes non-remission status after bariatric surgery at 12 and 24 months. A total of 40 adults [mean ± sd body mass index 36 ± 3 kg/m(2) , age 48 ± 9 years, glycated haemoglobin (HbA1c) 9.7 ± 2%) undergoing bariatric surgery [Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG)] were enrolled in the present study, the Surgical Treatment and Medication Potentially Eradicate Diabetes Efficiently (STAMPEDE) trial. Type 2 diabetes remission was defined as HbA1c <6.5% and fasting glucose <126 mg/dl (i.e. <7 mmol/l) without antidiabetic medication. Indices of insulin secretion and sensitivity were calculated from plasma glucose, insulin and C-peptide values during a 120-min mixed-meal tolerance test. Body fat, incretins (glucagon-like polypeptide-1, gastric inhibitory peptide, ghrelin) and adipokines [adiponectin, leptin, tumour necrosis factor-α, high-sensitivity C-reactive protein (hs-CRP)] were also assessed. At 24 months, 37 patients had available follow-up data (RYGB, n = 18; SG, n = 19). Bariatric surgery induced type 2 diabetes remission rates of 40 and 27% at 12 and 24 months, respectively. Total fat/abdominal fat loss, insulin secretion, insulin sensitivity and β-cell function (C-peptide0-120 /glucose0-120 × Matsuda index) improved more in those with remission at 12 and 24 months than in those without remission. Incretin levels were unrelated to type 2 diabetes remission, but, compared with those without remission, hs-CRP decreased and adiponectin increased more in those with remission. Only baseline adiponectin level predicted lower HbA1c levels at 12 and 24 months, and elevated adiponectin correlated with enhanced β-cell function, lower triglyceride levels and fat loss. Smaller rises in adiponectin level, a mediator of insulin action and adipose mass, characterize type 2 diabetes non-remission up to 2 years after bariatric surgery. Adjunctive strategies promoting greater fat loss and/or raising

Could there be a fine-tuning role for brain-derived adipokines in the regulation of bodyweight and prevention of obesity?

PubMed Central

Brown, Russell E.

2008-01-01

Obesity is one of the most prevalent medical conditions, often associated with several negative stereotypes. Although it is true that weight gain occurs when food intake exceeds energy expenditure, it is important to note that even a 1% mismatch between the two can lead to a substantial weight gain after only a few years. Further, the body appears to balance energy metabolism via an endogenous lipostatic loop in which adipose stores send hormonal signals (e.g. adipokines such as leptin) to the hypothalamus in order to reduce appetite and increase energy expenditure. However, the brain is also a novel site of expression of many of these adipokine genes. This led to the hypothesis that hypothalamic-derived adipokines might also be involved in bodyweight regulation by exerting some effect on the control of appetite or hypothalamic function. When RNA interference (RNAi) was used to specifically silence adipokine gene expression in various in vitro models, this led to increases in cell death, modification of the expression of key signaling genes (i.e. suppressor of cytokine signaling-3; SOCS-3), and modulation of the activation of cellular energy sensors (i.e. adenosine monophosphate-activated protein kinase; AMPK). Subsequently, when RNAi was used to inhibit the expression of brain-derived leptin in adult rats this resulted in minor increases in weight gain in addition to modifying the expression of other adipokine genes (eg. resistin). In summary, although adipokines secreted by adipose tissue appear to the main regulator of lipostatic loop, this review shows that the fine tuning that is required to maintain a stable bodyweight by this system might be accomplished by hypothalamic-derived adipokines. Perturbations in this central adipokine system could lead to alterations in normal hypothalamic function which leads to unintended weight gain. PMID:19148319

Proinflammatory adipokine leptin mediates disinfection byproduct bromodichloromethane-induced early steatohepatitic injury in obesity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Das, Suvarthi; Kumar, Ashutosh; Seth, Ratanesh Kumar

Today's developed world faces a major public health challenge in the rise in the obese population and the increased incidence in fatty liver disease. There is a strong association among diet induced obesity, fatty liver disease and development of nonalcoholic steatohepatitis but the environmental link to disease progression remains unclear. Here we demonstrate that in obesity, early steatohepatitic lesions induced by the water disinfection byproduct bromodichloromethane are mediated by increased oxidative stress and leptin which act in synchrony to potentiate disease progression. Low acute exposure to bromodichloromethane (BDCM), in diet-induced obesity produced oxidative stress as shown by increased lipid peroxidation,more » protein free radical and nitrotyrosine formation and elevated leptin levels. Exposed obese mice showed histopathological signs of early steatohepatitic injury and necrosis. Spontaneous knockout mice for leptin or systemic leptin receptor knockout mice had significantly decreased oxidative stress and TNF-α levels. Co-incubation of leptin and BDCM caused Kupffer cell activation as shown by increased MCP-1 release and NADPH oxidase membrane assembly, a phenomenon that was decreased in Kupffer cells isolated from leptin receptor knockout mice. In obese mice that were BDCM-exposed, livers showed a significant increase in Kupffer cell activation marker CD68 and, increased necrosis as assessed by levels of isocitrate dehydrogenase, events that were decreased in the absence of leptin or its receptor. In conclusion, our results show that exposure to the disinfection byproduct BDCM in diet-induced obesity augments steatohepatitic injury by potentiating the effects of leptin on oxidative stress, Kupffer cell activation and cell death in the liver. - Highlights: ► BDCM acute exposure sensitizes liver to increased free radical stress in obesity. ► BDCM-induced higher leptin contributes to early steatohepatitic lesions. ► Increased leptin mediates

Second trimester amniotic fluid adiponectin level is affected by maternal tobacco exposure, insulin, and PAPP-A level.

PubMed

De Leon-Luis, Juan; Perez, Ricardo; Pintado Recarte, Pilar; Avellaneda Fernandez, Alfredo; Romero Roman, Carlos; Antolin Alvarado, Eugenia; Ortiz-Quintana, Luis; Izquierdo Martinez, Maravillas

2012-12-01

Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. The objectives of the present study were to determine the amniotic fluid (AF) concentration of adiponectin during the second trimester of pregnancy and to demonstrate its association with maternal and fetal variables and AF concentrations of insulin, leptin, and pregnancy-associated-plasma-protein A (PAPP-A). We performed a cross-sectional study of 222 pregnant women who underwent amniocentesis at 15-18 weeks for genetic reasons. No malformation or chromosomal disorder was found in the newborn after birth. AF adiponectin, leptin, PAPP-A, and insulin concentrations were measured using commercially available assays. All maternal, fetal, and biochemical variables were studied using univariate and multivariate linear regression analysis to determine their association with the AF concentration of adiponectin. Adiponectin concentration was negatively correlated with maternal smoking status (β=-5.208; p<0.001) and positively correlated with levels of insulin (β=0.621; p=0.002) and PAPP-A (β=40.150; p<0.001). Non-significant correlations were found between adiponectin concentration and maternal age, maternal body mass index, gestational age at amniocentesis, fetal gender, and AF level of leptin. These findings suggest that the fetus and its membrane adipocytokines, in relationship with maternal and other fetal variables, play a dynamic role in the regulation of energy and oxidative stress homeostasis due to its insulin-sensitizing and antiatherosclerotic effects. The association of these molecules with maternal tobacco consumption during pregnancy could have perinatal implications. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Impact of risperidone on leptin and insulin in children and adolescents with autistic spectrum disorders.

PubMed

Srisawasdi, Pornpen; Vanwong, Natchaya; Hongkaew, Yaowaluck; Puangpetch, Apichaya; Vanavanan, Somlak; Intachak, Boontarika; Ngamsamut, Nattawat; Limsila, Penkhae; Sukasem, Chonlaphat; Kroll, Martin H

2017-08-01

To evaluate the influence of dose and duration of risperidone treatment on cardiovascular and diabetes risk biomarkers in children and adolescents with autistic spectrum disorders (ASDs). In this cross-sectional analysis, a total of 168 ASDs patients (89% male) treated with a risperidone-based regimen for ≥12months were included. Blood samples were analyzed for glucose and lipid metabolic markers, adiponectin, leptin, prolactin, cortisol and high sensitive C-reactive protein. The mean concentrations of glucose, insulin, prolactin and leptin and HOMA-IR significantly rose with risperidone dosage (all P<0.025), but those of adiponectin and cortisol did not. Using regression analysis, insulin, leptin, prolactin and glucose concentrations and HOMA-IR show significant association with dosage. None of the markers except adiponectin showed dependence on duration of treatment. However, insulin and leptin concentrations and HOMA-IR clearly increased with increasing both dosage and duration. Dosage and duration of treatment had minimal effect on standard lipid profile and lipoprotein subclasses. Risperidone treatment disturbed glucose homeostasis and endocrine regulation (particularly leptin) in children and adolescents with ASDs, in a dose- and duration-dependent manner, being suggestive of leptin and insulin resistance mechanisms. Metabolic adverse effects, especially development of type 2 diabetes mellitus should be closely monitored, particularly in individuals receiving high doses and/or long-term risperidone treatment. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

The thymoprotective function of leptin is indirectly mediated via suppression of obesity.

PubMed

Sreenivasan, Jayasree; Schlenner, Susan; Franckaert, Dean; Dooley, James; Liston, Adrian

2015-09-01

Leptin is an adipokine that regulates metabolism and plays an important role as a neuroendocrine hormone. Leptin mediates these functions via the leptin receptor, and deficiency in either leptin or its receptor leads to obesity in humans and mice. Leptin has far reaching effects on the immune system, as observed in obese mice, which display decreased thymic function and increased inflammatory responses. With expression of the leptin receptor on T cells and supporting thymic epithelium, aberrant signalling through the leptin receptor has been thought to be the direct cause of thymic involution in obese mice. Here, we demonstrate that the absence of leptin receptor on either thymic epithelial cells or T cells does not lead to the loss of thymic function, demonstrating that the thymoprotective effect of leptin is mediated by obesity suppression rather than direct signalling to the cellular components of the thymus. © 2015 John Wiley & Sons Ltd.

Comparative measurement of ghrelin, leptin, adiponectin, EGF and IGF-1 in breast milk of mothers with overweight/obese and normal-weight infants.

PubMed

Khodabakhshi, A; Ghayour-Mobarhan, M; Rooki, H; Vakili, R; Hashemy, S-I; Mirhafez, S R; Shakeri, M-T; Kashanifar, R; Pourbafarani, R; Mirzaei, H; Dahri, M; Mazidi, M; Ferns, G; Safarian, M

2015-05-01

Obese infants are more susceptible to develop adulthood obesity and its related comorbidities. Previous studies have shown the presence of hormones and growth factors in maternal breast milk that may influence infant adiposity. The aim of this study was to investigate differences in concentrations of three hormones and two growth factors in the breast milk of mothers with obese and non-obese infants. In this cross-sectional study, 40 mothers with overweight or obese infants (weight for length percentile >97) and 40 age-matched mothers with normal-weight infant (-10 < weight for length percentile < 85) who were between 2 and 5 months of age were enrolled. Anthropometric indices of infants and mothers were measured by routine methods. Breast milk concentrations of ghrelin and adiponectin, leptin, epithelial growth factor (EGF) and insulin-like growth factor-1 (IGF-1) were measured using enzyme-linked immunosorbent assay methods. The mean breast milk concentration of ghrelin was higher in mothers with normal-weight infants, 137.50 pg/ml, than in mothers with obese infants, 132.00 pg/ml (P=0.001). This was also true regarding the concentration of EGF in mothers with (0/04 ng/ml) and without (0/038 ng/ml) normal-weight infants (P=0.01). No significant differences were observed in concentrations of leptin, adiponectin and IGF-1 between two groups (P > 0.05). There was also a significant positive correlation between EGF and ghrelin in both groups. This study revealed that there was a correlation between ghrelin and EGF level in breast milk of mothers with obese and non-obese infants, suggesting a possible regulatory effect of these two hormones on weight in infants.

Characteristics and potential functions of human milk adiponectin.

PubMed

Newburg, David S; Woo, Jessica G; Morrow, Ardythe L

2010-02-01

Adiponectin is a protein hormone produced by adipose tissue, whose circulating levels are inversely related to adiposity and inflammation. Adiponectin circulates as oligomers, from the low-molecular-weight trimer to the high-molecular-weight octodecamer (18 mer). Each oligomer has distinct biological activities, which include enhancement of insulin sensitivity and metabolic control and suppression of inflammation. Adiponectin occurs in human milk at higher concentrations than leptin. The adiponectin in human milk is almost entirely of the high-molecular-weight form, the form with the highest activity in controlling many types of metabolic processes. Human adiponectin fed to infant mice is transported across the intestinal mucosa into the serum. An inverse relationship between adiponectin levels in milk and adiposity (weight-for-height) of the breast-fed infant was observed and could be due to modulation of infant metabolism by milk adiponectin and may be related to the observed protection against obesity by breast-feeding. Human milk may be a medium whereby the hormonal milieu (in response to internal factors and the environment) of the mother can be used to communicate with the breast-fed infant to modify infant metabolic processes. Transmission of information from mother to infant through milk may allow adaptation to fluctuating environmental conditions. Copyright 2010 Mosby, Inc. All rights reserved.

Novel regulatory mechanisms for generation of the soluble leptin receptor: implications for leptin action.

PubMed

Schaab, Michael; Kausch, Henriette; Klammt, Juergen; Nowicki, Marcin; Anderegg, Ulf; Gebhardt, Rolf; Rose-John, Stefan; Scheller, Juergen; Thiery, Joachim; Kratzsch, Juergen

2012-01-01

The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity. To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding. Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases.

Novel Regulatory Mechanisms for Generation of the Soluble Leptin Receptor: Implications for Leptin Action

PubMed Central

Schaab, Michael; Kausch, Henriette; Klammt, Juergen; Nowicki, Marcin; Anderegg, Ulf; Gebhardt, Rolf; Rose-John, Stefan; Scheller, Juergen; Thiery, Joachim; Kratzsch, Juergen

2012-01-01

Background The adipokine leptin realizes signal transduction via four different membrane-anchored leptin receptor (Ob-R) isoforms in humans. However, the amount of functionally active Ob-R is affected by constitutive shedding of the extracellular domain via a so far unknown mechanism. The product of the cleavage process the so-called soluble leptin receptor (sOb-R) is the main binding protein for leptin in human blood and modulates its bioavailability. sOb-R levels are differentially regulated in metabolic disorders like type 1 diabetes mellitus or obesity and can, therefore, enhance or reduce leptin sensitivity. Methodology/Principal Findings To describe mechanisms of Ob-R cleavage and to investigate the functional significance of differential sOb-R levels we established a model of HEK293 cells transiently transfected with different human Ob-R isoforms. Using siRNA knockdown experiments we identified ADAM10 (A Disintegrin And Metalloproteinase 10) as a major protease for constitutive and activated Ob-R cleavage. Additionally, the induction of lipotoxicity and apoptosis led to enhanced shedding shown by increased levels of the soluble leptin receptor (sOb-R) in cell supernatants. Conversely, high leptin concentrations and ER stress reduced sOb-R levels. Decreased amounts of sOb-R due to ER stress were accompanied by impaired leptin signaling and reduced leptin binding. Conclusions Lipotoxicity and apoptosis increased Ob-R cleavage via ADAM10-dependent mechanisms. In contrast high leptin levels and ER stress led to reduced sOb-R levels. While increased sOb-R concentrations seem to directly block leptin action, reduced amounts of sOb-R may reflect decreased membrane expression of Ob-R. These findings could explain changes of leptin sensitivity which are associated with variations of serum sOb-R levels in metabolic diseases. PMID:22545089

The role of established East Asian obesity-related loci on pediatric leptin levels highlights a neuronal influence on body weight regulation in Chinese children and adolescents: the BCAMS study

PubMed Central

Fu, Junling; Li, Ge; Li, Lujiao; Yin, Jinhua; Cheng, Hong; Han, Lanwen; Zhang, Qian; Li, Naishi; Xiao, Xinhua; Grant, Struan F.A.; Li, Mingyao; Gao, Shan; Mi, Jie; Li, Ming

2017-01-01

Genome-wide association studies have identified multiple variants associated with adult obesity, mostly in European-ancestry populations. We aimed to systematically assess the contribution of key loci, which had been previously shown to be associated in East Asian adults, to childhood obesity, related adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and retinol binding protein 4) were evaluated in 3,506 Chinese children and adolescents aged 6-18. After correction for multiple comparisons, six of these SNPs were robustly associated with childhood obesity: FTO-rs1558902 (P=5.6×10−5), MC4R-rs2331841 (P=4.4×10−4), GNPDA2-rs16858082 (P = 3.4×10−4), PCSK1-rs261967 (P = 0.001), SEC16B-rs516636 (P = 0.004) and MAP2K5-rs4776970 (P = 0.004), with odds ratios ranging from 1.211 to 1.421; while ITIH4-rs2535633 and BDNF-rs2030323 yielded nominal association with the same trait (P < 0.05). Moreover, the risk alleles of six SNPs displayed significant (P < 0.004) or nominal (P < 0.05) association with leptin levels, namely at in/near PCSK1, MC4R, FTO, MAP2K5, GNPDA2 and BDNF plus their cumulative genetic score yielded stronger association with increased leptin levels (P = 6.2×10−11). Our results reveal that key obesity-associated loci previously reported in Europeans, but also associated with East Asian adults, are also associated with obesity and/or metabolic quantitative traits in Chinese children. These associations coincide with six brain-expressed loci that correlate with leptin levels, thus may point to an important neuronal influence on body weight regulation in the pediatric setting. PMID:29212175

Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows.

PubMed

Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

2015-06-01

Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (P<0.05). Adiponectin is strongly associated with AMPK. The increases of adiponectin and AMPK may be one of the mechanisms to maintain homeostasis in heat-stressed dairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat

Effects of heat stress on serum insulin, adipokines, AMP-activated protein kinase, and heat shock signal molecules in dairy cows*

PubMed Central

Min, Li; Cheng, Jian-bo; Shi, Bao-lu; Yang, Hong-jian; Zheng, Nan; Wang, Jia-qi

2015-01-01

Heat stress affects feed intake, milk production, and endocrine status in dairy cows. The temperature-humidity index (THI) is employed as an index to evaluate the degree of heat stress in dairy cows. However, it is difficult to ascertain whether THI is the most appropriate measurement of heat stress in dairy cows. This experiment was conducted to investigate the effects of heat stress on serum insulin, adipokines (leptin and adiponectin), AMP-activated protein kinase (AMPK), and heat shock signal molecules (heat shock transcription factor (HSF) and heat shock proteins (HSP)) in dairy cows and to research biomarkers to be used for better understanding the meaning of THI as a bioclimatic index. To achieve these objectives, two experiments were performed. The first experiment: eighteen lactating Holstein dairy cows were used. The treatments were: heat stress (HS, THI average=81.7, n=9) and cooling (CL, THI average=53.4, n=9). Samples of HS were obtained on August 16, 2013, and samples of CL were collected on April 7, 2014 in natural conditions. The second experiment: HS treatment cows (n=9) from the first experiment were fed for 8 weeks from August 16, 2013 to October 12, 2013. Samples for moderate heat stress, mild heat stress, and no heat stress were obtained, respectively, according to the physical alterations of the THI. Results showed that heat stress significantly increased the serum adiponectin, AMPK, HSF, HSP27, HSP70, and HSP90 (P<0.05). Adiponectin is strongly associated with AMPK. The increases of adiponectin and AMPK may be one of the mechanisms to maintain homeostasis in heat-stressed dairy cows. When heat stress treatment lasted 8 weeks, a higher expression of HSF and HSP70 was observed under moderate heat stress. Serum HSF and HSP70 are sensitive and accurate in heat stress and they could be potential indicators of animal response to heat stress. We recommend serum HSF and HSP70 as meaningful biomarkers to supplement the THI and evaluate moderate heat

Leptin and the brain: influences on brain development, cognitive functioning and psychiatric disorders.

PubMed

Farr, Olivia M; Tsoukas, Michael A; Mantzoros, Christos S

2015-01-01

Receptors of leptin, the prototypical adipokine, are expressed throughout the cortex and several other areas of the brain. Although typically studied for its role in energy intake and expenditure, leptin plays a critical role in many other neurocognitive processes and interacts with various other hormones and neurotransmitters to perform these functions. Here, we review the literature on how leptin influences brain development, neural degradation, Alzheimer's disease, psychiatric disorders, and more complicated cognitive functioning and feeding behaviors. We also discuss modulators of leptin and the leptin receptor as they relate to normal cognitive functioning and may mediate some of the actions of leptin in the brain. Although we are beginning to better understand the critical role leptin plays in normal cognitive functioning, there is much to be discovered. Copyright © 2015 Elsevier Inc. All rights reserved.

The Rab11 Effector Protein FIP1 Regulates Adiponectin Trafficking and Secretion

PubMed Central

Moreno-Navarrete, Jose Maria; Fernandez-Real, Jose Manuel; Mora, Silvia

2013-01-01

Adiponectin is an adipokine secreted by white adipocytes involved in regulating insulin sensitivity in peripheral tissues. Secretion of adiponectin in adipocytes relies on the endosomal system, however, the intracellular machinery involved in mediating adiponectin release is unknown. We have previously reported that intracellular adiponectin partially compartmentalizes with rab 5 and rab11, markers for the early/sorting and recycling compartments respectively. Here we have examined the role of several rab11 downstream effector proteins (rab11 FIPs) in regulating adiponectin trafficking and secretion. Overexpression of wild type rab11 FIP1, FIP3 and FIP5 decreased the amount of secreted adiponectin expressed in HEK293 cells, whereas overexpression of rab11 FIP2 or FIP4 had no effect. Furthermore shRNA-mediated depletion of FIP1 enhanced adiponectin release whereas knock down of FIP5 decreased adiponectin secretion. Knock down of FIP3 had no effect. In 3T3L1 adipocytes, endogenous FIP1 co-distributed intracellularly with endogenous adiponectin and FIP1 depletion enhanced adiponectin release without altering insulin-mediated trafficking of the glucose transporter Glut4. While adiponectin receptors internalized with transferrin receptors, there were no differences in transferrin receptor recycling between wild type and FIP1 depleted adipocytes. Consistent with its inhibitory role, FIP1 expression was decreased during adipocyte differentiation, by treatment with thiazolidinediones, and with increased BMI in humans. In contrast, FIP1 expression increased upon exposure of adipocytes to TNFα. In all, our findings identify FIP1 as a novel protein involved in the regulation of adiponectin trafficking and release. PMID:24040321

Ambient air pollution, adipokines, and glucose homeostasis: The Framingham Heart Study.

PubMed

Li, Wenyuan; Dorans, Kirsten S; Wilker, Elissa H; Rice, Mary B; Kloog, Itai; Schwartz, Joel D; Koutrakis, Petros; Coull, Brent A; Gold, Diane R; Meigs, James B; Fox, Caroline S; Mittleman, Murray A

2018-02-01

To examine associations of proximity to major roadways, sustained exposure to fine particulate matter (PM 2.5 ), and acute exposure to ambient air pollutants with adipokines and measures of glucose homeostasis among participants living in the northeastern United States. We included 5958 participants from the Framingham Offspring cohort examination cycle 7 (1998-2001) and 8 (2005-2008) and Third Generation cohort examination cycle 1 (2002-2005) and 2 (2008-2011), who did not have type 2 diabetes at the time of examination visit. We calculated 2003 annual average PM 2.5 at participants' home address, residential distance to the nearest major roadway, and daily PM 2.5 , black carbon (BC), sulfate, nitrogen oxides (NO x ), and ozone concentrations. We used linear mixed effects models for fasting glucose, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) which were measured up to twice, and used linear regression models for adiponectin, resistin, leptin, and hemoglobin A1c (HbA1c) which were measured only once, adjusting for demographics, socioeconomic position, lifestyle, time, and seasonality. The mean age was 51years and 55% were women. Participants who lived 64m (25th percentile) from a major roadway had 0.28% (95% CI: 0.05%, 0.51%) higher fasting plasma glucose than participants who lived 413m (75th percentile) away, and the association appeared to be driven by participants who lived within 50m from a major roadway. Higher exposures to 3- to 7-day moving averages of BC and NO x were associated with higher glucose whereas the associations for ozone were negative. The associations otherwise were generally null and did not differ by median age, sex, educational attainment, obesity status, or prediabetes status. Living closer to a major roadway or acute exposure to traffic-related air pollutants were associated with dysregulated glucose homeostasis but not with adipokines among participants from the Framingham Offspring and Third Generation

Cutoff points of waist circumference and trunk and visceral fat for identifying children with elevated inflammation markers and adipokines: The Healthy Growth Study.

PubMed

Karatzi, Kalliopi; Moschonis, George; Polychronopoulou, Maria Christina; Chrousos, George P; Lionis, Christos; Manios, Yannis

2016-10-01

Excessive fat storage is accompanied by several comorbidities in children and early identification of elevated abdominal fat may be extremely valuable in early prevention of cardiometabolic risk. The aim of the present study was to establish cutoff points for waist circumference trunk and visceral fat, thus identifying increased likelihood of elevated inflammatory markers and adipokines in children. A representative sample of schoolchildren (aged 9-13 y) participated in a cross-sectional epidemiologic study conducted in Greece. Anthropometric and physical examination data, biochemical indices, and socioeconomic information (collected from parents) were assessed for all children. Central adiposity markers (trunk and visceral fat) were collected with bioelectrical impedance analysis for 999 children. Specific cutoff values of abdominal adiposity indices indicating increased likelihood of elevated levels of C-reactive protein, interleukin-6, and leptin and decreased levels of adiponectin were calculated by sex. These cutoff values were; 67.5 cm for boys and 69.5 cm for girls for waist circumference, 17.75% for boys and 22.65% for girls for trunk fat mass percentage, and 3.95 for boys and 2.55 for girls for visceral fat rating. To our knowledge, this is the first study to establish simple cutoff points for abdominal adiposity indices identifying children at high risk for elevated inflammatory markers and decreased adipokine levels. Future studies are essential to confirm these findings. Copyright © 2016 Elsevier Inc. All rights reserved.

Exercise improves adiponectin concentrations irrespective of the adiponectin gene polymorphisms SNP45 and the SNP276 in obese Korean women.

PubMed

Lee, Kyoung-Young; Kang, Hyun-Sik; Shin, Yun-A

2013-03-10

The effects of exercise on adiponectin levels have been reported to be variable and may be attributable to an interaction between environmental and genetic factors. The single nucleotide polymorphisms (SNP) 45 (T>G) and SNP276 (G>T) of the adiponectin gene are associated with metabolic risk factors including adiponectin levels. We examined whether SNP45 and SNP276 would differentially influence the effect of exercise training in middle-aged women with uncomplicated obesity. We conducted a prospective study in the general community that included 90 Korean women (age 47.0±5.1 years) with uncomplicated obesity. The intervention was aerobic exercise training for 3 months. Body composition, adiponectin levels, and other metabolic risk factors were measured. Prior to exercise training, only body weight differed among the SNP276 genotypes. Exercise training improved body composition, systolic blood pressure, maximal oxygen consumption, high-density lipoprotein cholesterol, and leptin levels. In addition, exercise improved adiponectin levels irrespective of weight gain or loss. However, after adjustments for age, BMI, body fat (%), and waist circumference, no differences were found in obesity-related characteristics (e.g., adiponectin) following exercise training among the SNP45 and the 276 genotypes. Our findings suggest that aerobic exercise affects adiponectin levels regardless of weight loss and this effect would not be influenced by SNP45 and SNP276 in the adiponectin gene. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

Less favorable body composition and adipokines in South Asians compared with other US ethnic groups: results from the MASALA and MESA studies.

PubMed

Shah, A D; Kandula, N R; Lin, F; Allison, M A; Carr, J; Herrington, D; Liu, K; Kanaya, A M

2016-04-01

Small studies have shown that South Asians (SAs) have more total body, subcutaneous, visceral and hepatic fat and abnormal adipokine levels compared with Whites. However, comprehensive studies of body composition and adipokines in SAs compared with other ethnic groups are lacking. Using harmonized data, we performed a cross-sectional analysis of two community-based cohorts: Mediators of Atherosclerosis of South Asians Living in America (MASALA, n=906) and Multi-Ethnic Study of Atherosclerosis (MESA which included 2622 Whites, 803 Chinese Americans, 1893 African Americans and 1496 Latinos). General linear models were developed to assess the ethnic differences in ectopic fat (visceral, intermuscular and pericardial fat; and hepatic attenuation), lean muscle mass and adipokines (adiponectin and resistin). Models were adjusted for age, sex, site, alcohol use, smoking, exercise, education, household income and body mass index. Ectopic fat models were additionally adjusted for hypertension, diabetes, high-density lipoprotein and triglycerides. Adipokine models were adjusted for subcutaneous, visceral, intermuscular and pericardial fat; and hepatic attenuation. Compared with all ethnic groups in MESA (Whites, Chinese Americans, African Americans and Latinos), SAs had greater intermuscular fat (pairwise comparisons with each MESA group, P<0.01), lower hepatic attenuation (P<0.001) and less lean mass (P<0.001). SAs had greater visceral fat compared with Chinese Americans, African Americans and Latinos (P<0.05) and greater pericardial fat compared with African Americans (P<0.001). SAs had lower adiponectin levels compared with other ethnic groups (P<0.01; except Chinese Americans) and higher resistin levels than all groups (P<0.001), even after adjusting for differences in body composition. There are significant ethnic differences in ectopic fat, lean mass and adipokines. A less favorable body composition and adipokine profile in SAs may partially explain the increased

Understanding leptin-dependent regulation of skeletal homeostasis

PubMed Central

Motyl, Katherine J.; Rosen, Clifford J.

2012-01-01

Despite growing evidence for adipose tissue regulation of bone mass, the role of the adipokine leptin in bone remodeling remains controversial. The majority of in vitro studies suggest leptin enhances osteoblastic proliferation and differentiation while inhibiting adipogenic differentiation from marrow stromal cells. Alternatively, some evidence demonstrates either no effect or a pro-apoptotic action of leptin on stromal cells. Similarly, in vivo work has demonstrated both positive and negative effects of leptin on bone mass. Most of the literature supports the idea that leptin suppresses bone mass by acting in the brainstem to reduce serotonin-dependent sympathetic signaling from the ventromedial hypothalamus to bone. However, other studies have found partly or entirely contrasting actions of leptin. Recently one study found a significant effect of surgery alone with intracerebroventricular administration of leptin, a technique crucial for understanding centrally-mediated leptin regulation of bone. Thus, two mainstream hypotheses for the role of leptin on bone emerge: 1) direct regulation through increased osteoblast proliferation and differentiation and 2) indirect suppression of bone formation through a hypothalamic relay. At the present time, it remains unclear whether these effects are relevant in only extreme circumstances (i.e. models with complete deficiency) or play an important homeostatic role in the regulation of peak bone acquisition and skeletal remodeling. Ultimately, determining the actions of leptin on the skeleton will be critical for understanding how the obesity epidemic may be impacting the prevalence of osteoporosis. PMID:22534195

Endogenous hormones, inflammation, and body size in premenopausal Mexican women: results from the Mexican Teachers' Cohort (MTC, ESMaestras).

PubMed

Rinaldi, Sabina; Biessy, Carine; de la Luz Hernandez, Maria; Lajous, Martin; Ortiz-Panozo, Eduardo; Yunes, Elsa; Lopez-Ridaura, Ruy; Torres-Mejia, Gabriela; Romieu, Isabelle

2015-03-01

Obesity is a major risk factor for several cancers, including female cancers. Endogenous hormones and inflammatory factors may mediate the association between anthropometric measures and cancer risk, although these associations have been studied mainly in Caucasians. The aim of the current study was to explore the association of circulating hormones, adipokines, and inflammatory factors with obesity and overweight in premenopausal Mexican women. We conducted a cross-sectional analysis of 504 premenopausal women from the large Mexican Teachers' Cohort (MTC, ESMaestras) study to determine the association of insulin-like growth factor I (IGF-I), its major circulating binding protein (IGFBP-3), leptin, adiponectin, C-peptide, and C-reactive protein with comprehensive measures of body size. Biomarkers were measured by immunoassays. Multivariate regression analyses were performed to compare geometric mean biomarker concentrations with measured markers of body size and adiposity. Mean IGF-I and IGFBP-3 concentrations significantly increased with increasing height and leg length. Concentrations of IGF-I, adiponectin, and the IGF-I/IGFBP-3 ratio strongly decreased with increasing BMI, weight, waist and hip circumferences, waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR), while CRP, leptin, C-peptide concentrations, and the leptin/adiponectin ratio strongly increased. Adiponectin and the leptin/adiponectin ratio remained significantly related to measures of central adiposity (waist circumference, WHpR, and WHtR) after adjustment by body mass index. The results of our study suggest a strong relation between biomarkers and body size in this study population and suggest that different fat depots may have different metabolic properties.

Impact of nutritional recovery with linear growth on the concentrations of adipokines in undernourished children living in Brazilian slums.

PubMed

Martins, Vinicius J B; Neves, Andrea P O; Franco, Maria do C P; Clemente, Ana P G; Sawaya, Ana L

2014-09-28

Undernutrition in early life has been reported to be closely associated with the development of non-communicable diseases in adulthood. Adequate treatment is important for reversing these effects. In the present study, we investigated the effects of undernutrition and anthropometric recovery on the weights and heights of children in relation to the concentrations of leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). A total of 119 children (aged 6-16 years) from the slums of São Paulo were selected according to their nutritional status and divided into three groups as follows: control (healthy without intervention, n 38) with a height-for-age Z score (HAZ) and a BMI-for-age Z score (BAZ) > -1·6; undernourished (HAZ and/or BAZ < -1·6, n 54); recovered from undernutrition (after treatment in a rehabilitation centre; HAZ and BAZ > -1·6, n 27). Blood samples were collected to determine insulin, glucose, leptin, adiponectin and PAI-1 concentrations. Leptin concentrations in the undernourished group were lower than those in the control and recovered groups (mean 0·92 (95% CI 0·67, 1·25), 2·03 (95% CI 1·46, 2·82) and 1·66 (95% CI 1·15, 2·44) ng/ml, P=0·003), which had similar leptin concentrations. There were no differences in adiponectin and PAI-1 concentrations among the groups. A positive correlation between waist circumference and leptin concentrations was observed in all the girls and boys of the control group (control: r 0·729, P<0·01; undernourished: r 0·490, P<0·05; and recovered: r 0·829, P<0·01; r 0·673, P<0·05). Stronger correlations between leptin and insulin concentrations were observed in the recovered group. The results of the present study indicate that normal leptin concentrations are found when normal height and weight are achieved.

Fisetin up-regulates the expression of adiponectin in 3T3-L1 adipocytes via the activation of silent mating type information regulation 2 homologue 1 (SIRT1)-deacetylase and peroxisome proliferator-activated receptors (PPARs).

PubMed

Jin, Taewon; Kim, Oh Yoen; Shin, Min-Jeong; Choi, Eun Young; Lee, Sung Sook; Han, Ye Sun; Chung, Ji Hyung

2014-10-29

Adiponectin, an adipokine, has been described as showing physiological benefits against obesity-related malfunctions and vascular dysfunction. Several natural compounds that promote the expression and secretion of adipokines in adipocytes could be useful for treating metabolic disorders. This study investigated the effect of fisetin, a dietary flavonoid, on the regulation of adiponectin in adipocytes using 3T3-L1 preadipocytes. The expression and secretion of adiponectin increased in 3T3-L1 cells upon treatment with fisetin in a dose-dependent manner. Fisetin-induced adiponectin secretion was inhibited by peroxisome proliferator-activated receptor (PPAR) antagonists. It was also revealed that fisetin increased the activities of PPARs and silent mating type information regulation 2 homologue 1 (SIRT1) in a dose-dependent manner. Furthermore, the up-regulation of adiponectin and the activation of PPARs induced by fisetin were prevented by a SIRT1 inhibitor. Fisetin also promoted deacetylation of PPAR γ coactivator 1 (PGC-1) and its interaction with PPARs. SIRT knockdown by siRNA significantly decreased both adiponectin production and PPARs-PGC-1 interaction. These results provide evidence that fisetin promotes the gene expression of adiponectin through the activation of SIRT1 and PPARs in adipocytes.

Adipokines, Oxidized Low-Density Lipoprotein, and C-Reactive Protein Levels in Lean, Overweight, and Obese Portuguese Patients with Type 2 Diabetes

PubMed Central

Neuparth, Maria João; Proença, Jorge Brandão; Santos-Silva, Alice; Coimbra, Susana

2013-01-01

Aim. Our aim was to study how different BMI scores may influence the levels of inflammation, oxidative stress, adipogenesis, glucose, and lipid metabolism, in lean, overweight, and obese Portuguese patients with type 2 diabetes mellitus (T2DM). Methods. We studied 28 lean, 38 overweight, and 17 obese patients with T2DM and 20 controls (gender and age matched). The circulating levels of oxLDL, CRP, and some adipokines—adiponectin, leptin, and chemerin—and the lipid profile were evaluated. Results. Obese patients presented significantly lower levels of adiponectin and higher leptin, oxLDL, and chemerin levels, as compared to the overweight, lean, and control groups. Overweight, compared to lean and control, subjects showed significantly lower adiponectin and higher leptin and chemerin levels; oxLDL values were significantly higher in overweight than in lean patients. Lean patients presented significantly higher chemerin values than the control. Obese patients presented significantly higher CRP values, as compared to lean patients and the control group. Obese and overweight patients presented significantly higher triglycerides values than lean patients. Except for CRP, all the observed significant changes between control and patients remained significant after statistical adjustment for the body mass index (BMI). Conclusion. The levels of leptin, adiponectin, oxLDL, CRP, and triglycerides in patients with T2DM seem to be more associated with obesity and less with diabetes. Chemerin levels were raised in lean, overweight, and obese patients, suggesting that, independently of BMI, an adipocyte dysfunction occurs. Moreover, chemerin may provide an important early biomarker of adipocyte dysfunction and a link between obesity and type 2 diabetes mellitus. PMID:24634792

A Prospective Study of Gynecological Cancer Risk in Relation to Adiposity Factors: Cumulative Incidence and Association with Plasma Adipokine Levels

PubMed Central

Wu, Meei-Maan; You, San-Lin; Cheng, Wen-Fang; Chen, Chi-An; Lee, Te-Chang; Chen, Chien-Jen

2014-01-01

Background Associations of obesity and obesity-related metabolic factors (adiposity factors) with uterine corpus cancer (UCC) and ovarian cancer (OVC) risk have been described. Still, a cause-effect relationship and the underlying mediators remain unclear, particularly for low-incidence populations. We aimed to prospectively determine whether adiposity factors could predict the development of UCC and OVC in Taiwanese women. To explore the biological mediators linking adiposity factors to cancer risk, we examined the association of two adipokines, leptin and adiponectin, with the gynecological cancers. Methods Totally, 11,258 women, aged 30–65, were recruited into the Community-Based Cancer Screening Program (CBCSP) study during 1991–1993, and were followed for UCC and OVC cases until December 31, 2011. Cox proportional hazard models were used to estimate hazard ratios (HRs). Adiposity factors and risk covariates were assessed at recruitment. Newly-developed cancer cases were determined from data in the government’s National Cancer Registry and Death Certification System. For adipokienes study, a nested case-control study was conducted within the cohort. Baseline plasma samples of 40 incident gynecological cancer cases and 240 age-menopause-matched controls were assayed for adipokines levels. Findings There were 38 and 30 incident cases of UCC and OVC, respectively, diagnosed during a median 19.9 years of follow-up. Multivariate analysis showed that alcohol intake (HR = 16.00, 95% = 4.83–53.00), high triglyceride levels (HR = 2.58, 95% = 1.28–5.17), and years of endogenous estrogen exposure per 5-year increment (HR = 1.91, 95% = 1.08–3.38) were associated with increased UCC risk. High body mass index (BMI≥27 kg/m2, HR = 2.90, 95% = 1.30–6.46) was associated with increased OVC risk. Analysis further showed an independent effect of adipokines on UCC and OVC risk after adjustment of the risk covariates. Conclusion We

The relationship between insulin sensitivity and serum adiponectin levels in three population groups.

PubMed

Ferris, W F; Naran, N H; Crowther, N J; Rheeder, P; van der Merwe, L; Chetty, N

2005-11-01

Reduced plasma adiponectin levels are associated with insulin resistance. Black South Africans, like African Americans, are more insulin-resistant than BMI-matched white subjects, as are Asian Indians. We investigated whether this interethnic variation in insulin resistance is due to differences in plasma adiponectin levels. Blood and anthropometric measurements were taken from black, white and Asian-Indian subjects. Serum adiponectin, lipids, glucose and insulin were measured; insulin sensitivity was calculated using HOMA. Black (HOMA = 2.62 +/- 0.99) and Asian-Indian subjects (HOMA = 3.41 +/- 2.85) were more insulin-resistant than BMI-matched white (HOMA = 1.76 +/- 0.63) subjects (p = 0.0001). Furthermore, the white subjects had higher adiponectin levels (8.11 +/- 4.39 microg/ml) compared to black (5.71 +/- 2.50 microg/ml) and Asian Indian (5.86 +/- 2.50 microg/ml) subjects (p = 0.003). When all ethnic groups were combined, multiple regression analysis demonstrated that serum adiponectin levels corrected for BMI and ethnicity did not correlate with HOMA, but did explain 10.0 % of the variance in HDL-cholesterol levels. Within each ethnic group, adiponectin only correlated inversely with HOMA in white subjects. Adiponectin may play a role in determining serum HDL-cholesterol levels, but ethnic variation in insulin sensitivity is not dependent on serum levels of this adipokine. The relationship between adiponectin and insulin resistance varies across ethnic groups.

The benefits of ω-3 supplementation depend on adiponectin basal level and adiponectin increase after the supplementation: A randomized clinical trial.

PubMed

Barbosa, Milena Maria de Araújo Lima; Melo, Alexandra Lorenzzi Trinanes Raposo de; Damasceno, Nágila Raquel Teixeira

2017-02-01

The aim of this study was to analyze whether ω-3 supplementation improves cardiometabolic profile in individuals with cardiovascular risk factors and to determine the effect of adiponectin levels on these changes. In this double-blind, placebo-controlled, 2-mo clinical trial, we randomized 80 individuals of both sexes (mean age 52 y) with at least one cardiovascular risk factor (excess weight, hypertension, dyslipidemia, diabetes, or smoking) into two groups: ω-3 (supplemented with 3 g/d of fish oil containing 37% eicosapentaenoic acid and 23% docosahexaenoic acid) and placebo (3 g/d of sunflower oil containing 65% linoleic acid). At baseline and after the intervention, we evaluated serum adiponectin, leptin, lipid profile, apolipoproteins (apo), electronegative low-density lipoprotein (LDL[-]), and glucose metabolism (glucose and insulin). After supplementation, the ω-3 group showed an increase in serum adiponectin. After stratifying the ω-3 group by adiponectin concentration at baseline, participants with lower adiponectin concentration showed a higher reduction of total cholesterol, LDL, LDL/high-density lipoprotein ratio, LDL/apo B, and LDL(-). Individuals with a higher variation of adiponectin concentration after ω-3 supplementation presented with reduced blood glucose. The variation of serum adiponectin induced by ω-3 supplementation was negatively correlated with the Framingham and Adult Treatment Panel IV scores (r = -0.4 and P < 0.05 for both). Adiponectin is shown as one of the mechanisms by which ω-3 improves cardiometabolic profile in persons with cardiovascular risk. Moreover, the benefit varies according to the adiponectin basal level and adiponectin variation after supplementation. Copyright © 2016 Elsevier Inc. All rights reserved.

Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates insulin resistance by upregulating glucose transporter-4, peroxisome proliferator-activated receptor-gamma, adiponectin, and leptin levels in vitro.

PubMed

Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V; Manjunath, Kirangadur; Viswanatha, Gollapalle L; Ashok, Godavarthi

2016-01-01

The present study was undertaken to evaluate the effect of methanolic leaf extract of Gymnema sylvestre (MLGS) on glucose transport (GLUT) and insulin resistance in vitro. Peroxisome proliferator-activated receptor-gamma (PPAR-γ) and GLUT-4 expression were assessed in L6 myotubes for concluding the GLUT activity, and adiponectin and leptin expression was studied in 3T3 L1 murine adipocyte cell line to determine the effect of MLGS (250-750 μg/ml) on insulin resistance. The findings of the experiments have demonstrated a significant and dose-dependent increase in glucose uptake in all the tested concentrations of MLGS, further the glucose uptake activity of MLGS (750 μg/ml) was at par with rosiglitazone (50 μg/ml). Concomitantly, MLGS has shown enhanced GLUT-4 and PPAR-γ gene expressions in L6 myotubes. Furthermore, cycloheximide (CHX) had completely abolished the glucose uptake activity of MLGS when co-incubated, which further confirmed that glucose uptake activity of MLGS was linked to enhanced expression of GLUT-4 and PPAR-γ. In addition, in another experimental set, MLGS showed enhanced expression of adiponectin and leptin, thus confirms the ameliorative effect of MLGS on insulin resistance. These findings suggest that MLGS has an enhanced glucose uptake activity in L6 myotubes, and ameliorate the insulin resistance in 3T3 L1 murine adipocyte cell line in vitro.

Preoptic leptin signaling modulates energy balance independent of body temperature regulation.

PubMed

Yu, Sangho; Cheng, Helia; François, Marie; Qualls-Creekmore, Emily; Huesing, Clara; He, Yanlin; Jiang, Yanyan; Gao, Hong; Xu, Yong; Zsombok, Andrea; Derbenev, Andrei V; Nillni, Eduardo A; Burk, David H; Morrison, Christopher D; Berthoud, Hans-Rudolf; Münzberg, Heike

2018-05-15

The adipokine leptin acts on the brain to regulate energy balance but specific functions in many brain areas remain poorly understood. Among these, the preoptic area (POA) is well known to regulate core body temperature by controlling brown fat thermogenesis, and we have previously shown that glutamatergic, long-form leptin receptor (Lepr)-expressing neurons in the POA are stimulated by warm ambient temperature and suppress energy expenditure and food intake. Here we further investigate the role of POA leptin signaling in body weight regulation and its relationship to body temperature regulation in mice. We show that POA Lepr signaling modulates energy expenditure in response to internal energy state, and thus contributes to body weight homeostasis. However, POA leptin signaling is not involved in ambient temperature-dependent metabolic adaptations. Our study reveals a novel cell population through which leptin regulates body weight. © 2018, Yu et al.

Serum biochemistry profile, inflammatory cytokines, adipokines and cardiovascular findings in obese dogs.

PubMed

Piantedosi, Diego; Di Loria, Antonio; Guccione, Jacopo; De Rosa, Angela; Fabbri, Silvia; Cortese, Laura; Carta, Sergio; Ciaramella, Paolo

2016-10-01

The aim of this study was to evaluate the serum biochemistry profile, inflammatory cytokines, adipokines and cardiovascular findings in obese dogs. Twenty obese and 20 normal weight healthy pet dogs were recruited into the study, where they underwent blood testing and assessment of cardiovascular function (blood pressure analysis, electrocardiography and echocardiography). Higher concentrations of total cholesterol, triglycerides, lactate dehydrogenase, total serum proteins, α-globulins, total bilirubin, insulin, insulin:glucose ratio, alkaline phosphate and alanine aminotransferase were observed in obese dogs than dogs of normal weight. There were no differences in concentrations of tumour necrosis factor (TNF)-α or interleukin (IL)-6 between the two groups. Obese dogs had higher serum leptin but lower adiponectin concentrations than dogs of normal weight. Systolic arterial blood pressure was higher in obese dogs than dogs of normal weight. The values for the thickness of the free wall of the left ventricle and interventricular septal thickness were greater at end-diastole in obese dogs compared to dogs of normal weight. Four of 20 obese dogs were determined to have obesity-related metabolic dysfunction (ORMD). The findings indicate that a chronic inflammatory state is not necessarily evident in obese dogs, as has been described in human beings, and the criteria used for ORMD can be used to define this syndrome in dogs. In this study, canine obesity was associated with cardiac and vascular dysfunction. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of Leptin with Body Pain in Women

PubMed Central

Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D.; Stefanick, Marcia L.

2016-01-01

Abstract Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia. PMID:27028709

Association of Leptin with Body Pain in Women.

PubMed

Younger, Jarred; Kapphahn, Kristopher; Brennan, Kathleen; Sullivan, Shannon D; Stefanick, Marcia L

2016-07-01

Leptin, an appetite-regulatory hormone, is also known to act as a proinflammatory adipokine. One of the effects of increased systemic leptin concentrations may be greater sensitivity to pain. We report the results of two studies examining the association between leptin and pain: a small pilot longitudinal study, followed by a large cross-sectional study. In Study 1, three women with physician-diagnosed fibromyalgia provided blood draws daily for 25 consecutive days, as well as daily self-reported musculoskeletal pain. Daily fluctuations in serum leptin were positively associated with pain across all three participants (F (1,63) = 12.8, p < 0.001), with leptin predicting ∼49% of the pain variance. In Study 2, the relationship between leptin and body pain was examined in a retrospective cross-sectional analysis of 5676 generally healthy postmenopausal women from the Women's Health Initiative. Leptin levels obtained from single blood draws were tested for a relationship with self-reported body pain. Body mass index (BMI) was also included as a predictor of pain. Both leptin and BMI were found to be independently associated with self-reported pain (p = 0.001 and p < 0.001, respectively), with higher leptin levels and greater BMI each being associated with greater pain. Leptin appears to be a predictor of body pain both within- and between-individuals and may be a driver of generalized pain states such as fibromyalgia.

Leptin-Aldosterone-Neprilysin Axis: Identification of Its Distinctive Role in the Pathogenesis of the Three Phenotypes of Heart Failure in People With Obesity.

PubMed

Packer, Milton

2018-04-10

Obesity (especially visceral adiposity) can be associated with 3 different phenotypes of heart failure: heart failure with a reduced ejection fraction, heart failure with a preserved ejection fraction, and high-output heart failure. All 3 phenotypes are characterized by an excessive secretion of aldosterone and sodium retention. In addition, obesity is accompanied by increased signaling through the leptin receptor, which can promote activation of both the sympathetic nervous system and the renin-angiotensin system and can directly stimulate the secretion of aldosterone. The deleterious interaction of leptin and aldosterone is potentiated by the simultaneous action of adiposity and the renal sympathetic nerves to cause overactivity of neprilysin; the loss of the counterbalancing effects of natriuretic peptides is exacerbated by an additional effect of both obesity and heart failure to interfere with adiponectin signaling. This intricate neurohormonal interplay leads to plasma volume expansion as well as to adverse ventricular remodeling and cardiac fibrosis. Furthermore, the activity of aldosterone and neprilysin is not only enhanced by obesity, but these mechanisms can also promote adipogenesis and adipocyte dysfunction, thereby enhancing the positive feedback loop. Last, in elderly obese women, changes in quantity and biology of epicardial adipose tissue further enhances the release of leptin and other proinflammatory adipokines, thereby leading to cardiac and systemic inflammation, end-organ fibrosis, and multiple comorbidities. Regardless of the phenotypic expression, activation of the leptin-aldosterone-neprilysin axis appears to contribute importantly to the evolution and progression of heart failure in people with obesity. Efforts to interfere with the detrimental interactions of this distinctive neurohormonal ecosystem with existing or novel therapeutic agents are likely to yield unique clinical benefits. © 2018 American Heart Association, Inc.

A Microfluidic Interface for the Culture and Sampling of Adiponectin from Primary Adipocytes

PubMed Central

Godwin, Leah A.; Brooks, Jessica C.; Hoepfner, Lauren D.; Wanders, Desiree; Judd, Robert L.; Easley, Christopher J.

2014-01-01

Secreted from adipose tissue, adiponectin is a vital endocrine hormone that acts in glucose metabolism, thereby establishing its crucial role in diabetes, obesity, and other metabolic disease states. Insulin exposure to primary adipocytes cultured in static conditions has been shown to stimulate adiponectin secretion. However, conventional, static methodology for culturing and stimulating adipocytes falls short of truly mimicking physiological environments. Along with decreases in experimental costs and sample volume, and increased temporal resolution, microfluidic platforms permit small-volume flowing cell culture systems, which more accurately represent the constant flow conditions through vasculature in vivo. Here, we have integrated a customized primary tissue culture reservoir into a passively operated microfluidic device made of polydimethylsiloxane (PDMS). Fabrication of the reservoir was accomplished through unique PDMS “landscaping” above sampling channels, with a design strategy targeted to primary adipocytes to overcome issues of positive cell buoyancy. This reservoir allowed three-dimensional culture of primary murine adipocytes, accurate control over stimulants via constant perfusion, and sampling of adipokine secretion during various treatments. As the first report of primary adipocyte culture and sampling within microfluidic systems, this work sets the stage for future studies in adipokine secretion dynamics. PMID:25423362

Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case-control study within the B~FIT cohort.

PubMed

Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; Lacroix, Andrea; Tice, Jeffrey A; Chia, Victoria M; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

2013-02-01

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case-control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n=15,595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992-1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m(2)), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (OR(T3 vs T1)=2.96; 95% CI, 1.21-7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (OR(T3 vs T1)=2.11; 95% CI, 0.69-6.44; P trend=0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin-BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity-endometrial cancer associations.

Paracrine-acting adiponectin promotes mammary epithelial differentiation and synergizes with genistein to enhance transcriptional response to estrogen receptor beta signaling

USDA-ARS?s Scientific Manuscript database

Mammary stromal adipocytes constitute an active site for the synthesis of the adipokine adiponectin (APN) that may influence the mammary epithelial microenvironment. The relationship between 'local', mammary tissue-derived APN and breast cancer risk is poorly understood. Herein, we identify a novel ...

Adiponectin and catecholamine concentrations during acute exercise in children with type 1 diabetes.

PubMed

2008-06-01

Adiponectin, an adipokine secreted by the adipocyte, is inversely related to adiposity and directly related to insulin sensitivity. In type 1 diabetes mellitus (T1DM), however, data thus far are contradictory. We investigated the relationship between adiponectin and exercise inT1DM. Forty-nine children (14.5 +/- 2.0 yr, range 8-17 yr) with T1DM on an insulin pump were studied during two 75-min exercise sessions with and without continuation of the basal rate within 4 wk. Adiponectin and epinephrine concentrations were measured before and during exercise. Mean preexercise adiponectin concentration was 11.2 +/- 4.7 mg/L (range 2.7-23.0 mg/L) with a mean absolute difference of 1.7 mg/L between the 2 d. Adiponectin concentrations did not change meaningfully during exercise (mean change: -0.1 +/- 1.2 mg/L; p = 0.17). Adiponectin correlated inversely with body mass index percentile (p = 0.02) but not with age, gender, duration of diabetes, hemoglobin A1c, or preexercise glucose. However, those with higher baseline adiponectin concentrations were less likely to become hypoglycemic during exercise, 36% becoming hypoglycemic when baseline adiponectin concentration was <10 mg/L, 42% when 10 to <15 mg/L, and 15% when > or =15 mg/L (p = 0.02). Baseline epinephrine concentrations were not associated with adiponectin, and in those whose nadir glucose was < or =100 mg/dL, there was no correlation between epinephrine response and adiponectin (p = 0.16). Adiponectin concentrations are stable from day to day, are not affected by acute exercise or metabolic control, and vary inversely with adiposity. Higher adiponectin concentration appears to be associated with a decrease in hypoglycemia risk during exercise. Further studies are needed to examine whether adiponectin protects against exercise-induced hypoglycemia by directly enhancing the oxidation of alternate fuels.

Leptin, cardiovascular diseases and type 2 diabetes mellitus.

PubMed

Katsiki, Niki; Mikhailidis, Dimitri P; Banach, Maciej

2018-06-07

Leptin, an adipokine that is implicated in the control of food intake via appetite suppression, may also stimulate oxidative stress, inflammation, thrombosis, arterial stiffness, angiogenesis and atherogenesis. These leptin-induced effects may predispose to the development of cardiovascular diseases. In the present review we discuss the evidence linking leptin levels with the presence, severity and/or prognosis of both coronary artery disease and non-cardiac vascular diseases such as stroke, carotid artery disease, peripheral artery disease (PAD) and abdominal aortic aneurysms (AAA) as well as with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). Leptin levels have been positively associated with the presence, severity, extent and lesion complexity of coronary atherosclerosis as well as with the presence, severity and poor clinical outcomes of both ischemic and hemorrhagic strokes. But conflicting results also exist. Furthermore, leptin was reported to independently predict common carotid intima-media thickness and carotid plaque instability. A link between hyperleptinemia and PAD has been reported, whereas limited data were available on the potential association between leptin and AAA. Elevated leptin concentrations have also been related to CKD incidence and progression as well as with insulin resistance, T2DM, micro- and macrovascular diabetic complications. Statins and antidiabetic drugs (including sitagliptin, metformin, pioglitazone, liraglutide and empagliflozin) may affect leptin levels. Further research is needed to establish the potential use (if any) of leptin as a therapeutic target in these diseases.

Exercise Training Modifies Ghrelin and Adiponectin Concentrations and Is Related to Inflammation in Older Adults

PubMed Central

Carrillo, Andres E.; Timmerman, Kyle L.; Jennings, Kristofer; Coen, Paul M.; Pence, Brandt D.; Flynn, Michael G.

2014-01-01

The purpose of this study was to observe exercise training–induced effects on adiponectin, leptin, and ghrelin. Twenty-nine older, healthy participants were classified as physically active (comparison group: N = 15, 70.9±1.2 years) or physically inactive (exercise group: N = 14, 70.5±1.4 years). Exercise group participants completed 12 weeks of combined aerobic and resistance exercise training, whereas comparison group participants maintained their current level of exercise and served as a physically active comparison group. Monocyte phenotype, as well as serum ghrelin, leptin, adiponectin, and soluble tumor necrosis factor receptor II were analyzed prior to and following the 12-week period. Ghrelin and adiponectin increased 47% and 55%, respectively, in exercise group participants following exercise training. Percent change in ghrelin (post and pre) was negatively correlated with the percent change in CD14+CD16+ monocytes (post and pre) in exercise group participants. Despite no changes in body mass, these data contribute to evidence for the anti-inflammatory effects of exercise. PMID:24013674

Uptake of leptin and albumin via separate pathways in proximal tubule cells.

PubMed

Briffa, Jessica F; Grinfeld, Esther; Poronnik, Philip; McAinch, Andrew J; Hryciw, Deanne H

2016-10-01

The adipokine leptin and oncotic protein albumin are endocytosed in the proximal tubule via the scavenger receptor megalin. Leptin reduces megalin expression and activates cell signalling pathways that upregulate fibrotic protein expression. The aim of this study was to investigate if leptin uptake in proximal tubule cells was via the albumin-megalin endocytic complex. In immortalised proximal tubule Opossum kidney cells (OK) fluorescent leptin and albumin co-localised following 5min exposure, however there was no co-localisation at 10, 20 and 30min exposure. In OK cells, acute exposure to leptin for 2h did not alter NHE3, ClC-5, NHERF1 and NHERF2 mRNA. However, acute leptin exposure increased NHERF2 protein expression in proximal tubule cells. In OK cells, immunoprecipitation experimentation indicated leptin did not bind to ClC-5. Leptin uptake in OK cells was enhanced by bafilomycin and ammonium chloride treatment, demonstrating that uptake was not dependent on lysosomal pH. Thus, it is likely that two pools of megalin exist in proximal tubule cells to facilitate separate uptake of leptin and albumin by endocytosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in Serum Adiponectin in Mice Chronically Exposed to Inorganic Arsenic in Drinking Water.

PubMed

Song, Xuanbo; Li, Ying; Liu, Junqiu; Ji, Xiaohong; Zhao, Lijun; Wei, Yudan

2017-09-01

Cardiovascular disease and diabetes mellitus are prominent features of glucose and lipid metabolism disorders. Adiponectin is a key adipokine that is largely involved in glucose and lipid metabolism processes. A growing body of evidence suggests that chronic exposure to inorganic arsenic is associated with cardiovascular disease and diabetes mellitus. We hypothesized that arsenic exposure may increase the risk of cardiovascular disease and diabetes mellitus by affecting the level of adiponectin. In this study, we examined serum adiponectin levels, as well as serum levels of metabolic measures (including fasting blood glucose, insulin, total cholesterol, triglyceride, and high-density lipoprotein (HDL)-cholesterol) in C57BL/6 mice exposed to inorganic arsenic in drinking water (5 and 50 ppm NaAsO 2 ) for 18 weeks. Body mass and adiposity were monitored throughout the study. We found no significant changes in serum insulin and glucose levels in mice treated with arsenic for 18 weeks. However, arsenic exposure decreased serum levels of adiponectin, triglyceride, and HDL-cholesterol. Further, an inverse relationship was observed between urinary concentrations of total arsenic and serum levels of adiponectin. This study suggests that arsenic exposure could disturb the metabolism of lipids and increase the risk of cardiovascular disease by reducing the level of adiponectin.

Role of leptin as a link between metabolism and the immune system.

PubMed

Pérez-Pérez, Antonio; Vilariño-García, Teresa; Fernández-Riejos, Patricia; Martín-González, Jenifer; Segura-Egea, Juan José; Sánchez-Margalet, Víctor

2017-06-01

Leptin is an adipocyte-derived hormone not only with an important role in the central control of energy metabolism, but also with many pleiotropic effects in different physiological systems. One of these peripheral functions of leptin is a regulatory role in the interplay between energy metabolism and the immune system, being a cornerstone of the new field of immunometabolism. Leptin receptor is expressed throughout the immune system and the regulatory effects of leptin include cells from both the innate and adaptive immune system. Leptin is one of the adipokines responsible for the inflammatory state found in obesity that predisposes not only to type 2 diabetes, metabolic syndrome and cardiovascular disease, but also to autoimmune and allergic diseases. Leptin is an important mediator of the immunosuppressive state in undernutrition status. Placenta is the second source of leptin and it may play a role in the immunomodulation during pregnancy. Finally, recent work has pointed to the participation of leptin and leptin receptor in the pathophysiology of inflammation in oral biology. Therefore, leptin and leptin receptor should be considered for investigation as a marker of inflammation and immune activation in the frontier of innate-adaptive system, and as possible targets for intervention in the immunometabolic mediated pathophysiology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methanolic leaf extract of Gymnema sylvestre augments glucose uptake and ameliorates insulin resistance by upregulating glucose transporter-4, peroxisome proliferator-activated receptor-gamma, adiponectin, and leptin levels in vitro

PubMed Central

Kumar, Puttanarasaiah Mahesh; Venkataranganna, Marikunte V.; Manjunath, Kirangadur; Viswanatha, Gollapalle L.; Ashok, Godavarthi

2016-01-01

Aims: The present study was undertaken to evaluate the effect of methanolic leaf extract of Gymnema sylvestre (MLGS) on glucose transport (GLUT) and insulin resistance in vitro. Materials and Methods: Peroxisome proliferator-activated receptor-gamma (PPAR-γ) and GLUT-4 expression were assessed in L6 myotubes for concluding the GLUT activity, and adiponectin and leptin expression was studied in 3T3 L1 murine adipocyte cell line to determine the effect of MLGS (250-750 μg/ml) on insulin resistance. Results: The findings of the experiments have demonstrated a significant and dose-dependent increase in glucose uptake in all the tested concentrations of MLGS, further the glucose uptake activity of MLGS (750 μg/ml) was at par with rosiglitazone (50 μg/ml). Concomitantly, MLGS has shown enhanced GLUT-4 and PPAR-γ gene expressions in L6 myotubes. Furthermore, cycloheximide (CHX) had completely abolished the glucose uptake activity of MLGS when co-incubated, which further confirmed that glucose uptake activity of MLGS was linked to enhanced expression of GLUT-4 and PPAR-γ. In addition, in another experimental set, MLGS showed enhanced expression of adiponectin and leptin, thus confirms the ameliorative effect of MLGS on insulin resistance. Conclusion: These findings suggest that MLGS has an enhanced glucose uptake activity in L6 myotubes, and ameliorate the insulin resistance in 3T3 L1 murine adipocyte cell line in vitro. PMID:27104035

Inverse association of leptin levels with renal cell carcinoma: results from a case-control study.

PubMed

Spyridopoulos, Themistoklis N; Petridou, Eleni Th; Dessypris, Nick; Terzidis, Agapios; Skalkidou, Alkistis; Deliveliotis, Charalambos; Chrousos, George P

2009-01-01

Leptin is primarily produced in adipose tissue and appears to play a modulatory role between metabolism and immunity. Given that obesity, a state of chronic inflammation, is an established risk factor for Renal Cell Carcinoma (RCC), we investigated the association between plasma leptin levels and RCC risk. This case-control study included 70 patients with newly diagnosed, histologically confirmed RCC and 280 age-, gender- and district of residence-matched controls. Anthropometric data, socio-demographic variables, medical history, lifestyle habits and dietary data were derived from a personal interview. Serum leptin and adiponectin levels were determined using standard commercial kits. Adjusted odds ratios for RCC risk were derived through multiple logistic regression analyses. Leptin levels were inversely associated with RCC risk (OR: 0.53, CI: 0.28- 0.99, p = 0.05), even after controlling for potential confounding factors, such as Body Mass Index (BMI), recent weight change, history of diabetes mellitus and other obesity related hormones, notably adiponectin. The precise mechanism linking obesity with RCC remains unclear; however, the inverse association of leptin with RCC might be attributed, at least in part, to hormonal cross-talk with complex neuron-endocrine and immune circuits. These findings, if confirmed in prospective and interventional studies, might further elucidate the underlying mechanisms.

Swim training and the genetic expression of adipokines in monosodium glutamate-treated obese rats.

PubMed

Svidnicki, Paulo Vinicius; Leite, Nayara Carvalho; Vicari, Marcelo Ricardo; Almeida, Mara Cristina de; Artoni, Roberto Ferreira; Favero, Giovani Marino; Grassiolli, Sabrina; Nogaroto, Viviane

2015-06-01

The aim of this study was to evaluate the genetic expression of adipokines in the adipocytes of monosodium glutamate (MSG)-treated obese rats submitted to physical activity. Obesity was induced by neonatal MSG administration. Exercised rats (MSG and control) were subjected to swim training for 30 min for 10 weeks, whereas their respective controls remained sedentary. Total RNA was obtained from sections of the mesenteric adipose tissue of the rats. mRNA levels of adiponectin (Adipoq), tumor necrosis factor alpha (Tnf), peroxisome proliferator-activated receptor alpha (Ppara), and peroxisome proliferator-activated receptor gamma (Pparg) adipokines were quantified by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). In the exercise-trained control group, the expression of Adipoq increased compared to the sedentary control, which was not observed in the MSG-obese rats. Increased levels of Tnf in MSG-obese rats were not reversed by the swim training. The expression of Ppara was higher in sedentary MSG-obese rats compared to the sedentary control. Swimming increased this adipokine expression in the exercise-trained control rats compared to the sedentary ones. mRNA levels of Pparg were higher in the sedentary MSG-rats compared to the sedentary control; however, the exercise did not influenced its expression in the groups analyzed. In conclusion, regular physical activity was not capable to correct the expression of proinflammatory adipokines in MSG-obese rat adipocytes.

Pro-Inflammatory Adipokines as Predictors of Incident Cancers in a Chinese Cohort of Low Obesity Prevalence in Hong Kong

PubMed Central

Yeung, Chun-Yip; Tso, Annette Wai-Kwan; Xu, Aimin; Wang, Yu; Woo, Yu-Cho; Lam, Tai-Hing; Lo, Su-Vui; Fong, Carol Ho-Yee; Wat, Nelson Ming-Sang; Woo, Jean; Cheung, Bernard Man-Yung; Lam, Karen Siu-Ling

2013-01-01

Background Cytokines released from adipose tissues induce chronic low-grade inflammation, which may enhance cancer development. We investigated whether indices of obesity and circulating adipokine levels could predict incident cancer risk. Materials and Methods This longitudinal community-based study included subjects from the Hong Kong Cardiovascular Risk Factors Prevalence Study (CRISPS) study commenced in 1995-1996 (CRISP-1) with baseline assessments including indices of obesity. Subjects were reassessed in 2000-2004 (CRISPS-2) with measurement of serum levels of adipokines including interleukin-6 (IL-6), soluble tumor necrosis factor receptor 2 (sTNFR2; as a surrogate marker of tumor necrosis factor-α activity), leptin, lipocalin 2, adiponectin and adipocyte-fatty acid binding protein (A-FABP). Incident cancer cases were identified up to 31 December 2011. Results 205 of 2893 subjects recruited at CRISPS-1 had developed incident cancers. More of the subjects who developed cancers were obese (22.1 vs 16.1%) or had central obesity (36.6 vs 24.5%) according to Asian cut-offs. Waist circumference (adjusted HR 1.02 [1.00-1.03] per cm; p=0.013), but not body mass index (adjusted HR 1.04 [1.00-1.08] per kg/m2; p=0.063), was a significant independent predictor for incident cancers after adjustment for age, sex and smoking status. 99 of 1899 subjects reassessed at CRISPS-2 had developed cancers. Subjects who developed cancers had significantly higher level of hsCRP, IL-6, sTNFR2 and lipocalin 2. After adjustment for conventional risk factors, only IL-6 (HR 1.51, 95% CI 1.18-1.95) and sTNFR2 (HR 3.27, 95%CI 1.65-6.47) predicted cancer development. Conclusions Our data supported the increased risk of malignancy by chronic low grade inflammation related to central obesity. PMID:24205276

Myocardial Adiponectin Isoform Shift in Dogs with Congestive Heart Failure—A Comparison to Hibernating Brown Bears (Ursus arctos horribilis)

PubMed Central

Nelson, O. Lynne; Wood, Rachael M.; Häggström, Jens; Kvart, Clarence; Robbins, Charles T.

2017-01-01

Adiponectin is the most abundant plasma adipokine, and is well known for its role in energy homeostasis and cardiac protection. In humans with dilated cardiomyopathy, myocardial adiponectin protein expression is reduced compared to normal hearts and has been implicated in the pathology of cardiomyopathy. Serum adiponectin levels are often conflicting, with higher levels associated with poor survival in humans with congestive heart failure (CHF). We evaluated adiponectin serum concentrations and myocardial protein expression in dogs with naturally occurring myxomatous mitral valve disease and CHF. We compared the findings to active and hibernating brown bears as bears are adapted to endure an extreme period of low cardiac output during their annual hibernation. Bears exhibited largely the active high-molecular weight (HMW) versus the low-molecular weight isoforms of myocardial adiponectin (HMW:LMW = 6.3) during both the active period and hibernation, while healthy dogs exhibited a more balanced mix of isoforms. Dogs with CHF expressed predominately HMW isoforms of adiponectin (HMW:LMW = 12.5), appearing more similar to bears. In contrast to humans, serum adiponectin was significantly lower in dogs with CHF and lowest levels in the severest CHF class. In both dogs and bears, myocardial adiponectin was expressed independent of circulating adiponectin concentrations, suggesting a local regulatory mechanism within the heart. PMID:29056695

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance

PubMed Central

Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

2017-01-01

Background: The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. Methods: To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Results: Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Conclusions: Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to

Epac2a-null mice exhibit obesity-prone nature more susceptible to leptin resistance.

PubMed

Hwang, M; Go, Y; Park, J-H; Shin, S-K; Song, S E; Oh, B-C; Im, S-S; Hwang, I; Jeon, Y H; Lee, I-K; Seino, S; Song, D-K

2017-02-01

The exchange protein directly activated by cAMP (Epac), which is primarily involved in cAMP signaling, has been known to be essential for controlling body energy metabolism. Epac has two isoforms: Epac1 and Epac2. The function of Epac1 on obesity was unveiled using Epac1 knockout (KO) mice. However, the role of Epac2 in obesity remains unclear. To evaluate the role of Epac2 in obesity, we used Epac2a KO mice, which is dominantly expressed in neurons and endocrine tissues. Physiological factors related to obesity were analyzed: body weight, fat mass, food intake, plasma leptin and adiponectin levels, energy expenditure, glucose tolerance, and insulin and leptin resistance. To determine the mechanism of Epac2a, mice received exogenous leptin and then hypothalamic leptin signaling was analyzed. Epac2a KO mice appeared to have normal glucose tolerance and insulin sensitivity until 12 weeks of age, but an early onset increase of plasma leptin levels and decrease of plasma adiponectin levels compared with wild-type mice. Acute leptin injection revealed impaired hypothalamic leptin signaling in KO mice. Consistently, KO mice fed a high-fat diet (HFD) were significantly obese, presenting greater food intake and lower energy expenditure. HFD-fed KO mice were also characterized by greater impairment of hypothalamic leptin signaling and by weaker leptin-induced decrease in food consumption compared with HFD-fed wild-type mice. In wild-type mice, acute exogenous leptin injection or chronic HFD feeding tended to induce hypothalamic Epac2a expression. Considering that HFD is an inducer of hypothalamic leptin resistance and that Epac2a functions in pancreatic beta cells during demands of greater work load, hypothalamic Epac2a may have a role in facilitating leptin signaling, at least in response to higher metabolic demands. Thus, our data indicate that Epac2a is critical for preventing obesity and thus Epac2a activators may be used to manage obesity and obesity-mediated metabolic

Adiponectin gene therapy ameliorates high-fat, high-sucrose diet-induced metabolic perturbations in mice

PubMed Central

Kandasamy, A D; Sung, M M; Boisvenue, J J; Barr, A J; Dyck, J R B

2012-01-01

Background and Design: Adiponectin is an adipokine secreted primarily from adipose tissue that can influence circulating plasma glucose and lipid levels through multiple mechanisms involving a variety of organs. In humans, reduced plasma adiponectin levels induced by obesity are associated with insulin resistance and type 2 diabetes, suggesting that low adiponectin levels may contribute the pathogenesis of obesity-related insulin resistance. Methods and Results: The objective of the present study was to investigate whether gene therapy designed to elevate circulating adiponectin levels is a viable strategy for ameliorating insulin resistance in mice fed a high-fat, high-sucrose (HFHS) diet. Electroporation-mediated gene transfer of mouse adiponectin plasmid DNA into gastrocnemius muscle resulted in elevated serum levels of globular and high-molecular weight adiponectin compared with control mice treated with empty plasmid. In comparison to HFHS-fed mice receiving empty plasmid, mice receiving adiponectin gene therapy displayed significantly decreased weight gain following 13 weeks of HFHS diet associated with reduced fat accumulation, and exhibited increased oxygen consumption and locomotor activity as measured by indirect calorimetry, suggesting increased energy expenditure in these mice. Consistent with improved whole-body metabolism, mice receiving adiponectin gene therapy also had lower blood glucose and insulin levels, improved glucose tolerance and reduced hepatic gluconeogenesis compared with control mice. Furthermore, immunoblot analysis of livers from mice receiving adiponectin gene therapy showed an increase in insulin-stimulated phosphorylation of insulin signaling proteins. Conclusion: Based on these data, we conclude that adiponectin gene therapy ameliorates the metabolic abnormalities caused by feeding mice a HFHS diet and may be a potential therapeutic strategy to improve obesity-mediated impairments in insulin sensitivity. PMID:23446660

Associations of erythrocyte palmitoleic acid with adipokines, inflammatory markers, and the metabolic syndrome in middle-aged and older Chinese123

PubMed Central

Zong, Geng; Ye, Xingwang; Sun, Liang; Li, Huaixing; Yu, Zhijie; Hu, Frank B

2012-01-01

Background: Palmitoleic acid has been shown to regulate adipokine expression and systemic metabolic homeostasis in animal studies. However, its association with human metabolic diseases remains controversial. Objective: We aimed to investigate associations of erythrocyte palmitoleic acid with adipokines, inflammatory markers, and metabolic syndrome (MetS) in a Chinese population. Design: Erythrocyte fatty acids were measured in a population-based sample of 3107 men and women aged 50–70 y, for whom plasma glucose, insulin, lipid profile, adiponectin, retinol binding protein 4 (RBP-4), plasminogen activator inhibitor type 1, and high-sensitivity C-reactive protein (hsCRP) were measured. MetS was defined according to the updated National Cholesterol Education Program Adult Treatment Panel III criteria for Asian Americans. Results: The mean (±SD) erythrocyte palmitoleic acid value was 0.41 ± 0.20% of total fatty acids. Palmitoleic acid was positively correlated with RBP-4 (r = 0.14, P < 0.001) and inversely correlated with adiponectin (r = −0.15, P < 0.001). After multivariable adjustment, palmitoleic acid was strongly associated with MetS and its components. ORs (95% CIs) for comparisons of extreme quartiles of palmitoleic acid were 3.50 (2.66, 4.59) for MetS, 7.88 (5.90, 10.52) for hypertriglyceridemia, 2.13 (1.66, 2.72) for reduced HDL cholesterol, 1.99 (1.60, 2.48) for central obesity, and 1.86 (1.41, 2.44) for elevated blood pressure (all P < 0.001). Further control for adipokines and hsCRP abolished the association of palmitoleic acid with central obesity but not with other MetS components. Conclusion: Erythrocyte palmitoleic acid is associated with an adverse profile of adipokines and inflammatory markers and an increased risk of MetS in this Chinese population. PMID:23015321

Leptin plays a catabolic role on articular cartilage.

PubMed

Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

2010-10-01

Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA.

Obesity-related hormones and endometrial cancer among postmenopausal women: a nested case–control study within the B~FIT cohort

PubMed Central

Dallal, Cher M; Brinton, Louise A; Bauer, Douglas C; Buist, Diana S M; Cauley, Jane A; Hue, Trisha F; LaCroix, Andrea; Tice, Jeffrey A; Chia, Chia; Falk, Roni; Pfeiffer, Ruth; Pollak, Michael; Veenstra, Timothy D; Xu, Xia; Lacey, James V

2014-01-01

Endometrial cancer risk is strongly influenced by obesity, but the mechanisms of action remain unclear. Leptin and adiponectin, secreted from adipose tissue, reportedly play a role in such carcinogenic processes as cell proliferation, angiogenesis, and insulin regulation. In this case–control study, nested within the Breast and Bone Follow-up of the Fracture Intervention Trial (n = 15 595), we assessed pre-diagnostic serum leptin, total adiponectin, and high-molecular-weight (HMW) adiponectin in relation to endometrial cancer among postmenopausal women. During the 10-year follow-up, 62 incident endometrial cases were identified and matched to 124 controls on age, geographical site, time of fasting blood draw at baseline (1992–1993), and trial participation status. Adipokines and C-peptide were measured by ELISA. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated via conditional logistic regression, with exposures categorized in tertiles (T). Multivariable models considered C-peptide, BMI (kg/m2), and estradiol (E2) as potential confounders. Endometrial cancer risk was significantly associated with higher leptin levels, adjusted for E2 and C-peptide (ORT3 vs T1 = 2.96; 95% CI, 1.21–7.25; P trend <0.01). After further adjustment for BMI, the estimates were attenuated and the positive trend was no longer statistically significant (ORT3 vs T1 = 2.11; 95% CI, 0.69–6.44; P trend = 0.18). No significant associations were observed with adiponectin or HMW adiponectin and endometrial cancer. Our findings with leptin suggest that the leptin–BMI axis might increase endometrial cancer risk through mechanisms other than estrogen-driven proliferation. Continued exploration of these pathways in larger prospective studies may help elucidate mechanisms underlying observed obesity–endometrial cancer associations. PMID:23222000

Sex Dimorphism in Late Gestational Sleep Fragmentation and Metabolic Dysfunction in Offspring Mice

PubMed Central

Khalyfa, Abdelnaby; Carreras, Alba; Almendros, Isaac; Hakim, Fahed; Gozal, David

2015-01-01

Background: Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates. Methods: Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed. Results: Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF. Conclusion: Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood. Citation: Khalyfa A, Carreras A, Almendros I, Hakim F, Gozal D. Sex

Sex dimorphism in late gestational sleep fragmentation and metabolic dysfunction in offspring mice.

PubMed

Khalyfa, Abdelnaby; Carreras, Alba; Almendros, Isaac; Hakim, Fahed; Gozal, David

2015-04-01

Excessive sleep fragmentation (SF) is common in pregnant women. Adult-onset metabolic disorders may begin during early development and exhibit substantial sex dimorphism. We hypothesized that metabolic dysfunction induced by gestational SF in male mice would not be apparent in female littermates. Body weight and food consumption were measured weekly in male and female offspring after late gestational SF or control sleep (SC). At 20 weeks, plasma leptin, adiponectin, lipid profiles, and insulin and glucose tolerance tests were assessed. Leptin and adiponectin, M1, and M2 macrophage messenger RNA expression and polarity were examined. Adiponectin gene promoter methylation levels in several tissues were assessed. Food intake, body weight, visceral fat mass, and insulin resistance were higher, and adiponectin levels lower in male but not female offspring exposed to gestational SF. However, dyslipidemia was apparent in both male and female offspring exposed to SF, albeit of lesser magnitude. In visceral fat, leptin messenger RNA expression was selectively increased and adiponectin expression was decreased in male offspring exposed to gestational SF, but adiponectin was increased in exposed female offspring. Differences in adipokine expression also emerged in liver, subcutaneous fat, and muscle. Increased M1 macrophage markers were present in male offspring exposed to SF (SFOM) while increased M2 markers emerged in SF in female offspring (SFOF). Similarly, significant differences emerged in the methylation patterns of adiponectin promoter in SFOM and SFOF. Gestational sleep fragmentation increases the susceptibility to obesity and metabolic syndrome in male but not in female offspring, most likely via epigenetic changes. Thus, sleep perturbations impose long-term detrimental effects to the fetus manifesting as sex dimorphic metabolic dysfunction in adulthood. © 2015 Associated Professional Sleep Societies, LLC.

DYSREGULATION OF MATERNAL SERUM ADIPONECTIN IN PRETERM LABOR

PubMed Central

Mazaki-Tovi, Shali; Romero, Roberto; Vaisbuch, Edi; Erez, Offer; Mittal, Pooja; Chaiworapongsa, Tinnakorn; Kim, Sun Kwon; Pacora, Percy; Yeo, Lami; Gotsch, Francesca; Dong, Zhong; Nhan-Chang, Chia-Ling; Jodicke, Cristiano; Yoon, Bo Hyun; Hassan, Sonia S.; Kusanovic, Juan Pedro

2013-01-01

maternal age, BMI, gestational age at sampling, and parity. Conclusion 1) Preterm labor is characterized by a change in the profile of adiponectin multimers concentrations and their relative isoforms. These changes were observed in patients with an episode of preterm labor not leading to preterm delivery, in patients with intra-amniotic inflammation, or in those without evidence of intra-amniotic inflammation; 2) The changes in adiponectin multimer concentrations reported in preterm labor are different from those previously reported in spontaneous labor at term, suggesting that there is a fundamental difference between preterm labor and labor at term; 3) The findings reported herein, provide the first evidence for the participation of adiponectin multimer in preterm parturition. We propose that adiponectins and adipokines in general provide a mechanism to organize the metabolic demands generated by the process of preterm parturition regardless of the nature of the insult (intra-amniotic inflammation or not). PMID:19579094

Cold-Induced Browning Dynamically Alters the Expression Profiles of Inflammatory Adipokines with Tissue Specificity in Mice.

PubMed

Luo, Xiao; Jia, Ru; Zhang, Qiangling; Sun, Bo; Yan, Jianqun

2016-05-23

Cold exposure or β₃-adrenoceptor agonist treatment induces the adipose tissues remodeling, relevant for beige adipogenesis within white adipose tissue (WAT). It remains unclear whether this process influences inflammatory adipokines expression in adipose tissues. We determine the temporal profile of cold or β₃-adrenoceptor agonist (CL316,243)-induced changes in the expression of inflammatory adipokines in adipose tissues in mice or primary mice adipocytes. Male C57BL/6J mice at eight weeks old were exposed to 4 °C for 1-5 days. Interscapular brown adipose tissue (iBAT), inguinal subcutaneous WAT (sWAT) and epididymal WAT (eWAT) were harvested for gene and protein expression analysis. In addition, cultured primary mice brown adipocyte (BA) and white adipocyte (WA) treated with or without CL316,243 were harvested for gene expression analysis. The inflammatory adipokines expressed significantly higher in WAT than BAT at baseline. They were rapidly changed in iBAT, while down-regulated in sWAT and up-regulated in eWAT during the cold acclimation. Upon CL316,243 treatment, detected inflammatory adipokines except Leptin were transiently increased in both BA and WA. Our in vivo and in vitro data demonstrate that the browning process alters the inflammatory adipokines expression in adipose tissues, which is acutely responded to in iBAT, dynamically decreased in sWAT whilst increased in eWAT for compensation.

The influence of sex, body composition, and nonesterified fatty acids on serum adipokine concentrations.

PubMed

Plaisance, Eric P; Grandjean, Peter W; Judd, Robert L; Jones, Kathy W; Taylor, J Kyle

2009-11-01

Serum adiponectin concentrations are higher in women than men. The sexual dimorphism for adiponectin has been attributed to the direct effects of testosterone on adipose tissue adiponectin secretion. However, serum testosterone and adiponectin concentrations are generally lower in obese men than lean men, suggesting that sex steroids may not be the only factor that contributes to sex differences in serum adiponectin. The primary objective of this study was to examine the influence of sex, body composition, and nonesterified fatty acids (NEFAs) on serum adiponectin concentrations. Women and men between the ages of 18 and 35 years were consecutively accrued into the study. Sixty-one participants were partitioned into normal-weight (15 female and 16 male) or obese (14 female and 16 male) groups. Blood samples were obtained after a 12-hour fast. Differences between groups were determined by analysis of variance with Tukey-Kramer post hoc testing. Serum adiponectin was 26% higher in women compared with men. Body mass index was associated with total serum adiponectin in men (r = -0.63, P < .05) but not women. Adiponectin was correlated with the homeostasis model assessment index in women (r = -0.56, P < .05) and men (r = -0.58, P < .05) and with NEFAs (r = -0.68, P < .05) in men only. After partitioning men and women into normal-weight and obese groups, serum adiponectin was lower and NEFAs were higher in obese men only. Homeostasis model assessment was similar between obese women and men despite higher NEFAs in the obese men. Leptin and plasminogen activator inhibitor-1 were higher in obese participants but were not associated with serum NEFAs. These results suggest that serum NEFAs may reduce adiponectin concentrations independent of their effects on insulin sensitivity in obese young men.

Hair cycle control by leptin as a new anagen inducer.

PubMed

Sumikawa, Yasuyuki; Inui, Shigeki; Nakajima, Takeshi; Itami, Satoshi

2014-01-01

Our purpose is to clarify the physiological role of leptin in hair cycle as leptin reportedly causes activation of Stat3, which is indispensable for hair cycling. While hair follicles in dorsal skin of 5-week-old C57/BL6 mice had progressed to late anagen phase, those in dorsal skin of 5-week-old leptin receptor deficient db/db mice remained in the first telogen and later entered the anagen at postnatal day 40, indicating that deficiency in leptin receptor signalling delayed the second hair cycle progression. Next, we shaved dorsal hairs on wild-type mice at postnatal 7 weeks and injected skin with mouse leptin or a mock. After 20 days, although mock injection showed no effect, hair growth occurred around leptin injection area. Human leptin fragment (aa22-56) had similar effects. Although the hair cycle of ob/ob mice was similar to that of wild-type mice, injection of mouse leptin on ob/ob mice at postnatal 7 weeks induced anagen transition. Immunohistochemically, leptin is expressed in hair follicles from catagen to early anagen in wild-type mice, suggesting that leptin is an anagen inducer in vivo. Phosphorylation of Erk, Jak2 and Stat3 in human keratinocytes was stimulated by leptin and leptin fragment. In addition, RT-PCR and ELISA showed that the production of leptin by human dermal papilla cells increased under hypoxic condition, suggesting that hypoxia in catagen/telogen phase promotes leptin production, preparing for entry into the next anagen. In conclusion, leptin, a well-known adipokine, acts as an anagen inducer and represents a new player in hair biology. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Skeletal muscle mitochondrial energetics in obesity and type 2 diabetes mellitus: endocrine aspects.

PubMed

Aguer, Céline; Harper, Mary-Ellen

2012-12-01

During the development of type 2 diabetes mellitus, skeletal muscle is a major site of insulin resistance. The latter has been linked to mitochondrial dysfunction and impaired fatty acid oxidation. Some hormones like insulin, thyroid hormones and adipokines (e.g., leptin, adiponectin) have positive effects on muscle mitochondrial bioenergetics through their direct or indirect effects on mitochondrial biogenesis, mitochondrial protein expression, mitochondrial enzyme activities and/or AMPK pathway activation--all of which can improve fatty acid oxidation. It is therefore not surprising that treatment with these hormones has been proposed to improve muscle and whole body insulin sensitivity. However, treatment of diabetic patients with leptin and adiponectin has no effect on muscle mitochondrial bioenergetics showing resistance to these hormones during type 2 diabetes. Furthermore, treatment with most thyroid hormones has unexpectedly revealed negative effects on muscle insulin sensitivity. Future research should focus on development of agents that improve metabolic dysfunction downstream of hormone receptors. Copyright © 2012 Elsevier Ltd. All rights reserved.

The 148 M allele of the PNPLA3 is associated with plasma irisin levels in a population sample of Caucasian children: The PANIC Study.

PubMed

Viitasalo, Anna; Atalay, Mustafa; Pihlajamäki, Jussi; Jääskeläinen, Jarmo; Korkmaz, Ayhan; Kaminska, Dorota; Lindi, Virpi; Lakka, Timo A

2015-07-01

There are no previous data on the association of PNPLA3 I148M polymorphism (rs738409) with circulating adipokines and myokines in children. Subjects were a population sample of 481 Caucasian children aged 6-8 years. We assessed circulating levels of irisin together with IL-6, TNF-α, leptin, high molecular weight (HMW)-adiponectin, alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) while the subjects were stratified according to PNPLA3 I148M variants. The PNPLA3 rs738409 polymorphism had a linear relationship with plasma levels of irisin after adjustment for age, sex and body height (p=0.007) but it was not associated with circulating levels of interleukin- 6 (IL-6), tumor-necrosis factor α (TNF-α), leptin or HMW-adiponectin. PNPLA3 148M allele carriers had higher plasma levels of irisin than the non-carriers. This might be due to compensatory mechanism to limit early steatotic and inflammatory changes in the liver. Copyright © 2015 Elsevier Inc. All rights reserved.

An acute intake of a walnut-enriched meal improves postprandial adiponectin response in healthy young adults.

PubMed

Lozano, Aquiles; Perez-Martinez, Pablo; Marin, Carmen; Tinahones, Francisco J; Delgado-Lista, Javier; Cruz-Teno, Cristina; Gomez-Luna, Purificacion; Rodriguez-Cantalejo, Fernando; Perez-Jimenez, Francisco; Lopez-Miranda, Jose

2013-12-01

A deficit in adiponectin plays an important causal role in insulin resistance and metabolic syndrome. We hypothesized that as seen during the fasting state, the intake of a walnut-enriched meal increased postprandial adiponectin. Twenty-one healthy white men followed a 4-week baseline diet and then consumed 3 fat-loaded meals that included 1 g fat/kg body weight (65% fat) according to a randomized crossover design: olive oil-enriched meal (22% saturated fatty acids [SFA], 38% monounsaturated fatty acids [MUFA], 4% polyunsaturated fatty acids [PUFA]), butter-enriched meal (35% SFA, 22% MUFA, 4% PUFA), and walnut-enriched meal (20% SFA, 24% MUFA, 16% PUFA, and 4% α-linolenic acid). Leptin, resistin, adiponectin, and free fatty acids were determined at 0, 3, 6, and 8.5 hours after the fat load. After the walnut-enriched meal, plasma adiponectin concentrations were higher at 3 and 6 hours (P = .011, P = .046, respectively) compared with the butter-enriched meal and higher at 6 hours compared with the olive oil-enriched meal (P = .036). Free fatty acid levels decreased from baseline at 3 hours after the walnut-enriched meal (P = .001). No differences were observed between the 3 meals for leptin and resistin responses. Our data confirmed a beneficial profile in the postprandial response to walnuts, source of omega-3 PUFA with an increased postprandial adiponectin and lower postprandial free fatty acid responses. These findings suggest that the postprandial state is important for understanding the possible cardioprotective effects associated with omega-3 PUFA dietary fat. © 2013 Elsevier Inc. All rights reserved.

The role of production of adipsin and leptin in the development of insulin resistance in patients with abdominal obesity.

PubMed

Vasilenko, M A; Kirienkova, E V; Skuratovskaia, D A; Zatolokin, P A; Mironyuk, N I; Litvinova, L S

2017-07-01

We investigated the tissue-specific features of the production of adipokines (leptin and adipsin) by adipose tissue in obese patients depending on the degree of obesity and the state of carbohydrate metabolism. An increase in the content of adipsin and leptin in the blood plasma was found. In patients with varying degrees of obesity with and without type 2 diabetes mellitus (DM 2), we determined the level of tissue-specific expression of LEP and CFD genes encoding leptin and adipsin, respectively. The contribution of different adipose tissue depots to the blood plasma level of adipsin and leptin in obese patients with and without DM 2 was established. The disturbance of reciprocal relationships between adipsin and leptin in obesity is associated with the development of insulin resistance.

Central insulin and leptin-mediated autonomic control of glucose homeostasis

PubMed Central

Marino, Joseph S.; Xu, Yong; Hill, Jennifer W.

2016-01-01

Largely as a result of rising obesity rates, the incidence of type 2 diabetes is escalating rapidly. Type 2 diabetes results from multi-organ dysfunctional glucose metabolism. Recent publications have highlighted hypothalamic insulin- and adipokine-sensing as a major determinant of peripheral glucose and insulin responsiveness. The preponderance of evidence indicates that the brain is the master regulator of glucose homeostasis, and that hypothalamic insulin and leptin signaling in particular play a crucial role in the development of insulin resistance. This review discusses the neuronal crosstalk between the hypothalamus, autonomic nervous system, and tissues associated with the pathogenesis of type 2 diabetes, and how hypothalamic insulin and leptin signaling are integral to maintaining normal glucose homeostasis. PMID:21489811

ADIPOQ single nucleotide polymorphism: Association with adiponectin and lipoproteins levels restricted to men

PubMed Central

Tureck, Luciane Viater; Leite, Neiva; Souza, Ricardo Lehtonen Rodrigues; da Silva Timossi, Luciana; Osiecki, Ana Claudia Vecchi; Osiecki, Raul; Alle, Lupe Furtado

2015-01-01

Adiponectin is an adipokine inversely correlated with obesity, which has beneficial effect on insulin resistance and lipid metabolism. Considering its potential as a therapeutic target in the metabolic disorder contexts, and in order to add knowledge in the area, our study evaluated the ADIPOQ 276G > T polymorphism effect on adiponectin levels, and on lipoproteins of clinical interest in a population sample composed of 211 healthy individuals. Significant effects were observed only among men: the carriers of heterozygous genotype (GT) showed high levels of adiponectin (p = 0.018), while the rare homozygous genotype (TT) gave its carriers a negative phenotype, represented by higher levels of low density lipoprotein cholesterol (LDL-C) (p = 0.004 and p = 0.005) and total cholesterol (TC) (p = 0.010 and p = 0.005) compared to carriers of other genotypes (GG and GT respectively), the independent effect of SNP on LDL-C and TC levels was confirmed by multiple regression analysis (p = 0.008 and p = 0.044). We found no evidence of correlation between circulating adiponectin levels and biochemical markers, which suggests, therefore, an SNP 276G > T independent effect on adiponectin levels and on lipoprotein metabolism in men enrolled in this study. PMID:26137445

Pegylated Leptin Antagonist Is a Potent Orexigenic Agent: Preparation and Mechanism of Activity

PubMed Central

Elinav, Eran; Niv-Spector, Leonora; Katz, Meirav; Price, Tulin O.; Ali, Mohammed; Yacobovitz, Michal; Solomon, Gili; Reicher, Shay; Lynch, Jessica L.; Halpern, Zamir; Banks, William A.; Gertler, Arieh

2009-01-01

Leptin, a pleiotropic adipokine, is a central regulator of appetite and weight and a key immunomodulatory protein. Although inborn leptin deficiency causes weight gain, it is unclear whether induced leptin deficiency in adult wild-type animals would be orexigenic. Previous work with a potent competitive leptin antagonist did not induce a true metabolic state of leptin deficiency in mice because of a short circulating half-life. In this study, we increased the half-life of the leptin antagonist by pegylation, which resulted in significantly increased bioavailability and retaining of antagonistic activity. Mice administered the pegylated antagonist showed a rapid and dramatic increase in food intake with weight gain. Resulting fat was confined to the mesenteric region with no accumulation in the liver. Serum cholesterol, triglyceride, and hepatic aminotransferases remained unaffected. Weight changes were reversible on cessation of leptin antagonist treatment. The mechanism of severe central leptin deficiency was found to be primarily caused by blockade of transport of circulating leptin across the blood-brain barrier with antagonisms at the arcuate nucleus playing a more minor role. Altogether we introduce a novel compound that induces central and peripheral leptin deficiency. This compound should be useful in exploring the involvement of leptin in metabolic and immune processes and could serve as a therapeutic for the treatment of cachexia. PMID:19342450

Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling.

PubMed

Kopp, Christina; Hosseini, Afshin; Singh, Shiva P; Regenhard, Petra; Khalilvandi-Behroozyar, Hamed; Sauerwein, Helga; Mielenz, Manfred

2014-11-18

The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001) and the mRNA abundances of GPR109A (p ≤ 0.05) and chemerin (p ≤ 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows.

Nicotinic Acid Increases Adiponectin Secretion from Differentiated Bovine Preadipocytes through G-Protein Coupled Receptor Signaling

PubMed Central

Kopp, Christina; Hosseini, Afshin; Singh, Shiva P.; Regenhard, Petra; Khalilvandi-Behroozyar, Hamed; Sauerwein, Helga; Mielenz, Manfred

2014-01-01

The transition period in dairy cows (3 weeks prepartum until 3 weeks postpartum) is associated with substantial mobilization of energy stores, which is often associated with metabolic diseases. Nicotinic acid (NA) is an antilipolytic and lipid-lowering compound used to treat dyslipidaemia in humans, and it also reduces non-esterified fatty acids in cattle. In mice the G-protein coupled receptor 109A (GPR109A) ligand NA positively affects the secretion of adiponectin, an important modulator of glucose and fat metabolism. In cattle, the corresponding data linking NA to adiponectin are missing. Our objective was to examine the effects of NA on adiponectin and AMPK protein abundance and the expression of mRNAs of related genes such as chemerin, an adipokine that enhances adiponectin secretion in vitro. Differentiated bovine adipocytes were incubated with pertussis toxin (PTX) to verify the involvement of GPR signaling, and treated with 10 or 15 µM NA for 12 or 24 h. NA increased adiponectin concentrations (p ≤ 0.001) and the mRNA abundances of GPR109A (p ≤ 0.05) and chemerin (p ≤ 0.01). Pre-incubation with PTX reduced the adiponectin response to NA (p ≤ 0.001). The NA-stimulated secretion of adiponectin and the mRNA expression of chemerin in the bovine adipocytes were suggestive of GPR signaling-dependent improved insulin sensitivity and/or adipocyte metabolism in dairy cows. PMID:25411802

Adiponectin/resistin interplay in serum and in adipose tissue of obese and normal-weight individuals.

PubMed

Jonas, Marta Izabela; Kurylowicz, Alina; Bartoszewicz, Zbigniew; Lisik, Wojciech; Jonas, Maurycy; Domienik-Karlowicz, Justyna; Puzianowska-Kuznicka, Monika

2017-01-01

The interplay between adiponectin and resistin, the two adipokines of opposite effects, may determine the metabolic profile of obese individuals and development of obesity-related complications. The current study was conducted to assess how adiponectin/resistin interplay in sera and adipose tissues may influence the metabolic profile of obese and normal-weight subjects. Concentrations of adiponectin and resistin were measured on protein level by immunoassay in visceral and subcutaneous adipose tissues from 50 obese (body mass index > 40 kg/m 2 ) and 28 normal-weight (body mass index 20-24.9 kg/m 2 ) individuals. Simultaneously expression of ADIPOQ and RETN (encoding adiponectin and resistin, respectively) was assessed on mRNA level by real-time PCR. ADIPOQ mRNA (P = 0.0001) and adiponectin protein (P = 0.0013) levels were lower, while RETN mRNA (P = 0.0338) and resistin (P < 0.0001)-higher in subcutaneous adipose tissues of obese subjects. ADIPOQ and RETN mRNA levels did not correlate with protein concentrations in the investigated adipose tissues. In obesity adiponectin serum concentrations correlated positively with ADIPOQ mRNA in subcutaneous adipose tissue (P = 0.005) and negatively with protein levels in visceral adipose tissue (P = 0.001). Obesity was associated with higher adiponectin-resistin index value in sera (P < 0.0001) and decreased in subcutaneous adipose tissue (P < 0.001), but only adiponectin-resistin index measured in sera was significantly higher in obese with the metabolic syndrome (P = 0.04). Obesity affects synthesis of adiponectin and resistin mainly in subcutaneous adipose tissue. The adiponectin-resistin index assessed in the adipose tissues has a different prognostic value compared to the adiponectin-resistin index in serum and does not reflect a metabolic risk in obese individuals.

Regulation of intracellular trafficking and secretion of adiponectin by myosin II.

PubMed

Bedi, Deepa; Dennis, John C; Morrison, Edward E; Braden, Tim D; Judd, Robert L

2017-08-19

Adiponectin is a protein secreted by white adipocytes that plays an important role in insulin action, energy homeostasis and the development of atherosclerosis. The intracellular localization and trafficking of GLUT4 and leptin in adipocytes has been well studied, but little is known regarding the intracellular trafficking of adiponectin. Recent studies have demonstrated that constitutive adiponectin secretion is dependent on PIP2 levels and the integrity of cortical F-actin. Non-muscle myosin II is an actin-based motor that is associated with membrane vesicles and participates in vesicular trafficking in mammalian cells. Therefore, we investigated the role of myosin II in the trafficking and secretion of adiponectin in 3T3-L1 adipocytes. Confocal microscopy revealed that myosin IIA and IIB were dispersed throughout the cytoplasm of the adipocyte. Both myosin isoforms were localized in the Golgi/TGN region as evidenced by colocalization with the cis-Golgi marker, p115 and the trans-Golgi marker, γ-adaptin. Inhibition of myosin II activity by blebbistatin or actin depolymerization by latrunculin B dispersed myosin IIA and IIB towards the periphery while significantly inhibiting adiponectin secretion. Therefore, the constitutive trafficking and secretion of adiponectin in 3T3-L1 adipocytes occurs by an actin-dependent mechanism that involves the actin-based motors, myosin IIA and IIB. Copyright © 2017 Elsevier Inc. All rights reserved.

Development of second generation peptides modulating cellular adiponectin receptor responses

NASA Astrophysics Data System (ADS)

Otvos, Laszlo; Knappe, Daniel; Hoffmann, Ralf; Kovalszky, Ilona; Olah, Julia; Hewitson, Tim; Stawikowska, Roma; Stawikowski, Maciej; Cudic, Predrag; Lin, Feng; Wade, John; Surmacz, Eva; Lovas, Sandor

2014-10-01

The adipose tissue participates in the regulation of energy homeostasis as an important endocrine organ that secretes a number of biologically active adipokines, including adiponectin. Recently we developed and characterized a first-in-class peptide-based adiponectin receptor agonist by using in vitro and in vivo models of glioblastoma and breast cancer (BC). In the current study, we further explored the effects of peptide ADP355 in additional cellular models and found that ADP355 inhibited chronic myeloid leukemia (CML) cell proliferation and renal myofibroblast differentiation with mid-nanomolar IC50 values. According to molecular modeling calculations, ADP355 was remarkably flexible in the global minimum with a turn present in the middle of the peptide. Considering these structural features of ADP355 and the fact that adiponectin normally circulates as multimeric complexes, we developed and tested the activity of a linear branched dimer (ADP399). The dimer exhibited approximately 20-fold improved cellular activity inhibiting K562 CML and MCF-7 cell growth with high pM - low nM relative IC50 values. Biodistribution studies suggested superior tissue dissemination of both peptides after subcutaneous administration relative to intraperitoneal inoculation. After screening of a 397-member adiponectin active site library, a novel octapeptide (ADP400) was designed that counteracted 10-1000 nM ADP355- and ADP399-mediated effects on CML and BC cell growth at nanomolar concentrations. ADP400 induced mitogenic effects in MCF-7 BC cells perhaps due to antagonizing endogenous adiponectin actions or acting as an inverse agonist. While the linear dimer agonist ADP399 meets pharmacological criteria of a contemporary peptide drug lead, the peptide showing antagonist activity (ADP400) at similar concentrations will be an important target validation tool to study adiponectin functions.

Curcuminoids Lower Plasma Leptin Concentrations: A Meta-analysis.

PubMed

Atkin, Stephen L; Katsiki, Niki; Derosa, Giuseppe; Maffioli, Pamela; Sahebkar, Amirhossein

2017-12-01

Curcumin is a naturally occurring polyphenol that has been suggested to improve several metabolic diseases. Leptin is an adipokine involved in metabolic status and appetite, with marked crosstalk with other systems. Available data suggest that curcumin may affect leptin levels; therefore, this meta-analysis was performed to evaluate this. A systematic review and meta-analysis were undertaken on all randomized controlled trials of curcumin studies that included the measurement of leptin. The search included PubMed-Medline, Scopus, ISI Web of Knowledge, and Google Scholar databases. Quantitative data synthesis was performed by using a random-effects model, with standardized mean difference and 95% confidence interval as summary statistics. A funnel plot, Begg's rank correlation, and Egger's weighted regression tests assessed the presence of publication bias. Four eligible articles comprising five treatment arms were selected for the meta-analysis. Meta-analysis showed a significant decrease in plasma leptin concentrations following curcumin treatment (standardized mean difference: -0.69, 95% confidence interval: -1.16, -0.23, p = 0.003; I 2  = 76.53%). There was no evidence of publication bias. This meta-analysis showed that curcumin supplementation is associated with a decrease in leptin levels that may be regarded as a potential mechanism for the metabolic effects of curcumin. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Roles of leptin in bone metabolism and bone diseases.

PubMed

Chen, Xu Xu; Yang, Tianfu

2015-09-01

Adipose tissue has been more accepted as an active contributor to whole body homeostasis, rather than just a fat depot, since leptin, a 16 kDa protein, was discovered as the product of the obese gene in 1994. With more and more studies conducted on this hormone, it has been shown that there is a close relationship between adipose tissue and bone, which have important effects on each other. Bone is the source of many hormones, such as osteocalcin, that can affect energy metabolism and then the anabolism or catabolism of fat tissue. In contrast, the adipose tissue synthesizes and releases a series of adipokines, which are involved in bone metabolism through direct or indirect effects on bone formation and resorption. Interestingly, leptin, one of the most important cytokines derived from fat tissue, seems to account for the largest part of effects on bone, through direct or indirect involvement in bone remodeling and by playing a significant role in many bone diseases, such as osteoporosis, osteoarthritis, rheumatic arthritis, bone tumors and even fractures. In this review, we will discuss the progress in leptin research, particularly focusing on the roles of leptin in bone diseases.

Human NK Cell Subset Functions Are Differentially Affected by Adipokines

PubMed Central

Huebner, Lena; Engeli, Stefan; Wrann, Christiane D.; Goudeva, Lilia; Laue, Tobias; Kielstein, Heike

2013-01-01

Background Obesity is a risk factor for various types of infectious diseases and cancer. The increase in adipose tissue causes alterations in both adipogenesis and the production of adipocyte-secreted proteins (adipokines). Since natural killer (NK) cells are the host’s primary defense against virus-infected and tumor cells, we investigated how adipocyte-conditioned medium (ACM) affects functions of two distinct human NK cell subsets. Methods Isolated human peripheral blood mononuclear cells (PBMCs) were cultured with various concentrations of human and murine ACM harvested on two different days during adipogenesis and analyzed by fluorescent-activated cell sorting (FACS). Results FACS analyses showed that the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), granzyme A (GzmA) and interferon (IFN)-γ in NK cells was regulated in a subset-specific manner. ACM treatment altered IFN-γ expression in CD56dim NK cells. The production of GzmA in CD56bright NK cells was differentially affected by the distinct adipokine compositions harvested at different states of adipogenesis. Comparison of the treatment with either human or murine ACM revealed that adipokine-induced effects on NK cell expression of the leptin receptor (Ob-R), TRAIL and IFN-γ were species-specific. Conclusion Considering the growing prevalence of obesity and the various disorders related to it, the present study provides further insights into the roles human NK cell subsets play in the obesity-associated state of chronic low-grade inflammation. PMID:24098717

Nutritional Ingredients Modulate Adipokine Secretion and Inflammation in Human Primary Adipocytes

PubMed Central

Romacho, Tania; Glosse, Philipp; Richter, Isabel; Elsen, Manuela; Schoemaker, Marieke H.; van Tol, Eric A.; Eckel, Jürgen

2015-01-01

Nutritional factors such as casein hydrolysates and long chain polyunsaturated fatty acids have been proposed to exert beneficial metabolic effects. We aimed to investigate how a casein hydrolysate (eCH) and long chain polyunsaturated fatty acids could affect human primary adipocyte function in vitro. Incubation conditions with the different nutritional factors were validated by assessing cell vitality with lactate dehydrogenase (LDH) release and neutral red incorporation. Intracellular triglyceride content was assessed with Oil Red O staining. The effect of eCH, a non-peptidic amino acid mixture (AA), and long-chain polyunsaturated fatty acids (LC-PUFAs) on adiponectin and leptin secretion was determined by enzyme-linked immunosorbent assay (ELISA). Intracellular adiponectin expression and nuclear factor-κB (NF-κB) activation were analyzed by Western blot, while monocyte chemoattractant protein-1 (MCP-1) release was explored by ELISA. The eCH concentration dependently increased adiponectin secretion in human primary adipocytes through its intrinsic peptide bioactivity, since the non-peptidic mixture, AA, could not mimic eCH’s effects on adiponectin secretion. Eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and DHA combined with arachidonic acid (ARA) upregulated adiponectin secretion. However, only DHA and DHA/ARA exerted a potentanti-inflammatory effect reflected by prevention of tumor necrosis factor-α (TNF-α) induced NF-κB activation and MCP-1 secretion in human adipocytes. eCH and DHA alone or in combination with ARA, may hold the key for nutritional programming through their anti-inflammatory action to prevent diseases with low-grade chronic inflammation such as obesity or diabetes. PMID:25629558

Leptin and its potential interest in assisted reproduction cycles.

PubMed

Catteau, A; Caillon, H; Barrière, P; Denis, M G; Masson, D; Fréour, T

2016-04-01

Leptin, an adipose hormone, has been shown to control energy homeostasis and food intake, and exert many actions on female reproductive function. Consequently, this adipokine is a pivotal factor in studies conducted on animal models and humans to decipher the mechanisms behind the infertility often observed in obese women. A systematic PubMed search was conducted on all articles, published up to January 2015 and related to leptin and its actions on energy balance and reproduction, using the following key words: leptin, reproduction, infertility, IVF and controlled ovarian stimulation. The available literature was reviewed in order to provide an overview of the current knowledge on the physiological roles of leptin, its involvement in female reproductive function and its potential interest as a prognostic marker in IVF cycles. Animal and human studies show that leptin communicates nutritional status to the central nervous system and emerging evidence has demonstrated that leptin is involved in the control of reproductive functions by acting both directly on the ovaries and indirectly on the central nervous system. With respect to the clinical use of leptin as a biomarker in IVF cycles, a systematic review of the literature suggested its potential interest as a predictor of IVF outcome, as high serum and/or follicular fluid leptin concentrations have correlated negatively with cycle outcome. However, these preliminary results remain to be confirmed. Leptin regulates energy balance and female reproductive function, mainly through its action on hypothalamic-pituitary-ovarian function, whose molecular and cellular aspects are progressively being deciphered. Preliminary studies evaluating leptin as a biomarker in human IVF seem promising but need further confirmation. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.