Increased Adiponectin Concentrations Research Articles

Inhibition of Interleukin-1 Receptor-Associated Kinases 1/4, Increases Gene Expression and Serum Level of Adiponectin in Mouse Model of Insulin Resistance.

Insulin resistance is a feature of most patients with type 2 diabetes mellitus. Epidemiological evidence suggest a correlation between inflammation and insulin resistant states such as obesity, but the underlying mechanisms are largely unknown. Interleukin-1 receptor-associated kinases (IRAK) play a central role in inflammatory responses by regulating the expression of various inflammatory genes in immune cells. This study was aimed to investigate the effect of IRAK inhibitor on gene transcription and serum concentration of adiponectin in insulin-resistant mice. Experimental mice were randomly divided into 6 groups: the healthy control group was fed a regular chow diet while other groups were fed with a high-fat diet for 12 weeks. After this period, the animals were treated with IRAK inhibitor, pioglitazone, both IRAK and pioglitazone, and DMSO, for two weeks. Adiponectin gene expression level was analyzed by real-time PCR. Additionally, serum adiponectin levels were measured by ELISA. Homeostasis model assessment-adiponectin (HOMA-AD) as an insulin sensitivity index was calculated. IRAK inhibitor and pioglitazone increased significantly the expression of adiponectin gene. Also, adiponectin concentration in the control group (9.67±1.1 μg/ml) increased to 25.34±2.04 μg/ml in pioglitazone treatment group. IRAK inhibitor also increased adiponectin concentration (18.24±1.53 μg/ml) but did not show a synergistic effect with pioglitazone when administered simultaneously (26.66±2.5 μg/ml). HOMA-AD was 0.33±0.04 in pioglitazone treated group, 0.6±0.13 in IRAK inhibitor group, and 0.31±0.03 in animals that received IRAKi and pioglitazone. Our findings suggest that increased adiponectin secretion from adipose tissue mediated by IRAK inhibitor may increase the insulin sensitivity in an animal model of insulin resistance.

Relationships between adiponectin levels, the metabolic syndrome, and type 2 diabetes: a literature review.

Elevated hepatic glucose production, impaired insulin secretion, and insulin resistance - abnormalities of glucose metabolism typically found in subjects with obesity - are major factors underlying the pathogenesis of type 2 diabetes (DM2) and the metabolic syndrome (MS). Adiponectin is a major regulator of glucose and lipid homeostasis via its insulin-sensitizing properties, and lower levels seems to be associated with the development of DM2 and MS. The purpose of this review is to clarify the mechanisms whereby adiponectin relates to the development of DM2 and MS and the association between polymorphisms of the adiponectin gene, circulating levels of the hormone, and its relationships with DM2. In addition, the impact of dietary lipids in the circulating levels of adiponectin will be addressed. According to the literature, circulating adiponectin levels seem to decrease as the number of MS components increases. Lower adiponectin concentrations are associated with higher intra-abdominal fat content. Therefore, adiponectin could link intra-abdominal fat with insulin resistance and development of MS. Therapeutic strategies that target the MS and its components, such as lifestyle modification through physical activity and weight loss, have been shown to increase adiponectin concentrations. Possible roles of diets containing either low or high amounts of fat, or different types of fat, have been analyzed in several studies, with heterogeneous results. Supplementation with n-3 PUFA modestly increases adiponectin levels, whereas conjugated linoleic acid supplementation appears to reduce concentrations when compared with unsaturated fatty acid supplementation used as an active placebo.

ДИНАМІКА ПОКАЗНИКІВ ЛЕПТИНУ, АДИПОНЕКТИНУ ТА ІНТЕРЛЕЙКІНУ-6 ПРИ ПРИЗНАЧЕННІ САРТАНІВ, СТАТИНІВ ТА УРСОДЕЗОКСИХОЛЕВОЇ КИСЛОТИ У ПАЦІЄНТІВ З АРТЕРІАЛЬНОЮ ГІПЕРТЕНЗІЄЮ, ПОЄДНАНОЮ З ОЖИРІННЯМ ТА НЕАЛКОГОЛЬНИМ СТЕАТОГЕПАТИТОМ

Метою роботи було оцінити динаміку клініко-лабораторних показників у пацієнтів з артеріальною гіпертензією, поєднаною з ожирінням та неалкогольним стеатогепатитом при комбінованій терапії сартанами, статинами та урсодезоксихолевою кислотою (УДХК).Матеріали та методи. Обстежено 50 пацієнтів із ІІ-ІІІ стадією артеріальної гіпертензії, яких розділено на дві групи. Хворим першої групи призначали телмісартан (20 мг), аторвастатин (20 мг) та УДХК (10 мг/кг) 1 раз на добу. Пацієнтам другої групи призначали олмесартан (10 мг), аторвастатин (20 мг) та УДХК (10 мг/кг) 1 раз на добу. Проведено оцінку клініко-гемодинамічної та лабораторної ефективності комбінації цих препаратів через 12 тижнів лікування.Результати досліджень. Призначення впродовж 12 тижнів комбінації аторвастатину та УДХК в комплексній терапії з олмесартаном або телмісартаном у пацієнтів обох груп відзначено достовірне зниження усіх гемодинамічних показників, суттєве зменшення рівнів холестерину (p<0,01), ліпопротеїдів низької щільності (p<0,05) та аланінамінотрансферази.Також така схема лікування призводила до зниження рівнів інтерлейкіну-6 та лептину в обох групах, однак, зміни рівня лептину виявилися статистично недостовірними за рахунок значного діапазону показників. Відзначено достовірне підвищення концентрації адипонектину (до 25,94±0,65 мкг/мл) у першій групі, що свідчить про прямий вплив телмісартану на рівень адипонектину.Висновки.Призначення комбінації сартанів (телмісартану або олмесартану) в поєднанні з аторвастатином та урсодезоксихолевою кислотою впродовж 12 тижнів пацієнтам з артеріальною гіпертензією, поєднаною з ожирінням та неалкогольним стеатогепатитом, має позитивний вплив на загальний стан хворих за рахунок підтримання оптимального артеріального тиску, зменшення суб'єктивних скарг та покращення гемодинаміки серця.Така комбінація лікарських препаратів покращує показники ліпідного спектру крові (за рахунок зменшення рівнів загального холестерину (p<0,01) та ліпопротеїдів низької щільності (p<0,01)), знижує рівні лептину та інтерлейкіну-6 (p<0,01)Комбінація телмісартану з аторвастатином та урсодезоксихолевою кислотою у пацієнтам з артеріальною гіпертензією, поєднаною з ожирінням та неалкогольним стеатогепатитом призводить до достовірного зростання рівня адипонектину (p<0,01).

Circulating adiponectin concentration is inversely associated with glucose tolerance and insulin secretion in people with newly diagnosed diabetes.

To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and β-cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus. Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic β-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high-molecular-weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression. Among people with Type 2 diabetes, 2-year increases in high-molecular-weight adiponectin and in high-molecular-weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min (P = 0.020) and 0.8%/min (P = 0.013), respectively. Increases in high-molecular-weight/total adiponectin ratio were related to decreases in acute C-peptide secretion of 54.6% (P = 0.020). Among people with Type 1 diabetes, 2-year increases in total adiponectin were associated with 2-year decreases in acute C-peptide secretion of 56.2% (P = 0.035). Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093).

Abstract 2608: Dietary polyunsaturated fatty acids modulate adipose inflammation and the adipokine secretome to influence mammary stem cell self-renewal

Abstract Obesity strongly increases risk for multiple malignancies. One potential contributor may be the chronic low-grade inflammation that is likely driven by dysfunctional adipose characterized by aberrant adipokine production and macrophage activation/polarization. In adipose tissue, free fatty acids and their lipid mediators serve as important regulators of adipokine gene transcription. The adipocyte fatty acid composition is influenced by dietary availability. Here we present data demonstrating that dietary fish oil supplementation in obese rats (achieving a 2.5:1 ω6:ω3 PUFA ratio, comparable to a Mediterranean diet) attenuates adipose inflammation characterized reduction in the M1/M2 macrophage polarization ratio compared to a typical Western diet with a 20:1 ω6:ω3 PUFA ratio. We developed a novel adipose explant culture system to directly assay the secretome, and demonstrate that quenching adipose inflammation in obese animals is associated with a favorably rebalanced adipokine milieu, most notably increased adiponectin concentration and decreased leptin secretion. We previously showed that these two adipokines differentially modulate mammary stem cell self-renewal; here, we studied the effect of adipose conditioned media from obese rats on mammary stem cells using the mammosphere formation assay. Adipokines from obese rats fed the high-ω6 diet increased mammary stem cell symmetric self-renewal by 86.7 ± 7.5% (± SEM), whereas adipose-derived factors from the obese animals fed a low-ω6 diet supplemented with fish oil reduced the number of secondary mammospheres by 30.3 ± 10.1% by promoting either apoptosis, quiescence, or symmetric division-differentiation of the primary stem cells. Using a neutralizing antibody and a soluble receptor, we demonstrate that leptin contributes only 19% of the adipose-derived effect on mammary stem cell self-renewal. Taken together, our data suggests that a simple dietary intervention to modify the dietary PUFA ratio is an effective method to quench adipose inflammation and rebalance the adipokine milieu, which may modulate the mammary stem cell pool. If normal stem cells can give rise to breast cancer as has been theorized, then dietary interventions to quench adipose inflammation and reduce the rate of symmetric stem cell self-renewal might protect against the increased incidence of breast cancer seen in obese post-menopausal women. Citation Format: Raymond M. Esper, Evan Hill, Yan Jiang, Nadeem Aslam, Becky Simon, Max Wicha, William Smith, Dean E. Brenner. Dietary polyunsaturated fatty acids modulate adipose inflammation and the adipokine secretome to influence mammary stem cell self-renewal. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2608.

Changes in Maternal Plasma Adiponectin from Late Pregnancy to the Postpartum Period According to the Mode of Delivery: Results from a Prospective Cohort in Rio de Janeiro, Brazil.

IntroductionMaternal plasma adiponectin is inversely related to insulin resistance, atherosclerosis and child health. However, little is known about its concentrations in the perinatal period, especially according to mode of delivery. Our aim is to evaluate the association between mode of delivery and changes in maternal plasma adiponectin from 3rd trimester of pregnancy to 30–45 days postpartum.MethodsA cohort was recruited in Rio de Janeiro, Brazil, with four waves of follow-up: 5-13th, 22-26th, 30-36th gestational weeks and 30–45 days postpartum. Eligible subjects should be between 20–40 years of age, be free of chronic and infectious diseases and presenting with a singleton pregnancy. The mode of delivery was classified as vaginal (VD) or cesarean (CS). Plasma adiponectin concentration (μg/mL) was measured using commercial ELISA kits. Statistical analyses included the Wilcoxon rank-sum test and the multiple linear mixed effects model.ResultsA total of 159 participated in the study. Median adiponectin concentrations were higher for the VD group (n = 99; 8.25, IQR: 5.85–11.90) than for the CS group (n = 60; 7.34, IQR: 4.36–9.76; p = 0.040) in the postpartum samples but were not different between the two groups in the 3rd trimester. Women who underwent CS had a lower rate of increase in adiponectin concentration from the 3rd trimester to 30–45 days postpartum compared to those who underwent VD (β = -.15, 95% CI: -.28-.02, p = 0.030).ConclusionThe CS procedure was associated with lower maternal circulating concentrations of adiponectin at 30–45 days postpartum, compared to the VD.

Wild blueberries attenuate risk factors of the metabolic syndrome

The ability of a wild blueberry-enriched diet to improve risk factors related to Metabolic Syndrome (MetS) such as endothelial dysfunction and chronic inflammation in the Obese Zucker Rat (OZR), a model of the MetS, was studied. Obese Zucker Rats (OZRs) and their lean controls (LZR) were placed either on a Wild Blueberry-enriched (WB) or a control (C) diet for 8 weeks. Obese Zucker rats exhibited reduced vasoconstrictor response to phenylephrine (Phe) and exaggerated vasorelaxant response to acetylcholine (Ach). WB diet partially restored Phe-induced constrictor responses and attenuated Ach-induced relaxant responses in OZR. Plasma nitric oxide (NO) was significantly attenuated and aortic effluent prostaglandin I2 PGI2 concentration significantly increased in the WB diet. Downregulation of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expression in the OZR aorta was observed in the WB diet. WB consumption decreased plasma concentrations of tumor necrosis factor (TNF)(–25.6%, P< 0.05), interleukin (IL)-6 (–14.9%, P< 0.05), C-reactive protein (CRP) (–13.1%, P< 0.05) and increased adiponectin concentration (+21.8%, P< 0.05). Expression of IL-6, TNFand nuclear factor (NF)-kB was downregulated in both the liver (–65%, –59% and –25%, respectively) and the abdominal adipose tissue (–64%, –52% and –65%), while CRP expression was down regulated only in the liver (–25%). Thus, WB consumption improved endothelial function and exerted an anti-inflammatory effect in the OZR.

Intervention Trials with the Mediterranean Diet in Cardiovascular Prevention: Understanding Potential Mechanisms through Metabolomic Profiling

Large observational epidemiologic studies and randomized trials support the benefits of a Mediterranean dietary pattern on cardiovascular disease (CVD). Mechanisms postulated to mediate these benefits include the reduction of low-grade inflammation, increased adiponectin concentrations, decreased blood coagulation, enhanced endothelial function, lower oxidative stress, lower concentrations of oxidized LDL, and improved apolipoprotein profiles. However, the metabolic pathways through which the Mediterranean diet influences CVD risk remain largely unknown. Investigating specific mechanisms in the context of a large intervention trial with the use of high-throughput metabolomic profiling will provide more solid public health messages and may help to identify key molecular targets for more effective prevention and management of CVD. Although metabolomics is not without its limitations, the techniques allow for an assessment of thousands of metabolites, providing wide-ranging profiling of small molecules related to biological status. Specific candidate plasma metabolites that may be associated with CVD include branched-chain and aromatic amino acids; the glutamine-to-glutamate ratio; some short- to medium-chain acylcarnitines; gut flora metabolites (choline, betaine, and trimethylamine N-oxide); urea cycle metabolites (citrulline and ornithine); and specific lipid subclasses. In addition to targeted metabolites, the role of a large number of untargeted metabolites should also be assessed. Large intervention trials with the use of food patterns for the prevention of CVD provide an unparalleled opportunity to examine the effects of these interventions on plasma concentrations of specific metabolites and determine whether such changes mediate the benefits of the dietary interventions on CVD risk.

The Role of Adiponectin in Cardiometabolic Diseases: Effects of Nutritional Interventions

Adiponectin is an adipocyte-derived hormone abundantly present in plasma that exerts its effects through the activation of 3 receptors. Its concentrations are negatively regulated by the accumulation of visceral fat, and clinical studies implicate hypoadiponectinemia in the pathogenesis of diabetes mellitus type 2, coronary artery disease, hypertension, and left ventricular hypertrophy. In contrast, high concentrations of adiponectin are associated with a decreased risk of coronary artery disease, with an improvement in the differentiation of preadipocytes into adipocytes, and with increased endothelial nitric oxide production. Therefore, adiponectin appears to be an important molecule involved in limiting the pathogenesis of obesity-linked disorders, and it may have potential benefits in the treatment and prevention of cardiovascular disease. Caloric restriction, moderate alcohol consumption, and consuming a Mediterranean diet increase adiponectin concentrations, and current evidence suggests a positive, dose-dependent relation between ω-3 (n–3) fatty acid intake and circulating concentrations of adiponectin. Recently, it was reported that the administration of aged garlic extract and a single food intervention with pistachios can increase adiponectin concentrations in individuals with metabolic syndrome. Moreover, the Mediterranean diet is associated with higher adiponectin concentrations. Additional studies are needed to evaluate the potential benefits of increasing adiponectin by nutritional interventions in the treatment and prevention of cardiometabolic diseases.

Antihyperglycemic and antihyperlipidemic activities of protodioscin in a high-fat diet and streptozotocin-induced diabetic rats

Protodioscin attenuated hyperglycaemia and dyslipidemia in diabetic rats by improving the insulin sensitivity and increasing adiponectin concentrations.

Inhibiting myostatin signaling prevents femoral trabecular bone loss and microarchitecture deterioration in diet-induced obese rats.

Besides resulting in a dramatic increase in skeletal muscle mass, myostatin (MSTN) deficiency has a positive effect on bone formation. However, the issue about whether blocking MSTN can inhibit obesity-induced bone loss has not been previously investigated. In the present study, we have evaluated the effects of MSTN blocking on bone quality in high-fat (HF), diet-induced obese rats using a prepared polyclonal antibody for MSTN (MsAb). Twenty-four rats were randomly assigned to the Control, HF and HF + MsAb groups. Rats in the HF + MsAb group were injected once a week with purified MsAb for eight weeks. The results showed that MsAb significantly reduced body and fat weight, and increased muscle mass and strength in the HF group. MicroCT analysis demonstrated that obesity-induced bone loss and architecture deterioration were significantly mitigated by MsAb treatment, as evidenced by increased bone mineral density, bone volume over total volume, trabecular number and thickness, and decreased trabecular separation and structure model index. However, neither HF diet nor MsAb treatment had an impact on femoral biomechanical properties including maximum load, stiffness, energy absorption and elastic modulus. Moreover, MsAb significantly increased adiponectin concentrations, and decreased TNF-α and IL-6 levels in diet-induced obese rats. Taken together, blocking MSTN by MsAb improves bone quality in diet-induced obese rats through a mechanotransduction pathway from skeletal muscle, and the accompanying changes occurring in the levels of circulating adipokines and pro-inflammatory cytokines may also be involved in this process. It indicates that the administration of MSTN antagonists may be a promising therapy for treating obesity and obesity-induced bone loss.

Glycosylation patterns of proteins in trophoblast and decidua of the cat placenta

Glycosylation patterns of proteins in trophoblast and decidua of the cat placenta

Comparison of Glucose and Lipid Metabolism Abnormality during Nilotinib, Imatinib and Dasatinib Therapy – Results of Enigma 2 Study

Abstract Background: Recently we have published results of pilot study on CML patients demonstrating fast development of hyperinsulinaemia, peripheral insulin resistance, hypoadiponectinaemia and hypercholesterolemia during nilotinib therapy. Aims: To analyze results from follow up multicenter study “ENIGMA 2” with the aim to confirm or to exclude results from the pilot study, as well as to analyze whether these abnormalities are detected in control groups of patients treated with other TKIs - imatinib and dasatinib. Methods: Patients received intensive laboratory workup before the start of TKI and after 3 month of therapy. This included fasting insulin, glucose, adiponectin and lipid serum concentration, HbA1c and oral glucose tolerance test. Patients with TKI treatment interruption for &gt;2 weeks and/or dose reduction for &gt; 25% were excluded. Results: Between 2/2011-6/2014 in 5 centers 37 CML patients initiated therapy with nilotinib, 18 with imatinib and 8 with dasatinib. After 3 months patients treated with nilotinib developed significant hypersinulinaemia and hyperglycaemia as result of fast development of peripheral insulin resistance. This was proved by significant increase in HOMA-2 index during 3 months of nilotinib therapy (mean – 1.4 vs. 1.8; p = 0.0023). Moreover, we have proved significant decrease of adiponectin (major insulin sensitizer) concentration as well as significant increase in total and LDL cholesterol concentration after 3 month of nilotinib treatment. Details are presented in Table. Contrary – none of these abnormalities were detected in the control group of patients treated with imatinib and dasatinib, including any change in insulin resistance measured by HOMA-2 index (means – 0.9 vs. 1.3; p = 0.1046 and 1.1 vs. 1.1; p = 0.9255). Moreover, administration of imatinib (and probably also dasatinib, however only limited data are available at this moment) leads to increase of adiponectin concentration, which serves as major insulin sensitizer in peripheral tissues. Conclusions: Our study proved fast development of peripheral insulin resistance already during the first 3 months of nilotinib therapy as underlying cause of glucose and secondary also lipid metabolism impairment during this treatment. Moreover, this was not proved for patients treated with imatinib and dasatinb and significant increase in adiponectin concentration during imatinib (and probably dasatinib) therapy could at least partly explain observed amelioration of diabetes 2 during its administration described in some studies Supported by the CELL – the Czech Leukemia Study Group – for life Table. NILOTINIB THERAPY (n=37) Start Month 3 p mean (range) mean (range) Fasting glucose [mmol/l] 5.3 (4.5-6.7) 5.7 (4.6-8.2) &lt;0.0001 Fasting insulin [mU/l] 11.2 (2.4-28.3) 14,1 (2.5-32.7) 0.0037 Fasting C-peptide [pmol/ml] 0.73 (0.53-1.78) 0.76 (0.76-3.31) 0.4953 Fasting HbA1c [mmol/mol] 38.9 (24.0-55.0) 38.2 (25.0-57.0) 0.3900 Fasting adiponectin [mg/l] 16.6 (2.1-45.1) 8.6 (2.6-22.4) 0.0019* Total cholesterol [mmol/l] 4.8 (2.5-6.7) 5.9 (4.4-7.9) &lt;0.0001 LDL cholesterol [mmol/l] 2.8 (1.1-4.9) 3.6 (2.1-5.7) &lt;0.0001 IMATINIB THERAPY (n=18) Start Month 3 p mean (range) mean (range) Fasting glucose [mmol/l] 5.5 (4.4-7.7) 5.6 (4.2-6.4) 0.7567 Fasting insulin [mU/l] 6.7 (2.0-19.0) 9.8 (2.0-37.80) 0.1369 Fasting C-peptide [pmol/ml] 0.77 (0.25-1.55) 0.72 (0.27-1.78) 0.4569 Fasting HbA1c [mmol/mol] 44.8 (33.0-59.0) 41.1 (30.0-55.0) 0.005 Fasting adiponectin [mg/l] 10.8 (2.1-25.7) 26.1 (6.0-45.2) &lt;0.0001** Total cholesterol [mmol/l] 5.1 (3.3-7.1) 4,7 (2.6-7.1) 0.1123 LDL cholesterol [mmol/l] 3.1 (1.7-4.7) 2.7 (1.2-4.7) 0.064 DASATINIB THERAPY (n=8) Start Month 3 p mean (range) mean (range) Fasting glucose [mmol/l] 5.8 (4.6-6.8) 5.3 (3.3-6.7) 0.1764 Fasting insulin [mU/l] 8.1 (2.5-19.3) 8.4 (2.6-17.9) 0.8815 Fasting C-peptide [pmol/ml] 0.63 (0.16-1.11) 0.60 (0.24-1.03) 0.8223 Fasting HbA1c [mmol/mol] 38.8 (31.0-51.0) 37.8 (30.0-56.0) 0.684 Fasting adiponectin [mg/l] 17.3 (9.2-26.7) 12.9 (5.5-21.4) 0.0106*** Total cholesterol [mmol/l] 4.0 (3.0-5.0) 4.5 (3.6-5.8) 0.0831 LDL cholesterol [mmol/l] 2.2 (1.6-3.0) 2.5 (1.9-3.3) 0.1140 *number of paired measurements = 24 **number of paired measurements = 12 ***number of paired measurements = 3 Disclosures Zdenek: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Klamova:Novartis and Bristol Myers-Squibb: Consultancy, Honoraria. Mayer:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Nicotinic acid increases adiponectin secretion from differentiated bovine preadipocytes through G-protein coupled receptor signaling.

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.

Docosahexaenoic acid-enriched canola oil increases adiponectin concentrations: A randomized crossover controlled intervention trial

Background and aimsLittle is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes. We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid (ALA), linoleic acid (LA), oleic acid (OA) and docosahexaenoic acid (DHA) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells. Methods and resultsIn a randomized, crossover controlled nutrition intervention, 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each, separated by 4-week washout periods. Each diet provided 60 g/3000 kcal of different oils: 1) control corn/safflower oil blend (CornSaff; LA-rich), 2) flax/safflower oil blend (FlaxSaff; ALA-rich), 3) conventional canola oil (Canola; OA-rich), 4) high oleic canola oil (CanolaOleic; highest OA content), 5) DHA-enriched high oleic canola oil (CanolaDHA; OA- and DHA-rich). Gene expression in whole blood cells was assessed in a subset of 62 subjects. CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment (+4.5%, P = 0.04) and FlaxSaff (+6.9%, P = 0.0008). CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola (−11% and −13%, respectively, both P = 0.03). High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff (−17.8%, P = 0.047). ConclusionDHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources.CLINICALTRIALS.GOV REGISTRATION NUMBER AND DATE: NCT01351012; March 14, 2011.

Vitamin D and Dysfunctional Adipose Tissue in Obesity.

Vitamin D deficiency and dysfunctional adipose tissue are involved in the development of cardiometabolic disturbances (eg, hypertension, insulin resistance, type 2 diabetes mellitus, obesity, and dyslipidemia). We evaluated the relation between vitamin D and adipocytokines derived from adipose tissue. We studied 50 obese individuals who were classified into different subgroups according to medians of observed anthropometric parameters (body mass index, body fat percentage, waist circumference, and trunk fat mass). There was a negative correlation between vitamin D level and leptin and resistin (r = -.61, P < .01), while a positive association with adiponectin concentrations was found (r = .7, P < .001). Trend estimation showed that increase in vitamin D level is accompanied by intensive increase in adiponectin concentrations (growth coefficient: 12.13). In conclusion, a positive trend was established between vitamin D and the protective adipocytokine adiponectin. The clinical relevance of this relationship needs to be investigated in larger studies.

Aerobic plus resistance training was more effective in improving the visceral adiposity, metabolic profile and inflammatory markers than aerobic training in obese adolescents

The purpose of this study was to determine whether aerobic plus resistance training (AT + RT) is more effective than aerobic training (AT) at reducing inflammatory markers and cardiovascular risk in obese adolescents. A total of 139 obese adolescents were enrolled, aged 15–19 years, body mass index (BMI) ≥ 95th percentile and participated in 1 year of interdisciplinary intervention. They were randomised into two groups: AT (n = 55), AT + RT (n = 61). Blood samples were collected to analyse glycaemia, insulin, the lipid profile, leptin and adiponectin concentrations. Insulin resistance was measured by homeostasis model assessment of insulin resistance index (HOMA-IR). The AT + RT group showed better results with regard to decreased body fat mass, low-density lipoprotein concentration (LDL-c) levels, subcutaneous and visceral fat and increased body lean mass. Indeed, a reduction of hyperleptinaemia and an increase in adiponectin concentrations, promoting an improvement in the leptin/adiponectin ratio, was observed. Important clinical parameters were improved in both types of exercise; however, AT + RT was more effective in improving the visceral adiposity, metabolic profile and inflammatory markers than AT alone, suggesting clinical applications for the control of intra-abdominal obesity and cardiovascular risk in the paediatric population.

Association of nonalcoholic fatty liver disease with cardiovascular risk factors in obese adolescents: the role of interdisciplinary therapy.

Obesity is associated with several cardiovascular risk factors, including nonalcoholic fatty liver disease (NAFLD). These risk factors can induce changes in the arteries such as an increase in the carotid intima-media thickness (cIMT), which contributes to the early development of atherosclerosis. To determine whether NAFLD is associated with an atherogenic lipid profile, inflammatory markers, or cIMT in obese adolescents and to compare the effects of therapeutic lifestyle changes in NAFLD and non-NAFLD groups. A total of 79 obese adolescents were divided into two groups: 33 NAFLD and 46 non-NAFLD. They were submitted to an interdisciplinary therapy involving diet exercise and psychological support during the course of 1 year. The cIMT and estimates of fat mass (liver, intra-abdominal, and subcutaneous) were determined ultrasonographically. Body composition, glucose, lipid profile, and adipokines were analyzed before and after the therapy. At baseline, only in the NAFLD group was the homeostasis model assessment of insulin resistance positively correlated with cIMT and triglyceride/high-density lipoprotein cholesterol ratio. Therapy was associated with an increase in adiponectin concentrations and reduced visceral fat, cIMT, leptin, and plasminogen activator inhibitor-1 concentrations, as well as the ratios of total cholesterol/high-density lipoprotein cholesterol and triglycerides/high-density lipoprotein cholesterol in both groups. Only in the non-NAFLD group did therapy result in a reduction in the low-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio and increased high-density lipoprotein cholesterol concentration. In obese adolescents, NAFLD is associated with cardiovascular risk factors and inflammatory markers of atherosclerosis that were positively correlated with cIMT only in the NAFLD group. Nevertheless, the strength of the present study is that the interdisciplinary therapy effectively improved cIMT and other proinflammatory adipokines in both groups.

Trans-Cinnamic Acid Increases Adiponectin and the Phosphorylation of AMP-Activated Protein Kinase through G-Protein-Coupled Receptor Signaling in 3T3-L1 Adipocytes

Adiponectin and intracellular 5′adenosine monophosphate-activated protein kinase (AMPK) are important modulators of glucose and fat metabolism. Cinnamon exerts beneficial effects by improving insulin sensitivity and blood lipids, e.g., through increasing adiponectin concentrations and AMPK activation. The underlying mechanism is unknown. The Gi/Go-protein-coupled receptor (GPR) 109A stimulates adiponectin secretion after binding its ligand niacin. Trans-cinnamic acid (tCA), a compound of cinnamon is another ligand. We hypothesize whether AMPK activation and adiponectin secretion by tCA is transmitted by GPR signaling. Differentiated 3T3-L1 cells were incubated with pertussis toxin (PTX), an inhibitor of Gi/Go-protein-coupling, and treated with different tCA concentrations. Treatment with tCA increased adiponectin and the pAMPK/AMPK ratio (p ≤ 0.001). PTX incubation abolished the increased pAMPK/AMPK ratio and adiponectin secretion. The latter remained increased compared to controls (p ≤ 0.002). tCA treatment stimulated adiponectin secretion and AMPK activation; the inhibitory effect of PTX suggests GPR is involved in tCA stimulated signaling.

Salsalate and adiponectin ameliorate hepatic steatosis by inhibition of the hepatokine fetuin-A

Fetuin-A was recently identified as a novel hepatokine which is associated with obesity, insulin resistance and non-alcoholic fatty liver disease. Salsalate, a prodrug of salicylate with an anti-inflammatory effect and lower side effect profile, significantly lowers glucose and triglyceride levels, and increased adiponectin concentrations in randomized clinical trials. In this study, we examined the effects and regulatory mechanisms of salsalate and full length-adiponectin (fAd) on fetuin-A expression, steatosis and lipid metabolism in palmitate-treated HepG2 cells. Incubation of hepatocytes with palmitate significantly increased fetuin-A and SREBP-1c expression which lead to steatosis and knock-down of fetuin-A by siRNA restored these changes. Salsalate significantly down-regulated palmitate-induced fetuin-A mRNA expression and secretion in a dose- and time-dependent manner. Inhibition of palmitate-induced fetuin-A by salsalate was mediated by AMPK-mediated reduction of NFκB activity, which was blocked by AMPK siRNA or an inhibitor of AMPK. Salsalate attenuated the excessive steatosis by palmitate through SREBP-1c regulation in hepatocytes. Furthermore, fAd also showed suppression of palmitate-induced fetuin-A through the AMPK pathway and improvement of steatosis accompanied by restoration of SREBP-1c, PAPR-α and CD36. In preliminary in vivo experiments, salsalate treatment inhibited high fat diet (HFD)-induced steatosis as well as fetuin-A mRNA and protein expression in SD rats. In conclusion, salsalate and fAd improved palmitate-induced steatosis and impairment of lipid metabolism in hepatocytes via fetuin-A inhibition through the AMPK-NFκB pathway.