Circulating Adiponectin Concentrations Research Articles

Effects of Exhaustive Exercise on Adiponectin and High-Molecular-Weight Oligomer Levels in Male Amateur Athletes.

Physical activity promotes metabolic health and prevents lifestyle-related diseases. Adiponectin is specifically produced by adipose tissue and comes in three forms, differing in terms of weight: trimers (LMW), hexamers (MMW), and high-molecular-weight (HMW) oligomers. The oligomers are associated with the beneficial effects of adiponectin. In this study, we aimed to investigate the impact of a single bout of exhaustive exercise on adiponectin expression in 25 male amateur athletes, divided into two groups, one comprising young adults (YAs) (n = 15), and the other comprising middle-aged adults (MAs) (n = 10). Body fat was estimated through skinfold thickness. Adiponectin levels were assessed at baseline and at 15 min and 24 h post-exercise, while HMW oligomer levels were evaluated at baseline and at 24 h post-exercise. We observed a significant increase in total adiponectin at both 15 min and 24 h after exercise, with there being a more evident effect among the YA subjects. HMW oligomers also increased significantly after exercise both in the total sample and among the YA subjects, but this was not the case in the MA subjects. The increase in adiponectin levels was significantly associated with Powerpeak. Furthermore, a significant inverse correlation was found between basal adiponectin and VO2peak and Powerpeak. In conclusion, a single bout of exhaustive exercise can rapidly and significantly enhance the basal circulating adiponectin concentration, which seems to be negatively associated with maximal aerobic capacity.

The role of adiponectin in the association between abdominal obesity and type 2 diabetes: a mediation analysis among 232,438 Chinese participants.

Adiposity and adipokines are closely associated with obesity-related metabolic abnormalities, but little is known regarding whether abdominal obesity is linked to type 2 diabetes mellitus (T2DM) through circulating adiponectin levels. Thus, this large-population-based study was designed to investigate the mediating effect of adiponectin in the relationship between abdominal obesity and T2DM. A total of 232,438 adults who lived in Dongguan, Guangdong Province, China, were enrolled in the present study. The circulating adiponectin concentrations were measured using latex-enhanced immunoturbidimetric assay. The association between circulating adiponectin and other clinical parameters was detected by Spearman's correlation analysis. Restricted cubic spline (RCS) regression was also used to address the non-linearity of the relationship between waist circumference and diabetes. Mediation analyses of circulating adiponectin were conducted using linear and logistic regression. Subjects with abdominal obesity had lower levels of circulating adiponectin (P < 0.001). The circulating adiponectin value was inversely related to BMI (r = -0.370, P < 0.001), waist circumference (r = -0.361, P < 0.001), and fasting plasma glucose (r = -0.221, P < 0.001). The RCS plot showed a non-linear relation linking waist circumference with T2DM (P for non-linearity < 0.001). Patients with abdominal obesity presented 2.062 times higher odds of T2DM in comparison with those with non-abdominal obesity (odds ratio, 2.062; 95% confidence interval, 1.969-2.161) after adjusting for confounders. In the mediation analyses, the circulating adiponectin mediated the association between abdominal obesity and T2DM, with a mediation effect of 41.02% after adjustments. The above results were consistent in both men and women. The relationship between abdominal obesity and T2DM is mediated through circulating adiponectin level in adults, suggesting that circulating adiponectin might be a potential predictor for controlling the adverse progression from adiposity to T2DM.

Comparison of Levels of Telomerase, Oxidative Stress, Adiponectin, Leptin, and Interleukin-6 in First Degree Relatives of Diabetics, Prediabetics, and Diabetics: A Cross-sectional Study

Introduction: Rapid beta-cell senescence caused by telomere shortening is associated with type 2 diabetes. Hence, studying telomere dynamics in prediabetic stages or First Degree Relatives of Diabetics (FDRD) is crucial. Telomere attrition is influenced by oxidative stress, which is prevalent in diabetics, prediabetics, and FDRD due to dyslipidaemia. The relationship between telomerase activity and glycaemic control, insulin resistance, oxidative stress, dyslipidaemia, adipocytokines, and inflammatory markers remains unclear and requires further investigation. Aim: To assess and compare telomerase levels, oxidative stress (malondialdehyde), adipocytokines (leptin, adiponectin, and Interleukin-6 (IL-6), lipid profiles, and Body Fat Percentage (BF%) across the glycaemic spectrum in the Indian population. Materials and Methods: This cross-sectional study was conducted at the Department of Physiology, JIPMER, Puducherry, from 2016 to 2018, involving four groups: Group I (control group, non diabetic, healthy, non FDRD, n=63), Group II (FDRD, non diabetic, n=63), Group III (prediabetics, n=63), and Group IV (diabetics, n=63). Participants aged 30-50 years, matched for age and gender, were recruited. Anthropometric variables, cardiovascular parameters, telomerase levels, Malondialdehyde (MDA), adiponectin, leptin, IL-6, and lipid profiles were assessed. Mean differences were analysed using one-way Analysis of Variance (ANOVA) or Kruskal-Wallis test, while Pearson’s correlation analysis was performed to assess the correlation between telomerase levels, glucose concentration, and BF%. Results: An increasing trend in circulating telomerase levels, lipid profiles, and BF% was observed across the glycaemic spectrum. Circulating leptin concentrations did not differ between the groups. However, there was a decrease in circulating adiponectin concentration as the glycaemic status progressed. Increased MDA levels were observed only in the diabetics group. Telomerase levels showed a significant association with circulating glucose concentration (fasting and postprandial) and BF%. Conclusion: The circulating telomerase level increased along the glycaemic spectrum (non FDRD&lt;FDRD&lt;Prediabetics&lt; Diabetics). The major finding was that telomerase level increases even in normoglycaemic FDRD. Oxidative and inflammatory parameters did not significantly differ in FDRD compared to non FDRD individuals. Notably, adiponectin, Tumour Necrosis Factor (TNF)-α, Low-Density Lipoprotein (LDL), and HighDensity Lipoprotein (HDL) were the parameters that showed changes in FDRD.

Seasonal Change in Adiponectin Associated with Ovarian Morphology and Function in Wild Ground Squirrels (Citellus dauricus Brandt)

The goal of this study is to explore the relationship between altered circulating adiponectin concentration, ovarian tissue morphology, ovarian steroidogenesis, and sex hormone production in ovaries of wild ground squirrels. The ovarian mass differed significantly during the breeding and non-breeding seasons, and the circulating estradiol and progesterone concentrations were significantly higher in the breeding season, while the circulating adiponectin level was significantly lower. The expression levels of gonadotropin receptors (FSHR and LHR) and steroidogenic enzymes (StAR, P450scc, P450arom, and 3β-HSD) were significantly higher during the breeding season. Comparing the ovarian transcriptome data of wild ground squirrels between the two periods, we found that some differentially expressed genes were enriched for ovarian steroidogenesis and the adipocytokine signaling pathway, which correlated with our present results. Notably, the MAPK signaling pathway was also enriched and its related genes (Erk1, p38 Mapk, Jnk) were up-regulated by qPCR during the non-breeding season. These findings suggested that adiponectin may be involved in the regulation of seasonal changes in the ovarian function of wild ground squirrels, possibly by acting on the MAPK signaling pathway to regulate sex steroidogenesis in the ovaries.

Galactose in the Post-Weaning Diet Programs Improved Circulating Adiponectin Concentrations and Skeletal Muscle Insulin Signaling.

Short-term post-weaning nutrition can result in long-lasting effects in later life. Partial replacement of glucose by galactose in the post-weaning diet showed direct effects on liver inflammation. Here, we examined this program on body weight, body composition, and insulin sensitivity at the adult age. Three-week-old female C57BL/6JRccHsd mice were fed a diet with glucose plus galactose (GAL; 16 energy% (en%) each) or a control diet with glucose (GLU; 32 en%) for three weeks, and afterward, both groups were given the same high-fat diet (HFD). After five weeks on a HFD, an oral glucose tolerance test was performed. After nine weeks on a HFD, energy metabolism was assessed by indirect calorimetry, and fasted mice were sacrificed fifteen minutes after a glucose bolus, followed by serum and tissue analyses. Body weight and body composition were not different between the post-weaning dietary groups, during the post-weaning period, or the HFD period. Glucose tolerance and energy metabolism in adulthood were not affected by the post-weaning diet. Serum adiponectin concentrations were significantly higher (p = 0.02) in GAL mice while insulin, leptin, and insulin-like growth factor 1 concentrations were not affected. Expression of Adipoq mRNA was significantly higher in gonadal white adipose tissue (gWAT; p = 0.03), while its receptors in the liver and skeletal muscles remained unaffected. Irs2 expression was significantly lower in skeletal muscles (p = 0.01), but not in gWAT or Irs1 expression (in both tissues). Gene expressions of inflammatory markers in gWAT and the liver were also not affected. Conclusively, galactose in the post-weaning diet significantly improved circulating adiponectin concentrations and reduced skeletal muscle Irs2 expression in adulthood without alterations in fat mass, glucose tolerance, and inflammation.

Lack of serum albumin improves insulin sensitivity in both male and female mice

Insulin resistance is a global health problem. It has been shown that free fatty acids (FFA) play a major role in insulin resistance. Albumin acts as main fatty acid binding protein in blood. To improve understanding of the role of FFA in insulin resistance, we aimed to determine whether lack of serum albumin and the associated suppression of plasma FFA concentration would improve insulin sensitivity in albumin knockout mice compared to wild type mice. Male and female homozygous albumin knockout mice and C57BL/6J wild‐type controls, each fed a chow diet, were studied at 6‐8 weeks of age. Glucose tolerance test, insulin tolerance test, tissue analyses, and plasma proteomics were performed. In both sexes of albumin knockout mice compared to wild‐type mice, we observed lower levels of hepatic diacylglycerol content, as well as lower blood glucose during glucose tolerance test and insulin tolerance test (P &lt; 0.05). The level of mRNA measurement showed higher expression of adiponectin, lipoprotein lipase, diacylglycerol acyltransferase‐1 and ‐2, and glucose transporter‐4 in adipose tissue, as well as lower hepatic perilipin‐2 expression (P&lt;0.05). In agreement with adipose mRNA level analysis, plasma proteomics indicated that circulating adiponectin concentration was higher in albumin knockout compared to wild‐type mice (P&lt;0.05). The results indicate an important role of albumin and plasma FFA concentration in lipid and glucose metabolism. We suggest that the lower plasma FFA concentration in albumin knockout mice compared to wild‐type mice leads to less hepatic diacylglycerol accumulation, and the lower level of this lipotoxic compound may contribute to the enhanced insulin sensitivity.

Negative Correlation of Serum Adiponectin Level with Aortic Stiffness in Elderly Diabetic Persons.

Adiponectin has anti-inflammatory activity against atherosclerosis. Aortic stiffness is a common manifestation of atherosclerosis in diabetes mellitus and elderly persons. This study aimed to evaluate whether low serum adiponectin levels were associated with aortic stiffness in geriatric diabetic patients. Blood samples were obtained from 130 diabetic participants aged ≥ 65 years. We defined high aortic stiffness based on a carotid–femoral pulse wave velocity (cfPWV) of >10 m/s. Circulating adiponectin concentrations were examined using enzyme-linked immunosorbent assays. Sixty-six participants (50.8%) had aortic stiffness. Patients with aortic stiffness had lower serum adiponectin concentrations than those in the control group (p < 0.001). Multivariate logistic regression analysis showed that the adiponectin level (odds ratio: 0.939, 95% confidence interval: 0.898–0.981, p = 0.005) was an independent predictor of aortic stiffness in elderly diabetic persons. Multivariate forward stepwise linear regression analysis also demonstrated that the adiponectin level (β = −0.256, adjusted R2 change = 0.100, p = 0.003) was negatively associated with cfPWV values in older diabetic patients. In conclusion, serum adiponectin is negatively correlated with cfPWV and is an independent predictor of aortic stiffness in elderly diabetic persons.

Circulating adiponectin mediates the association between omentin gene polymorphism and cardiometabolic health in Asian Indians.

BackgroundPlasma omentin levels have been shown to be associated with circulating adiponectin concentrations and cardiometabolic disease-related outcomes. In this study, we aim to examine the association of omentin gene polymorphism with serum adiponectin levels and cardiometabolic health status using a genetic approach, and investigate whether these associations are modified by lifestyle factors.MethodsThe study included 945 normal glucose tolerant and 941 unrelated individuals with type 2 diabetes randomly selected from the Chennai Urban Rural Epidemiology Study (CURES), in southern India. Study participants were classified into cardiometabolically healthy and unhealthy, where cardiometabolically healthy were those without hypertension, diabetes, and dyslipidemia. Fasting serum adiponectin levels were measured by radioimmunoassay. The omentin A326T (rs2274907) single nucleotide polymorphism (SNP) was screened by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing.ResultsThe ‘A’ allele of the omentin SNP was significantly associated with lower adiponectin concentrations after adjusting for age, sex, body mass index (BMI), waist circumference (WC) and cardiometabolic health status (p = 1.90 x 10−47). There was also a significant association between circulating adiponectin concentrations and cardiometabolic health status after adjusting for age, sex, BMI, WC and Omentin SNP (p = 7.47x10-10). However, after adjusting for age, sex, BMI, WC and adiponectin levels, the association of ‘A’ allele with cardiometabolic health status disappeared (p = 0.79) suggesting that adiponectin serves as a mediator of the association between omentin SNP and cardiometabolic health status. There were no significant interactions between the SNP and dietary factors on adiponectin levels and cardiometabolic health status (p>0.25, for all comparisons).ConclusionsOur findings show that adiponectin might function as a mechanistic link between omentin SNP and increased risk of cardiometabolic diseases independent of common and central obesity in Asian Indians. Before strategies to promote adiponectin modulation could be implemented, further studies are required to confirm the molecular mechanisms involved in this triangular relationship between omentin gene, adiponectin and cardiometabolic diseases.

Impact of glucagon-like peptide-1 receptor agonists on adiponectin concentrations: A meta-analysis of randomized controlled trials.

Previous studies have reported an elevation in adiponectin concentrations using glucagon-like peptide-1 receptor agonists (GLP-1 RA) therapy; however, this possible pleiotropic effect is still uncertain. Thus, the objective of this meta-analysis of randomized controlled trials was to assess the impact of GLP-1 RA on adiponectin levels. This systematic review and meta-analysis included randomized controlled trials investigating the effect of GLP-1 RA on circulating adiponectin concentrations. Studies from PubMed, Web of Science, Scopus, and Google Scholar databases were included. A random-effects model and a sensitivity analysis using the leave 1-out method were conducted. A meta-analysis of 20 randomized controlled trials involving 1497 individuals demonstrated a significant increase in adiponectin levels after GLP-1 RA administration (weighted mean difference [WMD]: 0.59 μg/mL, 95% confidence interval [CI]: 0.10, 1.08, P= .02). Particularly, liraglutide had a significant effect on adiponectin (WMD: 0.55 μg/mL, 95% CI: 0.04, 1.06, P= .04), while exenatide did not affect these concentrations (WMD: 0.60 μg/mL, 95% CI: -0.23, 1.42, P= .16). GLP-1 RA treatment is associated with an increase in adiponectin levels.

Abstract 3493: Interactions between adiponectin pathway polymorphisms and obesity on breast cancer risk among African American postmenopausal women

Abstract Purpose: A decreased circulating adiponectin concentration is associated with obesity and an increased breast cancer risk among postmenopausal women. Yet, the interplay between adiponectin-associated genetic variants, obesity, and breast cancer risk is unclear in African American (AA) postmenopausal women. We examined adiponectin pathway polymorphisms for their association with breast cancer risk among AA postmenopausal women. We also explored a gene-environment interaction between adiponectin pathway polymorphisms and obesity for the risk of breast cancer. Method: Using the Women's Health Initiative SNP Health Association Resource Study, we identified 37 single-nucleotide polymorphisms (SNPs) in relation to the adiponectin pathway. Body-fat distributions were determined using three independent indices including body mass index (BMI), waist-to-hip ratio (WHR), and waist circumference (WC). We used multiple Cox proportional hazards regression models to estimate hazard ratios and 95% confidence intervals (CIs) for the association with breast cancer. Obesity-stratified analysis and tests for the joint effects with the SNPs were conducted. Results: Of 7,991 AA postmenopausal women, 402 reported of having an invasive breast cancer with a mean follow-up of 14.5 years. The majority were obese, had low WHR (&amp;lt; 0.85), and had high WC (&amp;lt; 88 cm). Of 37 adiponectin pathway-related SNPs, 3 SNPs were significantly associated with breast cancer risk (KCNK9 rs2468677, OR8S1-LALBA rs11168618, and EIF4A2 rs266719). Among women who have under or normal bodyweight, the minor allele GG genotype of NMU rs13434995 had an elevated risk of postmenopausal breast cancer compared to those with the major allele AA genotype. Women who carry the heterozygous TC genotype of OR8S1-LALBA rs11168618 and are obese jointly increased the risk of breast cancer (relative excess risk due to interaction = 0.58, 95% CI = 0.35, 0.80). Conclusion: Our findings revealed the association between the previously confirmed adiponectin pathway-related SNPs and breast cancer risk among AA postmenopausal women. We also demonstrated that obesity plays an important role as an effect modifier in the relationship between the SNPs and breast cancer, suggesting 1) the potential use of metabolic and genetic biomarkers for identifying a greater risk for breast cancer and 2) support for the research to promote interventions to those with risk genotypes, thus reducing breast cancer risk. Citation Format: Gina E. Nam, Zuo-Feng Zhang, Jianyu Rao, Hua Zhou, Su Yon Jung. Interactions between adiponectin pathway polymorphisms and obesity on breast cancer risk among African American postmenopausal women [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3493.

Higher Circulating Adiponectin Concentrations Predict Incident Cancer in Type 2 Diabetes - The Adiponectin Paradox.

Despite the beneficial cardiometabolic effects of adiponectin demonstrated in preclinical studies, paradoxically higher circulating adiponectin concentrations have been found in epidemiological studies to be associated with incident cardiovascular events, renal outcomes, and mortality in patients with diabetes. On the other hand, diabetes is also associated with an increased risk of cancer. Here, we investigated prospectively the association between circulating adiponectin concentrations and incident cancer using a cohort of exclusively individuals with type 2 diabetes. Baseline serum adiponectin concentrations were measured in 5658 participants recruited from the Hong Kong West Diabetes Registry. The associations of circulating adiponectin concentrations with incident cancer and cancer-related deaths were evaluated using multivariable Cox regression analysis, with hazard ratio (HR) for adiponectin referring to the respective risk per doubling of serum adiponectin concentration. Over a median-follow up of 6.5 years, 7.53% and 3% of participants developed cancer and had cancer-related deaths, respectively. Serum adiponectin concentrations were significantly higher in those who had incident cancer (9.8 μg/mL vs 9.1 μg/mL, P < 0.001) and cancer-related deaths (11.5 μg/mL vs 9.3 μg/mL, P < 0.001) compared with those without. Moreover, in multivariable analyses, serum adiponectin concentration was independently associated with both incident cancer (hazard ratio, 1.19; 95% confidence interval, 1.05-1.35; P = 0.006) and cancer-related deaths (hazard ratio, 1.23; 95% confidence interval, 1.03-1.47; P = 0.024). Higher serum adiponectin concentration was independently associated with incident cancer and cancer-related deaths in type 2 diabetes, indicating that adiponectin paradox can be observed in another major diabetic complication in addition to cardiovascular and kidney diseases.

Circulating adiponectin expression is elevated and associated with the IL-15/IL-15Rα complex in obese physically active humans.

Adiponectin is an adipokine with oxidative, anti-inflammatory and antiatherogenic effects in several peripheral tissues; however, circulating adiponectin expression is reduced in cardio-metabolic diseases. The aim of this study was to ascertain whether regular physical activity mediates circulating adiponectin concentrations at baseline in an obese population. Two hundred and twenty-one obese participants were divided into 6 groups according to gender, physical activity (PA), and type 2 diabetes mellitus (T2DM) diagnosis: A and B) obese PA females (N.=28) and males (N.=33); C and D) obese non-PA females (N.=40) and males (N.=40); E and F) obese non-PA females (N.=40) and males (N.=40) with T2DM. Serum adiponectin, IL-15 and IL-15Rα, blood glucose/lipid profile, and body composition were measured. Circulating adiponectin increased in PA participants compared to non-PA (ANOVA, P=0.001), finding higher concentrations in females compared to males (P<0.001), particularly in the PA group (P=0.005). Serum adiponectin was associated with age (R2=0.068), body mass (R2=-0.108), waist circumference (WC) (R2=-0.122), LDL (R2=-0.045), triglycerides (R2=-0.043), and serum IL-15Rα (R2=-0.243), as well as fat mass in females (R2=0.098), and WC in males (R2=0.112). Circulating adiponectin increased in obese PA participants (≥180 min/week) compared to non-PA counterparts, indicating that physical activity may mediate baseline adiponectin levels irrespective of the fat mass regulatory effect. The inverse relationship found between serum adiponectin and IL-15Rα may support the regulative role of the IL-15/IL-15Rα complex on this adipokine at baseline.

Androgens sensitise mice to glucocorticoid-induced insulin resistance and fat accumulation.

Chronic glucocorticoid therapy causes insulin resistance, dyslipidaemia, abnormal fat accumulation, loss of muscle mass and osteoporosis. Here we describe a hitherto unknown sexual dimorphism in the metabolic response to chronic glucocorticoid exposure in mice. This led us to investigate whether glucocorticoid-induced insulin resistance and obesity were dependent on sex hormones. Male and female CD1 mice were treated for 4weeks with supraphysiological doses (~250μg/day) of corticosterone, the main glucocorticoid in rodents, or equivalent volume of vehicle (drinking water without corticosterone). To investigate the effects of sex hormones, a separate group of mice were either orchidectomised or ovariectomised prior to corticosterone treatment, with or without dihydrotestosterone replacement. Body composition was determined before and after corticosterone treatment, and insulin tolerance was assessed after 7 and 28days of treatment. Adipocyte morphology was assessed in white and brown adipose tissues by immunohistochemistry, and fasting serum concentrations of NEFA, triacylglycerols, total cholesterol and free glycerol were measured using colorimetric assays. Obesity- and diabetes-related hormones were measured using multiplex assays, and RNA and protein expression in adipose tissues were measured by RT-PCR and immunoblotting, respectively. Chronic corticosterone treatment led to insulin resistance, fasting hyperinsulinaemia, increased adiposity and dyslipidaemia in male, but not female mice. In males, orchidectomy improved baseline insulin sensitivity and attenuated corticosterone-induced insulin resistance, but did not prevent fat accumulation. In androgen-deficient mice (orchidectomised males, and intact and ovariectomised females) treated with dihydrotestosterone, corticosterone treatment led to insulin resistance and dyslipidaemia. In brown adipose tissue, androgens were required for corticosterone-induced intracellular lipid accumulation ('whitening'), and dihydrotestosterone specifically exacerbated corticosterone-induced accumulation of white adipose tissue by increasing adipocyte hypertrophy. Androgens also suppressed circulating adiponectin concentrations, but corticosterone-induced insulin resistance did not involve additional suppression of adiponectin levels. In white adipose tissue, androgens were required for induction of the glucocorticoid target gene Gilz (also known as Tsc22d3) by corticosterone. In mice, androgens potentiate the development of insulin resistance, fat accumulation and brown adipose tissue whitening following chronic glucocorticoid treatment.

Normalisation of circulating adiponectin levels in obese pregnant mice prevents cardiac dysfunction in adult offspring

Background/objectivesAdiponectin concentrations are low in obese pregnant women. Restoring normal adiponectin concentrations by infusion in obese pregnant mice prevents placental dysfunction, foetal overgrowth and metabolic syndrome in the offspring. We hypothesised that normalising maternal adiponectin in obese late pregnant dams prevents cardiac dysfunction in the adult offspring.Subjects/methodsPregnant female mice with diet-induced obesity were infused with adiponectin (0.62 μg g−1 day−1, n = 24) or saline (n = 22) over days 14.5–18.5 of pregnancy (term = day 19.5). Control dams ate standard chow and received saline (n = 22). Offspring were studied at 3 and 6 months of age.ResultsMaternal obesity impaired ventricular diastolic function, increased cardiomyocyte cross-sectional area and upregulated cardiac brain natriuretic peptide (Nppb) and α-skeletal actin (Acta1) gene expression in adult male offspring, compared to control offspring. In adult female offspring, maternal obesity increased Nppb expression, decreased end-diastolic volume and caused age-dependent diastolic dysfunction but not cardiomyocyte hypertrophy. Maternal obesity also activated cardiac Akt and mechanistic target of rapamycin (mTOR) signalling in male, but not in female, offspring and inhibited cardiac extracellular signal-regulated kinase 1/2 (ERK1/2) in both sexes. Normalising maternal circulating adiponectin concentrations by infusing obese dams with adiponectin prevented offspring diastolic dysfunction and ventricular dilation and normalised cardiac Akt-mTOR signalling irrespective of sex. Maternal adiponectin infusion also reduced cardiac Nppb expression and increased ERK1/2 signalling in offspring of obese dams. Adiponectin infusion did not prevent cardiomyocyte hypertrophy but reduced ventricular wall thickness in male offspring and increased collagen content in female offspring of obese dams, compared to controls.ConclusionsLow maternal adiponectin levels in obese mice in late pregnancy are mechanistically linked to in utero programming of cardiac dysfunction in their offspring. Interventions enhancing endogenous adiponectin secretion or signalling in obese pregnant women could prevent the development of cardiac dysfunction in their children.

Beneficial Effects of Adiponectin on Glucose and Lipid Metabolism and Atherosclerotic Progression: Mechanisms and Perspectives.

Circulating adiponectin concentrations are reduced in obese individuals, and this reduction has been proposed to have a crucial role in the pathogenesis of atherosclerosis and cardiovascular diseases associated with obesity and the metabolic syndrome. We focus on the effects of adiponectin on glucose and lipid metabolism and on the molecular anti-atherosclerotic properties of adiponectin and also discuss the factors that increase the circulating levels of adiponectin. Adiponectin reduces inflammatory cytokines and oxidative stress, which leads to an improvement of insulin resistance. Adiponectin-induced improvement of insulin resistance and adiponectin itself reduce hepatic glucose production and increase the utilization of glucose and fatty acids by skeletal muscles, lowering blood glucose levels. Adiponectin has also β cell protective effects and may prevent the development of diabetes. Adiponectin concentration has been found to be correlated with lipoprotein metabolism; especially, it is associated with the metabolism of high-density lipoprotein (HDL) and triglyceride (TG). Adiponectin appears to increase HDL and decrease TG. Adiponectin increases ATP-binding cassette transporter A1 and lipoprotein lipase (LPL) and decreases hepatic lipase, which may elevate HDL. Increased LPL mass/activity and very low density lipoprotein (VLDL) receptor and reduced apo-CIII may increase VLDL catabolism and result in the reduction of serum TG. Further, adiponectin has various molecular anti-atherosclerotic properties, such as reduction of scavenger receptors in macrophages and increase of cholesterol efflux. These findings suggest that high levels of circulating adiponectin can protect against atherosclerosis. Weight loss, exercise, nutritional factors, anti-diabetic drugs, lipid-lowering drugs, and anti-hypertensive drugs have been associated with an increase of serum adiponectin level.

Adiponectin is associated with cardio-metabolic traits in Mexican children

The adipocyte-derived adiponectin hormone bridges obesity and its cardio-metabolic complications. Genetic variants at the ADIPOQ locus, in ADIPOR1, and ADIPOR2 have been associated with adiponectin concentrations and cardio-metabolic complications in diverse ethnicities. However, no studies have examined these associations in Mexican children. We recruited 1 457 Mexican children from Mexico City. Six genetic variants in or near ADIPOQ (rs182052, rs2241766, rs266729, rs822393), ADIPOR1 (rs10920533), and ADIPOR2 (rs11061971) were genotyped. Associations between serum adiponectin, genetic variants, and cardio-metabolic traits were assessed using linear and logistic regressions adjusted for age, sex, and recruitment center. Serum adiponectin concentration was negatively associated with body mass index, waist to hip ratio, low-density lipoprotein cholesterol, total cholesterol, triglycerides, fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, dyslipidemia and overweight/obesity status (7.76 × 10−40 ≤ p ≤ 3.00 × 10−3). No significant associations between genetic variants in ADIPOQ, ADIPOR1, and ADIPOR2 and serum adiponectin concentration were identified (all p ≥ 0.30). No significant associations between the six genetic variants and cardio-metabolic traits were observed after Bonferroni correction (all p < 6.9 × 10−4). Our study suggests strong associations between circulating adiponectin concentration and cardio-metabolic traits in Mexican children.

Circulating adiponectin concentrations during the transition from pregnancy to lactation in high-yielding dairy cows: testing the effects of farm, parity, and dietary energy level in large animal numbers

Dairy cows experience a negative energy balance due to increasing energy demands and insufficient voluntary feed intake in the transition from late pregnancy to early lactation. For supplying sufficient energy toward the conceptus and the mammary gland, insulin sensitivity in peripheral tissues is reduced leading to adipose tissue mobilization. Adiponectin, an insulin-sensitizing adipokine, is presumably related to energy metabolism and could play an important role in these metabolic adaptations. We hypothesize (1) that primiparous cows would differ from pluriparous cows in their circulating adiponectin concentrations during the transition from late pregnancy to early lactation and (2) that feeding different energy levels would affect the adiponectin concentrations during early lactation in dairy cows. For the first hypothesis, we examined 201 primiparous and 456 pluriparous Holstein dairy cows on three experimental farms. Ante partum, primiparous cows had lower adiponectin and greater NEFA concentrations than pluriparous cows, but vice versa post partum. Hence, adiponectin might be involved in the energy partitioning in primiparous cows (conceptus and lactation vs other still growing body tissues) with changing priorities from pregnancy to lactation. For the second hypothesis, 110 primiparous and 558 pluriparous Holstein and Simmental dairy cows in six experimental farms received either roughage with 6.1 or 6.5 MJ NEl/kg dry matter (adjusted with different amounts of wheat straw) ad libitum, combined with either 150 or 250 g concentrates/kg energy corrected milk. Greater amounts of concentrate lead to greater milk yield, but did not affect the blood variables. The higher energy level in the roughage led to greater glucose and IGF-1 but lower adiponectin in pluriparous cows. Further studies are needed to elucidate the mechanisms behind the roughage effect and its metabolic consequences.

Validity and application of immunoturbidimetric and enzyme-linked immunosorbent assays for the measurement of adiponectin concentration in ponies.

Circulating adiponectin concentrations were lower in ponies with a history of endocrinopathic laminitis and in nonlaminitic ponies that subsequently developed laminitis. The assays used in these studies have been discontinued or are no longer valid. (1) to determine the validity of immunoturbidimetric (IT) and enzyme linkedimmunosorbent (ELISA) assays for equine total and high molecular weight (HMW) [adiponectin] measurement and (2) to investigate the association between [adiponectin] measured using these assays and endocrinopathic laminitis. Method validation and cohort study. Accuracy and precision of IT and ELISA assays for measuring total (TAC) and HMW (HMWAC) [adiponectin] were determined. Using the IT assay, the effects of anti-coagulant and storage temperature were assessed, TAC was measured in previously laminitic (PL) and never laminitic (NL) ponies (n = 6/group). Comparison with a previously validated radioimmunoassay was made in NL ponies (n = 223). Association between TAC and subsequent laminitis development in NL ponies was investigated using univariable logistic regression and ROC curve analysis. The IT assay was precise and demonstrated good agreement with the previously validated radioimmunoassay. TAC was significantly (P<0.01) lower in PL (mean ± s.d. 8.9 ± 2.9 μg/mL) compared to NL (24.2 ± 11.8 μg/mL) ponies and in NL ponies that developed laminitis within 12 months (median 4.8 μg/mL; IQR 2.65-13.4 μg/mL) compared to those that remained nonlaminitic (19.9 μg/mL; 9.95-31.5 μg/mL). TAC was significantly (P = 0.01) associated with laminitis occurrence within 12 months. Use of the area under the ROC curve to distinguish animals that did and did not develop laminitis showed good accuracy (0.76). None of the ELISA methods validated satisfactorily. Laminitis risk is based on data from ponies in one region. The IT method is suitable for measurement of equine TAC. TAC is lower in ponies with previous or future laminitis. The ELISA methods are not suitable for measurement of equine HMWAC or TAC.

Probiotic Lactobacillus rhamnosus GG culture supernatant improves energy expenditure and glucose tolerance in high‐fat‐high‐fructose fed mice exposed to chronic intermittent hypoxia through regulation of intestinal microbiota and bile acid homeostasis

BackgroundObstructive sleep apnea syndrome (OSAS) has been recently connected to metabolic disorders such as nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes, which is characterized by gut dysbiosis in recent studies. Our previous studies have demonstrated that the probiotic Lactobacillus rhamnosus GG cultural supernatant (LGGs) prevents alcoholic liver disease (ALD) and fructose‐induced NAFLD. In the current study, we aimed to examine the effects of LGGs on glucose metabolisms and body energy expenditure in mice fed a high‐fathigh‐fructose (HFHF) diet and exposed to chronic intermittent hypoxia in order to understand the underlying mechanisms.MethodsC57BL/6 mice were fed HFHF diet or normal liquid diet (NLD) respectively for 15 weeks. After 3 weeks feeding, two groups of mice were exposed to chronic intermittent hypoxia (CIH) for 12 weeks, and one of the groups was supplemented with LGGs at a dose equivalent to 109 CFU bacteria/day. The effects of LGGs on body fat composition and energy expenditure were assessed by dual‐energy X‐ray absorptiometry (DEXA) using a GE Lunar PIXI and by indirect calorimetry using metabolic chamber system, respectively. Glucose tolerance and insulin tolerance were also evaluated. Hepatic and adipose tissue was examined by histological staining. Circulating adiponectin concentration was determined using an ELISA, and adipose tissue adiponectin protein expression was determined by Western blot. Hepatic and circulating bile acid composition were determined by LC‐MS‐based metabolomics analysis, and intestinal microbiota were analyzed by pyrosequencing.ResultsHFHF diet feeding significantly increased body fat mass, hepatic steatosis, glucose tolerance, and liver injury, and decreased energy expenditure. These indices of metabolic disorders were worsened in mice exposed to CIH, indicating that CIH has an additive effect on HFHF diet feeding. The HFHF‐fed mice supplemented with LGGs showed marked improvements in indices of metabolic disorder including fat mass, energy expenditure and glucose and insulin tolerance. LGGs treatment decreased hepatic fat content and adipocyte size. Adipose expression of HIF‐1α, a marker of tissue hypoxia, was increased in HFHF‐CIH mice, which was reduced by LGGs treatment. The reduction of adipose tissue hypoxia was associated with decreased inflammatory cytokines such as TNFα, IL‐1β and IL‐6. HFHF‐CIH mice had a markedly reduced circulating adiponectin, which is critical in the regulation of insulin sensitivity and was significantly elevated by LGGs treatment. Metabolomic analysis showed that LGGs supplementation significantly changed hepatic and fecal bile acid composition. Fecal concentrations of TαMCA and TβMCA, which are known FXR antagonists, were decreased in HFHF‐CIH mice but were significantly increased by LGGs treatment.ConclusionLGGs treatment prevents metabolic abnormalities induced by diet and hypoxia in HFHF‐CIH mice. The beneficial effects of LGGs are mediated by multiple mechanisms. LGGs modulates intestinal bile acid regulation and intestinal specific FXR inactivation, which has been shown to be a strategy in the prevention of NAFLD‐associated metabolic derangement. LGGs treatment decreases adipose hypoxia‐associated inflammation leading to improved adiponectin production, which plays an important role in insulin sensitivity. LGGs may be a potential prevention/treatment strategy in subjects with sleep disorder and metabolic syndrome.Support or Funding InformationSupported by grants from NIH and Veterans AdministrationThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Myocardial Adiponectin Isoform Shift in Dogs with Congestive Heart Failure-A Comparison to Hibernating Brown Bears (Ursus arctos horribilis).

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.