Higher Plasma Adiponectin Levels Research Articles

Exploring the Relationship between Plasma Adiponectin, Gender, and Underlying Diseases in Severe Illness.

Adiponectin is low in obesity, plays a crucial role in metabolic health, and, moreover, possesses immunoregulatory properties. However, studies examining its levels in patients with systemic inflammatory response syndrome (SIRS) or sepsis have yielded conflicting results. While females typically have higher systemic adiponectin levels than males, research on sex-specific associations in this context is limited. In this study of 156 SIRS/sepsis patients, including those with liver cirrhosis, we aimed to explore the relationship between plasma adiponectin, body mass index (BMI), gender, disease severity, and underlying etiological conditions. Our findings revealed that patients with liver cirrhosis, who are susceptible to infections, exhibited elevated circulating adiponectin levels, irrespective of sex. When excluding cirrhosis patients, plasma adiponectin levels were similar between male SIRS/sepsis patients and controls but lower in female patients compared to female controls. Plasma adiponectin was inversely related to BMI in female but not male patients. Further analysis within the non-cirrhosis subgroup demonstrated no significant differences in adiponectin levels between sexes among SIRS, sepsis, and septic shock patients. Ventilation, dialysis, and vasopressor therapy had no discernible impact on adiponectin levels in either sex. A negative correlation between adiponectin and C-reactive protein (CRP) existed in males only. Notably, patients with pancreatitis showed the lowest plasma adiponectin concentrations, although sex-specific differences were not significant. Infection with Gram-negative or Gram-positive bacteria had minimal effects on plasma adiponectin levels in both sexes. However, infection with the severe acute respiratory syndrome coronavirus type 2 led to decreased adiponectin levels in females exclusively. Multivariate analysis considering all factors affecting plasma adiponectin levels in males or females identified BMI in females and CRP levels in males to predict plasma adiponectin levels in SIRS/sepsis patients. Additionally, our study observed a trend where the 25 patients who did not survive had higher plasma adiponectin levels, particularly among males. In summary, our investigation highlights the influence of underlying diseases and sex on plasma adiponectin levels in SIRS/sepsis patients, shedding light on potential implications for disease management and prognosis.

Abstract 10095: Association of Plasma Adiponectin and Leptin Levels With All-Cause Mortality and New-Onset Ventricular Tachyarrhythmias in Patients With Hypertrophic Cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is one of the leading causes of sudden cardiac death in the young. The current models to predict ventricular tachycardia/fibrillation (VT/VF) and mortality perform poorly. Adipokines are secreted from the adipose tissue and regulate cardiac inflammation, fibrosis, and hypertrophy. Among the adipokines, adiponectin and leptin are related to cardiac remodeling in HCM. The present study examined the association of plasma adiponectin and leptin levels with all-cause mortality and VT/VF in patients with HCM. Hypothesis: Plasma adiponectin and leptin levels at enrollment are associated with all-cause mortality and VT/VF in patients with HCM. Methods: We performed a multicenter prospective cohort study of patients with HCM. We measured plasma adiponectin and leptin levels at enrollment. The outcome was a composite of all-cause mortality and new-onset VT/VF. After dividing the cohort into four groups according to the adiponectin and leptin levels, we compared the risk of the outcome event using the Cox proportional hazards model adjusting for age, body mass index, left atrium diameter, and maximum left ventricular wall thickness, using the largest group as a reference. Results: During a median follow-up of 3.3 years, the outcome event occurred in 37 out of 402 patients. The four groups divided by adiponectin and leptin levels had different risks of the outcome event (log-rank P <0.001). The Cox proportional hazards model revealed that the High-Adiponectin, Low-Leptin group had a significantly higher risk (adjusted HR 5.02, 95% CI 1.63-15.47, P =0.005. Figure ) compared with the reference (Low-Adiponectin, High-Leptin) group. Conclusions: The combination of high plasma adiponectin and low leptin levels is independently associated with mortality and new-onset VT/VF in patients with HCM. These adipokines have a potential to become novel biomarkers for risk stratification in HCM to improve the current prediction models.

Plasma adiponectin levels predict cognitive decline and cortical thinning in mild cognitive impairment with beta-amyloid pathology

BackgroundBlood adiponectin and leptin are adipokines that emerged as potential biomarkers for predicting Alzheimer’s disease (AD) owing to their strong connection with obesity. Although obesity affects the relation between beta-amyloid (Aβ) aggregation and cognitive decline, the longitudinal interactive effect of adipokines and Aβ on cognition and brain structures in humans remains unexplored. Hence, we investigated whether plasma levels of adiponectin and leptin are associated with future cognitive decline and cortical thinning across Aβ conditions (Aβ [+] and Aβ [−]) in individuals with mild cognitive impairment (MCI).MethodsOf 156 participants with MCI from the longitudinal cohort study of Alzheimer’s Disease Neuroimaging Initiative (ADNI), 31 were Aβ (−) and 125 were Aβ (+) as determined by CSF analysis. The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores and the thickness of the parahippocampal and entorhinal cortices were used to evaluate cognition and brain structure, respectively. After stratifying groups by Aβ conditions, the association of cognitive and brain structural changes with baseline plasma levels of adiponectin and leptin was examined.ResultsOf the total 156 participants, 51 were women (32.7%). The mean age of participants was 74.5 (standard deviation 7.57), and the mean follow-up period was 54.3 months, without a difference between the Aβ (+) and (−) groups. After adjustment for confounders, higher plasma adiponectin levels were associated with a faster increase in ADAS-Cog scores, indicating faster cognitive decline under the Aβ (+) condition (beta = 0.224, p = 0.018). Likewise, participants with higher plasma adiponectin presented faster cortical thinning in the bilateral parahippocampal cortices under the Aβ (+) condition (beta = − 0.004, p = 0.012 for the right side; beta = − 0.004, p = 0.025 for the left side). Interestingly, plasma adiponectin levels were not associated with longitudinal ADAS-Cog scores or cortical thickness in the Aβ (−) condition. Plasma leptin levels were not predictive of cognition or cortical thickness regardless of Aβ status.ConclusionPlasma adiponectin can be a potential biomarker for predicting the speed of AD progression in individuals with Aβ (+) MCI.

Krill Oil Supplementation Reduces Exacerbated Hepatic Steatosis Induced by Thermoneutral Housing in Mice with Diet-Induced Obesity.

Preclinical evidence suggests that n-3 fatty acids EPA and DHA (Omega-3) supplemented as phospholipids (PLs) may be more effective than triacylglycerols (TAGs) in reducing hepatic steatosis. To further test the ability of Omega-3 PLs to alleviate liver steatosis, we used a model of exacerbated non-alcoholic fatty liver disease based on high-fat feeding at thermoneutral temperature. Male C57BL/6N mice were fed for 24 weeks a lard-based diet given either alone (LHF) or supplemented with Omega-3 (30 mg/g diet) as PLs (krill oil; ω3PL) or TAGs (Epax 3000TG concentrate; ω3TG), which had a similar total content of EPA and DHA and their ratio. Substantial levels of TAG accumulation (~250 mg/g) but relatively low inflammation/fibrosis levels were achieved in the livers of control LHF mice. Liver steatosis was reduced by >40% in the ω3PL but not ω3TG group, and plasma ALT levels were markedly reduced (by 68%) in ω3PL mice as well. Krill oil administration also improved hepatic insulin sensitivity, and its effects were associated with high plasma adiponectin levels (150% of LHF mice) along with superior bioavailability of EPA, increased content of alkaloids stachydrine and trigonelline, suppression of lipogenic gene expression, and decreased diacylglycerol levels in the liver. This study reveals that in addition to Omega-3 PLs, other constituents of krill oil, such as alkaloids, may contribute to its strong antisteatotic effects in the liver.

Association between visceral/subcutaneous adipose tissue ratio and plasma inflammatory markers and score for cardiovascular risk prediction in a Brazilian cohort: Pró-Saúde Study.

Visceral adipose tissue (VAT) is associated with various metabolic disorders, and adipokines, secreted by adipose tissue, are involved in their pathogenesis. This study investigated associations between VAT/subcutaneous adipose tissue (SAT) ratio, inflammatory markers, and cardiovascular (CV) risk-score in adults. Plasma levels of adipokines, plasma lipid profile, blood pressure, and body composition (using dual-emission x-ray absorptiometry) were determined. CV risk-score based on the American College of Cardiology and the American Heart Association (ACC/AHA) score was calculated in a sample of 309 Brazilian civil servants aged <60 years. Participants' VAT/SAT ratio were categorized into quartiles. Among males, plasma leptin (2.8 ng/mL) and C reactive protein (CRP) (0.2 mg/dL) (P<0.05) levels were higher at P75 and P50 than P5, and the highest calculated CV risk-score was observed at P75 (7.1%). Among females, higher plasma adiponectin levels were observed at P25 (54.3 ng/mL) compared with P75 (36 ng/mL) (P<0.05). Higher plasma CRP levels were observed at P75 (0.4 mg/dL) compared with P5 (0.1 mg/dL) (P<0.05). Higher CV risk-score was observed at P75 (2.0%) compared with P5 (0.7%). In both sexes, VAT and VAT/SAT ratio were directly associated with plasma leptin, CRP, and CV risk-score, and inversely associated with adiponectin; SAT was directly associated with plasma leptin and CRP (P<0.01); interleukin (IL)-10 and CRP were directly associated with adiponectin and leptin, respectively (P<0.05). Among men only, IL-10 (inversely) and CRP (directly) were associated with CV risk-score (P=0.02). Our results strengthened the relevance of the VAT/SAT ratio in cardiovascular risk.

Methionine restriction prevents onset of type 2 diabetes in NZO mice

Dietary methionine restriction (MR) is well known to reduce body weight by increasing energy expenditure (EE) and insulin sensitivity. An elevated concentration of circulating fibroblast growth factor 21 (FGF21) has been implicated as a potential underlying mechanism. The aims of our study were to test whether dietary MR in the context of a high-fat regimen protects against type 2 diabetes in mice and to investigate whether vegan and vegetarian diets, which have naturally low methionine levels, modulate circulating FGF21 in humans. New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes, were placed on isocaloric high-fat diets (protein, 16 kcal%; carbohydrate, 52 kcal%; fat, 32 kcal%) that provided methionine at control (Con; 0.86% methionine) or low levels (0.17%) for 9 wk. Markers of glucose homeostasis and insulin sensitivity were analyzed. Among humans, low methionine intake and circulating FGF21 levels were investigated by comparing a vegan and a vegetarian diet to an omnivore diet and evaluating the effect of a short-term vegetarian diet on FGF21 induction. In comparison with the Con group, MR led to elevated plasma FGF21 levels and prevented the onset of hyperglycemia in NZO mice. MR-fed mice exhibited increased insulin sensitivity, higher plasma adiponectin levels, increased EE, and up-regulated expression of thermogenic genes in subcutaneous white adipose tissue. Food intake and fat mass did not change. Plasma FGF21 levels were markedly higher in vegan humans compared with omnivores, and circulating FGF21 levels increased significantly in omnivores after 4 d on a vegetarian diet. These data suggest that MR induces FGF21 and protects NZO mice from high-fat diet–induced glucose intolerance and type 2 diabetes. The normoglycemic phenotype in vegans and vegetarians may be caused by induced FGF21. MR akin to vegan and vegetarian diets in humans may offer metabolic benefits via increased circulating levels of FGF21 and merits further investigation.—Castaño-Martinez, T., Schumacher, F., Schumacher, S., Kochlik, B., Weber, D., Grune, T., Biemann, R., McCann, A., Abraham, K., Weikert, C., Kleuser, B., Schürmann, A., Laeger, T. Methionine restriction prevents onset of type 2 diabetes in NZO mice.

Macrophage CD40 plays a minor role in obesity-induced metabolic dysfunction.

Obesity is a low-grade inflammatory disease that increases the risk for metabolic disorders. CD40-CD40L signaling plays a central role in obesity-induced inflammation. Genetic deficiency of CD40L in diet-induced obesity (DIO) ameliorates adipose tissue inflammation, hepatic steatosis and increases insulin sensitivity. Unexpectedly, absence of CD40 worsened insulin resistance and caused excessive adipose tissue inflammation and hepatosteatosis. To investigate whether deficiency of macrophage CD40 is responsible for the phenotype observed in the CD40-/- mice, we generated CD40flflLysMcre and fed them a standard (SFD) and 54% high fat obesogenic diet (HFD) for 13 weeks. No differences in body weight, adipose tissue weight, adipocyte size, plasma cholesterol or triglyceride levels could be observed between CD40flflLysMcre and wild type (WT) mice. CD40flflLysMcre displayed no changes in glucose tolerance or insulin resistance, but had higher plasma adiponectin levels when fed a SFD. Liver weights, liver cholesterol and triglyceride levels, as well as the degree of hepatosteatosis were not affected by absence of macrophage CD40. CD40flflLysMcre mice displayed a minor increase in adipose tissue leukocyte infiltration on SFD and HFD, which did not result in differences in adipose tissue cytokine levels. We here show that loss of macrophage CD40 signaling does not affect obesity induced metabolic dysregulation and indicates that CD40-deficiency on other cell-types than the macrophage is responsible for the metabolic dysregulation, adipose tissue inflammation and hepatosteatosis that are observed in CD40-/- mice.

High plasma adiponectin levels are associated with frailty in a general old-old population: The Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study.

The objective of the present study was to investigate the association between frailty and plasma adiponectin levels in a general population of Japanese older adults. The volunteer older adults, aged approximately 83 years, were recruited randomly from a general population in the Japanese Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians study. We used the modified Cardiovascular Health Study criteria to assess the frailty status of the study participants. The study participants were classified as non-frail, pre-frail and frail according to their physical activities. We compared plasma adiponectin levels among these three groups and applied a multivariate logistic regression analysis including plasma adiponectin levels to clarify the factors associated with frailty status in the cross-sectional design. The mean age of the participants was 83.1 ± 0.9 years, and 51.8% were men. The frailty index was available to assess 353 participants, of whom 24.6% were classified as non-frail, 62.3% as prefrail and 13.0% as frail. The log-transformed plasma adiponectin levels increased stepwise in the following order: non-frail, pre-frail and frail. A multivariate logistic regression analysis showed that higher plasma adiponectin levels, a higher estimated glomerular filtration rate and lower hemoglobin levels were independent determinants for pre-frail/frail status compared with non-frail status. The present study showed that higher plasma adiponectin levels were associated with frailty status in older Japanese adults in the general population. Further longitudinal study is essential to clarify the role of plasma adiponectin in the progression of frailty. Geriatr Gerontol Int 2018; 18: 839-846.

T-cadherin gene variants are associated with nephropathy in subjects with type 1 diabetes.

High plasma adiponectin levels are associated with diabetic nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be associated with adiponectin levels. We investigated associations between allelic variations of CDH13 and DN in subjects with type 1 diabetes.Two CDH13 polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up), 'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and 'Génétique de la Néphropathie Diabétique' (GENEDIAB) (n = 456, 9-year follow-up for n = 283) cohorts. Adiponectin levels were measured in plasma samples from GENESIS and GENEDIAB cohorts.Pooled analysis of GENEDIAB and GENESIS studies showed that baseline plasma adiponectin levels were higher in subjects with established/advanced DN at inclusion (P < 0.0001) and in subjects who developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor allele of rs3865188 was associated with lower adiponectin levels (P = 0.006). rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P = 0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with baseline prevalence of established/advanced DN. These polymorphisms were also associated with the risk of ESRD (0.006 < P < 0.03). The association between rs11646213 (but not rs3865188) and renal function remained significant after adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR) 1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P = 0.04) were associated with risk of renal events (defined as progression to more severe DN stages).Plasma adiponectin levels are associated with the prevalence of DN and the incidence of ESRD in patients with type 1 diabetes. CDH13 polymorphisms are also associated with the prevalence and incidence of DN, and with the incidence of ESRD in these patients. The association between CDH13 and DN may be due to pleiotropic effects, both dependent and independent of plasma adiponectin levels.

T-cadherin gene variants are associated with nephropathy in subjects with type 1 diabetes.

High plasma adiponectin levels are associated with diabetic nephropathy (DN). T-cadherin gene (CDH13) variants have been shown to be associated with adiponectin levels. We investigated associations between allelic variations of CDH13 and DN in subjects with type 1 diabetes. Two CDH13 polymorphisms were analysed in 1297 Caucasian subjects with type 1 diabetes from the 'Survival Genetic Nephropathy' (SURGENE) (n = 340, 10-year follow-up), 'Genesis France-Belgium' (GENESIS) (n = 501, 5-year follow-up for n = 462) and 'Génétique de la Néphropathie Diabétique' (GENEDIAB) (n = 456, 9-year follow-up for n = 283) cohorts. Adiponectin levels were measured in plasma samples from GENESIS and GENEDIAB cohorts. Pooled analysis of GENEDIAB and GENESIS studies showed that baseline plasma adiponectin levels were higher in subjects with established/advanced DN at inclusion (P < 0.0001) and in subjects who developed end-stage renal disease (ESRD) at follow-up (P < 0.0001). The minor allele of rs3865188 was associated with lower adiponectin levels (P = 0.006). rs11646213 [odds ratio (OR) 1.47; 95% confidence interval (CI) 1.18-1.85; P = 0.0009] and rs3865188 (OR 0.71; 95% CI 0.57-0.90; P = 0.004) were associated with baseline prevalence of established/advanced DN. These polymorphisms were also associated with the risk of ESRD (0.006 < P < 0.03). The association between rs11646213 (but not rs3865188) and renal function remained significant after adjustment for plasma adiponectin. In SURGENE, rs11646213 [hazard ratio (HR) 1.69; 95% CI 1.01-2.71; P = 0.04] and rs3865188 (HR 0.74; 95% CI 0.55-0.99; P = 0.04) were associated with risk of renal events (defined as progression to more severe DN stages). Plasma adiponectin levels are associated with the prevalence of DN and the incidence of ESRD in patients with type 1 diabetes. CDH13 polymorphisms are also associated with the prevalence and incidence of DN, and with the incidence of ESRD in these patients. The association between CDH13 and DN may be due to pleiotropic effects, both dependent and independent of plasma adiponectin levels.

Adiponectin Plasma Levels and Albuminuria in Patients with Type 2 Diabetes and Different Stages of Diabetic Kidney Disease

Adiponectin is an inflammatory cytokine produced by adipose tissue and its protective role has been recognized in the pathogenesis of obesity. A lower concentration in obesity patients is noted, in conditions of resistance to insulin, diabetes mellitus, and CKD. Patients with type 2 diabetes mellitus have a potential risk of atherosclerosis, while low concentrations of adiponectin are considered as predictor for the occurrence of complications in patients with type 2 diabetes. The aim of this study was to investigate in patients with type 2 diabetes mellitus with and without diabetic nephropathy the correlation of adiponectin levels and CKD stage or degree of albuminuria. We studied 119 patients with type 2 diabetes mellitus with different stage of renal function, the levels of plasma adiponectin, and the BMI. A statistically significant difference of plasma adiponectin levels was noted between the initial and end stages of CKD, the highest levels seen in ESKD patients. Also, the levels of adiponectin were elevated in patients with greater albuminuria (statistically significant difference between groups 1 and 3, p=0.05). The levels of adiponectin were found to decrease with increasing the stage of obesity (ANOVA, p<0.05). Finally, the group of patients receiving glitazones had higher plasma adiponectin levels compared to those not receiving. It concluded that the levels of adiponectin increase with the deterioration of renal function and with enhancement of albuminuria, while decreasing as the stage of obesity worsens. The administration of glitazones was associated with increased plasma levels of adiponectin.

T-cadherin gene variants are associated with type 2 diabetes and the Fatty Liver Index in the French population

AimAdiponectin is an adipocyte-secreted protein associated with insulin sensitivity. T-cadherin is a receptor for high and medium molecular weight adiponectin. In GWAS, T-cadherin gene (CDH13) polymorphisms are associated with circulating adiponectin levels. This study investigated the associations between genetic variants of CDH13 and type 2 diabetes (T2D), and its related parameters, in a Caucasian population. MethodsTwo polymorphisms of CDH13 (rs11646213 and rs3865188) were genotyped in two French cohorts, a general population from the D.E.S.I.R. study (n=5212) and people with T2D in the DIABHYCAR study (n=3123). Baseline adiponectin levels were measured in D.E.S.I.R. participants who were normoglycaemic at baseline, but hyperglycaemic after 3 years (n=230), and in controls who remained normoglycaemic (n=226) throughout. ResultsIn a cross-sectional analysis, CDH13 genotype distributions differed between those with and without T2D, with T2D odds ratios (OR) of 1.11 (95% CI: 1.04–1.18; P=0.001) and 0.92 (95% CI: 0.87–0.98; P=0.01) for rs11646213 and rs3865188, respectively. The rs11646213 variant, associated with a higher OR for T2D, was also associated with higher BMI (P=0.03) and HbA1c (P=0.006), and lower plasma adiponectin levels (P=0.03) in the D.E.S.I.R. participants. Conversely, the rs3865188 variant, associated with a lower OR for T2D, was also associated with lower BMI (P=0.03), HbA1c (P=0.02) and Fatty Liver Index (FLI; P≤0.01), and higher plasma adiponectin levels (P=0.002). Associations with HbA1c, FLI and adiponectin levels persisted after adjusting for BMI. ConclusionCDH13 polymorphisms are associated with prevalent T2D in this French population study. The association may be mediated through effects on BMI and/or plasma adiponectin.

Effects of exercise on plasma adiponectin levels in athletes

Adipose tissue is an endocrine organ which releases biologically active adipokines. Adiponectin, an adipocyte-derived protein structurally similar to complement 1q, plays a significant role in metabolic disorders, due to its insulin sensitizing, anti-inflammatory and anti-atherogenic properties. AdipoR1 and AdipoR2, mediate the metabolic actions of adiponectin by activating adenosine monophosphate-activated protein kinase (AMPK) and peroxisome proliferator-activated receptors- alpha (PPAR-α) which leads to an increase in fatty acid combustion and energy consumption, fatty acid oxidation and glucose uptake in myocytes and reduces gluconeogenesis and thus leads to increased insulin sensitivity. Plasma adiponectin level is affected by multiple factors: gender (females have higher plasma adiponectin levels), obesity-linked diseases (metabolic syndrome, diabetes mellitus type 2 and atherosclerosis are associated with lower adiponectin levels), lifestyle -including exercise. Yet, to date, little is known about the response of adiponectin concentrations to exercise and, in particular, the response of this hormone to training in population of athletes. The aim of this review is to overview the published evidence for the effects of exercise on adiponectin levels in athletes. Adiponectin concentration presents a delayed increase (30 min) after short-term intense performance, by athletes, both male and female. It seems that adiponectin concentrations do not change in response to long-term exercise. No significant difference was found in total adiponectin and/or high-molecular weight (HMW) oligomers in long-term effects of high physical training in athletes. Adiponectin can serve to monitor training loads and the establishment of individual limit values of training loads. Further studies are needed to clarify possible mechanisms by which adiponectin might influence energy homeostasis during heavy training in elite athletes.

Association between plasma adiponectin levels and colorectal cancer risk in women.

Adiponectin, an adipocyte-secreted hormone, has insulin-sensitizing characteristics. It remains unclear whether adiponectin may influence colorectal cancer development. To determine whether prediagnostic levels of adiponectin were associated with risk of incident colorectal cancer in the Women's Health Study, we conducted a nested case-control study of 275 colorectal cancer cases and 275 matched controls. Each case was matched to a control by age, ethnicity, fasting status at the time of blood collection, time of day when blood was drawn, and month of blood draw. Multivariable logistic regression with adjustment for colorectal cancer risk factors was used to estimate the odds ratio (OR) and 95 % confidence interval (CI) for risk of colorectal cancer incidence and mortality by adiponectin quartiles based on the control distribution. Median plasma adiponectin level was similar in cases versus controls (6.00 vs. 6.24 μg/mL). In multivariable-adjusted logistic regression models, high plasma adiponectin levels were not significantly associated with risk of colorectal cancer [quartile 4 (Q4) vs. quartile 1 (Q1): OR (95 % CI) 0.86 (0.48-1.56), p trend = 0.63]. These results suggest no appreciable association between plasma adiponectin and risk of colorectal cancer in women. Confirmation of these observations in larger studies is needed.

Plasma Adiponectin Levels in Elderly Patients with Prediabetes.

BackgroundThe significance of adiponectin levels in elderly individuals with prediabetes has yet to be determined. Thus, the present study was performed to evaluate the relationships between adiponectin levels and anthropometric variables, body composition parameters, insulin sensitivity, and lipid profiles in elderly prediabetic patients.MethodsThe present study included 120 subjects with prediabetes who were >65 years of age and were selected from among 1,993 subjects enrolled in the Korea Rural Genomic Cohort Study. All subjects underwent a 75 g oral glucose tolerance test and tests for measurement of insulin sensitivity. All diagnoses of prediabetes satisfied the criteria of the American Diabetes Association.ResultsPlasma adiponectin levels were lower in elderly prediabetic subjects than elderly subjects with normal glucose tolerance (P<0.01) as well as in elderly prediabetic patients with metabolic syndrome (MetS) than in those without MetS (P<0.02). When the subjects were categorized into two groups according to plasma adiponectin levels, the waist-to-hip ratio and 2-hour insulin levels were significantly lower in individuals with high plasma adiponectin levels than in those with low plasma adiponectin levels. Additionally, the plasma adiponectin levels of elderly prediabetic subject were inversely correlated with body mass index (BMI), waist circumference (WC), waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels.ConclusionThe present findings demonstrated that the major factors correlated with adiponectin levels in elderly prediabetic subjects were BMI, WC, waist-to-hip ratio, visceral fat, visceral fat ratio, and 2-hour insulin levels.

Chronic intake of proanthocyanidins and docosahexaenoic acid improves skeletal muscle oxidative capacity in diet-obese rats

Obesity has become a worldwide epidemic. The cafeteria diet (CD) induces obesity and oxidative-stress-associated insulin resistance. Polyunsaturated fatty acids and polyphenols are dietary compounds that are intensively studied as products that can reduce the health complications related to obesity. We evaluate the effects of 21days of supplementation with grape seed proanthocyanidins extract (GSPE), docosahexaenoic-rich oil (DHA-OR) or both compounds (GSPE+DHA-OR) on skeletal muscle metabolism in diet-obese rats. The supplementation with different treatments did not reduce body weight, although all groups used more fat as fuel, particularly when both products were coadministered; muscle β-oxidation was activated, the mitochondrial functionality and oxidative capacity were higher, and fatty acid uptake gene expressions were up-regulated. In addition to these outcomes shared by all treatments, GSPE reduced insulin resistance and improved muscle status. Both treatments increased 5’-AMP-activated protein kinase (AMPK) phosphorylation, which was consistent with higher plasma adiponectin levels. Moreover, AMPK activation by DHA-OR was also correlated with an up-regulation of peroxisome proliferator-activated receptor alpha (Pparα). GSPE+DHA-OR, in addition to activating AMPK and enhancing fatty acid oxidation, increased the muscle gene expression of uncoupling protein 2 (Ucp2). In conclusion, GSPE+DHA-OR induced modifications that improved muscle status and could counterbalance the deleterious effects of obesity, and such modifications are mediated, at least in part, through the AMPK signaling pathway.

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

ObjectiveThe 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. MethodsThousand 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. ResultsTwenty 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. ConclusionThese 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.

Manganese supplementation increases adiponectin secretion by upregulating disulfide bond A‐like protein in endothelial cells and Zucker diabetic fatty rats (767.13)

Adiponectin is an insulin sensitizer that plays a role in the regulation of lipid and glucose homeostasis and has anti atherosclerotic effects. It is synthesized as a single polypeptide and is then assembled in the endoplasmic reticulum into different multimers. An adiponectin‐interacting protein named disulfide bond A‐like protein (DsbA‐L) was recently found to play an important role in multimerization of adiponectin; impairment in DsbA‐L is associated with diabetes and low adiponectin levels. Manganese (Mn) levels have been found to be low in atherosclerotic and diabetic patients. Previous studies in our lab have shown that Mn supplementation can lower blood cholesterol and ICAM‐1 levels in ZDF rats and reduce MCP‐1 secretion and monocyte adhesion to endothelial cells in HUVECs model (J. Biol. Chem, 2013 Mar 1; 288 (9):6409‐16). This study investigates the hypothesis that Mn supplementation affects DsbA‐L expression levels, and thereby adiponectin levels, in ZDF rats and endothelial cells (HUVECs). Results show that diabetic rats supplemented with Mn (gavaged daily with 16 mg/kg BW for seven weeks, n=5) have higher plasma adiponectin levels (41%, p=0.007) and higher DsbA‐L expression in the liver compared to control diabetic rats (n=6). Similarly, pre‐treatment with Mn (with 5 or 10 μM for 24 h) prevented the decrease in DsbAL expression and adiponectin levels in HUVECs and 3T3L1 adipocyte cells exposed to high glucose and MCP‐1. We further investigated the role of DsbA‐L protein by knocking down its expression in HUVECs. Preliminary studies with DsbA‐L siRNA show that beneficial effects of Mn supplementation on NOX4 expression and other biomarkers of vascular inflammation were abolished in DsbA‐L knocked down cells. Thus, this study demonstrates that DsbA‐L mediates the beneficial effects of Mn on adiponectin and provides a novel mechanism by which Mn supplementation reduces biomarkers of vascular inflammation in diabetes.

Manganese supplementation increases adiponectin secretion by upregulating disulfide bond A‐like protein in endothelial cells and Zucker diabetic fatty rats (249.1)

Adiponectin is an insulin sensitizer that plays a role in the regulation of lipid and glucose homeostasis and has anti atherosclerotic effects. It is synthesized as a single polypeptide and is then assembled in the endoplasmic reticulum into different multimers. An adiponectin‐interacting protein named disulfide bond A‐like protein (DsbA‐L) was recently found to play an important role in multimerization of adiponectin; impairment in DsbA‐L is associated with diabetes and low adiponectin levels. Manganese (Mn) levels have been found to be low in atherosclerotic and diabetic patients. Previous studies in our lab have shown that Mn supplementation can lower blood cholesterol and ICAM‐1 levels in ZDF rats and reduce MCP‐1 secretion and monocyte adhesion to endothelial cells in HUVECs model (J. Biol. Chem, 2013 Mar 1; 288 (9):6409‐16). This study investigates the hypothesis that Mn supplementation affects DsbA‐L expression levels, and thereby adiponectin levels, in ZDF rats and endothelial cells (HUVECs). Results show that diabetic rats supplemented with Mn (gavaged daily with 16 mg/kg BW for seven weeks, n=5) have higher plasma adiponectin levels (41%, p=0.007) and higher DsbA‐L expression in the liver compared to control diabetic rats (n=6). Similarly, pre‐treatment with Mn (with 5 or 10 μM for 24 h) prevented the decrease in DsbAL expression and adiponectin levels in HUVECs and 3T3L1 adipocyte cells exposed to high glucose and MCP‐1. We further investigated the role of DsbA‐L protein by knocking down its expression in HUVECs. Preliminary studies with DsbA‐L siRNA show that beneficial effects of Mn supplementation on NOX4 expression and other biomarkers of vascular inflammation were abolished in DsbA‐L knocked down cells. Thus, this study demonstrates that DsbA‐L mediates the beneficial effects of Mn on adiponectin and provides a novel mechanism by which Mn supplementation reduces biomarkers of vascular inflammation in diabetes.

Plasma Levels of Adiponectin and Primary Liver Cancer Risk in Middle-Aged Japanese Adults with Hepatitis Virus Infection: A Nested Case–Control Study

Excess body weight is an independent risk factor for primary liver cancer, and the role of adiponectin in the pathogenesis of obesity-related malignancies is a focus of research interest. Few prospective studies have examined the association between circulating adiponectin and liver cancer risk, so we investigated this association in a nested case-control study of a population-based prospective cohort in Japan. From 18,628 target participants of ages 40 to 69 years who returned the baseline questionnaire and provided blood samples, we selected those with either hepatitis B or C virus infection at baseline (n = 1,544). Among these, 90 were newly diagnosed with primary liver cancer from 1993 through 2006, and matched to 177 controls. The ORs of liver cancer development based on plasma levels of adiponectin were estimated with a conditional logistic regression model. Median values of total and high-molecular-weight (HMW) adiponectin tended to be higher in the patients with liver cancer, and plasma levels of adiponectin were positively associated with liver cancer risk. Body mass index- and diabetes-adjusted ORs for the highest tertile of total and HMW adiponectin levels versus the lowest were 3.30 [95% confidence interval (CI), 1.45-7.53; Ptrend < 0.01] and 3.41 (95% CI, 1.50-7.73; Ptrend < 0.01), respectively. There was no effect modification by body mass index and diabetes. Higher plasma adiponectin levels were associated with an increased risk of primary liver cancer in middle-aged Japanese adults with hepatitis virus infection. Circulating adiponectin levels may be a risk marker for primary liver cancer.