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1.
Adipose Insulin Resistance and Decreased Adiponectin Are Correlated With Metabolic Abnormalities in Nonobese Men.
Kiya, M, Tamura, Y, Takeno, K, Someya, Y, Kakehi, S, Sato, M, Yamasaki, N, Kadowaki, S, Suzuki, R, Furukawa, Y, et al
The Journal of clinical endocrinology and metabolism. 2021;(5):e2228-e2238
Abstract
CONTEXT Adipose tissue dysfunction is characterized by decreased adiponectin (AN) levels and impaired adipose tissue insulin sensitivity (ATIS) and is associated with metabolic disorders. While Asians readily develop metabolic disease without obesity, it remains unclear how decreased AN level and impaired ATIS affect metabolic abnormalities in nonobese Asians. DESIGN AND SETTING To investigate the relationships between decreased AN level, impaired ATIS, and metabolic abnormalities, we studied 94 Japanese men whose body mass index was less than 25 kg/m2. We divided the subjects into 4 groups based on their median AN level and ATIS, the latter calculated as the degree of insulin-mediated suppression of free fatty acids during hyperinsulinemic euglycemic clamp, and compared the metabolic parameters in the 4 groups. RESULTS The High-ATIS/High-AN group (n = 29) showed similar anthropometric data to the High-ATIS/Low-AN group (n = 18). In contrast, both the Low-ATIS/High-AN (n = 18) and Low-ATIS/Low-AN (n = 29) groups showed significantly lower muscle insulin sensitivity than the High-ATIS groups. The intrahepatic lipid level in the Low-ATIS/Low-AN group was significantly higher than that in the High-ATIS groups. In addition, the Low-ATIS/Low-AN group had a significantly higher fasting serum triglyceride level and significantly lower high-density lipoprotein cholesterol level than the other 3 groups. CONCLUSIONS In nonobese Japanese men with high ATIS, the AN level was not associated with metabolic characteristics. On the other hand, subjects with low ATIS showed reduced muscle insulin sensitivity, and those with a decreased AN level demonstrated multiple metabolic abnormalities, represented by fatty liver and dyslipidemia.
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Serum Adiponectin Levels Are Positively Associated With Diabetic Peripheral Neuropathy in Chinese Patients With Type 2 Diabetes.
Sun, Q, Yan, B, Yang, D, Guo, J, Wang, C, Zhang, Q, Shi, Y, Shi, X, Tian, G, Liang, X
Frontiers in endocrinology. 2020;:567959
Abstract
OBJECTIVE To investigate the association between serum adiponectin levels and diabetic peripheral neuropathy (DPN) in Chinese type 2 diabetes (T2D) patients. DESIGN AND METHODS Two hundred nineteen T2D patients aged 40-79 years were divided into two groups according to whether they had DPN. The systemic levels of five biomarkers were measured using a human adipokine multiplexed bead-based immunoassay. Diabetic peripheral neuropathy diagnostic criteria included both common DPN symptoms and neurological screening tests. RESULTS Most features of DPN (n=98) and non-DPN patients (n=121) are similar, but the DPN patients were slightly older, had longer diabetes duration, higher hemoglobin (Hb) A1c, lower estimated glomerular filtration rates (eGFR), less exercise, and used lipid-lowering drugs more often. Serum adiponectin levels of DPN patients were higher than that of non-DPN patients (8.13 vs. 9.63 mg/ml, P = 0.004). Serum adiponectin levels were positively associated with DPN after adjusting for age, gender, body mass index, hypertension, HbA1c, alcohol intake, smoking status, physical activity, log-transformed low density lipoprotein cholesterol, lipid-lowering drug usage, eGFR, and diabetes duration {odds ratio (OR) 1.72 [95% confidence interval (CI) 1.02-2.89], P = 0.041}. The OR refers to a doubling in biomarkers. CONCLUSIONS Serum adiponectin levels were higher in DPN patients compared to non‑DPN patients in this Chinese T2D population. Serum adiponectin levels were positively associated with DPN presence, independent of multiple confounders.
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Maternal Serum and Breast Milk Adiponectin: The Association with Infant Adiposity Development.
Mohamad, M, Loy, SL, Lim, PY, Wang, Y, Soo, KL, Mohamed, HJJ
International journal of environmental research and public health. 2018;(6)
Abstract
The prevalence of childhood obesity is increasing at an alarming rate in Malaysia. Metabolic changes during pregnancy are critical to the development of infant adiposity, due to imbalanced adipokines production. Hence, we aimed to investigate the association of maternal serum and breast milk adipokines with infant adiposity development. The study was conducted from April 2010 until December 2012. A total of 155 healthy pregnant mothers aged 19 to 40 years were recruited during the first and second trimester in Kelantan, Malaysia. Data consisted of maternal sociodemographic details, anthropometry and clinical biochemistry analysis; and the infant’s anthropometry and feeding patterns. Maternal fasting serum and breast milk samples were analysed for adiponectin and leptin levels. Data collection was performed in the second and third trimester of pregnancy, and continued with follow-up visits at birth, two, six, and 12 months postpartum. Multiple linear regression (MLR) analyses were performed to examine the associations between maternal serum and breast milk adiponectin and leptin and infant adiposity development. MLR models showed that, in the first year, as maternal serum and breast milk adiponectin increased, infant weight, BMI-for-age Z scores and abdominal circumference significantly decreased (p < 0.05). Maternal serum and/or breast milk adiponectin was associated with first-year infant adiposity development.
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Lifestyle intervention for morbid obesity: effects on liver steatosis, inflammation, and fibrosis.
Hohenester, S, Christiansen, S, Nagel, J, Wimmer, R, Artmann, R, Denk, G, Bischoff, M, Bischoff, G, Rust, C
American journal of physiology. Gastrointestinal and liver physiology. 2018;(3):G329-G338
Abstract
The prevalence of obesity-related nonalcoholic fatty liver disease (NAFLD) is rising. NAFLD may result in nonalcoholic steatohepatitis (NASH), progressing to liver cirrhosis. Weight loss is recommended to treat obesity-related NASH. Lifestyle intervention may improve NASH; however, pertinent trials have so far focused on overweight patients, whereas patients with obesity are at highest risk of developing NAFLD. Furthermore, reports of effects on liver fibrosis are scarce. We evaluated the effect of lifestyle intervention on NAFLD in a real-life cohort of morbidly obese patients. In our observational study, 152 patients underwent lifestyle intervention, with a follow-up of 52 weeks. Noninvasive measures of obesity, metabolic syndrome, liver steatosis, liver damage, and liver fibrosis were analyzed. Treatment response in terms of weight loss was achieved in 85.1% of patients. Dysglycemia and dyslipidemia improved. The proportion of patients with fatty liver dropped from 98.1 to 54.3% ( P < 0.001). Weight loss >10% was associated with better treatment response ( P = 0.0009). Prevalence of abnormal serum transaminases fell from 81.0 to 50.5% ( P < 0.001). The proportion fibrotic patients, as determined by the NAFLD fibrosis score, dropped from 11.8 to 0% ( P < 0.05). Low serum levels of adiponectin correlated with degree of liver damage, i.e., serum liver transaminases ( r = -0,32, P < 0.05). Serum levels of adiponectin improved with intervention. In conclusion, lifestyle intervention effectively targeted obesity and the metabolic syndrome. Liver steatosis, damage and fibrosis were ameliorated in this real-life cohort of morbidly obese patients, mediated in part by changes in the adipokine profile. Patients with weight loss of >10% seemed to benefit most. NEW & NOTEWORTHY We demonstrate new evidence that lifestyle intervention is effective in treating NAFLD in the important group of patients with (morbid) obesity. Although current guidelines on the therapy of NASH recommend weight loss of 5-7%, weight reduction >10% may be favorable in morbid obesity. Serum levels of adipokines correlate with liver damage, which is indicative of their pathogenetic importance in human NASH. Our study adds to the limited body of evidence that NAFLD-associated liver fibrosis may resolve with lifestyle intervention.
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The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies.
Larnkjær, A, Ong, KK, Carlsen, EM, Ejlerskov, KT, Mølgaard, C, Michaelsen, KF
Hormone research in paediatrics. 2018;(1):28-38
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Abstract
BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). METHODS Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. RESULTS At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. CONCLUSIONS Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin.
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Serum adiponectin levels predict acute coronary syndrome (ACS) in patients with severe carotid stenosis.
Liberale, L, Carbone, F, Bertolotto, M, Bonaventura, A, Vecchié, A, Mach, F, Burger, F, Pende, A, Spinella, G, Pane, B, et al
Vascular pharmacology. 2018;:37-43
Abstract
As endocrine organ, adipose tissue may modulate inflammatory response by releasing a wide range of mediators, known as adipocytokines. Due to the complex balance between pro- and anti-inflammatory activity their pathophysiological and prognostic role in cardiovascular (CV) diseases still remains debated. Here, we consider the potential associations of circulating adipocytokines adiponectin, leptin and their ratio (LAR), with metabolic and inflammatory profiles in 217 patients with severe carotid stenosis. A prospective analysis investigating their predictive role toward acute coronary syndromes (ACS) was also drawn over a 12-month follow-up period. Serum leptin was positively associated with fasting insulinemia and HOMA-IR, but not with lipid profile and inflammation. Conversely, adiponectin was negatively associated with glucose, insulin, HOMA-IR, triglycerides and both systemic and intraplaque inflammatory markers whereas a positive association with high-density lipoprotein cholesterol (HDL-c) was observed. Accordingly, a significant association with metabolic profile was reported for LAR. According to the cut-off point identified by ROC curve, adiponectin values≤2.56μg/mL were correlated with a higher risk of ACS occurrence at 12months' follow-up (p-value for Log Rank test=0.0003). At Cox regression analysis the predictive ability of low serum adiponectin was confirmed also after adjustment for age, male gender and diabetes. In conclusion, adiponectin may be considered a biomarker of metabolic compensation, inversely associated with chronic low-grade inflammation. Circulating adiponectin is also associated with lower risk of adverse CV events in patients with severe carotid stenosis.
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High-molecular-weight adiponectin is inversely associated with sympathetic activity in polycystic ovary syndrome.
Shorakae, S, Abell, SK, Hiam, DS, Lambert, EA, Eikelis, N, Jona, E, Sari, CI, Stepto, NK, Lambert, GW, de Courten, B, et al
Fertility and sterility. 2018;(3):532-539
Abstract
OBJECTIVE To examine the role of high-molecular-weight (HMW) adiponectin and its relationship to sympathetic activity in women with polycystic ovary syndrome (PCOS). DESIGN Cross sectional study using biobanked samples. SETTING Not applicable. PATIENT(S): Premenopausal women with PCOS (n = 46, Rotterdam diagnostic criteria) and without PCOS (n = 22). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): High-molecular-weight adiponectin levels with secondary outcomes of sympathetic activity and leptin levels. RESULT(S): The high-molecular-weight adiponectin level was lower in women with PCOS (median 2.2 [interquartile range (IQR)2.3] μg/mL) than in controls (median 3 [IQR2.5] μg/mL) (age and BMI adjusted), and it correlated inversely with the values measured for homeostatic model of assessment of insulin resistance (HOMA-IR), fasting insulin, triglycerides, and free androgen index and positively with sex hormone-binding globulin (SHBG) and high-density lipoprotein cholesterol in all participants and in the PCOS group. In the PCOS group, sympathetic activity (burst frequency) was statistically significantly higher than in controls (median 26 [IQR11] vs. median 22 [IQR14], respectively) and correlated inversely with HMW adiponectin (r = -0.230). The leptin levels were similar between the women with PCOS and controls and did not statistically significantly correlate with HMW adiponectin or sympathetic activity. On multiple regression analysis, burst frequency and SHBG explained 40% of the HMW adiponectin variability (B = -0.7; 95% CI -1.2 to -0.2; and B = 0.01; 95% CI 0.004-0.01) in PCOS. CONCLUSION(S): Alongside insulin resistance, increased sympathetic activity is associated with and may modulate HMW adiponectin levels in women with PCOS.
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The mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic patients with acute myocardial infarction during PCI treatment.
Zhang, CJ, Deng, YZ, Lei, YH, Zhao, JB, Wei, W, Li, YH
European review for medical and pharmacological sciences. 2018;(7):2169-2174
Abstract
OBJECTIVE To investigate the mechanism of exogenous adiponectin in the prevention of no-reflow phenomenon in type 2 diabetic (T2DM) patients with acute myocardial infarction (AMI) during percutaneous coronary intervention (PCI) treatment. PATIENTS AND METHODS 66 patients were randomly divided into control group and observation group, 33 cases in each group. According to the percutaneous coronary intervention (PCI) emergency treatment principle, patients from the control group were treated with an intracoronary injection of adenosine combined with a micro-pump intravenous infusion of tirofiban. Patients from the observation group were injected with exogenous adiponectin in addition to the adenosine and tirofiban treatments. RESULTS There were no significant differences in gender, age, location of the target lesion, degree of stenosis, stent implantation number, length and the inner diameter between control and observation group (p > 0.05). Lower frequent of slow blood flow and no-reflow and shorter interventional procedures were observed in observation group compared with those of control group (p < 0.05). Moreover, the increase of plasma creatine kinase (CK-MB) in patients of observation group was lower than that of the patients in control group (p < 0.05). In addition, the levels of troponin-I (cTnI), IL-6, TNF- α, endothelin-1 (ET-1), vascular endothelial adhesion molecular I (VCAM-1) and bax/Bcl-2 were significantly lower in observation group than those in control (p < 0.05). Furthermore, the occurrence of major adverse cardiac events (MACE) during a 12-month follow-up was significantly lower in the observation group than that of control (p < 0.05). CONCLUSIONS Exogenous adiponectin further reduced the no-reflow phenomenon during PCI treatment of the patients with T2DM combined with AMI. The function of exogenous adiponectin is associated with the reduced myocardial and endothelial cell injury and the inhibited inflammation and apoptosis. The application of exogenous adiponectin can significantly improve the clinical outcomes.
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T-cadherin gene variants are associated with nephropathy in subjects with type 1 diabetes.
Nicolas, A, Mohammedi, K, Bastard, JP, Fellahi, S, Bellili-Muñoz, N, Roussel, R, Hadjadj, S, Marre, M, Velho, G, Fumeron, F
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2017;(12):1987-1993
Abstract
BACKGROUND 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. METHODS 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. RESULTS 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). CONCLUSIONS 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.
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Leptin and adiponectin as new markers of undernutrition in cancer.
Bobin-Dubigeon, C, Lefrançois, A, Vansteene, D, Dupé, M, Joalland, MP, Bard, JM
Clinical biochemistry. 2017;(9):525-528
Abstract
OBJECTIVES To evaluate leptin and adiponectin as markers of undernutrition in cancer patients, and compare their performances with those of other biomarkers. DESIGN AND METHODS This was a prospective and observational study of 132 patients with various types of cancer. Following the recommended professional criteria, we diagnosed undernutrition at the time of blood sampling for the biological analysis of leptin, adiponectin, paraoxonase (hydrolysis rate of three substrates: paraoxon (PON), phenylacetate (ARE) and thiolactone (LAC)), and the calculation of the Prognostic Inflammatory and Nutritional Index (PINI). Patients were monitored for one year to establish the mortality rate of the group. Relationships between biological variables and undernutrition were evaluated using univariate and multivariate logistic regression models. The Kaplan Meier method was used to analyse survival curves. Hazard ratios for death were calculated according to the quartiles of each biological variable. RESULTS In the case of undernutrition, a decrease was observed in levels of leptin and in the lactonase activity (LAC) of paraoxonase, while adiponectin levels increased. Besides PINI, leptin was the only parameter that was independently related to undernutrition. While no relation was found between survival and leptin or adiponectin levels, evidence was found that PINI, LAC and ARE were associated with survival, even in multivariate analysis. CONCLUSIONS Leptin and PINI are good markers of installed undernutrition, and PINI and ARE or LAC are reliable markers of the risk of death in patients suffering from cancer.