Lower High Molecular Weight Adiponectin Research Articles

Cord Blood IGF-I, Proinsulin, Leptin, HMW Adiponectin, and Ghrelin in Short or Skinny Small-for-Gestational-Age Infants.

Small-for-gestational-age (SGA) is an indicator of poor fetal growth "programming" an elevated risk of type 2 diabetes in adulthood. Little is known about early-life endocrine characteristics in SGA subtypes. Stunting (short) and wasting (skinny) are considered distinct SGA phenotypes in neonatal prognosis. This work aimed to assess whether SGA infants with stunting or wasting have similar alterations in neonatal endocrine metabolic health biomarkers. This was a nested case-control study based on the 3D (Design, Develop, and Discover) birth cohort in Canada. The study subjects were 146 SGA (birth weight < 10th percentile) and 155 optimal-for-gestational age (OGA, 25th-75th percentiles) infants. Stunting was defined as birth length less than the 10th percentile, and wasting as body mass index less than the 10th percentile for sex and gestational age, respectively. Main outcome measures included cord plasma concentrations of insulin-like growth factor I (IGF-I), proinsulin, leptin, high-molecular-weight (HMW) adiponectin, and ghrelin. Comparing to OGA infants adjusted for maternal and neonatal characteristics, SGA infants with either stunting only or wasting only had lower cord plasma IGF-I and leptin concentrations. HMW adiponectin concentrations were lower in SGA infants with wasting only (P = .004), but similar in SGA infants with stunting only (P = .816). Only SGA infants with both stunting and wasting had substantially lower proinsulin (P < .001) and higher ghrelin concentrations (P < .001) than OGA infants. This study is the first to demonstrate that SGA infants with wasting only are characterized by low HMW adiponectin concentrations, whereas those with stunting only are not. SGA with both stunting and wasting are characterized by low proinsulin and high ghrelin concentrations.

Impaired peripheral insulin sensitivity in non-obese Japanese patients with type 2 diabetes mellitus and fatty liver.

Aims/IntroductionType two diabetes mellitus and fatty liver (FL) are not uncommon in Asians with normal body mass index. Previous studies reported a link between FL and insulin resistance. Thus, FL could coexist with insulin resistance in Asian type two diabetes mellitus patients with a normal body mass index. However, the clinical and metabolic features of such patients have not been characterized yet.Materials and MethodsWe recruited 29 non‐obese (body mass index <25 kg/m2) Japanese patients with early type two diabetes mellitus. Based on intrahepatic lipid level measured by H‐magnetic resonance spectroscopy, the participants were divided into the FL (intrahepatic lipid ≥5%, n = 7) and non‐FL groups (intrahepatic lipid <5%, n = 22).ResultsPeripheral insulin sensitivity measured by hyperinsulinemic euglycemic clamp was ~25% lower in the FL group than in the non‐FL group, whereas hepatic insulin sensitivity was comparable between the two groups. The subcutaneous fat area was larger, free fatty acid level was higher, C‐reactive protein was higher and high molecular weight adiponectin was lower in the FL group than the non‐FL group.ConclusionsThe present study showed that the metabolic features of non‐obese Japanese type two diabetes patients with FL include impaired peripheral (mainly muscle) insulin sensitivity, fat accumulation and related metabolic disorders, such as elevated free fatty acid, low high molecular weight adiponectin and low‐grade inflammation.

Soluble CRTC3: A Newly Identified Protein Released by Adipose Tissue That Is Associated with Childhood Obesity.

CREB-regulated transcription coactivator 3 (CRTC3) is found in adipocytes, where it may promote obesity through disruption of catecholamine signaling. We wished to assess whether CRTC3 is a soluble protein secreted by adipose tissue, explore whether CRTC3 is detectable and quantifiable in the circulation, and ascertain whether CRTC3 serum concentrations are related to metabolic markers in children. Explants of adipose tissue from 12 children were cultured to study adipocyte cell size and the secretion of CRTC3 (immunoblot and ELISA). We also performed a cross-sectional and longitudinal study in 211 asymptomatic prepubertal white children at age 7 years, 115 of whom were followed up at age approximately 10 years. We measured circulating concentrations of CRTC3 and studied associations between serum CRTC3 and metabolic markers. Measurable concentrations of CRTC3 were found in conditioned media of adipose tissue explants and in serum samples. CRTC3 concentrations in visceral adipose tissue were negatively associated with adipocyte cell size and positively related to adipocyte cell number (P < 0.05). In the cross-sectional study, higher CRTC3 concentrations were associated with higher body mass index (P = 0.001), waist circumference (P = 0.003), and systolic blood pressure (P = 0.007) and lower high molecular weight adiponectin (P = 0.003). In the longitudinal study, serum concentrations of CRTC3 at age approximately 7 years were associated with changes in waist circumference (β = 0.254; P = 0.004; r = 0.145) and high molecular weight adiponectin (β=-0.271; P = 0.014; r = 0.101), respectively, at age approximately 10 years. CRTC3, a newly identified protein that is related to childhood obesity, is present in the circulation, partly as a result of adipose tissue secretion. Higher serum CRTC3 concentrations are related to and predict a poorer metabolic profile in children.

Serum high‐molecular‐weight adiponectin level and incident dementia in patients with vascular risk factors

The involvement of metabolic factors in the development of dementia has received much attention. However, previous studies have yielded conflicting results regarding how blood adipocytokine level impacts cognitive decline and dementia. This study aimed to clarify whether serum high-molecular-weight (HMW) adiponectin level is related to incident dementia. Data were from 466 patients (mean age 67.8 years, male 57%)--who had normal cognitive function and received brain magnetic resonance imaging--from amongst the 1106 patients in the Osaka Follow-up Study for Carotid Atherosclerosis, Part 2, a prospective cohort study of cardiovascular events and dementia amongst patients with vascular risk factors enrolled between 2001 and 2009. Baseline HMW adiponectin levels were measured using frozen serum. Dementia occurrence was examined in June 2013. Serum HMW adiponectin level was 4.33 ± 2.95 μg/ml; the levels were lower in men than in women and negatively correlated with body mass index. During the follow-up period (median 6.9 years), 47 patients had incident dementia including Alzheimer's disease dementia (27), vascular dementia (13), mixed dementia (four), other dementia (three). Risks of dementia in patients with high versus low HMW adiponectin levels were almost identical (P = 0.689). No association was found between adiponectin levels and Alzheimer's disease dementia or vascular dementia in the whole group or amongst men and women separately. This study demonstrated that serum HMW adiponectin level has little association with future dementia. Determination of metabolic factors involved in dementia requires evaluation of other biomarkers or parameters.

Association between abdominal fat distribution, adipocytokines and metabolic alterations in obese low‐birth‐weight children

In addition to obesity, low birth weight (LBW) has been proposed as another independent risk factor associated with cardiovascular disease and type 2 diabetes mellitus. This study aimed to evaluate the influence of birth weight on abdominal fat distribution, adipocytokine levels and associated metabolic alterations in obese children. A cross-sectional study was conducted in 92 children. Children were divided into three groups according to their body mass index and birth weight. Glucose and insulin (0 and 120 min), lipid profile and adipocytokines were measured. Abdominal fat distribution was assessed by magnetic resonance imaging. Obese LBW children had higher fasting glucose (P = 0.054) and insulin (P < 0.001), and 120 min glucose (P < 0.001) and insulin levels (P < 0.001), such as increased HOMA-IR (homeostasis model assessment of insulin resistance index) (P < 0.001). Obesity and LBW were associated with lower concentrations of high molecular weight (HMW) adiponectin (-2.38 [IC 95% -4.27; -0.42, P = 0.018]) and higher subcutaneous adipose tissue (SAT) (28.05 [IC 95% 0.40; 55.7, P = 0.047]) compared with NBW obese children, independent of age or sex. LBW in obese children is associated with lower HMW adiponectin, increased insulin resistance and greater SAT.

Placental Sprouty 2 (SPRY2): Relation to Placental Growth and Maternal Metabolic Status

Background:SPROUTY2 (SPRY2) is a membrane-associated protein expressed by placental macrophages with regulatory roles in tissue growth and development. The SPRY2 locus was shown to be associated with body fat distribution and susceptibility to type 2 diabetes. Objectives: We assessed whether SPRY2 mRNA levels are related with maternal metabolic status and with placental weight. We also studied the association of placental mRNA of SPRY2 with macrophage-derived inflammatory genes. Methods: A maternal metabolic profile [C-peptide, post-load glucose and high-molecular-weight (HMW) adiponectin] was assessed between 24 and 28 weeks of gestation in 200 control women delivering adequate-for-gestational-age (AGA) infants. Placentas and newborns were weighed at delivery. Placental mRNA levels of SPRY2 and of macrophage-derived inflammatory genes MMP2, TNFα and CD163 were quantified by real-time PCR. Women delivering small-for-gestational-age infants (SGA, n = 25) and women with gestational diabetes (GDM, n = 25) were also studied as validation groups for placental growth. Results: In control women delivering AGA infants, placental SPRY2 mRNA levels showed positive associations with a more adverse maternal metabolic status (higher maternal C-peptide and post-load glucose and lower HMW adiponectin), with more placental weight and with a more placental inflammatory phenotype (higher placental mRNA levels of MMP2,TNFα and CD163) (all p < 0.05 to p = 0.001). Compared to AGA infants, placental weight and placental SPRY2 mRNA levels were lower in placentas from SGA infants and higher in placentas from women with GDM (all p < 0.0001). Conclusions: Our results suggest a link between placental SPRY2 mRNA levels and placental growth, which may be modulated by maternal metabolic status and placental inflammation.

Abstract A61: Smoking modifies the association of insulin sensitivity biomarkers and pancreatic cancer risk

Abstract Cigarette smoking is the most important known risk factor for pancreatic cancer. Smoking leads to imbalances in metabolic hormones that are conducive to insulin resistance. Cigarette smoke also damages the exocrine pancreas, which can lead to pancreatogenic diabetes, also known as Type 3c diabetes mellitus (T3cDM). In contrast to type 2 diabetes mellitus (T2DM), which is associated with obesity and characterized by high levels of C-peptide, a marker of insulin secretion, T3cDM is characterized by low C-peptide concentrations, reflecting low pancreatic function. High Molecular Weight (HMW) adiponectin, on the other hand, is the most biologically active isoform of the insulin-sensitizing hormone adiponectin, and is inversely associated with obesity and T2DM incidence. We evaluated the association of serum biomarkers [C-peptide, adiponectin, and HMW adiopnectin] and pancreatic cancer by smoking status in a nested case control study of 759 cases and 1069 controls from the Alpha-Tacopherol, Beta Carotene Cancer Prevention Study (ATBC n=888), the Cancer Prevention Study II Nutrition Cohort (CPS II n=180), and the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial (PLCO n=760). Controls were matched to cases on age, date of blood draw (+ 3 months), sex, and race and were free from pancreatic cancer on the date the matched case was diagnosed. Spline regression models were used to examine the possible non-linear relation between the biomarkers and pancreatic cancer risk and logistic regression stratified on smoking status was used to calculate odds ratios and 95% confidence intervals. Smoking status modified the association of pancreatic cancer risk and prediagnostic C-peptide (p interaction=0.009) and HMW adiponectin (p interaction=0.02). Prediagnostic C-peptide concentration was inversely associated with pancreatic cancer in smokers [Odds Ratio = 0.76 (95% Confidence Interval = 0.63-, 0.91) per standard deviation], while no association was found in non-smokers [1.09 (0.96, 1.24)]. Similarly, prediagnostic HMW adiponectin concentration was associated with increased risk in smokers [1.23 (1.02, 1.47)]. As expected, HMW adiponectin tended to be inversely associated with pancreatic cancer risk in non-smokers [0.81 (0.63, 1.05)]. Spline analysis showed that both the association of C-peptide (p=0.01) and HMW (p=0.004) with pancreatic cancer risk were linear. Total adiponectin was not associated with pancreatic cancer risk either in smokers or non-smokers. Our findings with c-peptide and HMW adiponectin may be consistent with Type 3c diabetes which has recently been recognized to play a role in pancreatic carcinogenesis. In smokers, low C-peptide concentration may reflect low pancreatic function from smoke-induced damage to the pancreas, which is concordant with increased pancreatic cancer risk. Given the functional interaction between hormone-secreting pancreatic cells and adipocytes, HMW adiponectin concentration is a marker for peripheral insulin sensitivity and may be elevated to compensate for diminished pancreatic function. Hence, the positive association for both low C-peptide and high HMW adiponectin with pancreatic cancer in smokers supports the notion that cigarette smoking both decreases pancreatic function leading to pancreatogenic diabetes and increases pancreatic cancer risk. These results suggest that the associations of C-Peptide and HMW Adiponectin with pancreatic cancer may be more complex than previously appreciated and differ according to smoking status. A better understanding of the metabolic profile of smokers may be helpful in identifying high-risk individuals who could be targeted for pancreatic cancer prevention interventions. Citation Format: Leticia Nogueira, Christina Newton, Debra Silverman, Demetrius Albanes, Satu Manniston, Eric Jacobs, Rachel Stolzemberg-Solomon. Smoking modifies the association of insulin sensitivity biomarkers and pancreatic cancer risk. [abstract]. In: Proceedings of the Twelfth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2013 Oct 27-30; National Harbor, MD. Philadelphia (PA): AACR; Can Prev Res 2013;6(11 Suppl): Abstract nr A61.

Blood-Based Indicators of Insulin Resistance and Metabolic Syndrome in Bottlenose Dolphins (Tursiops truncatus)

Similar to people with metabolic syndrome, bottlenose dolphins (Tursiops truncatus) can have a sustained postprandial hyperglycemia and hyperinsulinemia, dyslipidemia, and fatty liver disease. A panel of potential postprandial blood-based indicators of insulin resistance and metabolic syndrome were compared among 34 managed collection dolphins in San Diego Bay, CA, USA (Group A) and 16 wild, free-ranging dolphins in Sarasota Bay, FL, USA (Group B). Compared to Group B, Group A had higher insulin (2.1 ± 2.5 and 13 ± 13 μIU/ml), glucose (87 ± 19 and 108 ± 12 mg/dl), and triglycerides (75 ± 28 and 128 ± 45 mg/dl) as well as higher cholesterol (total, high-density lipoprotein cholesterol, and very low density lipoprotein cholesterol), iron, transferrin saturation, gamma-glutamyl transpeptidase (GGT), alanine transaminase, and uric acid. Group A had higher percent unmodified adiponectin. While Group A dolphins were older, the same blood-based differences remained when controlling for age. There were no differences in body mass index (BMI) between the groups, and comparisons between Group B and Group A dolphins have consistently demonstrated lower stress hormones levels in Group A. Group A dolphins with high insulin (greater than 14 μIU/ml) had higher glucose, iron, GGT, and BMI compared to Group A dolphins with lower insulin. These findings support that some dolphin groups may be more susceptible to insulin resistance compared to others, and primary risk factors are not likely age, BMI, or stress. Lower high-molecular weight adiponectin has been identified as an independent risk factor for type 2 diabetes in humans and may be a target for preventing insulin resistance in dolphins. Future investigations with these two dolphin populations, including dietary and feeding differences, may provide valuable insight for preventing and treating insulin resistance in humans.

Gender differences in serum high-molecular-weight adiponectin levels in metabolic syndrome

The objective of this study was to estimate gender-specific associations between metabolic syndrome (MS) and high-molecular-weight (HMW) adiponectin in an Estonian adult population. Plasma HMW adiponectin was measured in 458 subjects (191 men) who participated in a population-based cross-sectional multicenter study (n=495) on the prevalence of metabolic disorders in Estonia. MS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. Median HMW adiponectin levels (μg/ml) were significantly lower among all subjects with MS compared with subjects without MS: 2.1 vs 2.8 in men (P=0.002) and 3.1 vs 5.1 in women (P<0.001). In a fully adjusted, logistic regression model containing HMW adiponectin, homeostasis model assessment of insulin resistance (HOMA-IR), BMI, and age, HMW adiponectin was significantly associated with MS only in women. Comparison of HMW adiponectin and HOMA-IR as markers for MS indicated that HOMA-IR predicted MS better than did HMW adiponectin in both genders. However, after adjusting for age and BMI, HOMA-IR was a significantly better predictor only in men. HMW adiponectin and HOMA-IR predicted the presence of MS at the same level in women. Areas under the receiver operating characteristic curves for HMW adiponectin and HOMA-IR were 0.833 vs 0.88 in men (P=0.02) and 0.897 vs 0.907 in women (P=0.5). These data suggest that the association between low HMW adiponectin levels and presence of MS might be stronger in women compared with men.

Association of plasma total and high-molecular-weight adiponectin with risk of colorectal cancer: an observational study in Chinese male

The research is to investigate the association between plasma concentrations of total and high-molecular-weight (HMW) adiponectin and risk of early and advanced colorectal cancer. One hundred and sixty-five male colorectal cancer patients and one hundred and two controls were enrolled; based on the T factor of the TNM system, intraepithelial carcinoma and submucosally invasive carcinoma were defined as early cancer, and invasion into the muscularis propria or deeper was defined as advanced cancer. The plasma levels of glucose, fasting insulin, total cholesterol, triglyceride, and total and HMW adiponectin levels were measured. Each factor level was designated as low or high, and the risk of cancer was estimated by univariate and multivariate logistic regression analyses. In the patients with early cancer, high waist/hip ratio (WHR), high fasting insulin, high HOMA model insulin resistance index (HOMA-IR), low total adiponectin and HMW adiponectin were all associated with a significant increase in the odds ratio (OR) by univariate analysis. In multivariate analysis, WHR, HOMA-IR, total adiponectin and HMW adiponectin were all related to increased cancer risk. However, in the patients with advanced cancer, only low HMW adiponectin was associated with a significant increase in the OR by univariate analysis. In multivariate analysis, a low HMW adiponectin level was still related to increased cancer risk, with an adjusted OR of 3.971 (P = 0.036). In conclusion, a decreased level of adiponectin was a strong risk factor not only for early colorectal cancer but also for advanced colorectal in Chinese male patients. HMW adiponectin might be more closely associated with colorectal cancer risk than total adiponectin.

Age and obesity-associated changes in the expression and activation of components of the AMPK signaling pathway in human right atrial tissue

BackgroundObesity is associated with an increased incidence of left ventricular hypertrophy, diastolic dysfunction, heart failure, and premature cardiac aging. In the heart, intrinsic activation of the AMP-dependent protein kinase (AMPK) plays a pivotal role in the stress response to ischemia and hypertrophy. Furthermore, AMPK is an important regulator of cardiac mitochondrial biogenesis. The purpose of the present study was to investigate the influence of obesity and aging on the AMPK signaling pathway in human cardiac tissue. Methods60 male cardiac surgery patients were included in the study and divided into 4 groups (old normal weight: ON; old obese: OO; young normal weight: YN, young obese: YO) according to their body mass index (18.5–25: normal weight or 30–35: obese) and age (<55years: young or >70: old) with 15 patients each. Right atrial tissue (RA) was analyzed for the expression of the AMPK upstream kinases CAMKK and LKB1, activation of AMPK as well as phosphorylation of the AMPK downstream targets ACC, eEF2, mTOR and eNOS. Epicardial adipose tissue was analyzed for the expression of the endogenous AMPK activator adiponectin. The metabolic state of all patients was further characterized in fasting blood samples. ResultsOld patients (ON, OO) and young obese (YO) subjects displayed higher fasting glucose, insulin and leptin serum levels compared to the young, normal weight group, although HbA1c was below the threshold required for the diagnosis of type 2 diabetes. Serum adiponectin as well as total adiponectin protein expression in epicardial adipose tissue was decreased in these three groups. Analyses of adiponectin isoforms by native gel electrophoresis revealed significant differences in the high molecular weight (HMW) isoforms between the groups. Despite the low total serum adiponectin and HMW adiponectin, AMPK activation was high in the RA of obese patients (YO, OO). Among the AMPK upstream kinases, LKB1 expression showed a strong positive correlation with AMPK activation. While the phosphorylation of the AMPK downstream targets mTOR, eEF-2 and ACC was not altered, phospho-eNOS was significantly lower in old patients (ON, OO). Despite strong AMPK activation, mitochondrial biogenesis and respiration were impaired in old (ON, OO) and young obese (YO) subjects. ConclusionThese data indicate that obesity and aging result in significant changes although many direct parameters in the AMPK signaling pathway are not changed in the same direction. LKB1 may represent a stronger activator of the AMPK pathway than adiponectin or the CAMKKs in human right atrial tissue.

Catch-up growth in girls born small for gestational age precedes childhood progression to high adiposity

To study across childhood the features of small for gestational age (SGA) girls with spontaneous catch-up growth. Longitudinal study (age 2-8 years). University hospital. Post-catch-up SGA girls (n = 18) versus healthy control girls born appropriate for gestational age (AGA; n = 13). None. Height, weight, fasting glucose, insulin, IGF-I, high-molecular-weight (HMW) adiponectin, LDL and HDL cholesterol, triglycerides, body composition by absorptiometry (2-8 years); visceral fat by magnetic resonance imaging (6-8 years); bone age (by automated reading), sex hormone-binding globulin, DHEAS, and leptin (8 years). At age 2 years, AGA and SGA girls were comparable for all study markers. Between 2 and 8 years, girls were prepubertal; AGA and SGA girls gained height, lean mass, and bone mineral content similarly; other outcomes diverged so that, at age 8, SGA girls had markedly higher levels of circulating insulin, IGF-I, DHEAS, LDL cholesterol, and leptin; lower HMW adiponectin and SHBG levels; more total and visceral fat (without being obese); and an older bone age. After completing catch-up growth and before starting puberty, SGA girls develop an ensemble that includes not only central adiposity, hyperinsulinemia, and hypoadiponectinemia but also hyperleptinemia, dyslipidemia, lower SHBG and higher DHEAS levels, and faster bone maturation.

Low serum levels of total and high-molecular-weight adiponectin predict the development of metabolic syndrome in Japanese-Americans.

Adiponectin is thought to play a significant role in the development of both insulin resistance and metabolic syndrome. Yet, there is very few evidence about the association plasma adiponectin and metabolic syndrome in the prospective study. Adiponectin exists as multimers in serum, and high-molecular-weight (HMW) adiponectin is particularly considered to be the active form of the protein. We investigated whether serum HMW adiponectin as well as total adiponectin is associated with the development of metabolic syndrome in a longitudinal study. We enrolled 224 men and 312 women of Japanese- Americans without metabolic syndrome at baseline who were followed for an average of 3.2 yr. The association of plasma total and HMW adiponectin with a progression to metabolic syndrome was examined. Subjects who developed metabolic syndrome had significantly lower plasma total and HMW adiponectin levels at baseline than those who did not develop metabolic syndrome. In a Cox proportional hazards model, lower total and HMW adiponectin levels were independent risk factors for the development of metabolic syndrome after adjusting for age, body mass index, classification of 75-g glucose tolerance test, and homeostasis model assessment (hazards ratio: total, 0.684, p=0.017, in men; 0.606, p=0.003, in women; HMW, 0.687, p=0.014, in men; 0.704, p=0.029, in women, respectively). Low circulating levels of total and HMW adiponectin may be a possible predictor for the development of metabolic syndrome.

Relation between serum high molecular weight adiponectin and serum ferritin or prohepcidin in patients with type 2 diabetes

An increase of serum ferritin, an indicator of body iron store, is associated with insulin resistance and with an increased risk of type 2 diabetes in the general population. A low serum adiponectin is also associated with insulin resistance. Recently, hepcidin was identified as a regulator of iron metabolism. We investigated whether serum adiponectin was associated with serum ferritin or prohepcidin, a precursor of hepcidin, in healthy subjects and patients with type 2 diabetes. We studied 65 healthy subjects and 104 patients with type 2 diabetes. A serum ferritin concentration ≥300 ng/ml for men or ≥150 ng/ml for women was defined as hyperferritinemia. Serum ferritin was significantly higher and serum prohepcidin was significantly lower in diabetic patients than in control subjects. Serum total and high molecular weight (HMW) adiponectin correlated negatively with serum ferritin in control subjects or diabetic patients, while serum total and HMW adiponectin correlated positively with serum prohepcidin in diabetic patients, but not in control subjects. Serum total and HMW adiponectin were lower in patients with hyperferritinemia than in those without it. In conclusion, serum ferritin was increased in type 2 diabetic patients, while serum prohepcidin was decreased. A high serum ferritin was associated with insulin resistance, and with low serum total and HMW adiponectin in patients with type 2 diabetes.

Effects Of Exercise Training On High Molecular Weight Adiponectin In The Healthy Male Rat

PURPOSE: The high-molecular weight (HMW) form of adiponectin has been reported to be the most active form of this hormone and low plasma HMW adiponectin levels have been found to be associated with insulin resistance..This study was intended to investigate the effects of exercise intensity on plasma HMW adiponectin concentrations. METHODS: Thirty-two male Wistar rats (age 8 wks, wt. 185±50 g) were randomly assigned to one of four groups as follows: high intensity (HI: 34m/min ∼%80-%85 VO2max), moderate intensity (MI: 28m/min ∼ %70-%75 VO2max), low intensity (LI: 20m/min ∼ %50-%55 VO2max), and sedentary control (SED) groups. All experimental groups performed 12 weeks of exercise consisting of treadmill running on a 0° slope for 1 hr/day, 5 days/week. Fasting levels of circulating HMW adiponectin, testosterone, insulin resistance index (HOMA-IR) were measured after the exercise program. Data were analyzed using one-way ANOVA while Pearson's correlations were performed to identify possible relationships among the assessed variables. RESULTS: HMW adiponectin plasma concentration increased significantly at HI and MI exercise training groups (p<0.05). Also, HMW adiponectin was inversely related to HOMA-IR (r = -0.37, p=0.003), insulin (r = -0.46, p=0.008) and testosterone (r = -0.38, p=0. 03). CONCLUSIONS: It concluded that exercise intensity appear to be important parameter to increase plasma HMW adiponectin level in healthy male rat.

Diet‐induced obesity leads to decreased hepatic iron storage associated with inflammation

Increased risk for iron deficiency has been reported in obese subjects. We investigated the effects of high fat diet‐induced obesity on hepatic iron status and serum adipokine and inflammatory marker levels. Four‐ week old C57BL mice were fed diets containing 10 (ND) or 60 (HFD)% energy from fat for 16 wks. Consumption of HFD resulted in higher weight gain (16.3 vs. 30.4g). Serum leptin, total adiponectin, high molecular weight (HMW) adiponectin, and serum amyloid A (SAA) and hepatic non‐heme iron, ferritin, and hepcidin mRNA levels were measured. HFD group had higher leptin (42.6 vs. 104.3 ng/mL), and lower HMW adiponectin (4.80 vs. 3.67 ug/mL) levels. Higher level of SAA in HFD group (57.8 vs. 117.9 ug/mL) suggests inflammation in HFD‐induced obese animals. HFD group had lower hepatic non‐heme iron (3.12 vs 0.869 ug/mg protein) and ferritin levels. HFD group had lower hepcidin expression at 54% level of ND group, however, ratio of hepcidin expression to non‐heme iron was higher (2.5 fold higher in HFD than ND). Hepcidin is a homeostatic regulator of iron metabolism by restricting intestinal iron absorption, but, also known as a mediator of inflammation. Leptin and SAA showed positive correlation with weight gain while HMW adiponectin showed negative correlation. Increased SAA levels and higher hepcidin ratio to iron suggests that lower hepatic iron status in obese animals might be associated with inflammation. Supported by Korea Research Foundation Grant (C00305) and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009‐0063409).

Growth Hormone Therapy in Short Children Born Small for Gestational Age: Effects on Abdominal Fat Partitioning and Circulating Follistatin and High-Molecular-Weight Adiponectin

A high sensitivity to insulin and a low amount of sc fat are among the hallmarks of short children born small for gestational age (SGA). We studied the effects of GH therapy on fat partitioning (including in the abdominal region) and circulating levels of triacylglycerol and newly identified adipokines, such as follistatin and high-molecular-weight (HMW) adiponectin in short SGA children. The study was conducted at a university hospital. Patients included 35 short SGA children (mean age 7 yr, height -3.1 sd). All children received GH but they were randomized for an early start (GH for 4 months) vs. a delayed start (untreated for 4 months, then GH for 4 months). Mean GH dose after 4 months was 36 microg/kg x d. Outcomes included fasting serum glucose, insulin, triacylglycerol, HMW adiponectin, follistatin; body size and composition; and abdominal fat partitioning. GH therapy was accompanied by robust changes toward the norm (height, weight, lean mass, follistatin) but also by changes away from the norm (low HMW adiponectin, high triacylglycerol). Some baseline anomalies were amplified (more deficit of sc fat, both at total body level and in the abdominal region), whereas other baseline anomalies were overcorrected (from a highly insulin sensitive state to an insulin resistant state). GH therapy in short SGA children is accompanied by not only a more normal body size and follistatinemia but also insulin resistance, hypo-HMW-adiponectinemia, hypertriacylglycerolemia, and an amplification of the deficit in sc fat.

Total and high molecular weight adiponectin in patients with coronary artery disease

Serum adiponectin inversely correlates with the extent of coronary artery disease (CAD). To investigate the clinical significance of measuring high molecular weight (HMW) adiponectin in addition to total adiponectin from different samples (peripheral veins and ostia of coronary arteries) in patients with CAD. We studied 134 patients; 57 with acute coronary syndrome (ACS), 44 with stable angina and 33 healthy patients. Total and HMW adiponectin were measured in the coronary ostia and peripheral veins simultaneously. Venous levels of lipid profile, C-reactive protein, tumour necrosis factor-alpha, interleukin-6 and insulin were measured. Mean levels of HMW adiponectin in the coronary ostia were significantly correlated with the venous levels of total (r = 0.33, P = 0.002) and HMW (r = 0.37, P = 0.002) adiponectin. Mean levels of total and HMW adiponectin were lower in CAD patients versus controls (6.9 +/- 0.5 versus 7.9 +/- 0.7 microg/ml, P = 0.3 and 1.9 +/- 0.2 versus 3.1 +/- 0.3 microg/ml, P = 0.003). In the coronary ostia, levels of HMW adiponectin were higher in ACS than those with stable angina (1.1 +/- 0.1 versus 0.8 +/- 0.1 microg/ml, P = 0.2). In patients with CAD, levels of ostial adiponectin (total and HMW) were significantly lower in diabetic than non-diabetic patients (6.5 +/- 0.8 versus 9.4 +/- 1.1 microg/ml, P = 0.04 and 0.8 +/- 0.12 versus 1.2 +/- 0.1 microg/ml, P = 0.03). Mean levels of venous adiponectin (total and HMW) were non-significantly lower in diabetic patients (5.9 +/- 0.7 versus 7.7 +/- 0.7, P = 0.12 and 1.8 +/- 0.4 versus 1.9 +/- 0.1, P = 0.8). Measurement of HMW adiponectin and its ratio to total adiponectin may be a better marker for CAD than total adiponectin levels. Ostial levels of adiponectin in ACS may indicate re-distribution of adiponectin molecules towards the acute lesions. The low HMW adiponectin levels in diabetes mellitus may in part explain the worse outcome of CAD in diabetics.

Visceral Adiposity without Overweight in Children Born Small for Gestational Age

Children born small for gestational age (SGA) tend to develop catch-up growth in infancy and become overweight by the age of 6 yr. Weight control is advocated as a preventive measure, but it is unknown whether such control suffices to prevent visceral fat excess and hypoadiponectinemia. The study was performed at a university hospital. A total of 64 children (32 matched pairs) aged 6 yr, of whom 32 were born appropriate for gestational age and 32 were born SGA, and had subsequently developed spontaneous catch-up growth were included in the study; matching was performed for gender, height, weight, and, thus, body mass index. Fasting insulin, IGF-I, high molecular weight adiponectin, leptin, visfatin, and lean and fat mass were calculated by absorptiometry, and abdominally sc and visceral fat by magnetic resonance imaging. After strict matching, SGA children had a total lean mass, total fat mass, leptinemia, and visfatinemia comparable to those in the appropriate for gestational age children, but they still had higher fasting insulin and IGF-I levels (P < 0.01), much lower high molecular weight adiponectin levels (P < 0.0001), and a striking shift from abdominally sc to visceral fat (P < 0.0001). Fasting insulin (r = 0.52; P < 0.00001) was a major determinant of visceral fat in boys and girls, explaining 28% of its variance. SGA children tend to be viscerally adipose and hypo-adiponectinemic, even if they are not overweight. Therefore, measures beyond weight control seem to be needed to allow most SGA children to normalize their body composition and endocrine-metabolic homeostasis.

Decreased Serum Adiponectin Levels in Patients with Metastatic Renal Cell Carcinoma

Low levels of serum adiponectin are associated with increased risk and aggressiveness of obesity-related cancer. The purpose of the study reported here was to investigate the association between serum adiponectin levels and clinicopathological parameters of renal cell carcinoma. Preoperative serum total and high-molecular-weight (HMW) adiponectin levels were measured in 118 patients with renal cell carcinoma, and their association with clinicopathological parameters was analysed. There were no statistically significant associations between total adiponectin and HMW adiponectin and pathological stage, regional lymph node involvement, histological grade, histological type (clear cell carcinoma versus other types) or presence of venous invasion. Total and HMW adiponectin levels in patients with metastasis, however, were significantly lower than in patients without metastasis (P = 0.044 for total adiponectin and P = 0.041 for HMW adiponectin). Low total and HMW adiponectin levels were significantly associated with metastasis in patients with a normal BMI (<25 kg/m(2)) (P = 0.034 for total adiponectin and P = 0.028 for HMW adiponectin) but not in overweight and obese patients (P = 0.652 for total adiponectin and P = 0.489 for HMW adiponectin). Multivariate logistic regression analysis showed that total adiponectin level was an independent predictor of metastasis of renal cell carcinoma in all patients (P = 0.024, 95% CI = 1.031-1.560) and in patients with a normal BMI (P = 0.040, 95% CI = 1.043-6.534). Serum total and HMW adiponectin levels were decreased in patients with metastatic renal cell carcinoma. Adiponectin might be a molecular link between obesity and the progression of renal cell carcinoma.