Relationship of Serum Adiponectin and Leptin Concentrations with Body Fat Distribution in Humans

Objective: We investigated whether serum concentrations of adiponectin are determined by body fat distribution and compared the findings with leptin. Research Methods and Procedures: Serum concentrations of adiponectin and leptin were measured by radioimmunoassay (n = 394) and analyzed for correlation with sex, age, and body fat distribution, i.e., waist‐to‐hip ratio, waist and hip circumference, and subcutaneous adipose tissue area of the lower leg as assessed by magnetic resonance imaging. Results: After adjusting for sex and percentage of body fat, adiponectin was negatively (r = ?0.17, p < 0.001) and leptin was positively (r = 0.22, p < 0.001) correlated with waist‐to‐hip ratio. Leptin, but not adiponectin, correlated with both waist (r = 0.49, p < 0.001) and hip circumference (r = 0.46, p < 0.001). Furthermore, leptin, but not adiponectin, correlated with the proportion of subcutaneous fat of the lower leg cross‐sectional area (r = 0.37, p < 0.001). Discussion: These data suggest that both adipocytokines are associated with central body fat distribution, and serum adiponectin concentrations are determined predominantly by the visceral fat compartment.     

Circulating Adipocytokines and Chronic Kidney Disease

Background

Adipokines have been associated with atherosclerotic heart disease, which shares many common risk factors with chronic kidney disease (CKD), but their relationship with CKD has not been well characterized.

Methods

We investigated the association of plasma leptin, resistin and adiponectin with CKD in 201 patients with CKD and 201 controls without. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or presence of albuminuria. Quantile regression and logistic regression models were used to examine the association between adipokines and CKD adjusting for multiple confounding factors.

Results

Compared to controls, adjusted median leptin (38.2 vs. 17.2 ng/mL, p<0.0001) and adjusted mean resistin (16.2 vs 9.0 ng/mL, p<0.0001) were significantly higher in CKD cases. The multiple-adjusted odds ratio (95% confidence interval) of CKD comparing the highest tertile to the lower two tertiles was 2.3 (1.1, 4.9) for leptin and 12.7 (6.5, 24.6) for resistin. Median adiponectin was not significantly different in cases and controls, but the odds ratio comparing the highest tertile to the lower two tertiles was significant (1.9; 95% CI, 1.1, 3.6). In addition, higher leptin, resistin, and adiponectin were independently associated with lower eGFR and higher urinary albumin levels.

Conclusions

These findings suggest that adipocytokines are independently and significantly associated with the risk and severity of CKD. Longitudinal studies are warranted to evaluate the prospective relationship of adipocytokines to the development and progression of CKD.     

Measurement of waist circumference predicts coronary atherosclerosis beyond plasma adipokines

Objective:

The association of plasma adipokines beyond waist circumference (WC) with coronary artery calcification (CAC), a measure of subclinical atherosclerosis, is unknown.

Design and Methods:

Asymptomatic Caucasian individuals from two community‐based cross‐sectional studies (n = 1,285) were examined and multivariate analysis of traditional risk factors was performed, then WC and adipokines (adiponectin and leptin) were added. Incremental value of each was tested with likelihood ratio testing.

Results:

Beyond traditional risk factors, WC (Tobit regression ratio 1.69, P < 0.001) and plasma leptin (1.57, P < 0.001) but not plasma adiponectin (P = 0.75) were independently associated with CAC. In nested models, neither adiponectin (χ² = 0.76, P = 0.38) nor leptin (χ² = 1.32, P = 0.25) added value to WC beyond traditional risk factors, whereas WC added incremental value to adiponectin (χ² = 28.02, P < 0.0001) and leptin (χ² = 13.58, P = 0.0002).

Conclusion:

In the face of important biomarkers such as plasma adiponectin and leptin, WC remained a significant predictor of CAC beyond traditional risk factors underscoring the importance of WC measurement during cardiovascular risk assessment.     

F2-isoprostanes and adiposity in older adults

We examined whether a systemic marker of oxidative stress, F₂‐isoprostanes (F₂‐IPs), was associated with total and regional adiposity, adipocytokines, and change in adiposity. Using data from 726 participants enrolled in the Health, Aging, and Body Composition (Health ABC) study, F₂‐IPs and adipocytokines were measured from baseline plasma samples. Total adiposity was measured by whole‐body dual‐energy X‐ray absorptiometry and regional adiposity by abdominal and thigh computed tomography scans at baseline and 5‐year follow‐up. ANOVA models were estimated to examine associations between F₂‐IP tertiles and baseline adiposity and changes in body composition. Median F₂‐IPs was 54.3 pg/ml; women had significantly higher levels than men (61.5 vs. 48.9 pg/ml, P < 0.001). F₂‐IPs were associated with higher levels of adiponectin, leptin, and tumor necrosis factor‐α (TNF‐α). Positive associations were found between F₂‐IPs and all measures of total and regional adiposity among women. In linear regression models, adipocytokines mediated associations among women. Over 5 years of follow‐up, women in the highest vs. lowest F₂‐IP tertile exhibited significant loss of weight (lowest tertile: ?1.1 kg, highest tertile: ?2.7 kg, P < 0.05). In conclusion, F₂‐IPs were associated with measures of total and regional adiposity in women alone and these associations were partially explained by adipocytokines. F₂‐IPs predicted loss of total adiposity over time among women.     

Associations of leukocyte telomere length with body anthropometric indices and weight change in chinese women

Objective: This study evaluated associations of telomere length with various anthropometric indices of general and abdominal obesity, as well as weight change. Design and Methods: The study included 2,912 Chinese women aged 40‐70 years. Monochrome multiplex quantitative polymerase chain reaction was applied to measure relative telomere length. Results: Telomere length was inversely associated with body mass index (BMI), waist circumference, waist‐to‐height ratio, weight, and hip circumference (P_trend = 0.005, 0.004, 0.004, 0.010, and 0.026, respectively), but not waist‐to‐hip ratio (P_trend = 0.116) or height (P_trend = 0.675). Weight change since age 50 was further evaluated among women over age 55. Women who maintained their weight within ±5% since age 50, particularly within a normal range (BMI = 18.5‐24.9 kg/m²), or reduced their weight from overweight (BMI = 25‐29.9 kg/m²) or obesity (BMI ≥30 kg/m²) to normal range, had a longer mean of current telomere length than women who gained weight since age 50 (P_trend = 0.025), particularly those who stayed in obesity or gained weight from normal range or overweight to obesity (P = 0.023). Conclusion: Our findings show that telomere shortening is associated with obesity and that maintaining body weight within a normal range helps maintain telomere length.     

Adiponectin, visceral fat, oxidative stress, and early macrovascular disease: the Coronary Artery Risk Development in Young Adults Study

Objective: Adiponectin is a collagen‐like product of visceral fat that offers apparent protection against macrovascular disease. We evaluated the relationships of concentrations of adiponectin with oxidative stress and the major risk factors for and/or the presence of macrovascular disease. Research Methods and Procedures: Adiponectin was measured by radioimmunoassay in serum from 3045 fasting participants (ages 33 to 45) of the Coronary Artery Risk Development in Young Adults Study. Cross‐sectional correlation of the concentrations of adiponectin with F₂‐isoprostane concentrations (a marker of systemic oxidative damage), coronary artery calcification (CAC; an estimate of early macrovascular disease), and several macrovascular risk factors was analyzed. Results: F₂‐isoprostanes and CAC were unrelated to adiponectin after minimal adjustment for gender, race, and center. After additional adjustment for insulin resistance and waist circumference and other macrovascular risk factors, adiponectin correlated positively with high‐density lipoprotein‐cholesterol (p < 0.0001), F₂‐isoprostanes (p < 0.0001), and CAC (less strongly, p < 0.01) and negatively with triglycerides (p < 0.0001) and C‐reactive protein (marking inflammation, p = 0.01). Discussion: Although these data are consistent with reduced cardiovascular disease risk imparted by adiponectin, the higher circulating levels of adiponectin present with oxidative stress and CAC (adjusting for waist and insulin resistance) may indicate an enhanced adiponectin secretory response of adipose tissue to the metabolic environment present in the early development of macrovascular disease. Thus, the elevated levels of adiponectin may comprise an attempt to alleviate risk for additional development and progression of macrovascular disease in an at‐risk environment.     

Comparison of Overall Obesity and Body Fat Distribution in Predicting Risk of Mortality

Results of studies comparing overall obesity and abdominal adiposity or body fat distribution with risk of mortality have varied considerably. We compared the relative importance and joint association of overall obesity and body fat distribution in predicting risk of mortality. Participants included 5,799 men and 6,429 women aged 30–102 years enrolled in the third National Health and Nutrition Examination Survey who completed a baseline health examination during 1988–1994. During a 12‐year follow‐up (102,172 person‐years), 1,188 men and 925 women died. In multivariable‐adjusted analyses, waist‐to‐thigh ratio (WTR) in both sexes (P_trend <0.01 for both) and waist‐to‐hip ratio (WHR) in women (P_trend 0.001) were positively associated with mortality in middle‐aged adults (30–64 years), while BMI and waist circumference (WC) exhibited U‐ or J‐shaped associations. Risk of mortality increased with a higher WHR and WTR among normal weight (BMI 18.5–24.9 kg/m²) and obese (BMI ≥30.0 kg/m²) adults. In older adults (65–102 years), a higher BMI in both sexes (P_trend <0.05) and WC in men (P_trend 0.001) were associated with increased survival, while remaining measures of body fat distribution exhibited either no association or an inverse relation with mortality. In conclusion, ratio measures of body fat distribution are strongly and positively associated with mortality and offer additional prognostic information beyond BMI and WC in middle‐aged adults. A higher BMI in both sexes and WC in men were associated with increased survival in older adults, while a higher WHR or WTR either decreased or did not influence risk of death.     

Association of Adiposity Indices with Platelet Distribution Width and Mean Platelet Volume in Chinese Adults

Hypoxia is a prominent characteristic of inflammatory tissue lesions. It can affect platelet function. While mean platelet volume (MPV) and platelet distribution width (PDW) are sample platelet indices, they may reflect subcinical platelet activation. To investigated associations between adiposity indices and platelet indices, 17327 eligible individuals (7677 males and 9650 females) from the Dongfeng-Tongji Cohort Study (DFTJ-Cohort Study, n=27009) were included in this study, except for 9682 individuals with missing data on demographical, lifestyle, physical indicators and diseases relative to PDW and MPV. Associations between adiposity indices including waist circumstance (WC), waist-to-height ratio (WHtR), body mass index (BMI), and MPV or PDW in the participants were analyzed using multiple logistic regressions. There were significantly negative associations between abnormal PDW and WC or WHtR for both sexes (p _trend<0.001 for all), as well as abnormal MPV and WC or WHtR among female participants (p _trend<0.05 for all). In the highest BMI groups, only females with low MPV or PDW were at greater risk for having low MPV (OR=1.33, 95% CI=1.10, 1.62 p _trend<0.001) or PDW (OR=1.34, 95% CI=1.14, 1.58, p _trend<0.001) than those who had low MPV or PDW in the corresponding lowest BMI group. The change of PDW seems more sensitive than MPV to oxidative stress and hypoxia. Associations between reduced PDW and MPV values and WC, WHtR and BMI values in Chinese female adults may help us to further investigate early changes in human body.     

C-reactive protein modifies the association of plasma leptin with coronary calcium in asymptomatic overweight individuals

Evidence suggests putative interactions of leptin and C‐reactive protein (CRP) in the pathogenesis of adiposity‐related atherosclerotic cardiovascular disease (CVD). Therefore, we investigated whether CRP levels modify the relationship of leptin levels with coronary artery calcium (CAC). We examined 1,460 asymptomatic individuals from two community‐based cross‐sectional studies coordinated at a single, university‐based research center. We focused on subjects who were overweight or obese (BMI ≥25) given greater biologic plausibility in this setting. In multivariable CAC models, we analyzed the interaction of log‐transformed plasma leptin levels with higher CRP levels as defined by three cut‐points: two clinically based (2 mg/l, 3 mg/l) and one dataset specific (sex‐specific upper quartile). The association of plasma leptin with CAC was modified by higher CRP regardless of cut‐point (interaction term P values all <0.01 in fully adjusted models). Leptin levels were associated with CAC in those with high, but not low CRP levels (e.g., tobit ratio for a 1 unit increase in ln(leptin) (95% CI): 2.18 (1.29–3.66) if CRP level ≥3 mg/l; N = 461 vs. 0.94 (0.67–1.31) if CRP levels <3 mg/l; N = 999) in fully adjusted models. No interaction with CRP was present in control analyses with adiponectin, BMI and waist circumference. In conclusion, in asymptomatic overweight and obese adults, increased leptin levels were independently associated with increased CAC in the presence of high, but not low CRP levels, supporting a leptin‐CRP interface in atherosclerosis risk.     

Leptin and coronary heart disease risk: prospective case control study of British women

Objective: Prospective studies have shown a positive association between leptin concentrations and coronary heart disease (CHD) in men, but its effect in women is unclear. Our objective was to examine the association of serum leptin levels with CHD in a prospective study of women. Research Methods and Procedures: We conducted a prospective (4 year) case (N = 165) control (N = 335) study nested within a cohort of 4286 British women. Results: With mutual adjustment for each other and age, social class, smoking, and physical activity, leptin was positively associated with BMI, fasting insulin, total cholesterol, low‐density lipoprotein‐cholesterol, triglycerides, and hypertension and was inversely associated with homeostasis model assessment insulin sensitivity. Leptin was not associated with CHD risk (age‐adjusted relative risk for a doubling of leptin: 1.08 [95% confidence interval (CI): 0.91, 1.29]). This changed little with adjustment for childhood and adult social class, smoking, alcohol, and physical activity but attenuated to 1.00 (95% CI: 0.80, 1.26) with further adjustment for other metabolic risk factors (waist‐to‐hip ratio, low‐density lipoprotein‐cholesterol, triglycerides, C‐reactive protein, fasting insulin, hypertension). Discussion: We found no strong statistical evidence that leptin is associated with CHD risk in this study population of older British women. Further research is needed to compare associations of leptin with CHD in men and women and to determine whether the effect varies by gender.     

The Association between Subclinical Atherosclerosis and Uterine Fibroids

Objective(s)

To explore the atherogenic hypothesis of uterine fibroids among Chinese women.

Methods

In a case-control study, 335 patients confirmed by ultrasound or hysterectomy surgery and 539 controls were enrolled between October 1, 2009 and April 1, 2012. Unconditional logistic regressions were used to calculate the odds ratios (ORs) for the associations of subclinical atherogenic and cardiovascular risk parameters with uterine fibroids in the overall case group and hysterectomy-confirmed case group, respectively.

Results

Higher level of ankle-brachial index (ABI) was independently associated with increased odds of uterine fibroids. The odds of UF among women in the highest tertile of ABI were 1.88 times higher (95%CI: 1.17, 3.02, P_trend = 0.008) compared to those in the lowest tertile. The serum concentration of homocysteine was inversely related to fibroids (middle vs. low: OR 0.56, 95%CI: 0.36, 0.85; high vs. low: OR 0.50, 95% CI: 0.32, 0.79; P_trend = 0.002). In the hysterectomy-confirmed group, an inverse association was suggested between high-density lipoprotein cholesterol (HDL-C) and fibroids (OR 0.46, 95% CI: 0.25, 0.84, P_trend = 0.014). Moreover, the effect of homocysteine concentration was not observed in this group.

Conclusion(s)

These findings suggest that women with uterine fibroids might have an increased risk of subclinical atherosclerosis.     

Influence of Waist on Adiponectin and Insulin Sensitivity in Adolescence

It has been hypothesized that abdominal obesity leads to insulin resistance partly through decreased adiponectin. However, the cross‐sectional and longitudinal associations among waist, adiponectin, and insulin sensitivity have not been examined in older adolescents. Non‐Hispanic white and black children were recruited from the Minneapolis school district and underwent three examinations at mean ages 13, 15, and 19. Insulin sensitivity (measured using the gold‐standard euglycemic clamp) and waist circumference were measured at all exams. Adiponectin was measured at mean ages 15 and 19. Partial correlations were used to examine associations among waist, adiponectin, and insulin sensitivity at mean age 15 (n = 308) and mean age 19 (n = 218). Longitudinal correlations and a longitudinal regression model were used to predict adiponectin and insulin sensitivity measured at ages 15 and 19, from age 13 waist and change in waist. At age 15, waist and adiponectin were significantly correlated (r = ?0.32). At age 19, waist and adiponectin were significantly correlated (r = ?0.36), as were waist and insulin sensitivity (r = ?0.16). Both baseline waist and change in waist were significantly inversely associated with age 19 adiponectin but with age 19 insulin sensitivity only in men. In conclusion, in adolescents, the association between waist and adiponectin appears to develop several years before the association between waist and insulin sensitivity and there is a longitudinal association between waist and adiponectin. These results support the hypothesis that adiponectin may contribute to the association of waist and insulin sensitivity.     

Polymorphisms of stress-related genes and the risk of nonsyndromic cleft lip with or without cleft palate

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NCL/P) is a common structural malformation with a complex and multifactorial etiology. It has been shown that maternal psychological stress in the periconceptional period can contribute to an increase in the risk of NCL/P affecting pregnancy. METHODS: Twenty‐four single nucleotide polymorphisms of 11 stress‐related genes (COMT, CRHR1, FKBP5, GABRA6, HSD11β2, MAOA, NPY, NR3C1, SERPINA6, SLC6A4, and TPH2) were investigated in 220 healthy mothers of children with facial clefts and 210 matched controls using restriction fragment‐length polymorphism and high‐resolution melting analysis. RESULTS: We found that polymorphisms in SLC6A4, TPH2, and SERPINA6 appear to be maternal factors increasing the risk of having a child with facial clefts. The closest correlations with NCL/P were found for the SLC6A4 rs2020942 and TPH2 rs10879357 gene variants (odds ratio [OR], 1.720; 95% confidence interval [CI], 1.158–2.553; p = 0.0069; p_trend = 0.0036; and OR, 1.837; 95% CI, 1.226–2.753, p = 0.0030, p_trend = 0.0057; respectively). Moreover, haplotype analysis revealed that several combinations of markers in SLC6A4, TPH2, and SERPINA6 might be significantly associated with the risk of NCL/P affected pregnancies. However, these associations were not statistically significant after correction for multiple testing. CONCLUSION: This study suggests that nucleotide variants of genes encoding components of the hypothalamus‐pituitary‐adrenal axis and serotoninergic system have a role in the etiology of NCL/P in the Polish population. SLC6A4, TPH2, and SERPINA6 might be novel candidate genes for this common congenital anomaly. Birth Defects Research (Part A), 2011. © 2011 Wiley‐Liss, Inc.     

Associations of testosterone and sex hormone binding globulin with adipose tissue hormones in midlife women

Objective:

Regulators of adipose tissue hormones remain incompletely understood, but may include sex hormones. As adipose tissue hormones have been shown to contribute to numerous metabolic and cardiovascular disorders, understanding their regulation in midlife women is of clinical importance. Therefore, we assessed the associations between testosterone (T) and sex hormone binding globulin (SHBG) with leptin, high molecular weight (HMW) adiponectin, and the soluble form of the leptin receptor (sOB‐R) in healthy midlife women.

Design and Methods:

Cross‐sectional analyses were performed using data from 1,881 midlife women (average age 52.6 (±2.7) years) attending the sixth Annual follow‐up visit of the multiethnic Study of Women's Health Across the Nation.

Results:

T was weakly negatively associated with both HMW adiponectin and sOB‐R (r = ?0.12 and r = ?0.10, respectively; P < 0.001 for both), and positively associated with leptin (r = 0.17; P < 0.001). SHBG was more strongly and positively associated with both HMW adiponectin and sOB‐R (r = 0.29 and r = 0.24, respectively; P < 0.001 for both), and more strongly and negatively associated with leptin (r = ?0.27; P < 0.001). Adjustment for fat mass, insulin resistance, or waist circumference only partially diminished associations with HMW adiponectin and sOB‐R, but attenuated associations with leptin. In conclusion, in these midlife women, lower SHBG values, and to a lesser extent, higher T levels, were associated with lower, or less favorable, levels of adiponectin and sOB‐R, independent of fat mass.

Conclusions:

These data suggest that variation in these adipose hormones resulting from lower SHBG levels, and possibly, though less likely, greater androgenicity, may contribute to susceptibility for metabolic and cardiovascular outcomes during midlife in women.

     

Adiponectin Levels during Low‐ and High‐Fat Eucaloric Diets in Lean and Obese Women

Objective: Adiponectin influences insulin sensitivity (S_I) and fat oxidation. Little is known about changes in adiponectin with changes in the fat content of eucaloric diets. We hypothesized that dietary fat content may influence adiponectin according to an individual's S_I. Research Methods and Procedures: We measured changes in adiponectin, insulin, glucose, and leptin in response to high‐fat (HF) and low‐fat (LF) eucaloric diets in lean (n = 10) and obese (n = 11) subjects. Obese subjects were further subdivided in relation to a priori S_I. Results: We found significantly higher insulin, glucose, and leptin and lower adiponectin in obese vs. lean subjects during both HF and LF. The mean group values of these measurements, including adiponectin (lean, HF 21.9 ± 9.8; LF, 20.8 ± 6.6; obese, HF 10.0 ± 3.3; LF, 9.5 ± 2.3 ng/mL; mean ± SD), did not significantly change between HF and LF diets. However, within the obese group, the insulin‐sensitive subjects had significantly higher adiponectin during HF than did the insulin‐resistant subjects. Additionally, the change in adiponectin from LF to HF diet correlated positively with the obese subjects’ baseline S_I. Discussion: Although in lean and obese women, group mean values for adiponectin did not change significantly with a change in fat content of a eucaloric diet, a priori measured S_I in obese subjects predicted an increase in adiponectin during the HF diet; this may be a mechanism that preserves S_I in an already obese group.     

Interaction of FTO and physical activity level on adiposity in African-American and European-American adults: the ARIC study

Physical inactivity accentuates the association of variants in the FTO locus with obesity‐related traits but evidence is largely lacking in non‐European populations. Here we tested the hypothesis that physical activity (PA) modifies the association of the FTO single‐nucleotide polymorphism (SNP) rs9939609 with adiposity traits in 2,656 African Americans (AA) (1,626 women and 1,030 men) and 9,867 European Americans (EA) (5,286 women and 4,581 men) aged 45–66 years in the Atherosclerosis Risk in Communities (ARIC) study. Individuals in the lowest quintile of the sport activity index of the Baecke questionnaire were categorized as low PA. Baseline BMI, waist circumference (WC), and skinfold measures were dependent variables in regression models testing the additive effect of the SNP, low PA, and their interaction, adjusting for age, alcohol use, cigarette use, educational attainment, and percent European ancestry in AA adults, stratified by sex and race/ethnicity. rs9939609 was associated with adiposity in all groups other than AA women. The SNP × PA interaction was significant in AA men (P ≤ 0.002 for all traits) and EA men (P ≤ 0.04 for all traits). For each additional copy of the A (risk) allele, WC in AA men was higher in those with low PA (β_lowPA: 5.1 cm, 95% confidence interval (CI): 2.6–7.5) than high PA (β_highPA: 0.7 cm, 95% CI: ?0.4 to 1.9); P (interaction) = 0.002). The interaction effect was not observed in EA or AA women. FTO SNP × PA interactions on adiposity were observed for AA as well as EA men. Differences by sex require further examination.     

Adipokines,Ghrelin and Obesity‐Associated Insulin Resistance in Nondiabetic Patients with Acute Coronary Syndrome

Altered glucose metabolism negatively modulates outcome in acute coronary syndromes (ACS). Insulin resistance is commonly associated with increasing BMI in the general population and these associations may involve obesity‐related changes in circulating ghrelin and adipokines. We aimed at investigating interactions between BMI, insulin resistance and ACS and their associations with plasma ghrelin and adipokine concentrations. Homeostasis model assessment of insulin resistance (HOMA_IR)‐insulin resistance index, plasma adiponectin, leptin, total (T‐Ghrelin), acylated (Acyl‐Ghrelin), and desacylated ghrelin (Desacyl‐Ghrelin) were measured in 60 nondiabetic ACS patients and 44 subjects without ACS matched for age, sex, and BMI. Compared with non‐ACS, ACS patients had similar HOMA_IR and plasma adipokines, but lower T‐ and Desacyl‐Ghrelin and higher Acyl‐Ghrelin. Obesity (BMI > 30) was associated with higher HOMA_IR, lower adiponectin, and higher leptin (P < 0.05) similarly in ACS and non‐ACS subjects. In ACS (n = 60) HOMA_IR remained associated negatively with adiponectin and positively with leptin independently of BMI and c‐reactive protein (CRP) (P < 0.05). On the other hand, low T‐ and Desacyl‐Ghrelin with high Acyl‐Ghrelin characterized both obese and non‐obese ACS patients and were not associated with HOMA_IR. In conclusion, in ACS patients, obesity and obesity‐related changes in plasma leptin and adiponectin are associated with and likely contribute to negatively modulate insulin resistance. ACS per se does not however enhance the negative impact of obesity on insulin sensitivity. High acylated and low desacylated ghrelin characterize ACS patients independently of obesity, but are not associated with insulin sensitivity.     

Maternal and fetal leptin,adiponectin levels and associations with fetal insulin sensitivity

Objective:

It remains uncertain whether leptin and adiponectin levels are correlated in maternal vs. fetal circulations. Little is known about whether leptin and adiponectin affect insulin sensitivity during fetal life.

Design and Methods:

In a prospective singleton pregnancy cohort (n = 248), we investigated leptin and adiponectin concentrations in maternal (at 24‐28 and 32‐35 weeks of gestation) and fetal circulations, and their associations with fetal insulin sensitivity (glucose/insulin ratio, proinsulin level).

Results:

Comparing concentrations in cord vs. maternal blood, leptin levels were 50% lower, but adiponectin levels more than doubled. Adjusting for gestational age at blood sampling, consistent and similar positive correlations (correlation coefficients: 0.31‐0.34, all P < 0.0001) were observed in leptin or adiponectin levels in maternal (at 24‐28 or 32‐25 weeks of gestation) vs. fetal circulations. For each SD increase in maternal plasma concentration at 24‐28 weeks, cord plasma concentration increased by 12.7 (95% confidence interval 6.8‐18.5) ng/ml for leptin, and 2.9 (1.8‐4.0) µg/ml for adiponectin, respectively (adjusted P < 0.0001). Fetal insulin sensitivity was negatively associated with cord blood leptin (each SD increase was associated with a 5.4 (2.1‐8.7) mg/dl/µU/ml reduction in cord plasma glucose/insulin ratio, and a 5.6 (3.9, 7.4) pmol/l increase in proinsulin level, all adjusted P < 0.01) but not adiponectin (P > 0.4) levels). Similar associations were observed in nondiabetic full‐term pregnancies (n = 211).

Conclusions:

The results consistently suggest a maternal impact on fetal leptin and adiponectin levels, which may be an early life pathway in maternal‐fetal transmission of the propensity to obesity and insulin resistance.     

Improvements in Coronary Heart Disease Risk Indicators by Alternate‐Day Fasting Involve Adipose Tissue Modulations

The ability of alternate‐day fasting (ADF) to modulate adipocyte parameters in a way that is protective against coronary heart disease (CHD) has yet to be tested. Accordingly, we examined the effects of ADF on adipokine profile, body composition, and CHD risk indicators in obese adults. Sixteen obese subjects (12 women/4 men) participated in a 10‐week trial with three consecutive dietary intervention phases: (i) 2‐week baseline control phase, (ii) 4‐week ADF controlled feeding phase, and (iii) 4‐week ADF self‐selected feeding phase. After 8 weeks of treatment, body weight and waist circumference were reduced (P < 0.05) by 5.7 ± 0.9 kg, and 4.0 ± 0.9 cm, respectively. Fat mass decreased (P < 0.05) by 5.4 ± 0.8 kg, whereas fat‐free mass did not change. Plasma adiponectin was augmented (P < 0.05) by 30% from baseline. Leptin and resistin concentrations were reduced (P < 0.05) by 21 and 23%, respectively, post treatment. Low‐density lipoprotein cholesterol (LDL‐C) and triacylglycerol concentrations were 25% and 32% lower (P < 0.05), respectively, after 8 weeks of ADF. High‐density lipoprotein cholesterol (HDL‐C), C‐reactive protein, and homocysteine concentrations did not change. Decreases in LDL‐C were related to increased adiponectin (r = ?0.61, P = 0.01) and reduced waist circumference (r = 0.39, P = 0.04). Lower triacylglycerol concentrations were associated with augmented adiponectin (r = ?0.39, P = 0.04) and reduced leptin concentrations (r = 0.45, P = 0.03) post‐treatment. These findings suggest that adipose tissue parameters may play an important role in mediating the cardioprotective effects of ADF in obese humans.