Biomedical subjects

Christos S Mantzoros

Publications and source records attributed to Christos S Mantzoros.

At least 19 recordsLinked to original sources

PubMed2007

Low adiponectin levels are associated with renal cell carcinoma: a case-control study.

Adiponectin is a novel endogenous insulin sensitizer, secreted by mature adipocytes. Circulating levels of adiponectin are inversely associated with obesity and insulin resistance. Because obesity is a risk factor for renal cell carcinoma (RCC), we hypothesized that low adiponectin levels are associated with RCC. To evaluate this hypothesis, we conducted a case- control study of 70 patients with histologically confirmed RCC and 280 healthy controls matched by gender, age and county of residence. Study subjects were interviewed and blood samples were collected during a 32-month period in Athens, Greece. Serum adiponectin levels were statistically, significantly and inversely associated with RCC when compared with controls (OR=0.76, p=0.05) and this association remained practically unchanged after controlling for BMI; the introduction of waist to hip ratio along with adiponectin in the multiple logistic regression analysis model rendered the association between adiponectin and RCC risk insignificant, indicating that altered levels of adiponectin may mediate the effect of central or intra-abdominal obesity on RCC. Prospective studies as well as studies exploring underlying mechanisms are needed to fully explore the role of adiponectin in predicting future risk of RCC in humans.

Adiponectin↗

PubMed2007

Plasma adiponectin concentrations and risk of incident breast cancer.

INTRODUCTION: Previous retrospective case-control studies suggest that adiponectin, an obesity-related hormone, is inversely associated with breast cancer risk, particularly in postmenopausal women; however, no prospective studies exist. Therefore, we conducted a prospective case-control study nested within the Nurses' Health Study (NHS) and NHSII cohorts examining the association between plasma adiponectin concentrations and breast cancer risk. MATERIALS AND METHODS: Blood samples were collected from 1989 through 1990 (NHS) and 1996 through 1999 (NHSII); adiponectin was measured by RIA. The analysis included 1477 breast cancer cases diagnosed after blood collection and before June 2000 (NHS) or June 2003 (NHSII) who had one or two controls (n=2196) matched on age, menopausal status, postmenopausal hormone (PMH) use, fasting, and time of day and month of blood collection. We adjusted for body mass index at age 18, weight change from age 18 to blood draw, family history of breast cancer, history of benign breast disease, duration of PMH use, ages at menarche and first birth, and parity. RESULTS: Although we observed no association between adiponectin and breast cancer risk overall, there was a nearly significant interaction by menopausal status (P=0.08), with a relative risk, top vs. bottom quartile of 0.73 (95% confidence interval, 0.55-0.98; P trend=0.08) among postmenopausal women and 1.30 (95% confidence interval, 0.80-2.10; P trend=0.09) for premenopausal women. Among postmenopausal women, adiponectin appeared more strongly inversely associated in women who never used PMH (P heterogeneity=0.05) and women with low circulating estradiol levels (P heterogeneity=0.05). DISCUSSION: Our results suggest that adiponectin may be inversely associated with postmenopausal breast cancer risk, particularly in a low-estrogen environment.

Adiponectin↗

PubMed2007

Short-term fasting-induced autonomic activation and changes in catecholamine levels are not mediated by changes in leptin levels in healthy humans.

OBJECTIVE: In animal models, the adipocyte-secreted hormone leptin increases energy expenditure by increasing sympathetic outflow but its role in humans remains to be elucidated. We evaluated whether inducing hypoleptinaemia (with and without administration of leptin at replacement doses) for 3 days would influence catecholamine levels and sympathetic and parasympathetic activity in healthy humans. METHODS: We studied six normal-weight subjects in the General Clinical Research Center (GCRC) under three conditions: baseline fed state (control study) and two 72-h fasting studies (to decrease leptin levels), with administration of either placebo or replacement-dose recombinant methionyl human leptin (r-metHuLeptin) in a randomized, double-blind fashion. In each condition, 24-h urinary catecholamine levels, heart rate and heart rate variability (HRV), a standard tool for assessing cardiac autonomic modulation, were measured. RESULTS: Study parameters remained stable during the control condition and the baseline assessment of all three studies. In response to 72-h fasting, which decreased serum leptin levels by 80%, 24-h urinary norepinephrine and dopamine levels and heart rate increased while cardiac vagal modulation decreased (all P < 0.05). Replacement-dose r-metHuLeptin to keep leptin levels within the physiological range during fasting did not alter fasting-associated changes in heart rate, catecholamine levels or cardiac vagal tone. CONCLUSIONS: The findings of this controlled, interventional study indicate that changes in heart rate, catecholamine levels and cardiac vagal modulation associated with 72-h fasting are independent of regulation by leptin. Thus, changes in leptin levels within the physiological range do not seem to play a role in regulating autonomic function during short-term starvation in healthy humans.

Adult↗

PubMed2007

Circulating insulin and c-peptide levels and risk of breast cancer among predominately premenopausal women.

Insulin and insulin resistance have been hypothesized to increase the risk of breast cancer as insulin increases breast cell proliferation and inhibits sex hormone binding globulin. Although insulin is directly related to body weight, adiposity is inversely associated with breast cancer risk in premenopausal women but directly related to risk in postmenopausal women. To explore the association between insulin and c-peptide levels and breast cancer risk, we conducted a nested case-control study of predominantly premenopausal women within the Nurses' Health Study II cohort. From 1996 to 1999, blood samples were collected from 29,611 participants. A total of 317 cases were diagnosed after blood collection and before June 2003 and matched to 634 controls; 75% of these women were premenopausal at blood collection. Logistic regression models, controlling for breast cancer risk factors, were used to calculate relative risks (RR) and 95% confidence intervals (95% CI). Among women with fasting blood samples (n = 211 cases), insulin was suggestively inversely associated with breast cancer risk (highest versus lowest quartile: RR, 0.5; 95% CI, 0.3-1.0; P(trend) = 0.06). Among all women, c-peptide was not associated with breast cancer risk (highest versus lowest quartile: RR, 1.1; 95% CI, 0.7-1.7; P(trend) = 0.79); results were similar among fasting samples. These associations did not differ by age, body mass index, or waist-to-hip ratio. Overall, higher levels of insulin and c-peptide were not associated with a higher risk of breast cancer among predominantly premenopausal women.

Adult↗

PubMed2006

Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies.

BACKGROUND: Obesity is a major risk factor for breast cancer. We hypothesized that obesity-induced decreases in total and/or high-molecular-weight (HMW) adiponectin levels may underlie this association. METHODS: We measured serum total and HMW adiponectin in a hospital-based case-control study of 74 female breast cancer patients and 76 controls. In parallel, expression of adiponectin and its receptors AdipoR1/R2 were measured in tissue samples using RT-PCR, and protein expression of AdipoR1/R2 was localized and quantified using immunohistochemistry. Finally, we documented AdipoR1/R2 expression in several breast cancer cell lines and studied adiponectin signaling and the effect of adiponectin on proliferation in the T47D breast cancer cell line in vitro. RESULTS: Women with the highest adiponectin levels had a 65% reduced risk of breast cancer (P = 0.04). This association became stronger after adjustment for age, body mass index, and hormonal and reproductive factors (P = 0.02). Modeling HMW instead of total adiponectin produced similar results and did not offer any additional predictive value. Breast cancer cells expressed AdipoR1/R2 but not adiponectin. Expression of AdipoR1, but not AdipoR2, was higher in tumor tissue than both adjacent and control tissues. Exposure of T47D cells to adiponectin significantly inhibited the percentage of viable cells to 86% and proliferation to 66% but had no effect on apoptosis. These effects were associated with activation of ERK1/2 but not AMP-activated protein kinase or p38MAPK. CONCLUSION: These studies suggest that adiponectin may act as a biomarker of carcinogenesis and may constitute a molecular link between obesity and breast cancer.

Adiponectin↗

PubMed2006

Regulation of adiponectin and its receptors in response to development of diet-induced obesity in mice.

Adiponectin and its receptors play an important role in energy homeostasis and insulin resistance, but their regulation remains to be fully elucidated. We hypothesized that high-fat diet would decrease adiponectin but increase adiponectin receptor (AdipoR1 and AdipoR2) expression in diet-induced obesity (DIO)-prone C57BL/6J and DIO-resistant A/J mice. We found that circulating adiponectin and adiponectin expression in white adipose tissue are higher at baseline in C57BL/6J mice compared with A/J mice. Circulating adiponectin increases at 10 wk but decreases at 18 wk in response to advancing age and high-fat feeding. However, adiponectin levels corrected for visceral fat mass and adiponectin mRNA expression in WAT are affected by high-fat feeding only, with both being decreased after 10 wk in C57BL/6J mice. Muscle AdipoR1 expression in both C57BL/6J and A/J mice and liver adipoR1 expression in C57BL/6J mice increase at 18 wk of age. High-fat feeding increases both AdipoR1 and AdipoR2 expression in liver in both strains of mice and increases muscle AdipoR1 expression in C57BL/6J mice after 18 wk. Thus advanced age and high-fat feeding, both of which are factors that predispose humans to obesity and insulin resistance, are associated with decreasing adiponectin and increasing AdipoR1 and/or AdipoR2 levels.

Adiponectin↗

PubMed2006

Physical activity and risk of endometrial cancer: a population-based prospective cohort study.

Physical activity is involved in the regulation of metabolic and hormonal pathways and is one of the factors important for the maintenance of body weight; obesity is a risk factor for endometrial cancer. A connection between physical activity and endometrial cancer risk through hormonal mechanisms, possibly mediated by body weight, is biologically plausible. Only one study has investigated total physical activity, and no previous study has examined leisure time inactivity directly. We investigated the association of total physical activity and different types of physical activity with risk of endometrial cancer in the Swedish Mammography Cohort, a population-based prospective cohort, including 33,723 women and 199 endometrial cancer cases. After adjustments for potential confounders (age, body mass index, parity, history of diabetes, total fruit and vegetable intake, and education), the relative risks for endometrial cancer for the second to fourth quartile of total physical activity compared with the lowest one were 0.80 [95% confidence interval (95% CI), 0.54-1.18], 0.87 (95% CI, 0.59-1.28), and 0.79 (95% CI, 0.53-1.17). High leisure time inactivity (watching TV/sitting >or=5 hours daily) compared with low was associated with increased risk of endometrial cancer (relative risk, 1.66; 95% CI, 1.05-2.61). The associations were not modified by body mass index. Findings from this study suggest that total physical activity is weakly inversely associated with endometrial cancer risk and that leisure time inactivity is statistically significantly associated with increased risk for endometrial cancer.

Adult↗

PubMed2006

Differential regulation of metabolic, neuroendocrine, and immune function by leptin in humans.

To elucidate whether the role of leptin in regulating neuroendocrine and immune function during short-term starvation in healthy humans is permissive, i.e., occurs only when circulating leptin levels are below a critical threshold level, we studied seven normal-weight women during a normoleptinemic-fed state and two states of relative hypoleptinemia induced by 72-h fasting during which we administered either placebo or recombinant methionyl human leptin (r-metHuLeptin) in replacement doses. Fasting for 72 h decreased leptin levels by approximately = 80% from a midphysiologic (14.7 +/- 2.6 ng/ml) to a low-physiologic (2.8 +/- 0.3 ng/ml) level. Administration of r-metHuLeptin during fasting fully restored leptin to physiologic levels (28.8 +/- 2.0 ng/ml) and reversed the fasting-associated decrease in overnight luteinizing hormone pulse frequency but had no effect on fasting-induced changes in thyroid-stimulating hormone pulsatility, thyroid and IGF-1 hormone levels, hypothalamic-pituitary-adrenal and renin-aldosterone activity. FSH and sex steroid levels were not altered. Short-term reduction of leptin levels decreased the number of circulating cells of the adaptive immune response, but r-metHuLeptin did not have major effects on their number or in vitro function. Thus, changes of leptin levels within the physiologic range have no major physiologic effects in leptin-replete humans. Studies involving more severe and/or chronic leptin deficiency are needed to precisely define the lower limit of normal leptin levels for each of leptin's physiologic targets.

Adaptation, Physiological↗

PubMed2006

Recombinant methionyl human leptin therapy in replacement doses improves insulin resistance and metabolic profile in patients with lipoatrophy and metabolic syndrome induced by the highly active antiretroviral therapy.

CONTEXT: Highly active antiretroviral therapy (HAART) for HIV-1 infection has been associated with a metabolic syndrome characterized by insulin resistance, hyperlipidemia, and redistribution of body fat (lipodystrophy). A subset of patients with predominant lipoatrophy has low levels of the adipocyte-secreted hormone leptin. OBJECTIVE: The objective of the study was to assess whether administration of recombinant methionyl human leptin (r-metHuLeptin) improves insulin resistance and other metabolic abnormalities in HIV+ leptin-deficient subjects with HAART-induced lipoatrophy. DESIGN, SETTING, PATIENTS, AND INTERVENTION: We conducted a randomized, placebo-controlled, double-blinded, crossover study from 2002 to 2004 in seven HIV+ men with HAART-induced lipoatrophy, serum leptin level less than 3 ng/ml, and fasting triglyceride level greater than 300 mg/dl, who were administered placebo for 2 months before or after administration of r-metHuLeptin at physiological doses for an additional 2 months. MAIN OUTCOME MEASURES: Insulin resistance, lipid levels, inflammatory markers, body composition, and HIV control were measured. RESULTS: Compared with placebo, r-metHuLeptin therapy improved fasting insulin levels, insulin resistance (as expressed by the homeostasis model assessment index and an insulin suppression test), and high-density lipoprotein. Body weight and fat mass decreased on r-metHuLeptin, mainly due to a decrease in truncal fat but not peripheral fat or lean body mass. r-metHuLeptin was well tolerated, and HIV control was not adversely affected. CONCLUSIONS: r-metHuLeptin replacement at physiological doses in HIV+ leptin-deficient patients with HAART-induced lipoatrophy improves insulin resistance, high-density lipoprotein, and truncal fat mass. Future larger and more long-term studies in HAART-induced lipoatrophy, including patients with more severe metabolic abnormalities, are warranted to evaluate the physiological and potentially therapeutic role of r-metHuLeptin for this condition and to fully clarify the underlying mechanisms of action.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Ghrelin stimulates interleukin-8 gene expression through protein kinase C-mediated NF-kappaB pathway in human colonic epithelial cells.

Ghrelin, a newly identified gastric peptide, is known for its potent activity in growth hormone (GH) release and appetite. Although ghrelin is involved in several other responses such as stress and intestinal motility, its potential role in intestinal inflammation is not clear. Here, we show that expression of ghrelin and its receptor mRNA is significantly increased during acute experimental colitis in mice injected intracolonically with trinitrobenzene sulfate (TNBS). We found by PCR that ghrelin receptor mRNA is expressed in non-transformed human colonic epithelial NCM460 cells. Exposure of NCM460 cells stably transfected with ghrelin receptor mRNA to ghrelin, increased IkappaBalpha phosphorylation and its subsequent degradation. In addition, ghrelin stimulated NF-kappaB-binding activity and NF-kappaB p65 subunit phosphorylation, and induced IL-8 promoter activity and IL-8 protein secretion. Furthermore, our data show that ghrelin-induced IkappaBalpha and p65 phosphorylation was markedly reduced by pharmacological inhibitors of intracellular calcium mobilization (BAPTA/AM) and protein kinase C (GF 109203X). Pretreatment with BAPTA/AM or GF109203X also significantly attenuated ghrelin-induced IL-8 production. Together, our results strongly suggest that ghrelin may be a proinflammatory peptide in the colon. Ghrelin may participate in the pathophysiology of colonic inflammation by inducing PKC-dependent NF-kappaB activation and IL-8 production at the colonocyte level.

Animals↗

PubMed2006

Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels.

OBJECTIVE: Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP--two markers of inflammation and susceptibility to atherosclerosis. METHODS AND RESULTS: Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p=0.005), accounting for 3% of its variance (r2=0.030). The same block was also associated with CRP levels (p=0.049, r2=0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p=0.015). At rs1805096, it was 5% higher (p=0.007) and CRP 32% higher (p=0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. CONCLUSIONS: Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis.

Adipose Tissue↗

PubMed2006

Circulating adiponectin and expression of adiponectin receptors in human skeletal muscle: associations with metabolic parameters and insulin resistance and regulation by physical training.

CONTEXT: Adiponectin, an adipocyte-secreted hormone, is associated with insulin resistance and the metabolic syndrome. OBJECTIVE: The physiological regulation of circulating adiponectin levels and mRNA expression of its receptors (AdipoR1 and AdipoR2) in skeletal muscle remains to be fully elucidated. DESIGN/PATIENTS: We assessed circulating adiponectin and AdipoR1/R2 mRNA expression in human skeletal muscle in a cross-sectional study of 140 subjects with normal or impaired glucose tolerance or type 2 diabetes. In the context of an interventional study, the same measurements were performed in 60 of these subjects (20/glucose tolerance group) before and after 4 wk of physical training. Finally, we measured these same variables in addition to protein levels of AMP kinase (AMPK), acetyl phosphorylated AMPK, coenzyme A carboxylase, phosphorylated coenzyme A carboxylase, and phosphatidylinositol 3-kinase in muscle before and after 3 h of intensive exercise in a subgroup of five subjects. SETTING: This study was performed at an academic clinical research center. RESULTS: Circulating adiponectin was negatively associated, whereas AdipoR1/R2 mRNA levels were positively associated with obesity, glucose and lipid levels, and insulin resistance. Physical training for 4 wk resulted in increased circulating adiponectin levels and AdipoR1/R2 mRNA expression in muscle. Exercise for 3 h increased AdipoR1/R2 mRNA expression as well as phosphorylation of AMPK and acetyl coenzyme A carboxylase in muscle, but had no effect on circulating adiponectin. CONCLUSIONS: Adiponectin, AdipoR1, and AdipoR2 are all associated with body composition, insulin sensitivity, and metabolic parameters. Physical training increases circulating adiponectin and mRNA expression of its receptors in muscle, which may mediate the improvement of insulin resistance and the metabolic syndrome in response to exercise.

Adiponectin↗

PubMed2006

Drug Insight: the role of leptin in human physiology and pathophysiology--emerging clinical applications.

Leptin is an adipocyte-secreted hormone with a key role in energy homeostasis. Studies in animal models, in humans with congenital complete leptin deficiency, and observational and interventional studies in humans with relative leptin deficiency (lower than normal leptin levels) have all indicated that leptin regulates multiple physiological functions, primarily in states of energy deficiency. This information led to proof-of-concept clinical trials involving leptin administration to individuals with relative or complete leptin deficiency. These conditions include congenital complete leptin deficiency, due to mutations in the leptin gene, and states of relative leptin deficiency including lipoatrophy and some forms of hypothalamic amenorrhea. Leptin, in replacement doses, normalizes neuroendocrine, metabolic and immune function in patients with these conditions, but further clinical studies are required to determine its long-term efficacy and safety. Management of leptin-deficient states with replacement doses of leptin holds promise as a therapeutic option. In addition, elucidation of the mechanisms underlying leptin resistance, which characterizes hyperleptinemic states such as human obesity and diabetes, might provide novel therapeutic targets for these prevalent clinical problems.

Animals↗

PubMed2006

Peptide YY levels are elevated after gastric bypass surgery.

OBJECTIVE: Mechanisms that promote effective and sustained weight loss in persons who have undergone Roux-en-Y gastric bypass surgery are incompletely understood but may be mediated, in part, by changes in appetite. Peptide YY (PYY) is a gut-derived hormone with anorectic properties. We sought to determine whether gastric bypass surgery alters PYY levels or response to glucose. RESEARCH METHODS AND PROCEDURES: PYY and ghrelin levels after a 75-gram oral glucose tolerance test were measured in 6 morbidly obese patients 1.5 +/- 0.7 (SE) years after gastric bypass compared with 5 lean and 12 obese controls. RESULTS: After substantial body weight loss (36.8 +/- 3.6%) induced by gastric bypass, the PYY response to an oral glucose tolerance test was significantly higher than in controls (p = 0.01). PYY increased approximately 10-fold after a 75-gram glucose load to a peak of 303.0 +/- 37.0 pg/mL at 30 minutes (p = 0.03) and remained significantly higher than fasting levels for all subsequent time-points. In contrast, PYY levels in obese and lean controls increased to a peak of approximately 2-fold, which was only borderline significant. Ghrelin levels decreased in a symmetric but opposite fashion to that of PYY. DISCUSSION: Gastric bypass results in a more robust PYY response to caloric intake, which, in conjunction with decreased ghrelin levels, may contribute to the sustained efficacy of this procedure. The findings provide further evidence for a role of gut-derived hormones in mediating appetite changes after gastric bypass and support further efforts to determine whether PYY(3-36) replacement could represent an effective therapy for obesity.

Anti-Obesity Agents↗

PubMed2006

Adherence to the Mediterranean dietary pattern is positively associated with plasma adiponectin concentrations in diabetic women.

BACKGROUND: Although the typical diet of the Mediterranean region has received much recognition over the past several years for its association with substantial health benefits, it remains unknown whether its favorable effects are mediated through changes in adiponectin concentrations. OBJECTIVE: The objective was to determine whether adherence to a Mediterranean-type diet is associated with higher plasma adiponectin concentrations. DESIGN: This study was a prospective and cross-sectional evaluation of plasma adiponectin concentrations and dietary data from 987 diabetic women from the Nurses' Health Study who had no history of cardiovascular disease at the time blood was drawn in 1990. RESULTS: Women who scored highest on a 9-point scale that measures adherence to a Mediterranean-type dietary pattern tended to be older, were less likely to be current smokers, had lower body mass indexes and waist circumferences, and had higher total energy intakes, physical activities, and plasma adiponectin concentrations than did women with the lowest scores. Median plasma adiponectin concentrations were 23% higher in women who most closely followed a Mediterranean-type diet than in low adherers after adjustment for age and energy intake (P < 0.01). Body composition, lifestyle, and medical history explained some, but not all, of the observed association between diet and adiponectin concentrations because high adherers tended to have greater adiponectin concentrations than did moderate or low adherers, even after adjustment for these variables. CONCLUSIONS: Our data suggest that, of the several components of the Mediterranean dietary pattern score, alcohol, nuts, and whole grains show the strongest association with adiponectin concentrations. Close adherence to a Mediterranean-type diet is associated with higher adiponectin concentrations.

Adiponectin↗

PubMed2006

Adiponectin: a link between obesity and cancer.

Adiponectin, an insulin-sensitising hormone produced by adipocytes, has direct antidiabetic, antiatherogenic, anti-inflammatory and antiangiogenic properties. Circulating adiponectin levels are lower in obesity, a disease state that is associated with certain malignancies. Recently, accumulating evidence suggests that adiponectin may have an important protective role in carcinogenesis. There is also evidence that at least some, if not most, cancer cell types express adiponectin receptors; thus adiponectin may act on tumour cells directly by binding and activating adiponectin receptors and downstream signalling pathways. Through its antiangiogenic properties, and also possibly through other mechanisms regulating cell proliferation discussed in this review, adiponectin may prove to be an effective novel anticancer agent. Large association and prospective studies to assess adiponectin levels in relation to risk from cancer, as well as mechanistic studies to prove adiponectin's role in the development of malignancies, and interventional trials to address potential roles of adiponectin in cancer pathogenesis and therapeutics are needed.

Adiponectin↗

PubMed2006

Adiponectin genetic variability, plasma adiponectin, and cardiovascular risk in patients with type 2 diabetes.

Adiponectin is an adipocyte-derived hormone that has shown anti-inflammatory and antiatherogenic effects. We assessed the associations of variants in the adiponectin gene (ADIPOQ) with circulating adiponectin levels and cardiovascular risk among women with type 2 diabetes. Of 989 diabetic women from the Nurses' Health Study, 285 developed cardiovascular disease (CVD) during follow-up through 2000. We genotyped five ADIPOQ polymorphisms in the CVD case and control subjects. A promoter polymorphism -11365C-->G was significantly associated with lower plasma adiponectin levels (P = 0.004). The homozygotes of allele -4034C were significantly associated with approximately 60% increased cardiovascular risk (odds ratio 1.62 [95% CI 1.07-2.45]). Adjustment for age, BMI, and other covariates did not appreciably change the associations. In addition, a common haplotype possessing allele +276T (CAATT) was associated with a significantly lower CVD risk than the most common haplotype (CAATG) (0.70 [0.50-0.98]). In our meta-analysis of 827 CVD case and 1,887 CVD-free control subjects, polymorphism +276G-->T was significantly associated with approximately 45% (20-62%) decreased CVD risk under a recessive inheritance mode in diabetic patients. In conclusion, ADIPOQ promoter polymorphism -11365C-->G was associated with plasma adiponectin levels, whereas polymorphisms -4034A-->C and +276G-->T were associated with CVD risk in diabetic patients.

Adiponectin↗

PubMed2006

The emerging role of leptin in humans.

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Recent advances in leptin physiology have revealed that the main role of this hormone in humans is to signal energy availability in energy-deficient states. Interventional studies in leptin deficient children and observational studies in normal girls and boys support a role for leptin as a permissive factor for the initiation of puberty in children. Moreover, recent "proof of concept" studies involving leptin administration to humans further support its critical role in regulating energy homeostasis, neuroendocrine and immune function as well as insulin resistance in states of energy/caloric deprivation. Leptin's potential role in the therapy of several disease states, including hypothalamic amenorrhea, anorexia nervosa and syndromes of insulin resistance is under intensive investigation.

Adolescent↗