HL-81K Sigma-AldrichHuman Leptin RIA

Weight loss therapy to improve health in obese older adults is controversial because it causes further bone loss. Therefore, it is recommended that weight loss therapy should include an intervention such as exercise training (ET) to minimize bone loss. The purpose of this study was to determine the independent and combined effects of weight loss and ET on bone metabolism in relation to bone mineral density (BMD) in obese older adults. One-hundred-seven older (age >65 years) obese (body mass index [BMI] ? 30 ?kg/m(2) ) adults were randomly assigned to a control group, diet group, exercise group, and diet-exercise group for 1 year. Body weight decreased in the diet (-9.6%) and diet-exercise (-9.4%) groups, not in the exercise (-1%) and control (-0.2%) groups (between-group p? < ?0.001). However, despite comparable weight loss, bone loss at the total hip was relatively less in the diet-exercise group (-1.1%) than in the diet group (-2.6%), whereas BMD increased in the exercise group (1.5%) (between-group p? <? 0.001). Serum C-terminal telopeptide (CTX) and osteocalcin concentrations increased in the diet group (31% and 24%, respectively), whereas they decreased in the exercise group (-13% and -15%, respectively) (between-group p ?<? 0.001). In contrast, similar to the control group, serum CTX and osteocalcin concentrations did not change in the diet-exercise group. Serum procollagen propeptide concentrations decreased in the exercise group (-15%) compared with the diet group (9%) (p? =? 0.04). Serum leptin and estradiol concentrations decreased in the diet (-25% and -15%, respectively) and diet-exercise (-38% and -13%, respectively) groups, not in the exercise and control groups (between-group p? =? 0.001). Multivariate analyses revealed that changes in lean body mass (?? =? 0.33), serum osteocalcin (?? =?-0.24), and one-repetition maximum (1-RM) strength (?? =? 0.23) were independent predictors of changes in hip BMD (all p? <? 0.05). In conclusion, the addition of ET to weight loss therapy among obese older adults prevents weight loss-induced increase in bone turnover and attenuates weight loss-induced reduction in hip BMD despite weight loss-induced decrease in bone-active hormones.

The human proteins ciliary neurotrophic factor (CNTF) and interleukin-6 (IL6) and their receptors share structural homology with leptin and its receptor. In addition, uncoupling protein-2 (UCP2) has been shown to participate the regulation of leptin on food intake. All three proteins are active in the hypothalamus. Experiments have shown that CNTF and IL6, like leptin, can influence body weight in humans and animals, while the effect of UCP2 is not consistent. In a Dutch general population (n=545) we investigated associations of CNTF (null G/A, rs1800169), IL6 (174 G/C, rs1800795) and UCP2 (A55V, rs660339 and del/ins) polymorphisms with weight gain using interaction graphs and logistic regression analysis. The average follow-up period was 6.9 years. Individuals who gained weight (n=264) were compared with individuals who remained stable in weight (n=281). In women the CNTF polymorphism (odds ratio (OR)=2.15, 95%CI: 1.27-3.64, p=0.004) and in men the IL6 polymorphism by itself (OR=2.26, 95%CI: 1.08-4.75, p=0.03) or in combination with the CNTF polymorphism, were associated with weight gain. Furthermore, CNTF and IL6 polymorphisms in interaction with UCP2 polymorphisms had similar strong effects on weight gain in women and men, respectively. All observed effects were statistically shown to be independent of serum leptin level. These results are incorporated in a biological model for weight regulation with upstream effects of CNTF and IL6, and downstream effects of UCP2. The results of this study suggest a novel mechanism for weight regulation that is active in both women and men, but strongly influenced by sex.

CONTEXT: It is uncertain how between-meal variations in energy availability and physiological changes in ghrelin, leptin, and insulin affect appetite. Objective: The aim of the study was to examine the influence on human appetite of the meal size and its nutrient content or changes in energy availability and concentrations of ghrelin, leptin, and insulin. DESIGN: We conducted a crossover study manipulating meal size and energy availability through exercise energy expenditure and iv nutrient replacement (TPN). Setting: The study was performed at a Clinical Research Center. PARTICIPANTS: Ten healthy postmenopausal women (age, 59.7 +/- 1.5 yr; mean body mass index, 26 kg/m(2)) were studied. Interventions: We conducted trials based on different morning meal size (418 vs. 2090 KJ), presence or absence of exercise energy expenditure (2273 to 2361 KJ), energy replacement by TPN (1521 to 1538 KJ), and a midday ad libitum meal. Main Outcome Measures: Changes in hunger, fullness, midday ad libitum food consumption, and concentrations of ghrelin, leptin, insulin, and metabolic fuels were measured. We also performed midday meal tests for the presence of caloric compensation. RESULTS: Appetite was influenced by the size and energy content of the meals, but not by variation in energy availability which also did not trigger consummatory compensation. Exercise reduced hunger and increased fullness. Ghrelin, leptin, and insulin responded to changes in energy availability but not to meal size. Appetite was unaffected by physiological changes in ghrelin, leptin, or insulin. CONCLUSIONS: During rest, appetite is influenced by the size and energy content of meals, but it bears no homeostatic relationship to between-meal changes in energy availability due to small meals, exercise, or TPN, or concentrations of ghrelin, leptin, and insulin.

BACKGROUND: Although weight loss and exercise ameliorates frailty and improves cardiac risk factors in obese older adults, the long-term effect of lifestyle intervention on bone metabolism and mass is unknown. OBJECTIVE: The objective was to evaluate the effects of diet-induced weight loss in conjunction with exercise on bone metabolism and mass in obese older adults. DESIGN AND SETTING: We conducted a one-year randomized, controlled clinical trial in a university-based research center. PARTICIPANTS: Twenty-seven frail, obese (body mass index = 39 +/- 5 kg/m(2)), older (age 70 +/- 5 yr) adults participated in the study. Intervention: Participants were randomly assigned to diet and exercise (treatment group; n = 17) or no therapy (control group; n = 10). OUTCOME MEASURES: Body weight decreased in the treatment group but not in the control group (-10 +/- 2 vs. +1 +/- 1%, P 0.001). Compared with the control group, the treatment group had greater changes in bone mass, bone markers, and hormones, including 1) bone mineral density (BMD) in total hip (0.1 +/- 2.1 vs. -2.4 +/- 2.5%), trochanter (0.2 +/- 3.3 vs. -3.3 +/- 3.1%), and intertrochanter (0.3 +/- 2.7 vs. -2.7 +/- .3.0%); 2) C-terminal telopeptide (12 +/- 35 vs. 101 +/- 79%) and osteocalcin (-5 +/- 15 vs. 66 +/- 61%); and 3) leptin (2 +/- 12 vs. -30 +/- 25%) and estradiol (0.1 +/- 14% vs. -14 +/- 21%) (all P 0.05). Changes in weight (r = 0.55), bone markers (r = -0.54), and leptin (r = 0.61) correlated with changes in hip BMD (all P 0.05). CONCLUSION: Weight loss, even when combined with exercise, decreases hip BMD in obese older adults. It is not known whether the beneficial effects of weight loss and exercise on physical function lower the overall risk of falls and fractures, despite the decline in hip BMD.

Familial combined hyperlipidaemia (FCHL) is a complex genetic disorder conferring high risk of premature atherosclerosis, characterized by high cholesterol and/or triglyceride, low high density lipoprotein (HDL) cholesterol and insulin resistance. We examined whether pioglitazone, added to conventional lipid-lowering therapy, would favourably affect metabolic parameters and alter body fat content. We undertook a randomized, double blind, placebo-controlled study in 22 male patients with FCHL treated with pioglitazone or matching placebo 30 mg daily for 4 weeks, increasing to 45 mg for 12 weeks. Magnetic resonance imaging and proton magnetic resonance spectroscopy were performed to measure adipose tissue (AT) body content as well as intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL) at baseline and after treatment. Significantly improved in the pioglitazone group were: triglyceride/HDL (atherogenic index of plasma) -32.3% (p=0.002), plasma glucose -4.4% (p=0.03), alanine-aminotransferase (ALT) -7.7% (p=0.005) and adiponectin 130.1% (p=0.001). Pioglitazone treatment resulted in a significant increase in total (5.3%, p=0.02) and subcutaneous (7.1%, p=0.003) adipose tissue as well as in soleus-IMCL levels (47.4%, p=0.02) without alteration in intra-abdominal AT or IHCL. Changes in ALT and AST and IHCL were strongly correlated (r=0.72, p0.01; r=.0.86, p0.01, respectively). In patients with FCHL on conventional lipid-lowering therapy, the addition of pioglitazone acts favourably on several metabolic parameters.

The goal of this study was to determine whether short-term fasting changes in urinary biomarkers related to oxidative stress: malondialdehyde (MDA), 8-isoprostaglandin F2alpha (8-isoPGF), 8-hydroxydeoxy-guanosine (8-OHdG) and 1,N6-ethenodeoxyadenosine (epsilondA) among female volunteers participating in the short-term fasting program in South Korea. The study subjects were 52 healthy women (mean age 28, range 15-48 years old) who provided urine samples both before and after the fasting program (average 7.2, range: 3-11 days). Urinary MDA was measured by HPLC-UV and epsilondA levels were measured by immuno-affinity purification followed by HPLC-fluorescence detection. Urinary 8-OHdG and 8-isoPGF concentrations were determined by ELISA. Plasma leptin levels were also measured by radioimmunoassay. Information on demographic characteristics, personal habits (smoking and alcohol consumption) and previous medical history were collected by a self-administered questionnaire. Percent loss of body weight (average 6.3%, 4.28 +/- 0.25 kg) was significantly correlated with fasting duration (r = 0.70, n = 52, P 0.01). The plasma leptin levels after fasting (5.89 +/- 1.10 ng/ml) were significantly lower than before fasting (6.91 +/- 1.13 ng/ml) (n = 27, P = 0.05). Urinary MDA levels after fasting (0.18 +/- 1.10 mg/g creatinine) were significantly lower than before fasting (0.37 +/- 1.11) (n = 51, P 0.01). Urinary 8-isoPGF also were significantly reduced after fasting (n = 47, P 0.01). However, there was no significant difference in 8-OHdG or epsilondA. There was a statistically significant correlation between % change of urinary MDA level with % change of 8-isoPGF level (partial correlation coefficient r = 0.57, n = 46, P = 0.01). The correlations between % change of 8-OHdG and plasma leptin was also significant (partial correlation coefficient r = 0.51, n = 27, P = 0.02). Our results demonstrate that the short-term fasting reduces lipid peroxidation products but does not affect oxidative stress-induced DNA damage.

BACKGROUND: Bone loss often accompanies weight loss induced by caloric restriction (CR), but whether bone loss accompanies similar weight loss induced by exercise (EX) is unknown. We tested the hypothesis that EX-induced weight loss is associated with less bone loss compared with CR-induced weight loss. METHODS: Forty-eight adults (30 women; 18 men; mean +/- SD age, 57 +/- 3 years; and mean +/- SD body mass index, 27 +/- 2 kg/m2) were randomized to 1 of 3 groups for 1 year: CR group (n = 19), regular EX group (n = 19), or a healthy lifestyle (HL) control group (n = 10). Primary outcome measure was change in hip and spine bone mineral density (BMD). Secondary outcomes were bone markers and hormones. RESULTS: Body weight decreased similarly in the CR and EX groups (10.7% +/- 6.3% [-8.2 +/- 4.8 kg] vs 8.4% +/- 6.3% [-6.7 +/- 5.6 kg]; P = .21), whereas weight did not change in the HL group (-1.2% +/- 2.5% [-0.9 +/- 2.0 kg]). Compared with the HL group, the CR group had decreases in BMD at the total hip (-2.2% +/- 3.1% vs 1.2% +/- 2.1%; P = .02) and intertrochanter (-2.1% +/- 3.4% vs 1.7 +/- 2.8%; P = .03). The CR group had a decrease in spine BMD (-2.2% +/- 3.3%; P = .009). Despite weight loss, the EX group did not demonstrate a decrease in BMD at any site. Body weight changes correlated with BMD changes in the CR (R = 0.61; P = .007) but not in the EX group. Bone turnover increased in both CR and EX groups. CONCLUSIONS: CR-induced weight loss, but not EX-induced weight loss, is associated with reductions in BMD at clinically important sites of fracture. These data suggest that EX should be an important component of a weight loss program to offset adverse effects of CR on bone.

AIM: The tryptophan to arginine change in position 64 (Trp64Arg) polymorphism of the beta3-adrenergic receptor (beta3AR) gene has been associated with an increased prevalence of obesity, insulin resistance and type 2 diabetes. In this, decreased rates of energy expenditure and impaired insulin secretion could play a role. METHODS: In 10 male twin pairs discordant for the Trp64Arg polymorphism, we examined insulin response to glucose by an oral glucose tolerance test (OGTT), a frequently sampled intravenous glucose tolerance test (FSIGT), body composition by the bioimpedance method, dual-energy X-ray absorptiometry scanning and energy expenditure by indirect and direct calorimetry. RESULTS: Twins heterozygous for the Trp64Arg polymorphism showed significantly lower fat mass independent of the method used, and significantly lower fasting insulin and glucose concentrations compared with their homozygous wild-type co-twins. Correspondingly, insulin resistance and insulin secretion determined by homeostasis model assessment were significantly lower in twins carrying the Trp64Arg polymorphism. However, there were no significant differences in adiponectin levels, insulinogenic index assessed by OGTT, or insulin sensitivity, acute insulin response to glucose, glucose effectiveness or insulin disposition index assessed by minimal modelling of the FSIGT. Furthermore, there were no differences in sleeping, resting or post-prandial energy expenditure. CONCLUSIONS: In male twins with a high similarity in genetic and environmental background, the Trp64Arg polymorphism of the beta3AR gene is associated with lower fat mass, fasting insulin levels and an appropriate insulin response to glucose. Thus, heterozygosity for the Trp64Arg variant is unlikely to increase the risk of obesity, insulin resistance or type 2 diabetes.

Haptoglobin (Hp) is a glycoprotein involved in the acute phase response to inflammation. Our previous findings indicate that Hp mRNA and protein are present in the adipose tissue of rodents and that Hp gene expression is up-regulated in obese models. The aim of the present study was to establish whether Hp could be considered a marker of obesity in humans. In 312 subjects, serum Hp was correlated directly with body mass index (BMI), leptin, C-reactive protein (CRP), and age. In a multivariate stepwise regression analysis, BMI and CRP were independent determinants of serum Hp in females, with BMI having the strongest effect. CRP and age were independent determinants of serum Hp in males, although explaining only a modest percentage of the total variability. Serum Hp was positively associated with body fat, as assessed by dual-energy x-ray absorptiometry, both in female and in male groups. The level of significance improved when serum Hp was analyzed against fat mass adjusted for lean mass. Finally, Northern and Western blot analyses performed in biopsies of sc abdominal fat from 20 obese individuals showed the presence of Hp mRNA and protein in the human adipose tissue. In conclusion, serum Hp constitutes a novel marker of adiposity in humans, and the adipose tissue likely contributes to determine its levels.

OBJECTIVE: The purpose of this study was to determine whether maternal serum inhibin A and leptin concentrations changed in the first trimester of pregnancy in patients in whom severe preeclampsia subsequently developed. STUDY DESIGN: Blood samples were collected prospectively from patients during the first trimester of prenatal care. Patients in whom severe preeclampsia with no evidence of glucose intolerance or gestational diabetes mellitus subsequently developed were identified (study group, 30 patients) and matched with control subjects in a 1:2 ratio (control group, 60 patients). Inhibin A and leptin concentrations were determined in these first-trimester serum samples for both the study and control groups. RESULTS: Leptin levels were correlated highly with body mass index in both groups but were not correlated with the subsequent onset of preeclampsia. Serum inhibin A concentrations were significantly higher in women in whom preeclampsia subsequently developed than in women in whom it did not. With a specific cutoff value, the estimated odds for severe preeclampsia were almost five times higher in women with high inhibin A concentrations than in women with normal levels (odds ratio, 4.93; 95% CI, 1.83, 13.28). CONCLUSION: High serum inhibin A levels in the first trimester of pregnancy could be used as an early risk marker for preeclampsia.