Improved leptin sensitivity and increased soluble leptin receptor concentrations may underlie the additive effects of combining PYY [, , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , ] and exendin-4 on body weight lowering in diet-induced obese mice.

Objective: Co-treatment with long acting PYY and the GLP-1 receptor agonists has potential as an efficient obesity treatment. This study investigates whether the mechanisms behind additive reduction of food intake and weight loss depends on complementary effects in brain areas regulating food intake and if restoration of leptin sensitivity is involved. Methods: Diet-induced obese (DIO) mice were co-treated with PYY(3-36) and exendin-4 (Ex4, GLP-1R agonist) for 14 days using minipumps. Leptin responsiveness was evaluated by measuring food intake and body weight after leptin injection, and gene expression profile was investigated in various of brain regions and liver. Results: We show that weight loss associated with co-treatment of PYY(3-36) and Ex4 and Ex4 mono-treatment in DIO mice increased expression of several genes in area postrema (AP) known to be involved in appetite regulation and Cart, Pdyn, Bdnf and Klb were synergistically upregulated by the co-treatment. The upregulations were independent of weight loss, as shown by inclusion of a weight matched control. Moreover, PYY(3-36) and Ex4 co-treatment resulted in synergistically upregulated plasma concentrations of soluble leptin receptor (SLR) and improved sensitivity to exogenous leptin demonstrated by food intake lowering. Conclusion: The study results suggest that synergistic upregulation of appetite-regulating genes in AP and improved leptin sensitivity are important mediators for the additive weight loss resulting from PYY and Ex4 co-treatment.

The causal impact of gut microbiota on circulating adipokine concentrations: a two-sample Mendelian randomization study.

PURPOSE: Evidence from previous experimental and observational research demonstrates that the gut microbiota is related to circulating adipokine concentrations. Nevertheless, the debate as to whether gut microbiome composition causally influences circulating adipokine concentrations remains unresolved. This study aimed to take an essential step in elucidating this issue. METHODS: We used two-sample Mendelian randomization (MR) to causally analyze genetic variation statistics for gut microbiota and four adipokines (including adiponectin, leptin, soluble leptin receptor [sOB-R], and plasminogen activator inhibitor-1 [PAI-1]) from large-scale genome-wide association studies (GWAS) datasets. A range of sensitivity analyses was also conducted to assess the stability and reliability of the results. RESULTS: The composite results of the MR and sensitivity analyses revealed 22 significant causal associations. In particular, there is a suggestive causality between the family Clostridiaceae1 (IVW: ß = 0.063, P = 0.034), the genus Butyrivibrio (IVW: ß = 0.029, P = 0.031), and the family Alcaligenaceae (IVW: ß=-0.070, P = 0.014) and adiponectin. Stronger causal effects with leptin were found for the genus Enterorhabdus (IVW: ß=-0.073, P = 0.038) and the genus Lachnospiraceae (NK4A136 group) (IVW: ß=-0.076, P = 0.01). Eight candidate bacterial groups were found to be associated with sOB-R, with the phylum Firmicutes (IVW: ß = 0.235, P = 0.03) and the order Clostridiales (IVW: ß = 0.267, P = 0.028) being of more interest. In addition, the genus Roseburia (IVW: ß = 0.953, P = 0.022) and the order Lactobacillales (IVW: ß=-0.806, P = 0.042) were suggestive of an association with PAI-1. CONCLUSION: This study reveals a causal relationship between the gut microbiota and circulating adipokines and may help to offer novel insights into the prevention of abnormal concentrations of circulating adipokines and obesity-related diseases.

Inter-organ insulin-leptin signal crosstalk from the liver enhances survival during food shortages.

Crosstalk among organs/tissues is important for regulating systemic metabolism. Here, we demonstrate inter-organ crosstalk between hepatic insulin and hypothalamic leptin actions, which maintains survival during food shortages. In inducible liver insulin receptor knockout mice, body weight is increased with hyperphagia and decreased energy expenditure, accompanied by increased circulating leptin receptor (LepR) and decreased hypothalamic leptin actions. Additional hepatic LepR deficiency reverses these metabolic phenotypes. Thus, decreased hepatic insulin action suppresses hypothalamic leptin action with increased liver-derived soluble LepR. Human hepatic and circulating LepR levels also correlate negatively with hepatic insulin action indices. In mice, food restriction decreases hepatic insulin action and energy expenditure with increased circulating LepR. Hepatic LepR deficiency increases mortality with enhanced energy expenditure during food restriction. The liver translates metabolic cues regarding energy-deficient status, which is reflected by decreased hepatic insulin action, into soluble LepR, thereby suppressing energy dissipation and assuring survival during food shortages.

Insulin and Body Mass Index Decrease Serum Soluble Leptin Receptor Levels in Humans.

CONTEXT: Serum soluble leptin receptor (sOb-R) may protect against future type 2 diabetes or serve as a marker for protective features, but how sOb-R is regulated is largely unknown. OBJECTIVE: This work aimed to test how serum sOb-R is influenced by glucose, insulin, body fat, body mass index (BMI), food intake, and physical activity. METHODS: We performed an epidemiological triangulation combining cross-sectional, interventional, and Mendelian randomization study designs. In 5 independent clinical studies (n = 24-823), sOb-R was quantified in serum or plasma by commercial enzyme-linked immunosorbent assay kits using monoclonal antibodies. We performed mixed-model regression and 2-sample Mendelian randomization. RESULTS: In pooled, cross-sectional data, leveling by study, sOb-R was associated inversely with BMI (ß [95% CI] -0.19 [-0.21 to -0.17]), body fat (-0.12 [-0.14 to -0.10), and fasting C-peptide (-2.04 [-2.46 to -1.62]). sOb-R decreased in response to acute hyperinsulinemia during euglycemic glucose clamp in 2 independent clinical studies (-0.5 [-0.7 to -0.4] and -0.5 [-0.6 to -0.3]), and immediately increased in response to intensive exercise (0.18 [0.04 to 0.31]) and food intake (0.20 [0.06 to 0.34]). In 2-sample Mendelian randomization, higher fasting insulin and higher BMI were causally linked to lower sOb-R levels (inverse variance weighted, -1.72 [-2.86 to -0.58], and -0.20 [-0.36 to -0.04], respectively). The relationship between hyperglycemia and sOb-R was inconsistent in cross-sectional studies and nonsignificant in intervention studies, and 2-sample Mendelian randomization suggested no causal effect of fasting glucose on sOb-R. CONCLUSION: BMI and insulin both causally decreased serum sOb-R levels. Conversely, intensive exercise and food intake acutely increased sOb-R. Our results suggest that sOb-R is involved in short-term regulation of leptin signaling, either directly or indirectly, and that hyperinsulinemia may reduce leptin signaling.

[Population-based Study of the Effects of Adiponectin, Leptin and Soluble Leptin Receptor on Risks for Breast Cancer].

OBJECTIVE: To explore the individual or combined effects of adiponectin, leptin, and soluble leptin receptor (sOB-R) on risks for premenopausal and postmenopausal breast cancer, and to provide evidence for revealing the molecular mechanism between obesity and breast cancer. METHODS: 469 newly-diagnosed breast cancer cases were sequentially recruited for the study and 469 age-frequency-matched healthy women were enrolled as the controls over the same period of time. The participant baseline information was collected with questionnaires, and plasmic levels of adiponectin, leptin and sOB-R were checked with ELISA. Multivariate unconditional logistic regression was conducted and the analyses were further stratified according to waist-to-hip ratio (WHR) and body mass index (BMI) to explore the effect of the indicators on the risks for premenopausal and postmenopausal breast cancer. RESULTS: A total of 480 premenopausal and 458 postmenopausal women were included in the study. Among the premenopausal subjects, 249 were breast cancer patients and 231 were controls. The median BMI was 22.9 kg/m 2and 23.2 kg /m 2, respectively, and the median WHR was 0.80 and 0.83, respectively. Among the postmenopausal subjects, 220 were breast cancer patients and 238 were controls. The median BMI was 23.4 kg/m 2 and 23.7 kg/m 2, respectively, and the median WHR was 0.82 and 0.86, respectively. Multivariate logistic regression analysis showed that before and after model adjustment, the increase in sOB-R and adiponectin levels was correlated to reduced risks of premenopausal and postmenopausal breast cancer ( P<0.05), while the increase in the leptin/sOB-R ratio (also known as free leptin index, FLI) and leptin/adiponectin (L/A) ratio was only correlated to increased risks of postmenopausal breast cancer. After further stratification by WHR and BMI, the association between adiponectin, FLI and postmenopausal breast cancer remained statistically significant in all subgroups. Among subjects with normal-BMI central obesity (18.5 kg/m 2≤BMI<24 kg/m 2 & WHR≥0.85) , higher L/A ratio was associated with an increased risk of postmenopausal breast cancer. No clear association between leptin and premenopausal and risks for postmenopausal breast cancer was found in the study. CONCLUSION: Postmenopausal women with decreased levels of sOB-R and adiponectin, and increased FLI and L/A, and premenopausal women with decreased levels of sOB-R and adiponectin were found to be at high risks for breast cancer.

Body mass index and serum levels of soluble leptin receptor are sex-specifically related to alcohol binge drinking behavior.

OBJECTIVE: Binge drinking is a highly prevalent behavior in adolescents and young adults and a risk factor to develop alcohol use disorder. Body mass index (BMI) and blood levels of leptin peptide and its soluble receptor have been implicated in alcohol use disorder; however, their role in binge drinking remains to be investigated. METHOD: We studied associations of BMI, serum levels of soluble leptin receptor (ObRe) and leptin as well as the free leptin index with binge drinking in 93 male and 99 female young adults. RESULTS: In men, binge drinkers showed significantly higher BMI (kg/m2) than non-binge drinkers (23.67 vs. 22.08) and higher BMI correlated significantly with more severe binge drinking episodes (ρ = 0.251). In women, we found significantly higher ObRe (ng/ml) / BMI (kg/m2) values in binge drinkers than in non-binge drinkers (0.52 vs. 0.44) and ObRe/BMI values correlated significantly with more severe binge drinking episodes (ρ = 0.210). CONCLUSION: This study confirms that higher BMI associates with binge drinking in men and shows for the first time a role of ObRe/BMI in binge drinking in women. Our data emphasize the importance of further research in the field of metabolic markers and implications in neurobiological processes of binge drinking.

Obesity Affects HDL Metabolism, Composition and Subclass Distribution.

BACKGROUND: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. RESULTS: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. CONCLUSIONS: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.

Circulating adipokine concentrations and risk of five obesity-related cancers: A Mendelian randomization study.

Obesity is considered a chronic inflammatory state characterized by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines (adiponectin, leptin, soluble leptin receptor [sOB-R] and plasminogen activator inhibitor-1 [PAI-1]) with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma [RCC], ovarian and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin and 4 for both sOB-R and PAI-1 (P value for inclusion<5 × 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer (odds ratio per 1 µg/mL increment in adiponectin concentration: 0.90 [95% confidence interval = 0.84-0.97]; P = .01); but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, RCC, ovarian cancer and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R and PAI-1 concentrations on the development of five obesity-related cancers.

Disordered leptin and ghrelin bioactivity in adolescent idiopathic scoliosis (AIS): a systematic review and meta-analysis.

BACKGROUND: Adolescents with scoliosis consistently demonstrate lower body weight, lean muscle mass, and bone mineral density than healthy adolescent counterparts. Recent studies have focused on understanding how leptin and ghrelin signaling may play a role in adolescent idiopathic scoliosis (AIS). In our current study, we aim to evaluate the serum levels of leptin, soluble leptin receptor (sOB-R), and ghrelin in AIS patients through systematic review and meta-analysis. METHODS: We conducted our systematic review by searching the keywords in online databases including PubMed, Embase, Cochrane, Elsevier, Springer, and Web of Science from the time of database inception to January 2020. Inclusion criteria were studies that measure leptin, soluble leptin receptor (sOB-R), and ghrelin levels in AIS patients. Selection of studies, assessment of study quality, and data extraction were performed by two reviewers independently. Then, data was analyzed to calculate the mean difference and 95% confidence interval (CI). RESULTS: Seven studies concerning leptin/sOB-R and three studies concerning ghrelin were qualified for meta-analysis (one study concerning both leptin and ghrelin). Serum leptin of patients with AIS were significantly lower when compared with healthy controls, with the weighted mean difference (WMD) of - 0.95 (95% CI - 1.43 to - 0.48, p < 0.0001) after reducing the heterogeneity using six studies for meta-analysis, while sOB-R and ghrelin level was significantly higher in AIS group when compared with control group, with the WMD of 2.64 (95% CI 1.60 to 3.67, p < 0.001) and 1.42 (95% CI 0.48 to 2.35, p = 0.003), respectively. CONCLUSION: Our current meta-analysis showed that serum level of leptin in AIS patients was significantly lower when compared with control subjects, while serum sOB-R and ghrelin levels were significantly higher in AIS patients. More clinical studies are still required to further validate the predictive value of leptin or ghrelin for the curve progression for AIS patients.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary Cross-Sectional Study.

PURPOSE: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children. METHODS: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5-9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI. RESULTS: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak. CONCLUSION: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

Serum lipids, leptin, and soluble leptin receptor in alcohol dependence: A cross-sectional and longitudinal study.

OBJECTIVE: Alcohol dependence affects metabolic processes. Further research is needed to apply this knowledge clinically. In this study, possible differences in serum lipids and/or leptin activities between alcohol-dependent in-patients and healthy controls and possible associations with alcohol-related blood parameters and with prospective outcomes in alcohol dependence were assessed sex-specifically. METHOD: We measured and compared (median) serum lipids (triglycerides and total, HDL, and LDL cholesterol) and leptin activities (leptin, soluble leptin receptor [ObRe], and free leptin index) in 200 (males 56.5 %) early-abstinent alcohol-dependent in-patients and 240 (males 55.4 %) healthy controls and assessed alcohol-related readmissions during a 24 -month post-inclusion period. RESULTS: Male patients showed higher HDL cholesterol (61 versus 48 mg/dl), lower LDL/HDL ratios (2.06 versus 3.04), and lower free leptin index (0.30 versus 0.59) at study inclusion compared to healthy controls. In patients, ObRe levels were higher than in controls and decreased from inclusion to the second study-visit (at median 5 days later; males: 16.7-13.8 versus 11.0 ng/ml; females: 17.0-13.4 versus 12.1 ng/ml). The free leptin index increased between the two time points in females (0.80 versus 1.20). Lipids and leptin activities correlated with carbohydrate-deficient transferrin levels and liver enzyme activities. None of the serum parameters were significantly associated with alcohol-related readmissions. CONCLUSION: Our data support that serum lipid levels and leptin activities are involved in alcohol dependence. The parameters appear as possible indirect biomarkers for alcohol dependence.

Determinants of Circulating Soluble Leptin Receptor and Free Leptin Index in Indonesian Pre-Pubertal Obese Male Children: A Preliminary Cross-Sectional Study / 대한소아소화기영양학회지

PURPOSE: This study aimed to investigate the clinical and metabolic determinants of circulating soluble leptin receptor (CSLR) and free leptin index (FLI) in pre-pubertal obese male children.METHODS: We conducted a preliminary cross-sectional study at three tertiary hospitals and one public primary school. Eighty obese male children without growth and developmental abnormalities aged 5–9 years were recruited. In these children, obesity was solely caused by excessive food intake, and not by acute illness, medications, endocrine abnormalities, or any syndrome. Body mass index (BMI), body fat mass, carbohydrate intake, fat intake, high density lipoprotein cholesterol level, low density lipoprotein cholesterol level, triglyceride level, and Homeostatic Model Assessment for Insulin Resistance are the potential determinants for leptin regulation, which is represented by CSLR level and FLI.RESULTS: Carbohydrate was the main source of energy. BMI and body fat mass had negative weak correlation with CSLR and positive weak correlation with FLI. Furthermore, carbohydrate intake was found to be independently associated with CSLR based on the results of the multiple linear regression analysis. Following an increase in carbohydrate intake, CSLR level decreased progressively without any negative peak.CONCLUSION: Leptin regulation in prepubertal obese male children is associated with body composition and dietary intake. Carbohydrate intake is useful for predicting CSLR. Lipid profiles and insulin resistance are not related to both CSLR and FLI. Treatment and prevention of leptin resistance in obese children should focus on reducing BMI, fat mass, and carbohydrate intake.

Cortisol, leptin and free leptin index (FLI) in newborns in the first days of life and their importance for body weight programming.

BACKGROUND: Birth weight and leptin seem to be the factors responsible for early programming of body weight in later life. A marker for leptin action is free leptin index (FLI), which depends on soluble leptin receptor (Ob-Re) (FLI = leptin/Ob-Re). In the present article, we suggest that FLI is modulated partly by cortisol variations observed in newborns in the first days of life and is connected with their postnatal weight loss. METHODS: The study group consisted of 44 full-term newborns. Leptin, cortisol and Ob-Re concentrations were determined in the umbilical cord blood (UCB) and in the newborns' blood (NB) on the fourth day of life, free leptin index (FLI = leptin/Ob-Re) was calculated. Correlations between the assessed parameters and the somatic features of the newborns were examined. RESULTS: Birth weight, length and chest circumference of newborns were positively correlated with leptin concentration in the UCB but not with FLI in the UCB. Cortisol and leptin concentrations, as well as FLI values declined concomitantly with body weight, and were lower on the fourth day of life than on the first one; however, Ob-Re concentration increased (p < 0.0001). There was a positive correlation between the newborns' birth weight loss percentage evaluated on the fourth day of life and FLI in newborns (R = 0.39; p < 0.01). Positive correlations between cortisol and Ob-Re in UCB (R = 0.35; p < 0.02) and in NB (R = 0.36; p < 0.01), as well as a negative correlation between cortisol and FLI (R = -0.32; p < 0.03) in NB were noted. CONCLUSIONS: Our data suggest a possible relationship between cortisol and a soluble leptin receptor (Ob-Re), which changes free leptin index (FLI) and is connected with birth weight loss in newborns. Whether these observations are important for programming of future body weight of children requires further research.

Effects of Metformin Treatment on Soluble Leptin Receptor Levels in Women with Polycystic Ovary Syndrome.

The effects of metformin treatment on soluble leptin receptor (sOB-R) levels in women with polycystic ovary syndrome (PCOS) were investigated. This prospective and open-label study was conducted by the Department of Obstetrics & Gynecology at Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, China. Fifty-five women with PCOS and insulin resistance (IR) were treated with metformin for 6 months. According to body mass index (BMI), the patients were divided into two groups: lean PCOS group (BMI <23 kg/m2, n=34) and overweight or obese PCOS group (BMI ≥23 kg/m2, n=21). Before and after treatment, serum luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone (T), androstenedione (A), dehydroepiandrosterone sulfate (DHEAS), insulin and sOB-R levels were determined. Thirty-one BMI-matched ovulatory women served as controls. The results showed: (1) The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), androgen levels and hirsutism scores were higher, and sOB-R levels were lower in PCOS groups than in control group. A subgroup analysis of lean and overweight or obese PCOS patients revealed there was significant difference in sOB-R level between lean PCOS group and overweight or obese PCOS group. There were no significant differences in anthropometric parameters between lean PCOS patients and BMI-matched controls. However, sOB-R level was significantly lower in lean PCOS women than in controls. (2) There was no correlation between sOB-R level and BMI, waist and hip circumference, total testosterone, androstendione, DHEAS, LH or hirsutism scores in PCOS patients, but there was a significant negative correlation between sOB-R and HOMA-IR. (3) After treatment with metformin for 6 months, serum insulin levels decreased, and sOB-R levels increased significantly (P<0.01). It was suggested that considering low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance. It is likely that reduction of hyperinsulinemia produced by metformin effectively improves the sOB-R levels in PCOS.

Leptin resistance: underlying mechanisms and diagnosis.

Leptin and its receptors have been identified as key regulators of body weight and energy homeostasis. A decrease in tissue sensitivity to leptin leads to the development of obesity and metabolic disorders, such as insulin resistance and dyslipidemia. Mechanisms underlying the development of leptin resistance include mutations in the genes encoding leptin and its receptors, as well as proteins involved in self-regulation of leptin synthesis and blood-brain barrier permeability. Leptin resistance encompasses a complex pathophysiological phenomenon with a number of potential research lines. In this review, we analyze the existing data on the methods used to diagnose leptin resistance.

[Acupuncture Treatment Reduces Body Weight Possibly by Down-regulating Insulin and Leptin Resistance, and Up-regulating Soluble Leptin Receptor Level in Prediabetic Patients].

OBJECTIVE: To observe the effect of acupuncture of Feishu (BL 13), Pishu (BL 20), etc. on body weight, blood lipid, leptin (LP) and soluble leptin receptor (sOB-R) levels in prediabetic patients, so as to explore its mechanisms underlying treatment and prevention of prediabetes. METHODS: A total of 100 prediabetic patients were randomly assigned to medication (Metformin) group (n＝35), acupuncture group (n＝35) and simple lifestyle intervention group (n＝30) with random number table method. All the patients of the 3 groups were treated with lifestyle intervention (reasonable diet and moderate physical exercise) and ordered to stop administration of any hypoglycemic drugs during the treatment period. Bilateral Feishu (BL 13), Pishu (BL 20), Weishu (BL 21), Shenshu (BL 23), Zusanli (ST 36) and Sanyinjiao (SP 6) were punctured with filiform needles which were manipulated by lifting, thrusting and twirling repeatedly for about 2 min every 5 min during 30 minutes' needle retaining. The acupuncture treatment was conducted once every other day for 12 weeks. Patients of the medication group were ordered to orally take Metformin tablets (0.5 g/time, twice a day) for continuous 12 weeks. Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), 2 h-postprandial blood glucose (2 h-PBG), fasting blood glucose (FBG), glycosyla-ted hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), fasting insulin (FINS), serum LP and sOB-R levels were measured before and after the treatment. RESULTS: After the treatment, the BMI in the acupuncture group, and BMI, WC and WHR in the medication group were significantly decreased relevant to their own pre-treatment in each group (P<0.05, P<0.01). Following the treatment, the levels of FBG, 2 h-PBG, HbA1C, TC, TG, FINS, HOMA-IR and LP in both acupuncture and medication groups, and FBG in the simple lifestyle intervention group were significantly decreased in comparison with their own pre-treatment in each group (P<0.01, P<0.05), and the levels of FBG, 2 h-PBG, HbA1C, TC and TG, HOMA-IR and LP in both acupuncture and medication groups were all considerably lower than those of the simple lifestyle intervention group (P<0.01，P<0.05). The level of FINS in the medication group was significantly lower than that of the simple lifestyle intervention group (P<0.05). Additionally, following the treatment, serum sOB-R contents in both acupuncture and medication groups were obviously increased compared with their own pre-treatment in each group and also relevant to the simple lifestyle intervention group (P<0.01). No significant changes were found in the simple lifestyle intervention group in all the above-mentioned blood indexes except FBG (P>0.05). CONCLUSION: Acupuncture can induce body weight loss, down-regulate FINS, insulin resistance and LP resistance, and up-regulate sOB-R content in prediabetic patients, displaying a positive role in the treatment of prediabetes.

Serum leptin and leptin resistance correlations with NAFLD in patients with type 2 diabetes.

AIMS: Leptin/leptin resistance has been suggested to play a role in nonalcoholic fatty liver disease (NAFLD), and therefore we investigated the correlation of leptin/leptin-receptor system with markers of hepatic steatosis (HS) and fibrosis (HF) in patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In 159 T2D subjects with disease duration of 6.0 (0.0-27.0) years, HS was evaluated by semi-quantitative ultrasonographic scores and by clinical/biochemical variables: Fatty liver index and Hepatic steatosis index. HF was evaluated by NAFLD fibrosis score (NAFLD-FS). Serum leptin and leptin receptor (sObR) concentrations were measured and leptin resistance estimated by Free Leptin Index (FLpI). Both simple and multiple correlations between the HS and HF with the three parameters of interest were examined. RESULTS: Leptin levels and FLpI correlated with diabetes duration (0.25 [95%CI: 0.09-0.39] and 0.24 [95%CI: 0.08-0.39]; P < 0.01 for both). 76.1% of T2D patients had HS and 29% had HF. The univariate analysis indicated positive correlations of HS indexes with serum leptin, FLpI, and negative correlations with serum sObR (P < 0.0001 for all). In the multiple regression analysis leptin, sObR, FLpI, waist-to-hip ratio, HbA1c, lipids, and HOMA-IR correlated independently with HS (P < 0.0001 for all). Although the univariate analyses indicated weak correlations of NAFLD-FS with leptin, sObR, and FLpI, in the multiple regression analyses, only age and waist independently predicted HF. CONCLUSION: In patients with T2D, HS correlated positively with serum leptin and leptin resistance, and negatively with sObR, along with variables of adiposity and metabolic control, but neither of them made a significant contribution to HF.

[Association of plasma leptin levels and soluble leptin receptor with breast cancer].

Objective: To explore the association between plasma leptin (LEP) levels, soluble leptin receptor(SLR), free leptin index and breast cancer. Methods: 245 new female cases of primary breast cancer confirmed by histopathology examination were sequentially recruited into the study. A total of 245 age-matched healthy women were enrolled as controls during the same period. A standardized questionnaire was used to collect the demographic information of the subjects. Blood samples were collected and the levels of LEP and SLR in plasma were measured by enzyme linked immunosorbent assay. The differences of LEP, SLR and FLI expression between control and cases group, as well as different breast cancer subtypes and TNM stages were compared using t-test and ANOVA after stratification by menopause status. Multivariate logistic regression was used to explore the contributions of the three indexes to the risk of breast cancer. Results: Females in both cases and control group were (50.7 ± 9.4) years old. The level of SLR and FLI (P(50)(P(25),P(75))) in premenopausal women were 18.4 (11.2, 28.7), 0.5 (0.4, 0.6) µg/L in case group and 27.7 (19.2, 43.4), 0.3 (0.3, 0.4) µg/L in control group (P<0.001). While the level of postmenopausal women in case group were 20.3 (12.8, 31.8), 0.5 (0.4, 0.6) µ g/L (P<0.001), and 30.1 (18.8, 40.5), 0.3 (0.3, 0.5) µg/L in control group (P<0.001), respectively. After adjustment for confounding factors and BMI, the relationship between FLI and breast cancer remained significant for both pre- and postmenopausal women while the association between SLR and breast cancer was significant only in premenopausal women. Compared with the lowest level of SLR, higer levels of SLR is associated with a reduced risk of breast cancer (premenopausal women, OR=0.10, 95% CI: 0.04-0.29, P(trend)<0.001). Compared with the lowest level of FLI, FLI at higher levels is associated with an increased risk of breast cancer (premenopausal women, OR=7.14, 95% CI: 2.86-17.83, P(trend)<0.001; postmenopausal women, OR=8.10, 95% CI: 2.85-22.98, P(trend)<0.001). No significant association between LEP and breast cancer or association between the three indexes and breast cancer subtypes and TNM stages was found (P>0.05). Conclusion: SLR may be a protective factor for breast cancer while FLI may increase the risk of breast cancer.

Leptin and soluble leptin receptor in association with gestational diabetes: a prospective case-control study.

PURPOSE: To assess the association of serum leptin and its receptor (SLeptinR) with the risk of gestational diabetes mellitus (GDM) and to evaluate the longitudinal circulation of these peptides in pregnancy. METHODS: This study consisted of 53 subjects diagnosed with GDM and 43 normal glucose tolerance (NGT) pregnant women. Serum leptin and SLeptinR were measured at 24-28 weeks, prior and after delivery, and post-puerperium. RESULTS: Lower levels of leptin and SLeptinR were observed in GDM compared to NGT. Leptin [OR 0.97 (95% CI 0.94-1.0)] and SLeptinR [OR 0.86 (95% CI 0.79-0.93]) were inversely associated with GDM. Participants in the lowest tertile for leptin and SLeptinR had a 2.8-fold (95% CI 1.0-7.6) and a 5.7-fold (95% CI 1.9-17.3) higher risk of developing GDM compared with the highest tertile, respectively. These relationships were attenuated after adjustment for covariates. In both the groups, peak leptin was observed at 24-28 weeks, decreasing continuously during pregnancy (p > 0.05) and after delivery (p < 0.017). SLeptinR level increased (p < 0.001) during pregnancy and decreased (p < 0.005) after delivery in GDM, however, levels remained the same in NGT. In GDM, leptin and SLeptinR was positively and inversely correlated with BMI and HOMA-IR at 24-28 weeks and post-puerperium, respectively. The cord levels of both leptin and SLeptinR were lower than maternal levels. There were no significant differences in serum cord leptin and SLeptinR levels between the groups. CONCLUSION: Leptin and SLeptinR are independently and inversely associated with GDM. Lower levels of these peptides may play an important role in the pathophysiology of GDM and pre-diabetic state in post-puerperium.

Association of plasma leptin levels and soluble leptin receptor with breast cancer / 中华预防医学杂志

Objective@#To explore the association between plasma leptin (LEP) levels, soluble leptin receptor(SLR), free leptin index and breast cancer.@*Methods@#245 new female cases of primary breast cancer confirmed by histopathology examination were sequentially recruited into the study. A total of 245 age-matched healthy women were enrolled as controls during the same period. A standardized questionnaire was used to collect the demographic information of the subjects. Blood samples were collected and the levels of LEP and SLR in plasma were measured by enzyme linked immunosorbent assay. The differences of LEP, SLR and FLI expression between control and cases group, as well as different breast cancer subtypes and TNM stages were compared using t-test and ANOVA after stratification by menopause status. Multivariate logistic regression was used to explore the contributions of the three indexes to the risk of breast cancer.@*Results@#Females in both cases and control group were (50.7 ± 9.4) years old. The level of SLR and FLI (P50(P25,P75)) in premenopausal women were 18.4 (11.2, 28.7), 0.5 (0.4, 0.6) μg/L in case group and 27.7 (19.2, 43.4), 0.3 (0.3, 0.4) μg/L in control group (P<0.001). While the level of postmenopausal women in case group were 20.3 (12.8, 31.8), 0.5 (0.4, 0.6) μ g/L (P<0.001), and 30.1 (18.8, 40.5), 0.3 (0.3, 0.5) μg/L in control group (P<0.001), respectively. After adjustment for confounding factors and BMI, the relationship between FLI and breast cancer remained significant for both pre- and postmenopausal women while the association between SLR and breast cancer was significant only in premenopausal women. Compared with the lowest level of SLR, higer levels of SLR is associated with a reduced risk of breast cancer (premenopausal women, OR=0.10, 95% CI: 0.04-0.29, Ptrend<0.001). Compared with the lowest level of FLI, FLI at higher levels is associated with an increased risk of breast cancer (premenopausal women, OR=7.14, 95% CI: 2.86-17.83, Ptrend<0.001; postmenopausal women, OR=8.10, 95% CI: 2.85-22.98, Ptrend<0.001). No significant association between LEP and breast cancer or association between the three indexes and breast cancer subtypes and TNM stages was found (P>0.05).@*Conclusion@#SLR may be a protective factor for breast cancer while FLI may increase the risk of breast cancer.