Leptin Binding Protein Research Articles

Observational study of effects of HIV acquisition and antiretroviral treatment on biomarkers of systemic immune activation.

To assess whether biomarkers of systemic inflammation are associated with HIV acquisition or with the timing of ART initiation ("immediate", at diagnosis, versus "deferred", at 24 weeks post-diagnosis) in men-who-have-sex-with-men (MSM) and transgender women, we conducted a retrospective study comparing inflammatory biomarkers in participants' specimens collected before infection and after ≥2 years of effective ART. We measured biomarkers in four longitudinally collected plasma, including two specimens collected from each participant before and two after HIV acquisition and confirmed ART-suppression. Biomarkers were quantified by enzyme-linked immuno-assay or Meso Scale Discovery. When evaluating systematic variation in these markers over time, we found that multiple biomarkers consistently varied across participants' two pre-infection or two post-ART-suppression specimens. Additionally, we compared changes in biomarkers after vs before HIV acquisition. Across 47 participants, the levels of C-reactive protein (CRP), monocyte chemo-attractant protein-1, tumor necrosis factor-α and interferon gamma-induced protein-10 significantly increased while leptin and lipopolysaccharide binding protein (LBP) significantly decreased following HIV infection. Randomization to deferred-ART initiation was associated with greater increases in CRP and no decrease in LBP. Acquisition of HIV appeared to induce systemic inflammation, with elevation of biomarkers previously associated with infections and cardiovascular disease. Initiation of ART during the early weeks of infection tempered the increase in pro-inflammatory biomarkers compared to delaying ART for ~24 weeks after HIV diagnosis. These findings provide insight into potential mediators by which immediate-ART initiation improves health outcomes, perhaps because immediate-ART limits the size of the HIV reservoir or limits immune dysregulation that in turn trigger systemic inflammation.

Adipokines in depressed women with and without adverse childhood experiences

BackgroundAdverse childhood experiences (ACE) elevate the risk of both major depressive disorder (MDD) and metabolic diseases. The underlying pathophysiology might include alterations of adipokine levels as a consequence of ACE. In this study, we used a full-factorial design to investigate the levels of select adipokines in women with ACE-only (n = 23), MDD-only (n = 27), ACE+MDD (n = 25) and healthy controls (HC, n = 29) to identify metabolic makers associated with vulnerability and resilience of developing MDD after ACE exposure. MethodsSerum levels of adiponectin, leptin, adiponectin-to-leptin (A/L) ratio, and retinol binding protein 4 (RBP4) were measured using enzyme-linked immunosorbent assay (ELISA). ResultsAdiponectin levels did not differ between groups. Individuals with vs. without MDD showed higher leptin serum concentrations. As predicted, A/L ratio indicated lower values in individuals with vs. without ACE. RBP4 showed a more nuanced pattern with reduced levels in the ACE-only and MDD-only groups compared to HC. Furthermore, the ACE-only group showed lower RBP4 concentrations compared to ACE+MDD. These results were not accounted by BMI or medication status. ConclusionOur results do not support the utility of adiponectin and leptin as predictors of vulnerability or resilience of developing MDD after ACE. In contrast, RBP4 might play a role in resilience towards the development of MDD following ACE. Further research on this more recently discovered adipokine seems warranted.

Study on the Association Between Dietary Quality and Overweight/Obesity of Han Nationality with Cold in Yunnan Plateau by DBI-16 - A Study Based on a Multi-Ethnic Cohort in China.

In recent years, with the rapidly development of economic globalization, residents' dietary structure has undergone major changes, and diet have emerged as an important environmental factors linked to the increased incidence of obesity. Therefore, evaluating the overall dietary quality and structure of residents, further clarifying the main dietary factors that lead to disease occurrence, is of great practical significance for disease prevention and control. Baseline data from the China Multi-Ethnic Cohort study (CMEC), Han people living in high-altitude and cold regions of Yunnan Province, which was 1518 participants. In this study, the dietary balance index (DBI-16) was used (i) To evaluate the dietary quality of Han nationality residents 30-79 years old in the Yunnan plateau; (ii) To analyze the correlation between the dietary quality and overweight/obesity; (iii) And to provide reference basis of nutritional intervention for local residents and explore the main dietary factors affecting their health status. The dietary structure of the Han nationality residents in the cold regions of Yunnan plateau is unreasonable. Firstly, the intake of cereals, fruits, dairy, eggs and fishes is insufficient to varying degrees, while the intake of beans, poultry, and cooking oil is relatively high. Secondly, the dietary patterns of normal groups, the overweight and obese groups obeyed the A, E, H and I dietary patterns, and the serum Leptin and adipocyte fatty acid binding protein (A-FABP) levels of the overweight and obese group were higher than the normal group between the different dietary patterns (P < 0.05, r > 0). Additionally, excessive dietary intake was positively correlated with a higher serum UCP1 level (P < 0.05, r > 0). In comparison, insufficient dietary intake was positively correlated with a higher serum A-FABP level (P < 0.05, r > 0). Through the DBI-16, it is found that the dietary structure of the Han nationality residents in the cold regions of Yunnan plateau was in a serious imbalance state, and nutritional guidance and intervention should be further strengthened.

Association of Leptin and Retinol Binding Protein 4 with the Risk of Gestational Diabetes: A Systematic Review and Meta-Analysis of Observational Studies.

The positive correlation between serum levels of retinol binding protein 4 (RBP4) and gestational diabetes (GDM) has been proven in the previous meta-analysis on case-control studies. However, its association with serum levels of leptin is not studied in any meta-analysis. Therefore, we performed an updated systematic review of observational studies evaluating the association between serum RBP4 and leptin with the risk of GDM. A systematic search was performed on four databases, including PubMed, Scopus, Web of Science, and Google Scholar, up to March 2021. After screening and deleting duplicates, nine articles met our inclusion criteria. Studies had case-control and cohort design, and included 5074 participants with a mean age range between 18 and 32.65 years (2359 participants for RBP4 and 2715 participants for leptin). Interestingly, this meta-analysis revealed higher levels of RBP4 (OR=2.04; 95% CI: 1.37, 3.04) and leptin (OR=2.32; 95% CI: 1.39, 3.87) are significantly associated with the increased risk of overall GDM. The subgroup analysis approved the results based on the study design, trimester of pregnancy and serum/plasms to investigate the source of heterogeneity. The present meta-analysis determines serum leptin and RBP4 levels as predictors of GDM occurrence. However, studies included in this meta-analysis showed significant heterogeneity.

Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population

Type 2 diabetes (T2D) has a heterogeneous etiology influencing its progression, treatment, and complications. A data driven cluster analysis in European individuals with T2D previously identified four subtypes: severe insulin deficient (SIDD), severe insulin resistant (SIRD), mild obesity-related (MOD), and mild age-related (MARD) diabetes. Here, the clustering approach was applied to individuals with T2D from the Qatar Biobank and validated in an independent set. Cluster-specific signatures of circulating metabolites and proteins were established, revealing subtype-specific molecular mechanisms, including activation of the complement system with features of autoimmune diabetes and reduced 1,5-anhydroglucitol in SIDD, impaired insulin signaling in SIRD, and elevated leptin and fatty acid binding protein levels in MOD. The MARD cluster was the healthiest with metabolomic and proteomic profiles most similar to the controls. We have translated the T2D subtypes to an Arab population and identified distinct molecular signatures to further our understanding of the etiology of these subtypes.

In silico analyses of leptin and leptin receptor of spotted snakehead Channa punctata

The present study, in addition to molecular characterization of leptin (lepa) and its receptor (lepr) of spotted snakehead Channa punctata, is focussed on physicochemical, structural, evolutionary and selection pressure analyses which are poorly elucidated in teleosts in spite of that existence of these genes is well reported in several fish species. The putative full-length Lep and Lepr of C. punctata showed conserved structural and functional domains, especially the residues responsible for structural integrity and signal transduction. Conversely, residues predicted essential for Lep-Lepr interaction displayed divergence between teleosts and tetrapods. Impact of substitutions/deletions predicted using protein variation effect analyser tool highlighted species specificity in ligand-receptor interaction. Physicochemical properties of ligand and receptor predicted for the first time in vertebrates revealed high aliphatic and instability indices for both Lepa and Lepr, indicating thermostability of proteins but their instability under ex vivo conditions. Positive grand average of hydropathy score of Lepa suggests its hydrophobic nature conjecturing existence of leptin binding proteins in C. punctata. In addition to disulphide bonding, a novel posttranslational modification (S-126 phosphorylation) was predicted in Lepa of C. punctata. In Lepr, disulphide bond formation and N-linked glycosylation near WSXWS motif in ECD, and phosphorylation at tyrosine residues in ICD were predicted. Leptin and its receptor sequence of C. punctata cladded with its homolog from C. striata and C. argus of order Anabantiformes. Leptin system of Anabantiformes was phylogenetically closer to that of Pleuronectiformes, Scombriformes and Perciformes. Selection pressure analysis showed higher incidence of negative selection in teleostean leptin genes indicating limited adaptation in their structure and function. However, evidence of pervasive and episodic diversifying selection laid a foundation of co-evolution of Lepa and Lepr in teleosts.

Immunometabolic factors in adolescent chronic disease are associated with Th1 skewing of invariant Natural Killer T cells

Invariant Natural Killer T (iNKT) cells respond to the ligation of lipid antigen-CD1d complexes via their T-cell receptor and are implicated in various immunometabolic diseases. We considered that immunometabolic factors might affect iNKT cell function. To this end, we investigated iNKT cell phenotype and function in a cohort of adolescents with chronic disease and immunometabolic abnormalities. We analyzed peripheral blood iNKT cells of adolescents with cystic fibrosis (CF, n = 24), corrected coarctation of the aorta (CoA, n = 25), juvenile idiopathic arthritis (JIA, n = 20), obesity (OB, n = 20), and corrected atrial septal defect (ASD, n = 25) as controls. To study transcriptional differences, we performed RNA sequencing on a subset of obese patients and controls. Finally, we performed standardized co-culture experiments using patient plasma, to investigate the effect of plasma factors on iNKT cell function. We found comparable iNKT cell numbers across patient groups, except for reduced iNKT cell numbers in JIA patients. Upon ex-vivo activation, we observed enhanced IFN-γ/IL-4 cytokine ratios in iNKT cells of obese adolescents versus controls. The Th1-skewed iNKT cell cytokine profile of obese adolescents was not explained by a distinct transcriptional profile of the iNKT cells. Co-culture experiments with patient plasma revealed that across all patient groups, obesity-associated plasma factors including LDL-cholesterol, leptin, and fatty-acid binding protein 4 (FABP4) coincided with higher IFN-γ production, whereas high HDL-cholesterol and insulin sensitivity (QUICKI) coincided with higher IL-4 production. LDL and HDL supplementation in co-culture studies confirmed the effects of lipoproteins on iNKT cell cytokine production. These results suggest that circulating immunometabolic factors such as lipoproteins may be involved in Th1 skewing of the iNKT cell cytokine response in immunometabolic disease.

Circulating Level of Soluble Leptin Receptor and its Association with Cardiometabolic Risk Factors among Obese Subjects in Kerala, South India

Background and Aims: Leptin, the peptide hormone secreted mainly by adipose tissue is reported to play the central role in the pathogenesis of obesity. Leptin exerts its biological effects through specific receptor molecules present in target tissues. Among the different isoforms of leptin receptor, the Soluble Leptin Receptor (SLR) is the major leptin binding protein seen in circulation which modulates the bioavailability of leptin. Our objectives were to analyse the level of circulating SLR among obese subjects and its association with biomarkers of obesity, serum leptin, insulin and cardiometabolic risk factors in comparison with healthy age and sex matched control subjects.&#x0D; Methods: About 173 study participants of both genders were selected and grouped as case (n=102) and control (n=71) with a cut off point of BMI 25kg/m2. Waist to hip ratio (WHR) and body fat percentage (BF%) were calculated from anthropometric measurements. Leptin, insulin, soluble leptin receptor were estimated in fasting blood samples by sandwich ELISA method. Fasting plasma glucose and lipid profile were measured by standard enzymatic methods in autoanalyzer. Homeostasis Model Assessment of Insulin resistance (HOMA-IR) was calculated. Comparison between groups was done by independent sample ‘t’ test. P values &lt;.05 were considered statistically significant.&#x0D; Results: The SLR level was found to be increased in obese group in comparison with control group(P =.001). A significant increase in serum leptin and insulin level was observed in obese group when compared to control (P =.001). Obese group showed more than two fold increase in insulin resistance expressed as HOMA-IR when compared to control subjects (P =.001). But no significant difference in the synthesis of insulin expressed as HOMA-beta between the groups. No significant difference in serum lipoprotein levels was observed between the two groups.&#x0D; Conclusion: Increased level of circulating soluble leptin receptor has been observed in obese subjects in comparison with control subjects and is associated with hyperleptinemia, hypertension and insulin resistance.

Anti-obesity potential of Moringa olifera seed extract and lycopene on high fat diet induced obesity in male Sprauge Dawely rats.

Present research explored the anti-obesity effect of Moringa olifera seed oil extract and lycopene (LYC). Forty eight male Sprauge Dawely rats were divided equally into 6 groups. Group Ι (C) served as control, group ΙΙ (MC) was given Moringa olifera seed oil extract (800 mg/kg b.wt) for 8 weeks, group ΙΙΙ (LC) was given (20 mg/kg b.wt) LYC for 8 weeks, group ΙV (O) received high fat diet (HFD) for 20 weeks, group Ѵ (MO), was given HFD for 20 weeks and received (800 mg/kg b.wt) Moringa olifera seed oil extract for last 8 weeks and group ѴΙ (LO), received HFD for 20 weeks and was given (20 mg/kg b.wt) LYC for last 8 weeks. Hematology, lipid peroxidation and antioxidants, non-esterified fatty acids (NEFA), glucose, lipid profile, serum liver and kidney biomarkers, inflammatory markers, leptin, resistin and heart fatty acid binding protein (HFABP) were determined. Also histopathology for liver, kidney and aorta were performed besides immunohistochemistry (IHC) for aortic inducible nitric oxide synthase (iNOS). Administration of Moringa olifera seed oil extract and LYC significantly ameliorated the HFD induced hematological and metabolic perturbations as well as reduced leptin and resistin. Both treatments exerted these effects through promotion of antioxidant enzymes and reducing lipid peroxidation as well as inflammatory cytokines along with reduced iNOS protein expression. Administration of Moringa olifera seed oil extract and LYC have anti-obesity potential in HFD induced obesity in male Sprauge Dawely rats.

SAT-028 Leptin, Leptin Soluble Receptor and FLI in Healthy and Preeclamptic Pregnancies

ContextLeptin is an adipokine involved in many pleiotropic and key physiological actions and circulates free and active, or inactive bound to the leptin binding protein and sOB-r. Thus, the ratio Leptin/sOB-r or free leptin index (FLI) is commonly used as a marker of leptin sensitivity in different pathologies.ObjectiveEvaluate serum concentrations of leptin and sOB-r and determine FLI in healthy pregnant and mild pre – eclamptic women in the three trimesters of gestation.DesignA nested case-control study within a prospective cohort study of pregnant women, enrolled in the Department of Obstetrics and Gynecology of the School of Medicine at Universidad Nacional.Main Outcome Measure and MethodsFrom the initial cohort, 46 healthy pregnant women and 19 mild pre – eclamptic pregnant women were randomly selected. Anthropometric, biochemical and clinical parameters were determined during three stages of pregnancy [1st (11.3±2.3 weeks), 2nd (24.4±3.10 weeks) and 3rd (34.84±4.41 weeks) periods of gestation]. Data were presented as mean ± SD. A p value <0.05 was considered to be statistically significant.ResultsSerum leptin levels and sOB-r levels rose significantly throughout pregnancy in both healthy women [Leptin (1st 23.28±9.87 ng/mL; 2nd 34.58±18.45 ng/mL; 3rd 38.27±19.64 ng/mL trimester) (p=0.0001); sOB-r (1st 32.12±7.29 ng/mL; 2nd 43.26±9.25 ng/mL; 3rd 45.16±10.70 ng/mL trimester) (p<0.0000)] and preeclamptic women [Leptin (1st 29.91±9.91 ng/mL; 2nd 47.10±25.70 ng/mL; 3rd 63.00±3012 ng/mL trimester) (p<0.0000); sOB-r (1st 32.09±6.97 ng/mL; 2nd 37.54±6.33 ng/mL; 3rd 36.96±7.66 ng/mL trimester) (p=0.0380)].Serum leptin levels were significantly higher in preeclamptic pregnant women compared to healthy pregnant women at 2nd (p=0.029) and 3rd trimesters of pregnancy (p<0.000). Additionally, serum sOB-r levels were also significantly lower in pre - eclamptic pregnant women during the 2nd (p=0.017) and 3rd trimester (p=0.0036) of pregnancy compared to healthy pregnant women. As a result, the FLI index did not vary significantly during any of the three periods of pregnancy studied in healthy pregnant women [(1st 7.99±4.85; 2nd 8.72±6.5; 3rd 9.15±5.84 trimester) (p >0.05)], whereas, in contrast, this index markedly increased throughout pregnancy in pre - eclamptic women [(1st 8.69±4.96; 2nd 13.54±8.78; 3rd 18.06±10.35 trimester) (p=0.0044)]. Indeed, the FLI index was significantly higher at 2nd (p=0.0186) and 3rd (p<0.000) trimesters of pregnancy in pre - eclamptic women compared to healthy pregnant.ConclusionsThe present results demonstrate for the first time in a longitudinal study that FLI increases significantly in pre - eclamptic pregnant women towards the end of pregnancy. Hence, high FLI index values should be further explored as a potentially valuable indicator for the clinical manifestations of this pathology.

Effects of colostrum instead of formula feeding for the first 2 days postnatum on whole-body energy metabolism and its endocrine control in neonatal calves

Colostrum provides high amounts of nutritive and non-nutritive substrates, which are essential for calf nutrition and passive immunization. Colostral growth factors and hormones have beneficial effects on postnatal maturation and may affect substrate utilization and energy expenditure in neonatal calves. We tested the hypothesis that energy metabolism and its endocrine regulation differ during the first 10 d of life in calves fed either colostrum or a milk-based formula with a similar nutrient composition to colostrum, but largely depleted of bioactive substances, for the first 2 d postnatum. Male Holstein calves (n = 18) were fed either pooled colostrum (COL; n = 9) or a milk-based formula (FOR; n = 9) for the first 2 d of life. From d 3 on, all calves received same milk replacer. On d 2 and 7 of life, calves were placed in a respiration chamber for indirect calorimetric measurements to calculate heat production, fat (FOX) and carbohydrate oxidation (COX), as well as respiratory quotient. Blood was sampled on d 1 before first colostrum intake and on d 2, 3, 7, 8, 9, and 10 before morning feeding, to measure plasma concentrations of immunoglobulins, metabolites, and hormones. Additional postprandial blood samples were taken on d 1 and 9 at 30, 60, 120, 240, and 420 min after milk feeding. Liver samples were collected on d 10 of life to determine gene expression related to energy metabolism. Formula-fed calves showed lower plasma concentrations of total protein, immunoglobulins, haptoglobin, leptin, adiponectin, and insulin-like growth factor (IGF) binding protein (IGFBP)-4 during the whole study but temporarily higher plasma concentrations of urea, insulin, glucagon, triglyceride, and cholesterol on the first day after feeding, compared with concentrations in COL. The temporary increase in glucagon, triglyceride, and cholesterol on d 1 reversed on d 2 or 3, showing higher concentrations in COL than in FOR calves. In FOR, IGF-I, IGFBP-2, and IGFBP-3 were lower on d 3 than in COL. Interestingly, FOR calves had higher heat production during respiratory measurements on d 2 and higher body temperature on d 2, 3, and 5 than those of COL. The hepatic mRNA abundance of cytosolic phosphoenolpyruvate carboxykinase was higher in FOR than in COL. Our results indicate that first milk feeding after birth influenced whole-body energy expenditure but not FOX and COX in neonatal calves, and the absorption of colostral leptin and adiponectin might affect insulin sensitivity on d 1 of life.

41: Fetal metabolic biomarkers after late preterm betamethasone and their association with neonatal hypoglycemia

Late preterm betamethasone significantly reduced neonatal respiratory morbidity, but also increased neonatal hypoglycemia through an uncertain mechanism. Our objective was to define the fetal metabolic effects of antenatal late preterm betamethasone. Secondary analysis of a randomized trial of antenatal betamethasone versus placebo in women with threatened late preterm birth (2010-2015). Mother-neonate dyads with stored umbilical cord blood plasma were included. Major congenital anomalies were excluded. Magnetic bead-based multiplex assays were used to measure metabolic biomarkers C-peptide, insulin, leptin and insulin-like growth factor binding protein 1 (IGFBP-1) in umbilical cord blood plasma. Baseline characteristics and biomarker levels were compared between betamethasone and placebo groups. Multivariable generalized linear regression estimated the association between betamethasone and biomarker levels, adjusting for BMI, GDM, hours from study drug exposure to delivery, and hospital as a random effect. Subsequently, the associations between the fetal biomarkers and neonatal hypoglycemia (glucose< 40mg/dL) were investigated. Of 2831 women in the primary trial, 203 met inclusion criteria for this analysis: 106 (52%) exposed to betamethasone and 97 (48%) exposed to placebo. A total of 173 (85%) women delivered preterm and 23 (11%) had GDM. Overall, 61 (30%) neonates had hypoglycemia. Betamethasone was associated with higher adjusted mean C-peptide, insulin, and leptin levels (Figure). There was no difference in IGFBP-1. Fetal C-peptide and insulin levels >90th percentile were associated with 3- to 6-fold higher odds of neonatal hypoglycemia (Table). Betamethasone given in late preterm is associated with altered fetal metabolic pathways, and these alterations are associated with neonatal hypoglycemia. Further studies are needed to confirm whether fetal hyperinsulinemia is the cause of neonatal hypoglycemia after late preterm betamethasone exposure, and if this outcome can be prevented.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Dietary protein restriction increases hepatic leptin receptor mRNA and plasma soluble leptin receptor in male rodents.

Leptin is an adipokine that regulates adipose tissue mass through membrane-anchored leptin receptor (Ob-R). Extracellular domain of Ob-R in plasma is called soluble leptin receptor (sOb-R), and is the main leptin-binding protein. Based on a previous DNA microarray analysis that showed induction of hepatic Ob-R mRNA in low-protein diet-fed mice, this study aimed to clarify the effect of dietary protein restriction on hepatic Ob-R mRNA and plasma sOb-R levels. First, the effect of protein restriction on hepatic Ob-R mRNA level was examined together with fasting and food restriction using male rats as common experimental model for nutritional research. Hepatic Ob-R mRNA level was increased by feeding low-protein diet for 7 d, although not significantly influenced by 12-h fasting and sixty percent restriction in food consumption. Then, effect of protein restriction on liver Ob-R and plasma sOb-R was investigated using male mice because specific sOb-R ELISA was more available for mice. Hepatic Ob-R mRNA level was also increased in protein restricted-mice although it did not increase in hypothalamus. Hepatic Ob-R protein was decreased, whereas plasma sOb-R was increased by protein restriction. Because the concentration of sOb-R increased without changing plasma leptin concentration, free leptin in plasma was significantly reduced. The direct effect of amino acid deprivation on Ob-R mRNA level was not observed in rat hepatoma cells H4IIE cultured in amino acid deprived medium. In conclusion, dietary protein restriction increased hepatic Ob-R mRNA, resulting in increased plasma sOb-R concentration, which in turn, reduces plasma free leptin level and may modulate leptin activity.

Psoriasis,Cardiovascular Disease,and Adipokines

Psoriasis usually combines with metabolic diseases,and the prevalence of cardiovascular disease remarkably increases in psoriatic patients. Adipokines,which play an important role in the cardiovascular diseases,also express abnormally in psoriasis and may induce or exacerbate the skin lesion. The adipokines associated with psoriasis and cardiovascular disease include adiponectin,leptin,resistin,omentin,visfatin,chemerin,and retinoid binding protein 4 (RBP-4). The levels of adiponectin and omentin apparently decrease in psoriatic patients compared to healthy controls,and thus they may play protective roles for psoriasis. Similarly,adiponectin plays a protective role in cardiovascular disease,but the role of retina in cardiovascular disease is still controversial. However,the concentrations of leptin,resistin,visfatin,chemerin,and RBP-4 in patients with psoriasis or cardiovascular disease are significantly higher than those of the controls;therefore,they may serve as the pathogenic factors for both diseases. Low adiponectin,leptin,visfatin,and chemerin levels may induce or aggravate psoriasis by activating plasmacytoid dendritic cells or T cells,as demonstrated in in vitro experiments. However,in vitro experiments also have shown that visfatin may inhibit cardiomyocyte apoptosis.

Early diagnosis of type 2 diabetes based on multiple biomarkers and non-invasive indices.

We previously reported that type 2 diabetes risk, early impaired glucose tolerance and insulin resistance can be predicted by measuring the fasting levels of certain biomarkers. Here we validated these findings in randomly recruited healthy volunteers (n = 101) based on biomarker expression as well as various non-invasive indices. Weight, body mass index, waist circumference and visceral fat differed between individuals with impaired fasting glucose and/or impaired glucose tolerance, and normal subjects. Fasting plasma levels of glycated hemoglobin, leptin, pro-insulin and retinol binding protein 4 differed between impaired fasting glucose/impaired glucose tolerance and normal subjects group and between newly detected diabetes and normal subjects group. Insulin resistance was correlated with fasting levels of insulin and leptin/adiponectin (r = 0.913); of insulin, retinol binding protein 4 and leptin/adiponectin (r = 0.903); and of insulin, glycated albumin, and leptin/adiponectin (r = 0.913). Type 2 diabetes risk, early impaired glucose tolerance and insulin resistance were predicted with >98% specificity and sensitivity by comparing fasting glucose levels to the estimated Matsuda Index based on fasting levels of insulin, adiponectin and leptin with or without oxidative lineolate metabolites. Non-invasive indices are slightly correlated with glucose tolerance and insulin resistance but do not increase the accuracy of predicting type 2 diabetes risk.

Space radiation exposure persistently increased leptin and IGF1 in serum and activated leptin-IGF1 signaling axis in mouse intestine.

Travel into outer space is fraught with risk of exposure to energetic heavy ion radiation such as 56Fe ions, which due to its high linear energy transfer (high-LET) characteristics deposits higher energy per unit volume of tissue traversed and thus more damaging to cells relative to low-LET radiation such as γ rays. However, estimates of human health risk from energetic heavy ion exposure are hampered due to lack of tissue specific in vivo molecular data. We investigated long-term effects of 56Fe radiation on adipokines and insulin-like growth factor 1 (IGF1) signaling axis in mouse intestine and colon. Six- to eight-week-old C57BL/6J mice were exposed to 1.6 Gy of 56Fe ions. Serum and tissues were collected up to twelve months post-irradiation. Serum was analyzed for leptin, adiponectin, IGF1, and IGF binding protein 3. Receptor expressions and downstream signaling pathway alterations were studied in tissues. Irradiation increased leptin and IGF1 levels in serum, and IGF1R and leptin receptor expression in tissues. When considered along with upregulated Jak2/Stat3 pathways and cell proliferation, our data supports the notion that space radiation exposure is a risk to endocrine alterations with implications for chronic pathophysiologic changes in gastrointestinal tract.

Impaired central leptin signaling and sensitivity in rainbow trout with high muscle adiposity

The hormone leptin has been identified in all vertebrate classes, but its physiological roles in non-mammalian vertebrates are not well defined. To elucidate leptin regulation in energy homeostasis in a teleost fish species, this study compares hypothalamic and pituitary leptin signaling systems in energetically divergent rainbow trout lines selected for low (lean line, LL) and high (fat line, FL) muscle adiposity under feeding and starvation conditions. In fed fish, hypothalamic gene expression and protein density of the full-functional leptin receptor (LepRL), as well as a leptin binding protein (LepBP) expression, are lower in FL than LL fish. The FL fish have also lower activation of leptin-relevant signaling pathways involving protein kinase B (Akt) and extracellular signal-related kinase. These observations suggests impaired central leptin action in FL fish. During fasting, hypothalamic LepRL and LepBP expression, as well as active Akt levels are downregulated after one week, while pituitary LepRL expression is upregulated, in the LL fish only. After four weeks, hypothalamic LepRL protein levels return to normal levels in both fish lines and Akt is reactivated, although not to the same extent in FL as in LL fish, indicating that FL fish have low leptin sensitivity to nutritional changes. Neuropeptide Y and orexin expression is downregulated to similar levels in both fish lines after one-week fasting. The divergent leptin system profiles between the two fish lines demonstrate that phenotypic selection for high muscle adiposity affects leptin endocrinology, indicating regulatory roles for leptin in rainbow trout energy homeostasis.

Adipose Tissue Depots and Their Cross-Sectional Associations With Circulating Biomarkers of Metabolic Regulation.

BackgroundVisceral adipose tissue (VAT) and fatty liver differ in their associations with cardiovascular risk compared with subcutaneous adipose tissue (SAT). Several biomarkers have been linked to metabolic derangements and may contribute to the pathogenicity of fat depots. We examined the association between fat depots on multidetector computed tomography and metabolic regulatory biomarkers.Methods and ResultsParticipants from the Framingham Heart Study (n=1583, 47% women) underwent assessment of SAT, VAT, and liver attenuation. We measured circulating biomarkers secreted by adipose tissue or liver (adiponectin, leptin, leptin receptor, fatty acid binding protein 4, fetuin‐A, and retinol binding protein 4). Using multivariable linear regression models, we examined relations of fat depots with biomarkers. Higher levels of fat depots were positively associated with leptin and fatty acid binding protein 4 but negatively associated with adiponectin (all P<0.001). Associations with leptin receptor, fetuin‐A, and retinol binding protein 4 varied according to fat depot type or sex. When comparing the associations of SAT and VAT with biomarkers, VAT was the stronger correlate of adiponectin (β=−0.28 [women]; β=−0.30 [men]; both P<0.001), whereas SAT was the stronger correlate of leptin (β=0.62 [women]; β=0.49 [men]; both P<0.001; P<0.001 for comparing VAT versus SAT). Although fetuin‐A and retinol binding protein 4 are secreted by the liver in addition to adipose tissue, associations of liver attenuation with these biomarkers was not stronger than that of SAT or VAT.Conclusions SAT, VAT, and liver attenuation are associated with metabolic regulatory biomarkers with differences in the associations by fat depot type and sex. These findings support the possibility of biological differences between fat depots.

Energy stores, lipid mobilization and leptin endocrinology of rainbow trout.

The physiological role of leptin in fish is not fully elucidated. In the present study, the involvement of the leptin system in lipid deposition and mobilization in rainbow trout during feeding and 1, 2 and 4weeks of fasting was investigated in two lines of rainbow trout with different muscle and visceral adiposity: a fat line (FL) with high total energy reserves, high muscle adiposity, but low visceral adiposity and a lean line (LL) with lower total energy reserves and lower muscle adiposity, but higher visceral adiposity. During 4weeks of fasting, muscle lipids decreased by 63% in the FL fish, while no such energy mobilization from muscle occurred in the LL fish. On the other hand, lipid stores in liver and visceral adipose tissue was utilized to a similar extent by the two fish lines during fasting. Under normal feeding conditions, plasma leptin levels were higher in the LL than the FL fish, suggesting a possible contribution of visceral adipocytes to plasma leptin levels. Plasma leptin-binding protein levels did not differ between the lines and were not affected by fasting. After 4weeks of fasting, the long leptin receptor and the leptin-binding protein isoforms 1 and 3 muscle expression increased in the LL fish, as well as hepatic expression of leptin A1 and the two binding protein isoforms. These responses were not seen in the FL fish. The data suggest that the Lep system in rainbow trout is involved in regulation of energy stores and their mobilization.

Identification of a soluble leptin receptor in crucian carp with different binding affinity to leptin-a and leptin-b.

Soluble leptin receptor (sLepR) is the main leptin-binding protein in plasma and contributes to activation of circulating leptin. In this study, we identified a sLepR in plasma of crucian carp (Carassius carassius) using a pull-down assay, and the interaction of sLepR with its ligand is confirmed by a cross-linking study. In addition, we found that leptin-a has higher affinity than leptin-b for sLepR. According to our knowledge, this is the first experimental report about the main ligand of sLepR in teleost.