Lower Leptin Levels Research Articles

Modulation of the transcriptomic profile of the R2C tumor Leydig cell line by the adipose tissue derived hormone leptin

Leptin is an important adipose derived hormone being secreted by adipocytes and involved in appetite regulation. Disruption of normal plasma levels of leptin has been associated with the pathogenesis of obesity. It is now well established that obesity is associated to an increased risk of cancer development, including testicular cancers. Recently, we have shown that high levels of leptin have inhibitory effects on cAMP-dependent steroidogenic genes expression in MA-10 Leydig cells. Hence, we examined if leptin could alter the transcriptome of the constitutively steroidogenic rat tumor Leydig cell line R2C. These cells were treated with high levels of leptin (1000 ng/ml) for 4 h, followed by mRNA extraction and RNA-Seq analysis. Interestingly, leptin had no effect on steroidogenic gene expression or pathways promoting tumorigenesis of this cell line. Genes being upregulated or downregulated by leptin were enriched in biological processes that were non-relevant to Leydig cell function. Surprisingly, lepr isoforms were weakly expressed in R2C cells and may explain in part the low levels of leptin’s response for tumor Leydig cells. Hence, the current findings suggest that acute treatments of tumor Leydig cells with high levels of leptin have negligible effects on transcriptomics and rather supports that leptin would have a central effect on the hypothalamus to influence testicular function.

Serum leptin level is associated with phase angle in CKD5 patients not undergoing dialysis.

ObjectiveMalnutrition is very complex in patients with end-stage renal disease (ESRD) and is associated with poor prognosis. This is because hemodynamic changes, hormonal changes, persistent inflammatory reactions, and fluid overloads are more complicated as uremia is worsening. Bio-impedance spectroscopy (BIS) is a useful method to estimate fluid balance (Overhydration/ extracellular water, OH/ECW) and nutritional status (Phase angle, PhA). We aimed to evaluate the volume and nutritional status by BIS and to investigate the relationship between the appetite regulating hormones and the parameters of BIS in patients with stage 5 chronic kidney disease not undergoing dialysis (CKD5-ND).MethodsWe enrolled a total of 91 CKD5-ND patients. We measured routine serum markers including albumin and NT-proBNP and the appetite regulating hormones, leptin and ghrelin. We defined poor nutritional status as a PhA < 4.5°, and proper nutritional status as a PhA ≥ 4.5°. We also evaluated each patient’s nutritional status by assessing their geriatric nutritional risk index (GNRI) and their volume status by measuring NT-proBNP.ResultsForty-one patients (45%) had poor nutritional status. Patients with a poor nutritional status had significantly higher OH/ECW (29.6 ± 12.7% vs. 6.2 ± 10.3%, p<0.001) and lower levels of leptin (3.8 ± 3.1 vs. 7.0 ± 6.2 ng/mL, p = 0.004) than those with proper nutritional status. PhA was associated with GNRI (r = 0.597, P<0.001) and NT-proBNP was associated with OH/ECW (r = 0.384, P<0.001). Leptin was negatively correlated with OH/ECW (r = -0.288, p = 0.006). In contrast, leptin was positively correlated with PhA (r = 0.263, p = 0.012). In multivariate logistic regression, high level of leptin (OR 7.00, 95% CI 1.74–28.10) was associated with proper nutrition, while an increased OH/ECW (OR 0.65, 95% CI 0.51–0.84) was associated with poor nutrition.ConclusionsOur study demonstrates that CKD5-ND patients with poor nutrition generally also suffer from excessive body fluid. Low leptin level suggests poor nutrition in CKD5-ND patients. PhA could be used as a nutritional index for ESRD patients.

High Ghrelin Level Predicts the Curve Progression of Adolescent Idiopathic Scoliosis Girls.

Background Adolescent idiopathic scoliosis (AIS) is common deformity with unknown cause. Previous studies have suggested the abnormal serum leptin and ghrelin level in AIS girls. The aim of present study was to evaluate whether the serum leptin and ghrelin level could serve as risk factor in predicting the curve progression in AIS girls. The associations between them and the physical characteristics were also investigated. Materials and Methods Circulating leptin and ghrelin levels from 105 AIS girls and 40 age-matched non-AIS girls were examined by enzyme-linked immunosorbent assay. The correlations between ghrelin and leptin levels and growth-related parameters (age, weight, corrected height, corrected BMI, main Cobb angle, and Risser sign) were analyzed in AIS group. Multivariate logistic regression was used to investigate factors predicting curve progression in AIS girls. Results A significantly lower leptin level (6.55 ± 2.88 vs. 8.01 ± 3.12 ng/ml, p < 0.05) and a higher ghrelin level (6.33 ± 2.46 vs. 4.46 ± 2.02 ng/ml, p < 0.05) were found in all AIS patients, as compared with normal controls. Curve progression patients had a higher ghrelin level than stable curve patients (7.61 ± 2.48 vs. 5.54 ± 2.11 ng/ml, p < 0.01); for leptin level, there was no significant difference between progression and stable group. The results of multivariate logistic stepwise regression showed that premenarche status, initial main Cobb magnitude that was more than or equal to 23°, high ghrelin level (≥7.30 ng/ml), and lower Risser grade (grades 0 to 2) were identified as risk factors in predicting curve progression. Ghrelin levels of >6.48 ng/ml were predictive for curve progression with 70.00 % sensitivity and 72.31 % specificity, and the area under the curve (AUC) was 0.741 (95 % confidence interval 0.646-0.821). Conclusions High ghrelin level may serve as a new quantitative indicator for predicting curve progression in AIS girls.

Leptin and ghrelin in chronic kidney disease: their associations with protein-energy wasting.

This study aimed to evaluate plasma concentrations of leptin and total ghrelin in children with chronic kidney disease (CKD) and assess their roles in protein-energy wasting (PEW). This study consisted of three different CKD populations [CKD group (20 patients with non-dialysis CKD), dialysis group (39 patients on dialysis), and kidney transplant (KTx) group (35 KTx recipients)] and control group (18 healthy children). Plasma leptin and total ghrelin levels were measured. Multi-frequency bioimpedance analysis was used for the assessment of fat and lean mass. PEW was defined using criteria including body mass, muscle mass, growth, serum albumin level, and protein intake. While plasma leptin levels did not differ among the study groups, total ghrelin levels were significantly higher in the dialysis group (P< 0.001). Seven dialysis patients (18%) and one CKD patient (5%) but none of the KTx recipients met the criteria of PEW. Dialysis patients with PEW had lower plasma leptin levels compared to their counterparts (P= 0.018); however, total ghrelin levels did not differ between the two groups (P= 0.10). Low leptin level in dialysis patients was independently associated with lower fat mass index (P< 0.001) and lower height-specific SD scores of BMI (P= 0.019). PEW is prevalent in dialysis patients. Low levels of leptin seem to be associated with PEW. Our result suggests that low leptin levels may be a consequence rather than a cause of PEW. Longitudinal studies are required to investigate this complex relationship between leptin and PEW in pediatric dialysis patients.

Obesity and Breast Cancer: Association of Serum Adiponectin, Leptin, and Adiponectin–Leptin Ratio as Risk Biomarkers

AbstractIntroduction: Obesity has been associated with the development of breast cancer. The objectives were to study the association of serum adiponectin, serum leptin, and adiponectin–leptin ratio (ALR) in patients with breast cancer and matched controls, and to study their relationship with the various clinicopathological characteristics of breast cancer. Materials and Methods: A prospective, hospital-based case–control study was conducted on 40 patients with a first-confirmed histopathology diagnosis of breast cancer and 40 controls comprising individuals without a history of cancer simultaneously recruited from the health examination clinics during the same study period. Serum adiponectin and leptin concentrations were measured in a single run using commercially available kits (Human ADP/Acrp30 [adiponectin] enzyme-linked immune-sorbent assay [ELISA] kit and Human Leptin ELISA kit, Elabscience Biotechnology Co., Ltd) according to the manufacturer's instructions. Results:: Serum adiponectin levels were reduced significantly in breast cancer patients, in comparison to controls (P = 0.04), while serum leptin levels were increased significantly in breast cancer patients, in comparison to controls (P = 0.03). ALR was significantly lower in breast cancer cases, in comparison to controls (P = 0.05). There was no correlation between receptor status (estrogen receptor, progesterone receptor, Her2/neu), aggressiveness of disease in terms of tumor size, nodal metastases, stage, tumor grade, and serum adiponectin levels, leptin levels, or ALR. Body mass index was negatively correlated with serum adiponectin levels and ALR (r = 0.33, P = 0.03; r = 0.39, P = 0.01, respectively) and positively correlated with serum leptin levels (r = 0.34, P = 0.02). Conclusion: In summary, our results suggest that low serum adiponectin levels, ALR, and high serum leptin levels are associated with breast cancer.

Efficacy of Metreleptin for Weight Loss in Overweight and Obese Adults with Low Leptin Levels

Leptin, an adipokine, regulates appetite, glucose and fat metabolism, and neuroendocrine function. A post-hoc pooled analysis of 4 studies (N=1064) in adults with BMI 27.0-40.0 kg/m2 showed that metreleptin (MTL), a leptin analogue, reduced weight in subgroups of adults with low baseline (BL) leptin levels (Fig. 1). A subsequent study (N=267) in adults with low BL leptin (females, ≤16 ng/mL; males, ≤5 ng/mL) and BMI 27.5-38.0 kg/m2 was conducted. Subjects (64% female; mean [SD] BL leptin, 14.2 [13.3] ng/mL) received QD subcutaneous MTL 10 mg, MTL 20 mg, or placebo. Both MTL doses decreased weight over time among subjects with low BL leptin (Fig. 2). MTL 20 mg showed statistically significant decreases by week 8. MTL was well tolerated. Thus, MTL 20 mg QD holds promise for weight loss among overweight and obese adults with low leptin levels. Disclosure A. DePaoli: Research Support; Self; Eli Lilly and Company, Merck Sharp &amp; Dohme Corp. A. Long: Employee; Self; Aegerion Pharmaceuticals. G.M. Fine: Employee; Self; Aegerion Pharmaceuticals. M. Stewart: Employee; Self; Novelion. Stock/Shareholder; Self; Novelion. S. O'rahilly: Advisory Panel; Self; Aegerion Pharmaceuticals, Pfizer Inc., AstraZeneca, MedImmune, Novo Nordisk Inc., ERX Pharmaceuticals, Inc..

Novel Associations of Adipokines and Atherosclerotic Markers with Rising Levels of Insulin Resistance in a Mexican-American Border Population

Background: Epidemiological studies suggest that increased levels of leptin and resistin, and decreased levels of adiponectin are associated with worsening insulin resistance (IR) and atherosclerosis. However, it is unclear if these findings apply to Mexican-Americans, as few have been studied. We examined the relationship of these adipokines and carotid intima media thickness (cIMT) to IR and atherosclerosis in a Mexican-American population. Methods: A retrospective cross-sectional analysis of the Cameron County Hispanic Cohort (CCHC) was performed. Adult participants were stratified into three groups of IR: no-diabetes, prediabetes, and diabetes mellitus (DM). We examined differences in levels of adipokines and cIMT across groups. We constructed multivariable linear and logistic regression models to account for confounding factors. There were 819 subjects (43%, 35%, and 22% for no-diabetes, prediabetes, and DM, respectively) for the study of adipokines and 249 subjects for the study of cIMT (34%, 50%, and 16% for no-diabetes, prediabetes, and DM, respectively). Results: After controlling for gender, hypertension, age, and BMI, adiponectin levels lowered significantly across increasing levels of IR (p=0.002) and resistin levels did not change significantly across groups (p=0.10). Compared to no-diabetes, leptin levels surprisingly decreased significantly in DM (p=0.013). cIMT levels heightened across increasing levels of IR (p=0.01). Conclusion: In a Mexican-American population, participants with DM unexpectedly displayed lower levels of leptin compared to no diabetes. Surprisingly, there was also no change in resistin across IR groups. In DM, adiponectin levels decreased and cIMT measurements increased. These findings support the need for more research to understand the relationship of leptin deficiency to DM in this population. Disclosure A.D. Gutierrez: Speaker's Bureau; Self; AstraZeneca, Med Learning Group. C.A. Flores: None. M. Lee: None. S. Laing: None. P. Asgarisabet: None. M. Resman: None. S. Naik: None. M. Lee: None. J.B. McCormick: None. S.P. Fisher-Hoch: None.

Combined use of leptin and mechanical stress has osteogenic effects on ossification of the posterior longitudinal ligament

To evaluate the effects of leptin/leptin receptor (LepR) combined with mechanical stress on the development of ossification of the posterior longitudinal ligament (OPLL), which is a disease characterized by ectopic bone formation of the posterior longitudinal ligament (PLL) and can lead to radiculopathy and myelopathy. Six human samples of the PLL were analyzed for the expression of leptin and LepR by RT-PCR and western blotting. PLL cells were stimulated with leptin and mechanical stress delivered via a Flexcell tension system, and osteogenic differentiation was evaluated by RT-PCR and western blotting analysis of osteogenic marker expression as well as by alkaline phosphatase (ALP) staining and alizarin red S staining. Activation of mitogen-activated protein kinase (MAPK), Janus kinase (JAK) 2-signal transducer, activator of transcription (STAT) 3 and phosphatidylinositol 3-kinase (PI3K)-Akt was evaluated by western blotting. Samples from the OPLL group had higher LepR mRNA and protein levels and lower leptin levels than those from healthy controls. Exposure to leptin and Flexcell increased the number of ALP-positive cells and calcium nodules in a dose-dependent manner; this effect was accompanied by upregulation of the osteogenic markers osteocalcin, runt-related transcription factor 2 (RUNX2) and osteopontin. Extracellular signal-regulated kinase, P38 MAPK, JAK2, STAT3, PI3K and Akt signaling, was also activated by the combined effects of leptin and mechanical stress. Leptin and LepR are differentially expressed in OPLL tissues, and the combined use of leptin/LepR and mechanical stress promotes osteogenic differentiation of PLL cells via MAPK, JAK2-STAT3 and PI3K/Akt signaling. These slides can be retrieved under Electronic Supplementary Material.

Stimulating lipolysis in subcutaneous adipose tissues by chronic dexamethasone administration in goats

The objective of this study was to investigate the effects of chronic stress induced by a low dosage of dexamethasone (Dex) on the lipolytic response in adipose tissue of goats. Ten male goats were randomly assigned to two groups; one group was injected subcutaneously with 0.2 mg/kg Dex, and the other group was injected subcutaneously with the same volume of saline as a control (Con) for 21 days. The result revealed that plasma triglycerides (TG) (P < 0.05) concentrations decreased in response to Dex administration. Plasma glycerol, mainly derived from degradation of TG, increased during the Dex treatment (P < 0.05). Expression of genes involved in lipolysis—including G protein β subunit (Gnb1) (P < 0.01), hormone-sensitive lipase (Lipe) (P < 0.05), and perilipin-3 (Plin3) (P < 0.05) — were up-regulated in adipose tissue by Dex. Paralleling the increase in gene expression, the pLIPE/LIPE ratio also increased in response to Dex, which reflected higher LIPE activity, in adipose tissue (P < 0.05). However, the expression of genes involved in fatty acids synthesis—such as acetyl CoA carboxylase (Acc), fatty acid synthase (Fas), and stearoyl-CoA desaturase (Scd)—were not changed by Dex, while the abundance of diglyceride acyltransferase 1 and 2 (Dgat1 and Dgat2) mRNA, which catalyze the formation of TGs from diacylglycerol and Acyl-CoA, increased (P < 0.05) in adipose tissue of Dex-treated goats compared with Con goats. Moreover, plasma leptin concentration decreased in response to Dex; however, Leptin mRNA expression tended to increase in adipose tissue, indicating a negative feedback regulatory mechanism. Adiponectin gene expression was also up-regulated in adipose tissue by Dex (P < 0.05). Taken together, our findings demonstrate that chronic glucocorticoid administration induces an imbalance in TG metabolism, resulting in a lower level of leptin and a higher level of glycerol in blood by promoting lipolysis and Gnb1 and Plin3 expression in adipose tissue, as well as increasing the pLIPE: LIPE ratio.

The Gravitostat Regulates Fat Mass in Obese Male Mice While Leptin Regulates Fat Mass in Lean Male Mice

Leptin has been the only known homeostatic regulator of fat mass, but we recently found evidence for a second one, named the gravitostat. In the current study, we compared the effects of leptin and increased loading (gravitostat stimulation) on fat mass in mice with different levels of body weight (lean, overweight, and obese). Leptin infusion suppressed body weight and fat mass in lean mice given normal chow but not in overweight or obese mice given a high-fat diet for 4 and 8 weeks, respectively. The maximum effect of leptin on body weight and fat mass was obtained already at <44 ng/mL of serum leptin. Increased loading using intraperitoneal capsules with different weights decreased body weight in overweight and obese mice. Although the implantation of an empty capsule reduced the body weight in lean mice, only a nonsignificant tendency of a specific effect of increased loading was observed in the lean mice. These findings demonstrate that the gravitostat regulates fat mass in obese mice, whereas leptin regulates fat mass only in lean mice with low endogenous serum leptin levels. We propose that activation of the gravitostat primarily protects against obesity, whereas low levels of leptin protect against undernutrition.

Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

Seipin deficiency is responsible for type 2 congenital generalized lipodystrophy with severe loss of adipose tissue (AT) and could lead to renal failure in humans. However, the effect of Seipin on renal function is poorly understood. Here we report that Seipin knockout (SKO) mice exhibited impaired renal function, enlarged glomerular and mesangial surface areas, renal depositions of lipid, and advanced glycation end products. Elevated glycosuria and increased electrolyte excretion were also detected. Relative renal gene expression in fatty acid oxidation and reabsorption pathways were impaired in SKO mice. Elevated glycosuria might be associated with reduced renal glucose transporter 2 levels. To improve renal function, AT transplantation or leptin administration alone was performed. Both treatments effectively ameliorated renal injury by improving all of the parameters that were measured in the kidney. The treatments also rescued insulin resistance and low plasma leptin levels in SKO mice. Our findings demonstrate for the first time that Seipin deficiency induces renal injury, which is closely related to glucolipotoxicity and impaired renal reabsorption in SKO mice, and is primarily caused by the loss of AT and especially the lack of leptin. AT transplantation and leptin administration are two effective treatments for renal injury in Seipin-deficient mice.-Liu, X.-J., Wu, X.-Y., Wang, H., Wang, S.-X., Kong, W., Zhang, L., Liu, G., Huang, W. Renal injury in Seipin-deficient lipodystrophic mice and its reversal by adipose tissue transplantation or leptin administration alone: adipose tissue-kidney crosstalk.

Increased concentrations of serum nesfatin-1 levels in childhood with idiopathic chronic malnutrition

Background/aim: Nesfatin-1, an anorexigenic molecule, seems to play a role in appetite regulation and energy homeostasis. The goal of this study was to evaluate the relation of nesfatin-1 with anthropometric and metabolic (ghrelin, leptin) parameters in children with idiopathic chronic malnutrition. Materials and methods: The study included 37 underweight and 38 healthy children who were similar regarding age, sex, and pubertal status. Anthropometric and biochemical (nesfatin-1, ghrelin, and leptin levels) variables were assessed. Results: A total of 37 underweight subjects (mean age 10.5 ± 2.6 years) and 38 heathy subjects (mean age 10.3 ± 2.3 years) were recruited. Underweight children had significantly higher nesfatin-1 (2.76 ± 0.4 vs. 1.56 ± 0.7, P < 0.001) and lower leptin levels (2.21 ± 2.0 vs. 5.21 ± 2.4, P < 0.001) than those of the control subjects. Nesfatin-1 levels were significantly associated with only leptin levels, after adjusting for age and BMI (r = –0.371, P = 0.001). Conclusion: The present study is the first to evaluate nesfatin-1 levels in relation with anthropometric and metabolic parameters in children with chronic malnutrition, who were subsequently found to have significantly higher nesfatin-1 levels. Our study underlines that nesfatin-1 may play a role in the development of malnutrition by inhibiting food intake in children.

Circulating and Adipose Tissue mRNA Levels of Zinc-α2-Glycoprotein, Leptin, High-Molecular-Weight Adiponectin, and Tumor Necrosis Factor-Alpha in Colorectal Cancer Patients With or Without Obesity.

To explore zinc-α2-glycoprotein (ZAG), leptin, high-molecular-weight adiponectin (HMW-ADPN), and tumor necrosis factor-alpha (TNF-α) levels in serum and subcutaneous and visceral white adipose tissue (sWAT and vWAT) among normal weight (NW) and overweight/obese (OW/OB) patients with colorectal cancer (CRC). A total of 76 Chinese CRC patients (42 NW + CRC, 34 OW/OB + CRC) and 40 healthy controls were recruited. Serum levels of the adipokines of interest were measured by an enzyme-linked immunosorbent assay method, and their mRNA levels in sWAT and vWAT were determined by reverse transcription quantitative PCR methods. Serum ZAG levels in the NW + CRC group were significantly increased by 11.7% compared with the healthy controls. Serum leptin levels in the OW/OB + CRC group were found to be increased by 57.7%, while HMW-ADPN levels were decreased by 23.5% when compared with the NW + CRC group of CRC patients. Additionally, ZAG mRNA levels in sWAT were significantly reduced by 78.8% in OB + CRC in comparison with NW + CRC patients. ZAG mRNA levels were negatively associated with body mass index (BMI) in sWAT but positively correlated with BMI in vWAT. TNF-α mRNA levels in vWAT of OB + CRC patients were significantly increased by 2.8-fold when compared with NW + CRC patients. In particular, CRC was independently associated with serum ZAG levels. The risk of CRC in participants with high tertile serum ZAG levels was 5.84-fold higher than in those with low tertile ZAG levels after adjusting for age, gender, and other confounders [odds ratio (OR) = 6.84, 95% confidence interval (CI) 1.70-27.54, P = 0.03]. The CRC risk in participants with high tertile leptin levels was only 10.7% of those with low tertile leptin levels (OR = 0.11, 95% CI 0.01-0.89, P = 0.04). The area under the receiver operating characteristic (ROC) curve of ZAG was 0.66 (95% CI 0.54-0.77, P < 0.05). At the cutoff value of 1.42 µg/mL serum ZAG, the sensitivity and specificity for differentiating patients with CRC from controls were 62.2 and 69.2%, respectively. Serum ZAG levels were significantly increased in CRC patients. Subjects with higher circulating ZAG and lower leptin levels were more likely to have CRC than those with lower ZAG and higher leptin levels. Serum ZAG might be a potential diagnostic biomarker for CRC in the Chinese population.

A role for TLR10 in obesity and adipose tissue morphology

Toll like receptors (TLRs) are expressed in adipose tissue and promote adipose tissue inflammation during obesity. Recently, anti-inflammatory properties have been attributed to TLR10 in myeloid cells, the only member of the TLR family with inhibitory activity. In order to assess whether TLR10-induced inhibition of inflammation may be protective during the development of obesity and metabolic abnormalities we used transgenic human TLR10 mice (hTLR10tg) and wild type (WT) controls on a C57B6J background. HFD-feeding enhanced TLR10 expression in the adipose tissue, and HFD-fed hTLR10tg mice displayed reduced adipocyte size, adipose tissue weight, and a trend toward lower plasma insulin levels compared to WT mice.In humans, obese individuals with polymorphisms in the TLR10 gene displayed reduced macrophage infiltration in the adipose tissue accompanied by a trend to lower leptin levels and higher adiponectin levels in plasma. In healthy individuals with the same polymorphisms in the TLR10 gene we did not observe any difference in plasma concentrations of leptin and adiponectin.We conclude that TLR10 impacts adipose tissue morphology in obesity. Larger studies in humans are warranted to assess its potential value as therapeutic target in metabolic syndrome and type 2 diabetes.

Alkaloid Fraction of Alstonia Boonei Stem Bark Demonstrate Antiobesity Potential on High Fat Diet Induced Obesity in Male Sprague‐Dawley Rats

The aim of this study was to investigate the anti‐obesity potential of alkaloid fraction of Alstonia boonei stem bark on high fat diet (HFD) induced obesity in male Sprague‐dawley rats.Preparation of neutral alkaloid fraction (NAF) was done through solvent partitioning of the methanol extract of Alstonia boonei stem bark, and NAF was subjected to LCMS‐MS analysis. To induce obesity, rats were fed with HFD (60% fat content) for 12 weeks preceding oral treatment with 125 and 250 mg/kg body weight of NAF for 4 weeks. Experimental procedures involving rats followed the European Community guidelines (EEC Directive of 1986; 86/609/EEC) for animal use.The major compounds found in NAF includes: Ajmalicine, 16‐Methoxy‐2,3‐dihydro‐3‐hydroxytabersonine, Vincamine, Aspidofractine, 3‐Hydroxyquinidine, 16‐Methoxytabersonine, Mitraphylline, 18‐Hydroxyyohimbine and Catharanthine. NAF significantly (p &lt; 0.05) decreased body weight, white adipose tissue, triglycerides, total cholesterol, low density lipoprotein cholesterol, very low density lipoprotein cholesterol, leptin, insulin and dopamine levels, but increased significantly (p &lt; 0.05) the high density lipoprotein cholesterol, cortisol, serotonin and noradrenaline levels in the treated groups compared to HFD control. However, there were no significant (p &gt; 0.05) changes in food intake, blood glucose, thyroxine, triiodothyronine and thyroid stimulating hormone levels in animals given NAF when compared to HFD control. The photomicrograph of liver of the rats treated with NAF showed slight fat changes unlike that of the HFD obese controls which showed presence of numerous prominent fat deposits on the livers.The findings in this study suggests that the alkaloid fraction of A. boonei possess antiobesity properties as indicated in improved lipid profile, leptin sensitivity, and decreased body weight of animals.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Potential association of LMNA-associated generalized lipodystrophy with juvenile dermatomyositis

BackgroundJuvenile dermatomyositis (JDM) is an auto-immune muscle disease which presents with skin manifestations and muscle weakness. At least 10% of the patients with JDM present with acquired lipodystrophy. Laminopathies are caused by mutations in the lamin genes and cover a wide spectrum of diseases including muscular dystrophies and lipodystrophy. The p.T10I LMNA variant is associated with a phenotype of generalized lipodystrophy that has also been called atypical progeroid syndrome.Case presentationA previously healthy female presented with bilateral proximal lower extremity muscle weakness at age 4. She was diagnosed with JDM based on her clinical presentation, laboratory tests and magnetic resonance imaging (MRI). She had subcutaneous fat loss which started in her extremities and progressed to her whole body. At age 7, she had diabetes, hypertriglyceridemia, low leptin levels and low body fat on dual energy X-ray absorptiometry (DEXA) scan, and was diagnosed with acquired generalized lipodystrophy (AGL). Whole exome sequencing (WES) revealed a heterozygous c.29C > T; p.T10I missense pathogenic variant in LMNA, which encodes lamins A and C. Muscle biopsy confirmed JDM rather than muscular dystrophy, showing perifascicular atrophy and perivascular mononuclear cell infiltration. Immunofluroscence of skin fibroblasts confirmed nuclear atypia and fragmentation.ConclusionsThis is a unique case with p.T10I LMNA variant displaying concurrent JDM and AGL. This co-occurrence raises the intriguing possibility that LMNA, and possibly p.T10I, may have a pathogenic role in not only the occurrence of generalized lipodystrophy, but also juvenile dermatomyositis. Careful phenotypic characterization of additional patients with laminopathies as well as individuals with JDM is warranted.

Bone status and adipokine levels in children on vegetarian and omnivorous diets

Measurements of bone mineral density (BMD) reflect bone status but not the dynamics of bone turnover. Biochemical markers, which show global skeletal activity, were validated for the assessment of bone formation and resorption processes. Adipokines also play a significant role in the regulation of bone metabolism. To assess body composition, bone mineral density, bone turnover markers and adipokine levels in relation to vegetarian and omnivorous diets. The study included 53 vegetarian and 53 omnivorous prepubertal healthy children matched for age and sex (median age 7.0 years). Body composition and BMD were assessed by dual-energy X-ray absorptiometry. 25-hydroxyvitamin D and parathormone levels were measured by chemiluminescence method. Serum carboxy-terminal propeptide of type I collagen (CICP), total osteocalcin (OC) and its forms carboxylated (c-OC) and undercarboxylated (uc-OC), C-terminal cross-linking telopeptide of collagen type I (CTX), leptin and adiponectin levels were determined using immunoenzymatic assays. Both groups of children were comparable in terms of body composition, except for the percentage of fat mass, which was lower (19.24 vs. 21.77%, p=0.018) in vegetarians. Mean values of total BMD z-score and lumbar spine BMD z-score were lower (-0.583 vs.-0.194, p=0.009 and-0.877 vs.-0.496, p=0.019, respectively) in vegetarians compared with omnivores. Serum leptin level was about 2-fold lower (1.39 vs. 2.94ng/mL, p<0.001) in vegetarians, however, adiponectin concentration was similar in both groups. Vegetarians had similar concentration of 25-hydroxyvitamin D, but higher parathormone (40.8 vs. 32.1pg/mL, p=0.015) and CTX (1.94 vs. 1.76ng/mL, p=0.077) levels than omnivores. Total osteocalcin and CICP concentrations were comparable in both groups, however, c-OC/uc-OC ratio was higher (1.43 vs. 1.04ng/mL, p<0.05) in vegetarians. We found positive correlation between c-OC and nutritional parameters adjusted for total energy intake (plant protein, phosphorus, magnesium and fiber intakes) in vegetarian children. Prepubertal children on a vegetarian diet had significantly lower total and lumbar spine BMD z-scores, but absolute values of bone mineral density did not differ. BMD z-scores did not correlate with bone metabolism markers and nutritional variables, but were positively associated with anthropometric parameters. Lower leptin levels in vegetarian children reflect lower body fat. Longitudinal studies are necessary to evaluate the impact of the observed association on bone health at adulthood.

Congenital generalized lipodystrophy in Taiwan.

Congenital generalized lipodystrophy (CGL) is a rare disorder characterized by scarce adipose tissue. This disease is distributed worldwide, but little is known about these patients in the Chinese population. Here, we delineate the phenotype and prognosis of CGL in our cohort. Patients diagnosed with CGL from 8 medical centers were reviewed. The initial presentation, laboratory findings, and molecular testing were retrospectively analyzed. A total of 16 patients were analyzed, and the current median age was 3.5 years (range, 9 months-17.5 years). In all patients, molecular results confirmed BSCL2 mutation. c.782dupG (p.Ile262Hisfs*12) was the most common genotype identified. All patients had triangular faces and muscular hypertrophy. In addition, 75% presented with hepatomegaly, 19% had cardiomegaly, and 44% exhibited acanthosis nigricans. Developmental delay was noted in 5 out of 9 patients (56%) with a median developmental quotient (DQ)/intelligence quotient (IQ) of 61. Thirteen patients (81.3%) had high triglyceride levels. Eight patients received leptin analysis, and 7 of them (88%) had low leptin levels. One patient exclusively received a lipid-lowering drug, 4 patients were exclusively placed on a fat-restricted diet, 5 patients were administered combination therapy, and 5 patients received no treatment. Three patients (19%) who developed diabetes mellitus received both oral hypoglycemic agents and insulin. Three patients (19%) experienced loss of ambulation and died prematurely. Our findings highlight the uniqueness of the genotype and phenotype in our cohort. Further long-term surveillance for comorbidities is necessary for early detection and management of these patients.

Anthropometric Profile, Serum Leptin, Antioxidant Vitamins, LEPR Q223R Polymorphism and Cardiovascular Risk Factors in Adolescents

Cardiovascular disease (CVD) risk factors, such as bad eating habits, are typical in adolescence and lead to the consumption of meals that are not always sufficient in vitamins A, E, β-carotene, excess calories and elevated serum leptin levels. The purpose of this research is to study the relationship between vitamin A deficiency (VAD), β-carotene deficiency (βcD), vitamin E deficiency (VED) and to explore the association of leptin receptor Q223R polymorphisms with obesity and other risk factors for CVD. Method: This observational study included 237 adolescents recruited from Adolescents Reference Center, Brazil. It was collected: socioeconomic and clinical data, laboratory and molecular samples. Results: The average age was 14.93 ± 2.18 years, 66.2 % were girls, 38.0 % had high levels of total cholesterol (TC) between 10-14 years Triceps (TSF) and subscapular skinfolds (SSF) measurements were inversely correlated with VAD. There was also an association between VAD, βcD and high triglyceride (TG) levels. Adolescents with the RR genotype presented a trend toward higher levels of body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), TC, TG, low density lipoprotein (LDLC), leptin and low levels of high-density lipoprotein (HDL-c). Conclusion: The girls had higher levels of leptin than boys. Abdominal fat, βcD and VED were observed in adolescents with VAD. Individuals with RR genotype have drawn attention to cardiovascular risk factors such as high rate of LDLC and reduced rate of HDLc. Thus, it is possible that individuals with this genotype may be more susceptible to the presence of cardiovascular risk factors.

Association of leptin, adiponectin, and ghrelin in breast milk with the growth of infants with exclusive breastfeeding

To investigate the association of leptin, adiponectin, and ghrelin in breast milk with the weight growth velocity of infants with exclusive breastfeeding. A total of 67 full-term singleton infants who received regular child care and exclusive breastfeeding and their mothers were enrolled. The nutritional status was evaluated based on the measurements of body weight and body length (underweight, growth retardation, emaciation, overweight, and obesity). Z score was used to calculate growth velocity, and according to the ΔZ score, the infants were divided into poor growth group, low growth velocity group, and normal growth velocity group. Mature breast milk samples were collected from their mothers, and ELISA was used to measure the levels of leptin, adiponectin, and ghrelin. The emaciation group had a significantly lower level of leptin in breast milk than the non-emaciation group (P<0.05), and the overweight/obesity group had a significantly lower level of adiponectin than the non-overweight/obesity group (P<0.05). The correlation analysis showed that the level of ghrelin in breast milk was positively correlated with Z score of current body weight and ΔZ score compared with birth weight (rs=0.280 and 0.290 respectively; P<0.05). The regression analysis showed that the level of ghrelin in breast milk was an important influencing factor for the Z score of body weight (β=0.161, P<0.05). Various active constituents in breast milk, including leptin, adiponectin, and ghrelin, may regulate the growth and development of infants to a certain degree, but long-term studies and observation are needed to investigate their association with offspring growth and development and the health-promoting effect of breast milk on offspring.