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1.
Linking the Endocannabinoidome with Specific Metabolic Parameters in an Overweight and Insulin-Resistant Population: From Multivariate Exploratory Analysis to Univariate Analysis and Construction of Predictive Models.
Depommier, C, Flamand, N, Pelicaen, R, Maiter, D, Thissen, JP, Loumaye, A, Hermans, MP, Everard, A, Delzenne, NM, Di Marzo, V, et al
Cells. 2021;(1)
Abstract
The global obesity epidemic continues to rise worldwide. In this context, unraveling new interconnections between biological systems involved in obesity etiology is highly relevant. Dysregulation of the endocannabinoidome (eCBome) is associated with metabolic complications in obesity. This study aims at deciphering new associations between circulating endogenous bioactive lipids belonging to the eCBome and metabolic parameters in a population of overweight or obese individuals with metabolic syndrome. To this aim, we combined different multivariate exploratory analysis methods: canonical correlation analysis and principal component analysis, revealed associations between eCBome subsets, and metabolic parameters such as leptin, lipopolysaccharide-binding protein, and non-esterified fatty acids (NEFA). Subsequent construction of predictive regression models according to the linear combination of selected endocannabinoids demonstrates good prediction performance for NEFA. Descriptive approaches reveal the importance of specific circulating endocannabinoids and key related congeners to explain variance in the metabolic parameters in our cohort. Analysis of quartiles confirmed that these bioactive lipids were significantly higher in individuals characterized by important levels for aforementioned metabolic variables. In conclusion, by proposing a methodology for the exploration of large-scale data, our study offers additional evidence of the existence of an interplay between eCBome related-entities and metabolic parameters known to be altered in obesity.
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2.
Leptin as a predictor of metabolic syndrome in prepubertal children.
Madeira, I, Bordallo, MA, Rodrigues, NC, Carvalho, C, Gazolla, F, Collett-Solberg, P, Medeiros, C, Bordallo, AP, Borges, M, Monteiro, C, et al
Archives of endocrinology and metabolism. 2017;(1):7-13
Abstract
OBJECTIVE Leptin has been suggested as a potential biomarker of cardiovascular risk. This paper aims to ascertain, based on a sample of prepubertal children, which serum leptin value best suited to identify metabolic syndrome (MS). SUBJECTS AND METHODS This observational, cross-sectional study recruited children from the outpatient pediatrics clinic, with the purpose of validating serum leptin level cutoffs to identify MS. All obese and overweight children who met eligibility criteria were included in the study, as was a sample of normal-weight children. The sample underwent clinical assessment and blood fasting glucose, lipid profile, insulin, and leptin were measured. Sensitivity and specificity were estimated for each leptin measurement, using MS as the outcome. These values were used to construct a receiver operating characteristic (ROC) curve. The association between MS and leptin was assessed using logistic models to predict MS. RESULTS A total of 65 normal weight, 46 overweight, and 164 obese children were analyzed (160 boys, 115 girls; age: 93.7 ± 17.8 months). The most appropriate leptin cutoff was 13.4 ng/mL (sensitivity 67.6%; specificity 68.9%; accuracy 72.1%). The logistic model indicated that leptin levels above 13.4 ng/dL were significantly associated with MS and that, for every 1 ng/dL increase in leptin levels, the odds of MS increase by 3% (p = 0.002; OR 1.03; 95% CI 1.01-1.05). CONCLUSIONS Leptin may be a useful biomarker of cardiovascular risk in prepubertal children, with an optimal cutoff of 13.4 ng/mL. Identification of potential new risk markers for cardiovascular disease in children could contribute to the development of preventive strategies.
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3.
Impact of Treatment with Metformin on Adipocytokines in Patients with Polycystic Ovary Syndrome: A Meta-Analysis.
Kong, W, Niu, X, Zeng, T, Lu, M, Chen, L
PloS one. 2015;(10):e0140565
Abstract
BACKGROUND Metformin is effective for the treatment of polycystic ovary syndrome, but conflicting results regarding its effect on adipocytokine levels (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving metformin treatment have been reported. To provide high-quality evidence about the effect of metformin treatment on adipocytokines in patients with polycystic ovary syndrome, relevant studies that assessed the levels of adipocytokines (adiponectin, resistin, visfatin, and leptin) in patients with polycystic ovary syndrome receiving treatment with metformin administration were reviewed and analyzed. METHODS A literature search was conducted in the SCI, PUBMED, EMBASE, and Elsevier databases, and personal contact was made with the authors. Standard mean differences and 95% confidence intervals were calculated and combined appropriately. To ensure synthesis of the best available evidence, sensitivity analyses were performed. RESULTS A total of 34 data sets were included in 4 different outcomes, involving 744 women with polycystic ovary syndrome and adipocytokine levels measured both before and after metformin administration. Metformin treatment was associated with significantly elevated serum adiponectin concentrations (standard mean differences [95% confidence interval], -0.43 [-0.75 to -0.11]) and decreased serum leptin concentrations (0.65 [0.26 to 1.04]), whereas no significant difference in resistin level (-0.01 [-0.49 to 0.45]) or visfatin level (-0.04 [-1.55 to 1.46]) was found. CONCLUSIONS Metformin administration was associated with increased serum adiponectin concentrations and decreased serum leptin levels. Further study is needed to elucidate whether this apparent effect decreases the incidence of type 2 diabetes and other metabolic diseases in patients with polycystic ovary syndrome later in life.
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4.
[Novel adipokines: their potential role in the pathogenesis of obesity and metabolic disorders].
Korek, E, Krauss, H
Postepy higieny i medycyny doswiadczalnej (Online). 2015;:799-810
Abstract
Since identification in 1994 of leptin, a hormone produced by adipocytes, adipose tissue has become the subject of intensive research. These studies contributed to the discovery that adipocytes have the ability to synthesize and secrete biologically active substances called "adipokines". Adipokines include a variety of cytokines, peptide hormones and enzymes that play a role in a wide variety of biological functions. For example, they are involved in the regulation of appetite, energy homeostasis, vascular hemostasis, blood pressure, inflammatory and immune processes and play a role in the metabolism of carbohydrates and fats. In obese patients, the secretion of adipokines is frequently abnormal. These changes may predispose to the development of insulin resistance, hypertension and inflammation. Therefore, adipokines are the subject of ongoing clinical trials. The family of adipokines is increasing by the newly discovered peptides. This paper presents the current state of knowledge about retinol binding protein 4 (RBP-4), fasting-induced adipose factor/angiopoietin-like protein 4 (FIAF/ANGPTL4), fibroblast growth factor-21 (FGF21), dipeptidyl peptidase-4 (DPP-4), irisin and their potential role in the pathogenesis of metabolic disorders associated with obesity. The knowledge of the role of newly discovered adipokines may help in the treatment of metabolic syndrome.
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5.
Ectopic fat and adipokines in metabolically benign overweight/obese women: the Kronos Early Estrogen Prevention Study.
Ogorodnikova, AD, Khan, UI, McGinn, AP, Zeb, I, Budoff, MJ, Harman, SM, Miller, VM, Brinton, EA, Manson, JE, Hodis, HN, et al
Obesity (Silver Spring, Md.). 2013;(8):1726-33
Abstract
OBJECTIVE It is unclear why despite a comparable cardiometabolic risk profile, "metabolically benign" overweight/obese individuals show an elevated risk of cardiovascular disease compared to normal weight individuals. DESIGN AND METHODS In cross-sectional analyses, we compared levels of ectopic fat (epicardial, pericardial, and hepatic fat) and adipokines (leptin, soluble leptin receptor, and high molecular weight [HMW] adiponectin) among metabolically benign (MBO) and at-risk overweight/obese (ARO), and metabolically benign normal weight (MBNW) women, screened for the Kronos Early Estrogen Prevention Study. We defined "metabolically benign" with ≤ 1, and "at-risk" with ≥2 components of the metabolic syndrome. RESULTS Compared to MBO women, ARO women had significantly elevated odds of being in the top tertile of epicardial fat (OR: 1.76, 95% CI: 1.04-2.99), hepatic fat (OR: 1.90, 95% CI:1.12-3.24) and leptin (OR: 2.15, 95% CI: 1.23-3.76), and the bottom tertile of HMW-adiponectin (OR: 2.90, 95% CI: 1.62-5.19). Compared to MBNW women, MBO women had significantly higher odds of being in the top tertile of epicardial fat (OR: 5.17, 95% CI: 3.22-8.29), pericardial fat (OR: 9.27, 95% CI: 5.52-15.56) and hepatic fat (OR: 2.72, 95% CI: 1.77-4.19) and the bottom tertile of HMW adiponectin levels (OR: 2.51, 95% CI: 1.60-3.94). CONCLUSIONS Levels of ectopic fat and the adverse adipokine profile increase on a continuum of BMI, suggesting that the metabolically benign phenotype may be a transient state.
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6.
Serum retinol-binding protein 4, leptin, and plasma asymmetric dimethylarginine levels in obese and nonobese young women with polycystic ovary syndrome.
Yildizhan, R, Ilhan, GA, Yildizhan, B, Kolusari, A, Adali, E, Bugdayci, G
Fertility and sterility. 2011;(1):246-50
Abstract
OBJECTIVE To evaluate retinol-binding protein 4 (RBP4), leptin, and asymmetric dimethylarginine (ADMA) levels in young women with polycystic ovary syndrome (PCOS) and to investigate their relationship with each other and with clinical, metabolic, and hormonal parameters. DESIGN Clinical study. SETTING University hospital. PATIENT(S): Fifty-seven young women with PCOS (obese [n = 27] and nonobese [n = 30]) and 27 age-matched healthy controls. INTERVENTION(S): History and physical examination, peripheral venous blood sampling. MAIN OUTCOME MEASURE(S): Asymmetric dimethylarginine, RBP4, leptin, LH, FSH, DHEAS, total T, E(2), total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride (TG), and homeostasis model assessment insulin resistance index (HOMA-IR). RESULT(S): Obese women with PCOS had significantly higher HOMA-IR, DHEAS, leptin, RBP4, and ADMA levels. Leptin levels were significantly increased in nonobese subjects with PCOS. Leptin and ADMA levels were positively correlated with HOMA-IR in PCOS. There was no correlation between RBP4 and HOMA-IR. Leptin, RBP4, and ADMA levels are positively correlated in PCOS. CONCLUSION(S): [1] Young obese women with PCOS have increased ADMA, RBP4, and leptin levels, and they are positively correlated with each other. [2] The increased levels of leptin are independent of obesity, and leptin seems to have an association with IR. [3] Levels of RBP4 may not reflect IR in PCOS.
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7.
Adiponectin, retinol-binding protein 4, and leptin in protracted critical illness of pulmonary origin.
Langouche, L, Vander Perre, S, Frystyk, J, Flyvbjerg, A, Hansen, TK, Van den Berghe, G
Critical care (London, England). 2009;(4):R112
Abstract
INTRODUCTION Critically ill patients requiring intensive care uniformly develop insulin resistance. This is most pronounced in patients with sepsis. Recently, several hormones secreted by adipose tissue have been identified to be involved in overall insulin sensitivity in metabolic syndrome-related conditions. However, little is known about these adipokines in critical illness. METHODS We studied circulating levels of the adipokines adiponectin, retinol-binding protein 4 (RBP4), and leptin during critical illness, and the impact of intensive insulin therapy, a therapy shown to affect insulin sensitivity, in serum samples from prolonged critically ill patients with a respiratory critical illness (n = 318). For comparison, we studied healthy subjects (n = 22) and acutely stressed patients (n = 22). RESULTS During acute critical illness, circulating levels of adiponectin, RBP4, and leptin were low. Patients with sepsis had lower levels of leptin and RBP4 than did nonseptic patients. When critical illness was sustained, adipokine levels returned to normal reference values. Insulin therapy enhanced adiponectin, blunted the rise of RBP4, and did not alter leptin levels. CONCLUSIONS Acute critical illness is associated with immediate, but transiently low serum adipokine levels. Adiponectin and RBP4 are associated with altered insulin resistance in critical illness.
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8.
Leptin and reproduction: a review.
Moschos, S, Chan, JL, Mantzoros, CS
Fertility and sterility. 2002;(3):433-44
Abstract
OBJECTIVE To review recent advances in understanding the role of leptin in the physiology and pathophysiology of reproduction, with a focus on relevant clinical situations. DESIGN A MEDLINE computer search was performed to identify relevant articles. RESULT(S): Leptin, an adipocyte hormone important in regulating energy homeostasis, interacts with the reproductive axis at multiple sites, with stimulatory effects at the hypothalamus and pituitary and inhibitory actions at the gonads. More recently, leptin has been shown to play a role in other target reproductive organs, such as the endometrium, placenta, and mammary gland, with corresponding influences on important physiologic processes such as menstruation, pregnancy, and lactation. As a marker of whether nutritional stores are adequate, leptin may act in concert with gonadotropins and the growth hormone axis to initiate the complex process of puberty. Conditions in which nutritional status is suboptimal, such as eating disorders, exercise-induced amenorrhea, and functional hypothalamic amenorrhea, are associated with low serum leptin levels; and conditions with excess energy stores or metabolic disturbances, such as obesity and polycystic ovarian syndrome, often have elevated serum or follicular fluid leptin levels, raising the possibility that relative leptin deficiency or resistance may be at least partly responsible for the reproductive abnormalities that occur with these conditions. CONCLUSION(S): Leptin may act as the critical link between adipose tissue and the reproductive system, indicating whether adequate energy reserves are present for normal reproductive function. Future interventional studies involving leptin administration are expected to further clarify this role of leptin and may provide new therapeutic options for the reproductive dysfunction associated with states of relative leptin deficiency or resistance.