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Adipokines underlie the early origins of obesity and associated metabolic comorbidities in the offspring of women with pregestational obesity.
Arroyo-Jousse, V, Jaramillo, A, Castaño-Moreno, E, Lépez, M, Carrasco-Negüe, K, Casanello, P
Biochimica et biophysica acta. Molecular basis of disease. 2020;(2):165558
Abstract
Maternal pregestational obesity is a well-known risk factor for offspring obesity, metabolic syndrome, cardiovascular disease and type 2 diabetes. The mechanisms by which maternal obesity can induce alterations in fetal and later neonatal metabolism are not fully elucidated due to its complexity and multifactorial causes. Two adipokines, leptin and adiponectin, are involved in fetal and postnatal growth trajectories, and both are altered in women with pregestational obesity. The placenta synthesizes leptin, which goes mainly to the maternal circulation and in lesser amount to the developing fetus. Maternal pregestational obesity and hyperleptinemia are associated with placental dysfunction and changes in nutrient transporters which directly affect fetal growth and development. By the other side, the embryo can produce its own leptin from early in development, which is associated to fetal weight and adiposity. Adiponectin, an insulin-sensitizing adipokine, is downregulated in maternal obesity. High molecular weight (HMW) adiponectin is the most abundant form and with most biological actions. In maternal obesity lower total and HMW adiponectin levels have been described in the mother, paralleled with high levels in the umbilical cord. Several studies have found that cord blood adiponectin levels are related with postnatal growth trajectories, and it has been suggested that low adiponectin levels in women with pregestational obesity enhance placental insulin sensitivity and activation of placental amino acid transport systems, supporting fetal overgrowth. The possible mechanisms by which maternal pregestational obesity, focusing in the actions of leptin and adiponectin, affects the fetal development and postnatal growth trajectories in their offspring are discussed.
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The Metabolic Syndrome: Emerging Novel Insights Regarding the Relationship between the Homeostasis Model Assessment of Insulin Resistance and other Key Predictive Markers in Young Adults of Western Algeria.
Belhayara, MI, Mellouk, Z, Hamdaoui, MS, Bachaoui, M, Kheroua, O, Malaisse, WJ
Nutrients. 2020;(3)
Abstract
Several biological markers have been identified as risk factors for cardiovascular disease and are associated with increased risk of metabolic syndrome (MetS). This study provides a factual information on promising biomarkers that are associated with MetS and can aid in early detection and management of MetS in young adults of Western Algeria. We studied a total of one hundred subjects aged between thirty and forty years with MetS, in which anthropometric measurements, insulin resistance, C peptide and HbA1c, lipid profile, circulating adipokines and glucagon-like peptide-1 were measured by suitable methods, in comparison to two groups of control. MetS is closely linked to altered glucose homeostasis, the plasma insulin/glucose ratio; i.e., the insulinogenic index helps to estimate the level of insulin secretion and also for assessing β-cell function. The correlation between homeostasis model assessment insulin resistance index (HOMA-IR) and HbA1c, body mass index or plasma triglycerides yielded positive and significant values. Biomarkers with a known and predictable association with MetS can provide a means to detect those at risk and intervene as needed. This could significantly decrease the burden complications impose on patients and the healthcare system.
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Zinc-alpha2-glycoprotein, dysglycaemia and insulin resistance: a systematic review and meta-analysis.
Pearsey, HM, Henson, J, Sargeant, JA, Davies, MJ, Khunti, K, Suzuki, T, Bowden-Davies, KA, Cuthbertson, DJ, Yates, TE
Reviews in endocrine & metabolic disorders. 2020;(4):569-575
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Abstract
To systematically review the current literature investigating associations between zinc-alpha2-glycoprotein (ZAG) and dysglycaemia (including type 2 diabetes (T2DM), poly-cystic-ovary syndrome (PCOS), pre-diabetes or insulin resistance). This included relationships between ZAG and continuous measures of insulin and glucose. Additionally, we performed a meta-analysis to estimate the extent that ZAG differs between individuals with or without dysglycaemia; whilst examining the potential influence of adiposity. A systematic search was performed on four databases for studies on circulating ZAG concentrations in adult human populations, comparing healthy controls to individuals with dysglycaemia. Key characteristics, including the mean ZAG concentrations (mg∙L-1), and any correlational statistics between ZAG and continuous measures of glucose, glycated haemoglobin (HbA1c) or insulin were extracted. Meta-analyses were performed to compare metabolically healthy controls to cases, and on studies that compared controls and cases considered overweight or obese (body mass index (BMI) ≥25 kg.m2). 1575 papers were identified and 14 studies (16 cohorts) were considered eligible for inclusion. Circulating ZAG was lower in individuals with dysglycaemia compared to metabolically healthy controls (-4.14 [-8.17, -0.11] mg.L-1; I2 = 98.5%; p < 0.001). When using data from only studies with overweight or obese groups with or without dysglycaemia (three studies (four cohorts); pooled n = 332), the difference in circulating ZAG was no longer significant (-0.30 [-3.67, 3.07] mg. L-1; I2 = 28.0%; p = 0.225). These data suggest that ZAG may be implicated in dysglycaemia, although there was significant heterogeneity across different studies and the mediating effect of adiposity cannot be excluded. Therefore, more research is needed before robust conclusions can be drawn.
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Evaluation of Agraz Consumption on Adipocytokines, Inflammation, and Oxidative Stress Markers in Women with Metabolic Syndrome.
Espinosa-Moncada, J, Marín-Echeverri, C, Galvis-Pérez, Y, Ciro-Gómez, G, Aristizábal, JC, Blesso, CN, Fernandez, ML, Barona-Acevedo, J
Nutrients. 2018;(11)
Abstract
Metabolic syndrome (MetS) is characterized by increased oxidative stress and a pro-inflammatory state. Vaccinium meridionale Swartz (known as "agraz") is a berry rich in polyphenolic compounds with demonstrated antioxidant activity and anti-inflammatory effects in preclinical studies. The aim of this study was to evaluate the effects of agraz consumption on inflammatory and oxidative stress markers in women with MetS. Forty women with MetS (47 ± 9 years) were randomly assigned to consume daily either 200 mL of agraz nectar or placebo over four weeks in a double-blind, cross-over design study, separated by a 4-week washout period. Metabolic and inflammatory markers in serum and antioxidant/oxidative stress markers in serum and urine were assessed at the end of each period. Serum antioxidant capacity measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was significantly higher (p = 0.028), while urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) was lower (p = 0.041) after agraz consumption, compared to placebo. In conclusion, consumption of agraz during four weeks increased serum antioxidant capacity and decreased a marker of DNA oxidative damage in women with MetS, compared to placebo. These results suggest that agraz consumption may play a protective role in patients with MetS.
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The Adipokine-Cardiovascular-Lifestyle Network: Translation to Clinical Practice.
Mechanick, JI, Zhao, S, Garvey, WT
Journal of the American College of Cardiology. 2016;(16):1785-1803
Abstract
Adipokines are peptides, secreted by adipocytes and other cell types with targets in other tissues, participating in a complex network of humoral factors involved in obesity, insulin resistance, and cardiovascular (CV) disease. This review describes recent information about adipokine effects on the CV system. Rather than simply providing a listing of adipokines and their respective effects, network analysis is used to enhance understanding. Various relationships and emergent processes in the adipokine-CV system network are discussed, with the most significant interactors being responses to hypoxia, regulation of cell migration, effects on blood coagulation, and platelet activation. Clinical translation is provided through network representations of the "obesity paradox," "metabolically healthy obese," "metabolic syndrome," and beneficial role of lifestyle medicine. As more translatable information about the larger adipokine-CV-lifestyle network is acquired from laboratory and clinical research, the strategic and precise role of lifestyle intervention can be fashioned to improve CV outcomes.
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Novel adipokines: their potential role in the pathogenesis of obesity and metabolic disorders.
Korek, E, Krauss, H
Postepy higieny i medycyny doswiadczalnej (Online). 2015;(0):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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Correcting vitamin D insufficiency improves insulin sensitivity in obese adolescents: a randomized controlled trial.
Belenchia, AM, Tosh, AK, Hillman, LS, Peterson, CA
The American journal of clinical nutrition. 2013;(4):774-81
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Abstract
BACKGROUND Obese adolescents are at a greater risk of vitamin D deficiency because vitamin D is thought to be sequestered by excess adipose tissue. Poor vitamin D status has been associated with a higher prevalence of the metabolic syndrome, type 2 diabetes, or both in adults and adolescents. OBJECTIVE The objective was to determine in obese adolescents the efficacy and safety of 4000 IU vitamin D3/d and whether subsequent increased circulating concentrations of 25-hydroxyvitamin D [25(OH)D] are associated with improved markers of insulin sensitivity and resistance and reduced inflammation. DESIGN Obese adolescent patients [n = 35; mean ± SD age: 14.1 ± 2.8 y; BMI (in kg/m(2)): 39.8 ± 6.1; 25(OH)D: 19.6 ± 7.1 ng/mL] were recruited from the University of Missouri Adolescent Diabetes and Obesity Clinic and were randomly assigned to receive either vitamin D3 (4000 IU/d) or placebo as part of their standard care. Anthropometric measurements, inflammatory markers (IL-6, TNF-α, C-reactive protein), adipokines (leptin, adiponectin), fasting glucose, fasting insulin, and HOMA-IR values were measured at baseline and at 2 follow-up visits (3 and 6 mo). RESULTS After 6 mo, there were no significant differences in BMI, serum inflammatory markers, or plasma glucose concentrations between groups. Participants supplemented with vitamin D3 had increases in serum 25(OH)D concentrations (19.5 compared with 2.8 ng/mL for placebo; P < 0.001), fasting insulin (-6.5 compared with +1.2 μU/mL for placebo; P = 0.026), HOMA-IR (-1.363 compared with +0.27 for placebo; P = 0.033), and leptin-to-adiponectin ratio (-1.41 compared with +0.10 for placebo; P = 0.045). Inflammatory markers remained unchanged. CONCLUSION The correction of poor vitamin D status through dietary supplementation may be an effective addition to the standard treatment of obesity and its associated insulin resistance. This trial was registered at clinicaltrials.gov as NCT00994396.
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Supplementation of highly concentrated β-cryptoxanthin in a satsuma mandarin beverage improves adipocytokine profiles in obese Japanese women.
Iwamoto, M, Imai, K, Ohta, H, Shirouchi, B, Sato, M
Lipids in health and disease. 2012;:52
Abstract
BACKGROUND Serum β-cryptoxanthin levels are lower in overweight subjects than in normal subjects. Abnormalities of adipocytokine profiles in obesity subjects have been reported. There are several reports that serum β-cryptoxanthin levels in them were relatively lower than normal subjects. OBJECTIVE We hypothesize that supplementation of highly concentrated β-cryptoxanthin improves serum adipocytokine profiles in obese subjects. This study tested the association between β-cryptoxanthin intake and serum adipocytokine levels. METHODS An intervention study consisted of a 3-week long before-and-after controlled trial, where β-cryptoxanthin (4.7 mg/day) was given to 17 moderately obese postmenopausal women. RESULTS The results indicated no significant changes in body weight or body mass index (BMI). Serum β-cryptoxanthin levels increased significantly by 4-fold. Serum high molecular weight (HMW)-adiponectin levels increased significantly, while serum plasminogen activator inhibitor (PAI)-1 levels decreased. CONCLUSIONS We concluded that increasing the intake of β-cryptoxanthin to approximately 4 mg per day for 3 weeks may have beneficial effects on the serum adipocytokine status and consequently alleviate progression of metabolic syndrome.
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Greater weight loss and hormonal changes after 6 months diet with carbohydrates eaten mostly at dinner.
Sofer, S, Eliraz, A, Kaplan, S, Voet, H, Fink, G, Kima, T, Madar, Z
Obesity (Silver Spring, Md.). 2011;(10):2006-14
Abstract
This study was designed to investigate the effect of a low-calorie diet with carbohydrates eaten mostly at dinner on anthropometric, hunger/satiety, biochemical, and inflammatory parameters. Hormonal secretions were also evaluated. Seventy-eight police officers (BMI >30) were randomly assigned to experimental (carbohydrates eaten mostly at dinner) or control weight loss diets for 6 months. On day 0, 7, 90, and 180 blood samples and hunger scores were collected every 4 h from 0800 to 2000 hours. Anthropometric measurements were collected throughout the study. Greater weight loss, abdominal circumference, and body fat mass reductions were observed in the experimental diet in comparison to controls. Hunger scores were lower and greater improvements in fasting glucose, average daily insulin concentrations, and homeostasis model assessment for insulin resistance (HOMA(IR)), T-cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were observed in comparison to controls. The experimental diet modified daily leptin and adiponectin concentrations compared to those observed at baseline and to a control diet. A simple dietary manipulation of carbohydrate distribution appears to have additional benefits when compared to a conventional weight loss diet in individuals suffering from obesity. It might also be beneficial for individuals suffering from insulin resistance and the metabolic syndrome. Further research is required to confirm and clarify the mechanisms by which this relatively simple diet approach enhances satiety, leads to better anthropometric outcomes, and achieves improved metabolic response, compared to a more conventional dietary approach.
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Nutrition education guided by Dietary Guidelines for Chinese Residents on metabolic syndrome characteristics, adipokines and inflammatory markers.
Zhang, SX, Guo, HW, Wan, WT, Xue, K
Asia Pacific journal of clinical nutrition. 2011;(1):77-86
Abstract
OBJECTIVE The objective of this study was to test whether "Dietary Guidelines for Chinese Residents" have beneficial effects on anthropometric and metabolic variables, adipokines and inflammatory markers in metabolic syndrome patients. METHODS AND PROCEDURES A multi-stage sampling method was applied to select metabolic syndrome patients in two districts of Shanghai. Two hundred and seventy-two metabolic syndrome patients were divided into control and intervention groups according to their district. Nutrition education guided by "Dietary Guidelines for Chinese Residents" was performed in the intervention group for one year. RESULTS Nutrition-related knowledge, attitudes and behavior were improved in the intervention group. Potassium intake and food to total energy ratio for grain, vegetable and fruit increased while sodium intake as well as fat to total energy ratio decreased in the intervention group compared to the control group (p<0.05). Correspondently, the intervention group significantly improved its waist circumference, waist to hip ratio, high-density lipoprotein cholesterol, adiponectin, leptin and tumor necrosis factor-α compared to the control group (p<0.05). Waist circumference changes from baseline to end of the study in the intervention and the control groups were -3.9±0.3 and -2.3±0.4 cm respectively. There was a significant difference between the two groups (p=0.004). Means of waist circumference, waist to hip ratio, leptin and tumor necrosis factor-α were lower, and high density lipoprotein-cholesterol was higher in the intervention group than the control group (p<0.05). CONCLUSION This study confirmed "Dietary Guidelines for Chinese Residents" had beneficial effects on anthropometric, lipids, adipokines and inflammatory markers in metabolic syndrome patients.