Inflammatory Adipokines, High Molecular Weight Adiponectin, and Insulin Resistance: A Population-Based Survey in Prepubertal Schoolchildren

Murdolo, Giuseppe; Nowotny, Bettina; Celi, Federica; Donati, Miranda; Bini, Vittorio; Papi, F.; Gornitzka, Gabi; Castellani, Serena; Roden, Michael; Falorni, A; Herder, Christian; Falorni, Alberto

doi:10.1371/journal.pone.0017264

Cited by 45 publications

(43 citation statements)

References 44 publications

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“…Considering the above as a whole, it is not surprising that a previous study demonstrated that, contrary to the situation in adults, visceral adipose tissue and inflammation markers were not correlated with insulin sensitivity in children (27). Moreover, another study showed that in prepubertal children, leptin emerged as a genderindependent discrimination marker of adiposity degree and as a useful, gender-associated predictor of systemic insulin resistance (28). These findings raise questions concerning the assessment and the role of visceral adiposity in children in contrast with the established data in adults.…”

Section: Discussionmentioning

confidence: 96%

Does visceral adiposity index signify early metabolic risk in children and adolescents?: Association with insulin resistance, adipokines, and subclinical inflammation

et al. 2013

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Background: Visceral adiposity index (VAI) is a novel gender-specific index based on waist circumference (WC), BMI, and lipid parameters. Although VAI does not actually estimate visceral adiposity, it accurately reflects visceral fat function and insulin resistance. This index has not been studied in children thus far. This study aims to fill this gap. Methods: In a cohort of Saudi children and adolescents, anthropometric measurements and metabolic/hormonal profile were obtained. results: A total of 543 subjects, 292 of whom were boys, were included (mean age: 11.9 ± 3.3 y; BMI: 19.8 ± 5.6 kg/m 2 ). In all subjects, VAI was inferior to BMI and WC regarding its correlations with adiponectin, leptin, insulin resistance (homeostasis model of assessment-insulin resistance (HOMA-IR)), C-reactive protein (CRP) level, and systolic blood pressure, but it exhibited a stronger association with glucose in boys (r = 0.23; P < 0.01). In stepwise multivariate analyses, only BMI was consistent as an independent predictor of adiponectin, leptin, HOMA-IR, and CRP. VAI was the only index independently associated with glucose. conclusion: Although VAI is related to glucose in children, it seems to be inferior to BMI in terms of association with insulin resistance, adipokines, and subclinical inflammation. Until specific studies can be performed in children, VAI should be extrapolated with caution in this age range.

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Section: Discussionmentioning

confidence: 96%

Does visceral adiposity index signify early metabolic risk in children and adolescents?: Association with insulin resistance, adipokines, and subclinical inflammation

et al. 2013

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“…Oppositely, no relation between lipid profile and adiponectin was reported in other paediatric studies [14,21]. Concerning adiponectin multimers, while LMW adiponectin seems to be linked with a worse lipid profile, through a positive association with TG [5], HMW adiponectin has shown opposite effects [6], even in PP individuals [11].…”

Section: Lipid Profilementioning

confidence: 87%

“…The negative associations of HMW adiponectin with IR and adiposity appear to be present even in pre-pubertal (PP) individuals [9,10]. Zimmet et al reported that in PP children, HMW adiponectin was negatively associated with body mass index (BMI) z-score, IR, triglycerides (TG), leptin and soluble intracellular adhesion molecule (sICAM); however, after adjustment for age and sex, only BMI z-score and TG maintained their negative association with HMW adiponectin [11]. These authors did not detect correlations between HMW adiponectin and proinflammatory mediators, such as resistin, interleukin (IL)-8 and IL-18 [11].…”

Section: Adiponectin and Its Isoformsmentioning

confidence: 99%

“…Zimmet et al reported that in PP children, HMW adiponectin was negatively associated with body mass index (BMI) z-score, IR, triglycerides (TG), leptin and soluble intracellular adhesion molecule (sICAM); however, after adjustment for age and sex, only BMI z-score and TG maintained their negative association with HMW adiponectin [11]. These authors did not detect correlations between HMW adiponectin and proinflammatory mediators, such as resistin, interleukin (IL)-8 and IL-18 [11]. This lack of correlation with inflammatory mediators suggests that the levels of adiponectin multimers might be more linked to changes in glucose and lipid metabolisms at young ages.…”

Section: Adiponectin and Its Isoformsmentioning

confidence: 99%

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Adiponectin, Inflammation and Cardiometabolic Risk Factors in Paediatric Obese Patients: Impact of Interventional Studies

Nascimento¹,

Coimbra²,

Rêgo³

et al. 2017

Adiposity - Omics and Molecular Understanding

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Paediatric obesity has significant physic, social and psychological implications. Childhood obesity is usually associated in adulthood with increased risk of type 2 diabetes, metabolic syndrome and cardiovascular diseases. Aggregation of cardiometabolic risk factors is already observed at young ages, with a nonlinear association with enhancement of adiposity. Adiponectin is an adipokine that inhibits inflammation, oxidative stress and metabolic syndrome components, namely dyslipidaemia, high blood pressure and insulin resistance. Obesity has been associated with hypoadiponectinaemia in both adult and paediatric patients, which may contribute to co-morbidities observed in these patients. Interventional studies that aim to tackle obesity reported controversial results. Although the general positive effect on weight loss, inflammatory and cardiometabolic markers has been studied, the impact of these interventional studies on adiponectin remains unclear. Some studies reported that the improvement in adiponectin might only occur in paediatric obese patients with great weight loss or intensive physical exercise; the magnitude of the changes in body composition appears to be of particular importance. A revision about the knowledge on the relation between adiponectin, inflammation and cardiometabolic risk factors in paediatric patients is performed; the impact of interventional studies on adiponectin levels and markers of cardiometabolic risk is also addressed.

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“…Controversially, another study found no difference between obese and lean prepubertal boys regarding total and HMW adiponectin (19).…”

mentioning

confidence: 96%

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program

et al. 2014

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Background: Adiponectin circulates as low-, medium-, and high-molecular-weight multimers (LMW, MMW, and HMW) and influences lipid profile and insulin resistance (IR), HMW being considered as the most biologically active form. We aimed to study the relation between adiponectin and markers of metabolic syndrome (MS) in pediatric obesity, and the impact of physical exercise. Methods:The study consisted of a cross-sectional part and an 8-mo physical exercise program. Lipid profile, insulin, glucose, C-reactive protein (CRP), total adiponectin (TA), and homeostasis model assessment IR (HOMA-IR) were measured. Adiponectin multimers were studied in a prepubertal group. results: Obesity is associated with increased dyslipidemia, IR, and inflammation. TA is correlated inversely with adiposity, triglycerides, HOMA-IR, and CRP, and positively with highdensity lipoprotein cholesterol (HDLc)/total cholesterol (TC) ratio. HMW mimicked TA associations. The intervention program led to a reduction of TC, low-density lipoprotein cholesterol (LDLc), insulin, HOMA-IR, and trunk percentage of fat, and an increase of HDLc/TC ratio, in the obese group. BMI improvements prevented adiponectin reduction and correlated with increments in HMW and MMW. conclusion: Obesity-related increase in MS features might be linked to lower adiponectin. HMW and MMW were the multimers that most explained the MS features. The intervention program improved the lipid profile and IR, and prevented the reduction of adiponectin. a diponectin is mainly secreted by adipocytes in humans (1,2), but total adiponectin (TA) levels are paradoxically lower in obese children, and even lower in obese individuals with metabolic syndrome (MS) (3,4).Adiponectin improves lipid metabolism by lowering the synthesis of free fatty acid and stimulating β-oxidation (5).Furthermore, it is inversely related with triglyceride (TG) levels and positively related with high-density lipoprotein cholesterol (HDLc) concentration. A study from our group showed that adiponectin modulates the effect of apo E genotype on lipid profile (6). Adiponectin also presents an anti-inflammatory action, e.g., it inhibits proinflammatory tumor necrosis factor-α (TNF-α) secretion by macrophages. This activity might have an important role in insulin resistance (IR), as TNF-α inhibits insulin signaling (7,8), while adiponectin increases insulin sensitivity (9).In pediatric ages, adiponectin levels correlate negatively with age (6). The difference between genders is well established, with women presenting with higher adiponectin concentrations (6,10). Sexual hormones might underlie sex-related changes as before puberty; no differences are found between genders (11).The body fat distribution influences adiponectin levels, with abdominal obesity associated with lower concentrations (4,12). The association between central adiposity and reduced adiponectin was seen with visceral fat accumulation in children (13) and adults (14).Adiponectin circulates as three complexes: trimers, hexamers (two trimers), and larger...

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Inflammatory Adipokines, High Molecular Weight Adiponectin, and Insulin Resistance: A Population-Based Survey in Prepubertal Schoolchildren

Cited by 45 publications

References 44 publications

Does visceral adiposity index signify early metabolic risk in children and adolescents?: Association with insulin resistance, adipokines, and subclinical inflammation

Does visceral adiposity index signify early metabolic risk in children and adolescents?: Association with insulin resistance, adipokines, and subclinical inflammation

Adiponectin, Inflammation and Cardiometabolic Risk Factors in Paediatric Obese Patients: Impact of Interventional Studies

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program

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