Adiponectin and Cardiovascular Risk. From Pathophysiology to Clinic: Focus on Children and Adolescents

Abstract

Adiponectin (Ad) is a cytokine produced by adipocytes that acts on specific receptors of several tissues through autocrine, paracrine, and endocrine signaling mechanisms. Ad is involved in the regulation of cell survival, cell growth, and apoptosis. Furthermore, Ad plays an important pathophysiological role in metabolic activities by acting on peripheral tissues involved in glucose and lipid metabolism such as skeletal muscle, and the liver. Adiponectin has anti-inflammatory, anti-atherogenic, and insulin-sensitizing effects. For this reason, low levels of Ad are associated with the development of cardiovascular complications of obesity in adulthood. Numerous studies have shown that, even in children and adolescents, Ad is associated with risk factors for cardiovascular diseases. In obese children, reduced levels of Ad have been reported and Ad plasma levels are inversely related with abdominal obesity. Moreover, lower Ad concentrations are associated with the development of metabolic syndrome, insulin resistance and hypertension in pediatric subjects. In addition to a higher prevalence of cardiovascular risk factors, plasma values of Ad are also inversely associated with early organ damage, such as an increase in carotid intima-media thickness. It has been suggested that low Ad levels in childhood might predict the development of atherosclerosis in adulthood, suggesting the possibility of using Ad to stratify cardiovascular risk in obese children. Some evidence suggests that lifestyle modification may increase Ad plasma levels. The aim of this review is to summarize the evidence on the relationship between Ad, obesity, metabolic alterations and hypertension in children and adolescents, and to address the possibility that Ad represents an early marker of cardiovascular risk in pediatric subjects. Furthermore, the effects of non-pharmacological treatment (weight loss and physical activity) on Ad levels are considered.

High molecular weight adiponectin levels are inversely associated with adiposity in pediatric brain tumor survivors

“…The HMW adiponectin levels trended higher in females when compared to male participants. Our results are consistent with current data in the general pediatric population 26 , 46 , 52 – 55 , with obese boys having the lowest levels when compared to girls and lean children, as the androgen rise with puberty in boys is associated with reduced adiponectin level 55 , 56 . In our cohort, the majority of participants were pubertal, and the number of prepubertal subjects was quite small and we could not verify the impact of puberty on adiponectin levels in survivors.…”

“…The Endoplasmic Reticulum Oxidoreductase 1 alpha (Ero1-La) releases the ERp44-bound oligomers 45 . Adiponectin has significant Immunometabolic effects, including actions in insulin sensitivity and inflammation 19 , 46 . The mechanisms of adiponectin downregulation in obesity are not fully understood, but it may be related to adipose tissue macrophage secretion of Tumor Necrosis Factor Alpha (TNFα) and oxidative stress suppressing adiponectin gene expression 47 – 51 .…”

Adiponectin levels decrease independently of body mass index and diabetes type after the normalization of hyperglycemia

“…This is the first clinical study that has demonstrated the effect of correction of acute hyperglycemia on adiponectin levels. Adiponectin is known to inversely correlate with body weight and abdominal obesity [18]. The decreases in adiponectin levels were independent of BMI in our study.…”

Heat shock protein 60 (HSP60) modulates adiponectin signaling by stabilizing adiponectin receptor

“…Adiponectin is the most abundant adipokine produced and secreted by adipocytes. Through binding with its specific receptors adiponectin receptor 1 (AdipoR1) and AdipoR2, adiponectin initiates intracellular signaling pathways and exerts promising effects in the prevention or treatment of diabetes and metabolic syndrome, cardiovascular diseases, cancers, central nervous system disorders and so on [1][2][3][4]. Previous researches have confirmed that adiponectin signaling could be mediated by adaptor protein APPLs (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper) including APPL1 and APPL2 [5,6].…”