**2. Adiponectin and its isoforms**

Adiponectin is important as a mediator of inflammatory factors and as an anti‐atherogenic, anti‐dyslipidaemic and insulin sensitiser factor. Adiponectin has particular characteristics, different from most of the other mediators: each one of its three circulating isoforms (high‐ (HMW), medium‐ (MMW) and low‐molecular weight (LMW)) appears to be linked with different, sometimes opposite, actions in the organism. High‐molecular weight (HMW) isoform has been considered a better metabolic marker than total adiponectin [5, 6].

Total and HMW adiponectin concentration were reported to be lower in obese (OB) children and adolescents, when compared to lean controls (CT) [6, 7]. Besides, the relative percentages of the isoforms are, usually, altered: HMW% adiponectin decreases, while low‐molecular weight (LMW)% adiponectin increases. In children, HMW adiponectin multimer is usually linked to an improvement in insulin resistance (IR) and lipid profile [6], and it has been negatively associated with cardiometabolic complications [8]. 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]. 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.

**Figure 1** resumes the reported associations between total, HMW and LMW adiponectin with inflammatory mediators, hormones and other factors [12–31].

**1. Introduction**

84 Adiposity - Omics and Molecular Understanding

nectin [5, 6].

at young ages.

The worldwide increase in obesity at paediatric ages has been accompanied by the appearance of diseases that were considered exclusive of adults, namely type 2 diabetes (T2D), dyslipidaemia and hypertension. These pathologies are commonly associated with central

Obesity is closely associated with hypoadiponectinaemia, and low levels of circulating adiponectin are a potential predictor of some obesity‐related co‐morbidities. Therefore, adiponectin has been studied as a possible link between these conditions. Furthermore, growing evidence supports a relationship between obesity in childhood and low levels of adiponectin,

Adiponectin is important as a mediator of inflammatory factors and as an anti‐atherogenic, anti‐dyslipidaemic and insulin sensitiser factor. Adiponectin has particular characteristics, different from most of the other mediators: each one of its three circulating isoforms (high‐ (HMW), medium‐ (MMW) and low‐molecular weight (LMW)) appears to be linked with different, sometimes opposite, actions in the organism. High‐molecular weight (HMW) isoform has been considered a better metabolic marker than total adipo-

Total and HMW adiponectin concentration were reported to be lower in obese (OB) children and adolescents, when compared to lean controls (CT) [6, 7]. Besides, the relative percentages of the isoforms are, usually, altered: HMW% adiponectin decreases, while low‐molecular weight (LMW)% adiponectin increases. In children, HMW adiponectin multimer is usually linked to an improvement in insulin resistance (IR) and lipid profile [6], and it has been negatively associated with cardiometabolic complications [8]. 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]. 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

**Figure 1** resumes the reported associations between total, HMW and LMW adiponectin with

inflammatory mediators, hormones and other factors [12–31].

obesity, and this association is related with increased cardiometabolic risk [1, 2].

and increased cardiometabolic risk factors in adulthood [3, 4].

**2. Adiponectin and its isoforms**

**Figure 1. Studies reporting associations between inflammatory markers and total, high‐molecular weight (HMW) and low‐molecular weight (LMW) adiponectin**. Underlined are the inflammatory factors that appear in both columns (ambiguous results). °, pre‐pubertal; \*, post‐pubertal; Ac, acid; CRP, C‐reactive protein; FABP, fat acid‐binding protein; FGF, fibroblast growth factor; IL, interleukin; IFN, interferon; MCP, monocyte chemoattractant protein; NEFA, non‐ esterified fatty acid; RBP, retinol‐binding protein; T4, thyroxine; TNF, tumour necrosis factor.
