**5. Conclusions and final remarks**

The relation between adiponectin and cardiometabolic risk in children and adolescents is still under research.

Considering the different adiponectin multimers, HMW adiponectin has been associated with a better metabolic control, improving IR, while the LMW multimer presents an opposite effect. The concentrations and the relative percentage of the multimers should be considered as potential markers of CVD risk.

Obesity, and particularly abdominal obesity, is closely associated with lower adiponectin values in paediatric ages. Adiponectin acts as an insulin sensitiser, decreasing as the IR rises. Nevertheless, there might be a negative feedback mechanism, causing a relative decrease in adiponectin as insulin sensitivity improves. Higher adiponectin levels are associated with an improvement in lipid profile, with decreased TG and increased HDLc, being the influence on LDLc more limited. Besides the contribution to a less atherogenic lipid profile, adiponectin further prevents atherosclerosis by a direct positive effect on blood vessels. It reduces the formation of foam cells, macrophage infiltration and activation, and the vascular wall remodelling. Adiponectin is also associated with smaller arterial IMT and increased vessel elasticity, in children. Likewise, increased adiponectin is linked to reduced, healthier, BP.

Combining the specific effects of adiponectin in lipid profile, BP and IR, a decrease in this adipokine will induce clustering of several cardiovascular risk factors in OB children and adolescents that predicts cardiometabolic diseases in the future.

HMW adiponectin seems to be a better predictor of cardiometabolic risk factors than total adiponectin. An increase in total and HMW adiponectin is achieved following interventional programmes, particularly those involving exercise and diet interventions. Changes in body composition, with reduction of total and central body fat, more than changes in body weight, appear to be the key for therapeutic success.

The positive effects of adiponectin on general metabolism are not so clear in PP individuals, particularly the improvement in IR. No significant differences are usually observed between genders in PP individuals. After puberty, and possibly through a mechanism involving sexual hormones, adiponectin decreases with age in both genders, more markedly in boys [72, 130]. Several studies have reported similar adiponectin levels for both genders, even in OB paediatric populations involving post‐pubertal subjects [10, 29, 61, 111, 131].

The controversial data on adiponectin following interventional programmes are, probably, related to different study designs and strategies used, including age, nutritional/body composition characterisation and pubertal stage of the studied subjects, PE or PA practice and type (e.g. aerobic, endurance, strength), group or individual therapy, among others; the population background should also be considered, as genetics plays an important part on adiponectin‐circulating levels and, thus, might affect the results. Different populations also have different diets, and nutritional influence on adiponectin levels deserves further studies. Thus, although it is hard to control all variables, a good characterisation of the interventional studies is crucial for future comparisons.

Adiponectin, obesity and IR are so closely associated that it is hard to establish which are causes and which are consequences. The clarification of adiponectin physiological role, the evolution of its normal values throughout life and its relation with other metabolic markers and diseases need well‐designed and objective longitudinal studies. These studies should focus on increased follow‐up periods, including PP and CT individuals, and evaluate adiponectin isoforms, considering the lack of information on individual multimer levels and function. Further studies would help to better understand the metabolic changes in obesity, and to find new therapeutic targets to obesity itself and obesity‐related complications.
