Our study found that adiponectin levels are associated with MetS as a whole and with each of its components, mainly in obese children.
Considering the age of participants, some of them could be in the pubertal stage, especially girls who can enter this phase up to two years earlier than boys . Unfortunately, the pubertal stage was not measured in the study, and we cannot discriminate the potential influence of sexual hormones on changes in adiponectin. However, in studies in which the pubertal stage has been controlled, results regarding the association between adiponectin and MetS are controversial. Some of them show that pubertal stage mediates the association between adiponectin and MetS [26, 27], while others performed in Latin-American children did not find this observation [14, 28]. In the present study, adiponectin concentration between boys and girls were similar with values of 12.8 and 13.3 μg/mL, respectively (p = 0.362).
Concerning the prevalence of 13% of MetS in obese children reported herein, and in order to properly locate this figure in relationship to others, we compared this prevalence with other studies in which the IDF definition was applied. In doing so, we found that the prevalence of MetS in obese children has a wide variation; in Greek children is 7.7%, in Colombian is 11.7% [27, 29], in Chinese and Spanish obese children is 27.6 and 19.6% respectively [30, 31], and in another study on Mexican obese children the prevalence was 20% . Notwithstanding the same IDF definition of MetS, variation could be explained by the differences in the environment in which the children live.
It is noteworthy that independent of nutritional status of the children, when their adiponectin levels are in the lowest tertile all the components of MetS worsen; WC, diastolic BP, glucose, and triglycerides increase and HDL-C values decrease. On the other hand, when adiponectin levels are in the high tertiles, each component of MetS improves even in obese children, although it is not possible to say that these individuals are metabolically healthy.
A similar phenomenon but with less magnitude is observed in eutrophic children. Nowadays, we do not have a plausible way of explaining why adiponectin in eutrophic children decreases because they are not exposed to the inflammatory environment of obesity; however, eutrophic children with adiponectin concentrations in the low tertile have significantly higher values of HOMA IR, WC and diastolic BP than those in the high tertile. To our knowledge, the present work is the first to show that adiponectin also influences metabolic changes in eutrophic children, even after adjustment of adiponectin levels by BMI and gender.
In a recent bariatric surgery study that was made up of morbidly obese patients, the association between adiponectin genes and adiponectin expression was studied in eight patients with T2D and four control patients . Adiponectin production was downregulated in obese patients but upregulated once obesity was reduced. Its production rose to levels close to the control group, suggesting that adiponectin expression is dysregulated with obesity. The versatile replenishment of this adipokine with weight loss supports the importance of using this cytokine as a biomarker in prevention programs as well as in treatment and control of diseases, especially T2D.
Although there are reports in which adiponectin has not been shown to be a useful biomarker for monitoring changes observed in MetS [16, 17], evidence exists for postulating this cytokine as a biomarker of MetS and T2D in obese children and adolescents [13, 14, 34, 35]. However, the molecular mechanisms that establish the relationship between adiponectin and metabolic derangements observed in clinical and epidemiological studies, have not been fully elucidated . The most plausible explanation is that obesity, mainly visceral, is a condition in which there is an inflammatory state characterized by dysregulated production of adipokines in which anti-inflammatory agents such as adiponectin decrease while pro-inflammatory cytokines such TNFα and IL-6, IL 1β increase. Unfortunately pro- inflammatory cytokines were not measured in order to demonstrate their predominance, although at present, there is practically no discussion about the negative association between central obesity and adiponectin levels [37, 38].
The use of adiponectin as a marker for MetS has already been shown in a 3-year prospective study where adiponectin levels in Korean children predicted the development of the MetS .
In addition to aforementioned limitations, it is necessary to highlight that this study is cross-sectional in design, which only permits associations but not causality to be established among different variables. Lastly, because the study was performed in an ethnically homogenous population in Mexico City its results may not apply to other populations. Despite these limitations, the negative association between adiponectin and the components of MetS suggest that these children have an imbalance in inflammatory adipokines.