Our findings suggest that total abdominal adipose tissue is inversely correlated with BMC in Latino children. SAAT has a stronger inverse association with BMC and BA compared to IAAT. While IAAT was also independently associated with BMC and BA in girls, these observations were not significant in boys. The sex difference in the inverse correlation between IAAT and BMC was unexpected. We found that girls were more mature, had a higher percentage of body fat, higher serum leptin and estradiol levels but lower testosterone compared to boys. Since the partial correlations between IAAT and BMC were adjusted for age, Tanner stage, weight and SAAT, the sex difference in the association between IAAT and BMC may be explained by endocrine differences.
In the entire cohort, we observed a positive correlation between IAAT and leptin, a cytokine-like protein produced by the ob
gene thought to be integral in regulating appetite and energy expenditure [16
]. Since girls were more mature than boys, leptin and Tanner stage were positively correlated in girls but negatively correlated in boys, and leptin and BMC were inversely correlated, it is plausible to conclude that the adverse effect of IAAT on BMC in girls may be explained, at least partially, by leptin.
Besides the fact that Tanner stage and leptin were inversely related in boys, other explanations for the lack of significant findings with respect to IAAT and BMC in boys include an inverse association between testosterone concentrations and leptin. Since boys had higher levels of testosterone than girls, these inverse associations are additional support. The possible links between leptin and developmental changes in children have been reported [17
]. Previous researchers [18
] have indicated that leptin may play a role in pubertal initiation. However, the associations between leptin and sex hormones need to be validated by other researchers, examined in different ethnic populations of adolescents and explored further in longitudinal studies of this cohort.
Previous research on the role of leptin in bone mineral density and BMC has been inconclusive, partly due to the fact that confounders of the relationships have not always been taken into account. In children, Matkovic et al. [19
] found an inverse relationship between leptin and total-body BA in pubertal girls. In contrast, after adjusting for age, Tanner stage, BMI and fat mass, Huang et al. [20
] did not find correlations between leptin and BMC in 105 Taiwanese adolescents; however, they did not adjust for lean mass, estradiol or testosterone. Similarly, Roemmich et al. [21
] concluded that leptin did not contribute to the prediction of BMC in 59 Caucasian children, after accounting for age, fat mass, fat-free mass and estradiol, but they did not include Tanner stage in their models. On the other hand, Garnett et al. [22
] concluded that leptin had a positive effect on spine bone mineral density of 255 children, but no such effect was observed on BMC, which is a more accurate and reliable measure of bone in children [23
]. The current investigation is the first to examine the independent effect of leptin on BMC while adjusting for important confounders in pre- and postpubertal Latino children.
The inconclusive effect of leptin on BMC may also be explained by its dual role and alternative pathways, one involving a direct stimulatory effect on bone formation and another involving an indirect effect through the central nervous system that suppresses bone formation [24
]. Our results are consistent with in vitro experiments and animal studies that show that leptin has an inhibitory effect on new bone formation and that the effect does not seem to be mediated through endocrine or paracrine action, but through the effect of leptin on the central nervous system [25
]. Studies have shown specific groups of neurons in the hypothalamus which are involved in the antiosteogenic function of leptin, and these neurons are different from the ones that regulate energy metabolism [25
The interrelationships between abdominal adipose tissue, leptin and puberty will remain speculative until they are assessed in longitudinal studies of children. Until then, the detrimental effects of central adiposity on the skeletal system of adolescents should not be ignored. As the obesity epidemic in children continues to be a health crisis, whether visceral and subcutaneous fat and total central adiposity are risk factors for inadequate acquisition of BMC during growth and for osteopenia and fracture risk later in life should be of paramount concern.