Obesity as the Main Risk Factor for Metabolic Syndrome in Children

Abstract

Obesity in childhood is the main determinant of whole body reduced insulin sensitivity. This association has been demonstrated in multiple adult and pediatric cohorts. The mechanistic link explaining this association is the pattern of lipid partitioning in the face of excess calories and energy surplus. A tight relation exists between typical lipid deposition patterns, specifically within the skeletal muscle and liver, as well as the intra-abdominal compartment and whole body insulin sensitivity. The impact of lipid deposition within insulin responsive tissues such as the liver and skeletal muscle relates to the ability of fatty acid derivates to inhibit elements of the insulin signal transduction pathway. Strengthening the relation of obesity and reduced insulin sensitivity are the observations that weight gain reduces insulin sensitivity while weight loss increases it. This manifests as the appearance of cardiovascular risk factor clustering with weight gain and its recovery in the face of weight loss. Both obesity per se, via the adipocytokine profile it induces, and low insulin sensitivity, are independent determinants of the adverse metabolic phenotype characteristic of the metabolic syndrome.

Keywords: childhood & adolescence; insulin resistance; metabolic syndrome (MetS); obesity; weight loss.

Figure 1

Obesity in childhood along with a contribution of additional factors (such as pubertal hormonal changes, specific ethnic backgrounds, exposure to stress among others) may have different metabolic/clinical results, based on the flux and deposition of excess lipid. (A) A favorable lipid partitioning pattern in which subcutaneous fat is capable of storing excess lipids and insulin responsive tissues (muscle and liver) are protected from excess lipid deposition. (B) Subcutaneous fat is incapable of storing excess lipid resulting in increased deposition of lipid in insulin responsive tissues leading to insulin resistance of these issues, specifically in pathways related to glucose metabolism. This results in the development of cardiovascular risk factor clustering (CVRFC) and manifests as accelerated atherogenesis.