Fat Cell Size, Insulin Sensitivity, and Inflammation in Obese Children

Department of Mother and Child, Biology-Genetics, Section of Pediatrics, University of Verona, Verona, Italy.
The Journal of pediatrics (Impact Factor: 3.79). 12/2007; 151(6):647-52. DOI: 10.1016/j.jpeds.2007.04.053
Source: PubMed


To assess the association between adiposity indexes (body mass index [BMI], fat mass, adipocyte size) and circulating inflammation markers with known metabolic relevance or insulin sensitivity in overweight/obese children.
Twenty-eight children (males/females: 13/15) with different degrees of overweight (BMI z-score: 1.64-3.1; fat mass: 14.1-49.8 kg) were studied. BMI, body composition (dual-energy x-ray absorptiometry scanning), subcutaneous adipocyte diameter (needle biopsy of subcutaneous abdominal fat), blood tumor necrosis factor-alpha and interleukin-6 concentrations and insulin sensitivity (frequently sampled intravenous glucose tolerance test) were assessed.
Adipocyte diameter, more than BMI and fat mass, was significantly associated with interleukin-6 (r = 0.62, P < .001) and tumor necrosis factor-alpha (r = 0.61, P < .001). Moreover adipocyte size was associated with insulin sensitivity (R2 = 0.15, F = 4.69, P = .04) independently from fat mass.
Adipocyte size is a factor linked to both inflammation and insulin resistance in overweight/obese children. This is similar to the findings in adults and lends support to the tenet that the earlier obesity ensues, the more severe the biologic consequences may be.

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    • "In the later stages of terminal differentiation, proteins such as adipocyte-specific fatty acid–binding protein (aP2), adiponectin, and leptin are expressed (8). A fine balance between adipocyte hypertrophy and adipogenesis exists to prevent the formation of dysfunctional adipose tissue, since large cells are more likely to be insulin resistant (9,10) and therefore can influence adipose tissue metabolism. Despite significant progress over the last few years, additional genes and factors that influence adipogenesis, adipose tissue metabolism, and ultimately energy homeostasis still remain to be uncovered. "
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    ABSTRACT: Regulation of energy metabolism is critical for the prevention of obesity, diabetes, and hepatic steatosis. Here, we report an important role for the pleckstrin homology-related domain family member, T-cell death-associated gene 51 (TDAG51), in the regulation of energy metabolism. TDAG51 expression was examined during adipocyte differentiation. Adipogenic potential of preadipocytes with knockdown or absence of TDAG51 was assessed. Weight gain, insulin sensitivity, metabolic rate, and liver lipid content were also compared between TDAG51-deficient (TDAG51(-/-)) and wild-type mice. In addition to its relatively high expression in liver, TDAG51 was also present in white adipose tissue (WAT). TDAG51 was downregulated during adipogenesis, and TDAG51(-/-) preadipocytes exhibited greater lipogenic potential. TDAG51(-/-) mice fed a chow diet exhibited greater body and WAT mass, had reduced energy expenditure, displayed mature-onset insulin resistance (IR), and were predisposed to hepatic steatosis. TDAG51(-/-) mice had increased hepatic triglycerides and SREBP-1 target gene expression. Furthermore, TDAG51 expression was inversely correlated with fatty liver in multiple mouse models of hepatic steatosis. Taken together, our findings suggest that TDAG51 is involved in energy homeostasis at least in part by regulating lipogenesis in liver and WAT, and hence, may constitute a novel therapeutic target for the treatment of obesity and IR.
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    • "Nevertheless, this association is not always observed [Mundi et al., 2010]. Inflammatory markers, which are thought to be the primary mediators of the pathological consequences of obesity, are also strongly correlated with adipocyte diameter in subcutaneous adipose tissue [Maffeis et al., 2007]. In middle-aged women, adipocyte size was reported to be a predictor of type 2 diabetes, independent from total body fat and distribution [Lonn et al., 2010]. "
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    Preview · Article · Jul 2011 · Journal of Cellular Biochemistry
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    • "In adults, obesity is associated with increases in systemic inflammatory markers, as evidenced by studies documenting the association of BMI and visceral obesity with circulating levels of cytokines and acute-phase reactants [9] [10] [11]. In children, the presence of obesity also appears to be associated with increased levels of high-sensitivity CRP (hsCRP) [12], as well as other inflammatory mediators [13] [14] [15] [16] [17], that promote the development of endothelial and metabolic dysfunction [18] [19] [20] [21]. "
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    ABSTRACT: The impact of obesity as a systemic low-grade inflammatory process has only partially been explored. To this effect, 704 community-based school-aged children (354 obese children and 350 age-, gender-, and ethnicity-matched controls) were recruited and underwent assessment of plasma levels of fasting insulin and glucose, lipids, and a variety of proinflammatory mediators that are associated with cardiometabolic dysfunction. Obese children were at higher risk for abnormal HOMA and cholesterol levels. Furthermore, BMI z score, HOMA, and LDL/HDL ratio strongly correlated with levels of certain inflammatory mediators. Taken together, obesity in children is not only associated with insulin resistance and hyperlipidemia, but is accompanied by increased, yet variable, expression of markers of systemic inflammation. Future community-based intervention and phenotype correlational studies on childhood obesity will require inclusion of expanded panels of inflammatory biomarkers to provide a comprehensive assessment of risk on specific obesity-related morbidities.
    Full-text · Article · Jan 2010 · International Journal of Pediatrics
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