Fat cell size, insulin sensitivity, and inflammation in obese children
ABSTRACT 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.
SourceAvailable from: repositorio-aberto.up.pt
[Show abstract] [Hide abstract]
ABSTRACT: Many adult chronic diseases are thought to be influenced during early life by maternal nutrition; however, the underlying mechanisms remain largely unknown. Obesity-related diseases may be due partly to high fat consumption. Herein we evaluated mammary tumor risk in female MMTV-Wnt1-transgenic (Tg) offspring exposed to high fat (HFD) or control (CD) diet (45% and 17% kcal from fat, respectively) during gestation and lactation, with CD provided to progeny at weaning. In Tg offspring, maternal HFD exposure increased mammary tumor incidence and decreased tumor latency without affecting tumor volume. Tumor risk was associated with higher TNFα and insulin and altered oxidative stress biomarkers in sera and with early changes in mammary expression of genes linked to tumor promotion (Il6) or inhibition (Pten, Bcl2). Corresponding WT progeny exposed to maternal HFD displayed accelerated mammary development, higher mammary adiposity, increased insulin resistance and early changes in Pten, Bcl2 and Il6, than CD-exposed offspring. Dams fed HFD showed higher serum glucose and oxidative stress biomarkers but comparable adiposity compared to CD-fed counterparts. In human breast cancer MCF-7 cells, sera from maternal HFD-exposed Tg offspring elicited changes in PTEN, BCL2, and IL6 gene expression, mimicking in vivo exposure; increased cell viability and mammosphere formation; and induced measures (IRS-1, IRS-2) of insulin sensitivity. Serum effects on IRS-1 were recapitulated by exogenous insulin and the PTEN-specific inhibitor SF1670. Hyper-insulinemia and PTEN loss-of-function may thus, couple maternal high fat diet exposure to enhanced insulin sensitivity via increased mammary IRS-1 expression in progeny, to promote breast cancer risk.Carcinogenesis 05/2014; DOI:10.1093/carcin/bgu106 · 5.27 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The prevalence of obesity in children and adolescents has reached significant proportions worldwide, escalating the potential for the development of co-morbid conditions such as type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Obesity represents a toxic low-grade inflammatory condition contributing to the pathogenesis of these comorbidities. While the detrimental health effects of the obesity-related chronic inflammatory state are extensively studied in adults, data on the long-term consequences of obesity-driven, low-grade inflammation that begins in childhood and its potential impact on future CVD are scarce. The purpose of this paper is to review: (i) the role of inflammatory factors such as hepatic acute phase proteins, cytokines and adipokines in pediatric obesity and understand whether these pose the same threat as the inflammatory profile in adults and (ii) the effectiveness of lifestyle-based therapies in improving obesity related subclinical inflammation in children.Current Cardiovascular Risk Reports 12/2012; 6(6):579-590. DOI:10.1007/s12170-012-0271-z