RESUMO
Elevated branched chain amino acids (BCAAs: valine, leucine, and isoleucine) are well-established biomarkers of obesity-associated insulin resistance (IR). Mounting evidence suggests that low- and middle-income countries are suffering from a "double burden" of both undernutrition (growth stunting) and overnutrition (obesity) as these countries undergo a "nutrition transition". The purpose of this study was to examine if pre-pregnancy body mass index (BMI, kg/m²) and a daily lipid-based micronutrient supplement (LNS, Nutriset) would lead to cross-sectional differences in circulating levels of branched chain amino acids (BCAAs) in Guatemalan women experiencing short stature during early pregnancy. Using data from an ongoing randomized controlled trial, Women First, we studied women who were normal weight (NW, BMI range for this cohort = 20.1â»24.1 kg/m²) or overweight/obese (OW/OB, BMI range for this cohort = 25.6â»31.9 kg/m²), and divided into two groups: those who received daily LNS ≥ 3 months prior to conception through 12 weeks gestation (+LNS), or no LNS (-LNS) (n = 9â»10/group). BCAAs levels were obtained from dried blood spot card samples (DBS) assessed at 12 weeks gestation. DBS cards provide a stable, efficient, and reliable means of collecting, transporting, and storing blood samples in low resource or field settings. Circulating maternal leptin, adiponectin, and insulin were determined by immunoassays from serum samples collected at 12 weeks gestation. We found maternal pre-pregnancy body mass index (ppBMI) was associated with higher circulating BCAAs (r² = 0.433, p = 0.002) and higher leptin/adiponectin ratio (r = 0.466, p = 0.044) in -LNS mothers at 12 weeks gestation. +LNS mothers demonstrated no correlations between BCAAs or leptin/adiponectin ratio across ppBMI suggesting LNS may be effective at improving metabolic status in OW/OB mothers during early pregnancy.
Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Suplementos Nutricionais , Micronutrientes/administração & dosagem , Obesidade/dietoterapia , Cuidado Pré-Concepcional/métodos , Adiponectina/sangue , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Estudos Transversais , Regulação para Baixo , Feminino , Idade Gestacional , Guatemala , Humanos , Insulina/sangue , Leptina/sangue , Fenômenos Fisiológicos da Nutrição Materna , Estado Nutricional , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/fisiopatologia , Gravidez , Resultado do Tratamento , Adulto JovemRESUMO
Maternal obesity increases the risk for pediatric obesity; however, the molecular mechanisms in human infants remain poorly understood. We hypothesized that mesenchymal stem cells (MSCs) from infants born to obese mothers would demonstrate greater potential for adipogenesis and less potential for myogenesis, driven by differences in ß-catenin, a regulator of MSC commitment. MSCs were cultured from the umbilical cords of infants born to normal-weight (prepregnancy [pp] BMI 21.1 ± 0.3 kg/m(2); n = 15; NW-MSCs) and obese mothers (ppBMI 34.6 ± 1.0 kg/m(2); n = 14; Ob-MSCs). Upon differentiation, Ob-MSCs exhibit evidence of greater adipogenesis (+30% Oil Red O stain [ORO], +50% peroxisome proliferator-activated receptor (PPAR)-γ protein; P < 0.05) compared with NW-MSCs. In undifferentiated cells, total ß-catenin protein content was 10% lower and phosphorylated Thr41Ser45/total ß-catenin was 25% higher (P < 0.05) in Ob-MSCs versus NW-MSCs (P < 0.05). Coupled with 25% lower inhibitory phosphorylation of GSK-3ß in Ob-MSCs (P < 0.05), these data suggest greater ß-catenin degradation in Ob-MSCs. Lithium chloride inhibition of GSK-3ß increased nuclear ß-catenin content and normalized nuclear PPAR-γ in Ob-MSCs. Last, ORO in adipogenic differentiating cells was positively correlated with the percent fat mass in infants (r = 0.475; P < 0.05). These results suggest that altered GSK-3ß/ß-catenin signaling in MSCs of infants exposed to maternal obesity may have important consequences for MSC lineage commitment, fetal fat accrual, and offspring obesity risk.