RESUMO
We investigated whether excessive retroperitoneal adipose tissue (AT) expansion programmed by maternal obesity (MO) affects adipocyte size distribution and gene expression in relation to adipocyte proliferation and differentiation in male and female offspring (F1) from control (F1C) and obese (F1MO) mothers. Female Wistar rats (F0) ate a control or high-fat diet from weaning through pregnancy and lactation. F1 were weaned onto a control diet and euthanized at 110 postnatal days. Fat depots were weighed to estimate the total AT. Serum glucose, triglyceride, leptin, insulin, and the insulin resistance index (HOMA-IR) were determined. Adipocyte size and adipogenic gene expression were examined in retroperitoneal fat. Body weight, retroperitoneal AT and adipogenesis differed between male and female F1Cs. Retroperitoneal AT, glucose, triglyceride, insulin, HOMA-IR and leptin were higher in male and female F1MO vs. F1C. Small adipocytes were reduced in F1MO females and absent in F1MO males; large adipocytes were increased in F1MO males and females vs. F1C. Wnt, PI3K-Akt, and insulin signaling pathways in F1MO males and Egr2 in F1MO females were downregulated vs. F1C. MO induced metabolic dysfunction in F1 through different sex dimorphism mechanisms, including the decreased expression of pro-adipogenic genes and reduced insulin signaling in males and lipid mobilization-related genes in females.
Assuntos
Leptina , Obesidade Materna , Humanos , Ratos , Feminino , Animais , Masculino , Gravidez , Mães , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Wistar , Obesidade/etiologia , Obesidade/metabolismo , Obesidade Materna/metabolismo , Glucose/metabolismo , Insulina , Dieta Hiperlipídica/efeitos adversos , Triglicerídeos , Tecido Adiposo/metabolismoRESUMO
Adipocyte size (AS) shows asymmetric distribution related to current metabolic state, e.g., adipogenesis or lipolysis. We profiled AS distribution using different statistical approaches in offspring (F1) of control (C) and obese (MO) mothers (F0) with and without F0 or F1 exercise. Offspring from F0 exercise were designated CF0ex and MOF0ex. Exercised F1 of sedentary mothers were designated CF1ex and MOF1ex. F1 retroperitoneal fat cross-sectional AS was measured by median, cumulative distributions, data dispersion and extreme values based on gamma distribution modeling. F1 metabolic parameters: body weight, retroperitoneal fat, adiposity index (AI), serum leptin, triglycerides (TG) and insulin resistance index (IRI) were measured. Male and female F1 AS showed different cumulative distribution between C and MO (p < 0.0001) therefore comparisons were performed among C, CF0ex and CF1ex groups and MO, MOF0ex and MOF1ex groups. MO AI was higher than C (p < 0.05) and male MOF1ex AI lower than MO (p < 0.05). Median AS was higher in male and female MO vs. C (p < 0.05). Male and female MOF0ex and MOF1ex reduced median AS (p < 0.05). Lower AS dispersion was observed in male CF1ex and MOF1ex vs. CF0ex and MOF0ex, respectively. MO reduced small and increased large adipocyte proportions vs. C (p < 0.05); MOF0ex increased small and MOF1ex the proportion of large adipocytes vs. MO (p < 0.05). MOF0ex reduced male IRI and female TG vs. MO (p < 0.05). MOF1ex reduced male and female leptin (p < 0.05); CF1ex reduced male leptin (p < 0.05). Conclusions: several factors, diet, physical activity and gender modify AS distribution. Conventional AS distribution methods normally do not include analyzes of extreme, large and small adipocytes, which characterize different phenotypes. Maternal high fat diet affects F1 AS distribution, which was programmed during development. F0ex and F1ex have gender specific F1 beneficial effects. AS distribution characterization helps explain adipose tissue metabolic changes in different physiological conditions and will aid design of efficacious interventions to prevent and/or recuperate adverse developmental programming outcomes. Finally, precise identification of effects of specific interventions as exercise of F0 and/or F1 are needed to improve outcomes in obese women and their obesity prone offspring.