Effects of maternal diet-induced obesity on metabolic disorders and age-associated miRNA expression in the liver of male mouse offspring

Objective: This study investigated the effect of maternal obesity on aged-male offspring liver phenotype and hepatic expression of a programmed miRNA. Methods: A mouse model (C57BL/6 J) of maternal diet-induced obesity was used to investigate fasting-serum metabolites, hepatic lipid content, steatosis, and relative mRNA levels (RT-PCR) and protein expression (Western blotting) of key components involved in hepatic and mitochondrial metabolism in 12-month-old offspring. We also measured hepatic lipid peroxidation, mitochondrial content, fibrosis stage, and apoptosis in the offspring. To investigate potential mechanisms leading to the observed phenotype, we also measured the expression of miR-582 (a miRNA previously implicated in liver cirrhosis) in 8-week-old and 12-month-old offspring. Results: Body weight and composition was similar between 8-week-old offspring, however, 12-month-old offspring from obese mothers had increased body weight and fat mass (19.5 ± 0.8 g versus 10.4 ± 0.9 g, p < 0.001), as well as elevated serum levels of LDL and leptin and hepatic lipid content (21.4 ± 2.1 g versus 12.9 ± 1.8 g, p < 0.01). This was accompanied by steatosis, increased Bax/Bcl-2 ratio, and overexpression of p-SAPK/JNK, Tgfβ1, Map3k14, and Col1a1 in the liver. Decreased levels of Bcl-2, p-AMPKα, total AMPKα and mitochondrial complexes were also observed. Maternal obesity was associated with increased hepatic miR-582-3p (p < 0.001) and miR-582-5p (p < 0.05). Age was also associated with an increase in both miR-582-3p and miR-582-5p, however, this was more pronounced in the offspring of obese dams, such that differences were greater in 12-month-old animals (−3p: 7.34 ± 1.35 versus 1.39 ± 0.50, p < 0.0001 and −5p: 4.66 ± 1.16 versus 1.63 ± 0.65, p < 0.05). Conclusion: Our findings demonstrate that maternal diet-induced obesity has detrimental effects on offspring body composition as well as hepatic phenotype that may be indicative of accelerated-ageing phenotype. These whole-body and cellular phenotypes were associated with age-dependent changes in expression of miRNA-582 that might contribute mechanistically to the development of metabolic disorders in the older progeny

Early exposure to distinct sources of lipids affects differently the development and hepatic inflammatory profiles of 21-day-old rat offspring

La&iacute;s Vales Mennitti,1&nbsp;Lila Missae Oyama,2 Aline Boveto Santamarina,1 Claudia Maria da Penha Oller do Nascimento,2 Luciana Pellegrini Pisani3 1PhD Program &lsquo;Interdisciplinar in Health Sciences&rsquo;, Federal University of S&atilde;o Paulo (UNIFESP), Santos, SP, Brazil; 2Department of Physiology, Discipline of Nutrition Physiology, Federal University of S&atilde;o Paulo (UNIFESP), S&atilde;o Paulo, SP, Brazil; 3Department of Biosciences, Institute of Health and Society, Federal University of S&atilde;o Paulo (UNIFESP), Santos, SP, Brazil Introduction: Maternal diet composition of fatty acids during pregnancy and lactation seems to modify the fetal programming, epigenetic pattern and offspring phenotype. Aim: Herein, we investigated the effects of maternal consumption of normal-fat diets with distinct lipid sources during pregnancy and lactation on the somatic development and proinflammatory status of 21-day-old rat offspring. Materials and Methods: On the first day of pregnancy, female Wistar rats were divided into four groups as follows: soybean oil (M-SO), lard (M-L), hydrogenated vegetable fat (M-HVF) and fish oil (M-FO). Diets were maintained during pregnancy and lactation. Male offspring constituted the SO, L, HVF and FO groups. Pups were weighed and measured weekly. Lipopolysaccharide serum concentration was determined. Tumor necrosis factor alpha, interleukin (IL)-6 and IL-10 in the liver were evaluated by enzyme-linked immunosorbent assay. Liver gene expressions were determined by real-time polymerase chain reaction. Protein expressions in the liver were analyzed by Western blotting. Results: We observed an increase in body weight and adiposity in L and HVF groups. Moreover, HVF group showed an increase in the toll-like receptor 4 mRNA levels, IL10R&alpha; and phosphorylated form of I&kappa;B kinase (IKK; p-IKK&alpha;+&beta;) protein expression. The FO group presented a decrease in body weight, relative weight of retroperitoneal adipose tissue, ADIPOR2 gene expression, lipopolysaccharide and p-IKK&alpha;+&beta; and phosphorylated form of nuclear transcription factor kappa B (NF&kappa;B) p50 (p-NF&kappa;B p50) protein expression. Conclusion: Summarily, whereas maternal intake of normal-fat diets based on L and HVF appear to affect the somatic development negatively, only early exposure to HVF impairs the pups&rsquo; proinflammatory status. In contrast, maternal diets based on FO during pregnancy and lactation have been more beneficial to the adiposity and toll-like receptor 4 signaling pathway of the 21-day-old rat offspring, particularly when compared to L or HVF diets. Keywords: fatty acids, pregnancy and lactation, adiposity, proinflammatory status, pup

Consequences of maternal obesity on neonatal outcomes and cardio-metabolic health in infancy

Obesity is a growing global health problem and is well-recognized to be a major contributing factor for increased risk of several non-communicable diseases including cardiovascular disease, diabetes and cancer in both the developed and developing world. This development is multi-factorial, but an increasingly seden- tary lifestyle coupled with unhealthy dietary practices are key risk factors. Effective interventions for weight management would therefore not only be seen to reduce the epidemic of obesity, but also to lessen the risk for obesity-related morbidities. This article will briefly describe some factors that can cause obesity. Since men and women are different in their fat mass and distribution profile, and that ethnic groups are disproportionately affected by obesity, it is conceivable that disparities also exist in the occurrence of obesity and the consequential development of non-communicable diseases. Although the major adverse health outcomes due to obesity are mentioned, the influence and the role of sex, specifically women’s health, and ethnicity in the increased risk as well as development of obesity-induced health complications will also be discussed