Leucine supplementation in maternal high-fat diet alleviated adiposity and glucose intolerance of adult mice offspring fed a postweaning high-fat diet.

Combined maternal and postnatal high-fat (HF) diet intake predisposes offspring to metabolic dysregulation during adulthood. As the inhibitory effects of leucine consumption on obesity and metabolic disorders have been reported, the effects of maternal leucine supplementation on metabolic dysregulation in adult offspring were investigated. Female mice were exposed to a control (C) or HF diet, with or without leucine (L) supplementation (1.5%, w/v), 3 weeks before mating, during pregnancy, and during lactation (C, CL, HF, and HFL). Male offspring were exposed to an HF diet for 12 weeks after weaning (C/HF, CL/HF, HF/HF, and HFL/HF). Serum biochemical parameters were determined for both the dams and offspring. Oral glucose tolerance test and qRT-PCR analysis were used to investigate metabolic dysregulation in the offspring. HFL dams exhibited higher relative adipose tissue weights than HF dams. Body weight, relative adipose tissue weight, and serum glucose levels were lower in the HFL/HF offspring than in the HF/HF offspring. Maternal leucine supplementation tended to alleviate glucose intolerance in the offspring of HF diet-fed dams. Additionally, mRNA levels of fibroblast growth factor 21 (FGF21), a hepatokine associated with glucose homeostasis, were higher in HFL/HF offspring than in HF/HF offspring and were negatively correlated with adiposity and serum glucose levels. The mRNA levels of genes encoding a FGF21 receptor complex, Fgf receptor 1 and klotho β, and its downstream targets, proliferator-activated receptor-γ co-activator 1α and sirtuin 1, were higher in adipose tissues of the HFL/HF offspring than in those of the HF/HF offspring. Serum lipid peroxide levels were lower in HFL dams than in HF dams and positively correlated with body and adipose tissue weights of offspring. Leucine supplementation in HF diet-fed dams, but not in control diet-fed dams, resulted in an anti-obesity phenotype accompanied by glucose homeostasis in male offspring challenged with postnatal HF feeding. Activation of FGF21 signaling in the adipose tissue of offspring may be responsible for these beneficial effects of leucine.

Kim J ，Kim J ，Kwon YH 《Lipids in Health and Disease》

Prenatal Choline Supplementation during High-Fat Feeding Improves Long-Term Blood Glucose Control in Male Mouse Offspring.

Korsmo HW ，Edwards K ，Dave B ，Jack-Roberts C ，Yu H ，Saxena A ，Salvador M ，Dembitzer M ，Phagoora J ，Jiang X ... -  《Nutrients》

Early postweaning exercise improves central leptin sensitivity in offspring of rat dams fed high-fat diet during pregnancy and lactation.

Sun B ，Liang NC ，Ewald ER ，Purcell RH ，Boersma GJ ，Yan J ，Moran TH ，Tamashiro KL ... -  《-》

Interaction between maternal and postnatal high fat diet leads to a greater risk of myocardial dysfunction in offspring via enhanced lipotoxicity, IRS-1 serine phosphorylation and mitochondrial defects.

Maternal overnutrition is associated with heart diseases in adult offspring. However, combined effect of maternal and postnatal fat intake on cardiac function is unknown. This study was designed to examine the impact of maternal and postnatal fat intake on metabolic, myocardial, insulin and mitochondrial responses in adult offspring. Pregnant FVB mice were fed a low fat (LF) or high fat (HF) diet during gestation and lactation. Weaning male offspring were placed on either LF or HF (calorie-restricted HF-fed mice used as weight control) for 4 months prior to assessment of metabolic indices, myocardial histology, cardiac function, insulin signaling, mitochondrial integrity and reactive oxygen species (ROS) generation. Compared with LF- and HF-fed weight-control mice, postnatal HF intake resulted in obesity, adiposity, dyslipidemia, insulin resistance, cardiac hypertrophy, interrupted cardiac contractile, intracellular Ca(2+) and mitochondrial properties, all of which were significantly accentuated by prenatal fat exposure. Despite the preserved cardiac contractile function, LF offspring from HF-fed dams displayed higher body weights, increased adiposity and glucose intolerance. HF-fed mice with prenatal HF exposure displayed upregulated serine phosphorylation of IRS-1, PTP1B, the rate-limiting fatty acid synthesis enzyme stearoyl-CoA desaturase (SCD1) and hypertrophic markers (calcineurin A, GATA4, ANP, β-MHC and skeletal α-actin), while suppressing AMP-dependent protein kinase, glucose uptake and PGC-1α levels. Importantly, myocardial and mitochondrial ultrastructural abnormalities were more pronounced in HF-fed offspring with prenatal fat exposure, shown as loss of mitochondrial density and membrane potential, increased ROS generation and apoptosis. Our data suggest that prenatal dietary fat exposure predisposes offspring to postnatal dietary fat-induced cardiac hypertrophy and contractile defect possibly via lipotoxicity, glucose intolerance and mitochondrial dysfunction. This article is part of a Special Issue entitled "Focus on Cardiac Metabolism".

Turdi S ，Ge W ，Hu N ，Bradley KM ，Wang X ，Ren J ... -  《-》

Effect of maternal protein restriction during pregnancy and postweaning high-fat feeding on diet-induced thermogenesis in adult mouse offspring.

Sellayah D ，Dib L ，Anthony FW ，Watkins AJ ，Fleming TP ，Hanson MA ，Cagampang FR ... -  《-》