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Objective: According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates predispose offspring to white adipose tissue (WAT) accumulation. In rodents, adipogenesis mainly develops during lactation. The mechanisms underlying the phenomenon known as developmental programming remain elusive. We previously reported that adult rat offspring from high-fat diet-fed dams (called HF) exhibited hypertrophic adipocyte, hyperleptinemia and increased leptin mRNA levels in a depot-specific manner. We hypothesized that leptin upregulation occurs via epigenetic malprogramming, which takes place early during development of WAT., Methods: As a first step, we identified in silico two potential enhancers located upstream and downstream of the leptin transcription start site that exhibit strong dynamic epigenomic remodeling during adipocyte differentiation. We then focused on epigenetic modifications (methylation, hydroxymethylation, and histone modifications) of the promoter and the two potential enhancers regulating leptin gene expression in perirenal (pWAT) and inguinal (iWAT) fat pads of HF offspring during lactation (postnatal days 12 (PND12) and 21 (PND21)) and in adulthood., Results: PND12 is an active period for epigenomic remodeling in both deposits especially in the upstream enhancer, consistent with leptin gene induction during adipogenesis. Unlike iWAT, some of these epigenetic marks were still observable in pWAT of weaned HF offspring. Retained marks were only visible in pWAT of 9-month-old HF rats that showed a persistent "expandable" phenotype., Conclusions: Consistent with the DOHaD hypothesis, persistent epigenetic remodeling occurs at regulatory regions especially within intergenic sequences, linked to higher leptin gene expression in adult HF offspring in a depot-specific manner.

According to the Developmental Origin of Health and Disease (DOHaD) concept, alterations of nutrient supply in the fetus or neonate result in long-term programming of individual body weight (BW) setpoint. In particular, maternal obesity, excessive nutrition, and accelerated growth in neonates have been shown to sensitize offspring to obesity. The white adipose tissue may represent a prime target of metabolic programming induced by maternal obesity. In order to unravel the underlying mechanisms, we have developed a rat model of maternal obesity using a high-fat (HF) diet (containing 60% lipids) before and during gestation and lactation. At birth, newborns from obese dams (called HF) were normotrophs. However, HF neonates exhibited a rapid weight gain during lactation, a key period of adipose tissue development in rodents. In males, increased BW at weaning (+30%) persists until 3months of age. Nine-month-old HF male offspring was normoglycemic but showed mild glucose intolerance, hyperinsulinemia, and hypercorticosteronemia. Despite no difference in BW and energy intake, HF adult male offspring was predisposed to fat accumulation showing increased visceral (gonadal and perirenal) depots weights and hyperleptinemia. However, only perirenal adipose tissue depot exhibited marked adipocyte hypertrophy and hyperplasia with elevated lipogenic (i.e. sterol-regulated element binding protein 1 (Srebp1), fatty acid synthase (Fas), and leptin) and diminished adipogenic (i.e. peroxisome proliferator-activated receptor gamma (Pparγ), 11β-hydroxysteroid dehydrogenase type 1 (11β-Hds1)) mRNA levels. By contrast, very few metabolic variations were observed in HF female offspring. Thus, maternal obesity and accelerated growth during lactation program offspring for higher adiposity via transcriptional alterations of visceral adipose tissue in a depot- and sex-specific manner., (© 2016 Society for Endocrinology.)

The concept of Developmental Origin of Health and Disease (DOHaD) postulates that adult-onset metabolic disorders may originate from suboptimal conditions during critical embryonic and fetal programming windows. In particular, nutritional disturbance during key developmental stages may program the set point of adiposity and its associated metabolic diseases later in life. Numerous studies in mammals have reported that maternal obesity and the resulting accelerated growth in neonates may affect adipocyte development, resulting in persistent alterations in adipose tissue plasticity (i.e., adipocyte proliferation and storage) and adipocyte function (i.e., insulin resistance, impaired adipokine secretion, reduced thermogenesis, and higher inflammation) in a sex- and depot-specific manner. Over recent years, adipose progenitor cells (APCs) have been shown to play a crucial role in adipose tissue plasticity, essential for its development, maintenance, and expansion. In this review, we aim to provide insights into the developmental timeline of lineage commitment and differentiation of APCs and their role in predisposing individuals to obesity and metabolic diseases. We present data supporting the possible implication of dysregulated APCs and aberrant perinatal adipogenesis through epigenetic mechanisms as a primary mechanism responsible for long-lasting adipose tissue dysfunction in offspring born to obese mothers. [ABSTRACT FROM AUTHOR]

Early puberty is associated with adverse health outcomes, but little is known regarding early-life determinants influencing pubertal timing. We examined the associations between maternal gestational weight gain (GWG) and the timing of the onset of breast development (thelarche) and pubic hair development (pubarche) in a cohort of 2,070 girls born in a Kaiser Permanente Northern California facility between 2005 and 2006. Using Weibull regression models accommodating interval censoring and adjusting for important confounders, we found that excess GWG was associated with increased risk of early thelarche (hazard ratio (HR) = 1.50, 95% confidence interval (CI): 1.26, 1.78) and early pubarche (HR = 1.35, 95% CI: 1.10, 1.66). Inadequate GWG was associated with early thelarche (HR = 1.36, 95% CI: 1.08, 1.71). The associations between excess or inadequate GWG and risk of earlier thelarche were stronger if mothers were obese before or at the beginning of pregnancy (body mass index ≥30 kg body weight per m height squared) (HR = 2.01, 95% CI: 1.53, 2.63; HR = 2.08, 95% CI: 1.45, 2.98, respectively). Similar associations were found for pubarche outcome. Inclusion of girls' prepubertal body mass index slightly attenuated these associations, but they remained significant. Monitoring of maternal weight before and throughout pregnancy might help prevent early pubertal onset and subsequent negative health outcomes.

The article discusses the contibution of gut microbiota in the developmental programming of brain, health, and disease. It cites the experiment on the influence of gut microbiota on the brain development of germ-free (GF) and specific pathogen free (SPF) mice as well as on the developmental programming of obesity and modulation of adult gut microbiota. It notes the contribution of gut microbiota in during embryogenesis in the transgenerational transmission of endophenotypes in the experiment.