Acute metabolic acidosis (MA), a feature mostly associated with chronic kidney disease, decreases glucose tolerance and insulin sensitivity. By contrast, the effects of chronic MA on glucose homeostasis remain elusive. Here, we evaluated glucose homeostasis and metabolic parameters in male mice exhibiting chronic MA via long-term NH4Cl administration. Unlike acute MA, chronic MA resulted in lower body weight, increased energy expenditure, lower basal glycemia, improved glucose tolerance without changes in insulin secretion or sensitivity. No overall glucose uptake changes were observed. However, hepatic and intestinal gluconeogenesis were decreased whereas renal endogenous glucose production was increased in mice with chronic MA. The elevated glucose urinary excretion was associated with lower expression of renal sodium/glucose co-transporters. Transcriptomic analysis revealed that chronic MA potentiates anion transport, glucose and lipid metabolism, mitochondrial and oxidative phosphorylation pathways in the kidney. Overall, chronic MA improves glucose tolerance without changes in insulin secretion or sensitivity, likely due to reduced hepatic gluconeogenesis, decreased renal glucose reabsorption and increased energy demands in the kidney.

The bone marrow microenvironment is a dynamic and complex niche that plays a central role in the development, progression, and therapeutic resistance of leukemia. Among the various stromal and immune cells that compose this microenvironment, adipocytes are increasingly recognized as active participants rather than passive bystanders. These cells contribute to leukemia pathophysiology by supplying leukemic cells with vital metabolic fuels such as free fatty acids and glutamine, which support cellular bioenergetics and biosynthesis. Furthermore, adipocytes secrete adipokines—including leptin, adiponectin, and others—that influence leukemic cell proliferation, apoptosis, and chemoresistance. Leukemic cells, in turn, are not merely recipients of these signals, but actively remodel the marrow niche to their advantage. They can suppress adipogenesis, inhibit the differentiation of mesenchymal stem cells into adipocytes, or reprogram existing adipocytes to adopt a tumor-supportive phenotype. These transformed adipocytes may enhance leukemic cell survival, dampen immune responses, and create a metabolic sanctuary that enables resistance to standard chemotherapies. This reciprocal and dynamic interaction between leukemic cells and adipocytes contributes significantly to minimal residual disease and relapse, posing a major challenge for durable remission. Recent advances in tissue engineering—such as organ-on-chip and 3D co-culture systems—offer promising platforms to recapitulate and study these leukemia–adipocyte interactions with high fidelity. These models facilitate mechanistic insights and provide a foundation for developing novel therapeutic strategies aimed at disrupting the metabolic and paracrine crosstalk within the leukemic niche. Targeting the adipocyte–leukemia axis represents a compelling and underexplored avenue for improving leukemia treatment by sensitizing malignant cells to existing therapies and overcoming the protective influence of the bone marrow microenvironment.

Adipose tissue is far more than a passive reservoir for surplus energy: it is an active metabolic and endocrine organ that senses nutrient availability and orchestrates systemic energy balance. When caloric intake chronically exceeds expenditure, adipocytes become engorged with lipids and exposed to metabolic, mechanical, and hypoxic stress. To adapt, they initiate a fibro-inflammatory response that may be protective in the short term. As this response becomes chronic, adipocytes lose their metabolic flexibility, acquire a maladaptive fibro-inflammatory phenotype, and contribute to the cascade of inflammation, insulin resistance, and metabolic disease that characterizes obesity. In this review, we dissect the cellular and molecular cues that trigger fibro-inflammation, from nutrient excess and mitochondrial stress to hypoxia and immunometabolic rewiring, and highlight how these processes reshape adipocyte identity and tissue homeostasis.

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.

Human induced pluripotent stem cells (hiPSCs) have the potential to be differentiated into any cell type, making them a relevant tool for therapeutic purposes such as cell-based therapies. In particular, they show great promise for obesity treatment as they represent an unlimited source of brown/beige adipose progenitors (hiPSC-BAPs). However, the low brown/beige adipocyte differentiation potential in 2D cultures represents a strong limitation for clinical use. In adipose tissue, besides its cell cycle regulator functions, the cyclin-dependent kinase inhibitor 2A (CDKN2A) locus modulates the commitment of stem cells to the brown-like type fate, mature adipocyte energy metabolism and the browning of adipose tissue. Here, using a new method of hiPSC-BAPs 3D culture, via the formation of an organoid-like structure, we silenced CDKN2A expression during hiPSC-BAP adipogenic differentiation and observed that knocking down CDKN2A potentiates adipogenesis, oxidative metabolism and the browning process, resulting in brown-like adipocytes by promoting UCP1 expression and beiging markers. Our results suggest that modulating CDKN2A levels could be relevant for hiPSC-BAPs cell-based therapies.

According to the developmental origin of health and disease concept, the risk of many age-related diseases is not only determined by genetic and adult lifestyle factors but also by factors acting during early development. In particular, maternal obesity and neonatal accelerated growth predispose offspring to overweight and type 2 diabetes (T2D) in adulthood. This concept mainly relies on the developmental plasticity of adipose tissue and pancreatic β-cell programming in response to suboptimal milieu during the perinatal period. These changes result in unhealthy hypertrophic adipocytes with decreased capacity to store fat, low-grade inflammation and loss of insulin-producing pancreatic β-cells. Over the past years, many efforts have been made to understand how maternal obesity induces long-lasting adipose tissue and pancreatic β-cell dysfunction in offspring and what are the molecular basis of the transgenerational inheritance of T2D. In particular, rodent studies have shed light on the role of epigenetic mechanisms in linking maternal nutritional manipulations to the risk for T2D in adulthood. In this review, we discuss epigenetic adipocyte and β-cell remodeling during development in the progeny of obese mothers and the persistence of these marks as a basis of obesity and T2D predisposition.

According to the “developmental origins of health and disease” (DOHaD) concept, maternal obesity predisposes the offspring to non-communicable diseases in adulthood. While a preconceptional weight loss (WL) is recommended for obese women, its benefits on the offspring have been poorly addressed. We evaluated whether preconceptional WL was able to reverse the adverse effects of maternal obesity in a mouse model, exhibiting a modification of foetal growth and of the expression of genes encoding epigenetic modifiers in liver and placenta. We tracked metabolic and olfactory behavioural trajectories of offspring born to control, obese or WL mothers. After weaning, the offspring were either put on a control diet (CD) or a high-fat (HFD). After only few weeks of HFD, the offspring developed obesity, metabolic alterations and olfactory impairments, independently of maternal context. However, male offspring born to obese mother gained even more weight under HFD than their counterparts born to lean mothers. Preconceptional WL normalized the offspring metabolic phenotypes but had unexpected effects on olfactory performance: a reduction in olfactory sensitivity, along with a lack of fasting-induced, olfactory-based motivation. Our results confirm the benefits of maternal preconceptional WL for male offspring metabolic health but highlight some possible adverse outcomes on olfactory-based behaviours.

Selon le concept des « origines développementales de la santé et des maladies », l’obésité maternelle prédispose la descendance aux maladies chroniques. Pour de multiples raisons, une perte de poids préconceptionnelle est recommandée aux femmes obèses. Cependant, les avantages et les potentiels inconvénients pour l’enfant à naître sont encore mal étudiés. Nous avons évalué le développement fœtal et analysé l’expression de modificateurs épigénétiques et de gènes métaboliques dans le foie et le placenta. Les descendants nés de mère « contrôle », « obèse » ou « perte de poids » ont été soumis après le sevrage à un régime contrôle ou hyperlipidique. Nous avons suivi les paramètres métaboliques et les comportements olfactifs jusqu’à l’âge adulte. Les fœtus de mère obèse présentent une restriction de croissance et une altération de l’expression de modificateurs épigénétiques de la voie d’acétylation des histones. Les phénotypes métaboliques et olfactifs (obésité, dyslipidémie, intolérance au glucose et faible motivation et capacité à trouver une récompense alimentaire) s’expliquent principalement par le régime post-sevrage, mais l’obésité maternelle a un effet notable de conditionnement dépendant du sexe : les mâles nés de mère obèse développent une obésité accrue par rapport à leurs congénères. La perte de poids préconceptionnelle normalise les phénotypes fœtaux et métaboliques décrits ci-dessus, mais certains gènes restent différentiels. De plus, elle a des effets inattendus sur les performances olfactives : la sensibilité olfactive périphérique et la motivation induite par le jeûne sont réduites. Nos résultats confirment les avantages d’une perte de poids préconceptionnelle pour la santé métabolique des descendants, mais révèlent de potentiels effets indésirables tels qu’observés pour le comportement olfactif. According to the “developmental origins of health and disease” concept, maternal obesity predisposes the offspring to non-communicable diseases. Epigenetic patterns could be affected by maternal weight changes, in turn modifying the expression of key developmental genes with long-lasting consequences. A preconceptional weight loss is widely recommended to obese women. However, its long-term outcomes on the offspring have been poorly assessed. We recorded E18.5 mouse development and measured the mRNA expression of epigenetic modifiers and metabolic genes in foetal liver and placenta. Offspring born to “control”, “obese” or “weight-loss after diet-induced obesity” mothers were put on a control or high-fat diet, and we tracked their metabolic parameters and olfactory behaviour. Foetuses from obese dams showed growth restriction and altered mRNA expression of candidate epigenetic modifiers, particularly the histone acetylation pathway. Preconceptional weight loss normalised foetal growth, but did not normalise the mRNA expression of all differentially expressed epigenetic genes. After birth, the offspring's own diet explained most of the variability in metabolic and olfactory phenotypes (obesity, dyslipidemia, glucose intolerance and low motivation and learning capacities to find a food reward), but maternal obesity had a noticeable sex-specific conditioning effect. Specifically, males born to obese dams were more susceptible to diet-induced obesity. In addition, maternal preconceptional weight loss had positive effects on offspring metabolism, but showed a programming effect on peripheral olfactory sensitivity. These results confirm the benefits of maternal preconceptional weight loss, but also highlight some possible adverse outcomes.

Besides its role as a cell cycle and proliferation regulator, the INK4a/ARF (CDKN2A) locus and its associated pathways are thought to play additional functions in the control of energy homeostasis. Genome-wide association studies in humans and rodents have revealed that single nucleotide polymorphisms in this locus are risk factors for obesity and related metabolic diseases including cardiovascular complications and type-2 diabetes (T2D). Recent studies showed that both p16INK4a-CDK4-E2F1/pRB and p19ARF-P53 (p14ARF in humans) related pathways regulate adipose tissue (AT) physiology and adipocyte functions such as lipid storage, inflammation, oxidative activity, and cellular plasticity (browning). Targeting these metabolic pathways in AT emerged as a new putative therapy to alleviate the effects of obesity and prevent T2D. This review aims to provide an overview of the literature linking the INK4a/ARF locus with AT functions, focusing on its mechanisms of action in the regulation of energy homeostasis.

Purpose Poor maternal nutrition sensitises to the development of metabolic diseases and obesity in adulthood over several generations. The prevalence increases when offspring is fed with a high-fat (HF) diet after weaning. This study aims to determine whether such metabolic profiles can be transmitted to the second generation and even aggravated when the mothers were exposed to overnutrition, with attention to potential sex differences. Methods Pregnant Wistar rats were subjected to ad libitum (control) or 70% food-restricted diet (FR) during gestation (F0). At weaning, F1 females were allocated to three food protocols: (1) standard diet prior to and throughout gestation and lactation, (2) HF diet prior to and standard diet throughout gestation and lactation, and (3) HF diet prior to and throughout gestation and lactation. F2 offspring was studied between 16 and 32 weeks of age. Results FR-F2 offspring on standard diet showed normal adiposity and had no significant metabolic alterations in adulthood. Maternal HF diet resulted in sex-specific effects with metabolic disturbances more apparent in control offspring exposed to HF diet during gestation and lactation. Control offspring displayed glucose intolerance associated with insulin resistance in females. Female livers overexpressed lipogenesis genes and those of males the genes involved in lipid oxidation. Gene expression was significantly attenuated in the FR livers. Increased physical activity associated with elevated corticosterone levels was observed in FR females on standard diet and in all females from overnourished mothers. Conclusions Maternal undernutrition during gestation (F0) improves the metabolic health of second-generation offspring with more beneficial effects in females.

Clinical and animal studies have reported an association between low birth weight and the development of nonalcoholic fatty liver disease (NAFLD) in offspring. Using a model of prenatal maternal 70% food restriction diet (FR30) in the rat, we previously showed that maternal undernutrition predisposes offspring to altered lipid metabolism in adipose tissue, especially on a high-fat (HF) diet. Here, using microarray-based expression profiling combined with metabolic, endocrine, biochemical, histological, and lipidomic approaches, we assessed whether FR30 procedure sensitizes adult male offspring to impaired lipid metabolism in the liver. No obvious differences were noted in the concentrations of triglycerides, cholesterol, and bile acids in the liver of 4-mo-old FR30 rats whichever postweaning diet was used. However, several clues suggest that offspring's lipid metabolism and steatosis are modified by maternal undernutrition. First, lipid composition was changed (i.e., higher total saturated fatty acids and lower elaidic acid) in the liver, whereas larger triglyceride droplets were observed in hepatocytes of undernourished rats. Second, FR30 offspring exhibited long-term impact on hepatic gene expression and lipid metabolism pathways on a chow diet. Although the transcriptome profile was globally modified by maternal undernutrition, cholesterol and bile acid biosynthesis pathways appear to be key targets, indicating that FR30 animals were predisposed to impaired hepatic cholesterol metabolism. Third, the FR30 protocol markedly modifies hepatic gene transcription profiles in undernourished offspring in response to postweaning HF. Overall, FR30 offspring may exhibit impaired metabolic flexibility, which does not enable them to properly cope with postweaning nutritional challenges influencing the development of nonalcoholic fatty liver.

According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and the resulting accelerated growth in neonates predispose offspring to obesity and associated metabolic diseases that may persist across generations. In this context, the adipose tissue has emerged as an important player due to its involvement in metabolic health, and its high potential for plasticity and adaptation to environmental cues. Recent years have seen a growing interest in how maternal obesity induces long-lasting adipose tissue remodeling in offspring and how these modifications could be transmitted to subsequent generations in an inter- or transgenerational manner. In particular, epigenetic mechanisms are thought to be key players in the developmental programming of adipose tissue, which may partially mediate parts of the transgenerational inheritance of obesity. This review presents data supporting the role of maternal obesity in the developmental programming of adipose tissue through epigenetic mechanisms. Inter- and transgenerational effects on adipose tissue expansion are also discussed in this review.

OBJECTIVE:The lactation-suckling period is critical for white adipose tissue (WAT) development. Early postnatal nutrition influences later obesity risk but underlying mechanisms remain elusive. Here, we tested whether altered postnatal nutrition specifically during suckling impacts epigenetic regulation of key metabolic genes in WAT and alter long-term adiposity set point.METHODS:We analyzed the effects of maternal high-fat (HF) feeding in rats exclusively during lactation-suckling on breast milk composition and its impact on male offspring visceral epidydimal (eWAT) and subcutaneous inguinal (iWAT) depots during suckling and in adulthood.RESULTS:Maternal HF feeding during lactation had no effect on mothers' body weight (BW) or global breast milk composition, but induced qualitative changes in breast milk fatty acid (FA) composition (high n-6/n-3 polyunsaturated FA ratio and low medium-chain FA content). During suckling, HF neonates showed increased BW and mass of both eWAT and iWAT depot but only eWAT displayed an enhanced adipogenic transcriptional signature. In adulthood, HF offspring were predisposed to weight gain and showed increased hyperplastic growth only in eWAT. This specific eWAT expansion was associated with increased expression and activity of stearoyl-CoA desaturase-1 (SCD1), a key enzyme of FA metabolism. SCD1 converts saturated FAs, e.g. palmitate and stearate, to monounsaturated FAs, palmitoleate and oleate, which are the predominant substrates for triglyceride synthesis. Scd1 upregulation in eWAT was associated with reduced DNA methylation in Scd1 promoter surrounding a PPARγ-binding region. Conversely, changes in SCD1 levels and methylation were not observed in iWAT, coherent with a depot-specific programming.CONCLUSIONS:Our data reveal that maternal HF feeding during suckling programs long-term eWAT expansion in part by SCD1 epigenetic reprogramming. This programming events occurred with drastic changes in breast milk FA composition, suggesting that dietary FAs are key metabolic programming factors in the early postnatal period.

Pregnancy is a dynamic and precisely organized process during which one or more baby develops. Embryonic development relies on the formation of the placenta, allowing nutrient and oxygen exchange between the mother and the fetus. Dysfunction of placental formation lead to pregnancy disorders such as preeclampsia (PE) with serious deleterious consequences for fetal and maternal health. Identifying factors involved in fetoplacental homeostasis could inform better diagnostic and therapeutic strategies for these pathological pregnancies. Here, we summarize actions of elabela, apelin and their common receptor APJ in the fetoplacental unit. Studies indicate that elabela is crucial for embryo cardiovascular system formation and early placental development, while apelin acts in mid/late gestation to modulate fetal angiogenesis and energy homeostasis. Most of these findings, drawn from animal models, indicate a key role of elabela/apelin-APJ system in the fetoplacental unit. This review also provides an overview of clinical studies investigating elabela/apelin-APJ system in pathological complicated pregnancies such as PE and gestational diabetes mellitus (GDM). While elabela-deficient mice display all the features of PE, current clinical studies show no difference in circulating elabela levels between PE and control patients which does not support a role in PE development. Conversely, apelin levels are increased during PE, but the use of apelin as an early PE marker remains to be fully investigated.

According to the Developmental Origin of Health and Disease (DOHaD) concept, maternal obesity and accelerated growth in neonates program obesity later in life. White adipose tissue (WAT) has been the focus of developmental programming events, although underlying mechanisms remain elusive. In rodents, WAT development primarily occurs during lactation. We previously reported that adult rat offspring from dams fed a high-fat (HF) diet exhibited fat accumulation and decreased peroxisome proliferator-activated receptor γ (PPARγ) mRNA levels in WAT. We hypothesized that PPARγ down-regulation occurs via epigenetic malprogramming which takes place during adipogenesis. We therefore examined epigenetic modifications in the PPARγ1 and PPARγ2 promoters in perirenal (pWAT) and inguinal fat pads of HF offspring at weaning (postnatal d 21) and in adulthood. Postnatal d 21 is a period characterized by active epigenomic remodeling in the PPARγ2 promoter (DNA hypermethylation and depletion in active histone modification H3ac and H3K4me3) in pWAT, consistent with increased DNA methyltransferase and DNA methylation activities. Adult HF offspring exhibited sustained hypermethylation and histone modification H3ac of the PPARγ2 promoter in both deposits, correlated with persistent decreased PPARγ2 mRNA levels. Consistent with the DOHaD hypothesis, retained epigenetic marks provide a mechanistic basis for the cellular memory linking maternal obesity to a predisposition for later adiposity.-Lecoutre, S., Pourpe, C., Butruille, L., Marousez, L., Laborie, C., Guinez, C., Lesage, J., Vieau, D., Eeckhoute, J., Gabory, A., Oger, F., Eberlé, D., Breton, C. Reduced PPARγ2 expression in adipose tissue of male rat offspring from obese dams is associated with epigenetic modifications.

An adverse nutritional environment during the perinatal period increases the risk of adult-onset metabolic diseases, such as obesity, which may persist across generations. Adipose tissue (AT) from offspring of malnourished dams has been shown to display altered adipogenesis, lipogenesis, and adipokine expression, impaired thermogenesis, and low-grade inflammation. Although the exact mechanisms underlying these alterations remain unclear, epigenetic processes are believed to have an important role. In this review, we focus on epigenetic mechanisms in AT that may account for transgenerational dysregulation of adipocyte formation and adipose function. Understanding the complex interactions between maternal diet and epigenetic regulation of the AT in offspring may be valuable in improving preventive strategies against the obesity pandemic.

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.

Based on the Developmental Origin of Health and Disease concept, maternal undernutrition has been shown to sensitize adult offspring to metabolic pathologies such as obesity. Using a model of maternal 70% food restriction in pregnant female rats throughout gestation (called FR30), we previously reported that obesity-prone adult male rat offspring displayed hyperleptinemia with modifications in leptin and leptin receptor messenger RNA (mRNA) levels in white adipose tissue (WAT). Apelin is a member of the adipokine family that regulates various aspects of energy metabolism and WAT functionality. We investigated whether apelin and its receptor APJ could be a target of maternal undernutrition. Adult male rat offspring from FR30 dams showed increased plasma apelin levels and apelin gene expression in WAT. Post-weaning high-fat diet led to marked increase in APJ mRNA and protein levels in offspring’s WAT. We demonstrate that maternal undernutrition and post-weaning diet have long-term consequences on the apelinergic system of adult male rat offspring.

Le concept de l’origine développementale de la santé et des maladies (DOHaD) stipule qu’un environnement périnatal délétère prédispose la descendance à l’apparition de troubles métaboliques. En particulier, l’obésité maternelle, la surnutrition des nouveau-nés et la croissance postnatale accélérée sensibilisent la descendance à l’obésité. Le tissu adipeux blanc (TAB) constituerait une cible privilégiée de la programmation périnatale. Cependant, les mécanismes de programmation restent méconnus. Nous posons l’hypothèse qu’un environnement maternel obésogène modifierait l’activité enzymatique de la machinerie épigénétique lors de l’ontogenèse du TAB. Cela entraînerait la mise en place précoce d’empreintes épigénétiques au niveau de gènes clés impliqués dans la maturation du TAB conduisant à une modification de leur niveau d’expression. Le maintien de ces marques épigénétiques à l’âge adulte associé à des variations d’expression génique pourrait expliquer, en partie, la prédisposition de la descendance à l’adiposité. Afin d’étudier les mécanismes sous-jacents à cette programmation, nous avons développé un modèle d’obésité maternelle chez le rat consistant en un régime obésogène (hyperlipidique hypercalorique, 60 % de lipides [kcal]) appliqué en période préconceptionnelle, pendant la gestation et la lactation. Les paramètres métaboliques, les caractéristiques histologiques et les analyses transcriptionnelles (qPCR) et épigénétiques (ChiP-qPCR) du TAB chez la descendance mâle sont mesurés à trois stades différents du développement chez des animaux âgés de 12 (P12) et 21 (P21) jours (période de lactation) et de 9 mois (âge adulte). L’obésité maternelle ne modifie pas le poids de naissance mais accélère la croissance postnatale des nouveau-nés conduisant à un surpoids au sevrage. Ce surpoids développé au cours de la lactation (période clé du développement du TAB chez les rongeurs) est la conséquence d’une expansion rapide de ce tissu, caractérisé par une hyperplasie et une hypertrophie des adipocytes associées à des altérations de l’expression de gènes impliqués dans l’adipogenèse et la lipogenèse. La descendance mâle adulte issue de mère obèse conserve une masse de TAB plus importante avec des caractéristiques similaires. Dès P12, le TAB des ratons issus de mère obèse montrent des variations d’expression de PPARγ et de C/EBPα (gènes du développement adipocytaire) et de la leptine et de l’adiponectine (gènes de phénotype adipocytaire). Ces modifications transcriptionnelles sont corrélées à des altérations de l’expression d’enzymes de la machinerie épigénétique (HDAC1, DNMT1…). De plus, les promoteurs de ces gènes montrent un enrichissement différentiel en histones méthylés (H3K4me2, H3K9me2) et/ou acétylés (H4ac, H3ac) témoignant de la mise en place d’empreintes épigénétiques durant cette période. La cinétique de mise en place et l’étude des marques épigénétiques à l’âge adulte sont en cours d’investigation. Nos résultats démontrent que la période de lactation est le siège de modifications histologiques, transcriptionnelles et épigénétiques chez la descendance de mère obèse reflétant un développement précoce et accéléré du TAB.