Maternal perinatal undernutrition programs a "brown-like" phenotype of gonadal white fat in male rat at weaning
Fabien Delahaye, Marie-Amélie Lukaszewski, Jean-Sébastien Wattez, Ouma Cisse, Isabelle Dutriez-Casteloot, Isabelle Fajardy, Valérie Montel, Anne Dickes-Coopman, Christine Laborie, Jean Lesage, Christophe Breton, Didier Vieau
2010
American Journal of Physiology. Regulatory Integrative and Comparative Physiology
Several studies indicate that maternal undernutrition sensitizes the offspring to the development of metabolic disorders, such as obesity. Using a model of perinatal maternal 50% food-restricted diet (FR50), we recently reported that rat neonates from undernourished mothers exhibit decreased leptin plasma levels associated with alterations of hypothalamic proopiomelanocortin system. The present study aimed at examining the consequences of FR50 on the brain-adipose axis in male rat neonates.
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... g quantitative RT-PCR array containing 84 obesity-related genes, we demonstrated that most of the genes involved in energy metabolism regulation are expressed in rat gonadal white adipose tissue (WAT) and are sensitive to maternal perinatal undernutrition (MPU). In contrast, hypothalamic gene expression was not substantially affected by MPU. Gene expression of uncoupling protein 1 (UCP1), a marker of brown adipocytes, showed an almost 400-fold stimulation in postnatal day 21 (PND21) FR50 animals, suggesting that their gonadal WAT possesses a brown-like phenotype. This was confirmed by histological and immunoshistochemical procedures, which demonstrated that PND21 FR50 gonadal adipocytes are multilocular, resembling those present in interscapular brown adipose tissue, and exhibit an overexpression of UCP1 and neuropeptide Y (NPY) at the protein level. Control animals contained almost exclusively "classical" unilocular white adipocytes that did not show high UCP1 and NPY labeling. After weaning, FR50 animals exhibited a transient hyperphagia that was associated with the disappearance of brown-like fat pads in PND30 WAT. Our results demonstrate that MPU delays the maturation of gonadal WAT during critical developmental time windows, suggesting that it could have long-term consequences on body weight regulation in the offspring. maternal undernutrition; neuropeptide Y; uncoupling protein 1; peroxisome proliferator-activated receptor-␥ coactivator-1␣; adipose tissue programming A LARGE NUMBER OF EPIDEMIOLOGICAL studies have revealed a robust association between poor growth of the fetus/neonate and the subsequent development of type 2 diabetes, hypertension, and obesity. These findings have led to the developmental origin of health and disease hypothesis, which states that an adverse perinatal environment programs or imprints the development of several tissues, permanently determining physiological responses and ultimately producing dysfunction and dis-eases later in life (5, 18, 46, 48) . It is clear that altered weight gain during the perinatal period, due to over-or undernutrition, can significantly alter body weight in adulthood, but factors and/or mechanisms responsible for the development of abnormalities remain unclear. Intense attention has been focused on food intake itself, as well as the hypothalamic mechanisms that may be involved. In rodents, a large body of evidence suggests that hypothalamic "malprogramming" begins in utero, but continues in early postnatal life during the suckling period, leading to a disturbed organization and, consecutively, longlasting dysfunction in adulthood. For example, it has been shown that several modifications of energy status of the fetus or neonates, such as uterine artery ligated rat dams (41), perinatal low-protein-fed rat dams (39, 40), gestational diabetic rat dams (37, 38), undernourished rat dams (8), and perinatal over-and underfeeding neonatal rats (17, 32, 33), permanently alter hypothalamic nuclei structure and appetite programming system in later life. In contrast, little is known about the consequences of maternal perinatal undernutrition (MPU) on metabolic adaptations in peripheral tissues of the offspring. Since the discovery of leptin in the mid-1990s, interest has been aroused in feedback mechanisms between adipose tissue and the hypothalamic circuitry. Two types of adipose tissue coexist in mammals (10). White adipose tissue (WAT) has an essential role for storage of energy in the form of triacylglycerol. In situations of deficit, such as fasting, lipolysis in WAT controls the supply of energy to the body through the release of fatty acids into the plasma. Although it shares many features with WAT, brown adipose tissue (BAT) is specialized in adaptive thermogenesis, i.e., the regulated dissipation of energy as heat in response to cold and diet, through the oxidation of its stored lipids linked to the activity of uncoupling protein 1 (UCP1). UCP1 is a BAT-specific inner mitochondrial membrane protein capable of dissipating the proton electrochemical gradient generated by the respiratory chain during substrate oxidation, thus uncoupling oxidative phosphorylation (9). Brown adipocytes are rich in mitochondria, have cytoplasmic lipids arranged in numerous small droplets (multilocularity), and express high levels of UCP1, while white adipocytes do not express UCP1, are poor in mitochondria, store lipids in a unique big droplet (unilocularity), and have a low oxidative capacity. In rodents that belong to altricial species, the development of white fat depots is delayed and occurs almost exclusively during the postnatal period immediately after birth (2). In contrast, interscapular BAT (iBAT) develops precociously during fetal growth to provide the newborn with protection from cold exposure (49).
doi:10.1152/ajpregu.00604.2009
pmid:20463183
fatcat:kadiq56nlzhdjcx2e7tfeldjni
