Hypothalamic substrates of metabolic imprinting

Simerly, Richard B.

doi:10.1016/j.physbeh.2007.11.023

Cited by 64 publications

(52 citation statements)

References 145 publications

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“…15,16 In this sense, we have previously shown in rats that the intake of moderate amounts of leptin during the suckling period prevents the development of overweight in later life, 18 and these long-term effects of leptin on body weight control were associated with an increased sensitivity to the central effects of leptin 21 and with a protection against central leptin resistance induced by dietary treatment. 18 Indirect evidence of the role of maternal milk-derived leptin in body weight control of infants has also been found in humans.…”

Section: Discussionmentioning

confidence: 96%

“…13,14 Variations in both prenatal and postnatal nutritional environments influence the neuronal circuits that control energy metabolism, and, among other metabolic-related hormones, leptin has been proposed to be one of the main signals linking perinatal nutritional environment and energy balance programming. [15][16][17][18] We have described the importance of leptin during the lactation period, in both regulating neonate food intake and affecting the developmental events involved in the control of energy balance in adulthood. 16 During the suckling period, oral leptin can be absorbed by the immature stomach of the neonate 19,20 and be transferred to the neonatal circulation and exerts its effect as a satiety hormone, thus having a role in the short-term control of food intake.…”

Section: Introductionmentioning

confidence: 99%

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Leptin intake during the suckling period improves the metabolic response of adipose tissue to a high-fat diet

2010

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Background: The intake of leptin during the suckling period protects against obesity and improves insulin and central leptin sensitivity in adult rats. Objective: We analyzed whether leptin treatment to neonates may also improve later peripheral leptin sensitivity in adipose tissue under high-fat (HF) diet conditions. Design: Male rats were supplemented with a daily oral dose of leptin or the vehicle (controls) during the suckling period. After weaning, animals were fed a normal-fat or an HF diet until the age of 6 months. At this age, mRNA and protein levels of the longform leptin receptor (OB-Rb) and the expression of other genes related with energy metabolism were measured in various adipose depots (inguinal, mesenteric and retroperitoneal). Results: HF-diet feeding resulted in lower OB-Rb mRNA and protein levels in internal depots in controls but not in leptin-treated animals; these animals maintained OB-Rb mRNA and protein levels under HF-diet conditions in these depots, particularly in the mesenteric one, and this was accompanied by increased expression of genes related with energy uptake (GLUT4, CD36), fatty acid oxidation (peroxisome proliferator activated receptor-a (PPARa), CPT1, UCP3) and lipogenesis (PPARg, GPAT). Leptintreatment also ameliorated HF-diet-induced hepatic fat accumulation occurring in control animals. Conclusion: Leptin treatment during the suckling period may improve the lasting effects of HF-diet feeding on leptin receptor abundance in the adipose tissue and increase its oxidative capacity, resulting in a better handling and partitioning of excess fuel. This, together with the described improvement of central leptin sensitivity, may explain why these animals are more protected against diet-induced obesity and its metabolic-related disorders.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Leptin intake during the suckling period improves the metabolic response of adipose tissue to a high-fat diet

2010

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“…Within the hypothalamus are specialised regions called hypothalamic nuclei (such as the arcuate nucleus, paraventricular nucleus, etc.) with distinct functions, gene expression patterns, and epigenetic regulation (40)(41)(42) . Moreover, within the hypothalamus there are many different cell types; the broadest dichotomisation is neurons (which convey information by generating action potentials), and glia (which lack this ability and instead serve broad functions including structural integrity, maintenance, and immune regulation) (43) .…”

Section: Biological Determinants and Developmental Programming Of Phymentioning

confidence: 99%

Developmental programming of energy balance regulation: is physical activity more ‘programmable’ than food intake?

et al. 2015

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Extensive human and animal model data show that environmental influences during critical periods of prenatal and early postnatal development can cause persistent alterations in energy balance regulation. Although a potentially important factor in the worldwide obesity epidemic, the fundamental mechanisms underlying such developmental programming of energy balance are poorly understood, limiting our ability to intervene. Most studies of developmental programming of energy balance have focused on persistent alterations in the regulation of energy intake; energy expenditure has been relatively underemphasised. In particular, very few studies have evaluated developmental programming of physical activity. The aim of this review is to summarise recent evidence that early environment may have a profound impact on establishment of individual propensity for physical activity. Recently, we characterised two different mouse models of developmental programming of obesity; one models fetal growth restriction followed by catchup growth, and the other models early postnatal overnutrition. In both studies, we observed alterations in body-weight regulation that persisted to adulthood, but no group differences in food intake. Rather, in both cases, programming of energy balance appeared to be due to persistent alterations in energy expenditure and spontaneous physical activity (SPA). These effects were stronger in female offspring. We are currently exploring the hypothesis that developmental programming of SPA occurs via induced sexspecific alterations in epigenetic regulation in the hypothalamus and other regions of the central nervous system. We will summarise the current progress towards testing this hypothesis. Early environmental influences on establishment of physical activity are likely an important factor in developmental programming of energy balance. Understanding the fundamental underlying mechanisms in appropriate animal models will help determine whether early life interventions may be a practical approach to promote physical activity in man.Metabolic imprinting: Epigenetics: DNA methylation: Nutrition Developmental programming, epigenetics and obesity During critical periods of embryonic, fetal and early postnatal development, environmental influences can affect mammalian development, leading to permanent changes in the regulation of energy balance. There is increasing acceptance of the idea that such developmental programming of energy balance regulation is an †These authors contributed equally to this work.

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“…Links between the perinatal nutritional environment and metabolic phenotype have been known for decades; being born of either low or high birth weight confers an increased risk for obesity and diabetes. Manipulation of litter size also alters levels of the adipocyte-derived hormone leptin, which has been identified as a potent neurotrophic factor that functions during perinatal life to specify patterns of connectivity in the hypothalamus (Simerly, 2008).…”

Section: Experience-dependent Development Of Neural Circuitry In Thalmentioning

confidence: 99%

Molecular Pathways Controlling Development of Thalamus and Hypothalamus: From Neural Specification to Circuit Formation

et al. 2010

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The embryonic diencephalon gives rise to the vertebrate thalamus and hypothalamus, which play essential roles in sensory information processing and control of physiological homeostasis and behavior, respectively. In this review, we present new steps toward characterizing the molecular pathways that control development of these structures, based on findings in a variety of model organisms. We highlight advances in understanding how early regional patterning is orchestrated through the action of secreted signaling molecules such as Sonic hedgehog and fibroblast growth factors. We address the role of individual transcription factors in control of the regional identity and neural differentiation within the developing diencephalon, emphasizing the contribution of recent large-scale gene expression studies in providing an extensive catalog of candidate regulators of hypothalamic neural cell fate specification. Finally, we evaluate the molecular mechanisms involved in the experience-dependent development of both thalamo-cortical and hypothalamic neural circuitry. IntroductionThe developing vertebrate forebrain consists of two major parts: the telencephalon-which gives rise to cerebral cortex, striatum, amygdala, and associated structures-and the diencephalon. The diencephalon gives rise to two essential brain regions, the thalamus and hypothalamus (Fig. 1 A). Though both structures are derived from a common region of the anterior neural tube, they serve very different physiological functions. The thalamus acts as a central integrator of sensory information, receiving afferents from receptors of all sensory modalities save olfaction, and serves as the sole path by which integrated sensory information reaches the cerebral cortex and gives rise to conscious perception. The hypothalamus, on the other hand, serves a more diverse range of functions. It is a central regulator of critical homeostatic physiological processes, including temperature regulation, food intake,

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Hypothalamic substrates of metabolic imprinting

Cited by 64 publications

References 145 publications

Leptin intake during the suckling period improves the metabolic response of adipose tissue to a high-fat diet

Leptin intake during the suckling period improves the metabolic response of adipose tissue to a high-fat diet

Developmental programming of energy balance regulation: is physical activity more ‘programmable’ than food intake?

Molecular Pathways Controlling Development of Thalamus and Hypothalamus: From Neural Specification to Circuit Formation

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