Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture
| العنوان: | Neonatal GLP1R activation limits adult adiposity by durably altering hypothalamic architecture |
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| المؤلفون: | Andrea V. Rozo, Doris A. Stoffers, Patrick Seale, Rebecca A. Simmons, Daniella A. Babu, David N. Groff, Po Man A. Suen, Randy J. Seeley, Rexford S. Ahima |
| المصدر: | Molecular Metabolism, Vol 6, Iss 7, Pp 748-759 (2017) Molecular Metabolism |
| بيانات النشر: | Elsevier, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Hypothalamic architecture, medicine.medical_specialty, lcsh:Internal medicine, Hypothalamus, Adipose tissue, White adipose tissue, Biology, Glucagon, Incretins, Fat pad, Glucagon-Like Peptide-1 Receptor, 03 medical and health sciences, Mice, Internal medicine, Orexigenic, medicine, Animals, Obesity, lcsh:RC31-1245, Molecular Biology, Adiposity, 2. Zero hunger, Neurons, Fetus, Orexins, Venoms, Cell Biology, Incretin, Beige fat, medicine.disease, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, Metabolism, Exenatide, Original Article, Female, medicine.symptom, Peptides, Weight gain, medicine.drug |
| الوصف: | Objective Adult obesity risk is influenced by alterations to fetal and neonatal environments. Modifying neonatal gut or neurohormone signaling pathways can have negative metabolic consequences in adulthood. Here we characterize the effect of neonatal activation of glucagon like peptide-1 (GLP-1) receptor (GLP1R) signaling on adult adiposity and metabolism. Methods Wild type C57BL/6 mice were injected with 1 nmol/kg Exendin-4 (Ex-4), a GLP1R agonist, for 6 consecutive days after birth. Growth, body composition, serum analysis, energy expenditure, food intake, and brain and fat pad histology and gene expression were assessed at multiple time points through 42 weeks. Similar analyses were conducted in a Glp1r conditional allele crossed with a Sim1Cre deleter strain to produce Sim1Cre;Glp1rloxP/loxP mice and control littermates. Results Neonatal administration of Ex-4 reduced adult body weight and fat mass, increased energy expenditure, and conferred protection from diet-induced obesity in female mice. This was associated with induction of brown adipose genes and increased noradrenergic fiber density in parametrial white adipose tissue (WAT). We further observed durable alterations in orexigenic and anorexigenic projections to the paraventricular hypothalamic nucleus (PVH). Genetic deletion of Glp1r in the PVH by Sim1-Cre abrogated the impact of neonatal Ex-4 on adult body weight, WAT browning, and hypothalamic architecture. Conclusion These observations suggest that the acute activation of GLP1R in neonates durably alters hypothalamic architecture to limit adult weight gain and adiposity, identifying GLP1R as a therapeutic target for obesity prevention. Graphical abstract Image 1 Highlights • Neonatal Ex-4 attenuates diet-induced obesity in adult female mice. • Neonatal Ex-4 enhances adult energy expenditure and beiging of parametrial WAT. • Neonatal Ex-4 durably alters hypothalamic architecture. • The impact of neonatal Ex-4 was abrogated in Sim1Cre;Glp1rloxP/loxP mice. • GLP1R may be a therapeutic target for obesity prevention. |
| اللغة: | English |
| تدمد: | 2212-8778 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3eb2c1d7475d4343ed707fdb42334239Test http://www.sciencedirect.com/science/article/pii/S2212877817301023Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3eb2c1d7475d4343ed707fdb42334239 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22128778 |
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