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Updated: Jun 12, 2025
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Real-time Analysis of Gut-brain Neural Communication: Cortex wide Calcium Dynamics in Response to Intestinal Glucose Stimulation
Published on: December 29, 2023
620
Intestinal gluconeogenesis controls the neonatal development of hypothalamic feeding circuits.
Judith Estrada-Meza1, Jasmine Videlo1, Clara Bron1
1INSERM UMR-S1213, Université Claude Bernard Lyon 1, Lyon, France.
Molecular Metabolism
|September 20, 2024
Summary
Neonatal intestinal gluconeogenesis (IGN) programs hypothalamic feeding circuits and adipose tissue innervation. Early IGN induction at birth, but not later, improves adult metabolic health and protects against high-fat diets.
Area of Science:
- Metabolic regulation
- Neuroendocrinology
- Developmental biology
Background:
- Intestinal gluconeogenesis (IGN) plays a role in adult energy homeostasis, targeting hypothalamic pathways similar to leptin.
- A neonatal surge of leptin influences hypothalamic development and autonomic innervation, coinciding with IGN induction.
- The role of neonatal IGN in shaping these developmental processes remains unclear.
Purpose of the Study:
- To investigate the hypothesis that the neonatal peak of IGN regulates the development of hypothalamic feeding circuits and sympathetic innervation of adipose tissues.
- To determine if early-life IGN impacts adult metabolic regulation.
Main Methods:
- Genetically induced neonatal IGN by overexpressing glucose-6-phosphatase (G6pc1) at birth or postnatal day 12.
- Assessed hypothalamic Agouti-related protein (AgRP) and Pro-opiomelanocortin (POMC) fiber density to study feeding circuit development.
- Quantified tyrosine hydroxylase (TH) in adipose tissue to assess sympathetic innervation.
- Challenged adult mice with a high-fat/high-sucrose diet to evaluate metabolic consequences.
Main Results:
- Induction of G6pc1 at birth altered AgRP/POMC fiber density in the hypothalamus and increased brown adipose tissue TH levels.
- Early IGN induction conferred protection against diet-induced metabolic disorders in adulthood.
- Induction of G6pc1 at postnatal day 12 had no significant effects on neural development or adult metabolism.
Conclusions:
- Neonatal IGN, specifically at birth, is critical for establishing hypothalamic feeding circuits and sympathetic adipose tissue innervation.
- This early developmental programming by IGN promotes improved metabolic control in adulthood.
- The timing of IGN is crucial, with effects limited to a narrow neonatal window.
Keywords:
Agouti-related peptide (AgRP)Developmental programmingHypothalamic developmentIntestinal gluconeogenesisNeonatal periodObesityPro-opiomelanocortin (POMC)More Related Videos
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