Perinatal metabolic inflammation in the hypothalamus impairs the development of homeostatic feeding circuitry
Rahim Ullah1, Yi Shen2, Yu-Dong Zhou2
1Department of Endocrinology, Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, 310052, China; Institute of Neuroscience, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, Zhejiang University School of Brain Science and Brain Medicine, Hangzhou, China.
Insights
Perinatal metabolic inflammation, often linked to maternal obesity, can disrupt the development of crucial feeding-regulating neurons in the hypothalamus. This impacts metabolism and increases obesity risk in offspring.
Area of Science:
- Neuroscience
- Metabolism
- Endocrinology
Background:
- Childhood obesity is a growing global health concern, leading to metabolic dysfunction in children and adults.
- The hypothalamus, particularly the arcuate nucleus (ARC), regulates feeding behavior via proopiomelanocortin (POMC) and agouti-related peptide (AGRP) neurons.
- These neurons sense nutrients and hormones like insulin, leptin, and ghrelin, with their development continuing postnatally.
Purpose of the Study:
- To review how perinatal metabolic inflammation affects the development of POMC and AGRP neurons in the hypothalamus.
- To explore the unclear mechanisms linking maternal obesity and postnatal overfeeding to defective neuronal development.
Main Methods:
- Literature review focusing on animal models of maternal obesity and postnatal overfeeding/high-fat diet (HFD).
- Analysis of studies examining the impact of metabolic inflammation on hypothalamic neuronal development and signaling pathways.
Main Results:
- Maternal obesity and postnatal overfeeding/HFD induce metabolic inflammation.
- This inflammation disrupts signaling of metabolic hormones, netrin-1, and neurogenic factors.
- Neonatal obesity and defective development of POMC/AGRP neurons are observed in animal models.
Conclusions:
- Perinatal metabolic inflammation is a key factor influencing the development of hypothalamic feeding circuits.
- Understanding these mechanisms is crucial for addressing the rising rates of childhood obesity and associated metabolic disorders.
Abstract:
Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothalamus, specifically the arcuate nucleus (ARC), houses crucial neurons involved in regulating homeostatic feeding. These neurons include proopiomelanocortin (POMC) and agouti-related peptide (AGRP) secreting neurons. They play a vital role in sensing nutrients and metabolic hormones like insulin, leptin, and ghrelin. The neurogenesis of AGRP and POMC neurons completes at birth; however, axon development and synapse formation occur during the postnatal stages in rodents. Insulin, leptin, and ghrelin are the essential regulators of POMC and AGRP neurons. Maternal obesity and postnatal overfeeding or a high-fat diet (HFD) feeding cause metabolic inflammation, disrupted signaling of metabolic hormones, netrin-1, and neurogenic factors, neonatal obesity, and defective neuronal development in animal models; however, the mechanism is unclear. Within the hypothalamus and other brain areas, there exists a wide range of interconnected neuronal populations that regulate various aspects of feeding. However, this review aims to discuss how perinatal metabolic inflammation influences the development of POMC and AGRP neurons within the hypothalamus.
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