Summary: A new study reveals that the brain uses two distinct neural pathways to regulate sugar and fat intake. In mice, glucoprivation—a drop in blood sugar levels—activates separate circuits in the hypothalamus: AMPK-regulated CRH neurons drive high-carbohydrate consumption, while MC4R-expressing neurons promote high-fat food intake.
These pathways are triggered by NPY neurons in the brainstem, which respond to energy deficits. The discovery sheds light on how the brain distinguishes between nutrient types when balancing energy needs, offering clues for treating overeating and metabolic disorders.
Key Facts
- Dual Neural Circuits: High-carb and high-fat food intake are controlled by separate hypothalamic pathways.
- Energy Deficit Trigger: NPY neurons in the brainstem activate both circuits in response to glucoprivation.
- Feeding Insight: Understanding these pathways could inform interventions for obesity and disordered eating.
Source: NINS
Feeding in mammals is controlled by a complex neural system. Although several key neural pathways related to total calorie intake have been extensively studied, it is still unclear how food choices are regulated and how they influence overall feeding behavior.
Food selection among different types, such as an HCD and an HFD, is affected by various internal conditions. For example, mice usually consume only an HFD, but they will eat both an HCD and an HFD when glucoprivation occurs after 2DG administration.
However, the neural mechanisms behind this remain unknown.
The research team examined the neural mechanisms influencing food choice between an HCD and an HFD in mice after administering 2DG. They found that the consumption of HCD and HFD after 2DG is independently controlled by AMP kinase (AMPK)-regulated corticotropin-releasing hormone (CRH) neurons and melanocortin 4 receptor (MC4R) expressing neurons in the PVH, respectively.
The researchers also discovered that neuropeptide Y (NPY) neurons in the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM) activate both AMPK-regulated CRH neurons and MC4R neurons in the PVH, promoting HCD and HFD intake following 2DG treatment.
Conversely, NPY neurons in the arcuate nucleus of the hypothalamus (ARC) inhibit MC4R neurons in the PVH, resulting in increased HFD intake alone.
These findings first demonstrated that HCD and HFD intake are controlled by two separate neural pathways in the brain.
This could offer new insights into understanding the neural mechanisms behind food choices among foods with different nutrient compositions.
Key Questions Answered:
A: It activates separate neural circuits in the hypothalamus—one promoting carbohydrate consumption via CRH neurons and another driving fat intake through MC4R neurons.
A: When blood sugar drops (as during glucoprivation), NPY neurons in the brainstem stimulate both circuits, prompting intake of high-carb and high-fat foods to restore energy balance.
A: They uncover the brain’s nutrient-specific control of feeding, revealing potential targets for treating obesity, diabetes, and binge eating.
About this neuroscience and food craving research news
Author: Hayao KIMURA
Source: NINS
Contact: Hayao KIMURA – NINS
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Glucoprivation-induced nutrient preference relies on distinct NPY neurons that project to the paraventricular nucleus of the hypothalamus” by Nawarat Rattanajearakul et al. Metabolism
Abstract
Glucoprivation-induced nutrient preference relies on distinct NPY neurons that project to the paraventricular nucleus of the hypothalamus
Background
Neural pathways related to total calorie intake have been extensively studied. However, it remains unclear how these mechanisms control food selection.
Methods
Male mice were subjected to glucoprivation through the intraperitoneal (i.p.) administration of 2-deoxy-d-glucose (2DG) and were examined for food selection between a high-carbohydrate diet (HCD) and a high-fat diet (HFD) in a diet choice paradigm.
This involved the chemogenetic or optogenetic modulation of the neural activity of AMP-activated protein kinase (AMPK)-regulated corticotropin-releasing hormone (CRH) neurons, melanocortin-4 receptor (MC4R) neurons in the paraventricular nucleus of the hypothalamus (PVH), and neuropeptide Y (NPY) neurons projecting to the PVH.
Results
Glucoprivation induced by 2DG administration in mice influenced two distinct neural pathways in the PVH that separately promote the intake of an HCD or an HFD. Injection of 2DG activated PVH-projecting NPY neurons in the nucleus of the solitary tract (NTS) and ventrolateral medulla (VLM), resulting in a rapid increase in HCD intake through stimulation of PVH AMPK–regulated CRH neurons and recovery from glucoprivation. In contrast, PVH-projecting NPY neurons in the NTS, VLM, and arcuate nucleus of the hypothalamus (ARC) promoted HFD intake by inhibiting MC4R neurons in the PVH, reflecting the strong innate preference for an HFD in mice. The ARC NPY neurons specifically promoted HFD selection.
Conclusion
Our findings reveal a previously unrecognized mechanism for food selection between HCD and HFD during glucoprivation.
