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 kinase3) (AMPK)-regulated corticotropin-releasing hormone (CRH) 4) neurons and melanocortin 4 receptor (MC4R) 5)-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.
Notes
1) 2-deoxy-D-glucose (2DG)
Glucose analog. 2DG transiently causes glucopenia in the body when administered intraperitoneally.
2) The paraventricular nucleus of the hypothalamus (PVH)
A critical hypothalamic nucleus that regulates appetite and the release of pituitary hormones.
3) AMP kinase (AMPK)
AMPK is activated by cellular energy depletion, thereby stimulating glucose and lipid utilization in cells. In hypothalamic neurons, AMPK regulates feeding (Minokoshi, et al. Nature 428:569-574, 2004. doi: 10.1038/nature02440).
4) Corticotropin-releasing hormone (CRH) neuron
This neuron is widely expressed in the brain. However, the neurons in the PVH regulate the hypothalamus-pituitary-adrenal axis, and its activation causes several stress-related behaviors. This research team discovered that activation of PVH AMPK-activated CRH neurons causes carbohydrate selection in mice (Okamoto S, et al. Cell Reports 22:706-721, 2018. doi: 10.1016/j.celrep.2017.11.10）.
5) Melanocortin 4 receptor (MC4R)-expressing neuron
MC4R plays an essential role in the total calorie intake regulation. The gene mutations and polymorphisms cause obesity and increase its susceptibility in humans.
