Distinct basal forebrain-originated neural circuits promote homoeostatic feeding and suppress hedonic feeding in male mice.
Hailan LiuJonathan Carter BeanYongxiang LiMeng YuOlivia Z GinnardKristine M CondeMengjie WangXing FangHesong LiuLonglong TuNa YinJunying HanYongjie YangQingchun TongBenjamin R ArenkielChunmei WangYang HeYong XuPublished in: Nature metabolism (2024)
Feeding behaviour is influenced by two primary factors: homoeostatic needs driven by hunger and hedonic desires for pleasure even in the absence of hunger. While efficient homoeostatic feeding is vital for survival, excessive hedonic feeding can lead to adverse consequences such as obesity and metabolic dysregulations. However, the neurobiological mechanisms that orchestrate homoeostatic versus hedonic food consumption remain largely unknown. Here we show that GABAergic proenkephalin (Penk) neurons in the diagonal band of Broca (DBB) of male mice respond to food presentation. We further demonstrate that a subset of DBB Penk neurons that project to the paraventricular nucleus of the hypothalamus are preferentially activated upon food presentation during fasting periods and transmit a positive valence to facilitate feeding. On the other hand, a separate subset of DBB Penk neurons that project to the lateral hypothalamus are preferentially activated when detecting a high-fat high-sugar (HFHS) diet and transmit a negative valence to inhibit food consumption. Notably, when given free choice of chow and HFHS diets, mice with the whole DBB Penk population ablated exhibit reduced consumption of chow but increased intake of the HFHS diet, resulting in accelerated development of obesity and metabolic disturbances. Together, we identify a molecularly defined neural population in male mice that is crucial for the maintenance of energy balance by facilitating homoeostatic feeding while suppressing hedonic overeating.
Keyphrases
- weight loss
- insulin resistance
- weight gain
- metabolic syndrome
- spinal cord
- high fat diet induced
- type diabetes
- physical activity
- human health
- signaling pathway
- body mass index
- emergency department
- blood pressure
- minimally invasive
- adipose tissue
- spinal cord injury
- climate change
- case report
- adverse drug
- electronic health record