A synaptic amplifier of hunger for regaining body weight in the hypothalamus.
Cell Metab
; 35(5): 770-785.e5, 2023 05 02.
Article
in En
| MEDLINE
| ID: mdl-36965483
ABSTRACT
Restricting caloric intake effectively reduces body weight, but most dieters fail long-term adherence to caloric deficit and eventually regain lost weight. Hypothalamic circuits that control hunger drive critically determine body weight; yet, how weight loss sculpts these circuits to motivate food consumption until lost weight is regained remains unclear. Here, we probe the contribution of synaptic plasticity in discrete excitatory afferents on hunger-promoting AgRP neurons. We reveal a crucial role for activity-dependent, remarkably long-lasting amplification of synaptic activity originating from paraventricular hypothalamus thyrotropin-releasing (PVHTRH) neurons in long-term body weight control. Silencing PVHTRH neurons inhibits the potentiation of excitatory input to AgRP neurons and diminishes concomitant regain of lost weight. Brief stimulation of the pathway is sufficient to enduringly potentiate this glutamatergic hunger synapse and triggers an NMDAR-dependent gaining of body weight that enduringly persists. Identification of this activity-dependent synaptic amplifier provides a previously unrecognized target to combat regain of lost weight.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hunger
/
Hypothalamus
Aspects:
Determinantes_sociais_saude
Limits:
Humans
Language:
En
Journal:
Cell Metab
Journal subject:
METABOLISMO
Year:
2023
Document type:
Article
Affiliation country:
Alemania