Biology subjects

Tsang, A. H.

Publications and source records attributed to Tsang, A. H..

2 recordsLinked to original sources

bioRxiv2024

Cav3.1 is a leucine sensor in POMC neurons mediating appetite suppression and weight loss

Hypothalamic leucine sensing promotes satiety and weight loss but an understanding of how leucine regulates neuronal activity is lacking. Here we show that Cacna1g, encoding the T-type voltage-gated calcium channel Cav3.1, is enriched in hypothalamic leucine-sensing neurons and mediates leucine sensing. Pharmacological inhibition of Cav3.1 blunts leucine-induced activation of POMC neurons as well as the anorectic response to leucine in vivo. In addition, genetic deletion of Cacna1g in POMC neurons abolishes the appetite- and weight-suppressive effects of high-protein feeding. Mechanistically, we show that leucine binds to the voltage-sensing segment of Cav3.1, thereby reducing its threshold for voltage-dependent activation. Last, pharmacological activation of hypothalamic Cav3.1 promotes weight loss in diet-induced obese mice and potentiates the weight loss response to GLP-1 receptor agonism. These results reveal that Cav3.1 is a neuronal leucine sensor and a relevant weight loss target.

neuroscience↗

bioRxiv2020

Nutrient sensing in the nucleus od the solitary tract mediates non-aversive suppression of feeding via inhibition of AgRP neurons.

The nucleus of the solitary tract (NTS) is emerging as a major site of action for the appetite-suppressive effects of leading pharmacotherapies currently investigated for the treatment of obesity. However, our understanding of how NTS neurons regulate appetite remains incomplete. Here we used NTS nutrient sensing as an entry point to characterize stimulus-defined neuronal ensembles engaged by the NTS to produce physiological satiety. Using activity-dependent expression of genetically-encoded circuit analysis tools, we found that NTS detection of leucine engages NTS prolactin-releasing peptide (PrRP) neurons to inhibit AgRP neurons via a population of leptin-receptor-expressing neurons in the dorsomedial hypothalamus. This circuit is necessary for the anorectic response to NTS leucine, the appetite-suppressive effect of high protein diets, and the long-term control of energy balance. These results extends the integrative capability of AgRP neurons to include brainstem nutrient sensing inputs.

neuroscience↗