The TUB variant impairs leptin sensitivity and AgRP neuronal response, leading to obesity - PubMed
3 months ago
- #genetics
- #obesity
- #leptin
- The TUB variant p.R364G disrupts protein localization and is linked to obesity.
- Knock-in mice with the TUB p.R363G variant showed hyperphagia and obesity, especially on a high-fat diet.
- The variant impairs leptin sensitivity, leading to leptin resistance in mice.
- TUB interacts with STAT3 to regulate the leptin pathway, an interaction disrupted by the p.R364G variant.
- Silencing TUB reduces leptin's inhibitory effects on AgRP neurons, leading to hyperphagic obesity.
- Conditional ablation of TUB in AgRP+ neurons in mice resulted in obesity and reduced leptin-induced appetite suppression.
- Rare loss-of-function variants in TUB predispose to young-onset obesity in humans by impairing leptin sensitivity in AgRP neurons.