Dgat1
M. musculus
diacylglycerol O-acyltransferase 1
What the model saw
Gene: Dgat1 Organism: Mus musculus Known functions: diacylglycerol O-acyltransferase 1. 2-acylglycerol O-acyltransferase activity. O-acyltransferase activity. acyltransferase activity. diacylglycerol O-acyltransferase activity. diacylglycerol binding. fatty acid binding. identical protein binding. retinol O-fatty-acyltransferase activity.
View unredacted entry
diacylglycerol O-acyltransferase 1. 2-acylglycerol O-acyltransferase activity. O-acyltransferase activity. acyltransferase activity. diacylglycerol O-acyltransferase activity. diacylglycerol binding. fatty acid binding. identical protein binding. retinol O-fatty-acyltransferase activity.
Solver output
DGAT1 catalyzes the final and committed step in triglyceride biosynthesis, esterifying diacylglycerol with a fatty acyl-CoA to form triacylglycerol. Elevated DGAT1 activity promotes lipid storage and adiposity, which is associated with insulin resistance and impaired nutrient-sensing pathways including insulin/IGF-1 signaling. Notably, Dgat1 knockout mice are protected from diet-induced obesity, show improved insulin sensitivity, and exhibit extended lifespan, indicating that the normal pro-lipogenic function of DGAT1 is detrimental to longevity. The enzyme's diacylglycerol binding and fatty acid binding activities further facilitate lipotoxic DAG accumulation when overactive, impairing downstream metabolic signaling. This places DGAT1's normal function squarely in opposition to longevity through deregulated lipid/nutrient sensing.
GenAge curators classify each gene's normal function as promoting (Pro-Longevity) or opposing (Anti-Longevity) longevity, based on synthesis across studies. Loss-of-function effects can vary from this depending on the manipulation.
Advisor judgment
The model correctly predicted anti_longevity for Dgat1. The mechanistic reasoning is accurate and well-supported: DGAT1 catalyzes the final step in triglyceride biosynthesis, Dgat1 knockout mice are indeed protected from diet-induced obesity, show improved insulin sensitivity, and have extended lifespan. The model correctly identifies the mechanism as involving deregulated nutrient sensing through lipid accumulation and impaired insulin/IGF-1 signaling. The reasoning about DAG accumulation and lipotoxicity is also relevant. Confidence of 0.72 is appropriate given the specificity of the claim about lifespan extension in knockouts.
Raw API responses
solver
{
"reasoning": "DGAT1 catalyzes the final and committed step in triglyceride biosynthesis, esterifying diacylglycerol with a fatty acyl-CoA to form triacylglycerol. Elevated DGAT1 activity promotes lipid storage and adiposity, which is associated with insulin resistance and impaired nutrient-sensing pathways including insulin/IGF-1 signaling. Notably, Dgat1 knockout mice are protected from diet-induced obesity, show improved insulin sensitivity, and exhibit extended lifespan, indicating that the normal pro-lipogenic function of DGAT1 is detrimental to longevity. The enzyme's diacylglycerol binding and fatty acid binding activities further facilitate lipotoxic DAG accumulation when overactive, impairing downstream metabolic signaling. This places DGAT1's normal function squarely in opposition to longevity through deregulated lipid/nutrient sensing.",
"confidence": 0.72,
"key_pathways": [
"triglyceride biosynthesis / lipid storage",
"insulin/IGF-1 nutrient sensing",
"lipotoxicity and diacylglycerol signaling"
],
"mechanism_class": "deregulated_nutrient_sensing",
"longevity_influence": "anti_longevity"
}advisor
{
"notes": "The model correctly predicted anti_longevity for Dgat1. The mechanistic reasoning is accurate and well-supported: DGAT1 catalyzes the final step in triglyceride biosynthesis, Dgat1 knockout mice are indeed protected from diet-induced obesity, show improved insulin sensitivity, and have extended lifespan. The model correctly identifies the mechanism as involving deregulated nutrient sensing through lipid accumulation and impaired insulin/IGF-1 signaling. The reasoning about DAG accumulation and lipotoxicity is also relevant. Confidence of 0.72 is appropriate given the specificity of the claim about lifespan extension in knockouts.",
"failure_mode": "correct",
"answer_correct": true,
"mechanism_correct": true,
"reasoning_quality": 5,
"ground_truth_questionable": false
}