Validation experiment designed to validate causal mechanisms targeting Hmgcs2, Cd36, Cpt1a, Acat1 in C57BL/6J wild-type mice. Primary outcome: β-hydroxybutyrate levels and ketogenesis gene expression
This experiment evaluated multiple ketogenic diet formulations with varying fat content (80-95%) in C57BL/6J wild-type mice to determine the fat threshold required for sustained ketosis. Researchers measured plasma, hepatic, and intestinal β-hydroxybutyrate (BHB) levels and assessed expression of ketogenesis and fatty acid oxidation genes including Cd36, Cpt1a, Acat1, and Hmgcs2. Body weight, adipose distribution, and liver morphology were monitored. The study found that only diets exceeding 85% fat induced robust ketogenesis with elevated BHB and hepatic upregulation of key metabolic genes, while moderate KDs (80-85%) failed to trigger ketosis and resembled standard high-fat feeding.
Multiple KD formulations (80-95% fat) feeding with measurement of plasma, hepatic, and intestinal BHB levels and gene expression analysis
Identification of fat threshold for sustained ketosis and associated metabolic changes
Elevated BHB levels and upregulation of ketogenesis genes
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