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Islets RNA-seq from male C57Bl/6J on ketogenic diet

GSE268020 Mus musculus Expression profiling by high throughput sequencing 9 samples Submitted 2025/08/18 Platform GPL34328
Summary
A ketogenic diet (KD) is a very low-carbohydrate, very high-fat diet recently proposed to treat obesity and type 2 diabetes. While KD grows in popularity, its effects on metabolic health are understudied. (here) We show that, while KD protects against weight gain and induces weight loss, over long-term, mice develop hyperlipidemia, hepatic steatosis, and severe glucose intolerance. Unlike HFD-fed mice, KD mice are not insulin resistant and have low levels of insulin. Hyperglycemic clamp and ex vivo GSIS revealed cell-autonomous and whole-body impairments in insulin secretion. Major ER/Golgi stress and disrupted ER-Golgi protein trafficking was indicated by transcriptomic profiling of KD islets and confirmed by electron micrographs showing a dilated and fragmented Golgi network compatible with defects in insulin granule biogenesis and secretion. Overall, our results suggest long-term KD leads to multiple aberrations of metabolic parameters that caution its systematic use as a health promoting dietary intervention.
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Also filed as BioProject PRJNA1114063 and SRA study SRP508991. Searching any of these in the dataset finder brings you back here.

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