Project description:Specific pathogen free wild-type C57Bl/6 male mice fed ketogenic diet (Bio-Serv AIN-76-A) for 4 weeks Keywords: RNA Expression Array Hearts from 12 week-old mice that were maintained on a standard polysacchardide-rich chow until the age of 8 weeks, at which time they were switched to a ketogenic diet (ad libitum) and maintained for 4 additional weeks prior to collection of tissues
Project description: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.
Project description: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
Project description:Analysis of liver gene transcription during feeding of a ketogenic diet. Ketogenic diets may alter physiologic and metabolic profiles in a direction that favors weight loss. C57BL/6J mice were maintained for six weeks on either chow or ketogenic diet. Mice eating KD had lower weights, 90% reduction in insulin levels and increased energy expenditure compared to animals fed chow. Despite consumpiton of a very high fat diet serum lipids remained normal. Here we show that consumption of KD shifted liver metabolism to drastically increased fatty acid oxidation. Concurrently, expression of genes involved in fatty acid synthesis were markedly suppressed. Keywords: Hepatic profile
Project description:Analysis of liver gene transcription during feeding of a ketogenic diet. Ketogenic diets may alter physiologic and metabolic profiles in a direction that favors weight loss. C57BL/6J mice were maintained for six weeks on either chow or ketogenic diet. Mice eating KD had lower weights, 90% reduction in insulin levels and increased energy expenditure compared to animals fed chow. Despite consumption of a very high fat diet serum lipids remained normal. Here we show that consumption of KD shifted liver metabolism to drastically increased fatty acid oxidation. Concurrently, expression of genes involved in fatty acid synthesis were markedly suppressed. Reference: A high fat, ketogenic diet induces a unique metabolic state in mice. Kennedy AR, Pissios P, Out H, Xue B, Asakura K, Furukawa N, Marino FE, Liu FF, Kahn BB, Liberman TA, Maratos-Flier E. in press, 2007, Am J Physiol Metab 292. Experiment Overall Design: Eight week old C57BL/6 mice were fed either chow (Labdiet 5008, Pharmserv) or KD (F3666, Bio-Serv) for six weeks. Livers were harvested in the morning in ad lib fed animals. Total RNA from 2-3 animals in each group was used for Affymetrix analysis.
Project description:Male C57Bl/6J mice were fed 45%kcal fat diet (HF) or regular rodent chow (NC) from 4 weeks to 16 weeks of age. Gene expression was compared between RNA obtained from pancreatic islets of HF fed mice and NC mice.
Project description:The ketogenic diet has long been used to treat epilepsy, but its mechanism is not yet clearly understood. To explore the potential mechanism, the changes in gene expression induced by the ketogenic diet in the rat kainic acid (KA) epilepsy model were analyzed. Two-condition experiment, Normal diet-fed rat brain vs. Ketogenic diet-fed rat brain. Duplicate per array