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Published on: March 11, 2017
Divergent Liver and Kidney Metabolic Responses to Ketogenic, High-Fat, and Sucrose-Enriched Diets in Mice
Giulia Grillo1,2, Nathalie Vega1, Agnieszka Zaczek1,3
1INSERM Unit 1060, South Lyon Medical Faculty, Lyon-1 University, 69495 Pierre Benite, France.
Background/Objectives:
Feeding with a ketogenic diet (KD), nutritionally devoid of carbohydrates, may be metabolically beneficial. The administration of a KD to mice after previous feeding with a high-fat, high-carbohydrate diet (HFD) induced weight loss, ketonemia, and glycemic normalization. Here, to compare organ-specific responses to KD, we analyzed lipogenic and gluconeogenic enzymes and genes in the liver and kidney of mice submitted to KD versus (i) HFD or (ii) a saccharose-enriched diet.
Methods:
Liver and kidney were from (i) mice fed a HFD followed by an 8-week switch to a chow diet (CD), KD continuation of HFD, and (ii) mice submitted to CD, KD, or a saccharose-enriched diet for 1 week. Protein expression levels were determined by Western blotting, and gene expression by qPCR. Hepatic lipid accumulation was visualized by red oil-O.
Results:
Switch to a KD led to a simultaneous decrease in lipogenic FASN (Fatty Acid Synthase), ACC (Acetyl-CoenzymeA Carboxylase), and its phosphorylated form (pACC-Ser79) in the liver and kidney. In parallel, we observed increased activating phosphorylation of AMPK, the kinase responsible for ACC phosphorylation. In the liver, but not in the kidney, the gluconeogenic rate-limiting enzyme G6Pase (Glucose 6-phosphatase) was repressed under a KD. The switch to a CD significantly reduced hepatic fat accumulation, while a switch to a KD did not allow a significant reversal of hepatic fat accumulation, suggesting resilience to hepatic fat loss under KD. Comparison of a KD versus saccharose-supplemented diet showed an opposite expression pattern of lipogenic enzymes.
Conclusions:
Administration of KD after previous HFD induced convergent repression of lipogenic enzymes in the liver and kidney, and specific repression of G6Pase in the liver, suggesting a role for kidney gluconeogenesis during KD. KD versus saccharose-supplemented diet had opposite effects on lipogenesis and glycemic control, but both induced loss of lean body mass.
