A high-fat, ketogenic diet induces a unique metabolic state in mice

Adam R. Kennedy, Pavlos Pissios, Hasan H Otu, Bingzhong Xue, Kenji Asakura, Noburu Furukawa, Frank E. Marino, Fen Fen Liu, Barbara B. Kahn, Towia A. Libermann, Eleftheria Maratos-Flier

Research output: Contribution to journalArticle

193 Citations (Scopus)

Abstract

Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume292
Issue number6
DOIs
StatePublished - Jan 1 2007

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Ketogenic Diet
High Fat Diet
Caloric Restriction
Diet
Gene Expression
Weights and Measures
Energy Metabolism
Weight Loss
Carbohydrate-Restricted Diet
Adenylate Kinase
Microarray Analysis
Inbred C57BL Mouse
Sucrose
Fatty Acids
Body Weight
Carbohydrates
Lipids
Glucose

Keywords

  • Gene expression
  • Liver

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

Cite this

A high-fat, ketogenic diet induces a unique metabolic state in mice. / Kennedy, Adam R.; Pissios, Pavlos; Otu, Hasan H; Xue, Bingzhong; Asakura, Kenji; Furukawa, Noburu; Marino, Frank E.; Liu, Fen Fen; Kahn, Barbara B.; Libermann, Towia A.; Maratos-Flier, Eleftheria.

In: American Journal of Physiology - Endocrinology and Metabolism, Vol. 292, No. 6, 01.01.2007.

Research output: Contribution to journalArticle

Kennedy, AR, Pissios, P, Otu, HH, Xue, B, Asakura, K, Furukawa, N, Marino, FE, Liu, FF, Kahn, BB, Libermann, TA & Maratos-Flier, E 2007, 'A high-fat, ketogenic diet induces a unique metabolic state in mice', American Journal of Physiology - Endocrinology and Metabolism, vol. 292, no. 6. https://doi.org/10.1152/ajpendo.00717.2006
Kennedy, Adam R. ; Pissios, Pavlos ; Otu, Hasan H ; Xue, Bingzhong ; Asakura, Kenji ; Furukawa, Noburu ; Marino, Frank E. ; Liu, Fen Fen ; Kahn, Barbara B. ; Libermann, Towia A. ; Maratos-Flier, Eleftheria. / A high-fat, ketogenic diet induces a unique metabolic state in mice. In: American Journal of Physiology - Endocrinology and Metabolism. 2007 ; Vol. 292, No. 6.
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