A high-fat, ketogenic diet induces a unique metabolic state in mice.
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.
Kennedy
Adam R
AR
Division of Endocrinology, Departmentof Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave., Boston, MA 02215, USA.
Pissios
Pavlos
P
Otu
Hasan
H
Roberson
Russell
R
Xue
Bingzhong
B
Asakura
Kenji
K
Furukawa
Noburu
N
Marino
Frank E
FE
Liu
Fen-Fen
FF
Kahn
Barbara B
BB
Libermann
Towia A
TA
Maratos-Flier
Eleftheria
E
D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors; D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D031204:Caloric Restriction; D050528:Diet, Carbohydrate-Restricted; D004041:Dietary Fats / Q000008:administration & dosage* / Q000494:pharmacology; D004734:Energy Metabolism; D015870:Gene Expression; D005951:Glucose Tolerance Test; D007657:Ketone Bodies / Q000096:biosynthesis*; D007662:Ketosis / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015431:Weight Loss
D004041:Dietary Fats; D007657:Ketone Bodies; D000263:Adenylate Kinase; D000103:Acetyl-CoA Carboxylase