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Clinical Science (2007) 113, (417–425) (Printed in Great Britain)

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Increasing the fat-to-carbohydrate ratio in a high-fat diet prevents the development of obesity but not a prediabetic state in rats

Natalia SINITSKAYA*, Sylviane GOURMELEN*, Carole SCHUSTER-KLEIN†, Béatrice GUARDIOLA-LEMAITRE†, Paul PÉVET* and Etienne CHALLET*

*Département de Neurobiologie des Rythmes, Institut de Neurosciences Cellulaires et Intégratives, CNRS, Université Louis Pasteur, 5 rue Blaise pascal, 67084 Strasbourg, France, and †Institut de Recherches Internationales Servier (IRIS-Servier), 29/31 rue du Pont, 92578 Neuilly sur Seine, France

Key words: adiponectin, high-fat diet, insulin resistance, leptin, metabolic syndrome, obesity, Type 2 diabetes.

Abbreviations: a.u., arbitrary units; BMI, body mass index; CV, coefficient of variation; HCD, low-fat and high-carbohydrate diet; HDL-C, high-density lipoprotein cholesterol; HFD1, high-fat and medium-carbohydrate diet; HFD2, very-high-fat and low-carbohydrate diet; HFD3, very-high-fat and carbohydrate-free diet; HOMA, homoeostatic model assessment; HOMA-IR, HOMA of insulin resistance; LDL-C, low-density lipoprotein cholesterol; NEFA, non-esterified fatty acid.

Correspondence: Dr Etienne Challet (email challet@neurochem.u-strasbg.fr).

Metabolic disorders induced by high-fat feeding in rodents evoke some, if not all, of the features of human metabolic syndrome. The occurrence and severity of metabolic disorders, however, varies according to rodent species, and even strain, as well as the diet. Therefore, in the present study, we investigated the long-term obesogenic and diabetogenic effects of three high-fat diets differing by their fat/carbohydrate ratios. Sprague–Dawley rats were fed a control high-carbohydrate and low-fat diet [HCD; 3:16:6 ratio of fat/carbohydrate/protein; 15.48 kJ/g (3.7 kcal/g)], a high-fat and medium-carbohydrate diet [HFD1; 53:30:17 ratio of fat/carbohydrate/protein; 19.66 kJ/g (4.7 kcal/g)], a very-high-fat and low-carbohydrate diet [HFD2; 67:9:24 ratio of fat/carbohydrate/protein; 21.76 kJ/g (5.2 kcal/g)] or a very-high-fat and carbohydrate-free diet [HFD3; 75:0:25 ratio of fat/carbohydrate/protein; 24.69 kJ/g (5.9 kcal/g)] for 10 weeks. Compared with the control diet (HCD), rats fed with high-fat combined with more (HFD1) or less (HFD2) carbohydrate exhibited higher BMI (body mass index; +13 and +10% respectively; P<0.05) and abdominal fat (+70% in both HFD1 and HFD2; P<0.05), higher plasma leptin (+130 and +135% respectively; P<0.05), lower plasma adiponectin levels (-23 and -30% respectively; P<0.05) and impaired glucose tolerance. Only the HFD1 group had insulin resistance. By contrast, a very-high-fat diet devoid of carbohydrate (HFD3) led to impaired glucose tolerance, insulin resistance and hypoadiponectinaemia (-50%; P<0.05), whereas BMI, adiposity and plasma leptin did not differ from respective values in animals fed the control diet. We conclude that increasing the fat-to-carbohydrate ratio to the uppermost (i.e. carbohydrate-free) in a high-fat diet prevents the development of obesity, but not the prediabetic state (i.e. altered glucose tolerance and insulin sensitivity).

Received 5 June 2007/26 June 2007; accepted 4 July 2007

Published as Immediate Publication 4 July 2007, doi:10.1042/CS20070182

© The Authors Journal compilation © 2007 Biochemical Society