title: Long-term low carbohydrate diet leads to deleterious metabolic manifestations in diabetic mice.
abstract: We investigated long-term effects of low carbohydrate diets on wild type mice, streptozotocin-injected and KKAy obese diabetic mice. These mice were pair-fed three different types of diets, standard chow (SC, C∶P∶F = 63∶15∶22), a low carbohydrate (LC, C∶P∶F = 38∶25∶37) diet and a severely carbohydrate restricted (SR, C∶P∶F = 18∶45∶37) diet for 16 weeks. Despite comparable body weights and serum lipid profiles, wild type and diabetic mice fed the low carbohydrate diets exhibited lower insulin sensitivity and this reduction was dependent on the amount of carbohydrate in the diet. When serum fatty acid compositions were investigated, monounsaturation capacity, i.e. C16:1/C16:0 and C18:1/C18:0, was impaired in all murine models fed the low carbohydrate diets, consistent with the decreased expression of hepatic stearoyl-CoA desaturase-1 (SCD1). Interestingly, both the hepatic expressions and serum levels of fibroblast growth factor 21 (FGF21), which might be related to longevity, were markedly decreased in both wild type and KKAy mice fed the SR diet. Taking into consideration that fat compositions did not differ between the LC and SR diets, we conclude that low carbohydrate diets have deleterious metabolic effects in both wild type and diabetic mice, which may explain the association between diets relatively low in carbohydrate and the elevated risk of cardiovascular events observed in clinical studies.
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Handa
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Inukai
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Onuma
authors.affiliation: Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Kudo
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Otsu, Shiga Japan.
authors.forename: Fumiyuki
authors.initials: F
authors.lastname: Nakagawa
authors.affiliation: Division of Molecular Biology, Institute for Genome Research, The University of Tokushima, Kuramoto, Tokushima, Japan.
authors.forename: Kazue
authors.initials: K
authors.lastname: Tsugawa
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Atsuko
authors.initials: A
authors.lastname: Kitahara
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Rie
authors.initials: R
authors.lastname: Moriya
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Kazuto
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sumitani
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Hosaka
authors.affiliation: Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Hayato
authors.initials: H
authors.lastname: Kawakami
authors.affiliation: Division of Molecular Biology, Institute for Genome Research, The University of Tokushima, Kuramoto, Tokushima, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Oyadomari
authors.affiliation: Third Department of Internal Medicine, Division of Diabetes, Endocrinology and Metabolism, Kyorin University School of Medicine, Mitaka, Tokyo, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishida
mesh_terms: D000818:Animals; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology*; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics; D005786:Gene Expression Regulation; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics
chemical_list: D005227:Fatty Acids; D012333:RNA, Messenger; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D013230:Stearoyl-CoA Desaturase