title: Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.
abstract: Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.
authors: Endocrine Research Unit, Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität (LMU Munich, Germany;
authors: Maximilian
authors: M
authors: Bielohuby
authors: Stephanie
authors: S
authors: Sisley
authors: Darleen
authors: D
authors: Sandoval
authors: Nadja
authors: N
authors: Herbach
authors: Ayse
authors: A
authors: Zengin
authors: Michael
authors: M
authors: Fischereder
authors: Dominik
authors: D
authors: Menhofer
authors: Barbara J M
authors: BJ
authors: Stoehr
authors: Kerstin
authors: K
authors: Stemmer
authors: Rüdiger
authors: R
authors: Wanke
authors: Matthias H
authors: MH
authors: Tschöp
authors: Randy J
authors: RJ
authors: Seeley
authors: Martin
authors: M
authors: Bidlingmaier
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism; D031204:Caloric Restriction; D004032:Diet; D050528:Diet, Carbohydrate-Restricted / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D015309:Glucose Clamp Technique; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000378:metabolism; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006728:Hormones / Q000097:blood; D006946:Hyperinsulinism / Q000378:metabolism; D007150:Immunohistochemistry; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008055:Lipids / Q000097:blood; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D051275:Glucose Transporter Type 4; D006728:Hormones; D008055:Lipids; C495694:Slc2a4 protein, rat; D014280:Triglycerides; D019893:Ribosomal Protein S6 Kinases
keywords: Atkins-style and ketogenic diet; dietary intervention; hyperinsulinemic euglycemic clamps; insulin resistance; macronutrients