title: A small amount of dietary carbohydrate can promote the HFD-induced insulin resistance to a maximal level.
abstract: Both dietary fat and carbohydrates (Carbs) may play important roles in the development of insulin resistance. The main goal of this study was to further define the roles for fat and dietary carbs in insulin resistance. C57BL/6 mice were fed normal chow diet (CD) or HFD containing 0.1-25.5% carbs for 5 weeks, followed by evaluations of calorie consumption, body weight and fat gains, insulin sensitivity, intratissue insulin signaling, ectopic fat, and oxidative stress in liver and skeletal muscle. The role of hepatic gluconeogenesis in the HFD-induced insulin resistance was determined in mice. The role of fat in insulin resistance was also examined in cultured cells. HFD with little carbs (0.1%) induced severe insulin resistance. Addition of 5% carbs to HFD dramatically elevated insulin resistance and 10% carbs in HFD was sufficient to induce a maximal level of insulin resistance. HFD with little carbs induced ectopic fat accumulation and oxidative stress in liver and skeletal muscle and addition of carbs to HFD dramatically enhanced ectopic fat and oxidative stress. HFD increased hepatic expression of key gluconeogenic genes and the increase was most dramatic by HFD with little carbs, and inhibition of hepatic gluconeogenesis prevented the HFD-induced insulin resistance. In cultured cells, development of insulin resistance induced by a pathological level of insulin was prevented in the absence of fat. Together, fat is essential for development of insulin resistance and dietary carb is not necessary for HFD-induced insulin resistance due to the presence of hepatic gluconeogenesis but a very small amount of it can promote HFD-induced insulin resistance to a maximal level.
authors: Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors: Shuang
authors: S
authors: Mei
authors: Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors: Xuefeng
authors: X
authors: Yang
authors: Department of Nutrition, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors: Huailan
authors: H
authors: Guo
authors: Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors: Haihua
authors: H
authors: Gu
authors: Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Nutrition and Food Hygiene, South Medical University, Guangzhou, China.
authors: Longying
authors: L
authors: Zha
authors: Department of Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors: Junwei
authors: J
authors: Cai
authors: Department of Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China.
authors: Xuefeng
authors: X
authors: Li
authors: Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, United States of America.
authors: Zhenqi
authors: Z
authors: Liu
authors: Department of Human Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
authors: Brian J
authors: BJ
authors: Bennett
authors: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America.
authors: Ling
authors: L
authors: He
authors: Nutrition Research Institute at Kannapolis, Department of Nutrition, Gillings School of Global Public Health, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China; Department of Medicine (Endocrinology and Metabolism), Duke University School of Medicine, Durham, North Carolina, United States of America.
authors: Wenhong
authors: W
authors: Cao
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects*; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005663:Furans / Q000494:pharmacology; D005943:Gluconeogenesis / Q000187:drug effects; D007004:Hypoglycemic Agents / Q000494:pharmacology; D015151:Immunoblotting; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D004040:Dietary Carbohydrates; D005230:Fatty Acids, Nonesterified; D005663:Furans; D007004:Hypoglycemic Agents; D007328:Insulin; D014280:Triglycerides; C014289:5-(tetradecyloxy)-2-furancarboxylic acid; D002784:Cholesterol; D051057:Proto-Oncogene Proteins c-akt