1. Mechanisms Preserving Insulin Action during High Dietary Fat Intake
- Author
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Sophia Doll, Atul S. Deshmukh, Even Fjære, Lene Secher Myrmel, Jørgen F. P. Wojtaszewski, Erik A. Richter, Bente Kiens, Benjamin A. H. Jensen, Anne-Marie Lundsgaard, Trine S. Nicolaisen, Kirstine N. Bojsen-Møller, Jens J. Holst, Karsten Kristiansen, Kim A. Sjøberg, Philipp E. Geyer, Janne R. Hingst, Sine L. Hansen, Jacob Bak Holm, and Lise Madsen
- Subjects
Blood Glucose ,Male ,medicine.medical_specialty ,Physiology ,medicine.medical_treatment ,Carbohydrate metabolism ,Diet, High-Fat ,Mice ,Dietary Fats, Unsaturated ,Internal medicine ,medicine ,Animals ,Humans ,Insulin ,Molecular Biology ,chemistry.chemical_classification ,biology ,Lipogenesis ,Muscles ,Fatty Acids ,Gluconeogenesis ,Fatty acid ,Cell Biology ,Healthy Volunteers ,Mice, Inbred C57BL ,Insulin receptor ,Endocrinology ,Glucose ,chemistry ,Liver ,Saturated fatty acid ,Ketone bodies ,biology.protein ,Insulin Resistance ,Polyunsaturated fatty acid - Abstract
Summary Prolonged intervention studies investigating molecular metabolism are necessary for a deeper understanding of dietary effects on health. Here we provide mechanistic information about metabolic adaptation to fat-rich diets. Healthy, slightly overweight men ingested saturated or polyunsaturated fat-rich diets for 6 weeks during weight maintenance. Hyperinsulinemic clamps combined with leg balance technique revealed unchanged peripheral insulin sensitivity, independent of fatty acid type. Both diets increased fat oxidation potential in muscle. Hepatic insulin clearance increased, while glucose production, de novo lipogenesis, and plasma triacylglycerol decreased. High fat intake changed the plasma proteome in the immune-supporting direction and the gut microbiome displayed changes at taxonomical and functional level with polyunsaturated fatty acid (PUFA). In mice, eucaloric feeding of human PUFA and saturated fatty acid diets lowered hepatic triacylglycerol content compared with low-fat-fed control mice, and induced adaptations in the liver supportive of decreased gluconeogenesis and lipogenesis. Intake of fat-rich diets thus induces extensive metabolic adaptations enabling disposition of dietary fat without metabolic complications.
- Published
- 2018