Mechanisms preserving insulin action during high dietary fat intake

Research output: Contribution to journalJournal articleResearchpeer-review

Annemarie Lundsgaard, Jacob Bak Holm, Kim Anker Sjøberg, Kirstine N Bojsen-Møller, Lene S Myrmel, Even Fjære, Benjamin Anderschou Holbech Jensen, Trine Sand Nicolaisen, Janne Rasmuss Hingst, Sine L Hansen, Sophia Doll, Philip E Geyer, Atul S Desmukh, Jens Juul Holst, Lise Madsen, Karsten Kristiansen, Jørgen Wojtaszewski, Erik Richter, Bente Kiens

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.

Original languageEnglish
JournalCell Metabolism
Volume29
Issue number1
Pages (from-to)50-63, e1-e4
Number of pages19
ISSN1550-4131
DOIs
Publication statusPublished - 2019

ID: 203561036