TY - JOUR
T1 - Mechanisms preserving insulin action during high dietary fat intake
AU - Lundsgaard, Annemarie
AU - Holm, Jacob Bak
AU - Sjøberg, Kim Anker
AU - Bojsen-Møller, Kirstine N
AU - Myrmel, Lene S
AU - Fjære, Even
AU - Jensen, Benjamin Anderschou Holbech
AU - Nicolaisen, Trine Sand
AU - Hingst, Janne Rasmuss
AU - Hansen, Sine L
AU - Doll, Sophia
AU - Geyer, Philip E
AU - Deshmukh, Atul Shahaji
AU - Holst, Jens Juul
AU - Madsen, Lise
AU - Kristiansen, Karsten
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
AU - Kiens, Bente
N1 - A correction to this publication has been published at: https://doi.org/10.1016/j.cmet.2018.10.002
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
U2 - 10.1016/j.cmet.2018.08.022
DO - 10.1016/j.cmet.2018.08.022
M3 - Journal article
C2 - 30269983
VL - 29
SP - 50-63, e1-e4
JO - Cell Metabolism
JF - Cell Metabolism
SN - 1550-4131
IS - 1
ER -