Mechanisms Preserving Insulin Action during High Dietary Fat Intake
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-ri...
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Veröffentlicht in: | Cell metabolism 2019-01, Vol.29 (1), p.50-63.e4 |
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Sprache: | eng |
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Zusammenfassung: | 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.
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•Insulin sensitivity is maintained in both men and mice with high PUFA or SFA intake•Hepatic glucose production and de novo lipogenesis are decreased with high fat intake•High fat intake decreases fasting insulin and triacylglycerol levels•High fat intake changes the plasma proteome in an immune-supporting direction
Lundsgaard et al. reveal the adaptations in muscle, liver, blood, and gut that maintain peripheral insulin sensitivity, lower circulating lipids, and decrease hepatic de novo lipogenesis and gluconeogenesis when humans and mice ingest a high-fat diet for 6 weeks enriched in either polyunsaturated or saturated fatty acids. |
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ISSN: | 1550-4131 1932-7420 |
DOI: | 10.1016/j.cmet.2018.08.022 |