TY - JOUR

T1 - Small amounts of dietary medium-chain fatty acids protect against insulin resistance during caloric excess in humans

AU - Lundsgaard, Anne-Marie

AU - Fritzen, Andreas Mæchel

AU - Sjøberg, Kim Anker

AU - Kleinert, Maximilian

AU - Richter, Erik A.

AU - Kiens, Bente

N1 - © 2020 by the American Diabetes Association.

PY - 2021

Y1 - 2021

N2 - Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a three-day hypercaloric high-fat diet (+75% energy, 81-83E% fat) in randomized order. For one group (n=8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n=9) ingested a matched diet, but with ∼30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated LCFAs. A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal FA oxidation, maintained glucose metabolic flexibility, increased non-oxidative glucose disposal related to lower starting glycogen content and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.

AB - Medium-chain fatty acids (MCFAs) have in rodents been shown to have protective effects on glucose homeostasis during high-fat overfeeding. In this study, we investigated whether dietary MCFAs protect against insulin resistance induced by a hypercaloric high-fat diet in humans. Healthy, lean men ingested a eucaloric control diet and a three-day hypercaloric high-fat diet (+75% energy, 81-83E% fat) in randomized order. For one group (n=8), the high-fat diet was enriched with saturated long-chain FAs (LCSFA-HFD), while the other group (n=9) ingested a matched diet, but with ∼30 g (5E%) saturated MCFAs (MCSFA-HFD) in substitution for a corresponding fraction of the saturated LCFAs. A hyperinsulinemic-euglycemic clamp with femoral arteriovenous balance and glucose tracer was applied after the control and hypercaloric diets. In LCSFA-HFD, whole body insulin sensitivity and peripheral insulin-stimulated glucose disposal were reduced. These impairments were prevented in MCSFA-HFD, accompanied by increased basal FA oxidation, maintained glucose metabolic flexibility, increased non-oxidative glucose disposal related to lower starting glycogen content and increased glycogen synthase activity, together with increased muscle lactate production. In conclusion, substitution of a small amount of dietary LCFAs with MCFAs rescues insulin action in conditions of lipid-induced energy excess.

KW - Faculty of Science

KW - Metabolism

U2 - 10.2337/db20-0582

DO - 10.2337/db20-0582

M3 - Journal article

C2 - 33122393

VL - 70

SP - 91

EP - 98

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 1

ER -