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

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posted on 29.10.2020, 15:50 by Ada Admin, Anne-Marie Lundsgaard, Andreas M. Fritzen, Kim. A. Sjøberg, Maximilian Kleinert, Erik A. Richter, Bente Kiens
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.

Funding

Alfred Benzon Foundation Det Frie Forskningsråd 4004-00233 4092-00309 4183-00249 Lundbeckfonden R288-2018-78 Novo Nordisk Fonden NNF17SA0031406

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