Metabolic effects of medium-chain triacylglycerol consumption are preserved in obesity

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Abstract

Several health-beneficial effects are associated with intake of medium-chain triacylglycerol (MCT); however, the underlying mechanisms are unknown. Furthermore, it remains uncertain whether the acute metabolic effects of MCT differ between lean individuals and individuals with obesity—and whether these effects are sustained following chronic intake. This study aimed to elucidate the postprandial physiological and metabolic effects of MCT before and after 8 days intake compared with intake of energy-matched triacylglycerol consisting of long-chain fatty acids (long-chain triacylglycerols, LCT) using a randomized cross-over design in lean individuals (n ¼ 8) and individuals with obesity (n ¼ 8). The study revealed that consumption of MCT increased ketogenesis and metabolic rate while lowering blood glucose levels over 5 h. The hypoglycemic action of MCT intake was accompanied by a concomitant transient increase in plasma insulin and glucagon levels. Interestingly, the effects on ketogenesis, metabolic rate, and glycemia were preserved in individuals with obesity and sustained after 8 days of daily supplementation. Lipidomic plasma analysis in lean individuals (n ¼ 4) showed that a part of the ingested MCT bypasses the liver and enters the systemic circulation as medium-chain fatty acids (MCFAs). The findings suggest that MCFAs, along with ketone bodies from the liver, may act as signaling molecules and/or substrates in the peripheral tissues, thereby contributing to the effects of MCT intake. In summary, these findings underscore the health benefits of MCT in metabolically compromised individuals after daily supplementation. Moreover, we uncover novel aspects of MCFA biology, providing insights into how these fatty acids orchestrate physiological effects in humans. NEW & NOTEWORTHY We reveal that medium-chain triacylglycerol (MCT) intake increases postprandial ketogenesis and metabolic rate and reduces plasma glucose levels in humans. Notably, these responses persist in individuals with obesity and are maintained following chronic MCT supplementation. Some medium-chain fatty acids entered the circulation, suggesting that these, together with ketone bodies, act as signaling molecules/substrates in peripheral tissues. The findings highlight health beneficial effects of dietary MCT in individuals with obesity and reveal new insights into lipid biology.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Physiology - Endocrinology and Metabolism
Vol/bind328
Udgave nummer1
Sider (fra-til)E1-E20
ISSN0193-1849
DOI
StatusUdgivet - 2025

Bibliografisk note

Funding Information:
We thank Irene Bech Nielsen for skilled technical assistance and the experimental contributions from Jacob Kr\u00F8ll Jensen, Casper M\u00F8ller Sigvardsen, Amanda Schaufuss, Benjamin la Cour Sveistrup, Emil Kornbo Kirkegaard, Martin Winther Andreasen, Christian D\u00F8ssing Storgaard, Filip Hansen, and Kasper Kristoffer Alsing (University of Copenhagen). We gratefully recognize the volunteers for participating in the study. This study was supported by the Novo Nordisk Foundation under Grant No. NNF20OC0063744, Arla Food for Health, and the Danish Dairy Research Foundation. PhD scholarship of J.M.K. was supported by a research grant from the Danish Cardiovascular Academy, which is funded by the Novo Nordisk Foundation under Grant No. NNF20SA0067242 and the Danish Heart Foundation. A.M.L. and A.M.F. were funded by the Danish Diabetes Academy, funded by the Novo Nordisk Foundation under Grant No. NNF17SA0031406. A.M.F. was also funded directly by the Novo Nordisk Foundation under Grant No. NNF22OC0074110. M.K. was supported by the Deutsche Forschungsgemeinschaft (DFG) under Grant No. KL 3285/5-1, the German Center for Diabetes Research under Grant Nos. 82DZD03D03 and 82DZD03D1Y, the Novo Nordisk Foundation under Grant No. NNF19OC0055192 and the Deutsche Diabetes Gesellschaft (DDG). J.G.K. is supported by a Novo Nordisk Fonden Excellence Emerging Investigator Grant\u2014Endocrinology & Metabolism under Grant No. 0054300 and a Sapere Aude Fellowship from the Independent Research Fund Denmark. J.F.H and N.J.F.: LC/MS-based lipidomic analyses were supported by grants to the VILLUM Center for Bioanalytical Sciences at SDU (VILLUM Foundation) under Grant No. 7292 and by Independent Research Fund Denmark-Natural Sciences under Grant No. 2032-00062B.

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Copyright © 2025 the American Physiological Society.

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