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

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 (<i>n</i> = 8) and individuals with obesity (<i>n</i> = 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 (<i>n</i> = 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.<b>NEW & NOTEWORTHY</b> 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.