Medium-Chain Triglycerides-Specific Appetite is Regulated by the β-oxidation of Medium-Chain Fatty Acids in the Liver

Most studies on fat appetite have focused on long-chain triglycerides (LCTs) due to their obesogenic properties. Medium-chain triglycerides (MCTs), conversely, exhibit anti-obesogenic effects; however, the regulation of MCTs intake remains elusive. Here, we demonstrate that mice can distinguish between MCTs and LCTs, and the specific appetite for MCTs is governed by hepatic β-oxidation. We generated liver-specific medium-chain acyl-CoA dehydrogenase (MCAD)-deficient (MCAD^L-/-) mice and analyzed their preference for MCTs and LCTs solutions using glyceryl trioctanoate (C8-TG), glyceryl tridecanoate (C10-TG), corn oil, and lard oil in two-bottle choice tests conducted over 8 days. Additionally, we employed lick microstructure analyses to evaluate the palatability and appetite for MCTs and LCTs solutions. Finally, we measured the expression levels of genes associated with fat ingestion (Galanin, Qrfp, and Nmu) in the hypothalamus 2 h after oral gavage of fat. Compared to control mice, MCAD^L-/- mice exhibited a significantly reduced preference for MCTs solutions, with no alteration in the preference for LCTs. Lick analysis revealed that MCAD^L-/- mice displayed a significantly decreased appetite for MCTs solutions only, while the palatability of both MCTs and LCTs solutions remained unaffected. Hypothalamic Galanin expression in control mice was elevated by oral gavage of C8-TG but not by LCTs, and this response was abrogated in MCAD^L-/- mice. In summary, our data suggest that hepatic β-oxidation is required for MCTs-specific appetite but not for LCTs-specific appetite. The induction of hypothalamic galanin upon MCTs ingestion, dependent on hepatic beta-oxidation, could be involved in the regulation of MCTs-specific appetite.