Effects of Medium-Chain Versus Medium- and Long-Chain Triglycerides, Combined with Carotenoids, in a High-Fat Diet on Obese Mice

While medium-chain triglycerides (MCTs), medium- and long-chain triglycerides (MLCTs), and carotenoids individually possess anti-obesity properties, the synergistic metabolic regulatory effects of their combined intervention remain under-investigated. This study explored the effects of MCTs or structured MLCTs combined with natural carotenoids on high-fat diet (HFD)-induced obese mice. After establishing obesity in C57BL/6J mice using a 60% HFD, a ten-week intervention was conducted using 45% HFD containing 150 mg/kg carotenoids across three groups: MCT-C, MLCT-C, and a physical mixture of MCTs and long-chain triglycerides plus carotenoids (MCT+LCT-C), alongside a low-fat diet (LFD) control. Results showed that among the three HFD-fed intervention groups, the MCT-C group had the lowest body weight with significantly lower fat mass, fat pad coefficient, and adipocyte area, but higher liver coefficient and serum alanine aminotransferase levels compared to the LFD control group (p < 0.05). The MLCT-C and MCT+LCT-C groups exhibited higher body weight, white adipose tissue expansion, and adipocyte hypertrophy, with MCT+LCT-C showing the largest adipocyte volume and uniquely presenting hepatocyte necrosis, unlike other groups. Serum total cholesterol was lowest in MCT-C, while high-density lipoprotein cholesterol increased in MLCT-C and MCT+LCT-C. Notably, compared with the MCT+LCT-C group, MLCT-C demonstrated distinctly superior capabilities in maintaining gut microbiota homeostasis, as evidenced by enhanced community alpha diversity and significantly reduced the abundance of harmful Pseudomonadota, while preserving a highly comparable core functional profile. Collectively, these findings confirm that lipid structure differentially shapes gut microbiota and influences energy metabolism, providing a scientific basis for precision nutrition interventions.