HIGH-FAT DIET: THE EFFECTS OF SATURATED FAT TYPE

To combat the growing obesity pandemic, weight loss and maintenance are achieved primarily with dietary modification. One suggested modification is to replace saturated long-chain triglycerides (LCTs) with saturated medium-chain triglycerides (MCTs), as this reduces energy intake (Maher & Clegg, 2021), and can aid weight loss (He et al., 2024). Consistent with the human literature, in preclinical rodent models of high-fat diet (HFD)-induced obesity, shifting the HFD composition from LCTs to MCTs reduces overeating and weight gain (Ferreira et al., 2014). However, it is not fully understood how MCTs attenuate HFD-induced overeating and weight gain. According to one hypothesis, saturated fats, specifically LCTs, are overconsumed because they recruit activated microglia to the arcuate nucleus (ARC) (Salvi et al., 2024). Our central hypothesis is that MCT attenuate HFD-induced microgliosis in the ARC. To test this hypothesis, we performed three experiments to evaluate the effects of different MCTs on HFD-induced overeating, body weight gain, fat mass gain, lean mass gain, spontaneous alternations percentage in the y-maze, and microgliosis in the ARC and CA1. We found that LCT-rich HFDs did indeed induce overeating, body weight gain, and fat mass gain in both males and females. Fat mass gain, in particular, was greater in males than females. However, we found that LCT-rich HFDs did not decrease either total arm entries or spontaneous alternations in the y-maze. They also did not increase microgliosis in either the ARC or CA1 relative to chow-fed controls. However, there were a few methodological differences between these experiments and other studies that need to be resolved in order to properly test the hypothesis that MCTs attenuate HFD-induced microgliosis in the ARC. We also found that the replacement of LCT with MCT attenuated HFD-induced overeating, body weight gain, and fat mass gain. The attenuating effects were greater in C8/10 triglycerides than coconut oil. Collectively, these findings are consistent with the human literature regarding the effects of MCTs on body composition, indicating that C8/10 triglycerides are a better replacement for saturated LCTs than coconut oil to prevent body weight gain. However, future studies should compare C8/10 triglycerides to other, healthier, dietary fat options such as MUFAs and/or PUFAs to determine their clinical utility.