‘Sensing’ of long chain fatty acids (LCFA) by the hypothalamus reduces food intake and suppresses hepatic glucose production in rodents, however, the precise mechanisms involved in central fatty acid (FA) sensing are not fully understood. To determine the availability of FA to the hypothalamus, the FA composition of rat blood and cerebrospinal fluid (CSF) was assessed by mass spectrometry. While blood was predominantly composed of LCFA (74% of the FA pool), medium chain fatty acid (MCFA) was the main FA type in the CSF (57% of the CSF FA pool). Subsequent experiments demonstrated that the hypothalamic uptake of arterial-administered LCFA is negligible, while MCFA are readily taken up and oxidised by the hypothalamus. The results indicated an important role for MCFA rather than LCFA in central FA sensing.
To elucidate a potential role of MCFA in appetite and energy homeostasis, lean mice were gavaged with water, trioleic acid (long-chain triglyceride (LCT)) or tri-octanoic acid (medium-chain triglyceride (MCT)) prior to the main feeding time (1600 h). In the first 8 hours after gavage, MCT reduced food intake by 53% and 41% compared with water and LCT, respectively. There were no differences in food intake between treatment groups between 8 and 24 hours post-gavage, demonstrating no ‘rebound’ feeding effect. The reduction in food intake following MCT gavage was accompanied by an increase in energy expenditure, but not in physical activity. To ascertain whether obesity could cause a desensitisation to MCT, the experiment was repeated in HFD-fed mice. Energy expenditure was increased, however food intake was not reduced in HFD-fed mice following MCT administration. Together, these data indicate that MCFA acutely regulate energy balance. Understanding the mechanisms by which MCT can regulate energy balance may provide avenues for the development of novel therapeutics for treating obesity.