Oral Presentation Australian & New Zealand Obesity Society Annual Scientific Meeting 2013

Fatty acid oxidation and storage in the hypothalamic parenchyma of mice is limited by transport across the blood brain barrier (#30)

Vanessa R Haynes 1 , Melissa L Borg 1 , Russell D Brown 1 , Matthew J Watt 1
  1. Monash University, Clayton, VIC, Australia

Obesity is associated with lipid accumulation in non-adipose tissues, which can result in “lipotoxic” outcomes such as impaired insulin action and apoptosis. We have recently shown that “lipotoxicity” extends to the central nervous system (CNS), such that obesity induced by high-fat feeding results in lipid deposition in the hypothalamus of mice1. Lipid deposition in the brain is postulated to affect energy homeostasis and peripheral insulin action. Recent studies have challenged the dogma that the CNS does not oxidise fatty acids2. Interestingly, diets that contain medium-chain fatty acids (MCFA) have been shown to induce fatty acid (FA) oxidation, increase energy expenditure and improve insulin action when compared with diets containing long-chain fatty acids (LCFA)3. Hence, the aim of this research was to compare the metabolic fates of MCFA and LCFA in the hypothalamus.

FA metabolism was assessed using radiometric methods in immortalised and primary murine neurons, hypothalamic sections ex vivo and in mice in vivo. Neurons are capable of transporting FA across the plasma membrane, oxidizing FA and storing FA as triglycerides. The oxidation to storage ratio was 1:5 for LCFA and 4:1 for MCFA.  Whole hypothalamus isolated from lean mice exhibit a preference for FA oxidation rather than storage (3:1 ratio). LCFA and MCFA administered directly into the cerebrospinal fluid via the lateral ventricle were both oxidised and stored as glycerides (1:4 and 25:1 oxidation : storage ratio, respectively). When LCFA were administered via the carotid artery, CNS fatty acid uptake and storage were negligible. Conversely, MCFA were readily able to cross from the circulation to the CNS and were oxidised and stored at a 20:1 ratio. Thus, the parenchyma of the hypothalamus (including neurons) is capable of FA transport, oxidation and storage, and MCFA may have a greater influence on CNS fatty acid metabolism than LCFA.  

  1. Borg, M.L., et al., Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice. J Physiol, 2012. 590(Pt 17): p. 4377-89.
  2. Dieguez, C., G. Fruhbeck, and M. Lopez, Hypothalamic lipids and the regulation of energy homeostasis. Obes Facts, 2009. 2(2): p. 126-35.
  3. Turner, N., et al., Enhancement of muscle mitochondrial oxidative capacity and alterations in insulin action are lipid species dependent: potent tissue-specific effects of medium-chain fatty acids. Diabetes, 2009. 58(11): p. 2547-54.