Poster Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

Fatty acid oxidation and storage in the hypothalamic parenchyma of mice is limited by transport across the blood brain barrier (#284)

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 insulin-responsive, 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 hypothalamus1. 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. Hence, the aim of this research was to investigate the metabolic fate of fatty acids in the hypothalamus.

Free fatty acid (FFA) metabolism was assessed using radiometric methods ([1-14C]oleate) in immortalised and primary murine neurons, isolated hypothalamic sections ex vivo and in mice in vivo. Immortalised hypothalamic-derived neurons and primary neurons are capable of transporting fatty acids across the plasma membrane, oxidizing fatty acids and storing fatty acids as triglycerides. The oxidation to storage ratio was 1:11.  Further studies showed that whole hypothalamus isolated from lean mice exhibit a preference for fatty acid oxidation rather than storage (3:1 ratio). Fatty acids administered directly into the cerebrospinal fluid via the lateral ventricle in conscious mice were both oxidised and stored as glycerides (1:4 ratio), but when fatty acids were administered via the carotid artery, fatty acid uptake and storage were negligible.

Thus, the parenchyma of the hypothalamus (including neurons) is capable of fatty acid transport, oxidation and storage. However, fatty acid uptake and metabolism is negligible when fatty acids are delivered by their normal route, suggesting that FFA transport across the blood brain barrier limits CNS fatty acid metabolism in vivo

  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.