Obesity is characterised by increased storage of
fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of
insulin resistance.
Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store
lipids, and the effects of
obesity remain undefined. The aims of this study were (1) to examine hypothalamic
lipid content in mice with increased
dietary fat intake and in obese ob/ob mice fed a
low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic
lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic
lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic
lipid accumulation, and induced
glucose intolerance, while the HFD-ex mice had reduced
body weight and improved
glucose tolerance. A total of 335
lipid molecular species were identified and quantified.
Lipids known to induce
insulin resistance, including
ceramide (22%↑),
diacylglycerol (25%↑),
lysophosphatidylcholine (17%↑),
cholesterol esters (60%↑) and
dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic
lipids were unaltered with exercise training and in the ob/ob mice, suggesting that
obesity per se does not alter hypothalamic
lipids. Overall, hypothalamic
lipid accumulation is regulated by dietary
lipid content and is refractory to change with endurance exercise training.