The impact of ageing, fasting and high-fat diet on central and peripheral glucose tolerance and glucose-sensing neural networks in the arcuate nucleus

Abstract

Obesity and aging are risk factors for diabetes. Here we investigated effects of aging, obesity and fasting on central and peripheral glucose tolerance and on glucose-sensing neuronal function in the arcuate nucleus of rats, with a view to providing insight into central mechanisms regulating glucose homeostasis and how they change or are subject to dysfunction with aging and obesity. We show that following a glucose load, central glucose tolerance at the level of the cerebrospinal fluid (CSF) and plasma is significantly reduced in rats maintained on high fat diet (HFD). With aging, up to 2 years, central glucose tolerance was impaired in an age-dependent manner whilst peripheral glucose tolerance remained unaffected. Aging-induced peripheral glucose intolerance was improved by a 24 hour fast, whilst central glucose tolerance was not corrected. Pre-wean, immature animals have elevated basal plasma glucose levels and a delayed increase in central glucose levels following peripheral glucose injection compared to mature animals. Electrophysiological recording techniques revealed an energy-status-dependent role for glucose excited, inhibited and adapting neurons along with glucose-induced changes in synaptic transmission. We conclude that aging affects central whilst HFD profoundly affects central and peripheral glucose tolerance, and glucose-sensing neurons adapt function in an energy-status-dependent manner.

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