Adrenergically stimulated fat utilization and ageing

Ageing is associated with a diminished ability to use fat as a fuel during exercise. Also, middle-aged subjects have a blunted ability to mobilize fatty acids and to increase skeletal muscle fatty acid uptake and oxidation during intravenous beta-adrenergic stimulation, indicating that the sympathetic nervous system may play a role in the disturbed fat utilization. The blunted lipolytic response may be related to disturbances at the receptor level, eg a diminished number or agonist affinity of beta-adrenoceptors, or at the postreceptor level, eg a diminished activity of the hormone-sensitive lipase complex. As the rates of fatty acid availability are not limiting during exercise or beta-adrenergic stimulation in the elderly, the lowered skeletal muscle fat oxidation is probably related to an age-related decline in the capacity of skeletal muscle to oxidize fatty acids. Factors responsible for this decline may be a diminished content of oxidative enzymes, an increased glycolytic flux inhibiting fatty acid transport into the mitochondria, or a diminished (possibly beta-adrenergically-mediated) activation of fatty acid transport. It remains to be determined to what extent disturbances of fat metabolism may be related to the ageing process per se or whether they are secondary to age-related changes in body fat distribution and level of physical activity. Nevertheless, the impairments in sympathetically mediated lipolysis and fat oxidation may be of importance in the age-related increase in adiposity and insulin resistance and may thus be one of the links between ageing and increased prevalence of chronic diseases, such as obesity, type 2 diabetes mellitus, and cardiovascular disease.