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ß-Adrenergically Stimulated Fat Oxidation Is Diminished in Middle-Aged Compared to Young Subjects¹

Department of Human Biology, Nutrition Research Center, University of Maastricht, 6200 MD Maastricht, The Netherlands

Address all correspondence and requests for reprints to: Dr. E. E. Blaak, Department of Human Biology, Nutrition Research Center, Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands. E-mail: e.blaak{at}hb.unimaas.nl

The effect of aging on ß-adrenergically mediated substrate utilization was investigated in nine young (25.2 ± 1.7 yr old) and eight older males (52.9 ± 2.1 yr old), matched for body weight and body composition. In a first experiment, the nonselective ß-agonist isoprenaline (ISO) was infused in increasing standardized doses, and during each infusion period energy expenditure and substrate utilization were determined by indirect calorimetry. In a second experiment, forearm skeletal muscle metabolism was studied during a standardized infusion dose of ISO (19 ng/kg fat-free mass·min). During ß-adrenergic stimulation there was an increased carbohydrate oxidation (at an ISO infusion dose of 24 ng/kg fat-free mass·min, 31% vs. 21% of total energy expenditure; P < 0.05) and a decreased fat oxidation (51 vs. 62 of total energy expenditure; P < 0.05) in older compared to young subjects. Skeletal muscle lactate release significantly increased in the older subjects (from -175 ± 32 to -366 ± 66 nmol/100 mL forearm tissue·min), whereas there was no change in young subjects (from -32 ± 21 to 23 ± 57 nmol/100 mL forearm tissue·min; interaction group x ISO, P < 0.01). Additionally, there was a tendency toward a blunted ISO-induced increase in nonesterified fatty acid uptake in the older subjects (interaction group x ISO, P = 0.062). Thus, middle-aged subjects have a blunted ability to oxidize fat during ß-adrenergic stimulation compared to young subjects. This diminished fat oxidation may be an important etiological factor in the age-related increase in body fatness and obesity by favoring fat storage above oxidation.

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