BETA-ADRENERGIC STIMULATION OF SKELETAL-MUSCLE METABOLISM IN RELATIONTO WEIGHT-REDUCTION IN OBESE MEN

In a companion study [Blaak, E. E., M. A. van Baak, G. J. Kemerink, M. T. W. Pakbiers, G. A. K. Heidendal, and W. H. M. Saris. Am. J. Physio l. 267 (Endocrinol. Metab. 30): E306-E315, 1994.], we found that durin g infusion of the nonselective beta-agonist isoprenaline (Iso), obese males had a lowered Iso-induced rise in arterial glycerol and nonester ified fatty acids (NEFA) and a lowered muscle NEFA oxidation. The pres ent study was intended to investigate whether a period of weight reduc tion would alter this impaired fat utilization in obese males. Before and after a 5-wk diet intervention (very low calorie diet) whole body energy expenditure was determined during rest and during intravenous i nfusion of increasing doses of Iso. In addition, forearm muscle metabo lism was investigated with Iso infusion with and without simultaneous infusion of the beta(1)-blocker atenolol (AT) by measuring skeletal mu scle blood flow and arteriovenous concentration differences of various metabolites across muscle. The Iso-induced whole body thermogenesis t ended to increase as a result of weight loss when this response was re lated to the plasma Iso concentration (P = 0.09), whereas both before and after diet there were no changes in the respiratory exchange ratio during Iso infusion. The increases in arterial NEFA and glycerol conc entrations as a result of Iso infusion were not significantly differen t before and after weight reduction. In addition, muscle NEFA uptake d id not change as a result of Iso or Iso plus AT infusion both before a nd after diet, whereas muscle glucose uptake and lactate release tende d to be more pronounced after weight reduction. These data suggest tha t a diminished capacity to utilize fat may rather be a primary factor leading to the development of overweight than a secondary factor resul ting from the obese state.