Effect of exercise and obesity on skeletal muscle amino acid uptake JACOB E. FRIEDMAN, PETER W. R. LEMON, AND JUDITH A. FINKELSTEIN Applied Physiology Research Laboratory, Kent State University, Kent 44242; and Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272 FRIEDMAN,JACOB E., PETER W.R. LEMON,ANDJUDITH A. FINKELSTEIN. Effect of exercise and obesity on skeletal muscle amino acid uptake. J. Appl. Physiol. 69(4): 1347-1352, 1990.- The genetically obese Zucker rat has a reduced capacity to deposit dietary protein in skeletal muscle. To determine whether amino acid uptake by muscle of obese Zucker rats is impaired, soleus strip (SOL) and epitrochlearis (EPI) muscles from lo-wk-old lean and obese Zucker rats were studied in vitro by use of [14C]ar-aminoisobutyric acid (AIB). Muscles from fasted rats were incubated under basal conditions at rest or after a l-h treadmill run at 8% grade. To equate total work completed, lean and obese rats ran at 27 and 20 m/min, respec- tively. Muscles were pinned at resting length, preincubated for 30 min at 37°C in Krebs-Ringer bicarbonate buffer containing 5 mM glucose under 95% O,-5% COa, and then incubated up to 3 h in Krebs-Ringer bicarbonate with 0.5 mM AIB, [‘“Cl- AIB, and [3H]inulin as a marker of extracellular fluid. Basal AIB uptake in EPI and SOL from obese rats was significantly reduced by 40 and 30% (P < O.Ol), respectively, compared with lean rats. For both lean and obese rats, exercise increased (P < 0.05) basal AIB uptake in EPI and SOL, but the relative increases were greater in the obese rats (EPI 54% and SOL 71% vs. EPI 32% and SOL 37%). These results demonstrate that genetically obese Zucker rats have reduced basal skeletal muscle amino acid uptake and suggest that physical inactivity may partially contribute to this defect. contractile activity; slow-twitch muscle; fast-twitch muscle; Zucker rats SKELETAL MUSCLES from the genetically obese Zucker rat (fa/fa) are smaller, contain less protein, and have a decreased rate of protein synthesis compared with their lean littermates (7, 26). When fed ad libitum, the obese Zucker rat consumes significantly more food and deposits more fat and less body protein than its lean littermates (25). When pair fed to the food consumption of a lean littermate, the difference in muscle protein content be- tween lean and obese animals is even more pronounced (4925). In obese Zucker rats after an injection of a mixture of [U-14C]amino acids in vivo, a greater fraction of the labeled carbons is found in body lipids than in skeletal muscle (7, 14). The obese Zucker rat demonstrates a variety of hormonal alterations (5, 8, 19) that may con- tribute to the depressed skeletal muscle amino acid dep- osition, but it is not known whether the amino acid uptake mechanism itself, independent of hormonal influ- ences, is defective in muscles of the obese Zucker rat. Although a number of nonessential amino acids can be synthesized from glucose within skeletal muscle, most of the amino acids eventually incorporated into protein must first enter the muscle from the circulation by specific transport systems (13, 28). Because the uptake of amino acids into the intracellular free pool contributes to the expression of protein synthesis (24), it is reason- able to suggest that an impairment in amino acid trans- port could be an important factor limiting muscle protein deposition in the genetically obese Zucker rat. In addition, the obese Zucker rat displays a reduced level of spontaneous physical activity (29). It is well established that contractile activity increases amino acid uptake and protein synthesis independently of hormonal influences (10, 16). Experiments using electrical stimu- lation of muscles in vitro or constant stretch in vivo have demonstrated that the rate of amino acid uptake is directly linked to the degree of contractile activity (11, 21). Recent studies have also shown that after a more physiologically relevant stimulus, namely, acute endur- ance exercise, amino acid uptake by skeletal muscle increases substantially in the absence of hormones (33, 34). Whether this is true for muscles from obese animals that have a reduced capacity for protein deposition is, however, unknown. Therefore the purpose of the present study was to determine whether in vitro amino acid uptake is impaired in muscles of the genetically obese Zucker rat and, if so, whether a single endurance exercise bout could minimize this impairment. METHODS Animal care and exercise. Lean (Fa/-) and obese (fa/ fa) female Zucker rats were bred and maintained in the Zucker rat colony at Northeastern Ohio Universities College of Medicine within the Department of Compar- ative Medicine. At 4 wk of age, the anim .als were weaned, phen .otyped, and housed separately in animal quarters maintained at 24°C with a reversed 12:12-h light-dark cycle (dark 0600-1800 h). Rats were fed Purina rat chow and tap water ad libitum. At 8-10 wk of age, the rats were randomly assigned to either a sedentary control (n = 12 pairs) or an exercised group (n = 12 pairs). Both groups were familiarized with treadmill exercise by 5 min of running at speedsranging from 10 to 28 m/min on the 5th, 4th, and 3rd days before the experiment. All rats were fasted overnight to avoid variations in food intake. On the morning of the experimental day, the obese rats 0161-7567/90 $1.50 Copyright 0 1990 the American Physiological Society 1347