BROMOCRIPTINE REDIRECTS METABOLISM AND PREVENTS SEASONAL ONSET OF OBESE HYPERINSULINEMIC STATE IN SYRIAN-HAMSTERS

Bromocriptine redirects metabolism and prevents seasonal onset of the obese hyperinsulinemic state in Syrian hamsters. Metabolic and hormonal effects of bromocriptine were studied in seasonally obese female Syrian hamsters, Mesocricetus auratus. Daily injections of bromocriptine and vehicle (controls) were made at light onset (10:14-h light-dark cycle) for 10 wk. After 9 wk of treatment blood samples were taken every 4 h during a day for assays of hormones, glucose, triglyceride, and fatty acids, and after 10 wk of treatment, tests were carried out to measure insulin-stimulated glucose disposal during a hyperinsulinemic clamp, lipid mobilization (rate of glycerol appearance), protein turnover (lysine flux and deamination), and body composition (deuterium dilution). Bromocriptine reduced percent body fat by 53% and increased percent lean body mass by 8%. It also decreased triglyceride levels by 52% and plasma free fatty acid concentration during the dark-near light onset by 49% and glycerol appearance by 25%. Protein synthesis and catabolism were increased by 62 and 56%, respectively, and deamination of amino acid was decreased by 53% by bromocriptine. Bromocriptine reduced plasma concentration of insulin throughout the day, especially at light onset, by 78% without change in baseline glucose level and markedly decreased steady state plasma glucose (by 40%) during a continuous infusion of insulin and glucose. It also reduced the nocturnal plasma concentration of prolactin by 90%, cortisol by 70%, and thyroid hormones (thyroxine and triiodothyronine) by 50% and dramatically altered the circadian profiles of these hormones and insulin. Bromocriptine apparently shifts metabolism from that found in obese, hyperinsulinemic hamsters during winter to conditions resembling those of lean euinsulinemic hamsters during other seasons. These marked metabolic changes are thought to result from changes in the phase relations of circadian neuroendocrine oscillations that are believed to regulate seasonal metabolic conditions.