Bromocriptine inhibits in vivo free fatty acid oxidation and hepatic glucose output in seasonally obese hamsters (Mesocricetus auratus).
Seasonally obese hyperinsulinemic hamsters were treated for 5 weeks with bromocriptine (500 to 600 micrograms per animal) and tested for drug effects on energy balance, body fat stores, nocturnal whole-body free fatty acid (FFA) metabolism and hepatic glucose output, and diurnal glucose tolerance. After 5 weeks, bromocriptine treatment reduced retroperitoneal fat pad weight by 45% without altering either daily food consumption or end-treatment total daily energy expenditure. Also, 5 weeks of treatment improved the diurnal glucose tolerance, resulting in a 47% and 33% decrease in the area under glucose and insulin curves, respectively. After 4 weeks, bromocriptine treatment reduced nocturnal lipolysis by 28%, palmitate rate of appearance into plasma by 30%, palmitate oxidation by 33%, and hepatic glucose output by 28%. Moreover, these reductions were accompanied by a 75% reduction in plasma insulin concentration. The data suggest that bromocriptine may improve diurnal glucose tolerance in part by inhibiting the preceding nocturnal lipolysis and FFA oxidation. Reductions in nocturnal FFA oxidation and hepatic glucose production may result from bromocriptine's influences on circadian organization of hypothalamic centers known to regulate these activities. Available evidence suggests that bromocriptine may impact this neuroendocrine organization of metabolism by increasing the dopamine to noradrenaline activity ratio in central (hypothalamic) and peripheral (eg, liver and adipose) target tissues.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001971:Bromocriptine / Q000494:pharmacology*; D002940:Circadian Rhythm; D006224:Cricetinae; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006727:Hormone Antagonists / Q000494:pharmacology*; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D008066:Lipolysis / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008647:Mesocricetus; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D010084:Oxidation-Reduction; D012621:Seasons
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D006727:Hormone Antagonists; D007328:Insulin; D001971:Bromocriptine; D005947:Glucose