Beneficial effect of mineralocorticoid receptor antagonists seen in mice fed high-fat diet
WEDNESDAY, June 19 (HealthDay News) -- Mineralocorticoid receptor (MR) antagonists can counter high-fat (HF)-diet-induced metabolic dysfunction in mice, according to an experimental study presented at the annual meeting of The Endocrine Society, held from June 15 to 18 in San Francisco.
Andrea Armani, Ph.D., from IRCCS San Raffaele Pisana Research Center in Rome, and colleagues investigated responses to MR antagonists in a mouse model of diet-induced obesity. Female C57b16 mice were fed with normal chow or a HF diet for 12 weeks. Those fed a HF diet were concomitantly treated with a potent MR antagonist (drospirenone) or spironolactone.
The researchers identified significant increases in total body weight, fat mass, mean adipocyte size, expression of white adipose tissue markers, and impaired glucose tolerance in mice fed a HF diet. This weight gain and white fat mass expansion in parametrial, perivesical, and inguinal depots was prevented by drospirenone and spironolactone, with no effect on interscapular fat pad weight. MR antagonists were found to block the HF diet-driven expansion of abdomino-pelvic fat volume on magnetic resonance imaging. In mice fed a HF diet, drospirenone and spironolactone prevented impaired glucose tolerance and countered upregulation of white adipose tissue markers and adipocyte hypertrophy. Treatment with drospirenone or spironolactone also correlated with an increase in the number of uncoupling protein 1-positive brown-like adipocytes. In MR antagonist-treated mice, analyses showed increased glucose uptake in visceral abdomino-pelvic and interscapular fat.
"These data open new unexpected applications of MR antagonists in the treatment of obesity and its metabolic complications, since their use in animal models reverses the metabolic dysfunction induced by a high-fat diet, promoting the activation of brown-like fat in classical white fat depots," Armani said in a statement.
Abstract (http://edrv.endojournals.org/cgi/content/meeting_abstract/34/03_MeetingAbstracts/OR08-1 )More Information (https://www.endocrine.org/meetings/endo-annual-meeting/endo-2013#/nav/ )