TY - JOUR
T1 - Hypolipidemic, antiobesity, and hypoglycemic-hypoinsulinemic effects of β,β'-methyl-substituted hexadecanedioic acid in sand rats
AU - Tzur, R.
AU - Rose-Kahn, G.
AU - Adler, J. H.
AU - Bar-Tana, J.
PY - 1988
Y1 - 1988
N2 - Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with β,β'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect. The overall effect was sustained as long as the drug was administered. The hypolipidemic effect of MEDICA 16 consisted of a 70 and 40% decrease in plasma triacylglycerols and cholesterol, respectively, and resulted from inhibition of liver lipogenesis and cholesterogenesis. Adipose reduction by MEDICA 16 treatment or calorie restriction consisted of a 75-90% decrease in the perirenal, omental, epididymal, and subcutaneous fat, with a 50% decrease in liver neutral lipids. The reduction in adiposity was accounted for by a respective decrease in the lipid content of individual adipocytes, with a concomitant decrease in the number of adipocytes of selected adipose tissues. The decrease induced in adiposity by MEDICA 16 treatment could not be accounted for by anorectic or cathartic effects of the drug. The hypoglycemic-hypoinsulinemic effect of MEDICA 16 consisted of amelioration of the tolerance of glucose with normalization of plasma insulin. It was accompanied by an eightfold increase in the number of insulin receptors in epididymal adipocytes, which was, however, counteracted by a decrease in their affinity for insulin. The receptor and postreceptor effects exerted by MEDICA 16 were similar to those of calorie restriction. The overall effect of MEDICA 16 in sand rats may reflect the pharmacological potential of MEDICA compounds in pathological hyperlipidemic-obesity-diabetic syndromes.
AB - Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with β,β'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect. The overall effect was sustained as long as the drug was administered. The hypolipidemic effect of MEDICA 16 consisted of a 70 and 40% decrease in plasma triacylglycerols and cholesterol, respectively, and resulted from inhibition of liver lipogenesis and cholesterogenesis. Adipose reduction by MEDICA 16 treatment or calorie restriction consisted of a 75-90% decrease in the perirenal, omental, epididymal, and subcutaneous fat, with a 50% decrease in liver neutral lipids. The reduction in adiposity was accounted for by a respective decrease in the lipid content of individual adipocytes, with a concomitant decrease in the number of adipocytes of selected adipose tissues. The decrease induced in adiposity by MEDICA 16 treatment could not be accounted for by anorectic or cathartic effects of the drug. The hypoglycemic-hypoinsulinemic effect of MEDICA 16 consisted of amelioration of the tolerance of glucose with normalization of plasma insulin. It was accompanied by an eightfold increase in the number of insulin receptors in epididymal adipocytes, which was, however, counteracted by a decrease in their affinity for insulin. The receptor and postreceptor effects exerted by MEDICA 16 were similar to those of calorie restriction. The overall effect of MEDICA 16 in sand rats may reflect the pharmacological potential of MEDICA compounds in pathological hyperlipidemic-obesity-diabetic syndromes.
UR - http://www.scopus.com/inward/record.url?scp=0024205501&partnerID=8YFLogxK
U2 - 10.2337/diab.37.12.1618
DO - 10.2337/diab.37.12.1618
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C2 - 3056760
AN - SCOPUS:0024205501
SN - 0012-1797
VL - 37
SP - 1618
EP - 1624
JO - Diabetes
JF - Diabetes
IS - 12
ER -