Inhibition of Atherosclerosis and Myocardial Lesions in the JCR:LA-cp Rat by β,β′-Tetramethylhexadecanedioic Acid (MEDICA 16)

Atherosclerosis-prone, insulin-resistant JCR:LA-cp male rats were treated from 6 weeks to 39 weeks of age with β,β′-tetramethylhexadecanedioic acid (MEDICA 16). Body weights were reduced (13%, P<.001) at 36 weeks without any accompanying decrease in food consumption. The treatment did not cause any significant change in plasma glucose or fasting insulin concentrations. There was a significant decrease in the extreme hyperplasia of the islets of Langerhans (38%, P<.05). The marked VLDL hypertriglyceridemia was decreased by 70% (P<.001). with an accompanying significant reduction in cholesterol concentrations. The severity of raised atherosclerotic lesions on the aortic arch was very markedly reduced (P<.01) in treated rats. This was accompanied by a reduction (P<.01) in the incidence of ischemic myocardial lesions. We conclude that long-term (33 weeks) MEDICA 16 treatment of an animal model for the obesity/insulin-resistant/ hyperlipidemic syndrome not only markedly improved lipid metabolism, but also inhibited the development of advanced cardiovascular disease.