Disease relevance of MEDICA 16

• In contrast, treatment with MEDICA 16 from the time of weaning at 3 weeks of age results in the normalization of food intake and body weight to over 8 weeks of age [1].
• The effect of MEDICA 16 was evaluated in insulin-resistant Zucker (fa/fa) rats in terms of liver, muscle, and adipose tissue response to clamped euglycemic hyperinsulinemia in vivo [2].
• 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 [3].
• In other rodent strains, MEDICA 16 has prevented obesity diabetes and atherogenesis [4].

High impact information on MEDICA 16

• MEDICA 16 inhibits hepatic acetyl-CoA carboxylase and reduces plasma triacylglycerol levels in insulin-resistant JCR: LA-cp rats [5].
• Uncoupling by MEDICA 16 in isolated mitochondria was partially suppressed by added atractyloside [6].
• Similarly, MEDICA 16 induced a saturable decrease in membrane potential, proton gradient, and proton motive force in isolated liver and heart mitochondria accompanied by an increase in mitochondrial respiration [6].
• Intracellular reesterification of lipolysed FFA in adipose tissue was specifically activated by MEDICA 16, resulting in a pronounced decrease in FFA release, with a concomitant decrease in plasma FFA [2].
• In conclusion, MEDICA 16 treatment results in the sensitization of liver, muscle, and adipose tissue to insulin in an animal model for obesity-induced insulin resistance [2].

Biological context of MEDICA 16

• The decrease induced in adiposity by MEDICA 16 treatment could not be accounted for by anorectic or cathartic effects of the drug [7].
• In contrast with rats, MEDICA 16-treatment of male hamsters did not result in a hypotriacylglycerolaemic effect, inhibition of lipogenesis, nor in a substantial decrease in plasma apolipoprotein C-III content [8].
• Adipose reduction by MEDICA 16 was not compromised by a decrease in overall net caloric intake but was accompanied by a 40 percent increase in resting metabolic rate [9].
• The decrease in the lipid content resulted from (a) an extensive hypotriglyceridemia in MEDICA 16-treated rats; (b) inhibition of adipose lipogenesis by MEDICA 16; (c) increased sensitivity to catecholamines-. ACTH- and forskolin-induced lipolysis in MEDICA 16 adipocytes [9].

Anatomical context of MEDICA 16

• 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 [7].
• Treatment of 12-week JCR:LA-cp rats with MEDICA 16 (an ATP-citrate lyase inhibitor) resulted in a decrease in hepatic ACC and AMPK activities, but had no effect on skeletal muscle ACC and AMPK [5].
• The induction of liver peroxisomes by MEDICA 16 conforms to the previously defined requirement for an amphipathic carboxylate in initiating peroxisomal proliferation [10].
• Incubation of cultured rat hepatocytes in the presence of MEDICA 16 added to the culture medium resulted in a dose-dependent increase in peroxisomal beta-oxidation activities with a concomitant elevation of the volume density of peroxisomes [10].
• In contrast, egg yolk total polyunsaturated fatty acid content and the ratio of polyunsaturated to saturated fatty acids were both inversely related to the dietary content of MEDICA 16 [11].

Associations of MEDICA 16 with other chemical compounds

• Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect [7].
• In light of this similarity, MEDICA 16 was further evaluated here as a modulator of rat liver redox and phosphate potentials as well as an effector of cardiac high energy intermediates level in comparison to thyroid hormone [12].
• Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo [13].
• Treatment of rats by beta,beta'-methyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a dose- and time-dependent increase in liver peroxisomal enoyl-CoA hydratase and cyanide-insensitive palmitoyl-CoA oxidation with a concomitant increase in the volume density of peroxisomes as determined by morphometry [10].

Gene context of MEDICA 16

• The effect of beta,beta'-tetramethylhexadecanedioic acid (MEDICA 16) on plasma very-low-density lipoprotein metabolism in rats: role of apolipoprotein C-III [14].

Analytical, diagnostic and therapeutic context of MEDICA 16

• However, whether MEDICA 16 and other peroxisome proliferator drugs will have clinical utility in reverse-electron-transport therapy may hinge on their ability to induce key enzymes in human hepatocytes; cell culture studies to evaluate this are required [4].

References