of HDL and total cholesterol in the serum of students in adolescence and sex Serumcholesterols und H ufigkeit von Hypercholesterol mie bei Kindern und. Preferred Name. Pseudohomozygous familial hypercholesterolemia. ID. http:// Classified as. Preferred Name. Familial hypercholesterolemia. ID. ontology/MEDDRA/ Classified as. Type IIa hyperlipidaemia. cui.
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The Lipid Hypothesis – Closing in on the Truth
However, the mechanism of action is not yet clearly understood. Effects on target gene expressions in the intestine were analyzed by quantitative polymerase chain reaction in normal mice.
In patients with type 2 diabetes mellitus, dyslipidemia is an important modifiable cardiovascular risk factor, and it is often necessary to improve the lipid profile by drug intervention 123. To clarify the cholesterol transport from the small intestine, cholesterol uptake from the intestine after oral radiolabeled cholesterol loading was investigated in the B6.
Fecal cholesterol excretion was also assessed as follows A total of 27 male B6. Complementary deoxyribonucleic acid was synthesized from 0. Additionally, data hyperchollest triglyceride concentration of each fraction are shown in Figure S1. Effect of anagliptin on bodyweight, serum glucose, plasma dipeptidyl peptidase 4 activity and serum cholesterol levels in spontaneously hypercholesterolemic mice.
We also confirmed the inhibitory effect of anagliptin on the hepatic target gene expression related to cholesterol synthesis and on the serum total cholesterol concentration Figures S2 and S3. Actually, in the present data, the hepatic target gene expression related to cholesterol synthesis was decreased in mice with repeated treatment with anagliptin Figure S2which reproduced the results in the previous reports.
Although rabbits cannot synthesize cholesterol endogenously, the effect of anagliptin yypercholest to be attributable to reduction in the absorption of dietary cholesterol from the small intestine.
In fact, the serum concentrations of sitosterol and campesterol, both markers of cholesterol absorption, in these rabbits also showed a tendency to decrease with anagliptin treatment, and were closely correlated with the serum cholesterol concentrations.
In the present study, this effect was hgpercholest observed in the chylomicron and VLDL fractions, which is consistent with previous reports Cholesterol transport does not run in parallel with triglyceride transport. We also carried out quantitative polymerase chain reaction analysis of target gene expressions in the small intestine of mice to clarify the mechanisms underlying the suppression of cholesterol transport.
The transporter, NPC1L1, a target of ezetimibe, is mainly expressed on the gastrointestinal tract epithelial cells and regulates the absorption of dietary cholesterol from the intestinal lumen into the intestinal epithelial cells 29 In the present study, as the cholesterol radioactivity in the intestinal tissue was not decreased, but actually increased or remained unchanged after radiolabeled cholesterol loading, it would seem that anagliptin has no effect on the cholesterol absorption per sewhich is consistent with the results of the quantitative polymerase chain reaction analysis.
These proteins are known to rop roles in lipoprotein assembly and secretion from the intestinal mucosa to the lymph in the course of cholesterol transport and metabolism.
The Lipid Hypothesis | Statins | Ezetimibe | IMPROVE-IT trial
As MTTP catalyzes the transport of triglyceride, cholesteryl rkl and phosphatidylcholine between membranes, MTTP might have a role in lipoprotein assembly ACAT2 is known to be eol for cholesterol ester formation and secretion of lipoproteins One possible explanation for the mechanisms underlying the suppression of cholesterol hyprecholest is that these decreased proteins might inhibit the lipoprotein assembly and secretion, and lipoprotein lipase activity in the small intestine, resulting in the suppression of lipoprotein metabolism and delayed cholesterol transport into the intestinal lymph.
However, further studies are required to precisely clarify these mechanisms, because it remains unclear how anagliptin treatment changes the target gene expressions in the intestine. However, Kurozumi et al. Similar effects of anagliptin on cholesterol synthesis in the liver were reported by others 2025and we also confirmed them, as mentioned above.
National Center for Biotechnology InformationU. Journal List J Diabetes Investig v. Published online Jun 5. Author information Article notes Copyright and License information Disclaimer.
This is an open access article under the terms of the http: Cholesterol transport, Dipeptidyl peptidase 4 inhibitor, Hypercholesterolemia. Introduction In patients with type 2 diabetes mellitus, dyslipidemia is an important modifiable cardiovascular risk factor, and it is often roo to improve the lipid profile by drug intervention 123. Table 1 Effect of anagliptin on bodyweight, serum glucose, plasma dipeptidyl peptidase 4 activity and serum cholesterol levels in spontaneously hypercholesterolemic mice.
Open in a separate window. Click here for additional data file. Notes J Diabetes Investig.
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