microRNA-30c reduces plasma cholesterol in homozygous familial hypercholesterolemic and type 2 diabetic mouse models.

Abstract

High plasma cholesterol levels are found in several metabolic disorders and their reductions are advocated to reduce the risk of atherosclerosis. A way to lower plasma lipids is to curtail lipoprotein production; however, this is associated with steatosis. We previously showed that microRNA (miR)-30c lowers diet-induced hypercholesterolemia and atherosclerosis in C57BL/6J and Apoe-/- mice. Here, we tested the effect of miR-30c on plasma lipids, transaminases, and hepatic lipids in different mouse models. Hepatic delivery of miR-30c to chow-fed leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) hypercholesterolemic and hyperglycemic mice reduced cholesterol in total plasma and VLDL/LDL by ∼28% and ∼25%, respectively, without affecting triglyceride and glucose levels. And these mice had lower plasma transaminases and creatine kinase activities than controls. Moreover, miR-30c significantly lowered plasma cholesterol and atherosclerosis in Western diet-fed Ldlr-/- mice with no effect on plasma triglyceride, glucose, and transaminases. In these studies, hepatic lipids were similar in control and miR-30c-injected mice. Mechanistic studies showed that miR-30c reduced hepatic microsomal triglyceride transfer protein activity and lipid synthesis. Thus miR-30c reduced plasma cholesterol in several diet-induced and diabetic hypercholesterolemic mice. We speculate that miR-30c may be beneficial in lowering plasma cholesterol in different metabolic disorders independent of the origin of hypercholesterolemia.

• Authors: Sara Irani, Jahangir Iqbal, W James Antoni, Laraib Ijaz, M Mahmood Hussain
• Journal: Journal of lipid research (J Lipid Res) Vol. 59 Issue 1 Pg. 144-154 (01 2018) ISSN: 1539-7262 [Electronic] United States
• PMID: 29122890 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• MIRN30b microRNA, human
• MicroRNAs
• Receptors, LDL
• Cholesterol

Topics

• Animals
• Cholesterol (blood)
• Diabetes Mellitus, Experimental (blood, genetics)
• Diabetes Mellitus, Type 2 (blood, genetics)
• Disease Models, Animal
• Humans
• Hypercholesterolemia (blood, genetics)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Obese
• MicroRNAs (metabolism)
• Receptors, LDL (deficiency, metabolism)