The Dipeptidyl Peptidase-4 Inhibitor Teneligliptin Reduces Aortic Damage from Hypercholesterolaemia in Apolipoprotein E-Deficient Mice

Abstract

Objective: Hypercholesterolaemia is a well-established risk factor for blood vessel damage, which can lead to cardiovascular diseases. An abundance of clinical data show that dipeptidyl peptidase-4 inhibitors protect against aortic damage in patients with diabetes. The goal of this study was to investigate the possible protective effects of teneligliptin against aortic damage in apolipoprotein E knockout (ApoE^-/-) mice. Methods: Eight-week-old male ApoE^-/- mice were randomly divided into 3 groups: a control group fed a normal diet, a high-cholesterol diet (HD group), and an HD diet mixed with teneligliptin (HD + Tene group), and all the groups were fed with the different treatments for 6 weeks. Results and Conclusion: The metabolic characteristics of total cholesterol, low-density lipoprotein-cholesterol, and high-sensitivity C-reactive protein were lower in ApoE^-/- HD + Tene mice than in ApoE^-/- HD mice. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) gene and protein expression were lower in the aortic tissue of ApoE^-/- HD + Tene mice than in ApoE^-/- HD mice. IL-6 and TNF-α gene expression were lower in ApoE^-/- HD + Tene mice than in ApoE^-/- HD mice. These results indicate that teneligliptin may provide a potential therapeutic target for the aortic damage from hypercholesterolaemia.

Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets

“…In an in vitro study conducted by Mostafa et al, the incubation of adipocytes with vildagliptin induced an increased cholesterol efflux through the raised expression of the gene encoding for the adenosine triphosphate (ATP) binding cassette transporters family [ 108 ]. Moreover, several animal studies showed how DPP4i could reduce the accumulation of lipids and triglycerides in the liver [ 106 , 109 ] and kidneys [ 110 ]. Specifically, DDP4i could suppress the accumulation of triacylglycerol and diacylglycerol in hepatocytes by raising mitochondrial carbohydrate use and hepatic triacylglycerol secretion [ 109 ].…”

“…Specifically, DDP4i could suppress the accumulation of triacylglycerol and diacylglycerol in hepatocytes by raising mitochondrial carbohydrate use and hepatic triacylglycerol secretion [ 109 ]. Similarly, the administration of teneligliptin reduced the lipid accumulation in the kidneys of apolipoprotein E knockout mice through the inhibition of renal lectin-like oxidized LDL receptor-1 [ 110 ]. Moreover, DPP4i could reduce fatty acids synthesis in the liver by upregulating the expression of carnitine palmitoyl-transferase-1 and increasing the activity of peroxisome proliferator-activated receptor-α and cyclic adenosine monophosphate (cAMP) reactive element binding homolog [ 111 ].…”