PMID- 37009790
OWN - NLM
STAT- MEDLINE
DCOM- 20230510
LR  - 20230512
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 55
IP  - 4
DP  - 2023 Apr
TI  - Evogliptin, a DPP-4 inhibitor, prevents diabetic cardiomyopathy by alleviating 
      cardiac lipotoxicity in db/db mice.
PG  - 767-778
LID - 10.1038/s12276-023-00958-6 [doi]
AB  - Dipeptidyl peptidase-4 (DPP-4) inhibitors are glucose-lowering drugs for type 2 
      diabetes mellitus (T2DM). We investigated whether evogliptin(R) (EVO), a DPP-4 
      inhibitor, could protect against diabetic cardiomyopathy (DCM) and the underlying 
      mechanisms. Eight-week-old diabetic and obese db/db mice were administered EVO 
      (100 mg/kg/day) daily by oral gavage for 12 weeks. db/db control mice and 
      C57BLKS/J as wild-type (WT) mice received equal amounts of the vehicle. In 
      addition to the hypoglycemic effect, we examined the improvement in cardiac 
      contraction/relaxation ability, cardiac fibrosis, and myocardial hypertrophy by 
      EVO treatment. To identify the mechanisms underlying the improvement in diabetic 
      cardiomyopathy by EVO treatment, its effect on lipotoxicity and the mitochondrial 
      damage caused by lipid droplet accumulation in the myocardium were analyzed. EVO 
      lowered the blood glucose and HbA1c levels and improved insulin sensitivity but 
      did not affect the body weight or blood lipid profile. Cardiac systolic/diastolic 
      function, hypertrophy, and fibrosis were improved in the EVO-treated group. EVO 
      prevented cardiac lipotoxicity by reducing the accumulation of lipid droplets in 
      the myocardium through suppression of CD36, ACSL1, FABP3, PPARgamma, and DGAT1 
      and enhancement of the phosphorylation of FOXO1, indicating its inhibition. The 
      EVO-mediated improvement in mitochondrial function and reduction in damage were 
      achieved through activation of PGC1a/NRF1/TFAM, which activates mitochondrial 
      biogenesis. RNA-seq results for the whole heart confirmed that EVO treatment 
      mainly affected the differentially expressed genes (DEGs) related to lipid 
      metabolism. Collectively, these findings demonstrate that EVO improves cardiac 
      function by reducing lipotoxicity and mitochondrial injury and provides a 
      potential therapeutic option for DCM.
CI  - (c) 2023. The Author(s).
FAU - Pham, Trong Kha
AU  - Pham TK
AD  - Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, 
      Department of Physiology, College of Medicine, Inje University, Busan, South 
      Korea.
AD  - Department of Health Sciences and Technology, Graduate School, Inje University, 
      Busan, South Korea.
AD  - University of Science, Vietnam National University, Hanoi, Vietnam.
FAU - Nguyen, To Hoai T
AU  - Nguyen THT
AD  - Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, 
      Department of Physiology, College of Medicine, Inje University, Busan, South 
      Korea.
AD  - Department of Health Sciences and Technology, Graduate School, Inje University, 
      Busan, South Korea.
FAU - Yi, Joo Mi
AU  - Yi JM
AD  - Department of Microbiology and Immunology, College of Medicine, Inje University, 
      Busan, South Korea.
FAU - Kim, Gwang Sil
AU  - Kim GS
AD  - Division of Cardiology, Department of Internal Medicine, Sanggye Paik Hospital, 
      Inje University, Seoul, South Korea.
FAU - Yun, Hyeong Rok
AU  - Yun HR
AD  - Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, 
      Department of Physiology, College of Medicine, Inje University, Busan, South 
      Korea.
FAU - Kim, Hyoung Kyu
AU  - Kim HK
AUID- ORCID: 0000-0002-1791-7865
AD  - Cardiovascular and Metabolic Disease Center, Smart Marine Therapeutic Center, 
      Department of Physiology, College of Medicine, Inje University, Busan, South 
      Korea. estrus74@gmail.com.
FAU - Won, Jong Chul
AU  - Won JC
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Sanggye Paik Hospital, Cardiovascular and Metabolic Disease Center, College of 
      Medicine, Inje University, Seoul, South Korea.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230403
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (Dipeptidyl-Peptidase IV Inhibitors)
RN  - 0 
      (4-(3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl)piperazin-2-one)
RN  - 0 (Hypoglycemic Agents)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Diabetic Cardiomyopathies/drug therapy/etiology/metabolism
MH  - *Dipeptidyl-Peptidase IV Inhibitors/pharmacology/therapeutic use
MH  - *Diabetes Mellitus, Type 2/complications/drug therapy
MH  - Hypoglycemic Agents/therapeutic use
MH  - Cardiomegaly
PMC - PMC10167305
COIS- This study was supported by a research fund from the Dong-A ST R&D Center (2019).
EDAT- 2023/04/04 06:00
MHDA- 2023/05/10 06:42
PMCR- 2023/04/03
CRDT- 2023/04/03 05:34
PHST- 2022/02/17 00:00 [received]
PHST- 2022/12/23 00:00 [accepted]
PHST- 2022/12/05 00:00 [revised]
PHST- 2023/05/10 06:42 [medline]
PHST- 2023/04/04 06:00 [pubmed]
PHST- 2023/04/03 05:34 [entrez]
PHST- 2023/04/03 00:00 [pmc-release]
AID - 10.1038/s12276-023-00958-6 [pii]
AID - 958 [pii]
AID - 10.1038/s12276-023-00958-6 [doi]
PST - ppublish
SO  - Exp Mol Med. 2023 Apr;55(4):767-778. doi: 10.1038/s12276-023-00958-6. Epub 2023 
      Apr 3.