PMID- 29512720
OWN - NLM
STAT- MEDLINE
DCOM- 20180913
LR  - 20211124
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 17
IP  - 5
DP  - 2018 May
TI  - Alogliptin alleviates hepatic steatosis in a mouse model of nonalcoholic fatty 
      liver disease by promoting CPT1a expression via Thr172 phosphorylation of AMPKalpha 
      in the liver.
PG  - 6840-6846
LID - 10.3892/mmr.2018.8673 [doi]
AB  - Pioglitazone (PIO) has been reported to be effective for nonalcoholic fatty liver 
      disease (NAFLD) and alogliptin (ALO) may have efficacy against NAFLD progression 
      in patients with type 2 diabetes mellitus (T2DM). The present study examined the 
      effectiveness of ALO in a rodent model of NAFLD and diabetes mellitus. KK‑Ay mice 
      were used to produce an NAFLD model via administration of a choline‑deficient 
      (CD) diet. To examine the effects of alogliptin, KK‑Ay mice were provided with a 
      CD diet with 0.03% ALO and/or 0.02% PIO orally for 8 weeks. Biochemical 
      parameters, pathological alterations and hepatic mRNA levels associated with 
      fatty acid metabolism were assessed. Severe hepatic steatosis was observed in 
      KK‑Ay mice fed with a CD diet, which was alleviated by the administration of ALO 
      and/or PIO. ALO administration increased the hepatic carnitine 
      palmitoyltransferase 1a (CPT1a) mRNA expression level and enhanced the Thr172 
      phosphorylation of AMP‑activated protein kinase alpha (AMPKalpha) in the liver. PIO 
      administration tended to decrease the hepatic fatty acid synthase mRNA expression 
      level and increase the serum adiponectin level. Homeostasis model of 
      assessment‑insulin resistance values tended to improve with ALO and PIO 
      administration. ALO and PIO alleviated hepatic steatosis in KK‑Ay mice fed with a 
      CD diet. ALO increased hepatic mRNA expression levels associated with fatty acid 
      oxidation. In addition, the results of the present study suggested that ALO 
      promotes CPT1a expression via Thr172 phosphorylation of AMPKalpha.
FAU - Tobita, Hiroshi
AU  - Tobita H
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
FAU - Sato, Shuichi
AU  - Sato S
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
FAU - Yazaki, Tomotaka
AU  - Yazaki T
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
FAU - Mishiro, Tsuyoshi
AU  - Mishiro T
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
FAU - Ishimura, Norihisa
AU  - Ishimura N
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
FAU - Ishihara, Shunnji
AU  - Ishihara S
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
FAU - Kinoshita, Yoshikazu
AU  - Kinoshita Y
AD  - Department of Gastroenterology and Hepatology, Shimane University Faculty of 
      Medicine, Izumo, Shimane 693‑8501, Japan.
LA  - eng
PT  - Journal Article
DEP - 20180301
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Piperidines)
RN  - 56HH86ZVCT (Uracil)
RN  - EC 2.3.1.21 (CPT1B protein, mouse)
RN  - EC 2.3.1.21 (Carnitine O-Palmitoyltransferase)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - JHC049LO86 (alogliptin)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Animals
MH  - Carnitine O-Palmitoyltransferase/*biosynthesis/genetics
MH  - Disease Models, Animal
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Non-alcoholic Fatty Liver Disease/*drug therapy/genetics/metabolism/pathology
MH  - Phosphorylation/drug effects
MH  - Piperidines/*pharmacology
MH  - Uracil/*analogs & derivatives/pharmacology
OTO - NOTNLM
OT  - nonalcoholic fatty liver disease
OT  - diabetes mellitus
OT  - alogliptin
OT  - carnitine palmitoyltransferase 1a
OT  - AMP-activated protein kinase alpha
OT  - KK-Ay mice
EDAT- 2018/03/08 06:00
MHDA- 2018/09/14 06:00
CRDT- 2018/03/08 06:00
PHST- 2017/11/14 00:00 [received]
PHST- 2018/02/06 00:00 [accepted]
PHST- 2018/03/08 06:00 [pubmed]
PHST- 2018/09/14 06:00 [medline]
PHST- 2018/03/08 06:00 [entrez]
AID - 10.3892/mmr.2018.8673 [doi]
PST - ppublish
SO  - Mol Med Rep. 2018 May;17(5):6840-6846. doi: 10.3892/mmr.2018.8673. Epub 2018 Mar 
      1.