PMID- 28665967
OWN - NLM
STAT- MEDLINE
DCOM- 20171002
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 12
IP  - 6
DP  - 2017
TI  - Effects of canagliflozin on weight loss in high-fat diet-induced obese mice.
PG  - e0179960
LID - 10.1371/journal.pone.0179960 [doi]
LID - e0179960
AB  - Canagliflozin, an inhibitor of sodium glucose co-transporter (SGLT) 2, has been 
      shown to reduce body weight during the treatment of type 2 diabetes mellitus 
      (T2DM). In this study, we sought to determine the role of canagliflozin in body 
      weight loss and liver injury in obesity. C57BL/6J mice were fed a high-fat diet 
      to simulate diet-induced obesity (DIO). Canagliflozin (15 and 60 mg/kg) was 
      administered to DIO mice for 4 weeks. Orlistat (10 mg/kg) was used as a positive 
      control. The body weight, liver weight, liver morphology, total cholesterol (TC) 
      and triglyceride (TG) levels were examined. Signaling molecules, including 
      diacylgycero1 acyltransferase-2 (DGAT2), peroxisome proliferation receptor 
      alpha-1 (PPARalpha1), PPARgamma1, PPARgamma2 mRNA levels and the protein expression of SGLT2 
      were evaluated. Canagliflozin reduced body weight, especially the high-dose 
      canagliflozin, and resulted in increased body weight loss compared with orlistat. 
      Moreover, canagliflozin reduced the liver weight and the ratio of liver weight to 
      body weight, lowered the serum levels of TC and TG, and ameliorated liver 
      steatosis. During the canagliflozin treatment, SGLT2, DGAT2, PPARgamma1 and PPARgamma2 
      were inhibited, and PPARalpha1 was elevated in the liver tissues. This finding may 
      explain why body weight was reduced and secondary liver injury was ameliorated in 
      response to canagliflozin. Together, the results suggest that canagliflozin may 
      be a potential anti-obesity strategy.
FAU - Ji, Wenjun
AU  - Ji W
AD  - Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
AD  - Department of Pharmacy, Taizhou People's Hospital, Taizhou, Jiangsu, China.
FAU - Zhao, Mei
AU  - Zhao M
AD  - Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
AD  - Department of Pharmacy, 302 Military Hospital of China, Beijing, China.
FAU - Wang, Meng
AU  - Wang M
AD  - Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
AD  - Department of Pharmacy, Shijiazhuang Maternity Hospital, Shijiazhuang, Hebei, 
      China.
FAU - Yan, Wenhui
AU  - Yan W
AD  - Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
FAU - Liu, Yuan
AU  - Liu Y
AD  - Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
FAU - Ren, Shuting
AU  - Ren S
AD  - Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong 
      University), Ministry of Education, Xi'an, Shaanxi, China.
AD  - Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
FAU - Lu, Jun
AU  - Lu J
AD  - Clinical Research Center, the First Affiliated Hospital, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
FAU - Wang, Bing
AU  - Wang B
AD  - Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong 
      University), Ministry of Education, Xi'an, Shaanxi, China.
AD  - Department of Pathology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
FAU - Chen, Lina
AU  - Chen L
AD  - Department of Pharmacology, School of Basic Medical Sciences, Xi'an Jiaotong 
      University Health Science Center, Xi'an, Shaanxi, China.
AD  - Key Laboratory of Environment and Genes Related to Diseases (Xi'an Jiaotong 
      University), Ministry of Education, Xi'an, Shaanxi, China.
LA  - eng
PT  - Journal Article
DEP - 20170630
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Peroxisome Proliferator-Activated Receptors)
RN  - 0 (Triglycerides)
RN  - 0SAC974Z85 (Canagliflozin)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.3.1.20 (DGAT2 protein, mouse)
RN  - EC 2.3.1.20 (Diacylglycerol O-Acyltransferase)
SB  - IM
MH  - Animals
MH  - Canagliflozin/*pharmacology
MH  - Cholesterol/blood
MH  - Diacylglycerol O-Acyltransferase/metabolism
MH  - *Diet, High-Fat
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Liver/drug effects/pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Obesity/enzymology/etiology/metabolism/*therapy
MH  - Peroxisome Proliferator-Activated Receptors/metabolism
MH  - Triglycerides/blood
MH  - Weight Loss/*drug effects
PMC - PMC5493335
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2017/07/01 06:00
MHDA- 2017/10/03 06:00
PMCR- 2017/06/30
CRDT- 2017/07/01 06:00
PHST- 2016/09/11 00:00 [received]
PHST- 2017/06/07 00:00 [accepted]
PHST- 2017/07/01 06:00 [entrez]
PHST- 2017/07/01 06:00 [pubmed]
PHST- 2017/10/03 06:00 [medline]
PHST- 2017/06/30 00:00 [pmc-release]
AID - PONE-D-16-36467 [pii]
AID - 10.1371/journal.pone.0179960 [doi]
PST - epublish
SO  - PLoS One. 2017 Jun 30;12(6):e0179960. doi: 10.1371/journal.pone.0179960. 
      eCollection 2017.