PMID- 36281369
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221026
IS  - 2405-8440 (Print)
IS  - 2405-8440 (Electronic)
IS  - 2405-8440 (Linking)
VI  - 8
IP  - 10
DP  - 2022 Oct
TI  - Beneficial effects of SGLT2 inhibitor on metabolic inflexibility and visceral fat 
      amount in animal model of obese type 2 diabetes.
PG  - e11012
LID - 10.1016/j.heliyon.2022.e11012 [doi]
LID - e11012
AB  - BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are often accompanied 
      with a disrupted diurnal rhythm of eating and sustained anabolic state, leading 
      to metabolic inflexibility. In the present study, we plan to investigate effects 
      of a sodium glucose co-transporter 2 (SGLT2) inhibitor, canagliflozin (CANA), on 
      such a metabolic inflexibility, especially on fat metabolism, in the obese type 2 
      diabetic rats. MATERIALS AND METHODS: Five-week-old male SDT (Spontaneously 
      Diabetic Torii) fatty rats as a model of obesity and T2DM and Sprague-Dawley (SD) 
      rats were treated by either CANA (10 mg/kg) or saline (vehicle) orally for 14 
      days. Then, after the measurement of respiratory quotient (RQ) and visceral and 
      subcutaneous fat volumes, rats were euthanized and blood and tissue samples were 
      collected. RESULTS: The treatment by CANA significantly enhanced beta-ketone 
      concentration in the blood during light period in the SDT fatty rats with no 
      effect on blood glucose concentration. The CANA treatment significantly reduced 
      visceral fat volume in the SDT fatty rats. A diurnal rhythm of RQ was severely 
      disrupted and persistently high throughout the day in the vehicle-treated SDT 
      fatty rats. By the administration of CANA clearly restored the disrupted diurnal 
      rhythm of RQ with a revival of the nadir during light period. Quantitative 
      real-time RT-PCR revealed a significant increase of AMP-activated protein kinase 
      and decrease of acetyl-CoA carboxylase-1 expression in the liver, and a 
      significant increase of hormone sensitive lipase and uncoupling protein-2 
      expression in the white adipose tissue by the treatment of CANA in the SDT fatty 
      rats. CONCLUSION: CANA as a SGLT2i reduced visceral fat amount via the 
      enhancement of fat oxidation during the light period, leading to an amelioration 
      of metabolic inflexibility in an obese diabetic model. A novel mechanism of CANA 
      prompts the possibility that this new class of anti-diabetic agent could be a 
      promising anti-obesity agent as well.
CI  - (c) 2022 The Author(s).
FAU - Hara, Kento
AU  - Hara K
AD  - Division of Endocrinology and Metabolism, Kurume University School of Medicine, 
      Kurume, Japan.
FAU - Sakai, Yusuke
AU  - Sakai Y
AD  - Institute of Animal Experimentation, Kurume University School of Medicine, 
      Kurume, Japan.
FAU - Tajiri, Yuji
AU  - Tajiri Y
AD  - Division of Endocrinology and Metabolism, Kurume University School of Medicine, 
      Kurume, Japan.
AD  - Diabetes Center, Kurume University Medical Center, Kurume, Japan.
FAU - Nomura, Masatoshi
AU  - Nomura M
AD  - Division of Endocrinology and Metabolism, Kurume University School of Medicine, 
      Kurume, Japan.
LA  - eng
PT  - Journal Article
DEP - 20221010
PL  - England
TA  - Heliyon
JT  - Heliyon
JID - 101672560
PMC - PMC9587290
OTO - NOTNLM
OT  - Fat oxidation
OT  - Metabolic inflexibility
OT  - Obesity
OT  - SGLT2 inhibitor
OT  - Type 2 diabetes mellitus
COIS- This work was supported in part by Mitsubishi Tanabe Pharma Corporation (Osaka, 
      Japan).
EDAT- 2022/10/26 06:00
MHDA- 2022/10/26 06:01
PMCR- 2022/10/10
CRDT- 2022/10/25 01:48
PHST- 2022/04/14 00:00 [received]
PHST- 2022/07/24 00:00 [revised]
PHST- 2022/10/05 00:00 [accepted]
PHST- 2022/10/25 01:48 [entrez]
PHST- 2022/10/26 06:00 [pubmed]
PHST- 2022/10/26 06:01 [medline]
PHST- 2022/10/10 00:00 [pmc-release]
AID - S2405-8440(22)02300-3 [pii]
AID - e11012 [pii]
AID - 10.1016/j.heliyon.2022.e11012 [doi]
PST - epublish
SO  - Heliyon. 2022 Oct 10;8(10):e11012. doi: 10.1016/j.heliyon.2022.e11012. 
      eCollection 2022 Oct.