Summary of Study ST001136
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000760. The data can be accessed directly via it's Project DOI: 10.21228/M8FH6C This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
| Study ID | ST001136 |
| Study Title | Metabolme analysis of OPC-163493 on the Liver of ZDF rats (part-II) |
| Study Type | Long-term in vivo test |
| Study Summary | Metabolome analysis were on the 24 samples of ZDF rats that were treated with OPC-163493 for 6-weeks. The 24 samples were composed of 3 different groups (Vehicles, OPC-163493 treatment, and baseline control; each n=8). |
| Institute | Otsuka Pharmaceutical Co., Ltd. |
| Last Name | Kanemoto |
| First Name | Naohide |
| Address | 463-10 Kagasuno Kawauchi-cho Tokushima 771-0192, Japan |
| Kanemoto.Naohide@otsuka.jp | |
| Phone | 81-03-6717-1400 |
| Submit Date | 2019-02-07 |
| Analysis Type Detail | LC-MS |
| Release Date | 2019-03-06 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR000760 |
| Project DOI: | doi: 10.21228/M8FH6C |
| Project Title: | Antidiabetic and cardiovascular beneficial effects of a liver-localized mitochondrial uncoupler |
| Project Summary: | Inducing mitochondrial uncoupling (mUncoupling) is an attractive therapeutic strategy for treating metabolic diseases because it leads to calorie-wasting by reducing the efficiency of oxidative phosphorylation (OXPHOS) in mitochondria. Here we report a safe mUncoupler, OPC-163493, which has unique pharmacokinetic characteristics. OPC-163493 shows a good bioavailability upon oral administration and primarily distributed to specific organs: the liver and kidneys, avoiding systemic toxicities. It exhibitsinsulin-independent antidiabetic effects in multiple animal models of type I and type II diabetes and antisteatotic effects in fatty liver models. These beneficial effects can be explained by the improvement of glucose metabolism and enhancement of energy expenditure by OPC-163493 in the liver. Moreover, OPC-163493 treatment lowered blood pressure, extended survival, and improved renal function in the rat model of stroke/hypertension, possibly by enhancing NO bioavailability in blood vessels and reducing mitochondrial ROS production. OPC-163493 is a liver-localized/targeted mUncoupler that ameliorates various complications of diabetes. |
| Institute: | Otsuka Pharmaceutical Co., Ltd. |
| Last Name: | Kanemoto |
| First Name: | Naohide |
| Address: | 463-10 Kagasuno Kawauchi-cho, Tokushima, Tokusima, 770-0865, Japan |
| Email: | Kanemoto.Naohide@otsuka.jp |
| Phone: | +81-88-665-2126 |
Subject:
| Subject ID: | SU001197 |
| Subject Type: | Mammal |
| Subject Species: | Rattus norvegicus |
| Taxonomy ID: | 10116 |
| Genotype Strain: | ZDF rats |
| Gender: | Not applicable |
| Species Group: | Mammals |
Factors:
Subject type: Mammal; Subject species: Rattus norvegicus (Factor headings shown in green)
| mb_sample_id | local_sample_id | Genotype | Treatment | Duration (weeks) |
|---|---|---|---|---|
| SA078237 | Baseline control-106 | 11-week-old ZDF rat | - | - |
| SA078238 | Baseline control-107 | 11-week-old ZDF rat | - | - |
| SA078239 | Baseline control-105 | 11-week-old ZDF rat | - | - |
| SA078240 | Baseline control-104 | 11-week-old ZDF rat | - | - |
| SA078241 | Baseline control-101 | 11-week-old ZDF rat | - | - |
| SA078242 | Baseline control-103 | 11-week-old ZDF rat | - | - |
| SA078243 | Baseline control-108 | 11-week-old ZDF rat | - | - |
| SA078244 | Baseline control-102 | 11-week-old ZDF rat | - | - |
| SA078253 | OPC-13 | 17-week-old ZDF rat | 6 | 6 |
| SA078254 | OPC-10 | 17-week-old ZDF rat | 6 | 6 |
| SA078255 | OPC-9 | 17-week-old ZDF rat | 6 | 6 |
| SA078256 | OPC-11 | 17-week-old ZDF rat | 6 | 6 |
| SA078257 | OPC-12 | 17-week-old ZDF rat | 6 | 6 |
| SA078258 | OPC-15 | 17-week-old ZDF rat | 6 | 6 |
| SA078259 | OPC-14 | 17-week-old ZDF rat | 6 | 6 |
| SA078260 | OPC-16 | 17-week-old ZDF rat | 6 | 6 |
| SA078245 | Vehicle-5 | 17-week-old ZDF rat | - | 6 |
| SA078246 | Vehicle-4 | 17-week-old ZDF rat | - | 6 |
| SA078247 | Vehicle-3 | 17-week-old ZDF rat | - | 6 |
| SA078248 | Vehicle-6 | 17-week-old ZDF rat | - | 6 |
| SA078249 | Vehicle-1 | 17-week-old ZDF rat | - | 6 |
| SA078250 | Vehicle-8 | 17-week-old ZDF rat | - | 6 |
| SA078251 | Vehicle-7 | 17-week-old ZDF rat | - | 6 |
| SA078252 | Vehicle-2 | 17-week-old ZDF rat | - | 6 |
| Showing results 1 to 24 of 24 |
Collection:
| Collection ID: | CO001191 |
| Collection Summary: | After euthanasia by exsanguination under isoflurane anesthesia, a piece of liver was taken from the left lateral lobe on the treated rats, weighed at approximately 50mg, and immediately frozen in liquid nitrogen. |
| Sample Type: | Liver |
| Storage Conditions: | -80℃ |
Treatment:
| Treatment ID: | TR001212 |
| Treatment Summary: | The baseline control, the liver samples of ZDF rats were taken from the baseline control group of 11-week-old ZDF rats. And at the same time, the other 2 comparing groups were started on oral administration of OPC-163493 or vehicle solution for 6-weeks. After 6-week dosing, liver samples were taken from both groups, and the liver metabolites of all three groups including the baseline controls were analyzed. |
| Treatment Dose: | 0mg/kg/day, 6mg/kg/day |
Sample Preparation:
| Sampleprep ID: | SP001205 |
| Sampleprep Summary: | The frozen liver samples were plunged into 50% acetonitrile/Milli-Q water containing internal standard. The sample was homogenized and then centrifuged. Subsequently, 800 uL of upper aqueous layer was filtered through a 5-kDa cutoff filter. The filtrate was centrifugally concentrated and re-suspended in 50 uL of Milli-Q water. |
| Processing Storage Conditions: | 4℃ |
| Extract Storage: | -80℃ |
| Sample Resuspension: | 50 uL Mili-Q |
Chromatography:
| Chromatography ID: | CH001348 |
| Chromatography Summary: | capillary electrophoresis was connected with time-of-flight mass spectrometry (CE-TOFMS) for cation analysis and tandem mass spectrometry (CE-MS/MS) for anion. |
| Instrument Name: | Agilent 7100 CE |
| Column Name: | Fused silica capillary, i.d. 50 μm × 80 cm |
| Chromatography Type: | CE |
Analysis:
| Analysis ID: | AN001862 |
| Analysis Type: | MS |
| Chromatography ID: | CH001348 |
| Num Factors: | 3 |
| Num Metabolites: | 52 |
| Units: | Concentration (nmol/g tissue) |
| Analysis ID: | AN001863 |
| Analysis Type: | MS |
| Chromatography ID: | CH001348 |
| Num Factors: | 3 |
| Num Metabolites: | 48 |
| Units: | Concentration (nmol/g tissue) |
