GQ-130, a novel analogue of thiazolidinedione, improves obesity-induced metabolic alterations in rats: Evidence for the involvement of PPARß/δ pathway.
Clin Exp Pharmacol Physiol
; 47(5): 798-808, 2020 05.
Article
in En
| MEDLINE
| ID: mdl-31909493
ABSTRACT
The present investigation aimed to characterize the effect of a short-time treatment with a new thiazolidinedione (TZD) derivative, GQ-130, on metabolic alterations in rats fed a high-fat diet (HFD). We investigated whether metabolic alterations induced by GQ-130 were mediated though a mechanism that involves PPARß/δ transactivation. Potential binding and transactivation of PPARα, PPARß/δ or PPARγ by GQ-130 were examined through cell transactivation, 8-anilino-1-naphthalenesulfonic acid (ANS) fluorescence quenching assays and thermal shift assay. For in vivo experiments, male 8-week-old Wistar rats were divided into three groups fed for 6 weeks with (a) a standard rat chow (14% fat) (control group), (b) a HFD (57.8% fat) alone (HFD group), or (c) a HFD associated with an oral treatment with GQ-130 (10 mg/kg/d) during the last week (HFD-GQ group). In 293T cells, unlike rosiglitazone, GQ-130 did not cause significant transactivation of PPARγ but was able to activate PPARß/δ by 153.9 folds in comparison with control values (DMSO). Surprisingly, ANS fluorescence quenching assay reveals that GQ-130 does not bind directly to PPARß/δ binding site, a finding that was further corroborated by thermal shift assay which evaluates the thermal stability of PPARß/δ in the presence of GQ-130. Compared to the control group, rats of the HFD group showed obesity, increased systolic blood pressure (SBP), insulin resistance, impaired glucose intolerance, hyperglycaemia, and dyslipidaemia. GQ-130 treatment abolished the increased SBP and improved all metabolic dysfunctions observed in the HFD group. Oral treatment with GQ-130 was effective in improving HFD-induced metabolic alterations probably through a mechanism that involves PPARß/δ activation.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Metabolic Syndrome
/
Thiazolidinediones
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PPAR-beta
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PPAR delta
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Energy Metabolism
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Obesity
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Clin Exp Pharmacol Physiol
Year:
2020
Type:
Article
Affiliation country:
Brazil