Amorfrutin B is an efficient natural peroxisome proliferator-activated receptor gamma (PPARγ) agonist with potent glucose-lowering properties.
Diabetologia
; 56(8): 1802-12, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23680913
ABSTRACT
AIMS/HYPOTHESIS:
The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) is an important gene regulator in glucose and lipid metabolism. Unfortunately, PPARγ-activating drugs of the thiazolidinedione class provoke adverse side effects. As recently shown, amorfrutin A1 is a natural glucose-lowering compound that selectively modulates PPARγ. In this study we aimed to characterise, in vitro, a large spectrum of the amorfrutins and similar molecules, which we isolated from various plants. We further studied in vivo the glucose-lowering effects of the so far undescribed amorfrutin B, which featured the most striking PPARγ-binding and pharmacological properties of this family of plant metabolites.METHODS:
Amorfrutins were investigated in vitro by binding and cofactor recruitment assays and by transcriptional activation assays in primary human adipocytes and murine preosteoblasts, as well as in vivo using insulin-resistant high-fat-diet-fed C57BL/6 mice treated for 27 days with 100 mg kg(-1) day(-1) amorfrutin B.RESULTS:
Amorfrutin B showed low nanomolar binding affinity to PPARγ, and micromolar binding to the isotypes PPARα and PPARß/δ. Amorfrutin B selectively modulated PPARγ activity at low nanomolar concentrations. In insulin-resistant mice, amorfrutin B considerably improved insulin sensitivity, glucose tolerance and blood lipid variables after several days of treatment. Amorfrutin B treatment did not induce weight gain and furthermore showed liver-protecting properties. Additionally, amorfrutins had no adverse effects on osteoblastogenesis and fluid retention. CONCLUSIONS/INTERPRETATION:
The application of plant-derived amorfrutins or synthetic analogues thereof constitutes a promising approach to prevent or treat complex metabolic diseases such as insulin resistance or type 2 diabetes.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Salicilatos
/
PPAR gama
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Hipoglicemiantes
Limite:
Animals
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Humans
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Male
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article