Community Research and Development Information Service - CORDIS

FP7

ADIPONRF2 Result In Brief

Project ID: 329442
Funded under: FP7-PEOPLE
Country: Greece

A molecular kick-start to combat obesity

Broccoli sprout extracts contain a molecule that activates a chemical pathway controlling the development of obesity. European researchers have investigated the exact role of this chemical, Nrf2.
A molecular kick-start to combat obesity
The ADIPONRF2 (Targeting the Keap1/Nrf2 pathway in adipose tissue for obesity prevention and treatment) project looked into how manipulation of Keap1/Nrf2 signalling in adipose tissue affects the development of obesity and metabolic syndrome.

Obesity is accompanied by chronic oxidative stress in adipose tissue. Mouse models and cell culture systems were therefore used with gain or loss of Nrf2, as this pathway is central to regulation of a range of antioxidant and cytoprotective genes.

Nrf2 activation in relation to fat formation and bioenergetics of brown and white fat cells showed partial inhibition of white adipocyte differentiation. Mature brown adipocytes consume increased oxygen when the Keap1/Nrf2 pathway is activated.

In the setting of a high-fat induced obesity model, Nrf2 pathway activation activates a transcription programme that gives repressed fat formation and glucose generation from non-carbohydrate substrates. The researchers also identified many Nrf2 target genes including Notch 1. Overexpression of Notch 1 in adipocytes results in a highly resistant diabetic phenotype due to blocked expansion of white adipose tissue.

Highlighted by the metabolic phenotype induced by a high-fat diet in mice lacking Nrf2, activation of the Nrf2 pathway is an effective way to prevent diet-induced obesity. The cell lines and ADIPONRF2 mouse models developed in the project could be the basis for further trials. Translating these findings into clinical trials should facilitate the development of this form of therapy for metabolic syndrome.

Particularly significant is the fact that sulphoraphane can be administered as a broccoli sprout extract to activate Nrf2. Papers have been published in the peer-reviewed journals Molecular Metabolism and Archives of Biochemistry and Biophysics.

Related information

Subjects

Life Sciences

Keywords

Obesity, broccoli, Nrf2, chronic oxidative stress, Notch 1, sulphoraphane
Record Number: 190744 / Last updated on: 2016-12-20