The Nrf2 pathway controls the transcription of at least 200 genes necessary to carry out functions that include neutralizing oxidative stress. Oxidative stress is a process that occurs through the natural metabolism of the cell. It was only recently that other process for the Nrf2 pathway have been found and include activating processes that are important for mitochondrial biogenesis and dictating the metabolism in adipose tissue and regulating adipogenesis. As discussed previously, pyrethroids are insecticides used in agriculture. One of their effects is that they may depress the Nrf2 pathway in adipose tissues through methylation and negatively impact adipose metabolism and function that leads to inflammation, obesity and possibly diabetes.
So how does Nrf2 activity prevent obesity? Sahin writes, "obesity is induced by adipose size and number. and their differentiation is dependent on metabolic, hormonal, gene and cell morphology changes. Several transcription factors control fat homeostasis as they regulate gene necessary for fat accumulation, fatty acid transport and lipolysis.
(1) Oxidative stress is an important cause of obesity- related diseases. To counteract this, the Nrf2-Ho-1 pathway neutralizes the free radicals that cause oxidative stress. Interestingly, Ho-1 metabolic role goes beyond oxidative stress. Therefore, the Nrf2-HO-1 pathway may be a link to preventing obesity and its related diseases.
To understand how Nrf2 pathway prevents obesity, Sahin used butein, a chalcone derived from natural plants as an Nrf2 activator. Butein had also been reported to inhibit adipocyte differentiation and used to treat inflammation. The purpose of the study was to determine if Nrf2 is responsible for the activation of adipocyte transcription factors known to effect fat homeostasis. To determine this, preadipocytes were treated with butein. After 6 days, the researchers found that treatment with butein significantly decreased lipid accumulation than fully differentiated adipocytes. Next, they showed that butein greatly increases Nrf2 translocation to the nucleus and transcription of Ho-1 in a dose dependent manner. The results suggested that the butein-induced Ho-1 reduced
lipid accumulation through key adipogenic transcription factors such as PPARγ and C/EBPα. In summary this study showed that butein inhibits lipid accumulation through the inhibition of key adipogenic regulators and also upregulates the Nrf2/HO-1 antioxidant pathway. (1)
1.
Inhibitory Effects of Butein on Adipogenesis through Upregulation of the Nrf2/HO-1 Pathway in 3T3-L1 Adipocytes. Preventive nutrition and food science, Vol. 22, No. 4. (December 2017), pp. 306-311 by Jinwoo Yang, Jeehye Sung, Younghwa Kim, Heon Sang S. Jeong, Junsoo Lee
