By Donavan Lim
In a significant breakthrough, A*STAR scientists from the Institute of Molecular and Cell Biology (IMCB) and the Singapore Bioimaging Consortium (SBIC) have discovered a new signalling pathway that controls both obesity and atherosclerosis.
The discovery was published in the journal Cell Metabolism on July 3, whereby the team demonstrated for the first time that mice deficient in the Wip1 gene were resistant to weight gain and atherosclerosis via regulation of the Ataxia telangiectasia mutated gene (ATM) and its downstream signalling molecule mTor.
Wip1 deficient mice fed with a high-fat diet were resistant to obesity and atherosclerosis by preventing the accumulation of lipid droplets. This appeared to be through increased autophagy, the normal process by which the body degrades its own cellular components.
The experiment showed that the Wip1 deficient mice exhibited increased activity of ATM which decreased mTor signalling, resulting in increased autophagy. This degraded the lipid droplets and suppressed obesity and atherosclerosis.
Obesity and atherosclerosis-related diseases account for over one-third of deaths in the Western world.
In Singapore, cardiovascular disease accounted for 31.9 per cent of all deaths in 2010. And around 10.8 per cent of the citystate population is obese.
The team is hopeful that this discovery could also lead to a cure for cancer.
In a scenario similar to the suppression of obesity and atherosclerosis, the activation of autophagy in cancer cells could result in degradation of cellular content hereby rendering cancer cells unable to sustain rapid proliferation which will suppress cancer growth.
Senior Principal Investigator at IMCB and lead author of this paper, Dr Dmitry Bulavin said “We are building on this research to investigate if the same mechanism could also control tumour progression and hence potentially unlock new therapeutic treatments targeting Wip1, ATM and mTor in cancer as well and the preliminary results are promising.”
This discovery adds significant weight to ATM as an important gene with a key role in protecting us from major pathological conditions
Prof Hong Wanjin, Executive Director of IMCB, said, “This is the first time that these important molecules have been integrated into a linear pathway that plays a prominent role in controlling obesity and atherosclerosis. It is a fine example of how fundamental research can shed light on biological and medical questions to potentially open new avenues of formulating therapeutic strategies for the benefit of patients.”
Obesity, atherosclerosis and cancer accounted for more than 70 per cent of mortality worldwide, making ATM-related pathways very attractive therapeutic targets.