Research conducted by CiMUS discovers the keys to cell adaptation during weight loss by intermittent fasting

Researchers at CiMUS, a member centre of the CIGUS Network, an initiative launched by the regional government (Xunta de Galicia) that groups  together centres of proven scientific excellence within the Galician university system, have recently discovered a new mechanism capable of protecting the liver from the damage caused by long periods of fasting. These findings, published recently in the international journal Cell Metabolism, open up opportunities for a better understanding of liver protection mechanisms during treatments with diets to drive weight loss.  

“It has been known for many years that diets low in methionine induce weight loss. However, our work goes further, showing that it is the hepatic decrease in SAMe – one of the by-products of methionine – that actually leads to weight loss and that an excessive or chronic decrease in its levels would damage the liver during calorie-restrictive diets”, explained Dr Marta Varela Rey, who has led the research from the CiMUS group for the Gene Regulatory Control in Disease,  in collaboration with Dr María Luz Martínez Chantar’s group at CICbioGUNE-CIBERehd in the Basque Country.

The “sprinkler system” that stops cell stress caused by fasting  

Their studies have found that hepatic SAMe acts as a metabolic sensor of nutrition, slowing down “fat burning” in the liver and protecting it. The results also showed that during periods of calorie restriction, this SAMe has to be produced in very specific cell sites, where its exerts its protective role.

Dr Varela’s team posits that chronic depletion of SAMe in the liver could be beneficial, signalling our body’s need to “burn fat” and thus enhancing further weight loss during fasting. The findings also showed that chronic SAMe depletion leaves the liver totally unprotected, putting it under excessive stress during the “fat burning”  process necessary for weight loss. 

According to the researchers, this is because SAMe in the liver would act like a “sprinkler system”, putting out the cell  stress that occurs when “fat burning” increases during fasting. Consequently, it is essential to establish a  fine balance between levels of SAMe in the liver that are sufficiently low to induce fat burning, but high enough to protect the liver from this process.