Lausanne, Switzerland – March 2nd, 2016. Restricting our calorie intake is the most powerful nutritional approach so far discovered to protect us against metabolic disease. Not only has it been shown to delay age-related physical decline; it can even increase lifespan in some organisms.
However, humans find it difficult to stick to a calorie restriction regime. The fact that an increasing number of us are suffering from obesity, cardiovascular disease and type 2 diabetes means there are potentially huge benefits to society in understanding exactly how calorie restriction can improve our health, in the hope of developing alternative treatments that mimic or boost its effects.
Research has shown that the enzyme SIRT1 might act as a mediator of the health benefits of calorie restriction. As a result, numerous attempts have been made to discover pharmacological ways to activate SIRT1 as a possible method to mimic the beneficial effects of calorie restriction.
Several SIRT1-activating compounds have been proposed during the last decade, including polyphenols such as resveratrol, but their exact mechanisms of action have been called into question. So researchers from the Nestlé Institute of Health Sciences set out to explore in detail the changes brought about by calorie restriction and SIRT1 activation in a range of tissues, and establish whether or not the enzyme really can mimic calorie restriction.
The results, published today in one of the top journals in the field, Cell Reports(1), demonstrate that SIRT1 activation neither mimics nor boosts the health benefits of calorie restriction. SIRT1 activation and calorie restriction both lead to improvements in glucose metabolism and insulin sensitivity, but the mechanism by which they provide these benefits is different. Furthermore, in some tissues, the two strategies can lead to opposite effects. This is the case, for example, in brown adipose tissue (also known as brown fat) where SIRT1 increases insulin sensitivity, while calorie restriction represses it. Exactly the opposite happens in several other tissues such as the liver, muscle and white adipose tissue, where SIRT1 activation has no major influence.
“Our research has finally shown that SIRT1 does not offer a ‘silver bullet’ to mimic the wide palette of health benefits promoted by calorie restriction”, explains Carles Cantó, who led the team. “While not mimicking calorie restriction, it is important to highlight that SIRT1 activation strategies still hold considerable potential in the management of metabolic disease, as we demonstrated in another recent publication(2).”
Cantó continues: “In addition, we have uncovered a number of potential gene sets regulated by calorie restriction. These, subject to further research, could lead to the design of better nutritional interventions which do indeed mimic the beneficial effects of calorie restriction. Such nutritional interventions could be particularly relevant not only for patients at risk of metabolic disease, but also for age-related metabolic complications.
Ed Baetge, head of NIHS, adds: “Unravelling the molecular aspects underlying the metabolic benefits of some lifestyle interventions, such as physical activity or calorie restriction, is of paramount interest to NIHS. Such findings allow us to better define strategies aimed to maintain health through targeted nutrition. In addition, this work sheds light on the unique and differential benefits of diverse strategies, including calorie restriction, exercise training or SIRT1 activation”.
Our goal is to take advantage of these different therapeutic edges to better tailor nutritional interventions to specific metabolic and patient needs.”
NIHS is a biomedical research institute, part of Nestlé’s global R&D network, dedicated to fundamental research aimed at understanding health and disease and developing science-based, targeted nutritional solutions for the maintenance of health. To achieve its aim, NIHS employs state-of-the-art technologies and biological models to characterise health and disease with a holistic and integrated approach. The ultimate goal of the Institute is to develop knowledge that can empower people to better maintain their health through nutritional approaches, especially in relation to their molecular profile and lifestyle status.
1) Boutant, M., Kulkarni, S.S., Joffraud, M., Raymond, F., Métairon, S., Descombes, P. and Cantó, C. SIRT1 gain-of-function does not mimic or enhance the adaptations to intermittent fasting. Cell Reports, 2016 March 8; 14: 1-8
2) Boutant, M., Joffraud, M., Kulkarni, S.S., García-Casarrubios, E., García-Roves, P.M., Ratajczak, J., Fernández-Marcos, P.J., Valverde, A.M., Serrano, M. and Cantó, C. SIRT1 enhances glucose tolerance by potentiating brown adipose tissue function. Mol Metab, 2014 Dec 18; 4(2): 118-31.
For enquiries, please contact:
Laura Camurri, Communications, NIHS