The findings, published in Cell Metabolism, focus on the role of a little-known hormone called Fibroblast Growth Factor 21 (FGF21) – the so-called ‘fountain of youth’ hormone produced primarily in the liver.
Previous studies have shown that FGF21 plays a role in curbing appetite, moderating metabolism, improving the immune system and extending lifespan. It is also currently being used as a therapeutic target for diabetes, though little is known about how this hormone is triggered and released in the body.
Now researchers from the Charles Perkins Centre in Sydney, Australia, have found that diets high in carbohydrate and low in protein are the best for boosting levels of FGF21 in mice.
“Fibroblast growth factor 21 (FGF21) is the first known endocrine signal activated by protein restriction. Although FGF21 is robustly elevated in low-protein environments, increased FGF21 is also seen in various other contexts such as fasting, overfeeding, ketogenic diets, and high-carbohydrate diets, leaving its nutritional context and physiological role unresolved,” the study notes.
Therefore, researchers used the Geometric Framework, a nutritional modelling platform, to help reconcile these apparently conflicting findings in mice confined to one of 25 diets that varied in protein, carbohydrate, and fat content.
These diets ranged from five to 60% protein and five to 75% carbohydrate and fat.
“We show that FGF21 was elevated under low protein intakes and maximally when low protein was coupled with high carbohydrate intakes,” the study adds.
Later life health
According to lead author Dr Samantha Solon-Biet, despite the popularity of high protein ‘paleo’ diets, “our research suggests the exact opposite may be best for us as we age – that a low protein, high carbohydrate diet was the most beneficial for later life health and longevity.”
“The nutritional context in which FGF21 is most elevated is dependent on the balance of protein to carbohydrate, and this balance was also shown to be important in how this hormone helps to mediate protein hunger.
“These findings take us one step closer to understanding how FGF21 works, and as an extension of that to be able to use FGF21 to help people live longer and healthier lives.”
The study also revealed that when high carbohydrate diets increased FGF21 levels, the mice compensated for the excess by burning more energy. Conversely in a starvation state, FGF21 promoted energy conservation.
“FGF21 has been shown to be elevated in really paradoxical conditions: in starvation and obesity, in cases of both insulin resistance and sensitivity and when there’s a high and a low intake of food,” said co-author Professor Stephen Simpson, academic director of the Charles Perkins Centre.
“It appears that FGF21 is really switched on by a low protein intake, and its metabolic effects vary on whether it’s coupled with high energy or low energy.”
He added that discovering more about how FGF21 is activated opens the way for nutritional interventions to chronic health problems, including as a potential drug target for the treatment of diabetes and other metabolic disorders.
The next step will be to identify FGF21’s exact signalling pathway in order to better tailor diets and nutritional guidelines to generate the maximum benefit from the hormone.
The study concluded: “We have shown that the geometric framework can help to reconcile apparently contradictory reports regarding the significance of an elevation of FGF21 and its metabolic effects, which are highly dependent on nutritional context. An important next step will be to determine whether elevation of FGF21 is coupled to the specific control of protein appetite, and how it modulates metabolic outcomes in a manner that reflects the nutritional context of the animal.”
The study was conducted in collaboration with the ANZAC Research Institute, Macquarie University, EWOS Innovation in Norway and the Pennington Biomedical Research Centre in Louisiana, USA.
Source: Cell Metabolism
http://dx.doi.org/10.1016/j.cmet.2016.09.
“Defining the Nutritional and Metabolic Context of FGF21 Using the Geometric Framework”
Authors: Samantha M. Solon-Biet, et al