A range of age-related metabolic diseases may be prevented by lowering the levels of certain proteins called "fatty acid-binding proteins."
Metabolic health may be preserved well into old age, a new study suggests, if we keep fatty acid-binding protein (FABP) levels very low. These proteins are tasked with "grabbing" fat molecules and "guiding" them within the cell.
In the new study, researchers from the Harvard T.H. Chan School of Public Health in Boston, MA, altered levels of these proteins in mice in an attempt to see whether doing so would promote metabolic health, and, implicitly, lifespan.
The team was led by Gökhan S. Hotamisligil, chair of the Department of Genetics and Complex Diseases and the Sabri Ülker Center at the Harvard T.H. Chan School of Public Health, and the findings were published in the journal Cell Reports.
Why study FABPs?
Hotamisligil and his team were prompted in their research by existing studies that have suggested that a high-calorie diet slows down metabolism and accelerates the aging process.
Conversely, calorie restriction has been shown to slow down aging and protect against age-related metabolic diseases.
Although this observation was made as early as 1935, researchers are still trying to unravel the mysterious mechanism behind the benefits of calorie restriction.
Moreover, as the authors of the new paper explain, it is unclear whether or not the "preservation of cardiometabolic health is sufficient to extend lifespan."
So, in an effort to find out, Hotamisligil and colleagues genetically engineered mice so that they lacked FABPs. These mice, they explain, shared "molecular and lipidomic features" with mouse models of calorie restriction.
Another reason for their decision to study FABPs is that previous work by Hotamisligil found that mice with deficient levels of FABPs who were fed a diet high in fat or cholesterol did not develop cardiometabolic diseases such as type 2 diabetes, fatty liver disease, or cardiovascular disease.
FABP deficiency extended metabolic lifespan
The researchers designed several cohorts of such FABP-deficient rodents and followed them throughout their lives.
The study found that insufficient FABP levels "extended metabolic healthspan, [protecting] against insulin resistance and glucose intolerance, inflammation, deterioration of adipose tissue integrity, and fatty liver disease."
But "surprisingly," write the authors, "FABP-deficient mice did not [show] any extension of lifespan."
"These data," the team explains, "indicate that extension of metabolic healthspan in the absence of [calorie restriction] can be uncoupled from lifespan, indicating the potential for independent drivers of these pathways."
In other words, the mice shared many similarities with rodents that had undergone calorie restriction. Therefore, some of the cardiometabolic benefits of calorie restriction could be selectively replicated by targeting FABPs.
"These simple proteins," says Hotamisligil, "carry many fascinating mysteries that could unlock some of the greatest challenges to human health."
"From a public health perspective, extending the number of years that people are healthy would be a huge achievement. [...] Our findings show that this may be possible through a mechanism that can be translated into human populations through pharmacological and nutritional interventions."
Gökhan S. Hotamisligil