Deleting fatty acid-binding proteins may lead to lifelong metabolic health.
Conditions such as obesity, inflammation, insulin resistance, type 2 diabetes, and fatty liver disease can threaten metabolic and overall health. While it is advised that individuals participate in physical activity and have a healthy lifestyle to prevent disease, many still develop these conditions.
Findings from a new Cell Reports study suggest that lifelong metabolic health may be achievable through deletion of fatty acid-binding proteins (FABPs). Although a lack of FABPs was found to drastically increase metabolic health in mouse models, it did not extend lifespan.
“From a public health perspective, extending the number of years that people are healthy would be a huge achievement,” said co-first author Gökhan S. Hotamisligil, PhD, MD. “Our findings show that this may be possible through a mechanism that can be translated into human populations through pharmacological and nutritional interventions.”
FABPs are escort proteins that bind to fat molecules, transport them inside cells, and regulate their biological effects, according to the authors.
Previous studies show that FABP-deficient mice fed a high-fat or high-cholesterol diet did not develop diabetes, fatty liver, or heart disease.
Metabolic health tends to worsen during aging, which may contribute to an increase in chronic disease and mortality later in life. Many studies have suggested that high-calorie diets affect metabolism and increase aging, while low-calorie diets can prevent metabolic diseases and extend life.
In the study, the authors investigated the metabolic health of FABP-deficient mice throughout their life.
They discovered that a lack of FABP lowered the prevalence of age-related weight gain, inflammation, insulin resistance, insulin sensitivity, and other metabolic factors, according to the study. These metabolic effects were most pronounced in female mice.
Interestingly, there was no improvement in lifespan or in muscular, cognitive, or cardiac function.
The authors noted distinct similarities between the changes in tissue gene expression and metabolite signatures in FABP-deficient mice and changes spurred by calorie restriction, according to the study.
These results suggest that mimicking the metabolic benefits of calorie restriction through targeting FABPs may be a possibility. Additionally, the authors hypothesize that it could be possible to identify other pathways that increase lifespan or other ways to preserve metabolic health, according to the study.
“These simple proteins carry many fascinating mysteries that could unlock some of the greatest challenges to human health,” Dr Hotamisligil said.