Targeting 'lipid chaperones' may preserve lifelong metabolic health

October 10, 2017

Researchers have found that, in a mouse model, it may be possible to achieve lifelong metabolic health. The Harvard T.H. Chan School of Public Health scientists found that mice that lack fatty acid-binding proteins (FABPs) exhibit substantial protection against obesity, inflammation, insulin resistance, type 2 diabetes, and fatty liver disease as they age compared with mice that have FABPs. However, this remarkable extension of metabolic health was not found to lengthen lifespan.

"From a public health perspective, extending the number of years that people are healthy would be a huge achievement," said Gökhan S. Hotamisligil, J.S. Simmons Professor of Genetics and Metabolism and chair of the Department of Genetics and Complex Diseases and Sabri Ülker Center at Harvard Chan School. "Our findings show that this may be possible through a mechanism that can be translated into human populations through pharmacological and nutritional interventions."

The study will appear online October 10, 2017 in Cell Reports.

FABPs are escort proteins or "lipid chaperones" that latch onto fat molecules, transport them within cells, and dictate their biological effects. Previous work from Hotamisligil's lab found that when FABP-deficient mice were fed high-fat or high-cholesterol-containing diets, they did not develop type 2 diabetes, fatty liver, or heart disease.

Metabolic health typically deteriorates with age, and researchers believe that this contributes to age-associated chronic diseases and mortality. Studies have shown that high-calorie diets impair metabolism and accelerate aging; conversely, calorie restriction has been shown to prevent age-related metabolic diseases and extend lifespan.

In the new study, Hotamisligil, co-first authors Khanichi Charles, Min-Dian Li, and colleagues examined metabolic function in multiple cohorts of FABP-deficient mice throughout their life. They found that FABP deficiency markedly reduced age-related weight gain, inflammation, deterioration of glucose tolerance, insulin sensitivity, and other metabolic malfunctions. This effect was more strongly observed in female than male mice. Surprisingly however, they did not find any improvement to lifespan or preservation of muscular, cognitive, or cardiac functions with age.

The researchers saw striking similarities between the alterations in tissue gene expression and metabolite signatures in the genetic model of FABP-deficiency developed for this study and the alterations that occur due to calorie restriction. The findings suggest that it may be possible to mimic part of the metabolic benefits of by targeting FABPs. In addition, by examining the molecular differences between these models, it may also be possible to identify other pathways that contribute to longer life span or alternative strategies to prevent metabolic diseases.

"These simple proteins carry many fascinating mysteries that could unlock some of the greatest challenges to human ," said Hotamisligil.

Explore further: How a low-calorie diet could extend lifespan

More information: "Uncoupling of Metabolic Health from Longevity through Genetic Alteration of Adipose Tissue Lipid-Binding Proteins," Khanichi N. Charles, Min-Dian Li, Feyza Engin, Ana Paula Arruda, Karen Inouye, Gökhan S. Hotamisligil, Cell Reports, online October 10, 2017, DOI: 10.1016/j.celrep.2017.09.051

Related Stories

How a low-calorie diet could extend lifespan

June 29, 2016
Overeating can lead to health issues that can shorten one's life, such as obesity, diabetes and heart disease. On the other end of the spectrum, several studies have shown that restricting calorie intake below what a normal ...

Targeting fat-tissue hormone may lead to type 2 diabetes treatment

December 23, 2015
A new study by researchers from Harvard T.H. Chan School of Public Health and colleagues describes the pre-clinical development of a therapeutic that could potentially be used to treat type 2 diabetes, fatty liver disease, ...

Different sugars, different risks to your liver

October 4, 2017
If you're one of the two billion people in the world who are over-weight or obese, or the one billion people with fatty liver disease, your doctor's first advice is to cut calories—and especially to cut down on concentrated ...

Benefits of calorie restriction on par with balancing protein and carb intake in mice

May 28, 2015
Cutting calories through dietary restriction has been shown to lower cholesterol, improve insulin sensitivity, and even prolong life in mammals. Now, new research publishing on May 28th in Cell Reports shows that, at least ...

How calorie restriction may prolong life

May 3, 2017
A new review proposes a theory to explain how calorie restriction can extend life across a variety of species.

Newly identified molecular mechanism plays role in type 2 diabetes development

July 30, 2015
New research from Harvard T.H. Chan School of Public Health describes a molecular mechanism that helps explain how obesity-related inflammation can lead to type 2 diabetes. The findings describe a surprising connection between ...

Recommended for you

Engineered protein treatment found to reduce obesity in mice, rats and primates

October 19, 2017
(Medical Xpress)—A team of researchers with pharmaceutical company Amgen Inc. report that an engineered version of a protein naturally found in the body caused test mice, rats and cynomolgus monkeys to lose weight. In their ...

New procedure enables cultivation of human brain sections in the petri dish

October 19, 2017
Researchers at the University of Tübingen have become the first to keep human brain tissue alive outside the body for several weeks. The researchers, headed by Dr. Niklas Schwarz, Dr. Henner Koch and Dr. Thomas Wuttke at ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Study reveals key molecular link in major cell growth pathway

October 19, 2017
A team of scientists led by Whitehead Institute has uncovered a surprising molecular link that connects how cells regulate growth with how they sense and make available the nutrients required for growth. Their work, which ...

Tracing cell death pathway points to drug targets for brain damage, kidney injury, asthma

October 19, 2017
University of Pittsburgh scientists are unlocking the complexities of a recently discovered cell death process that plays a key role in health and disease, and new findings link their discovery to asthma, kidney injury and ...

Inflammation trains the skin to heal faster

October 18, 2017
Scars may fade, but the skin remembers. New research from The Rockefeller University reveals that wounds or other harmful, inflammation-provoking experiences impart long-lasting memories to stem cells residing in the skin, ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.