Non-alcoholic fatty liver disease (NAFLD) is a liver condition characterized by hepatic fat accumulation (hepatic steatosis) in the absence of excessive alcohol consumption. This disorder represents the most common form of chronic liver disease and is associated with obesity, aging and diabetes. An increasing body of evidence suggests a strong connection between reduced skeletal muscle mass/function and NAFLD, but the underlying mechanisms remain unknown. It has been suggested that skeletal muscle mediates some of the systemic benefits of physical exercise through the secretion of multiple bioactive proteins called myokines. Follistatin- like-1 (Fstl1) is an emerging myokine that is upregulated in a mouse model that mimics strength training- induced muscle growth, and has been shown to be upregulated in humans by either aerobic or strength training. Nothing is known about the potential metabolic actions of this myokine. The present project will test the hypothesis that skeletal muscle-derived Fstl1 exerts protective metabolic actions in the liver, preventing obesity-induced hepatic lipid accumulation and associated insulin resistance. This project has two specific aims: 1. To examine the effects of skeletal muscle-derived Fstl1 in the development of hepatic steatosis and insulin resistance in obese mice; 2. To investigate the role of AMPK signaling in the protective effects of Fstl1 against hepatic steatosis

Public Health Relevance

An increasing body of evidence suggests a strong connection between reduced skeletal muscle mass/function and non-alcoholic fatty liver disease (NAFLD), but the underlying mechanisms remain unknown. It has been suggested that skeletal muscle mediates some of the systemic benefits of physical exercise through the secretion of multiple bioactive proteins called myokines. We hypothesize that Follistatin-like-1 (Fstl1) is a myokine with protective metabolic actions that attenuates NAFLD and associated insulin resistance.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21AG052160-01A1
Application #
9181162
Study Section
Integrative Physiology of Obesity and Diabetes Study Section (IPOD)
Program Officer
Macchiarini, Francesca
Project Start
2016-09-15
Project End
2018-05-31
Budget Start
2016-09-15
Budget End
2017-05-31
Support Year
1
Fiscal Year
2016
Total Cost
$246,750
Indirect Cost
$96,750
Name
Boston University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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