Colo. – A newly published study by researchers from the University
of Colorado School of Medicine has identified a potential therapeutic target
for treating obesity and diabetes.
scientists studied the biological function of an epigenetic modifier known as
histone deacetylase 11 (HDAC11), and determined that deleting it in mice
stimulates the formation of brown adipose tissue. The absence of HDAC11 also
triggered beiging of white adipose tissue. These changes are important because
white adipose tissue stores energy, while brown adipose tissue produces heat, thus
expending energy. These findings reveal a regulatory node that could lead to
the development of a pharmaceutical-based therapy for obesity and metabolic
disease based on increasing energy expenditure.
details of the study are
published in the August 9 edition of JCI Insight, a journal published by the
American Society for Clinical Investigation.
first author of the study is Rushita A. Bagchi, PhD, a postdoctoral fellow in
the laboratory of Timothy A. McKinsey, PhD, associate professor of medicine in
the Division of Cardiology, who is the corresponding author of the article.
Both are part of the Consortium for Fibrosis
Research & Translation, a program funded by the School of Medicine to
improve understanding of fibrotic diseases across various organ systems.
findings uncovered a druggable transcriptional pathway for regulation of energy
expenditure, and thus suggest novel approaches for combatting the global
pandemics of obesity and diabetes based on HDAC11 inhibition,” said McKinsey.
is an increasingly common health problem, with more than one-third of the U.S.
population considered obese. Obesity and associated chronic diseases, such as
type 2 diabetes, are projected to affect more than a half billion adults
worldwide by 2040.
lacking HDAC11 were protected from obesity, insulin resistance and other
effects of high-fat feeding. The findings suggest a previously unrecognized
role for HDAC11, and an associated protein known as BRD2, in the control of
our investigation we found that inhibiting HDAC11 increases energy
expenditure, which highlights its potential as a target in obesity and
metabolic disease therapeutic strategies,” said McKinsey. “We now need to
test the role of HDAC11 in large animal models of metabolic disease and in
human cell systems as we attempt to translate these exciting findings to the
authors were listed on the article, “HDAC11 suppresses the thermogenic program
of adipose tissue via BRD2.” Nine of the authors are members of the CU School
of Medicine. The research was supported with funding from the National
Institutes of Health, the American Heart Association, and the Canadian
Institutes of Health Research.