New Target for Fat-Burning Drugs Discovered in Mice Study
METHODOLOGY:
Brown and beige fat tissue burns energy to produce heat in response to cold exposure and, in rodents, protects against obesity and its metabolic consequences; inducing the browning of white adipose tissue in people may be a promising treatment strategy for obesity.
Researchers in China conducted animal experiments to investigate the role of BAP1 in the browning of white adipose tissue and its underlying mechanisms.
They examined BAP1 and its key molecular partners using several genetic variations in mice, including those with BAP1 knockdown or overexpression, those with a knockout of the principal brown fat mediating protein, and wild type.
Mice were evaluated under several conditions, including obesity induced with a high-fat diet and a cold challenge.
They assessed serum and tissues, as well as isolated cells from a fat deposit (inguinal) equivalent to human gluteal and thigh fat, for molecular and phenotypic changes, as well as metabolism-related parameters.
TAKEAWAY:
BAP1 expression was lower in the inguinal white adipose tissue of cold-induced mice but higher in obese conditions.
Overexpression of BAP1 suppressed browning of the white inguinal fat and blocked an energy-burning thermogenesis response.
On a high-fat diet, knockdown mice without BAP1 were spared most of the weight gain, impaired glucose tolerance, and insulin sensitivity experienced by mice with BAP1.
Mechanistically, BAP1 negatively regulates the browning of inguinal white adipose tissue, possibly through a mechanism that inhibits expression of genes essential for browning.
IN PRACTICE:
'Our findings unveil a novel function of BAP1 mediated by KDM1B in iWAT [inguinal white adipose tissue] browning, thereby offering a promising therapeutic target for the treatment of obesity and related metabolic disorders,' the study authors wrote.
SOURCE:
The study was led by Pengchao Wang, Medical College, Huazhong University of Science and Technology, Wuhan, China. It was published online in Diabetes .
LIMITATIONS:
While the study demonstrates BAP1 can inhibit the direct conversion of white fat into beige fat, it may also influence browning by modulating beige adipogenesis. Also, though BAP1 expression remains unchanged in brown adipose tissue during cold exposure, the researchers could not exclude its potential role in thermogenesis, suggesting the existence of other signaling pathways that bypass BAP1 in regulating thermogenesis in brown adipose tissue. Further animal studies are required to provide more compelling evidence, the authors noted.
DISCLOSURES:
The study was supported by grants from Non-Communicable Chronic Diseases – National Science and Technology Major Project, National Natural Science Foundation of China, and Natural Science Foundation of Hubei Province. The authors declared having no conflicts of interest.
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