Min, B.; Kang, H.; Choi, B.; Jeon, Y.H.; Cho, J.; Lee, I.; Kim, D.W. Phenylbutyrate Ameliorates High-Fat Diet-Induced Obesity via Brown Adipose Tissue Activation. Preprints2019, 2019010073. https://doi.org/10.20944/preprints201901.0073.v1
APA Style
Min, B., Kang, H., Choi, B., Jeon, Y.H., Cho, J., Lee, I., & Kim, D.W. (2019). Phenylbutyrate Ameliorates High-Fat Diet-Induced Obesity via Brown Adipose Tissue Activation. Preprints. https://doi.org/10.20944/preprints201901.0073.v1
Chicago/Turabian Style
Min, B., In-Kyu Lee and Dong Wook Kim. 2019 "Phenylbutyrate Ameliorates High-Fat Diet-Induced Obesity via Brown Adipose Tissue Activation" Preprints. https://doi.org/10.20944/preprints201901.0073.v1
Abstract
Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.
Keywords
Phenylbutyrate, PFKL, Obesity, UCP1, Brown adipose tissue
Subject
Biology and Life Sciences, Endocrinology and Metabolism
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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