TY - JOUR
T1 - Lipid-regulating properties of butyric acid and 4-phenylbutyric acid
T2 - Molecular mechanisms and therapeutic applications
AU - He, Bo
AU - Moreau, Régis
N1 - Funding Information:
This work was supported in part by the Nebraska Agricultural Experiment Station with funding from the Hatch Act (Accession Number 230874) through the USDA National Institute of Food and Agriculture.
Publisher Copyright:
© 2019 Elsevier Ltd
PY - 2019/6
Y1 - 2019/6
N2 - In the past two decades, significant advances have been made in the etiology of lipid disorders. Concomitantly, the discovery of liporegulatory functions of certain short-chain fatty acids has generated interest in their clinical applications. In particular, butyric acid (BA) and its derivative, 4-phenylbutyric acid (PBA), which afford health benefits against lipid disorders while being generally well tolerated by animals and humans have been assessed clinically. This review examines the evidence from cell, animal and human studies pertaining to the lipid-regulating effects of BA and PBA, their molecular mechanisms and therapeutic potential. Collectively, the evidence supports the view that intakes of BA and PBA benefit lipid homeostasis across biological systems. We reviewed the evidence that BA and PBA downregulate de novo lipogenesis, ameliorate lipotoxicity, slow down atherosclerosis progression, and stimulate fatty acid β-oxidation. Central to their mode of action, BA appears to function as a histone deacetylase (HDAC) inhibitor while PBA acts as a chemical chaperone and/or a HDAC inhibitor. Areas of further inquiry include the effects of BA and PBA on adipogenesis, lipolysis and apolipoprotein metabolism.
AB - In the past two decades, significant advances have been made in the etiology of lipid disorders. Concomitantly, the discovery of liporegulatory functions of certain short-chain fatty acids has generated interest in their clinical applications. In particular, butyric acid (BA) and its derivative, 4-phenylbutyric acid (PBA), which afford health benefits against lipid disorders while being generally well tolerated by animals and humans have been assessed clinically. This review examines the evidence from cell, animal and human studies pertaining to the lipid-regulating effects of BA and PBA, their molecular mechanisms and therapeutic potential. Collectively, the evidence supports the view that intakes of BA and PBA benefit lipid homeostasis across biological systems. We reviewed the evidence that BA and PBA downregulate de novo lipogenesis, ameliorate lipotoxicity, slow down atherosclerosis progression, and stimulate fatty acid β-oxidation. Central to their mode of action, BA appears to function as a histone deacetylase (HDAC) inhibitor while PBA acts as a chemical chaperone and/or a HDAC inhibitor. Areas of further inquiry include the effects of BA and PBA on adipogenesis, lipolysis and apolipoprotein metabolism.
KW - Chemical chaperone
KW - HDAC
KW - Lipogenesis
KW - Lipolysis
KW - Lipoprotein
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U2 - 10.1016/j.phrs.2019.04.002
DO - 10.1016/j.phrs.2019.04.002
M3 - Review article
C2 - 30954630
AN - SCOPUS:85064249672
SN - 1043-6618
VL - 144
SP - 116
EP - 131
JO - Pharmacological Research
JF - Pharmacological Research
ER -