Abstract
4-hydroxy-3-methoxycinnamic acid (ferulic acid, FA) is known to have numerous beneficial health effects, including anti-obesity and anti-hyperglycemic properties. However, the molecular networks that modulate the beneficial FA-induced metabolic effects have not been well elucidated. In this study, we explored the molecular mechanisms mediating the beneficial metabolic effects of FA. In mice, FA protected against high-fat diet-induced weight gain, reduced food intake and exhibited an overall improved metabolic phenotype. The food intake suppression by FA was accompanied by a specific reduction in hypothalamic orexigenic neuropeptides, including agouti-related protein and neuropeptide Y, with no significant changes in the anorexigenic peptides pro-opiomelanocortin and cocaine and amphetamine-regulated transcript. FA treatment also inhibited fat accumulation in the liver and white adipose tissue and suppressed the expression of gluconeogenic genes, including phosphoenolpyruvate carboxylase and glucose-6-phosphatase. Furthermore, we show that FA phosphorylated and inactivated the transcription factor FoxO1, which positively regulates the expression of gluconeogenic and orexigenic genes, providing evidence that FA might exert its beneficial metabolic effects through inhibition of FoxO1 function in the periphery and the hypothalamus.
Highlights
Obesity is a chronic disorder of energy homeostasis that is associated with numerous health complications, including type II diabetes.[1]
We observed that FA markedly reduced the high-fat diet (HFD)-induced increase in serum leptin level (Figure 1i) and decreased food intake (Figure 1b and c), suggesting that FA might be involved in the regulation of leptin sensitivity
We explored the molecular mechanisms mediating the beneficial metabolic effects of FA using a HFD-induced obese mouse model and in vitro analyses
Summary
Obesity is a chronic disorder of energy homeostasis that is associated with numerous health complications, including type II diabetes.[1]. The transcription factor FoxO1 is a downstream target of the PI3K/AKT pathway, which is important for various physiological processes including the regulation of energy homeostasis.[10,11,12] In the hypothalamus, insulin and leptin converge at the AKT/FoxO1 pathway to regulate the expression of both orexigenic and anorexigenic genes.[13,14,15,16] FoxO1 upregulates the expression of AgRP but inhibits POMC expression, promoting food intake. Leptin and insulin antagonize the effects of FoxO1 by phosphorylating and inactivating FoxO1 to suppress food intake.[17,18,19] In peripheral tissues, FoxO1 regulates the expression of key gluconeogenic genes, phosphoenolpyruvate carboxylase (PEPCK) and glucose6-phosphatase (G6P),[20] demonstrating the important role of
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
