Kaempferol reduces hepatic triglyceride accumulation by inhibiting Akt

Abstract

In this paper, we studied the mechanism of the triglyceride (TG)‐lowering effect of kaempferol in vitro and in vivo. Kaempferol showed LXR agonistic activities without inducing TGs or the expression of several lipogenic genes in cultured cells. A luciferase and qPCR analysis showed that kaempferol increased the transactivation of PPARα and PPARδ and stimulated gene expression associated with fatty acid oxidation and uptake in hepatocytes. More importantly, kaempferol inhibited protein kinase B (Akt) activity and suppressed SREBP‐1 activation via multiple mechanisms, including through increasing Insig‐2a expression, reducing SREBP‐1 phosphorylation, and increasing GSK‐3 phosphorylation. Collectively, these actions inhibited the SREBP‐1 activation process. Furthermore, as an Akt/mTOR pathway inhibitor, kaempferol led to the induction of hepatic autophagy and resulted in a decrease in lipid droplet formation in the mouse liver. These findings demonstrate that kaempferol exerts its TG‐lowering effect via Akt inhibition and activation of PPARα and PPARδ. Practical applications Kaempferol is a major dietary flavonoid in various plant‐based foods, and it is used as a valuable ingredient in functional foods, with numerous beneficial properties such as anticancer, antioxidant, and anti‐atherosclerotic activities. Kaempferol exerts its TG‐lowering effect via Akt inhibition and activation of PPARα and PPARδ. Currently, the number of people with hyperlipidemia is rapidly growing in both developed and developing societies; thus, we propose that kaempferol could be used for therapeutic interventions aimed at the treatment of these individuals.

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…As quercetin, kaempferol is also able to reduce lipid accumulation in liver of obese rodent models. In dyslipidemia-induced mice, kaempferol inhibited PKB (Akt) and SREBP-1 activities and blocked the Akt/mTOR pathway, thus inducing hepatic autophagy and decreasing hepatic lipid content [ 251 ]. Similarly, in ApoE deficient mice fed with a HFD, kaempferol attenuated metabolic syndrome via interacting with LXR receptors and inhibiting posttranslational activation of SREBP-1.…”

Flavonoid Library Screening Reveals Kaempferol as a Potential Antiviral Agent Against African Swine Fever Virus

“…Past studies have reported that kaempferol may induce autophagy in various cell lines ( Huang et al, 2013 ; Varshney et al, 2017 ; Hoang et al, 2019 ). On the other hand, it has been shown that autophagy induction hampers ASFV infection in vitro ( Hernaez et al, 2013 ).…”

“…Besides its anti-entry activity, kaempferol also displayed potent anti-ASFV activity at a post-entry stage, suppressing viral infection by more than 90% when it was added at early phases of infection (0 to 4h post-infection). It is well established that kaempferol may induce autophagy in different cell lines through the upregulation of p-AMP-activated protein kinase ( Huang et al, 2013 ; Varshney et al, 2017 ; Hoang et al, 2019 ). Autophagy is a self-degradation process that is conserved among eukaryotic cells.…”

Molecular Mechanism of Crataegi Folium and Alisma Rhizoma in the Treatment of Dyslipidemia Based on Network Pharmacology and Molecular Docking

“…They also inhibit the formation of foam cells by activating the PPAR γ -ABCA1 pathway and thereby improving lipid levels [ 37 , 38 ]. Kaempferol can inhibit Akt activity, reduce TG levels, as well as induce hepatocyte autophagy and reduce lipid droplet formation in mouse liver by attenuating the Akt/mTOR pathway and activating PPARs [ 39 ]. Zhang et al found that isorhamnetin was a dietary source of the PPAR γ antagonist, which reduced body weight, ameliorated insulin resistance, and alleviated hepatic steatosis through the suppression of PPAR γ transactivity, which was beneficial to obesity and hepatic steatosis [ 40 ].…”