Reduction of lipid accumulation in HepG2 Cells by luteolin is associated with activation of AMPK and Mitigation of oxidative stress

Abstract

The present study was carried out to investigate the lipid-lowering effect of luteolin by using a cell model of steatosis induced by palmitate. Incubation of HepG2 cells with palmitate markedly increased lipid accumulation (Oil Red O staining), the genes involved in lipogenesis, including fatty acid synthase (FAS) and its upstream regulator sterol regulatory element binding protein 1c (SREBP-1c), and reactive oxygen species (ROS) production. Luteolin enhanced the phosphorylation of AMP-activated protein kinase α (AMPKα) and its primary downstream targeting enzyme, acetyl-CoA carboxylase (ACC), up-regulated gene expression of carnitine palmitoyl transferase 1 (CPT-1), which is the rate-limiting enzyme in mitochondrial fatty acid β-oxidation, and down-regulated SREBP-1c and FAS mRNA levels in the absence and presence of palmitate. In addition, luteolin significantly decreased ROS production and ameliorated lipid accumulation in HepG2 cells caused by palmitate. Furthermore, intracellular triglyceride (TG) measurement indicated that the luteolin-mediated reduction of enhanced TG caused by palmitate was blocked by pretreatment with the AMPK inhibitor, compound C. The results suggested that the lipid-lowering effect of luteolin might be partially mediated by the up-regulation of CPT-1 and down-regulation of SREBP-1c and FAS gene expression, possibly by activation of the AMPK signaling pathway, and partially might be through its antioxidative actions.

Identification of the Flavonoid Luteolin as a Repressor of the Transcription Factor Hepatocyte Nuclear Factor 4α

“…However, we cannot exclude the possibility that the receptor localized to the plasma membrane senses luteolin and that the addition of glucoside makes it inaccessible to the receptor. It has been reported that luteolin enhances the phosphorylation of AMP-activated protein kinase in HepG2 cells (38), and AMP-activated protein kinase directly phosphorylates HNF4␣ and represses its transcriptional activity (39). Thus, it is conceivable that luteolin indirectly suppressed HNF4␣ activity through the stimulation of AMP-activated protein kinase signaling in addition to direct binding to its LBD as an antagonist.…”

Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages

“…It has previously been reported that LU can activate AMPK signalling in differentiated 3T3-L1 adipocytes [24] and HepG2 hepatocytes [23]. In addition, AMPK, as an important nutrient sensor, can promote fatty acid oxidation [37] and energy expenditure [38].…”

“…The catalytic subunit AMPKα1 is mainly expressed in macrophages and suppresses associated proinflammatory responses and polarisation [21,22]. Previous studies have reported that LU can enhance the phosphorylation of AMPK in HepG2 cells [23] and 3T3-L1 adipocytes [24]. Therefore, the functional correlation between LU and AMPKα1 signalling in ATM inflammation and polarisation should be assessed.…”

A comparative study of the antioxidant, antimicrobial, cytotoxic and thrombolytic potential of the fruits and leaves of Spondias dulcis

“…About 2.0 mL of methanol solution of each extract at different concentration (2,4,6,8,10 µg/mL) were mixed with 3.0 mL of DPPH methanol solution (20 µg/mL). After an incubation period of 30 min, the absorbance was measured at 517 nm against methanol as blank by using a UV-visible spectrophotometer.…”

“…Because of their potent pharmacological activity, low toxicity and economic feasibility, investigation of the medicinal properties of plant has been performed [1] . Along with the nutritional value, plants contribute in the protection from free radical deterioration by hindrance of lipid peroxidation via numerous mechanisms including scavenging free radicals [2] , inducing antioxidant enzymes [3] , modulating protein kinase, and lipid kinase signaling pathway [4] , inhibiting cyclooxygenase-2 (COX 2) and matrix metalloproteinases (MMP 2 and MMP 9) enzymatic activity [5,6] , influencing phytoestrogenic and nuclear transcription factor NF-κB [7,8] , inducing cell cycle arrest and phase 1 or phase 2 metabolizing enzymes [9,10] . Oxidative damage done by free radicals causes the pathogenesis of many deadly diseases like cancer, Alzheimer's and diabetes [11] .…”