Flavonoids from Triticum aestivum inhibit adipogenesis in 3T3-L1 cells by upregulating the insig pathway

Abstract

Abstract. The present study aimed to compare the potential anti-adipogenic effects and underlying mechanisms of the luteolin, isoscoparin and isoorientin flavonoids, purified from Triticum aestivum sprout (TA) in 3T3-L1 cells. The cells were treated with different concentrations of flavonoids for 8 days and the lipid accumulation was assessed using Oil-Red-O staining. The expression levels of the transcription factors and the genes involved in adipogenesis in the cells were assessed by reverse transcription-quantitative polymerase chain reaction and western blotting. The results demonstrated that 10 µM luteolin, isoscoparin or isoorientin inhibited lipid deposition in the cells by 74, 63 and 65%, respectively. The flavonoids also significantly inhibited the transcriptional regulators of adipogenesis, including peroxisome proliferator-activated receptor-γ, CAAT/enhancer binding protein-α and sterol regulatory element binding protein (SREBP)-1c, compared with the control cells. Similarly, there was a significant downregulation of the adipocyte specific markers associated with lipid metabolism, including activating protein-2, fatty acid synthase, hormone-sensitive lipase and lipoprotein lipase, in the flavonoid treated cells. Notably, the cells treated with the flavonoids demonstrated increased expression levels of the insulin-induced genes, insig-1 and insig-2, which may have inhibited the activation of the adipogenic transcription factor, SREBP, eventually leading to the inhibition of adipogenesis. Taken together, these results revealed that the flavonoids from TA possessed an inhibitory effect on adipogenesis through downregulation of adipogenic transcription factors and genes associated with lipid metabolism, and the upregulation of insig 1 and 2, suggesting that the flavonoids from TA may be potential therapeutic agents for the prevention and treatment of obesity. IntroductionObesity is a major risk factor of metabolic disorders, including type 2 diabetes, hypertension, hyperlipidemia and arteriosclerosis. The development of obesity is characterized by an increase in adipose tissue cell number (hyperplasia) and cell size (hypertrophy) (1). Genetic, metabolic and nutritional factors are crucial in the development of obesity (2). Therefore, understanding the nutrients that affect adipocyte differentiation may assist in reducing the healthcare burden associated with obesity (3). Adipogenesis is the process by which fibroblastic preadipocytes are converted into fat laden adipocytes. The 3T3-L1 cell line is considered an optimal in vitro model to investigate adipogenesis, as it exhibits a high potential to differentiate from a preadipocyte to an adipocyte and also exhibits morphological and biochemical properties similar to the development of obesity in humans (4). Adipogenesis involves the stimulation of a series of transcriptional factors, including peroxisome proliferator-activated receptor-γ (PPARγ), CAAT/enhancer binding protein-α (C/EBPα) and sterol regulatory element binding proteins (SREBPs) (5). Among thes...

Impact of Isoorientin on Metabolic Activity and Lipid Accumulation in Differentiated Adipocytes

“…Natural products are considered a safe approach in treating metabolic syndrome [1], and their therapeutic potential against obesity has been extensively reviewed [2][3][4]. Of interest is isoorientin, a C-glycosyl flavonoid, which is found in rooibos, among other plants, and which displays strong ameliorative effects on obesity-linked complications [5,6]. Isoorientin, also referred to as homoorientin, is a C-glucosyl flavone that was first isolated by Koeppen and colleagues in 1962 from Aspalathus linearis, a South African indigenous plant, which is widely consumed as herbal tea (rooibos) [7,8].…”

Triticumoside induces apoptosis via caspase-dependent mitochondrial pathway and inhibits migration through downregulation of MMP2/9 in human lung cancer cells

“…Previous reports have indicated that extract of TA has antidiabetic, antihyperlipidemic, and anticancer effects [4][5][6][7][8][9]. Moreover, TA extract is known to contain several phytocompounds such as leuteolin, isoscoparin, isoorientin, and triticumoside [10][11][12]. However, there have not yet been any studies on the effects and potential mechanisms of anticancer effects of compounds isolated from TA, until now.…”

Wheatgrass‐Derived Polysaccharide Has Antiinflammatory, Anti‐Oxidative and Anti‐Apoptotic Effects on LPS‐Induced Hepatic Injury in Mice

“…Recent studies have shown phenolic compounds and vitamins synthesized during the sprouting of wheat grass have potent antioxidant and antiinflammatory properties (Benedetti et al, ; Luyen et al, ; Mohan et al, ). In addition, it was also reported recently that a constituent of wheatgrass has anti‐obesity effects (Im et al, ; Luyen et al, ; Poudel et al, ). Furthermore, polysaccharide isolated from wheatgrass was found to reduce blood glucose level in streptozotocin (STZ)‐induced diabetic mice (Mohan et al, ) and has a stimulatory effect on insulin response (Lee et al, ).…”

“…Previous studies have shown that the antioxidant and antiinflammatory properties of wheatgrass constituents are due to the inhibition of NF‐κB activation (Poudel et al, ; Lee et al, ). Several studies have described the anti‐obesity and anti‐diabetic effects of wheatgrass (Luyen et al, ; Lee et al, ).…”