Citrus aurantium flavonoids inhibit adipogenesis through the Akt signaling pathway in 3T3-L1 cells

Kim, Gon Sup; Park, Hyoung Joon; Woo, Jong-Hwa; Kim, Mi-Kyeong; Koh, Phil-Ok; Min, Wongi; Ko, Yeoung-Gyu; Kim, Chung-Hei; Won, Chung-Kil; Cho, Jae‐Hyeon

doi:10.1186/1472-6882-12-31

Cited by 103 publications

(85 citation statements)

References 38 publications

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“…The expression of C/EBPα and PPAR-γ cross-regulate each other through a positive feedback loop and induce the expression of downstream target genes, such as aP2 and LPL, which leads to the appearance of lipid droplets. These markers appear sequentially during differentiation, following a time-dependent expression pattern (20,21). In the present study, we found that GLP-1 significantly promoted the expression of adipocyte-specific markers aP2 and LPL in a dose-and time-dependent manner.…”

Section: Discussionsupporting

confidence: 53%

“…Furthermore, it has been reported that phosphorylation of Akt reduces the expression of forkhead transcriptional factor 1 (Foxo1), which is an antagonist of PPAR-γ, thus enhancing the expression of PPAR-γ indirectly and promoting adipogenesis (25,26). In addition, Akt phosphorylation activates C/EBPα during preadipocyte differentiation (21). Our findings revealed that for cells cultured in induction medium, Akt phosphorylation was rapidly induced after 15 min and reached a peak level at 2 h, which was maintained for 24 h after the initial stimulation with induction medium.…”

Section: Discussionmentioning

confidence: 99%

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Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Yang

Ren

Song

et al. 2013

International Journal of Molecular Medicine

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Abstract. Glucagon-like peptide 1 (GLP-1), a gut-derived peptide, has been reported to have profound effects on metabolism and to reduce insulin resistance. Adipocyte hyperplasia stimulated by preadipocyte differentiation has a positive effect on adipose tissue insulin sensitivity. However, it remains less clear whether GLP-1 plays a role in adipogenesis. In this study, we examined the effect of GLP-1 on preadipocyte differentiation and investigated the mechanisms that may be involved in this effect. In our 3T3-L1 cell study, we tested the levels of adipocyte-specific markers and signaling pathways during preadipocyte differentiation. In addition, Oil Red O staining was used to examine lipid accumulation. Image Pro Plus 5.02 was used to analyze the size and number of lipid droplets. We found that GLP-1 elevated the protein expression levels of free fatty acid-binding protein 4 (aP2) and the transcription factor peroxisome proliferator-activated receptor-γ (PPAR-γ) in a dose-dependent manner during 3T3-L1 preadipocyte differentiation. Furthermore, RT-PCR results showed that GLP-1 promoted CCAAT/enhancer-binding protein α (C/EBPα) and lipoprotein lipase (LPL) expression at the transcriptional level. These data suggest that GLP-1 promotes preadipocyte differentiation. Our study also found that treatment of the cells with 100 nM GLP-1 enhanced the phosphorylation of Akt signaling during the first 24 h of differentiation. Although Oil Red O staining showed that GLP-1 had no significant effect on lipid accumulation, there were increased numbers of small adipocytes in the cells treated with 100 nM GLP-1. Taken together, these results indicate that GLP-1 regulates 3T3-L1 adipogenesis and the Akt signaling pathway may be involved in this process. The differentiated small adipocytes may have a positive effect against insulin resistance and obesity. IntroductionThe growing prevalence of obesity constitutes a major health problem worldwide (1). Obesity, particularly abdominal obesity, has a strong relationship with insulin resistance and is a major risk factor for type 2 diabetes and cardiovascular disease (2,3). The imbalance between energy intake and expenditure contributes to the development of obesity (1,4); the cellular mechanisms for which include the expansion of white adipose tissue via the hypertrophy of preexisting adipocytes and hyperplasia resulting from the adipogenesis of preadipocytes (4,5). When animals are maintained on a highfat diet, adipo cyte cell size initially increases, followed by an increase in fat cell number upon prolonged over-nutrition (6). In adults, ~10% of fat cells are renewed from preadipocytes annually (7). One study in adults demonstrated that short-term overfeeding increases the adipocyte cell numbers (8). Thus, adipogenesis probably has a role in the pathology of obesity in human adults. However, there are significant differences in lipid and glucose metabolism between adipocyte hypertrophy and hyperplasia (9-11). Recent studies have shown that adipocyte hypertrophy is negatively corre...

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes

Yang

Ren

Song

et al. 2013

International Journal of Molecular Medicine

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“…FAS is involved in energy metabolism, and is associated with various human diseases, including obesity, cardiovascular disease and cancer. Previous studies have reported that epigallocatechin 3-gallate (EGCG) in flavonoids may inhibit FAS in the liver of broiler chickens (32,33). In the present study, the majority of the flavonoids successfully reduced the relative weight of epididymal adipose tissue.…”

Section: Discussionsupporting

confidence: 56%

Hypolipidemic effects of flavonoids extracted from Lomatogonium rotatum

Zhang

Wang

2016

Experimental and Therapeutic Medicine

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Abstract. Contained in the Mongolian volumes of Chinese Materia Medica, Lomatogonium rotatum Fries ex Nym. may reduce blood lipid levels and prevent obesity; however, its exact mechanism of action remains unclear. The present study investigated the hypolipidemic and obesity-inhibiting effects of four similarly structured flavonoids extracted from L. rotatum. According to a well-established method, flavonoids such as decussatin were extracted from the whole herb of L. rotatum, and male Wistar rats were subsequently fed a high-fructose diet supplemented with flavonoids (20 mg/kg) for 12 weeks. The levels of total cholesterol, triglyceride (TG), low-density lipoprotein-cholesterol and high-density lipoprotein-cholesterol (HDL-C) were detected. In addition, hepatic and epididymal adipose tissues were weighed, and levels of blood glucose, alanine aminotransferase, aspartate aminotransferase, non-esterified fatty acid, insulin and leptin were determined. The mRNA expression levels of fatty acid synthase (FAS) were analyzed using a reverse transcription polymerase chain reaction; whereas FAS, adenosine monophosphate-activated protein kinase (AMPK) and threonine-172 phosphorylated AMPK protein levels were detected by western blotting. The epididymal adipose tissues of rats fed with flavonoids were lighter, as compared with those fed with fructose in the model group. Following a 12-week administration of flavonoids, the serum levels of fasting blood glucose, feeding blood glucose and leptin were decreased. Furthermore, flavonoid treatment reduced TG and cholesterol levels in the blood and increased serum HDL-C levels, as compared with the model group. High-fructose diet administration significantly increased FAS mRNA and protein expression levels, whereas the FAS protein levels of flavonoid-treated rats were markedly reduced.The flavonoid compounds also enhanced threonine-172 phosphorylation of AMPK in the liver lysate, and all flavonoids successfully downregulated leptin levels and the majority decreased the relative weights of epididymal adipose tissue. Therefore, flavonoids may function in a similar way to epigallocatechin gallate, which has previously been shown to inhibit FAS activity by stimulating AMPK in hepatocyte cells via the liver kinase B1 pathway.

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“…Plants contain phenolic compounds that experimentally exhibited properties of anti inflammatory (Menichini et al, 2011), anti microbial (Yi et al, 2008), anti adipogenesis (Kim et al, 2012a), and anti diabetic (Kim et al, 2009). All parts of plant such as fruit, seed, leave and root contain phenolic compounds to different extents (Kondo et al, 2002;Olabinri et al, 2009).…”

Section: Introductionmentioning

confidence: 99%