scholarly journals How Does Ginsenoside Rh2 Mitigate Adipogenesis in Cultured Cells and Obese Mice?

Molecules ◽  
2020 ◽  
Vol 25 (10) ◽  
pp. 2412
Author(s):  
Longyun Zhang ◽  
Carlos Virgous ◽  
Hongwei Si

Ginsenoside Rh2, an intermediate metabolite of ginseng, but not naturally occurring, has recently drawn attention because of its anticancer effect. However, it is not clear if and how Rh2 inhibits preadipocytes differentiation. In the present study, we hypothesized that ginsenoside Rh2 attenuates adipogenesis through regulating the peroxisome proliferator-activated receptor gamma (PPAR-γ) pathway both in cells and obese mice. Different concentrations of Rh2 were applied both in 3T3-L1 cells and human primary preadipocytes to determine if Rh2 inhibits cell differentiation. Dietary Rh2 was administered to obese mice to determine if Rh2 prevents obesity in vivo. The mRNA and protein expression of PPAR-γ pathway molecules in cells and tissues were measured by real-time polymerase chain reaction (RT-PCR) and Western blot, respectively. Our results show that Rh2 dose-dependently (30–60 μM) inhibited cell differentiation in 3T3-L1 cells (44.5% ± 7.8% of control at 60 μM). This inhibitory effect is accompanied by the attenuation of the protein and/or mRNA expression of adipogenic markers including PPAR-γ and CCAAT/enhancer binding protein alpha, fatty acid synthase, fatty acid binding protein 4, and perilipin significantly (p < 0.05). Moreover, Rh2 significantly (p < 0.05) inhibited differentiation in human primary preadipocytes at much lower concentrations (5–15 μM). Furthermore, dietary intake of Rh2 (0.1 g Rh2/kg diet, w/w for eight weeks) significantly (p < 0.05) reduced protein PPAR-γ expression in liver and hepatic glutathione reductase and lowered fasting blood glucose. These results suggest that ginsenoside Rh2 dose-dependently inhibits adipogenesis through down-regulating the PPAR-γ pathway, and Rh2 may be a potential agent in preventing obesity in vivo.

2016 ◽  
Vol 44 (03) ◽  
pp. 565-578 ◽  
Author(s):  
Yo-Han Han ◽  
Ji-Ye Kee ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Soyoung Shin ◽  
...  

Rutin, also called rutoside or quercetin-3-O-rutinoside and sophorin, is a glycoside between the flavonol quercetin and the disaccharide rutinose. Although many effects of rutin have been reported in vitro and in vivo, the anti-adipogenic effects of rutin have not been fully reported. The aim of this study was to confirm how rutin regulates adipocyte related factors. In this study, rutin decreased the expressions of adipogenesis-related genes, including peroxisome proliferators, activated receptor [Formula: see text] (PPAR[Formula: see text], CCAAT/enhancer-binding protein [Formula: see text] (C/EBP[Formula: see text], fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase in 3T3-L1 cells. Rutin also repressed the expression of lipin1, which is an upstream regulator that controls PPAR[Formula: see text] and C/EBP[Formula: see text]. In addition, when 3T3-L1 was transfected with lipin1 siRNA to block lipin1 function, rutin did not affect the expressions of PPAR[Formula: see text] and C/EBP[Formula: see text]. These results suggest that rutin has an anti-adipogenic effect that acts through the suppression of lipin1, as well as PPAR[Formula: see text] and C/EBP[Formula: see text].


Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1734 ◽  
Author(s):  
Na-Hyun Kim ◽  
Jonghwan Jegal ◽  
Yun Kim ◽  
Jeong-Doo Heo ◽  
Jung-Rae Rho ◽  
...  

Berries of Aronia melanocarpa (chokeberry) are known to be a rich source of biologically active polyphenols. In the present study, the effects of seven anti-adipogenic polyphenolic phytochemicals isolated from A. melanocarpa methanol extract on adipogenic transcription factors were investigated. Amygdalin and prunasin were found to inhibit 3T3-L1 adipocyte differentiation by suppressing the expressions of PPARγ (peroxisome proliferator-activated receptor γ), C/EBPα (CCAAT/enhancer binding protein α), SREBP1c (sterol regulatory element binding protein 1c), FAS (fatty acid synthase), and aP2 (adipocyte fatty-acid–binding protein). A. melanocarpa extract-treated (100 or 200 mg/kg/day on body weight) high fat diet (HFD)-induced obese mice showed significant decreases in body weight, serum triglyceride (TG), and low-density lipoprotein cholesterol (LDLC) levels and improved insulin sensitivity as compared with HFD controls. This research shows A. melanocarpa extract is potentially beneficial for the suppression of HFD-induced obesity.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Maria Fernanda Roca Rubio ◽  
Ulrika Eriksson ◽  
Robert J. Brummer ◽  
Julia König

AbstractThe intestinal barrier plays a crucial role in maintaining gut health, and an increased permeability has been linked to several intestinal and extra-intestinal disorders. There is an increasing demand for interventions aimed at strengthening this barrier and for in vivo challenge models to assess their efficiency. This study investigated the effect of sauna-induced dehydration on intestinal barrier function (clinicaltrials.gov: NCT03620825). Twenty healthy subjects underwent three conditions in random order: (1) Sauna dehydration (loss of 3% body weight), (2) non-steroidal anti-inflammatory drug (NSAID) intake, (3) negative control. Intestinal permeability was assessed by a multi-sugar urinary recovery test, while intestinal damage, bacterial translocation and cytokines were assessed by plasma markers. The sauna dehydration protocol resulted in an increase in gastroduodenal and small intestinal permeability. Presumably, this increase occurred without substantial damage to the enterocytes as plasma intestinal fatty acid-binding protein (I-FABP) and liver fatty acid-binding protein (L-FABP) were not affected. In addition, we observed significant increases in levels of lipopolysaccharide-binding protein (LBP), IL-6 and IL-8, while sCD14, IL-10, IFN-ɣ and TNF-α were not affected. These results suggest that sauna dehydration increased intestinal permeability and could be applied as a new physiological in vivo challenge model for intestinal barrier function.


2018 ◽  
Vol 46 (01) ◽  
pp. 107-118 ◽  
Author(s):  
Hwa-Jin Kim ◽  
Mi-Kyoung You ◽  
Ziyun Wang ◽  
Hyeon-A Kim

Obesity is the main risk factor for metabolic syndromes and there has been an upsurge in demand for effective therapeutic strategies. This study investigated the effect of red pepper seed water extract (RPS) on the process of differentiation in 3T3-L1 adipocytes. RPS treatment significantly suppressed cellular lipid accumulation and reduced the expression of adipocytes-associated proteins, peroxisome proliferator-activated receptor-[Formula: see text] (PPAR-[Formula: see text]), CCAAT/enhancer-binding proteins [Formula: see text] (C/EBP [Formula: see text]), sterol regulatory element binding protein-1c (SREBP-1c), as well as fatty acid synthase (FAS), and fatty acid binding protein 4 (FABP4). The inhibitory effect of RPS on differentiation was mainly through the modulation of the C/EBP [Formula: see text] and C/EBP [Formula: see text] expression at the early phase of differentiation. Moreover, at the early phase of differentiation, RPS markedly increased the phosphorylation of AMP-activated protein kinase (AMPK). Such enhancing effect of RPS was abolished in the presence of compound C. Our results suggest that activation of AMPK at early stage of adipogenesis is involved in the anti-adipogenesis effect of RPS.


2019 ◽  
Vol 97 (10) ◽  
pp. 4182-4192 ◽  
Author(s):  
Kelsey M Schubach ◽  
Reinaldo F Cooke ◽  
Alice P Brandão ◽  
Osvaldo A de Sousa ◽  
Thiago F Schumaher ◽  
...  

Abstract This study evaluated the effects of supplementing Ca salts of soybean oil (CSSO) to beef steers at 2 mo of age via creep-feeding, and/or during a 40-d preconditioning period on performance and carcass development responses. A total of 64 steers were enrolled in this study over 2 yr (32 steers per year), with 4 periods each year: creep-feeding (CF; day 0 to 60), preweaning (day 61 to weaning on day 124 and 127 of year 1 and 2, respectively), preconditioning (PC; day 132 to 172 in year 1 and day 135 to 175 of year 2), and feedlot (feedlot arrival to slaughter, day 173 to 378 in year 1 and day 176 to 385 in year 2). On day 0 steers were ranked by body weight (BW) and age (114 ± 4 kg of BW; 66.1 ± 0.9 d of age) and allocated to 1 of 16 pens. Pens were randomly assigned to receive CSSO during CF (80 g/d per steer) and/or PC (150 g/d per steer) in a 2 × 2 factorial arrangement of treatments. During CF and PC, nonsupplemented steers (CON) were provided an isolipidic prilled saturated fat supplement. Steer BW was recorded on day 0, 60, at weaning, and prior to feedlot shipping. Carcass traits were recorded upon slaughter. On day 0, 60, at weaning, prior to feedlot shipping, and during the feedlot period, blood samples were collected and longissimus muscle (LM) biopsies were collected. On day 60, steers that received CSSO during CF had greater (P < 0.01) plasma concentrations of linoleic and ω-6 compared with CON (CF treatment × day; P ≤ 0.05). Steers that received CSSO during PC had greater (P < 0.01) plasma concentrations of linoleic, ω-6, and total fatty acids compared with CON at feedlot shipping (PC treatment × day; P ≤ 0.05). A PC treatment × day interaction was also detected (P = 0.04) for mRNA expression of peroxisome proliferator-activated receptor gamma (PPAR-γ), which was greater (P = 0.04) at feedlot shipping for steers receiving CSSO during PC. Interactions between CF treatment × day were detected (P ≤ 0.01) for mRNA expression of adipocyte fatty acid-binding protein, fatty acid synthase, PPAR-γ, and stearoyl-CoA desaturase, which were greater (P ≤ 0.02) in the feedlot in steers receiving CSSO during CF. No treatment differences were detected for (P ≥ 0.18) performance or carcass traits, including marbling and backfat thickness. Results from this study suggest that supplementing CSSO to suckled beef steers via creep-feeding upregulated mRNA expression of the adipogenic genes investigated herein later in life. These outcomes, however, were not translated into improved carcass quality.


2019 ◽  
Vol 97 (9) ◽  
pp. 3823-3831 ◽  
Author(s):  
Yujuan Wang ◽  
Wenli Guo ◽  
Keqiong Tang ◽  
Yaning Wang ◽  
Linsen Zan ◽  
...  

Abstract Milk fat is a main nutritional component of milk, and it has become one of the important traits of dairy cow breeding. Recently, there is increasing evidence that microRNAs (miRNA) play significant roles in the process of milk fat synthesis in the mammary gland. Primary bovine mammary epithelial cells (BMEC) were harvested from midlactation cows and cultured in DMEM/F-12 medium with 10% fetal bovine serum, 100 units/mL penicillin, 100 µg/mL streptomycin, 5 µg/mL bovine insulin, 1 µg/mL hydrocortisone, and 2 µg/mL bovine prolactin. We found that miR-34b mimic transfection in BMEC reduced the content of intracellular triacylglycerol (TAG) and lipid droplet accumulation via triacylglycerol assay and Oil Red O staining; meanwhile, overexpression of miR-34b inhibited mRNA expression of lipid metabolism-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), and CCAAT enhancer binding protein alpha (C/EBPα). Whereas miR-34b inhibitor resulted in completely opposite results. Furthermore, q-PCR and western blot analysis revealed the mRNA and protein expression levels of DCP1A were downregulated in miR-34b mimic transfection group and upregulated in miR-34b inhibitor group. Moreover, luciferase reporter assays verified that DCP1A was the direct target of miR-34b and DCP1A gene silencing in BMEC-inhibited TAG accumulation and suppressed lipid droplet formation. In conclusion, these findings revealed a novel miR-34b–DCP1A axis that has a significant role in regulating milk fat synthesis and suggested that miR-34b may be used to improve the beneficial ingredients in milk.


2019 ◽  
Vol 59 (4) ◽  
pp. 673 ◽  
Author(s):  
Y. Jiang ◽  
X. D. Liao ◽  
M. Xie ◽  
J. Tang ◽  
S. Y. Qiao ◽  
...  

The present study was conducted to evaluate the regulatory role of threonine (Thr) on hepatic lipid metabolism by determining the effects of dietary Thr concentration on lipid deposition and on genes related to lipid expression in the liver of Pekin duck. In total, 240 1-day-old ducklings were randomly allocated according to the average bodyweight to one of five dietary treatments with six replicate cages of eight birds per cage for each treatment. Birds were fed diets with 0.52%, 0.59%, 0.66%, 0.73% and 0.80% Thr (as-fed basis) from 1 to 21 days of age respectively. The results showed that dietary Thr supplementation increased average daily gain (P &lt; 0.0001), average daily feed intake (P &lt; 0.0001) and abdominal fat percentage (P &lt; 0.04), while it decreased feed to gain ratio (P &lt; 0.0001), the hepatic contents of total lipid (P &lt; 0.003) and triglycerides (P &lt; 0.003) of Pekin ducks. However, dietary Thr supplementation had no influence (P &gt; 0.05) on the concentration of hepatic cholesterol, and plasma amino acids and biochemical parameters of Pekin ducks. Moreover, Thr-unsupplemented control diet upregulated (P &lt; 0.05) hepatic gene expression related to lipid uptake (fatty acid-binding protein, apolipoprotein A4, lipoprotein lipase), fatty acid synthesis (sterol regulatory element-binding protein 1c, malic enzyme), fatty acid β-oxidation (peroxisome proliferator-activated receptor α, fatty acyl– coenzyme A (CoA) oxidase), ketogenesis (hydroxymethylglutaryl–CoA synthase 1, and acetyl–CoA synthetase1), responsive genes to amino acid deficiency (general control non-derepressible 2 (GCN2), GCN1, eukaryotic initiation factor 2α, impact RWD domain protein (IMPACT)), and triglyceride transport (apolipoprotein B) of Pekin ducks. In addition, dietary Thr deficiency had no effect on the expression of stearoyl CoA desaturase, fatty acid synthase, and ATP–citrate lyase in the liver of Pekin ducks. It is suggested that dietary Thr supplementation improved hepatic lipid metabolism of Pekin ducks by regulating lipid synthesis, transport and oxidation.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2042 ◽  
Author(s):  
Yae Rim Choi ◽  
Jaewon Shim ◽  
Min Jung Kim

Soy isoflavones are popular ingredients with anti-adipogenic and anti-lipogenic properties. The anti-adipogenic and anti-lipogenic properties of genistein are well-known, but those of genistin and glycitein remain unknown, and those of daidzein are characterized by contrasting data. Therefore, the purpose of our study was to investigate the effects of daidzein, glycitein, genistein, and genistin on adipogenesis and lipogenesis in 3T3-L1 cells. Proliferation of 3T3-L1 preadipocytes was unaffected by genistin and glycitein, but it was affected by 50 and 100 µM genistein and 100 µM daidzein for 48 h. Among the four isoflavones, only 50 and 100 µM genistin and genistein markedly suppressed lipid accumulation during adipogenesis in 3T3-L1 cells through a similar signaling pathway in a dose-dependent manner. Genistin and genistein suppress adipocyte-specific proteins and genes, such as peroxisome proliferator-activated receptor γ (PPARγ), CCAAT-enhancer-binding protein α (C/EBPα), and adipocyte binding protein 2 (aP2)/fatty acid-binding protein 4 (FABP4), and lipogenic enzymes such as ATP citrate lyase (ACL), acetyl-CoA carboxylase 1 (ACC1), and fatty acid synthase (FAS). Both isoflavones also activate AMP-activated protein kinase α (AMPKα), an essential factor in adipocyte differentiation, and inhibited sterol regulatory element-binding transcription factor 1c (SREBP-1c). These results indicate that genistin is a potent anti-adipogenic and anti-lipogenic agent.


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