scholarly journals Antioxidant Resveratrol Increases Lipolytic and Reduces Lipogenic Gene Expression under In Vitro Heat Stress Conditions in Dedifferentiated Adipocyte-Derived Progeny Cells from Dairy Cows

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 905
Author(s):  
Gitit Kra ◽  
Jayasimha Rayalu Daddam ◽  
Hadar Gabay ◽  
Sara Yosefi ◽  
Maya Zachut

Heat stress (HS) induces oxidative stress by increasing reactive oxygen species (ROS), and the polyphenol resveratrol (RSV) has been shown to have antioxidant properties by reducing ROS. Hence, we aimed to examine the effects of RSV, HS and their interaction on bovine adipocytes. We generated bovine dedifferentiated adipocyte-derived progeny (DFAT) cells from subcutaneous adipose tissue and examined the effects of RSV (100 µM), heat conditions: isothermal (ISO-37 °C), short heat (SH-41.2 °C for 1 h) and long HS (LH-41.2 °C for 16 h), and their interaction on gene expression in DFAT-cells. In medium of DFAT-cells treated with RSV, malondialdehyde levels were reduced and oxygen-radical absorbance-capacity levels were increased compared to control. Treating DFAT-cells with RSV increased the relative mRNA expression of stress-induced-phosphoprotein-1 (STIP1) and the expression of hormone-sensitive-lipase (LIPE) and perilipin-1 (PLIN1), whereas it reduced the expressions of fatty-acid-synthase (FASN) and of pro-inflammatory chemotactic-C-C-motif-chemokine-ligand-2 (CCL2) also under HS. Moreover, reduced protein abundance of FASN was found in RSV-treated DFAT-cells compared to controls. Molecular docking of RSV with FASN confirmed its possible binding to FASN active site. This work demonstrates that RSV has an antioxidant effect on bovine DFAT cells and may induce adipose lipolysis and reduce lipogenesis also under in vitro HS conditions.

Author(s):  
De Xie ◽  
Hairong Zhao ◽  
Jiaming Lu ◽  
Furong He ◽  
Weidong Liu ◽  
...  

Uric acid is the end metabolite derived from the oxidation of purine compounds. Overwhelming evidence shows the vital interrelation between hyperuricemia (HUA) and non-alcoholic fatty liver disease (NAFLD). However, the mechanisms for this association remain unclear. In this study, we investigated the effect of HUA on fat accumulation in human HepG2 hepatoma cells and urate oxidase-knockout (Uox-KO) mice. HUA activated c-Jun N-terminal kinase (JNK) in vivo and in vitro. Furthermore, inhibiting JNK activation by a JNK-specific inhibitor, SP600125, decreased fat accumulation and lipogenic gene expression induced by HUA. Overexpression of the lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase 1 was via activation of JNK, which was blocked by the JNK inhibitor SP600125. HUA activated AP-1 to upregulate lipogenic gene expression via JNK activation. In addition, HUA caused mitochondrial dysfunction and reactive oxygen species production. Pre-treatment with the antioxidant N-acetyl-L-cysteine could ameliorate HUA-activated JNK and hepatic steatosis. These data suggest that ROS/JNK/AP-1 signaling plays an important role in HUA-mediated fat accumulation in liver.


1999 ◽  
Vol 19 (5) ◽  
pp. 3760-3768 ◽  
Author(s):  
Marc Foretz ◽  
Corinne Pacot ◽  
Isabelle Dugail ◽  
Patricia Lemarchand ◽  
Colette Guichard ◽  
...  

ABSTRACT The transcription of genes encoding proteins involved in the hepatic synthesis of lipids from glucose is strongly stimulated by carbohydrate feeding. It is now well established that in the liver, glucose is the main activator of the expression of this group of genes, with insulin having only a permissive role. While ADD1/SREBP-1 has been implicated in lipogenic gene expression through temporal association with food intake and ectopic gain-of-function experiments, no genetic evidence for a requirement for this factor in glucose-mediated gene expression has been established. We show here that the transcription of ADD1/SREBP-1c in primary cultures of hepatocytes is controlled positively by insulin and negatively by glucagon and cyclic AMP, establishing a link between this transcription factor and carbohydrate availability. Using adenovirus-mediated transfection of a powerful dominant negative form of ADD1/SREBP-1c in rat hepatocytes, we demonstrate that this factor is absolutely necessary for the stimulation by glucose of l-pyruvate kinase, fatty acid synthase, S14, and acetyl coenzyme A carboxylase gene expression. These results demonstrate that ADD1/SREBP-1c plays a crucial role in mediating the expression of lipogenic genes induced by glucose and insulin.


2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yusuf Abba ◽  
Hasliza Hassim ◽  
Hazilawati Hamzah ◽  
Mohamed Mustapha Noordin

Resveratrol is a potent polyphenolic compound that is being extensively studied in the amelioration of viral infections bothin vitroandin vivo. Its antioxidant effect is mainly elicited through inhibition of important gene pathways like the NF-κβpathway, while its antiviral effects are associated with inhibitions of viral replication, protein synthesis, gene expression, and nucleic acid synthesis. Although the beneficial roles of resveratrol in several viral diseases have been well documented, a few adverse effects have been reported as well. This review highlights the antiviral mechanisms of resveratrol in human and animal viral infections and how some of these effects are associated with the antioxidant properties of the compound.


2013 ◽  
Vol 109 (9) ◽  
pp. 1590-1597 ◽  
Author(s):  
Min Young Um ◽  
Mi Kyeong Moon ◽  
Jiyun Ahn ◽  
Tae Youl Ha

Coumarin is a natural compound abundant in plant-based foods such as citrus fruits, tomatoes, vegetables and green tea. Although coumarin has been reported to exhibit anti-coagulant, anti-inflammation and cholesterol-lowering properties, the effect of coumarin on hepatic lipid metabolism remains unclear. In the present study, we evaluated the ability of coumarin to protect against hepatic steatosis associated with a high-fat diet (HFD) and investigated potential mechanisms underlying this effect. C57BL/6J mice were fed a normal diet, HFD and HFD containing 0·05 % courmarin for 8 weeks. The present results showed that coumarin reduced weight gain and abdominal fat mass in mice fed the HFD for 8 weeks (P< 0·05). Coumarin also significantly reduced the HFD-induced elevation in total cholesterol, apoB, leptin and insulin (P< 0·05). In the liver of HFD-fed mice, coumarin significantly reduced total lipids, TAG and cholesterol (38, 22 and 9 % reductions, respectively; P< 0·05), as well as lipid droplet number and size. Additionally, thiobarbituric acid-reactive substance levels, as an indicator of hepatic steatosis, were attenuated by coumarin (P< 0·05). Finally, coumarin suppressed the HFD-induced up-regulation in fatty acid synthase (FAS) activity, and the expression of sterol regulatory element-binding protein-1, FAS, acetyl-CoA carboxylase 1, PPARγ and CCAAT/enhancer-binding protein-α in the liver. Taken together, these results demonstrate that coumarin could prevent HFD-induced hepatic steatosis by regulating lipogenic gene expression, suggesting potential targets for preventing hepatic steatosis.


2020 ◽  
Vol 21 (16) ◽  
pp. 5884
Author(s):  
Sara Balbuena-Pecino ◽  
Esmail Lutfi ◽  
Natàlia Riera-Heredia ◽  
Esther Gasch-Navalón ◽  
Emilio J. Vélez ◽  
...  

Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 μM, and 1 μM 17β-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 μM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 μM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout.


2017 ◽  
Vol 29 (1) ◽  
pp. 200 ◽  
Author(s):  
F. M. Dalanezi ◽  
F. C. Destro ◽  
R. A. Ferrazza ◽  
H. D. Mogollon García ◽  
F. F. Franchi ◽  
...  

There are several intrafollicular agents that have the ability to interfere with the metabolism and development of the oocyte, among these we highlight the exosomes (EXO). Thus, the aim of this study was to evaluate the capacity of EXO extracted from the follicular fluid of cows kept under thermoneutral or heat stress conditions to modulate oocyte maturation in vitro. Twenty-four Holstein cows were subjected to the following treatments for 14 days: heat stress (HS; n = 12), 38°C, 60% RH, temperature-humidity index = 88; and thermo-neutral (TN; n = 12), 24°C, 60% RH, temperature-humidity index = 71. Cows had their follicles aspirated when their diameter reached 9 to 12 mm; all follicles with this diameter were aspirated. All follicular fluid aspirated from cows subjected to HS or TN was pooled forming the groups (HS and TN). The EXO were obtained by ultracentrifugation of follicular fluid (120,000 × g for 70 min at 4°C, twice) and had their presence confirmed by transmission electron microscopy. Bos indicus cumulus-oocyte complexes (COC) collected from ovaries obtained in commercial slaughterhouse, were pooled in groups of 20 COC and randomly subjected to 1 of the following treatments: Control, matured in standard medium (TCM 199, supplemented with Earle’s salts, glutamine, NaHCO3, pyruvate, FSH, and amikacin); HS-EXO, matured in standard medium added with 10 µL of a solution of follicular EXO from HS cows; and TN-EXO, matured in standard medium added with 10 µL of a solution of follicular EXO from TN cows. The procedures were repeated 4 times, always with 20 COC per treatment in each replica. After 22 h of maturation, COC were recovered and the expression of genes related to apoptosis protection (BCL2), cell viability (STAT3), cell maintenance (RPL15), oocyte competence (BMP15), oxidative stress (CPT1B), cumulus cell expansion (HAS2), cell cycle (CDCA8), and heat stress protection (HSF1) were assessed. Oocyte genes were differentially expressed according to the source of EXO. Groups were statistically analysed using ANOVA and Tukey tests. All genes, except CPT1B, showed lower expression in TN-EXO oocytes when compared with control and HS-EXO (P < 0.05). CPT1B showed a higher expression in HS-EXO oocytes (P < 0.05). The results showed that the addition of EXO from exogenous follicles can modulate the expression of oocytes genes related to cell viability and survival. The lower expression of these genes in TN-EXO suggested that the EXO obtained in TN conditions attenuate several genes related to the oocytes maturation and viability. Surprisingly, the control oocytes showed a similar gene expression pattern of the HS-EXO. In conclusion, EXO derived from follicular fluid of cows submitted to TN or HS conditions can modulate the gene expression of oocytes matured in vitro. These results open new perspectives for the use of theses EXO as a tool to increase the efficiency of in vitro oocyte maturation. Financial support from FAPESP #12/18297–7.


2008 ◽  
Vol 197 (1) ◽  
pp. 111-119 ◽  
Author(s):  
A I Martín ◽  
E Castillero ◽  
M Granado ◽  
M López-Menduiña ◽  
M A Villanúa ◽  
...  

Adjuvant-induced arthritis is a model of rheumatoid arthritis that induces cachexia. In other cachectic situations, there is an increase in lipolysis resulting in a loss of adipose tissue mass. The aim of this work was to analyse the effect of chronic arthritis, induced by adjuvant injection, on white adipose tissue (WAT). For this purpose, rats were killed 10 days after adjuvant injection, when the first external symptoms appeared, on days 15 and 22 when the external signs of the illness reach their severest level. As arthritis decreases food intake, a pair-fed group was also included. Serum concentrations of insulin, leptin, adiponectin, glycerol and nitrites, as well as gene expression of leptin, adiponectin, hormone-sensitive lipase (HSL), fatty acid synthase (FAS), tumour necrosis factor α and zinc-α2-glycoprotein (ZAG) were determined. Arthritis decreased food intake between days 5 and 16, but not during the last 5 days of the experiment. There was a marked decrease in relative adipose tissue weight and in serum leptin and adiponectin as well as in their gene expression in WAT in arthritic rats. Arthritis decreased the gene expression of FAS in the WAT. However, none of these effects was found in pair-fed rats. Arthritis did not increase lipolysis, since arthritic rats have lower serum concentrations of glycerol, HSL mRNA in WAT, as well as liver ZAG mRNA than the pair-fed or control rats. These data suggest that in chronic arthritis the decrease in white adipose mass is secondary to a reduced adipose lipogenesis, and this effect is not mainly due to the decrease in food intake.


2019 ◽  
Vol 243 (3) ◽  
pp. 187-197
Author(s):  
Dan Wang ◽  
Chu-Dan Liu ◽  
Meng-Li Tian ◽  
Cheng-Quan Tan ◽  
Gang Shu ◽  
...  

Dietary fibers and their microbial fermentation products short-chain fatty acids promote metabolic benefits, but the underlying mechanisms are still unclear. Recent studies indicate that intestinal lipid handling is under regulatory control and has broad influence on whole body energy homeostasis. Here we reported that dietary inulin and propionate significantly decreased whole body fat mass without affecting food intake in mice fed with chow diet. Meanwhile, triglyceride (TG) content was decreased and lipolysis gene expression, such as adipose triglyceride lipase (A tgl), hormone-sensitive lipase (H sl) and lysosomal acid lipase (L al) was elevated in the jejunum and ileum of inulin- and propionate-treated mice. In vitro studies on Caco-2 cells showed propionate directly induced enterocyte Atgl, Hsl and Lal gene expression and decreased TG content, via activation of phosphorylation of AMP-activated protein kinase (p-AMPK) and lysine-specific demethylase 1 (LSD1). Moreover, inulin and propionate could increase intestinal lipolysis under high-fat diet (HFD)-fed condition which contributed to the prevention of HFD-induced obesity. Our study suggests that dietary fiber inulin and its microbial fermentation product propionate can regulate metabolic homeostasis through regulating intestinal lipid handling, which may provide a novel therapeutic target for both prevention and treatment of obesity.


2019 ◽  
Vol 31 (1) ◽  
pp. 211
Author(s):  
F. M. Dalanezi ◽  
R. A. Ferrazza ◽  
J. C. Ochoa ◽  
H. D. Mogllón ◽  
F. C. Destro ◽  
...  

Heat stress (HS) has a massive impact on bovine reproduction. In cows, some of these deleterious effects involve follicular development and oocyte quality. Extracellular vesicles (EV) secreted by granulosa cells play a critical role in the intrafollicular environment by directly influencing cumulus cells and oocyte functions. The objective of this study was to investigate the effect of follicular fluid EV obtained from Holstein cows kept under thermoneutral (TN) or HS conditions, on in vitro bovine oocyte maturation. Non-lactating Holstein cows were synchronized with the Ovsynch protocol and also received an intravaginal progesterone device. From ovulation day (Day 1), cows were randomly assigned to TN (26°C, 73% humidity; n=12) or HS (36°C, 70% humidity; n=12) environments. On Day 9, 2 follicles (F1 and F2) were individually aspirated and all remained follicles were ablated. Then, on Day 14, newly formed F1 and F2 were also aspirated. Follicular fluid from all follicles from each treatment was pooled and EV were obtained according to Silveira et al. (2017 PLoS One 12, 1-25) and diluted in PBS (100μL of PBS per mL of follicular fluid centrifuged). Pools of 20 cumulus-oocyte complexes (COC) grade 1 or 2 (Stojkovic et al. Biol Reprod 200164, 904-992], predominantly from Bos indicus, were submitted to the following treatment groups: Control (n=4): matured in 90μL of TCM-199 with Eagles’ salts, glutamine, NaHCO3, pyruvate, amikacin, and FSH (base medium); TN (n=4): matured in 81μL of base medium+9μL of TN EV suspension; and HS (n=4): matured in 81μL+9μL of HS EV suspension. All treatments were carried out at 38.5°C for 24h in a humid atmosphere with 5% CO2. After 24h of maturation, COC were evaluated for meiotic progression (Hoechst 33342 stain), DNA integrity (TUNEL stain), and expression of genes related to oocyte quality (TaqMan assay, Applied Biosystems/Thermo Fisher Scientific, Waltham, MA, USA). Results were analysed using ANOVA followed by Tukey post hoc test (P&lt;0.05). When the experimental groups were compared with the control group, there was no treatment effect on meiotic progression, DNA integrity, or gene expression of cumulus cells. In the oocytes of the TN group, the genes HSF1, IGFBP2, BMP15, GDF9, CDCA8, HAS2, RPL15, STAT3,and PFKP were less expressed. We concluded that oocytes matured in the presence of EV from follicular fluid of cows kept under TN conditions had lesser expression of genes related to oocyte quality. This study was supported by FAPESP (Grant #2012/18297-7) and CAPES Foundation of Brazil.


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