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Lakhveer Singh, Sara Aldosary, Abdulaziz S Saeedan, M Nazam Ansari, Gaurav Kaithwas
Hypoxia-inducible factor-1α (HIF-1α) shifts the metabolism of glucose from highly efficient oxidative phosphorylation to less efficient glycolysis. Pyruvic acid thus accumulated is oxidized to lactic acid which is pumped out in the tumor microenvironment. Protons generated from the pentose phosphate pathway (PPP) and upon hydrolysis of ATP further enhance the acidity in the tumor microenvironment. The resultant pH in the tumor microenvironment activates an endoplasmic reticulum protein: sterol regulatory element binding protein-1c (SREBP-1c), which once activated enhances proliferation of the tumor cell...
May 14, 2018: Drug Discovery Today
Xiaopeng Zhu, Hongmei Yan, Mingfeng Xia, Xinxia Chang, Xi Xu, Liu Wang, Xiaoyang Sun, Yan Lu, Hua Bian, Xiaoying Li, Xin Gao
BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased worldwide. Metformin decreases triglyceride (TG) accumulation in hepatocytes in vivo and in vitro. Stearyl-coenzyme A desaturase 1 (SCD1) knockout mice also show decreased liver TG accumulation; however, whether SCD1 plays a role in the effect of metformin on TG accumulation is unknown. Therefore, the aim of this study was to investigate whether SCD1 mediated the effect of metformin on TG accumulation...
May 14, 2018: Lipids in Health and Disease
Wei Zhao, Hailong Yang, Juntao Li, Yuan Chen, Jiaxue Cao, Tao Zhong, Linjie Wang, Jiazhong Guo, Li Li, Hongping Zhang
As a well-conserved microRNA, miR-183 is ubiquitously expressed in many tissues and cells including backfat and the 3T3-L1 adipocytes; however, the mechanisms regulating miR-183 in adipogenesis remain poorly understood. Here, we explored the expression pattern and role of miR-183 in adipogenesis using hircine preadipocytes. The results showed that miR-183 was up-regulated during preadipocyte differentiation, and overexpression of miR-183 enhanced lipid accumulation and dramatically increased the mRNA expression of the adipogenic genes PPARγ, C/EBPα, SREBP-1c, FAS, and ACC...
May 8, 2018: Gene
Youping Zhou, Shengjie Yu, Can Cai, Li Zhong, Huihong Yu, Wei Shen
Background: The aim of this study was to investigate how the signaling pathway downstream of mTOR/S6K1 contributes to the regulation of SREBP-1c expression during lipogenesis in HepG2 cells. Methods: The model of steatosis was established using human hepatocytes HepG2 and inducting them with sodium palmitate. mTOR, S6K1 and LXRα were inhibited by rapamycin, PF-4708671 and siRNA-LXRα, respectively. After a variety of different treatment, the levels of intracellular triglycerides, the accumulation of lipid droplets and the expression levels of related genes were detected...
2018: Nutrition & Metabolism
Fan Yang, Yanyan Dai, Cuiting Min, Xiaonan Li
Background: Postnatal overfeeding activates tissue glucocorticoid (GC) activity by up-regulating 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) and increasing sensitivity to high-fat (HF) diet-induced non-alcoholic fatty liver disease (NAFLD). The present study aimed to evaluate the effects of postnatal overfeeding on GC regulation and lipogenesis in the liver and to observe the impact of GC on hepatocyte lipid metabolism. Methods: In vivo , Male Sprague-Dawley rat pup litters were adjusted to litter sizes of three (small litter, SL) or ten (normal litter, NL) on postnatal day 3 and then given standard chow from postnatal week 3 (W3) to W13...
2018: Nutrition & Metabolism
Yong-Ping Zheng, Xian-Yang Zhong, Yu-Shu Huang, Can-Bin Zheng
INTRODUCTION AND AIM: Hepatitis C virus core-binding protein 6 (HCBP6) was previously found to be an hepatitis C virus corebinding protein, its biological function remains unclear. Our research aims to investigate the role of HCBP6 in the development of hepatic steatosis induced by high-fat diet and carbon tetrachloride (CCL4) in rats. MATERIAL AND METHODS: Eighteen Wistar rats were randomly allocated into 3 groups: control group, model group 1, and model group 2...
April 9, 2018: Annals of Hepatology
Sixto Reyna Gallegos, Génesis Torres Arrunátegui, Rodrigo Valenzuela, Miguel Ángel Rincón-Cervera, María Elena Villanueva Espinoza
Flavonoids upregulate gene expression of PPAR-α and underregulate the gene expression of SREBP-1c, and their intake increases the plasmatic concentration of n-3 LC-PUFAs. However, the biological mechanisms underlying these effects have not been elucidated. In this work, the effect of oral supplementation of ALA from chia (Salvia hispanica L.) seed oil and anthocyanins from a purple corn extract (PCE) on gene expression of SREBP-1c, PPAR-α and Δ5 and Δ6 desaturases (Δ5D and Δ6D), the activity of these enzymes in the liver as well as the hepatic lipid profile were evaluated in thirty-six female Sprague Dawley rats whose diet was supplemented with olive oil (OL), chia oil (CH), olive oil and PCE (OL + PCE) or chia oil and PCE (CH + PCE)...
May 2018: Prostaglandins, Leukotrienes, and Essential Fatty Acids
Nanako Nihei, Hinako Okamoto, Takahiro Furune, Naoko Ikuta, Kengo Sasaki, Gerald Rimbach, Yutaka Yoshikawa, Keiji Terao
We investigated the effect of α-cyclodextrin (α-CD) on the bacterial populations of gut microbiota, production of organic acids, and short-chain fatty acids (SCFAs), and lipid metabolism in obese mice induced by feeding a high-fat diet (HFD). Male C57BL/6J mice were assigned to three diet groups: normal diet (ND) (5% [w/w] fat), HFD (35% [w/w] fat), and HFD (35% [w/w] fat) + 5.5% (w/w) α-CD for 16 weeks. Increases in body and epididymal adipose tissue weights were observed in the HFD group compared with the ND group, which were attenuated in the HFD+α-CD group...
May 7, 2018: BioFactors
Biljana Bursać, Ana Djordjevic, Nataša Veličković, Danijela Vojnović Milutinović, Snježana Petrović, Ana Teofilović, Ljupka Gligorovska, Frederic Preitner, Luc Tappy, Gordana Matić
Both fructose overconsumption and increased glucocorticoids secondary to chronic stress may contribute to overall dyslipidemia. In this study we specifically assessed the effects and interactions of dietary fructose and chronic stress on lipid metabolism in the visceral adipose tissue (VAT) of male Wistar rats. We analyzed the effects of 9-week 20% high fructose diet and 4-week chronic unpredictable stress, separately and in combination, on VAT histology, glucocorticoid prereceptor metabolism, glucocorticoid receptor subcellular redistribution and expression of major metabolic genes...
May 2, 2018: Molecular and Cellular Endocrinology
Md Akil Hossain, Seung-Jin Lee, Na-Hye Park, Biruk Tesfaye Birhanu, Abraham Fikru Mechesso, Ji-Yong Park, Eun-Jin Park, Sam-Pin Lee, Sun-Joo Youn, Seung-Chun Park
The aim of this study was to evaluate the potentials of fermented Cucurbita moschata extract (FCME) in the treatment of obesity and nonalcoholic fatty liver disease (NAFLD). Five-week-old male C57BL/6 mice were assigned to 6 groups and treated for 8 weeks by feeding the normal diet (ND) and high fat diet (HFD) with and without FCME. Changes in body weight gain and consumption of feed and water were recorded. Major organs, adipose tissues, and blood samples were collected after the experimental period. The serum lipid profile, histological features of liver and adipose tissues, and mRNA expression of different adipogenic/lipogenic genes from liver tissue were evaluated...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Victoria Jideonwo, Yongyong Hou, Miwon Ahn, Sneha Surendran, Núria Morral
Sterol Regulatory Element Binding Protein-1 (SREBP-1) is a conserved transcription factor of the basic helix-loop-helix leucine zipper family (bHLH-Zip) that plays a central role in regulating expression of genes of carbohydrate and fatty acid metabolism in the liver. SREBP-1 activity is essential for the control of insulin-induced anabolic processes during the fed state. In addition, SREBP-1 regulates expression of key molecules in the insulin signaling pathway, including insulin receptor substrate 2 (IRS2) and a subunit of the phosphatidylinositol 3-kinase (PI3K) complex, PIK3R3, suggesting that feedback mechanisms exist between SREBP-1 and this pathway...
2018: PloS One
Rong Xiang, Liang-Liang Fan, Hao Huang, Ya-Qin Chen, Wanxia He, Shuai Guo, Jing-Jing Li, Jie-Yuan Jin, Ran Du, Riqiang Yan, Kun Xia
Background -Reticulon 3 (RTN3) is an endoplasmic reticulum protein that has been previously shown to play a role in neurodegenerative diseases, but little is known about its role in lipid metabolism. Methods -Obesity patients (149), hypertriglyceridemia patients (343), and healthy controls (84) were enrolled to assess their levels of RTN3. To explore pathophysiological roles of RTN3 in the control of lipid metabolism, we utilized Tg-RTN3 and RTN3-null transgenic mouse models and multiple C. elegans strains for molecular characterization...
May 1, 2018: Circulation
Chunyi Wang, Yan Li, Mengjiao Hao, Weimin Li
Objective: Insulin resistance (IR) is a risk factor for non-alcoholic fatty liver disease (NAFLD), which is characterized by lipid accumulation in hepatocytes. AMP-activated protein kinase (AMPK)-induced sterol regulatory element binding protein-1c (SREBP-1c) phosphorylation is crucial for proper regulation of lipid metabolism in the liver. Astragaloside IV (AST-IV) was found to decrease lipid accumulation in hepatocytes by activating AMPK, which is required to regulate lipid metabolism in liver tissue by inducing SREBP-1c phosphorylation...
2018: Frontiers in Pharmacology
Hee-Sung Chae, Byoung Hoon You, Dong-Yeop Kim, Hankyu Lee, Hyuk Wan Ko, Hyun-Jeong Ko, Young Hee Choi, Sun Shim Choi, Young-Won Chin
Whole-transcriptome analysis and western blotting of sauchinone-treated HepG2 cells demonstrated that sauchinone regulated genes relevant to cholesterol metabolism and synthesis. In particular, it was found that the expression of proprotein convertase subtilisin/kexin type 9 (PCSK9) was downregulated, and the expression of low density lipoprotein receptor (LDLR) was upregulated in sauchinone-treated HepG2 cells. Consequently, LDL-cholesterol (LDL-C) uptake was increased. As a transcriptional regulator of PCSK9 expression, sterol regulatory elements binding protein-2 (SREBP-2) was proposed by transcriptome analysis and western blotting...
April 30, 2018: Scientific Reports
Jason A Magida, Ronald M Evans
No abstract text is available yet for this article.
April 30, 2018: Proceedings of the National Academy of Sciences of the United States of America
Jamili D B Santos, Andrea A S Mendonça, Rafaela C Sousa, Thaiany G S Silva, Solange M Bigonha, Eliziária C Santos, Reggiani V Gonçalves, Romulo D Novaes
Remains unknown if dietary lipids and anabolic steroids (AS) can interact to modify energy metabolism, hepatic structure and function. We investigated the impact of AS on gene expression, lipid profile, redox status and the development of nonalcoholic fatty liver disease (NAFLD) in mice treated with a diet rich in trans fatty acids. Seventy-two C57BL/6 mice were equally randomized into six groups and treated with a standard diet (SD) or high-fat diet (HFD) alone or combined with testosterone cypionate (10 or 20 mg/kg) for 12 weeks...
April 25, 2018: Food and Chemical Toxicology
Joseph T Nickels
Individuals with elevated lipid levels are at risk for developing cardiovascular disease as well as cancer. Sterol regulatory element-binding protein transcription factors (SREBPs) are inducers of lipid synthesis. Elevated SREBPs levels are linked to cell proliferation and metastasis. Using biochemical and mouse models of cancer, Zhao et al. have discovered that nuclear SREBP-1a-dependent transcription is activated by pyruvate kinase M2 in cancer cells, which promotes tumor growth. Targeting the lipogenesis pathway may therefore be a promising avenue for cancer treatment...
April 27, 2018: Journal of Biological Chemistry
Ju-Hee Lee, Su Youn Baek, Eun Jeong Jang, Sae Kwang Ku, Kyu Min Kim, Sung Hwan Ki, Chang-Eop Kim, Kwang Il Park, Sang Chan Kim, Young Woo Kim
Oxyresveratrol (OXY) is a naturally occurring polyhydroxylated stilbene that is abundant in mulberry wood (Morus alba L.), which has frequently been supplied as a herbal medicine. It has been shown that OXY has regulatory effects on inflammation and oxidative stress, and may have potential in preventing or curing nonalcoholic fatty liver disease (NAFLD). This study examined the effects of OXY on in vitro model of NAFLD in hepatocyte by the liver X receptor α (LXRα)-mediated induction of lipogenic genes and in vivo model in mice along with its molecular mechanism...
April 24, 2018: Chemico-biological Interactions
Mingqiu Zhao, Yi Li, Huihui Yao, Lihua Dou, Shuya Zhang, Qihong Zhao, Li Li
Changes in dietary composition will have a significant impact on the nutritional status of the mother and the offspring. To examine the relevant hormone level changes during lactation and the expression of fatty acid transporters in the placenta and liver under the condition of a high-fat (HF) diet, we established HF animal models and conducted a cross-fostering program to mimic the shift in diet. On gestation day (GD)18, the weight of placenta in the HF group was significantly higher than that in the control group (p < 0...
March 2018: Lipids
Fatma Hadrich, Sami Sayadi
BACKGROUND: Apigetrin, a flavonoid found in many plant leaves and seeds, has been known to possess antimutagenic, anti-cancer, antioxidant and anti-inflammatory properties. Here, we are investigating the effect of the apigetrin on adipocytes differentiation in 3T3-L1 adipocytes, and elucidating the mechanism of its action. METHODS: Lipids accumulation was measured by Oil Red O staining and cell cycle was analyzed by flow cytometry. The antioxidant effect of apigetrin was evaluated against hydrogen peroxide...
April 25, 2018: Lipids in Health and Disease
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