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Eleonora Scorletti, Christopher D Byrne
For many years it has been known that high doses of long chain omega-3 fatty acids are beneficial in the treatment of hypertriglyceridaemia. Over the last three decades, there has also been a wealth of in vitro and in vivo data that has accumulated to suggest that long chain omega-3 fatty acid treatment might be beneficial to decrease liver triacylglycerol. Several biological mechanisms have been identified that support this hypothesis; notably, it has been shown that long chain omega-3 fatty acids have a beneficial effect: a) on bioactive metabolites involved in inflammatory pathways, and b) on alteration of nuclear transcription factor activities such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element-binding protein 1c (SREBP-1c) and carbohydrate-responsive element-binding protein (ChREBP), involved in inflammatory pathways and liver lipid metabolism...
March 12, 2018: Molecular Aspects of Medicine
Qian Chen, Mengyang Liu, Haiyang Yu, Jian Li, Sijian Wang, Yi Zhang, Feng Qiu, Tao Wang
Scutellaria baicalensis has been reported to improve the lipid metabolism of high-fat diet-induced liver dysfunction, but direct evidence is rare. This study aimed to explore the effects and mechanisms of S. baicalensis and its major constituent baicalin on hepatic lipotoxicity. KK-Ay mice and orotic acid (OA)-induced nonalcoholic fatty liver disease (NAFLD) rats were used to evaluate lipid metabolism regulatory effects. Sodium oleate-induced triglyceride-accumulated HepG2 cells were used for the mechanism study, pretreated with or without compound C or STO-609 or transfected with liver kinase B1 (LKB1) siRNA...
March 14, 2018: Journal of Natural Medicines
Deqiang Zhang, Xin Tong, Bradley B Nelson, Ethan Jin, Julian Sit, Nicholas Charney, Meichan Yang, M Bishr Omary, Lei Yin
Alcohol liver disease (ALD) is one of the major chronic liver diseases worldwide, ranging from fatty liver, alcoholic hepatitis, cirrhosis, and potentially hepatocellular carcinoma. Epidemiological studies suggest a potential link between ALD and impaired circadian rhythms, but the role of hepatic circadian proteins in the pathogenesis of ALD remains unknown. Here we show that the circadian clock protein BMAL1 in hepatocytes is both necessary and sufficient to protect mice from alcohol liver disease. Ethanol diet-fed mice with liver-specific knockout (Bmal1-LKO) or depletion of Bmal1 develop more severe liver steatosis and injury as well as a simultaneous suppression of both de novo lipogenesis and fatty acid oxidation, which can be rescued by the supplementation of synthetic PPARα ligands...
March 13, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Rahul Sharma, Bhumika Sharma, Ashish Gupta, Suman Kumar Dhar
Malaria parasites use an extensive secretory pathway to traffic a number of proteins within itself and beyond. In higher eukaryotes, Endoplasmic Reticulum (ER) membrane bound transcription factors such as SREBP are reported to get processed en route and migrate to nucleus under the influence of specific cues. However, a protein constitutively trafficked to the nucleus via classical secretory pathway has not been reported. Herein, we report the presence of a novel trafficking pathway in an apicomplexan, Plasmodium falciparum where a homolog of an Origin Recognition Complex 2 (Orc2) goes to the nucleus following its association with the ER...
March 7, 2018: Biochimica et Biophysica Acta
Tiange Li, Jing Gao, Min Du, Jiajia Song, Xueying Mao
Milk fat globule membrane (MFGM), a protein-lipid complex surrounding the fat globules in milk, has many health benefits. The aim of the current study was to investigate whether MFGM could prevent obesity through inhibiting adipogenesis and promoting brown remodeling of white adipose tissue (WAT) in mice fed with high-fat diet. C57BL/6 mice were fed a normal diet (ND), high-fat diet (HFD), HFD plus MFGM at 100 mg/kg BW, 200 mg/kg BW or 400 mg/kg BW for 8 weeks. Results showed that MFGM suppressed body weight gain induced by HFD, reduced white adipose tissue (WAT) mass accompanied with the decrease in adipocyte sizes...
March 9, 2018: Nutrients
Chang Liu, Yan-Jun Shen, Qing-Bo Tu, Yan-Ran Zhao, Hao Guo, Juan Wang, Li Zhang, Hua-Wei Shi, Yun Sun
Pedunculoside (PE) is a novel triterpene saponin extracted from the dried barks of Ilex rotunda Thunb. The present study aims to explore lipid-lowering effects of PE on hyperlipidemia rat induced by high-fat diet. The rats were fed with the high-fat diet and subjected to intragastric administration of PE at doses of 30, 15, or 5 mg/kg daily for 7 weeks. The results demonstrated that treatment with PE for 7-week dramatically decreased serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) and reduced liver TC in hyperlipidemia rat induced by high-fat diet...
March 5, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Xiaoping Zhao, Li Zhao, Hao Yang, Jiajin Li, Xuejie Min, Fajun Yang, Jianjun Liu, Gang Huang
Dysregulation of lipid metabolism is common in cancer cells, but the underlying mechanisms are poorly understood. Sterol regulatory element-binding proteins (SREBPs) stimulate lipid biosynthesis through transcriptional activation of lipogenic enzymes. However, SREBPs' roles and potential interacting partners in cancer cells are not fully defined. Using a biochemical approach, we found here that pyruvate kinase M2 (PKM2) physically interacts with the nuclear form of SREBP-1a (nBP1a), by binding to amino acids 43-56 in nBP1a...
March 7, 2018: Journal of Biological Chemistry
Yung-Tsung Chen, Yu-Chun Lin, Jin-Seng Lin, Ning-Sun Yang, Ming-Ju Chen
SCOPE: Non-alcoholic fatty liver disease (NAFLD) is a common disease that is concomitant with obesity, resulting in increased mortality. To date, the efficiency of NAFLD treatment still needs to be improved. Therefore, we aimed to evaluate the effect of Lactobacillus mali APS1, which was isolated from sugary kefir, on hepatic steatosis in rats fed a high-fat diet (HFD). METHODS AND RESULTS: Sprague Dawley rats were fed a control diet, a high-fat diet with saline and a high-fat diet with APS1 intervention by gavage daily for 12 weeks...
March 5, 2018: Molecular Nutrition & Food Research
Sung-Soo Park, Yeon-Joo Lee, Sooyeon Song, Boyong Kim, Hyuno Kang, Sejong Oh, Eungseok Kim
Obesity is a major threat to public health, and it is strongly associated with insulin resistance and fatty liver disease. Here, we demonstrated that administration of Lactobacillus acidophilus NS1 (LNS1) significantly reduced obesity and hepatic lipid accumulation, with a concomitant improvement in insulin sensitivity, in high fat diet (HFD)-fed mice. Furthermore, administration of LNS1 inhibited the effect of HFD feeding on the SREBP-1c and PPARα signaling pathways, and reduced lipogenesis with an increase in fatty acid oxidation in ex vivo livers from HFD-fed mice...
March 5, 2018: Journal of Endocrinology
Russell A DeBose-Boyd, Jin Ye
Sterol regulatory element-binding proteins (SREBPs) are a family of membrane-bound transcription factors that activate genes encoding enzymes required for synthesis of cholesterol and unsaturated fatty acids. SREBPs are controlled by multiple mechanisms at the level of mRNA synthesis, proteolytic activation, and transcriptional activity. In this review, we summarize the recent findings that contribute to the current understanding of the regulation of SREBPs and their physiologic roles in maintenance of lipid homeostasis, insulin signaling, innate immunity, and cancer development...
February 27, 2018: Trends in Biochemical Sciences
Piseth Nhoek, Hee-Sung Chae, Jagadeesh Nagarajappa Masagalli, Karabasappa Mailar, Pisey Pel, Young-Mi Kim, Won Jun Choi, Young-Won Chin
Nine flavonoids were isolated and identified from a chloroform-soluble fraction of the roots of Scutellaria baicalensis through a bioactivity-guided fractionation using a proprotein convertase subtilisin/kexin type 9 (PCSK9) monitoring assay in HepG2 cells. All structures were established by interpreting the corresponding spectroscopic data and comparing measured values from those in the literature. All compounds were assessed for their ability to inhibit PCSK9 mRNA expression; compounds 1 (3,7,2'-trihydroxy-5-methoxy-flavanone) and 4 (skullcapflavone II) were found to suppress PCSK9 mRNA via SREBP-1...
February 24, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Na Lu, Xingmei Li, Jiayao Yu, Yi Li, Chao Wang, Lili Zhang, Tian Wang, Xiang Zhong
N6 -methyladenosine (m6 A) regulates gene expression and affects cellular metabolism. In this study, we checked whether the regulation of lipid metabolism by curcumin is associated with m6 A RNA methylation. We investigated the effects of dietary curcumin supplementation on lipopolysaccharide (LPS)-induced liver injury and lipid metabolism disorder, and on m6 A RNA methylation in weaned piglets. A total of 24 Duroc × Large White × Landrace piglets were randomly assigned to control, LPS, and CurL (LPS challenge and 200 mg/kg dietary curcumin) groups (n = 8/group)...
January 2018: Lipids
Naoki Misawa, Takahiro Hosoya, Shuhei Yoshida, Osamu Sugimoto, Tomoe Yamada-Kato, Shigenori Kumazawa
To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα...
February 26, 2018: Phytotherapy Research: PTR
Nejat Kheiripour, Jamshid Karimi, Iraj Khodadadi, Heidar Tavilani, Mohammad Taghi Goodarzi, Mohammad Hashemnia
BACKGROUND: In this study, we have investigated whether silymarin intake influences lipid and glycogen content in conjunction with sirtuin1 (SIRT1) and sterol regulatory element-binding protein 1c (SREBP-1c) expressions in liver of type 2 diabetic rat. METHODS: Thirty-six male Wistar rats were randomly divided into six groups: control groups (C) and diabetic groups (D); the control groups received 60 or 120 mg/kg silymarin (C+S60 or C+S120), and the diabetic groups received 60 or 120 mg/kg silymarin (D+S60 or D+S120) daily for 8 weeks...
February 24, 2018: Journal of Basic and Clinical Physiology and Pharmacology
Di Li, Weiqing Long, Rong Huang, Ying Chen, Min Xia
OBJECTIVE: Although 27-hydroxycholesterol (27-HC) has been reported as a potent regulator of lipid homeostasis, its role in hepatic lipogenesis remains obscure. The present study was designed to investigate the impact of 27-HC on sterol regulatory element-binding protein 1 (SREBP-1) and hepatic steatosis. METHODS: In this study, the 27-HC level in mice was upregulated by overexpressing CYP27A1 or treating primary hepatocytes with 27-HC, and then the hepatic lipid accumulation was detected...
February 24, 2018: Obesity
Ángela Rojas, Paloma Gallego, Antonio Gil-Gómez, Rocío Muñoz-Hernández, Lourdes Rojas, Rosario Maldonado, Rocío Gallego, Marta García-Valdecasas, José A Del Campo, Juan D Bautista, Manuel Romero-Gómez
Background & aims. G-allele of PNPLA3 (rs738409) favours triglycerides accumulation and steatosis. In this study, we examined the effect of quercetin and natural extracts from mushroom and artichoke on reducing lipid accumulation in hepatic cells. MATERIAL AND METHODS: Huh7.5 cells were exposed to oleic acid (OA) and treated with quercetin and extracts to observe the lipid accumulation, the intracellular-TG concentration and the LD size. Sterol regulatory element binding proteins-1 (SREBP-1), peroxisome proliferator-activated receptor (PPARα-γ) and cholesterol acyltransferase (ACAT) gene expression levels were analysed...
March 1, 2018: Annals of Hepatology
Mariana Alejandra Rosas Fernández, Carlos Marcelo Concha Vilca, Leandro Oliveira Batista, Viviane Wagner Ramos, Leonardo Paes Cinelli, Kelse Tibau de Albuquerque
OBJECTIVE: We investigated the effect of intermittent food restriction (IFR) cycles on hypothalamic expression of lipogenic proteins and induction of overeating. METHODS: Female Wistar rats were distributed in three groups: free access to feed (control, C), 2 d feed restriction at 50% of C intake followed by 3 d (restricted 3, R3) or 5 d (restricted 5, R5) ad libitum feeding. After 6 wk, the rats were submitted to euthanasia and collected the hypothalamus and blood...
December 6, 2017: Nutrition
Runmei Yang, Xinxin Chu, Le Sun, Zhuoying Kang, Min Ji, Ying Yu, Ying Liu, Zhendan He, Nannan Gao
The aim of this study was to evaluate the hypolipidemic effect and mechanisms of total phenylpropanoid glycosides extracted from Ligustrum robustum (Roxb.) Blume (LRTPG) in hamsters fed a high-fat diet and to discover bioactive components in HepG2 cell model induced by oleic acid. LRTPG of high (1.2 g/kg), medium (0.6 g/kg), and low (0.3 g/kg) doses was administrated daily for 21 consecutive days in hamsters. We found that in hamsters fed a high-fat diet, LRTPG effectively reduced the concentrations of plasma triglycerides (TG), free fatty acid, total cholesterol, low-density lipoprotein cholesterol, and hepatic TG and total cholesterol...
February 22, 2018: Phytotherapy Research: PTR
M A Vithayathil, J R Gugusheff, Z Y Ong, S C Langley-Evans, R A Gibson, B S Muhlhausler
Background: While the adverse metabolic effects of exposure to obesogenic diets during both the prenatal and early postnatal period are well established, the relative impact of exposure during these separate developmental windows remains unclear. This study aimed to assess the relative contribution of exposure to a maternal cafeteria diet during pregnancy and lactation on body weight, fat mass and expression of lipogenic and adipokine genes in the offspring. Methods: Wistar rats were fed either a control chow (Control, n  = 14) or obesogenic cafeteria diet (CAF, n  = 12) during pregnancy and lactation...
2018: Nutrition & Metabolism
Ye Tian, Haihua Feng, Lu Han, Lin Wu, Hongming Lv, Bingyu Shen, Zheng Li, Qiaoling Zhang, Guowen Liu
Magnolol (MG) is a kind of lignin isolated from Magnolia officinalis , which serves several different biological functions, such as antifungal, anticancer, antioxidant, and hepatoprotective functions. This study aimed to evaluate the protective effect of MG against oleic acid (OA)-induced hepatic steatosis and inflammatory damage in HepG2 cells and in a tyloxapol (Ty)-induced hyperlipidemia mouse model. Our findings indicated that MG can effectively inhibit OA-stimulated tumor necrosis factor α (TNF-α) secretion, reactive oxygen species generation, and triglyceride (TG) accumulation...
2018: Frontiers in Immunology
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