scholarly journals Role of the stearyl-coenzyme A desaturase 1 gene in regulating palmitic acid tolerance of goose primary hepatocytes

2020 ◽  
Author(s):  
Bincheng Tang ◽  
Jia min Qiu ◽  
Shen qiang HU ◽  
Liang Li ◽  
Ji wen Wang

Abstract BackgroundUnlike mammals, goose fatty liver shows a strong tolerance to fatty acids without obvious injury. Stearyl-coenzyme A desaturase 1 (SCD1) serves crucial role in desaturation of saturated fatty acids (SAFs), but its role in the SAFs tolerance of goose hepatocytes has not been reported. This study was conducted to explore the role of SCD1 in regulating palmitic acid tolerance of goose primary hepatocytes.MethodsTo evaluate the palmitic acid tolerance of cultured hepatocytes, MTT was examined to reflect the effect of palmitic acid on cell viability, and quantitative PCR was used to detect the mRNA expression levels of several genes related to ER stress, inflammation, and apoptosis, and the role of SCD1 in palmitic acid tolerance of goose hepatocytes was explored using RNA interfere.ResultsOur results indicated that goose hepatocytes exhibited a higher tolerant capacity to palmitic acid than human hepatic cell line (LO2 cells). Furthermore, the mRNA levels of fatty acid desaturation-related genes (SCD1 and FADS2) and fatty acid elongate enzyme-related gene (ELOVL6) were significantly upregulated in goose primary hepatocytes treated with 0.6 mM palmitic acid. However, in cultured LO2 cells, expression of ER stress-related genes (XBP, BIP and ATF6), inflammatory response-related genes (IL-6, IL-1β and IFN-γ) and apoptosis-related genes (Bax, Bcl-2, Caspase-3 and Caspase-9) was significantly enhanced by the addition of 0.6 mM palmitic acid. Additionally, siRNA-mediated downregulation of SCD1 significantly reduced the palmitic acid tolerance of goose primary hepatocytes under the treatment of 0.6 mM palmitic acid; meanwhile, the mRNA expression of inflammatory-related genes (IL-6 and IL-1β) and several key genes involved in the PI3K/AKT, FoxO1, mTOR and AMPK pathways (AKT1, AKT2, FOXO1 and SIRT1), as well as the protein expression of cytochrome C and the apoptosis rate were also upregulated.ConclusionIn conclusion, our data suggested that SCD1 is involved in enhancing the palmitic acid tolerance of goose primary hepatocytes by regulating inflammation- and apoptosis-related genes expression.

2002 ◽  
Vol 2002 ◽  
pp. 206-206 ◽  
Author(s):  
Z.C.T.R. Daniel ◽  
R.J. Wynn ◽  
A.M. Salter ◽  
P.J. Buttery

Compared to meat from other animals lamb contains high levels of saturated fat, particularly stearic acid which comprises 18% of the total fatty acids (Enser et al, 1996). This stearic acid can be desaturated in the tissue by stearoyl coenzyme A desaturase (SCD) to produce oleic acid. In sheep SCD is produced from a single gene and the levels of SCD mRNA in the tissue correlate well with oleic acid (Ward et al, 1998, Barber et al, 2000) suggesting that an upregulation of SCD activity may increase the relative proportions of unsaturated and saturated fatty acids and so significantly improve the nutritional quality of sheep meat. Our recent studies have shown that insulin increases SCD mRNA levels and monounsaturated fatty acid synthesis in cultured ovine adipose tissue explants (Daniel et al, 2001). The present study was designed to investigate whether feeding a diet believed to manipulate SCD mRNA concentrations would significantly alter the fatty acid composition of lamb.


Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 751 ◽  
Author(s):  
Wu ◽  
Wei ◽  
Yang ◽  
Zhao ◽  
Luo

The autophagy-lysosome pathway, which involves many crucial genes and proteins, plays crucial roles in the maintenance of intracellular homeostasis by the degradation of damaged components. At present, some of these genes and proteins have been identified but their specific functions are largely unknown. This study was performed to clone and characterize the full-length cDNA sequences of nine key autolysosome-related genes (vps11, vps16, vps18, vps33b, vps41, lamp1, mcoln1, ctsd1 and tfeb) from yellow catfish Pelteobagrus fulvidraco. The expression of these genes and the transcriptional responses to a high-fat diet and fatty acids (FAs) (palmitic acid (PA) and oleic acid (OA)) were investigated. The mRNAs of these genes could be detected in heart, liver, muscle, spleen, brain, mesenteric adipose tissue, intestine, kidney and ovary, but varied with the tissues. In the liver, the mRNA levels of the nine autolysosome-related genes were lower in fish fed a high-fat diet than those fed the control, indicating that a high-fat diet inhibited formation of autolysosomes. Palmitic acid (a saturated FA) significantly inhibited the formation of autolysosomes at 12 h, 24 h and 48 h incubation. In contrast, oleic acid (an unsaturated FA) significantly induced the formation of autolysosomes at 12 h, but inhibited them at 24 h. At 48 h, the effects of OA incubation on autolysosomes were OA concentration-dependent in primary hepatocytes of P. fulvidraco. The results of flow cytometry and laser confocal observations confirmed these results. PA and OA incubation also increased intracellular non-esterified fatty acid (NEFA) concentration at 12 h, 24 h and 48 h, and influenced mRNA levels of fatty acid binding protein (fabp) and fatty acid transport protein 4 (fatp4) which facilitate FA transport in primary hepatocytes of P. fulvidraco. The present study demonstrated the molecular characterization of the nine autolysosome-related genes and their transcriptional responses to fat and FAs in fish, which provides the basis for further exploring their regulatory mechanism in vertebrates.


1970 ◽  
Vol 37 (3) ◽  
pp. 373-387 ◽  
Author(s):  
Anne-Marie Massart-Leën ◽  
S. Florescu ◽  
R. Verbeke ◽  
G. Peeters

SummaryLactating mammary glands of sheep and goats were perfused for several hours in the presence of [1-14C]palmitate or [1-14C]oleate. Adequate quantities of acetate, glucose, amino acids and chylomicrons were added to the perfusate.The fall in specific activity of [1-14C]palmitic acid or [1-14C]oleic acid across the gland and the labelling of milk triglyceride fatty acids indicates an extensive transfer of radioactivity from plasma free fatty acids (FFA). The plasma triglycerides showed large arterio-venous differences in concentration. The small [14C] incorporation in plasma triglycerides decreased across the gland. In a control experiment triglycerides were also slightly labelled.There were no significant arterio-venous differences in cholesterol esters and their fatty acid composition showed only slight changes during passage through the gland. Their specific activity showed a small rise across the gland.In milk components, the [14C] was mainly localized in the triglycerides. An appreciable proportion of the palmitoleate is derived from palmitate by dehydrogenation within the gland, while there is no evidence for the hydrogenation of oleic acid to stearic acid. Elongation of palmitic acid to C18-acids does not occur to any important extent. FFA are catabolized to a variable extent by the gland.The role of FFA in labelling of milk and blood plasma fatty acid fraction is discussed.


2002 ◽  
Vol 43 (8) ◽  
pp. 1303-1311 ◽  
Author(s):  
Song Lu ◽  
Mark Huffman ◽  
Ying Yao ◽  
Charles M. Mansbach ◽  
Xiangying Cheng ◽  
...  

To define the developmental expression of microsomal triglyceride transfer protein (MTP) large subunit mRNA and protein, samples of small intestine and liver were collected from 40-day gestation fetal, 2-day-old newborn, 3-week-old suckling, and 2-month-old weanling swine. In fetal animals, MTP mRNA expression was high in intestine and liver. Postnatally, jejunal expression paralleled the intake of a high-fat breast milk diet and declined after weaning. Ileal expression was comparable with that of jejunum in 2-day-old animals, but declined to low levels afterward. Hepatic expression declined postnatally and remained low. MTP protein expression generally paralleled mRNA expression, except in fetal intestine in which no 97 kDa protein was detected. In 2-day-old piglets, a high-triacylglycerol diet increased jejunal and ileal MTP mRNA levels, as compared to a low-triacylglycerol diet. To test the roles of glucocorticoids and fatty acids in MTP regulation, a newborn swine enterocyte cell line (IPEC-1) was used. Except at day 2 of differentiation, dexamethasone did not influence MTP expression. Fatty acids either up-regulated or down-regulated MTP expression, depending on the specific fatty acid and duration of exposure.Although programmed genetic cues regulate MTP expression during development, clearly the amount and fatty acid composition of dietary lipid also play regulatory roles.


Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 903
Author(s):  
Jen-Ying Hsu ◽  
Hui-Hsuan Lin ◽  
Charng-Cherng Chyau ◽  
Zhi-Hong Wang ◽  
Jing-Hsien Chen

Saturated fatty acid is one of the important nutrients, but contributes to lipotoxicity in the liver, causing hepatic steatosis. Aqueous pepino leaf extract (AEPL) in the previous study revealed alleviated liver lipid accumulation in metabolic syndrome mice. The study aimed to investigate the mechanism of AEPL on saturated long-chain fatty acid-induced lipotoxicity in HepG2 cells. Moreover, the phytochemical composition of AEPL was identified in the present study. HepG2 cells treated with palmitic acid (PA) were used for exploring the effect of AEPL on lipid accumulation, apoptosis, ER stress, and antioxidant response. The chemical composition of AEPL was analyzed by HPLC-ESI-MS/MS. AEPL treatment reduced PA-induced ROS production and lipid accumulation. Further molecular results revealed that AEPL restored cytochrome c in mitochondria and decreased caspase 3 activity to cease apoptosis. In addition, AEPL in PA-stressed HepG2 cells significantly reduced the ER stress and suppressed SREBP-1 activation for decreasing lipogenesis. For defending PA-induced oxidative stress, AEPL promoted Nrf2 expression and its target genes, SOD1 and GPX3, expressions. The present study suggested that AEPL protected from PA-induced lipotoxicity through reducing ER stress, increasing antioxidant ability, and inhibiting apoptosis. The efficacy of AEPL on lipotoxicity was probably concerned with kaempferol and isorhamnetin derived compounds.


2021 ◽  
Vol 3 (Supplement_1) ◽  
pp. i19-i19
Author(s):  
Divya Ravi ◽  
Carmen del Genio ◽  
Haider Ghiasuddin ◽  
Arti Gaur

Abstract Glioblastomas (GBM) or Stage IV gliomas, are the most aggressive of primary brain tumors and are associated with high mortality and morbidity. Patients diagnosed with this lethal cancer have a dismal survival rate of 14 months and a 5-year survival rate of 5.6% despite a multimodal therapeutic approach, including surgery, radiation therapy, and chemotherapy. Aberrant lipid metabolism, particularly abnormally active de novo fatty acid synthesis, is recognized to have a key role in tumor progression and chemoresistance in cancers. Previous studies have reported a high expression of fatty acid synthase (FASN) in patient tumors, leading to multiple investigations of FASN inhibition as a treatment strategy. However, none of these have developed as efficacious therapies. Furthermore, when we profiled FASN expression using The Cancer Genome Atlas (TCGA) we determined that high FASN expression in GBM patients did not confer a worse prognosis (HR: 1.06; p-value: 0.51) and was not overexpressed in GBM tumors compared to normal brain. Therefore, we need to reexamine the role of exogenous fatty acid uptake over de novofatty acid synthesis as a potential mechanism for tumor progression. Our study aims to measure and compare fatty acid oxidation (FAO) of endogenous and exogenous fatty acids between GBM patients and healthy controls. Using TCGA, we have identified the overexpression of multiple enzymes involved in mediating the transfer and activation of long-chain fatty acids (LCFA) in GBM tumors compared to normal brain tissue. We are currently conducting metabolic flux studies to (1) assess the biokinetics of LCFA degradation and (2) establish exogenous versus endogenous LCFA preferences between patient-derived primary GBM cells and healthy glial and immune cells during steady state and glucose-deprivation.


2009 ◽  
Vol 4 (10) ◽  
pp. 1934578X0900401 ◽  
Author(s):  
Christel Brunschwig ◽  
François Xavier Collard ◽  
Jean-Pierre Bianchini ◽  
Phila Raharivelomanana

In order to establish a chemical fingerprint of vanilla diversity, thirty samples of V. planifolia J. W. Moore and V. tahitensis G. Jackson cured beans from seven producing countries were examined for their aroma and fatty acid contents. Both fatty acid and aroma compositions were found to vary between vanilla species and origins. Vanillin was found in higher amounts in V. planifolia (1.7-3.6% of dry matter) than in V. tahitensis (1.0-2.0%), and anisyl compounds were found in lower amounts in V. planifolia (0.05%) than in V. tahitensis (1.4%-2.1%). Ten common and long chain monounsaturated fatty acids (LCFA) were identified and were found to be characteristic of the vanilla origin. LCFA derived from secondary metabolites have discriminating compositions as they reach 5.9% and 15.8% of total fatty acids, respectively in V. tahitensis and V. planifolia. This study highlights the role of the curing method as vanilla cured beans of two different species cultivated in the same country were found to have quite similar fatty acid compositions.


Diabetologia ◽  
2021 ◽  
Author(s):  
Yukina Takeichi ◽  
Takashi Miyazawa ◽  
Shohei Sakamoto ◽  
Yuki Hanada ◽  
Lixiang Wang ◽  
...  

Abstract Aims/hypothesis Mitochondria are highly dynamic organelles continuously undergoing fission and fusion, referred to as mitochondrial dynamics, to adapt to nutritional demands. Evidence suggests that impaired mitochondrial dynamics leads to metabolic abnormalities such as non-alcoholic steatohepatitis (NASH) phenotypes. However, how mitochondrial dynamics are involved in the development of NASH is poorly understood. This study aimed to elucidate the role of mitochondrial fission factor (MFF) in the development of NASH. Methods We created mice with hepatocyte-specific deletion of MFF (MffLiKO). MffLiKO mice fed normal chow diet (NCD) or high-fat diet (HFD) were evaluated for metabolic variables and their livers were examined by histological analysis. To elucidate the mechanism of development of NASH, we examined the expression of genes related to endoplasmic reticulum (ER) stress and lipid metabolism, and the secretion of triacylglycerol (TG) using the liver and primary hepatocytes isolated from MffLiKO and control mice. Results MffLiKO mice showed aberrant mitochondrial morphologies with no obvious NASH phenotypes during NCD, while they developed full-blown NASH phenotypes in response to HFD. Expression of genes related to ER stress was markedly upregulated in the liver from MffLiKO mice. In addition, expression of genes related to hepatic TG secretion was downregulated, with reduced hepatic TG secretion in MffLiKO mice in vivo and in primary cultures of MFF-deficient hepatocytes in vitro. Furthermore, thapsigargin-induced ER stress suppressed TG secretion in primary hepatocytes isolated from control mice. Conclusions/interpretation We demonstrated that ablation of MFF in liver provoked ER stress and reduced hepatic TG secretion in vivo and in vitro. Moreover, MffLiKO mice were more susceptible to HFD-induced NASH phenotype than control mice, partly because of ER stress-induced apoptosis of hepatocytes and suppression of TG secretion from hepatocytes. This study provides evidence for the role of mitochondrial fission in the development of NASH. Graphical abstract


2009 ◽  
Vol 34 (3) ◽  
pp. 315-322 ◽  
Author(s):  
Gregory R. Steinberg

During moderate-intensity exercise, fatty acids are the predominant substrate for working skeletal muscle. The release of fatty acids from adipose tissue stores, combined with the ability of skeletal muscle to actively fine tune the gradient between fatty acid and carbohydrate metabolism, depending on substrate availability and energetic demands, requires a coordinated system of metabolic control. Over the past decade, since the discovery that AMP-activated protein kinase (AMPK) was increased in accordance with exercise intensity, there has been significant interest in the proposed role of this ancient stress-sensing kinase as a critical integrative switch controlling metabolic responses during exercise. In this review, studies examining the role of AMPK as a regulator of fatty acid metabolism in both adipose tissue and skeletal muscle during exercise will be discussed. Exercise induces activation of AMPK in adipocytes and regulates triglyceride hydrolysis and esterfication through phosphorylation of hormone sensitive lipase (HSL) and glycerol-3-phosphate acyl-transferase, respectively. In skeletal muscle, exercise-induced activation of AMPK is associated with increases in fatty acid uptake, phosphorylation of HSL, and increased fatty acid oxidation, which is thought to occur via the acetyl-CoA carboxylase-malony-CoA-CPT-1 signalling axis. Despite the importance of AMPK in regulating fatty acid metabolism under resting conditions, recent evidence from transgenic models of AMPK deficiency suggest that alternative signalling pathways may also be important for the control of fatty acid metabolism during exercise.


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