Integrative analyses of gene expression and alternative splicing to gain insights into the effects of copper on hepatic lipid metabolism in swamp eel (Monopterus albus)

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 μg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1β mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1β mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.

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Altered hepatic lipid metabolism in C57BL/6 mice fed alcohol: a targeted lipidomic and gene expression study

The Journal of Lipid Research ◽

10.1194/jlr.m017368 ◽

2011 ◽

Vol 52 (11) ◽

pp. 2021-2031 ◽

Cited By ~ 66

Author(s):

Robin D. Clugston ◽

Hongfeng Jiang ◽

Man Xia Lee ◽

Roseann Piantedosi ◽

Jason J. Yuen ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Gene Expression Study ◽

Hepatic Lipid Metabolism ◽

Expression Study ◽

Hepatic Lipid

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Hypoxia-Inducible Factor 2 Regulates Hepatic Lipid Metabolism

Molecular and Cellular Biology ◽

10.1128/mcb.00200-09 ◽

2009 ◽

Vol 29 (16) ◽

pp. 4527-4538 ◽

Cited By ~ 195

Author(s):

Erinn B. Rankin ◽

Jennifer Rha ◽

Mary A. Selak ◽

Travis L. Unger ◽

Brian Keith ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Hypoxia Inducible Factor ◽

Hepatic Tissue ◽

Low Oxygen ◽

Hepatic Lipid Metabolism ◽

Peripheral Tissues ◽

Hepatic Lipid ◽

Normal Hepatocyte ◽

Oxygen Sensitive

ABSTRACT In mammals, the liver integrates nutrient uptake and delivery of carbohydrates and lipids to peripheral tissues to control overall energy balance. Hepatocytes maintain metabolic homeostasis by coordinating gene expression programs in response to dietary and systemic signals. Hepatic tissue oxygenation is an important systemic signal that contributes to normal hepatocyte function as well as disease. Hypoxia-inducible factors 1 and 2 (HIF-1 and HIF-2, respectively) are oxygen-sensitive heterodimeric transcription factors, which act as key mediators of cellular adaptation to low oxygen. Previously, we have shown that HIF-2 plays an important role in both physiologic and pathophysiologic processes in the liver. HIF-2 is essential for normal fetal EPO production and erythropoiesis, while constitutive HIF-2 activity in the adult results in polycythemia and vascular tumorigenesis. Here we report a novel role for HIF-2 in regulating hepatic lipid metabolism. We found that constitutive activation of HIF-2 in the adult results in the development of severe hepatic steatosis associated with impaired fatty acid β-oxidation, decreased lipogenic gene expression, and increased lipid storage capacity. These findings demonstrate that HIF-2 functions as an important regulator of hepatic lipid metabolism and identify HIF-2 as a potential target for the treatment of fatty liver disease.

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Effects of maternal treatment of dehydroepiandrosterone (DHEA) on serum lipid profile and hepatic lipid metabolism-related gene expression in embryonic chickens

Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology ◽

10.1016/j.cbpb.2009.12.005 ◽

2010 ◽

Vol 155 (4) ◽

pp. 380-386 ◽

Cited By ~ 9

Author(s):

Juan Chen ◽

Xue Tang ◽

Yuanshu Zhang ◽

Haitian Ma ◽

Sixiang Zou

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Lipid Profile ◽

Serum Lipid ◽

Serum Lipid Profile ◽

Related Gene ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Maternal Treatment

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Effects of perilipin 2 antisense oligonucleotide treatment on hepatic lipid metabolism and gene expression

Physiological Genomics ◽

10.1152/physiolgenomics.00045.2012 ◽

2012 ◽

Vol 44 (22) ◽

pp. 1125-1131 ◽

Cited By ~ 32

Author(s):

Yumi Imai ◽

Siobhan Boyle ◽

Gladys M. Varela ◽

Emilie Caron ◽

Xiaoyan Yin ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Liver Disease ◽

Fatty Liver ◽

Antisense Oligonucleotide ◽

High Fat Diet ◽

High Fat ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Perilipin 2

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide. We previously showed that Perilipin 2 (Plin2), a member of lipid droplet protein family, is markedly increased in fatty liver, and its reduction in the liver of diet-induced obese mice by antisense oligonucleotide (ASO) decreased steatosis and enhanced insulin sensitivity. Plin2-ASO treatment markedly suppressed lipogenic gene expression. To gain a better understanding of the biological role of Plin2 in liver, we performed microarray analysis to determine genes differentially regulated by Plin2-ASO compared with a control (scrambled) oligonucleotide (Cont). Male C57BL/6J mice on a high-fat diet were treated with Plin2- or Cont-ASO for 4 wk. Plin2-ASO decreased hepatic triglycerides, and this was associated with changes in expression of 1,363 genes. We analyzed the data for functional clustering and validated the expression of representative genes using real-time PCR. On the high-fat diet, Plin2-ASO decreased the expression of enzymes involved in fatty acid metabolism ( acsl1, lipe) and steroid metabolism ( hmgcr, hsd3b5, hsd17b2), suggesting that Plin2 affects hepatic lipid metabolism at the transcriptional level. Plin2-ASO also increased the expression of genes involved in regulation of hepatocyte proliferation ( afp, H19), mitosis ( ccna2, incenp, sgol1), and extracellular matrix ( col1a1, col3a1, mmp8). Plin2-ASO had similar effects on gene expression in chow-fed mice. Together, these results indicate that Plin2 has diverse metabolic and structural roles in the liver, and its downregulation promotes hepatic fibrosis and proliferation.

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A Soy Protein Diet Alters Hepatic Lipid Metabolism Gene Expression and Reduces Serum Lipids and Renal Fibrogenic Cytokines in Rats with Chronic Nephrotic Syndrome

Journal of Nutrition ◽

10.1093/jn/132.9.2562 ◽

2002 ◽

Vol 132 (9) ◽

pp. 2562-2569 ◽

Cited By ~ 75

Author(s):

Armando R. Tovar ◽

Fernanda Murguía ◽

Cristino Cruz ◽

Rogelio Hernández-Pando ◽

Carlos A. Aguilar-Salinas ◽

...

Keyword(s):

Gene Expression ◽

Nephrotic Syndrome ◽

Lipid Metabolism ◽

Soy Protein ◽

Serum Lipids ◽

Protein Diet ◽

Hepatic Lipid Metabolism ◽

Hepatic Lipid ◽

Lipid Metabolism Gene ◽

Metabolism Gene

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Altered Hepatic Lipid Metabolism Contributes to Nonalcoholic Fatty Liver Disease in Leptin-Deficient Ob/Ob Mice

Journal of Obesity ◽

10.1155/2013/296537 ◽

2013 ◽

Vol 2013 ◽

pp. 1-8 ◽

Cited By ~ 36

Author(s):

James W. Perfield ◽

Laura C. Ortinau ◽

R. Taylor Pickering ◽

Meghan L. Ruebel ◽

Grace M. Meers ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Liver Disease ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Fatty Liver Disease ◽

De Novo ◽

Hepatic Lipid Metabolism ◽

Nonalcoholic Fatty Liver ◽

Hepatic Lipid

Nonalcoholic fatty liver disease (NAFLD) is strongly linked to obesity, insulin resistance, and abnormal hepatic lipid metabolism; however, the precise regulation of these processes remains poorly understood. Here we examined genes and proteins involved in hepatic oxidation and lipogenesis in 14-week-old leptin-deficient Ob/Ob mice, a commonly studied model of obesity and hepatic steatosis. Obese Ob/Ob mice had increased fasting glucose, insulin, and calculated HOMA-IR as compared with lean wild-type (WT) mice. Ob/Ob mice also had greater liver weights, hepatic triglyceride (TG) content, and markers ofde novolipogenesis, including increased hepatic gene expression and protein content of acetyl-CoA carboxylase (ACC), fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD-1), as well as elevated gene expression of PPARγand SREBP-1c compared with WT mice. While hepatic mRNA levels for PGC-1α, PPARα, and TFAM were elevated in Ob/Ob mice, measures of mitochondrial function (β-HAD activity and complete (to CO2) and total mitochondrial palmitate oxidation) and mitochondrial OXPHOS protein subunits I, III, and V content were significantly reduced compared with WT animals. In summary, reduced hepatic mitochondrial content and function and an upregulation inde novolipogenesis contribute to obesity-associated NAFLD in the leptin-deficient Ob/Ob mouse.

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