scholarly journals The Role of Cation Diffusion Facilitator CDF-1 in Lipid Metabolism in Caenorhabditis elegans

2021 ◽  
Author(s):  
Ying Hu ◽  
Yanli Wang ◽  
Xuanjun Wang ◽  
Xiaoyun Wu ◽  
Lin Fu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Lipid Accumulation ◽  
Unsaturated Fatty Acids ◽  
Metabolic Diseases ◽  
Regulatory Element ◽  
Zinc Level ◽  
Zinc Homeostasis ◽  
Cation Diffusion ◽  
Cation Diffusion Facilitator

Abstract Zinc is one of the most important trace elements as it plays a vital role in many biological processes. As well, aberrant zinc metabolism has been implicated in lipid-related metabolic diseases. Previously, we showed that zinc antagonizes iron to regulate sterol regulatory element-binding proteins and the stearoyl-CoA desaturase (SREBP-SCD) pathway in lipid metabolism in the model organism Caenorhabditis elegans. In this study we present the identification of another cation diffusion facilitator, CDF-1, which regulates lipid metabolism along with SUR-7 in response to zinc. Inactivation of SBP-1, the only homolog of SREBPs, leads to an increased zinc level but decreased lipid accumulation. However, either the cdf-1(n2527) or sur-7(tm6523) mutation could successfully restore the altered fatty acid profile, fat content, and zinc level of the sbp-1(ep79) mutant. Furthermore, we found that CDF-1/SUR-7 may functionally bypass SBP-1 to directly affect the conversion activity of SCD in the biosynthesis of unsaturated fatty acids and lipid accumulation. Collectively, these results consistently support the link between zinc homeostasis and lipid metabolism via the SREBP-SCD axis by the cation diffusion facilitators CDF-1 and SUR-7.

scholarly journals The role of cation diffusion facilitator CDF-1 in lipid metabolism in Caenorhabditis elegans

2020 ◽  
Author(s):  
Ying Hu ◽  
Yanli Wang ◽  
Xuanjun Wang ◽  
Xiaoyun Wu ◽  
Lin Fu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Lipid Accumulation ◽  
Unsaturated Fatty Acids ◽  
Metabolic Diseases ◽  
Regulatory Element ◽  
Zinc Level ◽  
Zinc Homeostasis ◽  
Cation Diffusion ◽  
Cation Diffusion Facilitator

AbstractZinc is one of the most important trace elements that plays a vital role in many biological processes, and aberrant zinc metabolism has been implicated in lipid-related metabolic diseases. Previously, we showed that zinc antagonizes iron to regulate sterol regulatory element-binding proteins and stearoyl-CoA desaturase (SREBP-SCD) pathway in lipid metabolism in model organism Caenorhabditis elegans. Here, we further identified another cation diffusion facilitator CDF-1 in addition to SUR-7 in response to zinc to regulate lipid metabolism. Inactivation of SBP-1, the only homolog of SREBPs, leads to increased zinc level but decreased lipid accumulation reversely. However, either cdf-1(n2527) or sur-7(tm6523) mutation could successfully restore the altered fatty acid profile, fat content and zinc level of sbp-1(ep79) mutant. Furthermore, we found that CDF-1/SUR-7 may function bypass SBP-1 to directly affect the conversion activity of SCD in the biosynthesis of unsaturated fatty acids and lipid accumulation. Collectively, these results consistently support the link between zinc homeostasis and lipid metabolism via SREBP-SCD axis by cation diffusion facilitators CDF-1 and SUR-7.

scholarly journals Effects on Liver Lipid Metabolism of the Naturally Occurring Dietary Flavone Luteolin-7-glucoside

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Carla Sá ◽  
Ana Rita Oliveira ◽  
Cátia Machado ◽  
Marisa Azevedo ◽  
Cristina Pereira-Wilson
Keyword(s):  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Regulatory Element ◽  
Lipid Lowering ◽  
Whole Body ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Hepatic Expression

Disruptions in whole-body lipid metabolism can lead to the onset of several pathologies such as nonalcoholic fatty liver disease (NAFLD) and cardiovascular diseases (CVDs). The present study aimed at elucidating the molecular mechanisms behind the lipid-lowering effects of the flavone luteolin-7-glucoside (L7G) which we previously showed to improve plasma lipid profile in rats. L7G is abundant in plant foods of Mediterranean diet such as aromatic plants used as herbs. Results show that dietary supplementation with L7G for one week induced the expression of peroxisome proliferator-activated receptor-alpha (PPAR-α) and of its target gene carnitine palmitoyl transferase 1 (CPT-1) in rat liver. L7G showed a tendency to decrease the hepatic expression of sterol regulatory element-binding protein-1 (SREBP-1), without affecting fatty acid synthase (FAS) protein levels. Although SREBP-2 and LDLr mRNA levels did not change, the expression of HMG CoA reductase (HMGCR) was significantly repressed by L7G. L7G also inhibited this enzyme’sin vitroactivity in a dose dependent manner, but only at high and not physiologically relevant concentrations. These results add new evidence that the flavone luteolin-7-glucoside may help in preventing metabolic diseases and clarify the mechanisms underlying the beneficial health effects of diets rich in fruits and vegetables.

scholarly journals Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis

2019 ◽  
Vol 317 (4) ◽  
pp. H793-H810 ◽  
Author(s):  
Qiying Fan ◽  
Xing Yin ◽  
Abeer Rababa’h ◽  
Andrea Diaz Diaz ◽  
Cori S. Wijaya ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Protein Kinase ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Regulatory Element ◽  
Plaque Formation ◽  
High Fat ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Gravin, an A-kinase anchoring protein, is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development, namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat diet (HFD)-induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed a normal diet or an HFD for 16 wk. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared with WT mice on HFD. Furthermore, there was less aortic plaque formation coupled with decreased lipid accumulation and liver damage, as the gravin-t/t mice had lower levels of serum alanine aminotransferase and aspartate aminotransferase. Additionally, gravin-t/t HFD-fed mice had decreased expression of liver 3-hydroxy-3-methyl-glutaryl-CoA reductase, an essential enzyme for cholesterol synthesis and lower fatty acid synthase expression. Gravin-t/t HFD-fed mice also exhibited inhibition of sterol regulatory element binding protein-2 (SREBP-2) expression, a liver transcription factor associated with the regulation of lipid transportation. In response to platelet-derived growth factor receptor treatment, gravin-t/t vascular smooth muscle cells exhibited lower intracellular calcium transients and decreased protein kinase A- and protein kinase C-dependent substrate phosphorylation, notably involving the Erk1/2 signaling pathway. Collectively, these results suggest the involvement of gravin-dependent regulation of lipid metabolism via the reduction of SREBP-2 expression. The absence of gravin-mediated signaling lowers blood pressure, reduces plaque formation in the aorta, and decreases lipid accumulation and damage in the liver of HFD mice. Through these processes, the absence of gravin-mediated signaling complex delays the HFD-induced hyperlipidemia and atherosclerosis. NEW & NOTEWORTHY The gravin scaffolding protein plays a key role in the multiple enzymatic pathways of lipid metabolism. We have shown for the first time the novel role of gravin in regulating the pathways related to the initiation and progression of atherosclerosis. Specifically, an absence of gravin-mediated signaling decreases the lipid levels (cholesterol, triglyceride, and VLDL) that are associated with sterol regulatory element binding protein-2 downregulation.

scholarly journals Enhanced Liver Regeneration After Partial Hepatectomy in Sterol Regulatory Element-Binding Protein (SREBP)-1c-Null Mice is Associated with Increased Hepatocellular Cholesterol Availability

2018 ◽  
Vol 47 (2) ◽  
pp. 784-799 ◽  
Author(s):  
Jun Peng ◽  
Jingwei Yu ◽  
Hu Xu ◽  
Chen Kang ◽  
Philip W. Shaul ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Lipid Accumulation ◽  
Cellular Proliferation ◽  
Cholesterol Metabolism ◽  
Regulatory Element ◽  
Hepatocyte Proliferation ◽  
Sterol Regulatory Element

Background/Aims: Transient lipid accumulation within hepatocytes preceding the peak proliferative process is a characteristic feature of liver regeneration. However, molecular mediators responsible for this lipid accumulation and their functions are not well defined. Sterol regulatory element-binding proteins-1c (SREBP-1c) are critical transcriptional factors that regulate lipid homeostasis in the liver. We hypothesized that SREBP-1c deficiency induced alterations of lipid metabolism may influence hepatocyte proliferation and liver regeneration. Methods: 2/3 partial hepatectomy (PH) was performed in wild type C57BL/6J (WT) and Srebp-1c-/- mice. The lipid contents in serum and liver were measured by enzymatic colorimetric methods. Hepatic lipid droplets were detected by Oil Red O staining and immunohistological staining. Hepatic expression of genes involved in lipid metabolism and cellular proliferation was determined by real-time PCR and/or immunoblot. Hepatocyte proliferation and liver regeneration were assessed by BrdU staining and the weight of remanent liver lobes in Srebp-1c-/- mice, respectively. Results: Srebp-1c-/- mice displayed reduced triglyceride and fatty acids but increased cholesterol in the liver before PH. In response to PH, hepatocellular DNA synthesis was elevated and cell cycle progression was prolonged in Srebp-1c-/- mice, which was associated with enhanced liver regeneration. However, Srebp-1c-/- mice had comparable triglyceride and fatty acid contents and expressions of related genes compared with WT mice during the liver regeneration. In contrast, SREBP-1c-deficiency-induced alteration of cholesterol metabolism was retained during the liver regeneration after PH. Srebp-1c-/- mice exhibited higher cholesterol contents and enhanced expression of SREBP-2 and 3-hydroxy-3-methylglutaryl-Coenzyme A reductase (HMGCR) in the liver than WT mice after PH. Moreover, downregulation of genes involved in cholesterol elimination was observed after PH in Srebp-1c-/- mice. Conclusion: SREBP-1c deficiency in mice did not interfere with triglyceride and fatty acid metabolism but was associated with significant changes in cholesterol profiles during liver regeneration after PH. These results suggest that increased hepatocellular cholesterol storage and cholesterol availability with the enhanced liver regeneration are identified in Srebp-1c-/- mice. This study also shows that providing requisite cholesterol levels to proliferating hepatocytes and keeping appropriate cholesterol metabolism are required for normal liver regeneration.

scholarly journals Cation Diffusion Facilitator Cis4 Is Implicated in Golgi Membrane Trafficking via Regulating Zinc Homeostasis in Fission Yeast

2008 ◽  
Vol 19 (4) ◽  
pp. 1295-1303 ◽  
Author(s):  
Yue Fang ◽  
Reiko Sugiura ◽  
Yan Ma ◽  
Tomoko Yada-Matsushima ◽  
Hirotatsu Umeno ◽  
...  
Keyword(s):  
Fission Yeast ◽  
Membrane Trafficking ◽  
Zinc Homeostasis ◽  
Golgi Membrane ◽  
High Concentration ◽  
Cation Diffusion ◽  
Gene Encoding ◽  
Cation Diffusion Facilitator ◽  
Functional Complex ◽  
Mutant Cells

We screened for mutations that confer sensitivities to the calcineurin inhibitor FK506 and to a high concentration of MgCl2 and isolated the cis4-1 mutant, an allele of the gene encoding a cation diffusion facilitator (CDF) protein that is structurally related to zinc transporters. Consistently, the addition of extracellular Zn2+ suppressed the phenotypes of the cis4 mutant cells. The cis4 mutants and the mutant cells of another CDF-encoding gene SPBC16E9.14c (we named zrg17+) shared common and nonadditive zinc-suppressible phenotypes, and Cis4 and Zrg17 physically interacted. Cis4 localized at the cis-Golgi, suggesting that Cis4 is responsible for Zn2+ uptake to the cis-Golgi. The cis4 mutant cells showed phenotypes such as weak cell wall and decreased acid phosphatase secretion that are thought to be resulting from impaired membrane trafficking. In addition, the cis4 deletion cells showed synthetic growth defects with all the four membrane-trafficking mutants tested, namely ypt3-i5, ryh1-i6, gdi1-i11, and apm1-1. Interestingly, the addition of extracellular Zn2+ significantly suppressed the phenotypes of the ypt3-i5 and apm1-1 mutant cells. These results suggest that Cis4 forms a heteromeric functional complex with Zrg17 and that Cis4 is implicated in Golgi membrane trafficking through the regulation of zinc homeostasis in fission yeast.

scholarly journals The farnesoid X receptor modulates renal lipid metabolism and diet-induced renal inflammation, fibrosis, and proteinuria

2009 ◽  
Vol 297 (6) ◽  
pp. F1587-F1596 ◽  
Author(s):  
Xiaoxin X. Wang ◽  
Tao Jiang ◽  
Yan Shen ◽  
Luciano Adorini ◽  
Mark Pruzanski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Growth Factors ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Regulatory Element ◽  
Critical Role ◽  
Farnesoid X Receptor ◽  
Mesangial Expansion ◽  
Triglyceride Accumulation ◽  
Podocyte Loss

Diet-induced obesity is associated with proteinuria and glomerular disease in humans and rodents. We have shown that in mice fed a high-fat diet, increased renal expression of the transcriptional factor sterol-regulatory element binding protein-1 (SREBP-1) plays a critical role in renal lipid accumulation and increases the activity of proinflammatory cytokines and profibrotic growth factors. In the current study, we have determined a key role of the farnesoid X receptor (FXR) in modulating renal SREBP-1 activity, glomerular lesions, and proteinuria. We found that feeding a Western-style diet to DBA/2J mice results in proteinuria, podocyte loss, mesangial expansion, renal lipid accumulation, and increased expression of proinflammatory factors, oxidative stress, and profibrotic growth factors. Treatment of these mice with the highly selective and potent FXR-activating ligand 6-α-ethyl-chenodeoxycholic acid (INT-747) ameliorates triglyceride accumulation by modulating fatty acid synthesis and oxidation, improves proteinuria, prevents podocyte loss, mesangial expansion, accumulation of extracellular matrix proteins, and increased expression of profibrotic growth factors and fibrosis markers, and modulates inflammation and oxidative stress. Our results therefore indicate that FXR activation could represent an effective therapy for treatment of abnormal renal lipid metabolism with associated inflammation, oxidative stress, and kidney pathology in patients affected by obesity.

scholarly journals Recent insight into the correlation of SREBP-mediated lipid metabolism and innate immune response

2018 ◽  
Vol 61 (3) ◽  
pp. R123-R131 ◽  
Author(s):  
Hyeon Young Park ◽  
Hye Suk Kang ◽  
Seung-Soon Im
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Regulatory Element ◽  
Acid Synthesis ◽  
Metabolic Intermediates ◽  
Sterol Regulatory Element ◽  
Insight Into

Fatty acids are essential nutrients that contribute to several intracellular functions. Fatty acid synthesis and oxidation are known to be regulated by sterol regulatory element-binding proteins (SREBPs), which play a pivotal role in the regulation of cellular triglyceride synthesis and cholesterol biogenesis. Recent studies point to a multifunctional role of SREBPs in the pathogenesis of metabolic diseases, such as obesity, type II diabetes and cancer as well as in immune responses. Notably, fatty acid metabolic intermediates are involved in energy homeostasis and pathophysiological conditions. In particular, intracellular fatty acid metabolism affects an inflammatory response, thereby influencing metabolic diseases. The objective of this review is to summarize the recent advances in our understanding of the dual role of SREBPs in both lipid metabolism and inflammation-mediated metabolic diseases.

scholarly journals Effects of Phosphoethanolamine Supplementation on Mitochondrial Activity and Lipogenesis in a Caffeine Ingestion Caenorhabditis elegans Model

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3348
Author(s):  
Hyemin Min ◽  
Esther Youn ◽  
Jaehoon Kim ◽  
Su Young Son ◽  
Choong Hwan Lee ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Caenorhabditis Elegans ◽  
Regulatory Element ◽  
Caffeine Intake ◽  
Mitochondrial Activity ◽  
Mitochondrial Morphology ◽  
Caffeine Ingestion ◽  
C Elegans ◽  
Element Binding Protein ◽  
Amp Activated Protein Kinase

Caffeine intake is strongly linked to lipid metabolism. We previously reported the age-dependent physiological effects of caffeine intake in a Caenorhabditis elegans model. Since nutritional status can actively influence metabolism and overall health, in this study, we evaluated the effect of caffeine intake on lipid metabolism in adult-stage C. elegans. We found that, in C. elegans, fat storage and the level of phosphoethanolamine (PE) were significantly reduced with caffeine intake. In addition, mitochondrial activity decreased and mitochondrial morphology was disrupted, and the expression of oxidative stress response genes, hsp-6, gst-4, and daf-16, was induced by caffeine intake. Furthermore, the level of an energy metabolism sensor, phospho-AMP-activated protein kinase, was increased, whereas the expression of the sterol regulatory element binding protein gene and its target stearoyl-CoA desaturase genes, fat-5, -6, and -7, was decreased with caffeine intake. These findings suggest that caffeine intake causes mitochondrial dysfunction and reduces lipogenesis. Interestingly, these changes induced by caffeine intake were partially alleviated by PE supplementation, suggesting that the reduction in mitochondrial activity and lipogenesis is in part because of the low PE level, and proper dietary supplementation can improve organelle integrity.

scholarly journals How does hepatic lipid accumulation lead to lipotoxicity in non-alcoholic fatty liver disease?

2021 ◽  
Vol 15 (1) ◽  
pp. 21-35
Author(s):  
Yana Geng ◽  
Klaas Nico Faber ◽  
Vincent E. de Meijer ◽  
Hans Blokzijl ◽  
Han Moshage
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Lipid Uptake ◽  
Cellular Mechanisms ◽  
Alcoholic Fatty Liver ◽  
Lipid Species ◽  
Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD), characterized as excess lipid accumulation in the liver which is not due to alcohol use, has emerged as one of the major health problems around the world. The dysregulated lipid metabolism creates a lipotoxic environment which promotes the development of NAFLD, especially the progression from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Purposeand Aim This review focuses on the mechanisms of lipid accumulation in the liver, with an emphasis on the metabolic fate of free fatty acids (FFAs) in NAFLD and presents an update on the relevant cellular processes/mechanisms that are involved in lipotoxicity. The changes in the levels of various lipid species that result from the imbalance between lipolysis/lipid uptake/lipogenesis and lipid oxidation/secretion can cause organellar dysfunction, e.g. ER stress, mitochondrial dysfunction, lysosomal dysfunction, JNK activation, secretion of extracellular vesicles (EVs) and aggravate (or be exacerbated by) hypoxia which ultimately lead to cell death. The aim of this review is to provide an overview of how abnormal lipid metabolism leads to lipotoxicity and the cellular mechanisms of lipotoxicity in the context of NAFLD.

Sign in / Sign up

Export Citation Format

Share Document