scholarly journals TFEB: A Emerging Regulator in Lipid Homeostasis for Atherosclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Manman Li ◽  
Zitong Wang ◽  
Pengyu Wang ◽  
Hong Li ◽  
Liming Yang
Keyword(s):  
Lipid Metabolism ◽  
Lipid Homeostasis ◽  
Cell Physiology ◽  
Post Translational Modifications ◽  
Transcription Factor Eb ◽  
Lipid Transporters ◽  
Intracellular Activities ◽  
Atherosclerotic Process ◽  
External Stimuli

Atherosclerosis, predominantly characterized by the disturbance of lipid homeostasis, has become the main causation of various cardiovascular diseases. Therefore, there is an urgent requirement to explore efficacious targets that act as lipid modulators for atherosclerosis. Transcription factor EB (TFEB), whose activity depends on post-translational modifications, such as phosphorylation, acetylation, SUMOylation, ubiquitination, etc., is significant for normal cell physiology. Recently, increasing evidence implicates a role of TFEB in lipid homeostasis, via its functionality of promoting lipid degradation and efflux through mediating lipophagy, lipolysis, and lipid metabolism-related genes. Furthermore, a regulatory effect on lipid transporters and lipid mediators by TFEB is emerging. Notably, TFEB makes a possible therapeutic target of atherosclerosis by regulating lipid metabolism. This review recapitulates the update and current advances on TFEB mediating lipid metabolism to focus on two intracellular activities: a) how cells perceive external stimuli and initiate transcription programs to modulate TFEB function, and b) how TFEB restores lipid homeostasis in the atherosclerotic process. In-depth research is warranted to develop potent agents against TFEB to alleviate or reverse the progression of atherosclerosis.

scholarly journals High Fat Activates O-GlcNAcylation and Affects AMPK/ACC Pathway to Regulate Lipid Metabolism

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1740
Author(s):  
Yuning Pang ◽  
Xiang Xu ◽  
Xiaojun Xiang ◽  
Yongnan Li ◽  
Zengqi Zhao ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
High Fat Diet ◽  
Lipid Synthesis ◽  
Fat Deposition ◽  
Liver Fat ◽  
Lipid Homeostasis ◽  
High Fat ◽  
Dual Inhibitor ◽  
Regulate Lipid Metabolism

A high-fat diet often leads to excessive fat deposition and adversely affects the organism. However, the mechanism of liver fat deposition induced by high fat is still unclear. Therefore, this study aimed at acetyl-CoA carboxylase (ACC) to explore the mechanism of excessive liver deposition induced by high fat. In the present study, the ORF of ACC1 and ACC2 were cloned and characterized. Meanwhile, the mRNA and protein of ACC1 and ACC2 were increased in liver fed with a high-fat diet (HFD) or in hepatocytes incubated with oleic acid (OA). The phosphorylation of ACC was also decreased in hepatocytes incubated with OA. Moreover, AICAR dramatically improved the phosphorylation of ACC, and OA significantly inhibited the phosphorylation of the AMPK/ACC pathway. Further experiments showed that OA increased global O-GlcNAcylation and agonist of O-GlcNAcylation significantly inhibited the phosphorylation of AMPK and ACC. Importantly, the disorder of lipid metabolism caused by HFD or OA could be rescued by treating CP-640186, the dual inhibitor of ACC1 and ACC2. These observations suggested that high fat may activate O-GlcNAcylation and affect the AMPK/ACC pathway to regulate lipid synthesis, and also emphasized the importance of the role of ACC in lipid homeostasis.

scholarly journals Examining the role of ABC lipid transporters in pulmonary lipid homeostasis and inflammation

2017 ◽  
Vol 18 (1) ◽  
Author(s):  
Amanda B. Chai ◽  
Alaina J. Ammit ◽  
Ingrid C. Gelissen
Keyword(s):  
Lipid Homeostasis ◽  
Lipid Transporters

scholarly journals Circadian clock control of hepatic lipid metabolism: role of small heterodimer partner (Shp)

2016 ◽  
Vol 64 (7) ◽  
pp. 1158-1161 ◽  
Author(s):  
Li Wang ◽  
Suthat Liangpunsakul
Keyword(s):  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Homeostasis ◽  
Pas Domain ◽  
Hepatic Lipid Metabolism ◽  
Small Heterodimer Partner ◽  
Excessive Alcohol ◽  
Review Reports ◽  
Clock Mechanism

Hepatic steatosis, the accumulation of triglyceride droplets in the hepatocytes, is a common hepatic pathology seen in subjects with obesity/metabolic syndrome and those with excessive alcohol use. The pathogenesis underlying hepatic steatosis is complex. Recent studies have shown the specific role played by the molecular clock mechanism in the control of lipid metabolism and that the disruption of these tissue clocks may lead to the disturbances in lipid homeostasis. This review reports a novel role of small heterodimer partner in maintaining triglyceride and lipoprotein homeostasis through neuronal PAS domain protein 2.

scholarly journals Investigating the Role Intestinal-Specific FXR and SHP in Regulating Lipid Metabolism in Mice

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A810-A810
Author(s):  
James ThienToan Nguyen ◽  
Sayeepriyadarshini Anakk
Keyword(s):  
Lipid Metabolism ◽  
Bile Acid ◽  
Farnesoid X Receptor ◽  
Dietary Fats ◽  
Lipid Absorption ◽  
Mice Model ◽  
Simple Diffusion ◽  
Bile Acid Concentration ◽  
Lipid Transporters

Abstract Dysregulation of lipid metabolism is a causal factor that can lead to a variety of disorders, such as obesity and metabolic syndrome. Dietary fats are digested in the small intestine by the physiological detergents known as bile acids. They emulsify the fats and break them down into smaller molecules in order for the enterocytes to absorb the nutrients through simple diffusion or through the utilization of specific lipid transporters. Interestingly, the nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) not only regulates bile acid synthesis and circulation, but also lipid metabolism. Although many studies have examined the role of FXR in hepatic and intestinal lipid metabolism, studies investigating the role of SHP in the intestine are still lacking. Although FXR and SHP cooperate to regulate many metabolic pathways, FXR or SHP knockout models exhibit different lipid phenotypes. These data indicate there are FXR-dependent and -independent pathways of SHP that controls lipid metabolism. To delineate these two interconnecting yet separate pathways, we will utilize intestine-specific Shp knockout (IShpKO) and intestine-specific Fxr knockout (IFxrKO) mice model and place them on high fat diet to investigate their intestinal intestinal absorption and transportation of lipids. We will also monitor the bile acid pool in the intestine, serum, and liver in these knockouts to evaluate the consequence of intestinal deletion of Fxr as well as Shp on bile acid homeostasis and how this may affect lipid absorption. These experiments will identify how FXR and/or SHP regulates intestinal fat digestion and absorption and if this is secondary to the alterations in bile acid concentration and lipid transporters. In addition, we will also investigate the intestinal Fxr-Shp double knockout (IDKO) mice model to determine their combined contribution in intestinal lipid metabolism. Overall, the results obtained from this research will elucidate if intestinal FXR and SHP cooperate or can independently regulate lipid metabolism and homeostasis.

scholarly journals PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice

2020 ◽  
Vol 21 (6) ◽  
pp. 2061 ◽  
Author(s):  
Yaping Wang ◽  
Takero Nakajima ◽  
Frank J. Gonzalez ◽  
Naoki Tanaka
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Liver Cancer ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Lipid Homeostasis ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Metabolic Regulators

Peroxisome proliferator-activated receptor (PPAR) α, β/δ, and γ modulate lipid homeostasis. PPARα regulates lipid metabolism in the liver, the organ that largely controls whole-body nutrient/energy homeostasis, and its abnormalities may lead to hepatic steatosis, steatohepatitis, steatofibrosis, and liver cancer. PPARβ/δ promotes fatty acid β-oxidation largely in extrahepatic organs, and PPARγ stores triacylglycerol in adipocytes. Investigations using liver-specific PPAR-disrupted mice have revealed major but distinct contributions of the three PPARs in the liver. This review summarizes the findings of liver-specific PPAR-null mice and discusses the role of PPARs in the liver.

scholarly journals Linking Gut Microbiome and Lipid Metabolism: Moving beyond Associations

Metabolites ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 55
Author(s):  
Santosh Lamichhane ◽  
Partho Sen ◽  
Marina Amaral Alves ◽  
Henrique C. Ribeiro ◽  
Peppi Raunioniemi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Gut Microbiome ◽  
Systemic Circulation ◽  
Water Soluble ◽  
Lipid Homeostasis ◽  
Microbial Lipids ◽  
Human Gut ◽  
Polar Metabolites ◽  
Health And Disease

Various studies aiming to elucidate the role of the gut microbiome-metabolome co-axis in health and disease have primarily focused on water-soluble polar metabolites, whilst non-polar microbial lipids have received less attention. The concept of microbiota-dependent lipid biotransformation is over a century old. However, only recently, several studies have shown how microbial lipids alter intestinal and circulating lipid concentrations in the host, thus impacting human lipid homeostasis. There is emerging evidence that gut microbial communities play a particularly significant role in the regulation of host cholesterol and sphingolipid homeostasis. Here, we review and discuss recent research focusing on microbe-host-lipid co-metabolism. We also discuss the interplay of human gut microbiota and molecular lipids entering host systemic circulation, and its role in health and disease.

scholarly journals SEIPIN: A Key Factor for Nuclear Lipid Droplet Generation and Lipid Homeostasis

2020 ◽  
Vol 21 (21) ◽  
pp. 8208
Author(s):  
Yi Jin ◽  
Yanjie Tan ◽  
Pengxiang Zhao ◽  
Zhuqing Ren
Keyword(s):  
Endoplasmic Reticulum ◽  
Lipid Droplet ◽  
Normal Cell ◽  
Single Layer ◽  
Lipid Homeostasis ◽  
Cell Physiology ◽  
Phospholipid Membrane ◽  
Key Factor

Lipid homeostasis is essential for normal cell physiology. Generally, lipids are stored in a lipid droplet (LD), a ubiquitous organelle consisting of a neutral lipid core and a single layer of phospholipid membrane. It is thought that LDs are generated from the endoplasmic reticulum and then released into the cytosol. Recent studies indicate that LDs can exist in the nucleus, where they play an important role in the maintenance of cell phospholipid homeostasis. However, the details of nuclear lipid droplet (nLD) generation have not yet been clearly characterized. SEIPIN is a nonenzymatic protein encoded by the Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2) gene. It is associated with lipodystrophy diseases. Many recent studies have indicated that SEIPIN is essential for LDs generation. Here, we review much of this research in an attempt to explain the role of SEIPIN in nLD generation. From an integrative perspective, we conclude by proposing a theoretical model to explain how SEIPIN might participate in maintaining homeostasis of lipid metabolism.

scholarly journals Renaissance of VDAC: New Insights on a Protein Family at the Interface between Mitochondria and Cytosol

Biomolecules ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 107
Author(s):  
Vito De Pinto
Keyword(s):  
Unicellular Eukaryote ◽  
Cell Physiology ◽  
Therapeutic Application ◽  
Post Translational Modifications ◽  
Biochemical Characteristics ◽  
Voltage Dependent ◽  
Cellular Context ◽  
Selective Channel ◽  
Higher Eukaryotes

It has become impossible to review all the existing literature on Voltage-Dependent Anion selective Channel (VDAC) in a single article. A real Renaissance of studies brings this protein to the center of decisive knowledge both for cell physiology and therapeutic application. This review, after highlighting the similarities between the cellular context and the study methods of the solute carriers present in the inner membrane and VDAC in the outer membrane of the mitochondria, will focus on the isoforms of VDAC and their biochemical characteristics. In particular, the possible reasons for their evolutionary onset will be discussed. The variations in their post-translational modifications and the differences between the regulatory regions of their genes, probably the key to understanding the current presence of these genes, will be described. Finally, the situation in the higher eukaryotes will be compared to that of yeast, a unicellular eukaryote, where there is only one active isoform and the role of VDAC in energy metabolism is better understood.

scholarly journals Lipin-1, a Versatile Regulator of Lipid Homeostasis, Is a Potential Target for Fighting Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4419
Author(s):  
Laura Brohée ◽  
Julie Crémer ◽  
Alain Colige ◽  
Christophe Deroanne
Keyword(s):  
Lipid Metabolism ◽  
Tumor Microenvironment ◽  
Adjuvant Therapy ◽  
Cancer Cells ◽  
Therapeutic Strategy ◽  
Lipid Homeostasis ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Lipin 1

The rewiring of lipid metabolism is a major adaptation observed in cancer, and it is generally associated with the increased aggressiveness of cancer cells. Targeting lipid metabolism is therefore an appealing therapeutic strategy, but it requires a better understanding of the specific roles played by the main enzymes involved in lipid biosynthesis. Lipin-1 is a central regulator of lipid homeostasis, acting either as an enzyme or as a co-regulator of transcription. In spite of its important functions it is only recently that several groups have highlighted its role in cancer. Here, we will review the most recent research describing the role of lipin-1 in tumor progression when expressed by cancer cells or cells of the tumor microenvironment. The interest of its inhibition as an adjuvant therapy to amplify the effects of anti-cancer therapies will be also illustrated.

Comparative studies on phospholipase A2 as a marker for the gut microbiota-liver-brain axis in a rodent model of autism.

2020 ◽  
Vol 17 ◽  
Author(s):  
Abeer Al-Dbass ◽  
Abir Ben Bacha ◽  
Nadine MS Moubayed ◽  
Ramesa Shafi Bhat ◽  
Manar Al-Mutairi ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Treatment Group ◽  
Vitamin B12 ◽  
Phospholipase A2 ◽  
Combined Treatment ◽  
Lipid Homeostasis ◽  
Control Group ◽  
Peripheral Tissues ◽  
Group I

Background: Lipid homeostasis and gut flora can be related to many metabolic diseases, especially autism. Lipid metabolism in the brain can control neuronal structure and function and can also take part in signal transduction pathways to control metabolism in peripheral tissues, especially in the liver. Impaired phospholipid metabolism promotes oxidative stress and neuroinflammation and is therefore directly related to autism. Objective: The effect of propionic acid (PPA) toxicity on lipid homeostasis in the gut-liver-brain axis was evaluated to understand their inter-connection. Cytosolic phospholipase A2 (cPLA2) concentration and activity was measured in autistic model and protective role of omega-3 (ω-3) and vitamin B12 was evaluated. Methods: Animals were divided into five groups: Group I (control group); Group II (autistic model treated with neurotoxic dose of PPA); Group III (treated with vitamin B12 (16.7 mg/kg/day) for 30 days post PPA treatment); Group IV (treated with ω-3 (200 mg/kg body weight/day) for 30 days post PPA treatment ;Group V (combined dose of ω-3 and Vitamin B12, for 30 days post PPA treatment). Phospholipase A2 activity and protein expression level in the liver homogenate of all the groups was analyzed by western blotting and was compared to brain cPLA2. Results: PPA increased the levels of liver and brain cPLA2. However, independent or combined treatment with ω-3 and vitamin B12 was effective in neutralizing its effect. Moreover, PPA-induced dysbiosis, which was ameliorated with the above treatments. Conclusions: This study showed the role of cPLA2 as a lipid metabolism marker, related to PPA-induced inflammation through a highly interactive gut-liver-brain axis.

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