scholarly journals Role of the Gut in Lipid Homeostasis

2012 ◽  
Vol 92 (3) ◽  
pp. 1061-1085 ◽  
Author(s):  
Nada A. Abumrad ◽  
Nicholas O. Davidson
Keyword(s):  
Fatty Acid ◽  
Genetic Regulation ◽  
Density Lipoprotein ◽  
Microsomal Triglyceride Transfer Protein ◽  
Cholesterol Absorption ◽  
Lessons Learned ◽  
Lipid Homeostasis ◽  
Integrative View ◽  
Familial Hypobetalipoproteinemia

Intestinal lipid transport plays a central role in fat homeostasis. Here we review the pathways regulating intestinal absorption and delivery of dietary and biliary lipid substrates, principally long-chain fatty acid, cholesterol, and other sterols. We discuss the regulation and functions of CD36 in fatty acid absorption, NPC1L1 in cholesterol absorption, as well as other lipid transporters including FATP4 and SRB1. We discuss the pathways of intestinal sterol efflux via ABCG5/G8 and ABCA1 as well as the role of the small intestine in high-density lipoprotein (HDL) biogenesis and reverse cholesterol transport. We review the pathways and genetic regulation of chylomicron assembly, the role of dominant restriction points such as microsomal triglyceride transfer protein and apolipoprotein B, and the role of CD36, l-FABP, and other proteins in formation of the prechylomicron complex. We will summarize current concepts of regulated lipoprotein secretion (including HDL and chylomicron pathways) and include lessons learned from families with genetic mutations in dominant pathways (i.e., abetalipoproteinemia, chylomicron retention disease, and familial hypobetalipoproteinemia). Finally, we will provide an integrative view of intestinal lipid homeostasis through recent findings on the role of lipid flux and fatty acid signaling via diverse receptor pathways in regulating absorption and production of satiety factors.

Abstract 617: Intestine-Specific MTP Deficiency with ACAT2 Gene Ablation Lowers Acute Cholesterol Absorption With Chylomicrons and High-Density Lipoproteins

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Jahangir Iqbal ◽  
Mohamed Boutjdir ◽  
Lawrence L Rudel ◽  
M Mahmood Hussain
Keyword(s):  
Density Lipoprotein ◽  
Microsomal Triglyceride Transfer Protein ◽  
Cholesterol Absorption ◽  
High Density ◽  
High Density Lipoproteins ◽  
High Cholesterol ◽  
Intestinal Cholesterol Absorption ◽  
Triglyceride Accumulation ◽  
Abca1 Expression ◽  
Deficient Mice

Intestinal cholesterol absorption involves chylomicron and high density lipoprotein (HDL) pathways. Microsomal triglyceride transfer protein (MTP) and ATP binding cassette family A protein 1 (ABCA1) are critical for cholesterol transport by these pathways, respectively. Additionally, acyl Co-A:cholesterol acyltransferase 2 (ACAT2) plays an important role in cholesterol absorption. Intestinal MTP ablation significantly increased intestinal triglyceride and cholesterol levels and reduced their acute absorption. In contrast, ACAT2 deficiency had no effect on triglyceride absorption but significantly reduced cholesterol absorption. Individual deficiencies of ACAT2 and MTP reduced cholesterol absorption with chylomicrons. We hypothesized that their combined deficiency would increase cholesterol secretion with HDL; unexpectedly, their deficiency reduced secretion with both chylomicrons and HDL. Further, we observed significant reductions in intestinal ABCA1 expression in combined deficient mice. Thus, free cholesterol is unavailable for secretion by the HDL pathway in these mice. We speculate that reductions in ABCA1 expression and HDL secretion might be secondary to massive triglyceride accumulation associated with intestinal MTP deficiency. Besides its role in cholesterol absorption, ACAT2 deficiency causes mild hypertriglyceridemia and reduces steatosis in mice fed high cholesterol diets by increasing hepatic lipoprotein production by unknown mechanisms. We show that this phenotype is preserved in the absence of intestinal MTP in ACAT2 deficient mice fed a Western diet. Further, we observed increases in hepatic MTP activity in these mice. Thus, ACAT2 deficiency might increase MTP expression to avoid steatosis. Therefore, ACAT2 inhibition might avert steatosis associated with high cholesterol diets by increasing MTP expression.

scholarly journals Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition

2002 ◽  
Vol 22 (23) ◽  
pp. 8204-8214 ◽  
Author(s):  
Linda E. Hammond ◽  
Patricia A. Gallagher ◽  
Shuli Wang ◽  
Sylvia Hiller ◽  
Kimberly D. Kluckman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acids ◽  
Low Density Lipoprotein ◽  
Fatty Acid Content ◽  
Density Lipoprotein ◽  
Positional Analysis ◽  
Triacylglycerol Content ◽  
Hepatic Triacylglycerol

ABSTRACT Microsomal and mitochondrial isoforms of glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyze the committed step in glycerolipid synthesis. The mitochondrial isoform, mtGPAT, was believed to control the positioning of saturated fatty acids at the sn-1 position of phospholipids, and nutritional, hormonal, and overexpression studies suggested that mtGPAT activity is important for the synthesis of triacylglycerol. To determine whether these purported functions were true, we constructed mice deficient in mtGPAT. mtGPAT−/− mice weighed less than controls and had reduced gonadal fat pad weights and lower hepatic triacylglycerol content, plasma triacylglycerol, and very low density lipoprotein triacylglycerol secretion. As predicted, in mtGPAT−/− liver, the palmitate content was lower in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. Positional analysis revealed that mtGPAT−/− liver phosphatidylethanolamine and phosphatidylcholine had about 21% less palmitate in the sn-1 position and 36 and 40%, respectively, more arachidonate in the sn-2 position. These data confirm the important role of mtGPAT in the synthesis of triacylglycerol, in the fatty acid content of triacylglycerol and cholesterol esters, and in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids. The increase in arachidonate may be functionally significant in terms of eicosanoid production.

Participatory role of natural killer and natural killer T cells in atherosclerosis: lessons learned from in vivo mouse studiesThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 67-75 ◽  
Author(s):  
Stewart C. Whitman ◽  
Tanya A. Ramsamy
Keyword(s):  
Natural Killer ◽  
Complex Disease ◽  
Immune Cell ◽  
Disease Process ◽  
Density Lipoprotein ◽  
Nkt Cells ◽  
Lessons Learned ◽  
Natural Killer T

Atherosclerosis is a multifactor, highly complex disease with numerous aetiologies that work synergistically to promote lesion development. One of the emerging components that drive the development of both early- and late-stage atherosclerotic lesions is the participation of both the innate and acquired immune systems. In both humans and animal models of atherosclerosis, the most prominent cells that infiltrate evolving lesions are macrophages and T lymphocytes. The functional loss of either of these cell types reduces the extent of atherosclerosis in mice that were rendered susceptible to the disease by deficiency of either apolipoprotein E or the LDL (low density lipoprotein) receptor. In addition to these major immune cell participants, a number of less prominent leukocyte populations that can modulate the atherogenic process are also involved. This review will focus on the participatory role of two “less prominent” immune components, namely natural killer (NK) cells and natural killer T (NKT) cells. Although this review will highlight the fact that both NK and NKT cells are not sufficient for causing the disease, the roles played by both these cells types are becoming increasingly important in understanding the complexity of this disease process.

Role of Pancreatic Digestion in Cholesterol Absorption

1957 ◽  
Vol 190 (2) ◽  
pp. 214-220 ◽  
Author(s):  
T. M. Lin ◽  
Esko Karvinen ◽  
A. C. Ivy
Keyword(s):  
Fatty Acid ◽  
Pancreatic Juice ◽  
Essential Role ◽  
Corn Oil ◽  
Dietary Cholesterol ◽  
Cholesterol Absorption ◽  
Fatty Acid Esters ◽  
Acid Esters ◽  
Endogenous Cholesterol

The exclusion of pancreatic juice had no significant effect on elimination of endogenous cholesterol in the rat but increased it slightly in three dogs. Forty per cent of the dietary cholesterol was absorbed without and with pancreatic exclusion in the presence of a fat-free diet. Hence, pancreatic juice is not specifically necessary for the absorption of cholesterol. Pancreatic exclusion had no effect on the absorption of either dietary cholesterol or fatty acid, or both, when oleic and palmitic acid were fed. This indicates that any effect pancreatic exclusion may exert on cholesterol absorption when a fat containing diet is fed depends on the change in the utilization of the fat resulting from the exclusion. In the case of corn oil, triolein, trielaidin and tallow but not with tripalmitin, pancreatic exclusion was followed by an increased fecal elimination of both fatty acid and cholesterol. The increment of fatty acid elimination was large enough to dissolve the excess cholesterol excreted in the rats with pancreatic exclusion, except in the case of trielaidin. The only statistically significant decrease in the absorption of dietary cholesterol which resulted from pancreatic exclusion occurred when one of the unsaturated fatty acid esters, namely, corn oil, triolein, or trielaidin was the fat fed. These observations fail to show that pancreatic cholesterol esterase plays a specifically essential role in the absorption of free dietary cholesterol.

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.

The role of fatty acid composition and α-tocopherol concentration on low density lipoprotein autoxidation

1993 ◽  
Vol 15 (5) ◽  
pp. 487
Author(s):  
Michael J. Thomas ◽  
James Manning ◽  
Todd Thornburg ◽  
Kelly Hooper ◽  
Lawrence L. Rudel
Keyword(s):  
Fatty Acid Composition ◽  
Fatty Acid ◽  
Acid Composition ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Tocopherol Concentration

scholarly journals Revealing the Role of High-Density Lipoprotein in Colorectal Cancer

2021 ◽  
Vol 22 (7) ◽  
pp. 3352
Author(s):  
Aleksandra Zeljkovic ◽  
Jelena Vekic ◽  
Marija Mihajlovic ◽  
Tamara Gojkovic ◽  
Sandra Vladimirov ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Density Lipoprotein ◽  
Genetic Regulation ◽  
Density Lipoprotein ◽  
High Density ◽  
Colorectal Carcinogenesis ◽  
Qualitative Properties ◽  
Particle Structure ◽  
Comprehensive Overview

Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.

scholarly journals Role of Lipid Accumulation and Inflammation in Atherosclerosis: Focus on Molecular and Cellular Mechanisms

2021 ◽  
Vol 8 ◽  
Author(s):  
Khojasteh Malekmohammad ◽  
Evgeny E. Bezsonov ◽  
Mahmoud Rafieian-Kopaei
Keyword(s):  
Lipid Accumulation ◽  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Endothelial Damage ◽  
Lipid Homeostasis ◽  
Foam Cell Formation ◽  
Low Density ◽  
Cellular Mechanisms

Atherosclerosis is a chronic lipid-driven and maladaptive inflammatory disease of arterial intima. It is characterized by the dysfunction of lipid homeostasis and signaling pathways that control the inflammation. This article reviews the role of inflammation and lipid accumulation, especially low-density lipoprotein (LDL), in the pathogenesis of atherosclerosis, with more emphasis on cellular mechanisms. Furthermore, this review will briefly highlight the role of medicinal plants, long non-coding RNA (lncRNA), and microRNAs in the pathophysiology, treatment, and prevention of atherosclerosis. Lipid homeostasis at various levels, including receptor-mediated uptake, synthesis, storage, metabolism, efflux, and its impairments are important for the development of atherosclerosis. The major source of cholesterol and lipid accumulation in the arterial wall is proatherogenic modified low-density lipoprotein (mLDL). Modified lipoproteins, such as oxidized low-density lipoprotein (ox-LDL) and LDL binding with proteoglycans of the extracellular matrix in the intima of blood vessels, cause aggregation of lipoprotein particles, endothelial damage, leukocyte recruitment, foam cell formation, and inflammation. Inflammation is the key contributor to atherosclerosis and participates in all phases of atherosclerosis. Also, several studies have shown that microRNAs and lncRNAs have appeared as key regulators of several physiological and pathophysiological processes in atherosclerosis, including regulation of HDL biogenesis, cholesterol efflux, lipid metabolism, regulating of smooth muscle proliferation, and controlling of inflammation. Thus, both lipid homeostasis and the inflammatory immune response are closely linked, and their cellular and molecular pathways interact with each other.

Inflammatory Markers in Cardiovascular Disease; Lessons Learned and Future Perspectives

2020 ◽  
Vol 19 (3) ◽  
pp. 323-342
Author(s):  
Dimitrios Patoulias ◽  
Konstantinos Stavropoulos ◽  
Konstantinos Imprialos ◽  
Vasilios Athyros ◽  
Haris Grassos ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Inflammatory Markers ◽  
Low Density Lipoprotein ◽  
Relevant Literature ◽  
Density Lipoprotein ◽  
Cd40 Ligand ◽  
Lessons Learned ◽  
Model Assessment ◽  
Markers Of Inflammation

Background: Cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality worldwide. It is now established that inflammation plays a crucial role in atherosclerosis and atherothrombosis, and thus, it is closely linked to cardiovascular disease. Objective: The aim of the present review is to summarize and critically appraise the most relevant evidence regarding the potential use of inflammatory markers in the field of CVD. Method: We conducted a comprehensive research of the relevant literature, searching MEDLINE from its inception until November 2018, primarily for meta-analyses, randomized controlled trials and observational studies. Results: Established markers of inflammation, mainly C-reactive protein, have yielded significant results both for primary and secondary prevention of CVD. Newer markers, such as lipoprotein-associated phospholipase A2, lectin-like oxidized low-density lipoprotein receptor-1, cytokines, myeloperoxidase, cell adhesion molecules, matrix metalloproteinases, and the CD40/CD40 ligand system, have been largely evaluated in human studies, enrolling both individuals from the general population and patients with established CVD. Some markers have yielded conflicting results; however, others are now recognized not only as promising biomarkers of CVD, but also as potential therapeutic targets, establishing the role of anti-inflammatory and pleiotropic drugs in CVD. Conclusion: There is significant evidence regarding the role of consolidated and novel inflammatory markers in the field of diagnosis and prognosis of CVD. However, multimarker model assessment, validation of cut-off values and cost-effectiveness analyses are required in order for those markers to be integrated into daily clinical practice.

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