Analysis of Lipid Droplets in Hepatocytes

Wang, Huajin; Quiroga, Ariel D.; Lehner, Richard

doi:10.1016/b978-0-12-408051-5.00007-3

Cited by 28 publications

(21 citation statements)

References 397 publications

(615 reference statements)

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“…Hepatocytes contain lipid droplets in the lumen of the ER where VLDL particles are assembled . Kinetically, FFAs impair insulin‐induced VLDL1 suppression and this impairment enhances the secretion of triglyceride‐rich VLDL1 particles in individuals with NAFLD or insulin resistance .…”

Section: Pathological Role Of Nafld and Cardiometabolic Syndromementioning

confidence: 99%

Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

2018

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Nonalcoholic fatty liver disease (NAFLD) is a chronic condition characterized by fat accumulation combined with low-grade inflammation in the liver. A large body of clinical and experimental data shows that increased flux of free fatty acids from increased visceral adipose tissue and de novo lipogenesis can lead to NAFLD and insulin resistance. Thus, individuals with obesity, insulin resistance, and dyslipidaemia are at the greatest risk of developing NAFLD. Conversely, NAFLD is a phenotype of cardiometabolic syndrome. Notably, researchers have discovered a close association between NAFLD and impaired glucose metabolism and focused on the role of NAFLD in the development of type 2 diabetes. Moreover, recent studies provide substantial evidence for an association between NAFLD and atherosclerosis and cardiometabolic disorders. Even if NAFLD can progress into severe liver disorders including nonalcoholic steatohepatitis (NASH) and cirrhosis, the majority of subjects with NAFLD die from cardiovascular disease eventually. In this review, we propose a potential pathological link between NAFLD/NASH and cardiometabolic syndrome. The potential factors that can play a pivotal role in this link, such as inflammation, insulin resistance, alteration in lipid metabolism, oxidative stress, genetic predisposition, and gut microbiota are discussed. KEYWORDS cardiometabolic syndrome, nonalcoholic fatty liver disease, inflammation, oxidative stress 1 | INTRODUCTION | Prevalence of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH)NAFLD covers a spectrum of diseases ranging from simple steatosis to NASH, which is distinguished from the former by the presence of progressive hepatic fibrosis. 1,2 The prevalence of NAFLD or NASH in the general population varies according to the diagnostic criteria and tools used to stage the condition. 3,4 In the United States, liver biopsies performed on potential liver donors revealed that 20% of donors were ineligible for organ donation because of a high degree of steatosis (>30%). 5 A study in which liver biopsies were performed on 589 consecutive potential liver-transplant donors found an NAFLD prevalence of 51%. 6 A series of autopsies showed a broad range in the prevalence of NAFLD. The prevalence of NASH in autopsy cases of lean Abbreviations: ALT, alanine aminotransferase; apoB, apolipoprotein-B; AST, aspartate aminotransferase; ChREBP, carbohydrate-responsive element-binding protein; CV, cardiovascular; ER, endoplasmic reticulum; FFA, free fatty acid; FIAF, fasting-induced adipocyte factor; GSK-3β, glycogen synthase kinase-3β; IL-6, interleukin-6; IRS1, insulin receptor substrate-1

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Section: Pathological Role Of Nafld and Cardiometabolic Syndromementioning

confidence: 99%

Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

2018

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“…In addition to the critical role in TG synthesis and storage, hepatocytes contain lipid droplets in the lumen of the endoplasmic reticulum where very low density lipoprotein (VLDL) is assembled. 43 Thus, the liver secretes TG into the blood in apolipoprotein B (apoB)-containing VLDL particles. Fatty liver leads to hepatic insulin resistance, which induces hepatic VLDL production via changes in the rate of apoB synthesis and degradation or de novo lipogenesis.…”

Section: Nonalcoholic Fatty Liver Diseasementioning

confidence: 99%

Links Between Ectopic Fat and Vascular Disease in Humans

Lim

Meigs

2014

ATVB

166

130

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The average of overweight individual can have differential fat depots in target-organs or specific compartments of the body. This ectopic fat distribution may be more of a predictive factor for cardiovascular risk than obesity. Abdominal visceral obesity, a representative ectopic fat, is robustly associated with insulin resistance and cardiovascular risk. Fat depots in the liver and muscle tissue cause adverse cardiometabolic risk by affecting glucose and lipid metabolism. Pericardial fat and perivascular fat affect coronary atherosclerosis, cardiac function, and hemodynamics. Fat around the neck is associated with systemic vascular resistance. Fat around the kidney may increase blood pressure and induce albuminuria. Fat accumulation in or around the pancreas alters glucose metabolism, conferring cardiovascular risk. Ectopic fat may act as an active endocrine and paracrine organ that releases various bioactive mediators that influence insulin resistance, glucose and lipid metabolism, coagulation, and inflammation, which all contribute to cardiovascular risk. As both obese and apparently lean individuals can have ectopic fat, regional fat distribution may play an important role in the development of cardiovascular diseases in both non-obese and obese people.

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“…In order to study intracellular lipid droplets, various fluorescent probes have been developed for imaging . The traditional method of quantifying the lipid droplets uses lipid droplet affinity fluorescence dyes such as Nile Red or Oil Red O to stain HepG2 cells with a fluorescence microscope, fluorescence plate reader, flow cytometer, or high‐content imaging equipment to measure and compare the fluorescence intensity of each sample . This method has several disadvantages, such as: 1) strictly consistent (identical) fluorescence imaging settings are needed for all experimental conditions to allow comparison of measurements and a small variation of the setting can render unusable of the data; 2) if the dyes used have high background, this may result in inaccurate measurement and even lead to false negative results since HepG2 cells have high basal levels of lipid droplets; and 3) it is not possible to quantify and compare lipid droplet number and size.…”

Section: Methodsmentioning

confidence: 99%

Live Imaging and Quantitation of Lipid Droplets and Mitochondrial Membrane Potential Changes with Aggregation‐Induced Emission Luminogens in an in Vitro Model of Liver Steatosis

et al. 2019

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High specificity, low background, good biocompatibility and photostability are common properties of aggregation‐induced emission luminogens (AIEgens). In this study, an AIEgen FAS was used in live HepG2 cells, an in vitro model of liver steatosis, to quantify lipid droplet number and size instead of the traditional method of only measuring fluorescence intensity emitted from fluorescence dye stained in lipid droplet. In parallel, another AIEgen, TPE‐Ph‐In, was used to perform continuous monitoring and quantitation of mitochondrial membrane potential in the same batch of live HepG2 cells. The data show a significant increase in lipid droplet numbers after 24 h treatment by amiodarone and a significant increase in both lipid droplet numbers and size after 48 h amiodarone treatment. Moreover, the data suggest a significant increase in mitochondria membrane potential in cells treated with amiodarone for 24 and 48 h, with restoration to pre‐treatment level 24 h after removal of the amiodarone. Further investigation is needed to fully understand the underlying mechanism.

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Analysis of Lipid Droplets in Hepatocytes

Cited by 28 publications

References 397 publications

Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Crosstalk between nonalcoholic fatty liver disease and cardiometabolic syndrome

Links Between Ectopic Fat and Vascular Disease in Humans

Live Imaging and Quantitation of Lipid Droplets and Mitochondrial Membrane Potential Changes with Aggregation‐Induced Emission Luminogens in an in Vitro Model of Liver Steatosis

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