scholarly journals Lipid Droplets Promote Phase Separation of Ago2 to Accelerate Dicer1 Loss and Decelerate miRNA Activity in Lipid Exposed Hepatic Cells

2020 ◽  
Author(s):  
Diptankar Bandyopadhyay ◽  
Sudarshana Basu ◽  
Ishita Mukherjee ◽  
Ritobrita Chakraborty ◽  
Kamalika Mukherjee ◽  
...  
Keyword(s):  
Cell Death ◽  
Phase Separation ◽  
Lipid Droplets ◽  
Stress Condition ◽  
Liver Cells ◽  
Hepatic Tissue ◽  
High Fat ◽  
Hepatic Cells ◽  
Mirna Level ◽  
Mammalian Liver

AbstractmiR-122 is a liver specific miRNA that plays an important role in controlling metabolic homeostasis in mammalian liver cells. Interestingly, miR-122 on exposure to lipotoxic stress is reduced in liver cells. To fight stress, miRNA processor Dicer1 is depleted to cause reduced miR-122 production and the lowering of miRNA level ensures a better stress response in hepatocytes under lipotoxic stress. Interestingly, lipid droplets, formed in the liver cells on exposure to high fat, ensure cytoplasmic phase separation of Ago2 and prevent interaction of Ago2 with Dicer1. Lipid droplets bind miRNA and enhance miRNA-Ago2 uncoupling and Ago2 phase separation. Loss of interaction between Ago2 and Dicer1 eventually facilitates export and lowering of cellular Dicer1, a process also dependent on the endosomal maturation controller protein Alix, thereby ceasing pre-miRNA processing by Dicer1 in lipid exposed cells. Depletion of lipid droplets by downregulation of Perilipins with siRNAs resulted in a rescue of cellular Dicer1 level and Ago2-Dicer1 interaction. This is a novel mechanism that liver cells adopt to restrict cellular miRNA levels under stress condition. Thus, lipid droplets prevent cell death upon exposure to high fat by reducing intra and extracellular pool of miR-122 in hepatic tissue.

scholarly journals Raman Study on Lipid Droplets in Hepatic Cells Co-Cultured with Fatty Acids

2021 ◽  
Vol 22 (14) ◽  
pp. 7378
Author(s):  
Pradjna N. Paramitha ◽  
Riki Zakaria ◽  
Anisa Maryani ◽  
Yukako Kusaka ◽  
Bibin B. Andriana ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Cell Death ◽  
Linoleic Acid ◽  
Hepg2 Cells ◽  
Lipid Droplets ◽  
Morphological Changes ◽  
Growth Curves ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Cells ◽  
Oleic And Linoleic Acids

The purpose of the present study was to investigate molecular compositions of lipid droplets changing in live hepatic cells stimulated with major fatty acids in the human body, i.e., palmitic, stearic, oleic, and linoleic acids. HepG2 cells were used as the model hepatic cells. Morphological changes of lipid droplets were observed by optical microscopy and transmission electron microscopy (TEM) during co-cultivation with fatty acids up to 5 days. The compositional changes in the fatty chains included in the lipid droplets were analyzed via Raman spectroscopy and chemometrics. The growth curves of the cells indicated that palmitic, stearic, and linoleic acids induced cell death in HepG2 cells, but oleic acid did not. Microscopic observations suggested that the rates of fat accumulation were high for oleic and linoleic acids, but low for palmitic and stearic acids. Raman analysis indicated that linoleic fatty chains taken into the cells are modified into oleic fatty chains. These results suggest that the signaling pathway of cell death is independent of fat stimulations. Moreover, these results suggest that hepatic cells have a high affinity for linoleic acid, but linoleic acid induces cell death in these cells. This may be one of the causes of inflammation in nonalcoholic fatty liver disease (NAFLD).

scholarly journals Comparison of the effects of difenacoum and brodifacoum on the ultrastructure of rat liver cells

2016 ◽  
Vol 67 (3) ◽  
pp. 204-209 ◽  
Author(s):  
Nursel Gül ◽  
Nuri Yiğit ◽  
Fulya Saygılı ◽  
Ebru Demirel ◽  
Ceren Geniş
Keyword(s):  
Rat Liver ◽  
Lipid Droplets ◽  
Liver Cells ◽  
Mitochondrial Morphology ◽  
Cytotoxic Effects ◽  
Cytoplasmic Material ◽  
Transmission Electron ◽  
Biochemical Assays ◽  
Rat Liver Cells ◽  
Contrast Exposure

Abstract We used transmission electron microscopy to examine the cytotoxic effects of the second-generation anticoagulant rodenticides difenacoum and brodifacoum on rat liver. A single dose of difenacoum or brodifacoum was administered to rats by gastric gavage and liver samples were taken after 24 h, four days or seven days. In the livers of rats treated with difenacoum for 24 h, hepatocytes typically showed increased numbers of lysosomes, as well as enlargement of both the perinuclear space and the cisternae of the rough endoplasmic reticulum (RER), while sinusoids were irregularly shaped and contained Kupffer cells. Similar irregularities occurred in brodifacoum-treated rats at the same time point, but additionally increased numbers of vacuoles, damaged mitochondrial cristae, and clumping of chromatin were observed in hepatocytes, and hemolysed erythrocytes were noted in the sinusoids. Comparable findings were made in each group of rats after four days. After seven days of difenacoum treatment, hepatocytes suffered loss of cytoplasmic material and mitochondrial shrinkage, while RER cisternae became discontinuous. In contrast, exposure to brodifacoum for seven days caused the formation of numerous vacuoles and lipid droplets, disordered mitochondrial morphology, chromatin clumping and invagination of the nuclear envelope in hepatocytes. Sinusoids in the livers of rodenticide-treated rats contained an accumulation of dense material, lipid droplets, cells with pycnotic nuclei and hemolysed erythrocytes. Overall, our results show that brodifacoum causes more severe effects in liver cells than difenacoum. Thus our microscopic data along with additional biochemical assays point to a severe effect of rodenticide on vertebrates.

Transhepatic absorption and biliary excretion of insulin

1987 ◽  
Vol 65 (9) ◽  
pp. 1982-1987 ◽  
Author(s):  
Walter Zingg ◽  
Aron M. Rappaport ◽  
Bernard S. Leibel
Keyword(s):  
Intravenous Administration ◽  
Biliary Excretion ◽  
Venous Blood ◽  
Intraperitoneal Administration ◽  
Liver Cells ◽  
Insulin Concentration ◽  
Secretory Process ◽  
Insulin Administration ◽  
Hepatic Cells ◽  
Liver Surface

The application of insulin to the liver in rats is followed by an increase of the insulin concentration in the bile. The pathway of insulin from the liver surface to the bile may include a secretory process by the hepatic cells, or it may bypass the hepatic cells, using direct anatomical pathways from blood and lymph to bile. The concentration of insulin in arterial and venous blood, in lymph, and in bile was measured following application of insulin to the liver surface and following peritoneal or intravenous administration. The results confirm that insulin is absorbed from the surface of the liver, but the glucose modulating effect was less effective than after intravenous administration. The insulin concentration in bile was increased after insulin administration by all routes, with the highest and most prolonged increases found after intraperitoneal administration. The results suggest that following transhepatic and intravenous administration, insulin reaches the bile without passing through the liver cells.

scholarly journals High-Fat-High-Fructose Diet Decreases Hippocampal Neuron Number in Male Rats

2020 ◽  
Vol 12 (1) ◽  
pp. 1-7
Author(s):  
Inggita Kusumastuty ◽  
Frinny Sembiring ◽  
Sri Andarini ◽  
Dian Handayani
Keyword(s):  
Cell Death ◽  
Nerve Cell ◽  
Hippocampal Neurons ◽  
Sprague Dawley ◽  
High Fat ◽  
Group I ◽  
Sprague Dawley Rats ◽  
High Fructose ◽  
Group Ii ◽  
Nerve Cell Death

BACKGROUND: Consumption of foods and drinks high in energy, fat, and/or sugar beyond the recommended quantities can cause obesity, which triggers the incidence of brain nerve cell death related to oxidative stress, high levels of tumor necrosis factor (TNF)-α and triglycerides, and low high-density lipoprotein (HDL) levels. Progressive nerve cell death causes decreasing cognitive performance. This study aims to prove that an American Institute of Nutrition committee in 1993 (AIN-93M) diet modified with high-fat-high-fructose (HFHF) can decrease the number of hippocampal neurons. A decrease in the number of hippocampal neurons indicates progressive nerve cell death.METHODS: An experimental study using a post-test control group design was carried out using male Sprague Dawley rats. Samples were selected using simple random sampling to divide them into two groups, Group I was AIN-93M-modified HFHF diet (n=14) and Group II was AIN-93M standard (n=16). The number of visible neurons was measured in the hippocampus area of Sprague Dawley rats’ brains, stained with haemotoxylin and eosin (H&E) and scanned under 400x magnification. Neurons were counted in 10 visual fields using the "Cell_Count" application.RESULTS: The data were analysed by Pearson’s correlation test using SPSS. The results show that rats in Group I had a greater weight gain and fewer neurons than those in the Group II (p=0.023, r=-0.413).CONCLUSION: The consumption of foods high in fat and fructose can cause an increase in nerve cell death, as shown by the decrease in the number of hippocampal neurons.KEYWORDS: brain nerve cells, high fat, high fructose, increased body weight

scholarly journals A Decade of Mighty Lipophagy: What We Know and What Facts We Need to Know?

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Muhammad Babar Khawar ◽  
Muddasir Hassan Abbasi ◽  
Mussarat Rafiq ◽  
Naila Naz ◽  
Rabia Mehmood ◽  
...  
Keyword(s):  
Cell Death ◽  
Lipid Droplets ◽  
Lysosomal Enzymes ◽  
Lipid Homeostasis ◽  
Cellular Lipid ◽  
Biological Functions ◽  
Lysosomal Function ◽  
Selective Autophagy ◽  
Cellular Components ◽  
Different Levels

Lipids are integral cellular components that act as substrates for energy provision, signaling molecules, and essential constituents of biological membranes along with a variety of other biological functions. Despite their significance, lipid accumulation may result in lipotoxicity, impair autophagy, and lysosomal function that may lead to certain diseases and metabolic syndromes like obesity and even cell death. Therefore, these lipids are continuously recycled and redistributed by the process of selective autophagy specifically termed as lipophagy. This selective form of autophagy employs lysosomes for the maintenance of cellular lipid homeostasis. In this review, we have reviewed the current literature about how lipid droplets (LDs) are recruited towards lysosomes, cross-talk between a variety of autophagy receptors present on LD surface and lysosomes, and lipid hydrolysis by lysosomal enzymes. In addition to it, we have tried to answer most of the possible questions related to lipophagy regulation at different levels. Moreover, in the last part of this review, we have discussed some of the pathological states due to the accumulation of these LDs and their possible treatments under the light of currently available findings.

Growth and Function in the Foetal Liver

Development ◽  
1956 ◽  
Vol 4 (2) ◽  
pp. 97-109
Author(s):  
D. A. T. Dick
Keyword(s):  
Relative Weight ◽  
Liver Weight ◽  
Developmental Period ◽  
Hepatic Tissue ◽  
Relative Liver Weight ◽  
Hepatic Cells ◽  
Foetal Liver ◽  
And Function

Many investigators have demonstrated the decline which takes place in the relative weight of the liver during the development of the mammalian foetus; Carlyle (1945) and Wallace (1945) in the sheep, Jackson (1909) in man, Lowrey (1911) in the pig, Williamson (1948) and Addis & Gray (1950) in the rat, Latimer & Corder (1948) in the dog, and Latimer (1948) in the cat. The present work is an attempt to find the cause underlying this decline. Since the foetal liver contains not only hepatic tissue but also much haemopoietic tissue, it was first necessary to determine whether the decrease in the relative liver-weight represents a real diminution of true hepatic tissue or whether it simply reflects the progressive shift of haemopoiesis from liver to skeleton. In order to test these lternatives a method was devised for determining the total amount of true hepatic tissue, i.e. the total number of hepatic cells, in a given foetal liver, and applied to a series of foetuses covering the developmental period.

scholarly journals High-fat diet induces fibrosis in mice lacking CYP2A5 and PPARα: a new model for steatohepatitis-associated fibrosis

2020 ◽  
Vol 319 (5) ◽  
pp. G626-G635
Author(s):  
Xue Chen ◽  
George K. Acquaah-Mensah ◽  
Krista L. Denning ◽  
Jonathan M. Peterson ◽  
Kesheng Wang ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Lipid Droplets ◽  
Liver Inflammation ◽  
High Fat ◽  
New Model

PPARα is upregulated in cyp2a5−/− mice, but HFD-induced steatosis is still deteriorated. PPARα abrogation makes cyp2a5−/− mice more sensitive to HFD-induced steatosis, liver inflammation, and fibrosis, suggesting that PPARα upregulation in cyp2a5−/− mice is a compensation response. HFD-induced liver inflammation, fibrosis, and nitrotyrosine formation in pparα−/−/cyp2a5−/− mice are all within clusters of lipid droplets, and lipid droplets are all within CYP2E1-positive area.

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