An SOD1 deficiency enhances lipid droplet accumulation in the fasted mouse liver by aborting lipophagy

Kurahashi, Takashi; Hamashima, Shinji; Shirato, Takaya; Lee, Jae Yong; Homma, Takujiro; Kang, Eun Sil; Fujii, Junichi

doi:10.1016/j.bbrc.2015.10.052

Cited by 39 publications

(21 citation statements)

References 26 publications

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“…Fasting induces the formation of lipid droplets, not only in the liver but also other tissues that are dominantly involved in active β-oxidation. While feeding a high fat diet leads to lipid droplet accumulation in the liver[ 146 ] and intestinal epithelia[ 143 ] more intensely in SOD1-knockout mice than the wild-type mice, fasting induces severe and irreversible damage not only to the liver but to other aerobic organs as well[ 147 , 148 ]. Thus fasting may aggravate oxidative damage in these organs and become a serious pathogenic factor for NAFLD.…”

Section: Non-alcoholic Fatty Liver Disease As a Representative Injurymentioning

confidence: 99%

Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

Fujii

Homma

Kobayashi

et al. 2018

WJBC

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Reactive oxygen species (ROS) are produced during normal physiologic processes with the consumption of oxygen. While ROS play signaling roles, when they are produced in excess beyond normal antioxidative capacity this can cause pathogenic damage to cells. The majority of such oxidation occurs in polyunsaturated fatty acids and sulfhydryl group in proteins, resulting in lipid peroxidation and protein misfolding, respectively. The accumulation of misfolded proteins in the endoplasmic reticulum (ER) is enhanced under conditions of oxidative stress and results in ER stress, which, together, leads to the malfunction of cellular homeostasis. Multiple types of defensive machinery are activated in unfolded protein response under ER stress to resolve this unfavorable situation. ER stress triggers the malfunction of protein secretion and is associated with a variety of pathogenic conditions including defective insulin secretion from pancreatic β-cells and accelerated lipid droplet formation in hepatocytes. Herein we use nonalcoholic fatty liver disease (NAFLD) as an illustration of such pathological liver conditions that result from ER stress in association with oxidative stress. Protecting the ER by eliminating excessive ROS via the administration of antioxidants or by enhancing lipid-metabolizing capacity via the activation of peroxisome proliferator-activated receptors represent promising therapeutics for NAFLD.

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Section: Non-alcoholic Fatty Liver Disease As a Representative Injurymentioning

confidence: 99%

Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

Fujii

Homma

Kobayashi

et al. 2018

WJBC

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“…Similar effects of Sod-1-deficiency were found for TAG secretion and storage by the liver. The CLDs that accumulated in Sod-1-deficient hepatocytes were associated with impaired lipophagy [228, 229]. Together these results show that SOD1 is important for normal TAG secretion from and storage within enterocytes.…”

Section: Regulation Of Cytoplasmic Lipid Droplet (Cld) Metabolism mentioning

confidence: 99%

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes

D’Aquila

Hung

Carreiro

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

115

122

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Dietary fat provides essential nutrients, contributes to energy balance, and regulates blood lipid concentrations. These functions are important to health, but can also become dysregulated and contribute to diseases such as obesity, diabetes, cardiovascular disease, and cancer. Within enterocytes, the digestive products of dietary fat are re-synthesized into triacylglycerol, which is either secreted on chylomicrons or stored within cytoplasmic lipid droplets (CLDs). CLDs were originally thought to be inert stores of neutral lipids, but are now recognized as dynamic organelles function in multiple cellular processes in addition to lipid metabolism. This review will highlight recent discoveries related to dietary fat absorption with an emphasis on the presence, synthesis, and metabolism of cytoplasmic lipid droplets within this process.

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“…A similar phenomenon was observed in the livers of fasted mice with a global knockout of superoxide dismutase 1 (SOD1). (67) SOD1 converts superoxide (generated from reactive oxygen species) to hydrogen peroxide as a means of alleviating oxidative stress. Kurahashi et al (67) found that hepatocytes from SOD1-knockout mice exhibited a ballooned phenotype.…”

Section: Regulation Of Hepatic Lipophagymentioning

confidence: 99%

Hepatic lipophagy: New insights into autophagic catabolism of lipid droplets in the liver

Schulze

Drižytė

Casey

et al. 2017

Hepatology Communications

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The liver is a central fat‐storage organ, making it especially susceptible to steatosis as well as subsequent inflammation and cirrhosis. The mechanisms by which the liver mobilizes stored lipid for energy production, however, remain incompletely defined. The catabolic process of autophagy, a well‐known process of bulk cytoplasmic recycling and cellular self‐regeneration, is a central regulator of lipid metabolism in the liver. In the past decade, numerous studies have examined a selective form of autophagy that specifically targets a unique neutral lipid storage organelle, the lipid droplet, to better understand the function for this process in hepatocellular fatty acid metabolism. In the liver (and other oxidative tissues), this specialized pathway, lipophagy, likely plays as important a role in lipid turnover as conventional lipase‐driven lipolysis. In this review, we highlight several recent studies that have contributed to our understanding about the regulation and effects of hepatic lipophagy. (Hepatology Communications 2017;1:359–369)

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An SOD1 deficiency enhances lipid droplet accumulation in the fasted mouse liver by aborting lipophagy

Cited by 39 publications

References 26 publications

Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

Mutual interaction between oxidative stress and endoplasmic reticulum stress in the pathogenesis of diseases specifically focusing on non-alcoholic fatty liver disease

Recent discoveries on absorption of dietary fat: Presence, synthesis, and metabolism of cytoplasmic lipid droplets within enterocytes

Hepatic lipophagy: New insights into autophagic catabolism of lipid droplets in the liver

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