Peroxisomal β-oxidation stimulates cholesterol biosynthesis in the liver in diabetic mice

Zhang, Xiao; Wang, Yaoqing; Yao, Haoya; Deng, Shuai; Gao, Ting; Shang, Lin; Chen, Jiayao; Cui, Xiaojuan; Zeng, Jia

doi:10.1016/j.jbc.2022.101572

Cited by 9 publications

(9 citation statements)

References 64 publications

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“…However, this proportion elevated significantly in mice under the diabetic condition as liver peroxisomal FAO was stimulated in diabetes. Therefore, it was demonstrated that peroxisomal FAO plays an important role in regulating cholesterol synthesis, and enhanced peroxisomal FAO contributed to high cholesterol level in diabetes mice [ 12 ]. Also, in the present study, the stimulated peroxisomal FAO might primarily contribute to the enhanced cholesterol and bile acid synthesis in the liver of fish fed a short-term HFD, thereby reducing FFA accumulation and alleviating liver injury caused by lipotoxicity.…”

Section: Discussionmentioning

confidence: 99%

“…The acetyl-CoA for cholesterol biosynthesis mainly derives from the following two sources: one is generated by citrate cleavage, and the other is from acetate produced by fatty acid β -oxidation (FAO) [ 10 , 11 ]. A recent study about the mechanism of diabetes-induced hypercholesterolemia in mice revealed that stimulated liver peroxisomal FAO generated considerable free acetate, a precursor for cholesterol biosynthesis [ 12 ]. In a normal physiological condition, cholesterol homeostasis is tightly regulated in animals based on the cellular cholesterol level [ 13 , 14 ], and high cholesterol levels always promote cholesterol esterification and elimination to prevent lipotoxicity [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

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The Adaptive Characteristics of Cholesterol and Bile Acid Metabolism in Nile Tilapia Fed a High-Fat Diet

Qian

Zhou

et al. 2022

Aquaculture Nutrition

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Since high-fat diet (HFD) intake elevates liver cholesterol and enhanced cholesterol-bile acid flux alleviates its lipid deposition, we assumed that the promoted cholesterol-bile acid flux is an adaptive metabolism in fish when fed an HFD. The present study investigated the characteristic of cholesterol and fatty acid metabolism in Nile tilapia (Oreochromis niloticus) after feeding an HFD (13% lipid level) for four and eight weeks. Visually healthy Nile tilapia fingerlings (average weight 3.50 ± 0.05 g ) were randomly distributed into four treatments (4-week control diet or HFD and 8-week control diet or HFD). The liver lipid deposition and health statue, cholesterol/bile acid, and fatty acid metabolism were analyzed in fish after short-term and long-term HFD intake. The results showed that 4-week HFD feeding did not change serum alanine transaminase (ALT) and aspartate transferase (AST) enzyme activities, along with comparable liver malondialdehyde (MDA) content. But higher serum ALT and AST enzyme activities and liver MDA content were observed in fish fed 8-week HFD. Intriguingly, remarkably accumulated total cholesterol (mainly cholesterol ester, CE) was observed in the liver of fish fed 4-week HFD, along with slightly elevated free fatty acids (FFAs) and comparable TG contents. Further molecular analysis in the liver showed that obvious accumulation of CE and total bile acids (TBAs) in fish fed 4-week HFD was mainly attributed to the enhancement of cholesterol synthesis, esterification, and bile acid synthesis. Furthermore, the increased protein expressions of acyl-CoA oxidase 1/2 (Acox1 and Acox2), which serve as peroxisomal fatty acid β-oxidation (FAO) rate-limiting enzymes and play key roles in the transformation of cholesterol into bile acids, were found in fish after 4-week HFD intake. Notably, 8-week HFD intake remarkably elevated FFA content (about 1.7-fold increase), and unaltered TBAs were found in fish liver, accompanied by suppressed Acox2 protein level and cholesterol/bile acid synthesis. Therefore, the robust cholesterol-bile acid flux serves as an adaptive metabolism in Nile tilapia when fed a short-term HFD and is possibly via stimulating peroxisomal FAO. This finding enlightens our understanding on the adaptive characteristics of cholesterol metabolism in fish fed an HFD and provides a new possible treatment strategy against metabolic disease induced by HFD in aquatic animals.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Adaptive Characteristics of Cholesterol and Bile Acid Metabolism in Nile Tilapia Fed a High-Fat Diet

Qian

Zhou

et al. 2022

Aquaculture Nutrition

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“…In a type-1 diabetic mouse model, excessive hepatic peroxisomal β-oxidation was shown to generate a surplus of free acetate, which in turn stimulates and serves as a precursor for cholesterol biosynthesis without affecting the gene expression and abundance of key cholesterol biosynthetic enzymes. Moreover, inhibiting peroxisomal β-oxidation with the Acox1 inhibitor 10,12-tricosadiynoic acid decreases cholesterol biosynthesis by reducing acetate formation [ 126 ]. While the relationship between hepatic peroxisomal β-oxidation and circulating LDL-cholesterol levels was not explored, it is possible that activation of cholesterol biosynthesis by peroxisomal β-oxidation contributes to diabetes-associated hypercholesterolemia since peroxisomal fatty acid oxidation in the liver is strongly induced in the diabetic state [ [127] , [128] , [129] ].…”

Section: Peroxisomal β-Oxidation and The Regulation Of Lipid Homeosta...mentioning

confidence: 99%

Peroxisomal regulation of energy homeostasis: Effect on obesity and related metabolic disorders

Kleiboeker

Lodhi

2022

Molecular Metabolism

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“…Peroxisomes are a type of single membrane-bound organelles that are present in almost all kinds of eukaryotes. A variety of crucial metabolic processes are commonly in the peroxisome, such as the fatty acid β-oxidation and the degradation of the reactive oxygen species (ROSs) ( Reumann and Bartel, 2016 ; Zhang et al, 2022 ). The proteins involved in the peroxisome biogenies were normally assigned as peroxins, the peroxin-encoding genes were named as PEX genes, and up to now, there are 37 PEX proteins described ( Kiel et al, 2006 ; Jansen et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The peroxins BcPex8, BcPex10, and BcPex12 are required for the development and pathogenicity of Botrytis cinerea

Guo

et al. 2022

Front. Microbiol.

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Peroxisomes have been proved playing roles in infection of several plant pathogens. Although the contribution of a portion of peroxins in pathogenicity was demonstrated, most of them are undocumented in fungi, especially, Botrytis cinerea. The homologs of Pex8, Pex10, and Pex12 in B. cinerea were functionally characterized in this work using gene disruption strategies. Compared with the wild-type strain (WT), the Δbcpex8, Δbcpex10, and Δbcpex12 mutants exhibited significant reduction in melanin production, fatty acid utilization, and decreased tolerance to high osmotic pressure and reactive oxygen species (ROS). The mycelial growth and conidiation of were significantly inhibited in Δbcpex8, Δbcpex10, and Δbcpex12 strains. The mycelial growth rates of Δbcpex8, Δbcpex10, and Δbcpex12 were reduced by 32, 35, and 34%, respectively, compared with WT and ectopic transformant (ET), and the conidiation was reduced by approximately 89, 27, and 88%, respectively. The conidial germination, germ tube elongation, and the formation of initiate infection structures (IFSs) were also reduced by the deletion of the genes. The pathogenicity was tested on the leaves of tobacco and strawberry, and fruits of tomato. On the leaves of tobacco and strawberry, the Δbcpex8, Δbcpex10, and Δbcpex12 mutants could not induce necrotic lesions, and the lesions on tomato fruits infected with the mutants were significantly reduced than those of the wide type. The results indicated that BcPEX8, BcPEX10, and BcPEX12 are indispensable for the development and pathogenicity of B. cinerea.

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Peroxisomal β-oxidation stimulates cholesterol biosynthesis in the liver in diabetic mice

Cited by 9 publications

References 64 publications

The Adaptive Characteristics of Cholesterol and Bile Acid Metabolism in Nile Tilapia Fed a High-Fat Diet

The Adaptive Characteristics of Cholesterol and Bile Acid Metabolism in Nile Tilapia Fed a High-Fat Diet

Peroxisomal regulation of energy homeostasis: Effect on obesity and related metabolic disorders

The peroxins BcPex8, BcPex10, and BcPex12 are required for the development and pathogenicity of Botrytis cinerea

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