• Molecules and Cells
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• v.47 no.2
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• pp.100010.1-100010.12
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• 2024

Recently, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing due to the high prevalence of metabolic conditions, such as obesity and type 2 diabetes mellitus. Steatotic liver is a hotspot for cancer metastasis in MASLD. Altered lipid metabolism, a hallmark of MASLD, remodels the tissue microenvironment, making it conducive to the growth of metastatic liver cancer. Tumors exacerbate the dysregulation of hepatic metabolism by releasing extracellular vesicles and particles into the liver. Altered lipid metabolism influences the proliferation, differentiation, and functions of immune cells, contributing to the formation of an immunosuppressive and metastasis-prone liver microenvironment in MASLD. This review discusses the mechanisms by which the steatotic liver promotes liver metastasis progression, focusing on its role in fostering an immunosuppressive microenvironment in MASLD. Furthermore, this review highlights lipid metabolism manipulation strategies for the therapeutic management of metastatic liver cancer.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.6
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• pp.871-884
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• 2009

Gene expression profiling is a useful tool for identifying critical genes and pathways in metabolism. The objective of this study was to determine the major differences in the expression of genes associated with metabolism and metabolic regulation in liver and mammary tissues of lactating cows. We used the Michigan State University bovine metabolism (BMET) microarray; previously, we have designed a bovine metabolism-focused microarray containing known genes of metabolic interest using publicly available genomic internet database resources. This is a high-density array of 70mer oligonucleotides representing 2,349 bovine genes. The expression of 922 genes was different at p<0.05, and 398 genes (17%) were differentially expressed by two-fold or more with 222 higher in liver and 176 higher in mammary tissue. Gene ontology categories with a high percentage of genes more highly expressed in liver than mammary tissues included carbohydrate metabolism (glycolysis, glucoenogenesis, propanoate metabolism, butanoate metabolism, electron carrier and donor activity), lipid metabolism (fatty acid oxidation, chylomicron/lipid transport, bile acid metabolism, cholesterol metabolism, steroid metabolism, ketone body formation), and amino acid/nitrogen metabolism (amino acid biosynthetic process, amino acid catabolic process, urea cycle, and glutathione metabolic process). Categories with more genes highly expressed in mammary than liver tissue included amino acid and sugar transporters and MAPK, Wnt, and JAK-STAT signaling pathways. Real-time PCR analysis showed consistent results with those of microarray analysis for all 12 genes tested. In conclusion, microarray analyses clearly identified differential gene expression profiles between hepatic and mammary tissues that are consistent with the differences in metabolism of these two tissues. This study enables understanding of the molecular basis of metabolic adaptation of the liver and mammary gland during lactation in bovine species.

• Archives of Pharmacal Research
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• v.21 no.6
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• pp.677-682
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• 1998

The present study was designed to examine the metabolism of 1-anilino-8-naphthalene sulfonate (ANS), an anionic compound which is transported into liver via "multispecific organ ic anion transporter", with rat hepatic microsomes. TLC analysis indicated that the fluorescent metabolites were not produced to a measurable extent, which made it possible to assess the ANS metabolism by measuring the fluorescence disappearance. The metabolism of ANS was remarkably inhibited by the presence of SKF-525A as well as by the substitution of 02 by CO gas. ANS metabolism by microsomes also required NADPH as a cofactor. These results indicated that the microsomal monooxygenase system might be mainly responsible for the ANS metabolism. The maximum velocity ($V_{max}$) and Michaelis constant ($K_m$) were calculated to be $4.3{\pm}0.2$ nmol/min/mg protein and $42.1{\pm}2.0\;{\mu}M$, respectively. Assuming that 1g of liver contains 32mg of microsomal protein, the $V_{max}$ value was extrapolated to that per g of liver ($V_{max}^I$). The intrinsic metabolic clearance ($CL_{int}$) under linear conditions calculated from this in vitro metabolic study was 3.3ml/min/g liver, being comparable with that (3.0ml/min/g liver) calculated by analyzing the in vivo plasma disappearance curve in a previous study. Furthermore, the effects of other organic anions on the metabolism of ANS were examined. Bromophenolblue (BPB) and rose bengal (RB) competitively inhibited the metabolism of ANS, while BSP inhibited it only slightly. The inhibition constant ($K_i$) of BPB ($6\;{\mu}M$) was much smaller than that of RB ($200\;{\mu}M$). In conclusion, the microsomal monooxygenase system plays a major role in the metabolism of ANS, and other unmetabolizable organic anions (BPB and RB) compete for this metabolism.

• Korean Journal of Poultry Science
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• v.45 no.2
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• pp.109-118
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• 2018

A great progress in genetic selection, nutrition and management practices has contributed to the improved growth rate of broilers and egg production in laying hens. For the increased productivity of modern poultry, a healthy chicken liver needs to cope with the increased metabolic demands. The liver is the major site of de novo fatty acid synthesis; therefore, hepatic lipogenesis is crucial for producing better quality meat and eggs. When de novo lipogenesis exceeds the capacity of lipid metabolism and secretion, large amounts of lipids accumulate in the liver of broilers, leading to a fatty liver. Upon onset of egg-laying in hens, lipids including free fatty acids, triglycerides, and phospholipids are dramatically increased in blood plasma for the synthesis of yolk precursors in oocytes. Productive hens with fatty liver often have hemorrhagic syndrome and sudden death due to the heavy demands of yolk synthesis, which burdens the liver. Understanding the lipid metabolism and hepatic lipid disorders is a key point in the improvement of the growth and production of chickens. This review focuses on the recent studies on lipid metabolism, the hepatic lipid disorders, and the prevention or reduction of fatty liver in poultry.

• Asian-Australasian Journal of Animal Sciences
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• v.10 no.4
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• pp.402-407
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• 1997

This study was conducted to investigate the effects of effects of enprostil, a prostaglandin $E_2$, analogue, on liver triacylglycerol content and factors that regulate liver lipid metabolism in mice. Mice received vehicle or $10{\mu}g$ enprostil/kg body weight intraperitoneally every 6 h, and were killed at 0, 6, 12, 18 and 24 h after the first injection. Enprostil significantly lowered liver triacylglycerol content after 12 h of the first injection. However, the peroxisomal ${\beta}$-oxidation activity was inconsistent with the result of liver triacylglycerol content, because its activity was lovered by enprosil. In another experiment, the effect of enprostil on lipid metabolism in mice was investigated in a short period. Mice received $10{\mu}g$ enprostil/kg body weight intraperitoneally, and were killed after 0, 5, 10, 30 and 60 min. After 30 min, malic enzyme activity was significantly increased by the administration of enprostil compared with the activity at 5 min after. No significant changes in liver carnitine palmitoyltransferase and peroxisomal ${\beta}$-oxidation activities were observed. Plasma free fatty acid concentrations were markedly reduced from 5 through 60 min after the administration of enprostil. Consequently, enprostil suppressive effect on liver triacylglycerol concentration might result from the decreased entry of free fatty acid into liver.

• Archives of Pharmacal Research
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• v.27 no.2
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• pp.239-245
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• 2004

KR-31543, (2S,3R,4S)-6-amino-4-[N-(4-chlorophenyl)-N-(2 -methyl-2H-tetrazol-5-ylmethyl) amino]-3,4-dihydro-2-dimethoxymethyl-3-hydroxy-2-methyl-2H-1-benzopyran, is a new neuroprotective agent for preventing ischemia-reperfusion damage. This study was performed to identify the metabolic pathway of KR-31543 in human liver microsomes and to characterize cytochrome P450 (CYP) enzymes that are involved in the metabolism of KR-31543. Human liver microsomal incubation of KR-31543 in the presence of NADPH resulted in the formation of two metabolites, M1 and M2. M1 was identified as N-(4-chlorophenyl)-N-(2-methyl-2H-tetrazol-5-ylmethyl)amine on the basis of LC/MS/MS analysis with a synthesized authentic standard, and M2 was suggested to be hydroxy-KR-31543. Correlation analysis between the known CYP enzyme activities and the rates of the formation of M 1 and M2 in the 12 human liver microsomes have showed significant correlations with testosterone 6$\beta$-hydroxylase activity (a marker of CYP3A4). Ketoconazole, a selective inhibitor of CYP3A4, and anti-CYP3A4 monoclonal antibodies potently inhibited both N-hydrolysis and hydroxylation of KR-31543 in human liver microsomes. These results provide evidence that CYP3A4 is the major isozyme responsible for the metabolism of KR-31543 to M1 and M2.

• Biomedical Science Letters
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• v.7 no.3
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• pp.111-116
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• 2001

To investigate an effect of aging on the xylene metabolism in liver damaged animals, a study was conducted. 50% carbon tetrachloride ($CCl_4$) in olive oil (0.1 ml/100 g body weight) was intraperitoneally given to 5-week and 12-week rats 12 times every other day and then one dose of 50% xylene in olive oil (0.25 ml/100 g body weight) was intraperitoneally given to the rats, and after 24 hr, the animals were sacrificed. On the basis of the functional findings in rat liver, ie, serum levels of alanine aminotransferase activity, liver protein and malonedialdehyde contents, 5-week rats showed less liver damage than 12-week rats. The increasing rate of urinary methylhippuric acid concentration to the control was significantly higher in 5-week rats than 12-week rats in case of xylene treatment after induction of liver damage. On the other hand, liver damaged 5-week rats showed significant rise of hepatic cytochrome P45O content compared with the liver damaged 12-week rats by the xylene treatment. And increasing rate of hepatic alcohol or aldehyde dehydrogenase activities to each liver damaged animals was higher tendency in 5-week rats than 12-week rats by the xylene treatment. In conclusion, 5-week rat showed greater metabolic rate of xylene than 10-week rats in case of liver injury because 5-week rats led to a slight liver damaged compared with 12-week rats.

• Journal of Nutrition and Health
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• v.35 no.4
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• pp.421-430
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• 2002

This study was performed to investigate the influence of dietary and extract foods from A. capilliaris Thunberg on plasma and liver lipid metabolism in male Sprague-Dawley rats. For the experiment of liver and plasma lipid metabolism, Rats were find diets containing normal concentrations of fat or high concentrations of lard and two different preparations of A. capillaris Thunberg ; control diet (group C),50 mg/kg body weight A. capillary Thunberg methanol extract (group M), 6 g/kg diet A. capillary Thunberg dried powder (group P), high lard control diet (group L), 50 mg/kg body weight A. capillaris Thunberg with high lard (group LM) and 6 g/kg diet A. capillary Thunberg with hi\ulcorner lard (group LP). Effects of A. capillary Thunberg on plasma total cholesterol. High-density lipoprotein (HDL) cholesterol, Atherogenic index, triglyceride, plasma and liver peroxide contents, fatty acid composition of liver lipid and the distribution of fat droplets of liver. Supplementation of A. capillaris Thunberg resulted in lower plasma cholesterol, atherogenic index and triglyceride, and higher HDL-cholesterol in rats find high lard diets. However, these effects were not observed with low level of fat (groups C, M and P). A shift caused by feeding high lard diets in increased plasma and liver peroxides, saturated fatty arid composition of liver lipid and the more frequent distribution of fat droplets in liver could be reversed by feeding A. capillary Thunberg. This study suggests that A. capillary Thunberg co alter lipid metabolism in plasma and liver.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.144-145
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• 2003

Hangover is associated with ethanol metabolism in body after the ingestion of an alcoholic beverage. Especially. The metabolism in liver is forcused by many researcher because, alcohol (approximately 90％) is metabolized by the liver. Ethanol metabolism in liver involves both liver alcohol dehydrogenase(ADH) which actalyzes the oxidation of ethanol to acetaldehyde, and liver aldehyde dehydrogenase(ALDH) which metabilized rapidly acetaldehyde, product of ethanol oxidation, to acetate. (omitted)

• Molecules and Cells
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• v.42 no.1
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• pp.45-55
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• 2019

The liver is involved in a wide range of activities in vertebrates and some other animals, including metabolism, protein synthesis, detoxification, and the immune system. Until now, various methods have been devised to study liver diseases; however, each method has its own limitations. In situ liver perfusion machinery, originally developed in rats, has been successfully adapted to mice, enabling the study of liver diseases. Here we describe the protocol, which is a simple but widely applicable method for investigating the liver diseases. The liver is perfused in situ by cannulation of the portal vein and suprahepatic inferior vena cava (IVC), with antegrade closed circuit circulation completed by clamping the infrahepatic IVC. In situ liver perfusion can be utilized to evaluate immune cell migration and function, hemodynamics and related cellular reactions in each type of hepatic cells, and the metabolism of toxic or other compounds by changing the composition of the circulating media. In situ liver perfusion method maintains liver function and cell viability for up to 2 h. This study also describes an optional protocol using density-gradient centrifugation for the separation of different types of hepatic cells, allowing the determination of changes in each cell type. In summary, this method of in situ liver perfusion will be useful for studying liver diseases as a complement to other established methods.