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  1. Article ; Online: Lipidomic Analysis of Liver Lipid Droplets after Chronic Alcohol Consumption with and without Betaine Supplementation

    Arumugam, Madan Kumar / Perumal, Sathish Kumar / Rasineni, Karuna / Donohue, Terrence M. / Osna, Natalia A. / Kharbanda, Kusum K.

    Biology (Basel). 2023 Mar. 16, v. 12, no. 3

    2023  

    Abstract: The earliest manifestation of alcohol-associated liver disease is hepatic steatosis, which is characterized by fat accumulation in specialized organelles called lipid droplets (LDs). Our previous studies reported that alcohol consumption elevates the ... ...

    Abstract The earliest manifestation of alcohol-associated liver disease is hepatic steatosis, which is characterized by fat accumulation in specialized organelles called lipid droplets (LDs). Our previous studies reported that alcohol consumption elevates the numbers and sizes of LDs in hepatocytes, which is attenuated by simultaneous treatment with the methyl group donor, betaine. Here, we examined changes in the hepatic lipidome with respect to LD size and dynamics in male Wistar rats fed for 6 weeks with control or ethanol-containing liquid diets that were supplemented with or without 10 mg betaine/mL. At the time of sacrifice, three hepatic LD fractions, LD1 (large droplets), LD2 (medium-sized droplets), and LD3 (small droplets) were isolated from each rat. Untargeted lipidomic analyses revealed that each LD fraction of ethanol-fed rats had higher phospholipids, cholesteryl esters, diacylglycerols, ceramides, and hexosylceramides compared with the corresponding fractions of pair-fed controls. Interestingly, the ratio of phosphatidylcholine to phosphatidylethanolamine (the two most abundant phospholipids on the LD surface) was lower in LD1 fraction compared with LD3 fraction, irrespective of treatment; however, this ratio was significantly lower in ethanol LD fractions compared with their respective control fractions. Betaine supplementation significantly attenuated the ethanol-induced lipidomic changes. These were mainly associated with the regulation of LD surface phospholipids, ceramides, and glycerolipid metabolism in different-sized LD fractions. In conclusion, our results show that ethanol-induced changes in the hepatic LD lipidome likely stabilizes larger-sized LDs during steatosis development. Furthermore, betaine supplementation could effectively reduce the size and dynamics of LDs to attenuate alcohol-associated hepatic steatosis.
    Keywords alcohol abuse ; alcohol drinking ; betaine ; ceramides ; diacylglycerols ; ethanol ; fatty liver ; hepatocytes ; lipidomics ; liquids ; liver ; males ; metabolism ; organelles ; phosphatidylcholines ; phosphatidylethanolamines ; rats
    Language English
    Dates of publication 2023-0316
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article ; Online
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology12030462
    Database NAL-Catalogue (AGRICOLA)

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  2. Article: Lipidomic Analysis of Liver Lipid Droplets after Chronic Alcohol Consumption with and without Betaine Supplementation.

    Arumugam, Madan Kumar / Perumal, Sathish Kumar / Rasineni, Karuna / Donohue, Terrence M / Osna, Natalia A / Kharbanda, Kusum K

    Biology

    2023  Volume 12, Issue 3

    Abstract: The earliest manifestation of alcohol-associated liver disease is hepatic steatosis, which is characterized by fat accumulation in specialized organelles called lipid droplets (LDs). Our previous studies reported that alcohol consumption elevates the ... ...

    Abstract The earliest manifestation of alcohol-associated liver disease is hepatic steatosis, which is characterized by fat accumulation in specialized organelles called lipid droplets (LDs). Our previous studies reported that alcohol consumption elevates the numbers and sizes of LDs in hepatocytes, which is attenuated by simultaneous treatment with the methyl group donor, betaine. Here, we examined changes in the hepatic lipidome with respect to LD size and dynamics in male Wistar rats fed for 6 weeks with control or ethanol-containing liquid diets that were supplemented with or without 10 mg betaine/mL. At the time of sacrifice, three hepatic LD fractions, LD1 (large droplets), LD2 (medium-sized droplets), and LD3 (small droplets) were isolated from each rat. Untargeted lipidomic analyses revealed that each LD fraction of ethanol-fed rats had higher phospholipids, cholesteryl esters, diacylglycerols, ceramides, and hexosylceramides compared with the corresponding fractions of pair-fed controls. Interestingly, the ratio of phosphatidylcholine to phosphatidylethanolamine (the two most abundant phospholipids on the LD surface) was lower in LD1 fraction compared with LD3 fraction, irrespective of treatment; however, this ratio was significantly lower in ethanol LD fractions compared with their respective control fractions. Betaine supplementation significantly attenuated the ethanol-induced lipidomic changes. These were mainly associated with the regulation of LD surface phospholipids, ceramides, and glycerolipid metabolism in different-sized LD fractions. In conclusion, our results show that ethanol-induced changes in the hepatic LD lipidome likely stabilizes larger-sized LDs during steatosis development. Furthermore, betaine supplementation could effectively reduce the size and dynamics of LDs to attenuate alcohol-associated hepatic steatosis.
    Language English
    Publishing date 2023-03-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology12030462
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Glucagon-like peptide 1 receptor agonist, exendin-4, reduces alcohol-associated fatty liver disease.

    Mahalingam, Sundararajan / Bellamkonda, Ramesh / Arumugam, Madan Kumar / Perumal, Sathish Kumar / Yoon, Jessica / Casey, Carol / Kharbanda, Kusum / Rasineni, Karuna

    Biochemical pharmacology

    2023  Volume 213, Page(s) 115613

    Abstract: Fatty liver is the earliest response to excessive ethanol consumption, which increases the susceptibility of the liver to develop advanced stage of liver disease. Our previous studies have revealed that chronic alcohol administration alters metabolic ... ...

    Abstract Fatty liver is the earliest response to excessive ethanol consumption, which increases the susceptibility of the liver to develop advanced stage of liver disease. Our previous studies have revealed that chronic alcohol administration alters metabolic hormone levels and their functions. Of current interest to our laboratory is glucagon-like peptide 1 (GLP-1), a widely studied hormone known to reduce insulin resistance and hepatic fat accumulation in patients with metabolic-associated fatty liver disease. In this study, we examined the beneficial effects of exendin-4 (a GLP-1 receptor agonist) in an experimental rat model of ALD. Male Wistar rats were pair-fed the Lieber-DeCarli control or ethanol diet. After 4 weeks of this feeding regimen, a subset of rats in each group were intraperitoneally injected every other day with either saline or exendin-4 at a dose of 3 nmol/kg/day (total 13 doses) while still being fed their respective diet. At the end of the treatment, rats were fasted for 6 h and glucose tolerance test was conducted. The following day, the rats were euthanized, and the blood and tissue samples collected for subsequent analysis. We found that exendin-4 treatment had no significant effect on body weight gain among the experimental groups. Exendin-4-treated ethanol rats exhibited improved alcohol-induced alterations in liver/body weight and adipose/body weight ratio, serum ALT, NEFA, insulin, adiponectin and hepatic triglyceride levels. Reduction in indices of hepatic steatosis in exendin-4 treated ethanol-fed rats was attributed to improved insulin signaling and fat metabolism. These results strongly suggest that exendin-4 mitigates alcohol-associated hepatic steatosis by regulating fat metabolism.
    MeSH term(s) Rats ; Male ; Animals ; Exenatide/pharmacology ; Exenatide/therapeutic use ; Rats, Wistar ; Fatty Liver, Alcoholic/drug therapy ; Fatty Liver, Alcoholic/prevention & control ; Fatty Liver, Alcoholic/metabolism ; Insulin/metabolism ; Glucagon-Like Peptide 1/agonists ; Non-alcoholic Fatty Liver Disease ; Ethanol/toxicity ; Obesity/metabolism
    Chemical Substances Exenatide (9P1872D4OL) ; Insulin ; Glucagon-Like Peptide 1 (89750-14-1) ; Ethanol (3K9958V90M)
    Language English
    Publishing date 2023-05-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 208787-x
    ISSN 1873-2968 ; 0006-2952
    ISSN (online) 1873-2968
    ISSN 0006-2952
    DOI 10.1016/j.bcp.2023.115613
    Database MEDical Literature Analysis and Retrieval System OnLINE

    Full text online

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    In stock of ZB MED Cologne/Königswinter

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  4. Article: Mitochondrial Dysfunction-Associated Mechanisms in the Development of Chronic Liver Diseases.

    Arumugam, Madan Kumar / Gopal, Thiyagarajan / Kalari Kandy, Rakhee Rathnam / Boopathy, Lokesh Kumar / Perumal, Sathish Kumar / Ganesan, Murali / Rasineni, Karuna / Donohue, Terrence M / Osna, Natalia A / Kharbanda, Kusum K

    Biology

    2023  Volume 12, Issue 10

    Abstract: The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the ... ...

    Abstract The liver is a major metabolic organ that performs many essential biological functions such as detoxification and the synthesis of proteins and biochemicals necessary for digestion and growth. Any disruption in normal liver function can lead to the development of more severe liver disorders. Overall, about 3 million Americans have some type of liver disease and 5.5 million people have progressive liver disease or cirrhosis, in which scar tissue replaces the healthy liver tissue. An estimated 20% to 30% of adults have excess fat in their livers, a condition called steatosis. The most common etiologies for steatosis development are (1) high caloric intake that causes non-alcoholic fatty liver disease (NAFLD) and (2) excessive alcohol consumption, which results in alcohol-associated liver disease (ALD). NAFLD is now termed "metabolic-dysfunction-associated steatotic liver disease" (MASLD), which reflects its association with the metabolic syndrome and conditions including diabetes, high blood pressure, high cholesterol and obesity. ALD represents a spectrum of liver injury that ranges from hepatic steatosis to more advanced liver pathologies, including alcoholic hepatitis (AH), alcohol-associated cirrhosis (AC) and acute AH, presenting as acute-on-chronic liver failure. The predominant liver cells, hepatocytes, comprise more than 70% of the total liver mass in human adults and are the basic metabolic cells. Mitochondria are intracellular organelles that are the principal sources of energy in hepatocytes and play a major role in oxidative metabolism and sustaining liver cell energy needs. In addition to regulating cellular energy homeostasis, mitochondria perform other key physiologic and metabolic activities, including ion homeostasis, reactive oxygen species (ROS) generation, redox signaling and participation in cell injury/death. Here, we discuss the main mechanism of mitochondrial dysfunction in chronic liver disease and some treatment strategies available for targeting mitochondria.
    Language English
    Publishing date 2023-10-05
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology12101311
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Changing the phospholipid composition of lipid droplets alters localization of select lipid droplet proteins.

    Renier, Timothy J / Paetz, Olivia R / Paal, Matthew C / Long, Alex B / Brown, Margaret R / Vuong, Sunny H / Perumal, Sathish Kumar / Kharbanda, Kusum K / Listenberger, Laura L

    microPublication biology

    2023  Volume 2023

    Abstract: Our experiments aim to determine if decreasing the amount of phosphatidylcholine (PC) relative to phosphatidylethanolamine (PE) at the lipid droplet surface changes the localization of specific lipid droplet proteins. We manipulate lipid droplet ... ...

    Abstract Our experiments aim to determine if decreasing the amount of phosphatidylcholine (PC) relative to phosphatidylethanolamine (PE) at the lipid droplet surface changes the localization of specific lipid droplet proteins. We manipulate lipid droplet phospholipids in both a cultured mouse hepatocyte (AML12) cell line and on synthetic lipid droplets. Decreasing the PC:PE ratio increases perilipin 2, decreases DGAT2, and does not change rab18 or lanosterol synthase levels on lipid droplets. These differences may be explained by the distinct structural motifs that mediate the protein-lipid droplet interactions.
    Language English
    Publishing date 2023-11-03
    Publishing country United States
    Document type Journal Article
    ISSN 2578-9430
    ISSN (online) 2578-9430
    DOI 10.17912/micropub.biology.000960
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Structural stability of antimicrobial peptides rich in tryptophan, proline and arginine: a computational study.

    Marimuthu, Sathish Kumar / Nagarajan, Krishnanand / Perumal, Sathish Kumar / Palanisamy, Selvamani / Subbiah, Latha

    Journal of biomolecular structure & dynamics

    2020  Volume 40, Issue 8, Page(s) 3551–3559

    Abstract: The host defense peptides or antimicrobial peptides (AMPs) often contain short sequence of amino acids, either positive or negatively charged and express broad-spectrum antibacterial, antiviral and antifungal activity. Many researchers had reported that ... ...

    Abstract The host defense peptides or antimicrobial peptides (AMPs) often contain short sequence of amino acids, either positive or negatively charged and express broad-spectrum antibacterial, antiviral and antifungal activity. Many researchers had reported that tryptophan, arginine and proline rich AMPs have a promising source of next-generation antibiotics. Nowadays, AMPs are used as a possible therapeutic source for future antibiotics. In the present study, the amino acid sequences of 2924 AMPs belonging to various sources rich in Tryptophan, Proline and Arginine was chosen for investigation. The AMPs were further categorized according to their source, structure and antimicrobial activities. The AMPs with tryptophan, arginine, proline residues in abundance with maximum sequence length of 20 amino acids alone was obtained. Homology modeling was performed with PEP-FOLD and the modeled structures were evaluated using RAMPAGE to identify the structural information. Further, the stability of peptide in aqueous condition was probed using molecular dynamics simulations.Communicated by Ramaswamy H. Sarma.
    MeSH term(s) Amino Acids ; Anti-Bacterial Agents/chemistry ; Antimicrobial Cationic Peptides/chemistry ; Antimicrobial Peptides ; Arginine/chemistry ; Proline/chemistry ; Tryptophan/chemistry
    Chemical Substances Amino Acids ; Anti-Bacterial Agents ; Antimicrobial Cationic Peptides ; Antimicrobial Peptides ; Tryptophan (8DUH1N11BX) ; Arginine (94ZLA3W45F) ; Proline (9DLQ4CIU6V)
    Language English
    Publishing date 2020-11-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 49157-3
    ISSN 1538-0254 ; 0739-1102
    ISSN (online) 1538-0254
    ISSN 0739-1102
    DOI 10.1080/07391102.2020.1848631
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2093: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  7. Article: Insilico Alpha-Helical Structural Recognition of Temporin Antimicrobial Peptides and Its Interactions with Middle East Respiratory Syndrome-Coronavirus.

    Marimuthu, Sathish Kumar / Nagarajan, Krishnanand / Perumal, Sathish Kumar / Palanisamy, Selvamani / Subbiah, Latha

    International journal of peptide research and therapeutics

    2019  Volume 26, Issue 3, Page(s) 1473–1483

    Abstract: Many antimicrobial peptides (AMPs) have multiple antimicrobial immunity effects. One such class of peptides is temporins. Temporins are the smallest (AMPs) found in nature and are highly active against gram-positive bacteria. Nowadays, there was a rapid ... ...

    Abstract Many antimicrobial peptides (AMPs) have multiple antimicrobial immunity effects. One such class of peptides is temporins. Temporins are the smallest (AMPs) found in nature and are highly active against gram-positive bacteria. Nowadays, there was a rapid increase in the availability of the 3D structure of proteins in PDB (protein data bank). The conserved residues and 3D structural conformations of temporins (AMPs) were still unknown. The present study explores the sequence analysis, alpha-helical structural conformations of temporins. The sequence of temporins was deracinated from APD3 database, the three-dimensional structure was constructed by homology modeling studies. The sequence analysis results show that the conserved residues among the peptide sequences, the maximum of the sequences are 70% alike to each other. The secondary structure prediction results revealed that 99% of temporin (AMPs) exhibited in alpha-helical form. The 3D structure speculated using RAMPAGE exposes the alpha-helical conformation in all temporins (AMPs). The phylogenetic analysis reveals the evolutionary relationships of temporins (AMPs), which are branched into seven clusters. As a result, we identified a list of potential temporin AMPs which docked to the antiviral protein (MERS-CoV), it shows good protein-peptide binding. This computational approach may serve as a good model for the rationale design of temporin based antibiotics.
    Keywords covid19
    Language English
    Publishing date 2019-10-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2192632-3
    ISSN 1573-3904 ; 1573-3149
    ISSN (online) 1573-3904
    ISSN 1573-3149
    DOI 10.1007/s10989-019-09951-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article: Acute ethanol-induced liver injury is prevented by betaine administration.

    Arumugam, Madan Kumar / Chava, Srinivas / Perumal, Sathish Kumar / Paal, Matthew C / Rasineni, Karuna / Ganesan, Murali / Donohue, Terrence M / Osna, Natalia A / Kharbanda, Kusum K

    Frontiers in physiology

    2022  Volume 13, Page(s) 940148

    Abstract: Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the ... ...

    Abstract Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (
    Language English
    Publishing date 2022-10-04
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564217-0
    ISSN 1664-042X
    ISSN 1664-042X
    DOI 10.3389/fphys.2022.940148
    Database MEDical Literature Analysis and Retrieval System OnLINE

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