Publications by authors named "Nirajan Shrestha"

14 Publications

  • Page 1 of 1

Maternal diet high in linoleic acid alters offspring fatty acids and cardiovascular function in a rat model.

Br J Nutr 2021 Apr 16:1-14. Epub 2021 Apr 16.

Institute for Health and Sport, Victoria University, Melbourne, VIC, Australia.

Linoleic acid (LA), an essential n-6 fatty acid (FA), is critical for fetal development. We investigated the effects of maternal high LA (HLA) diet on offspring cardiac development and its relationship to circulating FA and cardiovascular function in adolescent offspring, and the ability of the postnatal diet to reverse any adverse effects. Female Wistar Kyoto rats were fed low LA (LLA; 1·44 % energy from LA) or high LA (HLA; 6·21 % energy from LA) diets for 10 weeks before pregnancy and during gestation/lactation. Offspring, weaned at postnatal day 25, were fed LLA or HLA diets and euthanised at postnatal day 40 (n 6-8). Maternal HLA diet decreased circulating total cholesterol and HDL-cholesterol in females and decreased total plasma n-3 FA in males, while maternal and postnatal HLA diets decreased total plasma n-3 FA in females. α-Linolenic acid (ALA) and EPA were decreased by postnatal but not maternal HLA diets in both sexes. Maternal and postnatal HLA diets increased total plasma n-6 and LA, and a maternal HLA diet increased circulating leptin, in both male and female offspring. Maternal HLA decreased slopes of systolic and diastolic pressure-volume relationship (PVR), and increased cardiac Col1a1, Col3a1, Atp2a1 and Notch1 in males. Maternal and postnatal HLA diets left-shifted the diastolic PVR in female offspring. Coronary reactivity was altered in females, with differential effects on flow repayment after occlusion. Thus, maternal HLA diets impact lipids, FA and cardiac function in offspring, with postnatal diet modifying FA and cardiac function in the female offspring.
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http://dx.doi.org/10.1017/S0007114521001276DOI Listing
April 2021

Maternal and Postnatal High Linoleic Acid Diet Impacts Lipid Metabolism in Adult Rat Offspring in a Sex-Specific Manner.

Int J Mol Sci 2021 Mar 14;22(6). Epub 2021 Mar 14.

Institute for Health and Sport, Victoria University, Melbourne, VIC 8001, Australia.

Linoleic acid (LA), an n-6 polyunsaturated fatty acid (PUFA), is essential for fetal growth and development. We aimed to investigate the effect of maternal and postnatal high LA (HLA) diet on plasma FA composition, plasma and hepatic lipids and genes involved in lipid metabolism in the liver of adult offspring. Female rats were fed with low LA (LLA; 1.44% LA) or HLA (6.21% LA) diets for 10 weeks before pregnancy, and during gestation/lactation. Offspring were weaned at postnatal day 25 (PN25), fed either LLA or HLA diets and sacrificed at PN180. Postnatal HLA diet decreased circulating total n-3 PUFA and alpha-linolenic acid (ALA), while increased total n-6 PUFA, LA and arachidonic acid (AA) in both male and female offspring. Maternal HLA diet increased circulating leptin in female offspring, but not in males. Maternal HLA diet decreased circulating adiponectin in males. Postnatal HLA diet significantly decreased aspartate transaminase (AST) in females and downregulated total cholesterol, HDL-cholesterol and triglycerides in the plasma of males. Maternal HLA diet downregulated the hepatic mRNA expression of in both male and female offspring and decreased the hepatic mRNA expression of and in females. Both maternal and postnatal HLA diet decreased hepatic mRNA expression of in females. Postnatal diet significantly altered circulating fatty acid concentrations, with sex-specific differences in genes that control lipid metabolism in the adult offspring following exposure to high LA diet in utero.
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http://dx.doi.org/10.3390/ijms22062946DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999727PMC
March 2021

Mitochondrial Function, Fatty Acid Metabolism, and Body Composition in the Hyperbilirubinemic Gunn Rat.

Front Pharmacol 2021 8;12:586715. Epub 2021 Mar 8.

School of Medical Science, Griffith University, Gold Coast, QLD, Australia.

Circulating bilirubin is associated with reduced adiposity in human and animal studies. A possible explanation is provided by data that demonstrates that bilirubin inhibits mitochondrial function and decreases efficient energy production. However, it remains unclear whether hyperbilirubinemic animals have similar perturbed mitochondrial function and whether this is important for regulation of energy homeostasis. To investigate the impact of unconjugated hyperbilirubinemia on body composition, and mitochondrial function in hepatic tissue and skeletal muscle. 1) Food intake and bodyweight gain of 14-week old hyperbilirubinemic Gunn ( = 19) and normobilirubinemic littermate (control; = 19) rats were measured over a 17-day period. 2) Body composition was determined using dual-energy X-ray absorptiometry and by measuring organ and skeletal muscle masses. 3) Mitochondrial function was assessed using high-resolution respirometry of homogenized liver and intact permeabilized extensor digitorum longus and soleus fibers. 4) Liver tissue was flash frozen for later gene (qPCR), protein (Western Blot and citrate synthase activity) and lipid analysis. Female hyperbilirubinemic rats had significantly reduced fat mass (Gunn: 9.94 ± 5.35 vs. Control: 16.6 ± 6.90 g, < 0.05) and hepatic triglyceride concentration (Gunn: 2.39 ± 0.92 vs. Control: 4.65 ± 1.67 mg g, < 0.01) compared to normobilirubinemic controls. Furthermore, hyperbilirubinemic rats consumed fewer calories daily ( < 0.01) and were less energetically efficient (Gunn: 8.09 ± 5.75 vs. Control: 14.9 ± 5.10 g bodyweight kcal, < 0.05). Hepatic mitochondria of hyperbilirubinemic rats demonstrated increased flux control ratio (FCR) via complex I and II (CI+II) (Gunn: 0.78 ± 0.16 vs. Control: 0.62 ± 0.09, < 0.05). Similarly, exogenous addition of 31.3 or 62.5 μM unconjugated bilirubin to control liver homogenates significantly increased CI+II FCR ( < 0.05). Hepatic gene expression was significantly increased in hyperbilirubinemic females while and was significantly greater in male hyperbilirubinemic rats ( < 0.05). Finally, hepatic mitochondrial complex IV subunit 1 protein expression was significantly increased in female hyperbilirubinemic rats ( < 0.01). This is the first study to comprehensively assess body composition, fat metabolism, and mitochondrial function in hyperbilirubinemic rats. Our findings show that hyperbilirubinemia is associated with reduced fat mass, and increased hepatic mitochondrial biogenesis, specifically in female animals, suggesting a dual role of elevated bilirubin and reduced UGT1A1 function on adiposity and body composition.
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http://dx.doi.org/10.3389/fphar.2021.586715DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7982585PMC
March 2021

Developmental programming of peripheral diseases in offspring exposed to maternal obesity during pregnancy.

Am J Physiol Regul Integr Comp Physiol 2020 11 2;319(5):R507-R516. Epub 2020 Sep 2.

Environmental Futures Research Institute, Griffith University, Nathan, Queensland, Australia.

Obesity is an increasing global health epidemic that affects all ages, including women of reproductive age. During pregnancy, maternal obesity is associated with adverse pregnancy outcomes that lead to complications for the mother. In addition, maternal obesity can increase the risk of poor perinatal outcomes for the infant due to altered development. Recent research has investigated the effects of maternal obesity on peripheral organ development and health in later life in offspring. In this review, we have summarized studies that investigated the programming effects of maternal obesity before and during pregnancy on metabolic, cardiovascular, immune, and microbiome perturbations in offspring. Epidemiological studies investigating the effects of maternal obesity on offspring development can be complex due to other copathologies and genetic diversity. Animal studies have provided some insights into the specific mechanisms and pathways involved in programming peripheral disease risk. The effects of maternal obesity during pregnancy on offspring development are often sex specific, with sex-specific changes in placental transport and function suggestive that this organ is likely to play a central role. We believe that this review will assist in facilitating future investigations regarding the underlying mechanisms that link maternal obesity and offspring disease risk in peripheral organs.
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http://dx.doi.org/10.1152/ajpregu.00214.2020DOI Listing
November 2020

Role for endocannabinoids in early pregnancy: recent advances and the effects of cannabis use.

Am J Physiol Endocrinol Metab 2020 09 3;319(3):E557-E561. Epub 2020 Aug 3.

Environmental Futures Research Institute, Griffith University, Nathan, Queensland, Australia.

The endocannabinoid system (ECS) is associated with several physiological processes, including reproduction. This system consists of the cannabinoid receptors, endocannabinoid ligands, and enzymes that metabolize and degrade these fatty acids. Recent evidence shows that cannabinoid receptors are expressed in cells of the reproductive system, including endometrial stromal cells, ovaries, and sperm cells. Emerging and recent research suggests that the ECS may play a significant role in reproduction. The endocannabinoid ligands anandamide and 2-arachidonoylglycerol are crucial for successful endometrium decidualization, placental development, and embryo implantation. Alteration in cannabinoid receptor expression or in endocannabinoid homeostasis by excessive intake of cannabis during pregnancy is associated with negative pregnancy outcomes, including preterm birth. The use of medicinal cannabis is becoming more widespread in Western countries, especially in people of reproductive age. Cannabis contains phytocannabinoids, which modulate the ECS, and emerging evidence suggests that phytocannabinoids, through their action on cannabinoid receptors, may have a negative impact on fertility, pregnancy outcome, and fetal health. In this mini-review, we highlight the recent advances in the field, which explore the role of endocannabinoids in early pregnancy and the effects of excessive intake of phytocannabinoids in pregnancy outcomes.
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http://dx.doi.org/10.1152/ajpendo.00210.2020DOI Listing
September 2020

Maternal High Linoleic Acid Alters Placental Fatty Acid Composition.

Nutrients 2020 Jul 23;12(8). Epub 2020 Jul 23.

Institute for Health and Sport, Victoria University, Melbourne, VIC 3000, Australia.

Fetal development is modulated by maternal nutrition during pregnancy. The dietary intake of linoleic acid (LA), an essential dietary n-6 polyunsaturated fatty acid (PUFA), has increased. We previously published that increased LA consumption during pregnancy does not alter offspring or placental weight but fetal plasma fatty acid composition; the developing fetus obtains their required PUFA from the maternal circulation. However, it is unknown if increased maternal linoleic acid alters placental fatty acid storage, metabolism, transport, and general placental function. Female Wistar-Kyoto rats were fed either a low LA diet (LLA; 1.44% of energy from LA) or high LA diet (HLA; 6.21% of energy from LA) for 10 weeks before pregnancy and during gestation. Rats were sacrificed at embryonic day 20 (E20, term = 22 days) and placentae collected. The labyrinth of placentae from one male and one female fetus from each litter were analyzed. High maternal LA consumption increased placental total n-6 and LA concentrations, and decreased total n-3 PUFA, alpha-linolenic acid (ALA), and docosahexaenoic acid (DHA). Fatty acid desaturase 1 (), angiopoietin-like 4 (), and diacylglycerol lipase beta () mRNA were downregulated in placentae from offspring from HLA dams. Maternal high LA downregulated the fatty acid transport protein 4 () and glucose transporter 1 () mRNA in placentae. IL-7 and IL-10 protein were decreased in placentae from offspring from HLA dams. In conclusion, a high maternal LA diet alters the placental fatty acid composition, inflammatory proteins, and expressions of nutrient transporters, which may program deleterious outcomes in offspring.
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http://dx.doi.org/10.3390/nu12082183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468786PMC
July 2020

Role of omega-6 and omega-3 fatty acids in fetal programming.

Clin Exp Pharmacol Physiol 2020 05 28;47(5):907-915. Epub 2020 Jan 28.

Institute for Health and Sport, Victoria University, Melbourne, Vic., Australia.

Maternal nutrition plays a critical role in fetal development and can influence adult onset of disease. Linoleic acid (LA) and alpha-linolenic acid (ALA) are major omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA), respectively, that are essential in our diet. LA and ALA are critical for the development of the fetal neurological and immune systems. However, in recent years, the consumption of n-6 PUFA has increased gradually worldwide, and elevated n-6 PUFA consumption may be harmful to human health. Consumption of diets with high levels of n-6 PUFA before or during pregnancy may have detrimental effects on fetal development and may influence overall health of offspring in adulthood. This review discusses the role of n-6 PUFA in fetal programming, the importance of a balance between n-6 and n-3 PUFAs in the maternal diet, and the need of further animal models and human studies that critically evaluate both n-6 and n-3 PUFA contents in diets.
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http://dx.doi.org/10.1111/1440-1681.13244DOI Listing
May 2020

Pregnancy and diet-related changes in the maternal gut microbiota following exposure to an elevated linoleic acid diet.

Am J Physiol Endocrinol Metab 2020 02 17;318(2):E276-E285. Epub 2019 Dec 17.

Institute for Health and Sport, Victoria University, Melbourne, Victoria, Australia.

Dietary intakes of linoleic acid (LA) have increased, including in women of reproductive age. Changes in maternal gut microbiome have been implicated in the metabolic adaptions that occur during pregnancy. We aimed to investigate whether consumption of a diet with elevated LA altered fecal microbiome diversity before and during pregnancy. Female Wistar-Kyoto rats consumed a high-LA diet (HLA: 6.21% of energy) or a low-LA diet (LLA: 1.44% of energy) for 10 wk before mating and during pregnancy. DNA was isolated from fecal samples before pregnancy [embryonic day 0 (E0)], or during pregnancy at E10 and E20. The microbiome composition was assessed with 16S rRNA sequencing. At E0, the beta-diversity of LLA and HLA groups differed with HLA rats having significantly lower abundance of the genera , and but higher abundance of and . Over gestation, in LLA but not HLA rats, there was a reduction in alpha-diversity and an increase in beta-diversity. In the LLA group, the abundance of , and decreased over gestation, whereas increased. In the HLA group; only the abundance of decreased. At E20, there were no differences in alpha- and beta-diversity, and the abundance of was significantly increased in the HLA group. In conclusion, consumption of a HLA diet alters gut microbiota composition, as does pregnancy in rats consuming a LLA diet. In pregnancy, consumption of a HLA diet does not alter gut microbiota composition.
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http://dx.doi.org/10.1152/ajpendo.00265.2019DOI Listing
February 2020

The effect of high maternal linoleic acid on endocannabinoid signalling in rodent hearts.

J Dev Orig Health Dis 2020 12 9;11(6):617-622. Epub 2019 Dec 9.

Institute for Health and Sport, Victoria University, Melbourne, Australia.

The endocannabinoid system (ECS), modulated by metabolites of linoleic acid (LA), is important in regulating cardiovascular function. In pregnancy, LA is vital for foetal development. We investigated the effects of elevated LA in H9c2 cardiomyoblasts in vitro and of a high linoleic acid (HLA, 6.21%) or low linoleic acid (LLA, 1.44%) diet during pregnancy in maternal and offspring hearts. H9c2 cell viability was reduced following LA exposure at concentrations between 300 and 1000 µM. HLA diet decreased cannabinoid receptor type 2 (CB2) mRNA expression in foetal hearts from both sexes. However, HLA diet increased CB2 expression in maternal hearts. The mRNA expression of fatty acid amide hydrolase (FAAH) in foetal hearts was higher in females than in males irrespective of diet and N-acyl phosphatidylethanolamine-specific phospholipase D (NAPE-PLD) mRNA expression showed an interaction between diet and sex. Data indicate that a high LA diet alters cell viability and CB2 expression, potentially influencing cardiac function during pregnancy and development of the offspring's heart.
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http://dx.doi.org/10.1017/S2040174419000813DOI Listing
December 2020

Elevated maternal linoleic acid reduces circulating leptin concentrations, cholesterol levels and male fetal survival in a rat model.

J Physiol 2019 07 2;597(13):3349-3361. Epub 2019 Jun 2.

School of Environment and Science, Griffith University, Nathan, QLD, Australia.

Key Points: Linoleic acid consumption is increasing in Western populations. We investigated whether elevated linoleic acid in pregnancy was deleterious to mothers or offspring. Maternal and fetal body and organ weights were not affected by elevated linoleic acid consumption. Maternal lipids and leptin were altered following elevated linoleic acid consumption. Male offspring numbers were reduced following elevated linoleic acid consumption.

Abstract: Dietary intakes of linoleic acid (LA) have increased dramatically in Western populations, including in women of reproductive age. Pro-inflammatory effects of LA may have detrimental effects on maternal and offspring outcomes. We aimed to investigate whether consumption of a maternal diet with elevated LA altered maternal inflammatory or metabolic markers during pregnancy, fetal growth and/or the sex ratio of the offspring. Female Wistar Kyoto rats consumed a diet high in LA (HLA) (6.21% of energy) or a diet low in LA (LLA) (1.44% of energy) for 10 weeks prior to mating and during pregnancy. Pregnant rats were killed at embryonic day 20 (E20). There were no differences in maternal or fetal body weights or organ weights in the HLA group compared to the LLA group. There was no difference in maternal circulating cytokine concentrations between dietary groups. In the maternal liver, IL-1α concentrations were significantly lower, and TNF-α and IL-7 significantly higher in the HLA group. Total plasma cholesterol, LDL-cholesterol, HDL cholesterol and the total:HDL cholesterol ratio were lower in dams fed the HLA diet. mRNA expression of sterol regulatory element binding transcription factor 1 (SREBF-1) and leptin in maternal adipose tissue was lower in the HLA group, as were circulating leptin concentrations. The proportion of male fetuses was lower and circulating prostaglandin E metabolite concentrations were increased in the HLA group. In conclusion, consumption of a maternal diet high in linoleic acid alters cholesterol metabolism and prostaglandin E metabolite concentrations, which may contribute to the reduced proportion of male offspring.
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http://dx.doi.org/10.1113/JP277583DOI Listing
July 2019

Linoleic Acid Increases Prostaglandin E2 Release and Reduces Mitochondrial Respiration and Cell Viability in Human Trophoblast-Like Cells.

Cell Physiol Biochem 2019 18;52(1):94-108. Epub 2019 Feb 18.

Institute for Health and Sport, Victoria University, Melbourne, Australia.

Background/aims: The omega 6 fatty acid (FA) linoleic acid (LA) is required for embryonic development; however, omega 6 FAs can alter cellular metabolism via inflammation or modulation of mitochondrial function. Fetal LA is obtained from the maternal diet, and FAs are transported to the fetus via placental FA transporters (FATPs) and binding proteins (FABPs), but specific proteins responsible for LA transport in placental trophoblasts are unknown. Dietary LA consumption is increasing, but the effect of elevated LA on trophoblast function is not clear.

Methods: Swan71 trophoblasts were exposed to physiological and supraphysiological concentrations of LA for 24 hours. Quantification of mRNA was determined using real time PCR, and protein concentration was determined by Western blot analysis. Cell viability, citrate synthase activity and mitochondrial respiration were determined.

Results: Exposure to 300 and 500 μM LA increased FATP1 and FATP4 mRNA expression. 500 μM LA increased FATP1 and FATP4 protein expression. Exposure to 500 μM increased FABP5 mRNA expression, while exposure to 100 to 500 μM LA decreased FABP3 mRNA expression. 300 and 500 μM LA decreased FABP3 protein expression. Cell viability was decreased by exposure to LA (100 to 1000 μM). Citrate synthase activity and routine mitochondrial respiration were significantly decreased by exposure to 300 and 500 μM LA, and maximal respiration and spare respiratory capacity were decreased by exposure to 100 to 500 μM LA. 300 and 500 μM LA increased reactive oxygen species generation in human trophoblasts. Moreover, exposure to 300 and 500 μM LA decreased IL-6 secretion. Exposure to 500 μM LA increased IL-8, NF-κB and PPAR-γ mRNA expression, but decreased NF-κB protein expression. 300 μM LA decreased IL-8 protein expression. Further, exposure to 100 to 500 μM LA increased prostaglandin E2 and leukotriene B₄ release.

Conclusion: Exposure to LA decreases cell viability, alters mRNA expression of FA transport related proteins, mitochondrial respiration and function, and inflammatory responses in trophoblasts. These findings may have implications on placental function when women consume high levels of LA.
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http://dx.doi.org/10.33594/000000007DOI Listing
March 2019

Peripheral modulation of the endocannabinoid system in metabolic disease.

Drug Discov Today 2018 03 10;23(3):592-604. Epub 2018 Jan 10.

Centre for Chronic Disease, College of Health and Biomedicine, Victoria University, Melbourne, VIC, Australia; School of Science, Menzies Health Institute Queensland, Griffith University, Nathan, QLD, Australia. Electronic address:

Dysfunction of the endocannabinoid system (ECS) has been identified in metabolic disease. Cannabinoid receptor 1 (CB) is abundantly expressed in the brain but also expressed in the periphery. Cannabinoid receptor 2 (CB) is more abundant in the periphery, including the immune cells. In obesity, global antagonism of overexpressed CB reduces bodyweight but leads to centrally mediated adverse psychological outcomes. Emerging research in isolated cultured cells or tissues has demonstrated that targeting the endocannabinoid system in the periphery alleviates the pathologies associated with metabolic disease. Further, peripheral specific cannabinoid ligands can reverse aspects of the metabolic phenotype. This Keynote review will focus on current research on the functionality of peripheral modulation of the ECS for the treatment of obesity.
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http://dx.doi.org/10.1016/j.drudis.2018.01.029DOI Listing
March 2018

Involvement of prolyl isomerase PIN1 in the cell cycle progression and proliferation of hepatic oval cells.

Pathol Res Pract 2017 Apr 18;213(4):373-380. Epub 2017 Jan 18.

Laboratory of Liver Regeneration, Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Geuman-dong, Duckjin-gu, Jeonju, 561-712, South Korea; Department of Surgery, Chonbuk National University Medical School, 634-18 Geuman-dong, Duckjin-gu, Jeonju, 516-712, South Korea. Electronic address:

Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation. In our study, the expression of Pin1 in the mice liver increased after three weeks feeding of 3, 5-diethoxycarbonyl-1, 4-dihydrocollidine (DDC) diet along with the proliferation of oval cells. The expression of Pin1 was higher in oval cells compared to the hepatocytes.Pin1 inhibition by Juglone reduced oval cell proliferation, which was restored to normal when oval cells were treated with IGF-1. Consistent with increased cell growth, expression of Pin1, β-catenin and PCNA were increased in IGF-1 treated cells in a time dependent manner. In FACS analysis, siRNA-mediated knockdown of the Pin1 protein in the oval cells significantly increased the numbers of cells in G0/G1 phase. Furthermore, hepatocyte when treated with TGF-β showed marked reduction in cell proliferation and expression of Pin1 whereas this effect was not seen in the oval cells treated with TGF-β. In conclusion, Pin1 plays important role in the cell cycle progression and increase oval cells proliferation which may be crucial in chronic liver injury.
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http://dx.doi.org/10.1016/j.prp.2017.01.005DOI Listing
April 2017

Glutamine inhibits CCl4 induced liver fibrosis in mice and TGF-β1 mediated epithelial-mesenchymal transition in mouse hepatocytes.

Food Chem Toxicol 2016 Jul 29;93:129-37. Epub 2016 Apr 29.

Laboratory of Liver Regeneration, Biomedical Research Institute, Chonbuk National University Hospital, 561-712, Jeonju, South Korea; Department of Surgery, Chonbuk National University Medical School, 561-712, Jeonju, South Korea. Electronic address:

Glutamine, traditionally a non-essential amino acid, now has been considered as essential in serious illness and injury. It is a major precursor for glutathione synthesis. However, the anti-fibrotic effect of glutamine and its molecular mechanism in experimental liver fibrosis have not been explored. In the present study we aimed to examine the potential role of glutamine in carbon tetrachloride (CCl4) induced liver fibrosis and TGF-β1 mediated epithelial mesenchymal transition (EMT) and apoptosis in mouse hepatocytes. Liver fibrosis was induced by intraperitoneal injection of CCl4 three times a week for 10 weeks. Glutamine treatment effectively attenuated liver injury and oxidative stress. Collagen content was significantly decreased in liver sections of glutamine treated mice compared to CCl4 model mice. Furthermore, glutamine decreased expression level of α-SMA and TGF-β in liver tissue. Our in vitro study showed that TGF-β1 treatment in hepatocytes resulted in loss of E-cadherin and increased expression of mesenchymal markers and EMT related transcription factor. In addition, TGF-β1 increased the expression of apoptotic markers. However, glutamine interestingly suppressed TGF-β1 mediated EMT and apoptosis. In conclusion, our results suggest that glutamine ameliorates CCl4 induced liver fibrosis and suppresses TGF-β1 induced EMT progression and apoptosis.
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http://dx.doi.org/10.1016/j.fct.2016.04.024DOI Listing
July 2016