Expression patterns of hepatic genes involved in lipid metabolism in cows with subclinical or clinical ketosis

Zhu, Yiwei; Liu, Zhaoxi; Du, Xiliang; Shi, Zhen; Jin, Meizhong; Sha, Xue-Ying; Li, Xiaobing; Wang, Zhe; Li, Xinwei

doi:10.3168/jds.2018-14965

Cited by 56 publications

(48 citation statements)

References 54 publications

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“…In this study, healthy human hepatocytes were used, and cell culture-based assays were adopted to confirm that the triglyceride increased after ACSL1overexpression, and decreased after ACSL1downregulation. Lipid accumulation in the liver was due to a combination of reduced fatty acid β-oxidation and increased fat synthesis [15]. This study indicated that human hepatocellular carcinoma cells (HepG2) overexpressing ACSL1 had 40% higher triglyceride content than the control group after 24 hours of exposure to 1.0mM oleic acid ester.…”

Section: Discussionmentioning

confidence: 82%

ACSL1 affects Triglyceride Levels through the PPARγ Pathway

Li¹,

Li²,

Meng³

et al. 2020

Int. J. Med. Sci.

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In clinical cohort studies, high expression of long-chain acyl-coenzyme A synthetases 1 (ACSL1 gene) in peripheral white blood cells of patients with acute myocardial infarction (AMI) has been utilized as molecular markers of myocardial infarction diagnosis. The plasma triglyceride level of AMI patients is significantly higher than that of healthy individuals. We hypothesized that the high expression of ACSL1 increases the level of triglyceride, which is one of the pathogenesis of AMI promoted by ACSL1. In this report, cell culture based methods were adopted to test the hypothesis and further investigate the effect and mechanism of ACSL1 on lipid metabolism. In this study, liver cells of healthy individuals were cultured, the overexpression and the knockdown vectors of ACSL1 were constructed and transfected into liver cells. The transfection was verified at the mRNA and protein level. Intracellular triglyceride content was quantitatively analyzed using ELISA. Changes of genes related to lipid metabolism were subsequently measured through PCR array. Overexpression of ACSL1 led to higher gene expression and protein levels compared to control and the triglyceride content was significantly increased in overexpressing cells. The expression level of fatty acid oxidation pathway PPARγ was significantly down-regulated compared with the control group, as were genes associated with fatty acid synthesis pathways: SREBP1, ACC, FAS, and SCD1. ACSL1 knockdown decreased the content of triglyceride whereas PPARγ was up-regulated and SREBP1, ACC, FAS, and SCD1 were down-regulated compared with the control group. In summary, high expression of ACSL1 reduced fatty acid β-oxidation through the PPARγ pathway, thereby increasing triglyceride levels.

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Section: Discussionmentioning

confidence: 82%

ACSL1 affects Triglyceride Levels through the PPARγ Pathway

Li¹,

Li²,

Meng³

et al. 2020

Int. J. Med. Sci.

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“…During this transition, lipid mobilization increases, resulting in greater nonesterified fatty acid (NEFA) uptake by the liver and increased triacylglycerol (TAG) accumulation (Loor et al, 2013b). This accumulation of TAG may be linked to increased NEFA uptake activating sterol regulatory element-binding protein 1c, which recent data indicate could promote transcription of lipogenic genes (Zhu et al, 2019), and the inherently low rate of verylow-density lipoprotein (VLDL) secretion in ruminants (Bauchart et al, 1996). A chronic state of TAG accumulation in the liver can lead to mitochondrial dysfunction and inflammation (Li et al, 2015;Du et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

Hepatic betaine-homocysteine methyltransferase and methionine synthase activity and intermediates of the methionine cycle are altered by choline supply during negative energy balance in Holstein cows

Coleman

Vailati-Riboni

Elolimy

et al. 2019

Journal of Dairy Science

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Although choline requirements are unknown, enhanced postruminal supply may decrease liver triacylglycerol (TAG) storage and increase flux through the methionine cycle, helping cows during a negative energy balance (NEB). The objective was to investigate effects of postruminal choline supply during NEB on hepatic activity of betaine-homocysteine methyltransferase (BHMT), methionine synthase (MTR), methionine adenosyltransferase, transcription of enzymes, and metabolite concentrations in the methionine cycle. Ten primiparous rumen-cannulated Holstein cows (158 ± 24 d postpartum) were used in a replicated 5 × 5 Latin square design with 4-d treatment periods and 10 d of recovery (14 d/period). Treatments were unrestricted intake with abomasal infusion of water (A0), restricted intake (R; 60% of net energy for lactation requirements to induce NEB) with abomasal infusion of water (R0) or R plus abomasal infusion of 6.25, 12.5, or 25 g/d of choline ion. Liver tissue was collected on d 5 after the infusions ended, blood on d 1 to 5, and milk on d 1 to 4. Statistical contrasts were A0 versus R0 (CONT1) and tests of linear (L), quadratic (Q), and cubic (C) effects of choline dose. Plasma choline increased with R (CONT1) and choline (L). Although R decreased milk yield (CONT1), choline increased milk yield and liver phosphatidylcholine (PC), but decreased TAG (L). No differences were observed in plasma PC or very-lowdensity lipoprotein concentrations with R or choline. Activity and mRNA abundance of BHMT were greater with R (CONT1) and increased with choline (L). Although activity of MTR was lower with R (CONT1), it tended to increase with choline (L). No effect of R was detected for activity of methionine adenosyltransferase, but it changed cubically across dose of choline. Those responses were associated with linear increases in the concentrations of liver tissue (+13%) and plasma methionine concentrations. The mRNA abundance of CP-T1A, SLC22A5, APOA5, and APOB, genes associated with fatty acid oxidation and lipoprotein metabolism, was upregulated by choline (Q). Overall, enhanced supply of choline during NEB increases hepatic activity of BHMT and MTR to regenerate methionine and PC, partly to help clear TAG. The relevance of these effects during the periparturient period merits further research.

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“…Thus, a side-by-side comparison of Met and Cho using an in vitro system would generate valuable data in terms of efficacy. Because of the recognition that certain metabolic organs also are immune responsive, data from this type of study would also help clarify the potential link between the immune and metabolic responses, especially in early lactation (Li et al, 2015;Du et al, 2018;Zhu et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Inflammation and oxidative stress transcription profiles due to in vitro supply of methionine with or without choline in unstimulated blood polymorphonuclear leukocytes from lactating Holstein cows

Lopreiato

Vailati-Riboni

Bellingeri

et al. 2019

Journal of Dairy Science

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Neutrophils are the most important polymorphonuclear leukocytes (PMNL), representing the front-line defense involved in pathogen clearance upon invasion. As such, they play a pivotal role in immune and inflammatory responses. Isolated PMNL from 5 mid-lactating Holstein dairy cows were used to evaluate the in vitro effect of methionine (Met) and choline (Chol) supplementation on mRNA expression of genes related to the Met cycle and innate immunity. The target genes are associated with the Met cycle, cell signaling, inflammation, antimicrobial and killing mechanisms, and pathogen recognition. Treatments were allocated in a 3 × 3 factorial arrangement, including 3 Lys-to-Met ratios (L:M, 3.6:1, 2.9:1, or 2.4:1) and 3 levels of supplemental Chol (0, 400, or 800 μg/mL). Three replicates per treatment group were incubated for 2 h at 37°C and 5% atmospheric CO 2. Both betaine-homocysteine S-methyltransferase and choline dehydrogenase were undetectable, indicating that PMNL (at least in vitro) cannot generate Met from Chol through the betaine pathway. The PMNL incubated without Chol experienced a specific state of inflammatory mediation [greater interleukin-1β (IL1B), myeloperoxidase (MPO), IL10, and IL6] and oxidative stress [greater cysteine sulfinic acid decarboxylase (CSAD), cystathionine gamma-lyase (CTH), glutathione reductase (GSR), and glutathione synthase (GSS)]. However, data from the interaction L:M × Chol indicated that this negative state could be overcome by supplementing additional Met. This was reflected in the upregulation of methionine synthase (MTR) and toll-like receptor 2 (TLR2); that is, pathogen detection ability. At the lowest level of supplemental Chol, Met downregulated GSS, GSR, IL1B, and IL6, suggesting it could reduce cellular inflammation and enhance antioxidant status. At 400 μg/mL Chol, supplemental Met upregulated PMNL recognition capacity [higher TLR4 and L-selectin (SELL)]. Overall, enhancing the supply of methyl donors to isolated unstimulated PMNL from mid-lactating dairy cows leads to a low level of PMNL activation and upregulates a cytoprotective mechanism against oxidative stress. Enhancing the supply of Met coupled with adequate Chol levels enhances the gene expression of PMNL pathogen-recognition mechanism. These data suggest that Chol supply to PMNL exposed to low levels of Met effectively downregulated the entire repertoire of innate inflammatory-responsive genes. Thus, Met availability in PMNL during an inflammatory challenge may be sufficient for mounting an appropriate biologic response.

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Expression patterns of hepatic genes involved in lipid metabolism in cows with subclinical or clinical ketosis

Cited by 56 publications

References 54 publications

ACSL1 affects Triglyceride Levels through the PPARγ Pathway

ACSL1 affects Triglyceride Levels through the PPARγ Pathway

Hepatic betaine-homocysteine methyltransferase and methionine synthase activity and intermediates of the methionine cycle are altered by choline supply during negative energy balance in Holstein cows

Inflammation and oxidative stress transcription profiles due to in vitro supply of methionine with or without choline in unstimulated blood polymorphonuclear leukocytes from lactating Holstein cows

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