Comparison of liver gene expression by RNAseq and PCR analysis after 8 weeks of feeding soy protein isolate- or casein-based diets in an obese liver steatosis rat model

Kozaczek, Melisa; Bottje, Walter; Greene, Elizabeth S.; Lassiter, Kentu; Kong, Byung-Whi; Dridi, Sami; Korourian, Soheila; Hakkak, Reza

doi:10.1039/c9fo01387c

Cited by 11 publications

(8 citation statements)

References 82 publications

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“…However, the precise mechanisms that lead to SPImediated attenuating liver steatosis is not completely understood. To better understand fundamental mechanisms by which SPI attenuated NAFLD, we conducted global transcriptomic (RNAseq) analysis on liver tissue obtained from obese rats fed the SPI-and CAS-based diets for 8 weeks (13). The results of this study indicated gene expression that would promote anti-inflammatory activities in SPI-fed rats and inflammatory activities in CAS-fed rats, which is consistent with the observation of reduced liver steatosis in SPI-fed rats (12).…”

Section: Introductionsupporting

confidence: 77%

“…Colony stimulating factor 2 (CSF2) ( Table 3A and Figure 6A) or granulocyte-macrophage colony-stimulating factor (GM-CSF) was predicted to be inhibited in SPI-fed rats at 16 weeks (activation z score = −2.29). Its receptor, CSF2 receptor beta (CSF2RB) was found to be down-regulated at 8 weeks on the SPI diet (13). CSF2 is a cytokine involved in inflammatory response that modulates the production and differentiation of macrophages and granulocytes (44,45).…”

Section: Discussionmentioning

confidence: 99%

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Long-Term Soy Protein Isolate Consumption Reduces Liver Steatosis Through Changes in Global Transcriptomics in Obese Zucker Rats

Kozaczek

Bottje²,

Kong³

et al. 2020

Front. Nutr.

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To determine how soy protein isolate (SPI) ameliorated liver steatosis in male obese Zucker rats, we conducted global transcriptomic expression (RNAseq) analysis on liver samples of male rats fed either the SPI or a control casein (CAS)-based diet (n = 8 per group) for 16 weeks. Liver transcriptomics were analyzed using an Ilumina HiSeq system with 2 × 100 base pair paired-end reads method. Bioinformatics was conducted using Ingenuity Pathway Analysis (IPA) software (Qiagen, CA) with P < 0.05 and 1.3-fold differential expression cutoff values. Regression analysis between RNAseq data and targeted mRNA expression analysis of 12 top differentially expressed genes (from the IPA program) using quantitative PCR (qPCR) revealed a significant regression analysis (r2 = 0.69, P = 0.0008). In addition, all qPCR values had qualitatively similar direction of up- or down-regulation compared to the RNAseq transcriptomic data. Diseases and function analyses that were based on differentially expressed target molecules in the dataset predicted that lipid metabolism would be enhanced whereas inflammation was predicted to be inhibited in SPI-fed compared to CAS-fed rats at 16 weeks. Combining upstream regulator and regulator effects functions in IPA facilitates the prediction of upstream regulators (e.g., transcription regulators) that could play important roles in attenuating or promoting liver steatosis due to SPI or CAS diets. Upstream regulators that were predicted to be activated (from expression of down-stream targets) linked to increased conversion of lipid and transport of lipid in SPI-fed rats included hepatocyte nuclear factor 4 alpha (HNF4A) and aryl hydrocarbon receptor (AHR). Upstream regulators that were predicted to be activated in CAS-fed rats linked to activation of phagocytosis and neutrophil chemotaxis included colony stimulating factor 2 and tumor necrosis factor. The results provide clear indication that long-term SPI-fed rats exhibited diminished inflammatory response and increased lipid transport in liver compared to CAS-fed rats that likely would contribute to reduced liver steatosis in this obese Zucker rat model.

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Section: Introductionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

Long-Term Soy Protein Isolate Consumption Reduces Liver Steatosis Through Changes in Global Transcriptomics in Obese Zucker Rats

Kozaczek

Bottje²,

Kong³

et al. 2020

Front. Nutr.

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“…This study used the methods described in the studies by Hakkak et al ( 29 ) and Kozaczek et al ( 32 ), and the description of the methods partly reproduces their wording ( 29 , 32 ). The protocol for this study (code number 3242) was approved by the Institutional Animal Care and Use Committee at the University of Arkansas for Medical Sciences (IACUC) on December 6, 2011.…”

Section: Methodsmentioning

confidence: 99%

“…The methods for RNA extraction from the liver samples and the pipeline followed to generate the RNAseq data are described in Kozaczek et al ( 32 ). More than 1,200 transcripts were differentially expressed (>1.3-fold difference and P < 0.05) and later evaluated with Ingenuity Pathway Analysis program (IPA, Qiagen, CA) to help in the analysis and understanding of the global gene expression data.…”

Section: Methodsmentioning

confidence: 99%

Effects of Short- and Long-Term Soy Protein Feeding on Hepatic Cytochrome P450 Expression in Obese Nonalcoholic Fatty Liver Disease Rat Model

Kozaczek

Bottje²,

Albataineh³

et al. 2021

Front. Nutr.

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Obesity can lead to chronic health complications such as nonalcoholic fatty liver disease (NAFLD). NAFLD is characterized by lipid aggregation in the hepatocytes and inflammation of the liver tissue as a consequence that can contribute to the development of cirrhosis and hepatocellular carcinoma (HCC). Previously, we reported that feeding obese Zucker rats with soy protein isolate (SPI) can reduce liver steatosis when compared with a casein (CAS) diet as a control. However, the effects of SPI on cytochrome P450 (CYP) in an obese rat model are less known. In addition, there is a lack of information concerning the consumption of soy protein in adolescents and its effect in reducing the early onset of NAFLD in this group. Our main goal was to understand if the SPI diet had any impact on the hepatic CYP gene expression when compared with the CAS diet. For this purpose, we used the transcriptomic data obtained in a previous study in which liver samples were collected from obese rats after short-term (eight-week) and long-term (16-week) feeding of SPI (n = 8 per group). To analyze this RNAseq data, we used Ingenuity Pathway Analysis (IPA) software. Comparing short- vs long-term feeding revealed an increase in the number of downregulated CYP genes from three at 8 weeks of SPI diet to five at 16 weeks of the same diet (P ≤ 0.05). On the other hand, upregulated CYP gene numbers showed a small increase in the long-term SPI diet compared to the short-term SPI diet, from 14 genes at 8 weeks to 17 genes at 16 weeks (P ≤ 0.05). The observed changes may have an important role in the attenuation of liver steatosis.

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“…Similarly, Narp protein has been reported to be present in rat testes but not in other peripheral tissues (O'Brien et al, 1999). However, recently, it has been shown that Narp protein is expressed in peripheral tissue such as the liver (Kozaczek et al, 2019).…”

Section: Expression Pattern and Function Of Np2mentioning

confidence: 98%

Exploring Novel Molecular Approaches to Promote Repair of the Damaged Nervous System: A Role for Neuronal Pentraxin 2

Shanmugalingam¹

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The mammalian central nervous system (CNS) does not spontaneously regenerate, thereby limiting functional recovery following numerous CNS injuries. Neural repair is restricted due to both the inhibitory extracellular environment post-injury and the limited intrinsic capabilities of adult neurons. The visual system, including retinal ganglion cells (RGCs), and their axons, the optic nerve, is widely used as a model to study molecular mechanisms associated with neuroprotection and regeneration following CNS injury.Many potential therapeutic strategies have been discovered using this model with variable success in terms of promoting axon regeneration. Recent work has suggested that modulating neural activity can protect neurons and promote axon regeneration after injury; however, this area of research remains in its infancy. Activity-dependent signalling molecules, such as neuronal pentraxin 2 (NP2), have been suggested as critical modulators of neuroplasticity but have not been previously implicated in CNS neuroprotection or axon regeneration. This thesis examined the role of NP2 in protecting RGCs and promoting axon regeneration, using in vitro, ex vivo and in vivo (optic nerve injury) techniques. Given that previous work has supported the notion that RGCs lose intrinsic capacity for regeneration with age, the developmental expression pattern of NP2 was characterized. Additionally, the impact of NP2 treatment on RGC survival, using an in vitro RGC culture model, was evaluated. Furthermore, the ability of NP2 to enhance RGC neurite outgrowth using both in vitro and ex vivo model systems was examined. To assess the in vivo impact of exogenous NP2 administration on RGC survival and axon Firstly, I thank God for giving me the strength to persevere and successfully complete this chapter of my life.I would like to express my sincerest gratitude to many people for their support and encouragement throughout my studies. I would like to start by thanking and expressing my immeasurable amount of gratitude to my supervisor, Dr. Patrice D. Smith. Anytime I was uncertain how to proceed, her door was always open; she always answered every question with a smile. Her guidance and support helped me build confidence in myself and made me a better researcher. It was a privilege to work under Dr. Smith's guidance and the completion of this thesis is a testament to her endless patience and constant encouragement. I would like to thank my thesis committee members, Dr. Hayley and Dr.Hildebrand, for their time, insight into my thesis and for their continued support. I would like to express my sincere appreciation to Dr.

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Comparison of liver gene expression by RNAseq and PCR analysis after 8 weeks of feeding soy protein isolate- or casein-based diets in an obese liver steatosis rat model

Abstract: Differential expression of genes provides insight into fundamental mechanisms associated with the ability of soy protein isolate to attenuate liver steatosis in genetically obese rats.

Cited by 11 publications

References 82 publications

Long-Term Soy Protein Isolate Consumption Reduces Liver Steatosis Through Changes in Global Transcriptomics in Obese Zucker Rats

Long-Term Soy Protein Isolate Consumption Reduces Liver Steatosis Through Changes in Global Transcriptomics in Obese Zucker Rats

Effects of Short- and Long-Term Soy Protein Feeding on Hepatic Cytochrome P450 Expression in Obese Nonalcoholic Fatty Liver Disease Rat Model

Exploring Novel Molecular Approaches to Promote Repair of the Damaged Nervous System: A Role for Neuronal Pentraxin 2

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