Lipid Metabolism is Closely Associated with Normal Testicular Growth Based on Global Transcriptome Profiles in Normal and Underdeveloped Testis of Obese Zucker (<i>fa/fa</i>) Rats

Datar, Jutika; Regassa, Alemu; Kim, Woo-Kyun; Taylor, Carla G.; Zahradka, Peter; Suh, Miyoung

doi:10.1007/s11745-017-4298-2

Cited by 15 publications

(9 citation statements)

References 42 publications

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“…In addition, testes weights are 29.2% lower in Cyp3a-null males than WT males fed a HFD although the decreased testes weights are primarily due to two males that showed very low testis weights. A drop in testis weights sometimes in only one testis is not uncommon in rodent HFD studies [55]. In contrast, liver weights are 8% higher in Cyp3a-null males than WT males fed a HFD and this result is consistent (Table 2).…”

Section: Resultssupporting

confidence: 69%

High fat diet induced obesity is mitigated in Cyp3a-null female mice

Kumar

Litoff

Boswell

et al. 2018

Chemico-Biological Interactions

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Recent studies indicate a role for the constitutive androstane receptor (CAR), pregnane X-receptor (PXR), and hepatic xenobiotic detoxifying CYPs in fatty liver disease or obesity. Therefore, we examined whether Cyp3a-null mice show increased obesity and fatty liver disease following 8-weeks of exposure to a 60% high-fat diet (HFD). Surprisingly, HFD-fed Cyp3a-null females fed a HFD gained 50% less weight than wild-type (WT; B6) females fed a HFD. In contrast, Cyp3a-null males gained more weight than WT males, primarily during the first few weeks of HFD-treatment. Cyp3a-null females also recovered faster than WT females from a glucose tolerance test; males showed no difference in glucose tolerance between the groups. Serum concentrations of the anti-obesity hormone, adiponectin are 60% higher and β-hydroxybutyrate levels are nearly 50% lower in Cyp3a-null females than WT females, in agreement with reduced weight gain, faster glucose response, and reduced ketogenesis. In contrast, Cyp3a-null males have higher liver triglyceride concentrations and lipidomic analysis indicates an increase in phosphatidylinositol, phosphatidylserine and sphingomyelin. None of these changes were observed in females. Last, Pxr, Cyp2b, and IL-6 expression increased in Cyp3a-null females following HFD-treatment. Cyp2b and Fatp1 increased, while Pxr, Cpt1a, Srebp1 and Fasn decreased in Cyp3a-null males following a HFD, indicating compensatory biochemical responses in male (and to a lesser extent) female mice fed a HFD. In conclusion, lack of Cyp3a has a positive effect on acclimation to a HFD in females as it improves weight gain, glucose response and ketosis.

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Section: Resultssupporting

confidence: 69%

High fat diet induced obesity is mitigated in Cyp3a-null female mice

Kumar

Litoff

Boswell

et al. 2018

Chemico-Biological Interactions

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“…Furthermore, the large number and homogeneity of the applied samples resulted in a low variance within the sample groups and a high sensitivity of the applied method. Arbitrary definition of the cut-offs in gene expression analysis is usually made without underlying biological arguments [61,62,63,64] and, therefore, is not regarded as an adequate test procedure [65,66] because it does not include variance and an accompanying level of confidence [65,67,68]. Thus, we applied two sample t -test of the null hypothesis and used the p -value for the identification of significantly differentially regulated genes, which is frequently applied in microarray studies [69] and has many benefits in comparison to the fold change method.…”

Section: Discussionmentioning

confidence: 99%

Expression of Hypoxia-Inducible Factor 1α (HIF-1α) and Genes of Related Pathways in Altered Gravity

Vogel

Thiel

Tauber

et al. 2019

IJMS

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Immune system deterioration in space represents a major risk, which has to be mitigated for exploration-class missions into the solar system. Altered gravitational forces have been shown to regulate adaptation processes in cells of the immune system, which are important for appropriate risk management, monitoring and development of countermeasures. T lymphocytes and cells of the monocyte-macrophage system are highly migratory cell types that frequently encounter a wide range of oxygen tensions in human tissues and in hypoxic areas, even under homeostatic conditions. Hypoxia-inducible factor 1 and 2 (HIF’s) might have an important role in activation of T cells and cells of the monocyte-macrophages system. Thus, we investigated the regulation of HIF-dependent and, therefore, hypoxia-signaling systems in both cell types in altered gravity and performed transcript and protein analysis from parabolic flight and suborbital ballistic rocket experiments. We found that HIF-1α and HIF-1-dependent transcripts were differently regulated in altered gravity, whereas HIF-1α-dependent gene expression adapted after 5 min microgravity. Inter-platform comparisons identified PDK1 as highly responsive to gravitational changes in human U937 myelomonocytic cells and in Jurkat T cells. We suggest HIF-1 as a potential pharmacological target for counteracting immune system deterioration during space flight.

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“…Among these candidate RGs, PPP1R11, UXT, MRPL39, RPS15, HMBS, YWHAZ, TBP, and ACTB have been reported to be optimal RGs for normalization in yak [13][14][15]21]. In addition, GAPDH, HPRT1, PPIA, SDHA, and RPL13A were the commonly used RGs for expression studies in testis tissue and primordial germ cells of mice and rats [22][23][24][25]. Primers for TBP, ACTB, PPIA, HPRT1, GAPDH, and SDHA were reported by Li et al [14].…”

Section: Selection Of Candidate Rgs and Primer Designmentioning

confidence: 99%

Validation of Suitable Reference Genes for Gene Expression Studies on Yak Testis Development

Zhou

Chen

et al. 2020

Animals

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Testis has an important function in male reproduction. Its development is regulated by a large number of genes. The real-time reserve transcriptase-quantitative polymerase chain reaction (RT-qPCR) is a useful tool to evaluate the gene expression levels. However, unsuitable reference genes (RGs) can cause the misinterpretation of gene expression levels. Unfortunately, the ideal RGs for yak testis development are yet to be studied. In this study, 13 commonly used RGs were selected to identify the most stable RGs in yak testis at four different developmental stages, including two immature stages (6 months and 18 months) and two mature stages (30 months and 6 years). This study used GeNorm, NormFinder, BestKeeper, ∆Ct, and RefFinder programs to evaluate the stability of 13 candidate genes. The results of RefFinder showed that the stabilities of TATA box-binding protein (TBP) and ubiquitously expressed transcript protein (UXT) were ranked the top two across all developmental stages. TBP and hydroxymethylbilane synthase (HMBS) were stably expressed in immature stages, while mitochondrial ribosomal protein L39 (MRPL39) and TBP had higher stability than other candidate genes in mature stages. This study provided valuable information for gene expression studies to assist further investigation on the molecular mechanisms in underlying yak testis development.

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Lipid Metabolism is Closely Associated with Normal Testicular Growth Based on Global Transcriptome Profiles in Normal and Underdeveloped Testis of Obese Zucker (fa/fa) Rats

Cited by 15 publications

References 42 publications

High fat diet induced obesity is mitigated in Cyp3a-null female mice

High fat diet induced obesity is mitigated in Cyp3a-null female mice

Expression of Hypoxia-Inducible Factor 1α (HIF-1α) and Genes of Related Pathways in Altered Gravity

Validation of Suitable Reference Genes for Gene Expression Studies on Yak Testis Development

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