Dynamic Changes in the Regulation of Energy Balance after Roux-en-Y Gastric Bypass Are Reflected in Time-Dependent Alterations in Liver Gene Expression

Abstract Consumption of caprine milk oligosaccharides (CMO) by dams during gestation and lactation, compared to a control diet or a diet supplemented with galacto-oligosaccharides (GOS), was associated with decreased maternal liver weight, increased offspring body weight and length at weaning, and increased offspring visceral fat and serum leptin concentration 30 days after weaning. These changes suggest that dietary CMO alters lipid metabolism, both in dams and offspring. We hypothesized that perinatal CMO intake affected expression of maternal genes in the liver involved in energy metabolism, and programmed pups’ metabolic function leading to increased post-weaning visceral adiposity. To characterise the effects of perinatal consumption of CMOs on maternal and offspring liver gene expression, C57BL/6 mice were fed either a control, CMO, or GOS diet from mating to weaning. From weaning, half of the pups from each maternal group were fed the control diet for 30 days. Microarray analysis was conducted on liver samples from dams and offspring. Differences in the expression of genes involved in lipid metabolism were observed in dams and changes in expression of hepatic genes involved in energy balance and steroid metabolism were observed in pups at weaning. Increased visceral fat was observed in pups 30 days. Perinatal consumption of CMO diet affected infant lipid metabolism, which may be related to altered expression of genes in the liver involved in energy balance and lipid metabolism in dams.

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Roux-en-Y Gastric Bypass Downregulates Angiotensin-Converting Enzyme 2 (ACE2) Gene Expression in Subcutaneous White Adipose Tissue: A Putative Protective Mechanism Against Severe COVID-19

Obesity Surgery ◽

10.1007/s11695-021-05271-7 ◽

2021 ◽

Author(s):

Leonardo Kristem ◽

Mariana Recamonde-Mendoza ◽

Giuliano C. Cigerza ◽

Jad Khoraki ◽

Guilherme M. Campos ◽

...

Keyword(s):

Gene Expression ◽

Gastric Bypass ◽

Adipose Tissue ◽

Angiotensin Converting Enzyme ◽

White Adipose Tissue ◽

Protective Mechanism ◽

Converting Enzyme ◽

Angiotensin Converting Enzyme 2 ◽

Subcutaneous White Adipose Tissue ◽

Ace2 Gene

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Moxifloxacin Activates the SOS Response in Mycobacterium tuberculosis in a Dose- and Time-Dependent Manner

Microorganisms ◽

10.3390/microorganisms9020255 ◽

2021 ◽

Vol 9 (2) ◽

pp. 255

Author(s):

Angelo Iacobino ◽

Giovanni Piccaro ◽

Manuela Pardini ◽

Lanfranco Fattorini ◽

Federico Giannoni

Keyword(s):

Gene Expression ◽

Mycobacterium Tuberculosis ◽

Physiological State ◽

Transcriptional Response ◽

Sos Response ◽

Resistant Mutant ◽

Time Dependent ◽

Dependent Manner ◽

Gyra Gene ◽

Drug Concentrations

Previous studies on Escherichia coli demonstrated that sub-minimum inhibitory concentration (MIC) of fluoroquinolones induced the SOS response, increasing drug tolerance. We characterized the transcriptional response to moxifloxacin in Mycobacterium tuberculosis. Reference strain H37Rv was treated with moxifloxacin and gene expression studied by qRT-PCR. Five SOS regulon genes, recA, lexA, dnaE2, Rv3074 and Rv3776, were induced in a dose- and time-dependent manner. A range of moxifloxacin concentrations induced recA, with a peak observed at 2 × MIC (0.25 μg/mL) after 16 h. Another seven SOS responses and three DNA repair genes were significantly induced by moxifloxacin. Induction of recA by moxifloxacin was higher in log-phase than in early- and stationary-phase cells, and absent in dormant bacilli. Furthermore, in an H37Rv fluoroquinolone-resistant mutant carrying the D94G mutation in the gyrA gene, the SOS response was induced at drug concentrations higher than the mutant MIC value. The 2 × MIC of moxifloxacin determined no significant changes in gene expression in a panel of 32 genes, except for up-regulation of the relK toxin and of Rv3290c and Rv2517c, two persistence-related genes. Overall, our data show that activation of the SOS response by moxifloxacin, a likely link to increased mutation rate and persister formation, is time, dose, physiological state and, possibly, MIC dependent.

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Massively parallel in vivo CRISPR screening identifies RNF20/40 as epigenetic regulators of cardiomyocyte maturation

Nature Communications ◽

10.1038/s41467-021-24743-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nathan J. VanDusen ◽

Julianna Y. Lee ◽

Weiliang Gu ◽

Catalina E. Butler ◽

Isha Sethi ◽

...

Keyword(s):

Gene Expression ◽

Genetic Screen ◽

Forward Genetics ◽

Epigenetic Mark ◽

Biological Processes ◽

Dynamic Changes ◽

Forward Genetic Screen ◽

High Resource ◽

Organ Systems

AbstractThe forward genetic screen is a powerful, unbiased method to gain insights into biological processes, yet this approach has infrequently been used in vivo in mammals because of high resource demands. Here, we use in vivo somatic Cas9 mutagenesis to perform an in vivo forward genetic screen in mice to identify regulators of cardiomyocyte (CM) maturation, the coordinated changes in phenotype and gene expression that occur in neonatal CMs. We discover and validate a number of transcriptional regulators of this process. Among these are RNF20 and RNF40, which form a complex that monoubiquitinates H2B on lysine 120. Mechanistic studies indicate that this epigenetic mark controls dynamic changes in gene expression required for CM maturation. These insights into CM maturation will inform efforts in cardiac regenerative medicine. More broadly, our approach will enable unbiased forward genetics across mammalian organ systems.

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Extensive changes in liver gene expression induced by Hereditary Tyrosinemia type I are not normalized by treatment with 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC)

Journal of Hepatology ◽

10.1016/s0168-8278(03)00433-1 ◽

2003 ◽

Vol 39 (6) ◽

pp. 901-909 ◽

Cited By ~ 28

Author(s):

Marjanka C Luijerink ◽

Saskia M.M Jacobs ◽

Ellen A.C.M van Beurden ◽

Leander P Koornneef ◽

Leo W.J Klomp ◽

...

Keyword(s):

Gene Expression ◽

Type I ◽

Tyrosinemia Type I ◽

Liver Gene ◽

Hereditary Tyrosinemia

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Time Dependent Gene Expression Changes in the Liver of Mice Treated with Benzene

Biomarker Insights ◽

10.4137/bmi.s590 ◽

2008 ◽

Vol 3 ◽

pp. BMI.S590 ◽

Cited By ~ 3

Author(s):

Han-Jin Park ◽

Jung Hwa Oh ◽

Seokjoo Yoon ◽

S.V.S. Rana

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

General Purpose ◽

Time Dependent ◽

Expression Data ◽

Benzene Exposure ◽

Microarray Analyses ◽

First Time ◽

Affymetrix Gene Chip

Benzene is used as a general purpose solvent. Benzene metabolism starts from phenol and ends with p-benzoquinone and o-benzoquinone. Liver injury inducted by benzene still remains a toxicologic problem. Tumor related genes and immune responsive genes have been studied in patients suffering from benzene exposure. However, gene expression profiles and pathways related to its hepatotoxicity are not known. This study reports the results obtained in the liver of BALB/C mice (SLC, Inc., Japan) administered 0.05 ml/100 g body weight of 2% benzene for six days. Serum, ALT, AST and ALP were determined using automated analyzer (Fuji., Japan). Histopathological observations were made to support gene expression data. c-DNA microarray analyses were performed using Affymetrix Gene-chip system. After six days of benzene exposure, twenty five genes were down regulated whereas nineteen genes were up-regulated. These gene expression changes were found to be related to pathways of biotransformation, detoxification, apoptosis, oxidative stress and cell cycle. It has been shown for the first time that genes corresponding to circadian rhythms are affected by benzene. Results suggest that gene expression profile might serve as potential biomarkers of hepatotoxicity during benzene exposure.

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