scholarly journals HDAC5 Inhibits Hepatic Lipogenic Genes Expression by Attenuating the Transcriptional Activity of Liver X Receptor

2016 ◽  
Vol 39 (4) ◽  
pp. 1561-1567 ◽  
Author(s):  
Hai-Yan Jia ◽  
Quan-Zhong Li ◽  
Li-Fang Lv
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Transcriptional Activity ◽  
Leptin Receptor ◽  
Liver X Receptor ◽  
Obese Mice ◽  
Quantitative Real Time Pcr ◽  
High Fat ◽  
Lipogenic Genes

Background/Aims: Liver X receptor (LXR), a member of the nuclear receptor superfamily, is known to induce the expression of SREBP-1c and ChREBP, two master regulators of hepatic lipogenesis. Histone deacyetylases (HDACs) have been shown to play critical roles in glucose and lipids metabolism. However, the exact role of HDAC5 in lipogenesis remains elusive. Methods: mRNA and protein levels of HDAC5 were analyzed by quantitative real-time PCR and Western blots in high-fat-diet-induced and leptin receptor deficiency-induced obese mice. HDAC5 was overexpressed or depleted in HepG2 cells, followed by analysis of cellular triglycerides contents. Quantitative real-time PCR was used to detect the expression levels of lipogenic genes. Luciferase reporter assay was used to determine the regulation of HDAC on the transcriptional activity of LXR. Co-immunoprecipitation experiment was used to determine the interaction between HDAC5 and LXR. Results: We found that mRNA and protein expression levels of hepatic HDAC5 were reduced in high-fat-diet-induced and leptin receptor deficiency-induced obese mice. In vitro studies further demonstrated that knockdown of HDAC5 promoted cellular triglycerides accumulation, accompanied with up-regulation of lipogenic genes. At the molecular level, HDAC5 was shown to interact with LXR, thereby attenuating its transcriptional activity. Conclusion: Overall, our data suggest that hepatic HDAC5 is an important regulator of lipogenesis.

scholarly journals Aberrant expression of HDL-bound microRNA induced by a high-fat diet in a pig model: implications in the pathogenesis of dyslipidaemia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guoyuan Sui ◽  
Lianqun Jia ◽  
Nan Song ◽  
Dongyu Min ◽  
Si Chen ◽  
...  
Keyword(s):  
Real Time ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Enrichment Analysis ◽  
Diet Group ◽  
High Fat ◽  
Positive Regulation ◽  
Aberrant Expression ◽  
Balanced Diet ◽  
Mirna Sequencing

Abstract Background A high-fat diet can affect lipid metabolism and trigger cardiovascular diseases. A growing body of studies has revealed the HDL-bound miRNA profiles in familial hypercholesterolaemia; in sharp contrast, relevant studies on high-fat diet-induced dyslipidaemia are lacking. In the current study, HDL-bound miRNAs altered by a high-fat diet were explored to offer some clues for elucidating their effects on the pathogenesis of dyslipidaemia. Methods Six pigs were randomly divided into two groups of three pigs each, namely, the high-fat diet and the balanced diet groups, which were fed a high-fat diet and balanced diet separately for six months. HDL was separated from plasma, which was followed by dissociation of the miRNA bound to HDL. miRNA sequencing of the isolated miRNA was performed to identify the differential expression profiles between the two groups, which was validated by real-time PCR. TargetScan, miRDB, and miRWalk were used for the prediction of genes targeted by the differential miRNAs. Results Compared with the balanced diet group, the high-fat diet group had significantly higher levels of TG, TC, LDL-C and HDL-C at six months. miRNA sequencing revealed 6 upregulated and 14 downregulated HDL-bound miRNAs in the high-fat diet group compared to the balanced diet group, which was validated by real-time PCR. GO enrichment analysis showed that dysregulated miRNAs in the high-fat diet group were associated with the positive regulation of lipid metabolic processes, positive regulation of lipid biosynthetic processes, and positive regulation of Ras protein signal transduction. Insulin resistance and the Ras signalling pathway were enriched in the KEGG pathway enrichment analysis. Conclusions Twenty HDL-bound miRNAs are significantly dysregulated in high-fat diet-induced dyslipidaemia. This study presents an analysis of a new set of HDL-bound miRNAs that are altered by a high-fat diet and offers some valuable clues for novel mechanistic insights into high-fat diet-induced dyslipidaemia. Further functional verification study using a larger sample size will be required.

scholarly journals Lactobacillus plantarum LMT1-48 exerts anti-obesity effect in high-fat diet-induced obese mice by regulating expression of lipogenic genes

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Woo Jin Choi ◽  
Hye Jin Dong ◽  
Hyun Uk Jeong ◽  
Dong Wook Ryu ◽  
Soo Min Song ◽  
...  
Keyword(s):  
Lactobacillus Plantarum ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Lipogenic Genes

scholarly journals High-fat diet-induced and genetically inherited obesity differentially alters DNA methylation profile in the germline of adult male rats

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Sharvari S. Deshpande ◽  
Harishankar Nemani ◽  
Gandhimathi Arumugam ◽  
Avinash Ravichandran ◽  
Nafisa H. Balasinor
Keyword(s):  
Dna Methylation ◽  
Real Time ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Male Rats ◽  
Global Dna Methylation ◽  
High Fat ◽  
Differential Effects ◽  
Male Germline ◽  
Embryo Loss

Abstract Background Paternal obesity has been associated with reduced live birth rates. It could lead to inheritance of metabolic disturbances to the offspring through epigenetic mechanisms. However, obesity is a multifactorial disorder with genetic or environmental causes. Earlier we had demonstrated differential effects of high-fat diet-induced obesity (DIO) and genetically inherited obesity (GIO) on metabolic, hormonal profile, male fertility, and spermatogenesis using two rat models. The present study aimed to understand the effect of DIO and GIO on DNA methylation in male germline, and its subsequent effects on the resorbed (post-implantation embryo loss) and normal embryos. First, we assessed the DNA methylation enzymatic machinery in the testis by Real-Time PCR, followed global DNA methylation levels in spermatozoa and testicular cells by ELISA and flow cytometry, respectively. Further, we performed Methylation Sequencing in spermatozoa for both the groups. Sequencing data in spermatozoa from both the groups were validated using Pyrosequencing. Expression of the differentially methylated genes was assessed in the resorbed and normal embryos sired by the DIO group using Real-Time PCR for functional validation. Results We noted a significant decrease in Dnmt transcript and global DNA methylation levels in the DIO group and an increase in the GIO group. Sequencing analysis showed 16,966 and 9113 differentially methylated regions in the spermatozoa of the DIO and GIO groups, respectively. Upon pathway analysis, we observed genes enriched in pathways involved in embryo growth and development namely Wnt, Hedgehog, TGF-beta, and Notch in spermatozoa for both the groups, the methylation status of which partially correlated with the gene expression pattern in resorbed and normal embryos sired by the DIO group. Conclusion Our study reports the mechanism by which diet-induced and genetically inherited obesity causes differential effects on the DNA methylation in the male germline that could be due to a difference in the white adipose tissue accumulation. These differences could either lead to embryo loss or transmit obesity-related traits to the offspring in adult life.

scholarly journals The Role of Exercise in Reducing Hyperlipidemia-Induced Neuronal Damage in Apolipoprotein E-Deficient Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Yumeng Bai ◽  
Yali Feng ◽  
Bo Jiang ◽  
Yan Yang ◽  
Zuowei Pei ◽  
...  
Keyword(s):  
Exercise Training ◽  
Apolipoprotein E ◽  
Real Time ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Neuronal Injury ◽  
Serum Levels ◽  
Normal Diet ◽  
High Fat ◽  
Expression Levels

Hyperlipidemia causes nervous system-related diseases. Exercise training has developed into an established evidence-based treatment strategy that is beneficial for neuronal injury. This study investigated the effect of exercise on hyperlipidemia-induced neuronal injury in apolipoprotein E-deficient (ApoE-/-) mice. Male ApoE-/- mice (age: 8 weeks) were randomly divided into four groups as follows: mice fed a normal diet (ND), normal diet+swimming training (ND+S), high-fat diet (HD), and high-fat diet+swimming (HD+S). Exercise training consisted of swimming for 40 min/day, 5 days/week for 12 weeks. After 12 weeks, we measured serum levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-c). We also evaluated glial fibrillary acidic protein (GFAP) expression levels using immunohistochemistry, real-time PCR, and immunoblotting. In addition, NLR family pyrin domain-containing 3 (NLRP3), interleukin- (IL-) 18, caspase-1, Bax, Bcl-2, and phosphorylated extracellular signal-regulated kinase (p-ERK) expression levels were measured using immunoblotting. Serum levels of TG, TC, and LDL-c were lower in ApoE-/- HD+S mice than in ApoE-/- HD mice. Immunohistochemistry, real-time PCR, and immunoblotting showed increased levels of GFAP in the ApoE-/- HD group. Immunoblotting revealed increased levels of NLRP3, IL-18, caspase-1, Bax, Bcl-2, and p-ERK in the ApoE-/- HD group; however, they were significantly suppressed in the ApoE-/- HD+S group. Therefore, exercise has protective effects against neuronal injury caused by hyperlipidemia.

Anti-Obesity Effects of Germinated Brown Rice Extract through Down-Regulation of Lipogenic Genes in High Fat Diet-Induced Obese Mice

2012 ◽  
Vol 76 (6) ◽  
pp. 1068-1074 ◽  
Author(s):  
Jin-Nyoung HO ◽  
Mi-Eun SON ◽  
Won-Chul LIM ◽  
Seung-Taik LIM ◽  
Hong-Yon CHO
Keyword(s):  
High Fat Diet ◽  
Brown Rice ◽  
Obese Mice ◽  
High Fat ◽  
Down Regulation ◽  
Germinated Brown Rice ◽  
Lipogenic Genes

scholarly journals Measurement of altered APP isoform expression in adipose tissue of diet-induced obese mice by absolute quantitative real-time PCR

2017 ◽  
Vol 21 (2) ◽  
pp. 100-107
Author(s):  
Hansol Min ◽  
Jinil Kim ◽  
Young-Jin Kim ◽  
Mi-Sook Yoon ◽  
Richard E. Pratley ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Real Time ◽  
Real Time Pcr ◽  
Obese Mice ◽  
Quantitative Real Time Pcr ◽  
Isoform Expression

scholarly journals Endogenous Omega-3 Polyunsaturated Fatty Acids Preserved Morphology and Function of Brown Fat Impaired by High-Fat Diet Feeding in Mice

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1214-1214
Author(s):  
Lei Hao ◽  
Chih-Yu Chen ◽  
Jingxuan Kang ◽  
Yonghui Nie
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Real Time ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Brown Fat ◽  
Separate Experiment ◽  
Omega 3 ◽  
High Fat ◽  
And Function

Abstract Objectives The role of omega-3 polyunsaturated fatty acids (PUFA) in regulation of energy homeostasis remains poorly understood. In this study, we aimed to investigate how omega-3 PUFA regulate the morphology and function of brown fat tissue (BAT) in mice. Methods Sixteen-week-old male wild type (WT) and transgenic fat-1 mice, which are capable of synthesizing omega-3 PUFA, were fed a low-fat diet (LFD) or a high-fat diet (HFD) for 13 weeks. Metabolic tissues, including BAT, white adipose tissues, and liver, were collected for biochemical and histological analysis. Results Transgenic fat-1 mice had significantly lower body weight and total fat mass compared with WT mic fed HFD. In addition, fat-1 mice had improved glucose tolerance compared with WT. We found that in WT mice, HFD induced larger lipid droplet accumulation (“whitening”) in BAT, whereas “whitening” in BAT was significantly alleviated in fat-1 mice. Real time PCR showed that some thermogenic markers, such as uncoupling protein 1 (UCP1), carnitine palmitoyltransferase I (CPT I), and cell death activator (CIDE-A), were expressed more in fat-1 mice compared with WT mice fed HFD. Moreover, fat-1 mice had significantly lower lipopolysaccharide levels compared with WT mice. Real time PCR showed that fat-1 mice had significantly lower levels of inflammatory markers, including monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor (TNFα), and mouse macrophage marker (F4/80) in BAT. In a separate experiment, we found that fat-1 mice resisted UCP suppression by LPS injection. Conclusions This study demonstrated that HFD led to obesity and “whitening” of BAT in WT mice; conversely, omega-3 PUFA in fat-1 mice preserved morphology and function of BAT impaired by HFD. We revealed that the dysfunction of BAT may be attributed to increased LPS production due to HFD feeding, and that omega-3 PUFA alleviate the dysfunction of BAT through inhibition of LPS production. Funding Sources This study was supported by the Fortune Education Foundation (New York, USA) and Sansun Life Sciences (Hong Kong, China).

scholarly journals Maternal high-fat diet alters expression of pathways of growth, blood supply and arachidonic acid in rat placenta

2013 ◽  
Vol 2 ◽  
Author(s):  
Marloes Dekker Nitert ◽  
Kanchan Vaswani ◽  
Melissa Hum ◽  
Hsiu-Wen Chan ◽  
Ryan Wood-Bradley ◽  
...  
Keyword(s):  
Gene Expression ◽  
Arachidonic Acid ◽  
Protein Expression ◽  
Real Time ◽  
Blood Supply ◽  
Real Time Pcr ◽  
High Fat Diet ◽  
Messenger Rna ◽  
Expression Patterns ◽  
High Fat

AbstractThe high fat content in Western diets probably affects placental function during pregnancy with potential consequences for the offspring in the short and long term. The aim of the present study was to compare genome-wide placental gene expression between rat dams fed a high-fat diet (HFD) and those fed a control diet for 3 weeks before conception and during gestation. Gene expression was measured by microarray and pathway analysis was performed. Gene expression differences were replicated by real-time PCR and protein expression was assessed by Western blot analysis. Placental and fetal weights at E17.25 were not altered by exposure to the maternal HFD. Gene pathways targeting placental growth, blood supply and chemokine signalling were up-regulated in the placentae of dams fed the HFD. The up-regulation in messenger RNA expression for five genes Ptgs2 (fatty acid cyclo-oxidase 2; COX2), Limk1 (LIM domain kinase 1), Pla2g2a (phospholipase A2), Itga1 (integrin α-1) and Serpine1 was confirmed by real-time PCR. Placental protein expression for COX2 and LIMK was also increased in HFD-fed dams. In conclusion, maternal HFD feeding alters placental gene expression patterns of placental growth and blood supply and specifically increases the expression of genes involved in arachidonic acid and PG metabolism. These changes indicate a placental response to the altered maternal metabolic environment.

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