Effects of Endurance Exercise and Rapamycin on Hepatic Energy Metabolism Gene Expression in Rats Fed a High-Fat Diet

BackgroundThe number of diet induced obese population is increasing every year, and the incidence of type 2 diabetes is also on the rise. Histone methylation and acetylation have been shown to be associated with lipogenesis and obesity by manipulating gene expression via the formation of repression or activation domains on chromosomes.ObjectiveIn this study, we aimed to explore gene activation or repression and related biological processes by histone modification across the whole genome on a high-fat diet (HFD) condition. We also aimed to elucidate the correlation of these genes that modulated by histone modification with energy metabolism and inflammation under both short-term and long-term HFD conditions.MethodWe performed ChIP-seq analysis of H3K9me2 and H3K9me3 in brown and white adipose tissues (WATs; subcutaneous adipose tissue) from mice fed with a standard chow diet (SCD) or HFD and a composite analysis of the histone modification of H3K9me2, H3K9me3, H3K4me1 and H3K27ac throughout the whole genome. We also employed and integrated two bulk RNA-seq and a single-nuclei RNA sequencing dataset and performed western blotting (WB) to confirm the gene expression levels in adipose tissue of the SCD and HFD groups.ResultsThe ChIP-seq and transcriptome analysis of mouse adipose tissues demonstrated that a series of genes were activated by the histone modification of H3K9me2, H3K9me3, H3K4me1, and H3K27ac in response to HFD condition. These genes were enriched in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways involved in lipogenesis, energy metabolism and inflammation. Several genes in the activated mitogen-activated protein kinase (MAPK) pathway might be related to both inflammation and energy metabolism in mice, rats and humans fed with HFD for a short or long term, as showed by bulk RNA-seq and single nuclei RNA-seq datasets. Western blot analyses further confirmed the increased expression of MET, VEGFA and the enhanced phosphorylation ratio of p44/42 MAPK upon HFD treatment.ConclusionThis study expanded our understanding of the influence of eating behavior on obesity and could assist the identification of putative therapeutic targets for the prevention and treatment of metabolic disorders in the future.

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GW0742 (PPAR-beta agonist) attenuates hepatic endoplasmic reticulum stress by improving hepatic energy metabolism in high-fat diet fed mice

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2018.03.013 ◽

2018 ◽

Vol 474 ◽

pp. 227-237 ◽

Cited By ~ 15

Author(s):

Flavia Maria Silva-Veiga ◽

Tamiris Lima Rachid ◽

Letícia de Oliveira ◽

Francielle Graus-Nunes ◽

Carlos Alberto Mandarim-de-Lacerda ◽

...

Keyword(s):

Endoplasmic Reticulum ◽

Energy Metabolism ◽

Endoplasmic Reticulum Stress ◽

High Fat Diet ◽

Beta Agonist ◽

High Fat ◽

Hepatic Energy Metabolism

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Osteocyte-specific ablation of Ppar[gamma] improves energy metabolism and prevents fat accumulation but not bone loss in response to a high fat diet

Bone Abstracts ◽

10.1530/boneabs.5.oc4.4 ◽

2016 ◽

Author(s):

Julia Brun ◽

Serge Ferrari ◽

Nicolas Bonnet

Keyword(s):

Energy Metabolism ◽

Bone Loss ◽

High Fat Diet ◽

Ppar Gamma ◽

High Fat ◽

Fat Accumulation

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Faculty Opinions recommendation of Epigenomics: maternal high-fat diet exposure in utero disrupts peripheral circadian gene expression in nonhuman primates.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.6519956.6650054 ◽

2010 ◽

Author(s):

Michael Symonds

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Nonhuman Primates ◽

In Utero ◽

Circadian Gene ◽

High Fat ◽

Diet Exposure

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Aberrant gene expression induced by a high fat diet is linked to H3K9 acetylation in the promoter-proximal region

Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms ◽

10.1016/j.bbagrm.2021.194691 ◽

2021 ◽

Vol 1864 (3) ◽

pp. 194691

Author(s):

Núria Morral ◽

Sheng Liu ◽

Abass M. Conteh ◽

Xiaona Chu ◽

Yue Wang ◽

...

Keyword(s):

Gene Expression ◽

High Fat Diet ◽

Proximal Region ◽

High Fat ◽

Aberrant Gene Expression ◽

H3k9 Acetylation ◽

Aberrant Gene ◽

Promoter Proximal Region

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Protective effects of a unique combination of nutritionally active ingredients on risk factors and gene expression associated with atherosclerosis in C57BL/6J mice fed a high fat diet

Food & Function ◽

10.1039/d0fo02867c ◽

2021 ◽

Author(s):

Joe W. E. Moss ◽

Jessica O Williams ◽

Wijdan Al-Ahmadi ◽

Victoria O'Morain ◽

Yee-Hung Chan ◽

...

Keyword(s):

Gene Expression ◽

Risk Factors ◽

Cardiovascular Disease ◽

High Fat Diet ◽

Inflammatory Disorder ◽

Protective Effects ◽

Unique Combination ◽

Omega 3 ◽

High Fat ◽

Food Ingredients

Atherosclerosis, an inflammatory disorder of the vasculature and the underlying cause of cardiovascular disease, is responsible for one in three global deaths. Consumption of active food ingredients such as omega-3...

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Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms22105390 ◽

2021 ◽

Vol 22 (10) ◽

pp. 5390

Author(s):

Qianhui Zeng ◽

Nannan Wang ◽

Yaru Zhang ◽

Yuxuan Yang ◽

Shuangshuang Li ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Insulin Sensitivity ◽

Energy Metabolism ◽

Glucose Tolerance ◽

High Fat Diet ◽

Chow Diet ◽

High Fat ◽

Glycolipid Metabolism ◽

Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

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Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽

10.1161/circ.118.suppl_18.s_1169-a ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Rieko Takanabe ◽

Koh Ono ◽

Tomohide Takaya ◽

Takahiro Horie ◽

Hiromichi Wada ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Body Weight ◽

Adipose Tissue ◽

High Fat Diet ◽

Control Cell ◽

High Fat ◽

Expression Levels ◽

Mesenteric Fat ◽

Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

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