scholarly journals Histone H3K4me3 modification is a transgenerational epigenetic signal for lipid metabolism in Caenorhabditis elegans

2020 ◽  
Author(s):  
Qinghua Zhou ◽  
Qin-Li Wan ◽  
Xiao Meng ◽  
Chongyang Wang ◽  
Wenyu Dai ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Epigenetic Inheritance ◽  
Chromatin Modifications ◽  
C Elegans ◽  
Metabolic Genes ◽  
Epigenetic Signal ◽  
Histone H3k4 ◽  
Delta 9 Desaturase

Abstract As a major risk factor to human health, obesity presents a massive burden to people and society. Interestingly, the obese status of parents could affect progeny’s lipid accumulation through multi-generational epigenetic inheritance. To date, many questions remain as to how lipid accumulation leads to signals that are transmitted across generations. In this study, we established a model of C. elegans fed with a high fat diet (HFD) that led to obvious lipid accumulation, which can be propagated their progeny. Using this model, we discovered that transcription factors DAF-16/FOXO and SBP-1, nuclear receptors NHR-49 and NHR-80, and delta-9 desaturase (fat-5, fat-6, and fat-7) are required for transgenerational fat accumulation. Additionally, histone H3K4 tri-methylation (H3K4me3) marks genes related to lipid metabolism and increases their transcription response to multigenerational obesogenic effects. In summary, this study establishes that a network of lipid metabolic genes and chromatin modifications work together to achieve multigenerational obesogenic effects.

scholarly journals Hepatic Lipid Accumulation Induced by a High-fat Diet Is Regulated by Nrf2 Through Multiple Pathways

2021 ◽  
Author(s):  
sheng Qiu ◽  
Zerong Liang ◽  
Qinan Wu ◽  
Miao Wang ◽  
Mengliu Yang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Underlying Mechanism ◽  
Luciferase Assay ◽  
High Fat ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract BackgroundNuclear factor erythroid 2-related factor 2 (Nrf2) is reportedly involved in hepatic lipid metabolism, but the results are contradictory and the underlying mechanism thus remains unclear. Herein we focused on elucidating the effects of Nrf2 on hepatic adipogenesis and on determining the possible underlying mechanism. We established a metabolic associated fatty liver disease (MAFLD) model in high fat diet (HFD) fed Nrf2 knockout (Nrf2 KO) mice; further, a cell model of lipid accumulation was established using mouse primary hepatocytes (MPHs) treated with free fatty acids (FAs). Using these models, we investigated the relationship between Nrf2 and autophagy and its role in the development of MAFLD.ResultsWe observed that Nrf2 expression levels were up-regulated in patients with MAFLD and diet-induced obese mice. Nrf2 deficiency led to hepatic lipid accumulation in vivo and in vitro, in addition to, promoting lipogenesis mainly by increasing SREBP-1 activity. Moreover, Nrf2 deficiency attenuated autophagic flux and inhibited the fusion of autophagosomes and lysosomes in vivo and in vitro. Weakened autophagy caused reduced lipolysis in the liver. Importantly, Chromatin immunoprecipitation-qPCR (ChIP-qPCR) and dual-luciferase assay results proved that Nrf2 bound to LAMP1 promoter and regulated its transcriptional activity. We accordingly report that Nrf2-LAMP1 interaction has an indispensable role in Nrf2-regulated hepatosteatosis. ConclusionsThese data collectively confirm that Nrf2 deficiency promotes hepatosteatosis by enhancing SREBP-1 activity and attenuating autophagy. To conclude, our data reveal a novel multi-pathway effect of Nrf2 on lipid metabolism in the liver, and we believe that multi-target intervention of Nrf2 signaling is a promising new strategy for the prevention and treatment of MAFLD.

scholarly journals Intramyocellular Lipid Accumulation After High-Fat Diet Is Associated with the Gene Expression Involved in Lipid Metabolism in Skeletal Muscle of Non-Obese Men

2016 ◽  
Vol 62 (Suppl.1) ◽  
pp. 144-145
Author(s):  
SAORI KAKEHI ◽  
YOSHIFUMI TAMURA ◽  
KAGEUMI TAKENO ◽  
YUKO SAKURAI ◽  
MINAKO KAWAGUCHI ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Intramyocellular Lipid ◽  
High Fat

scholarly journals Fisetin Protects Against Hepatic Steatosis Through Regulation of the Sirt1/AMPK and Fatty Acid β-Oxidation Signaling Pathway in High-Fat Diet-Induced Obese Mice

2018 ◽  
Vol 49 (5) ◽  
pp. 1870-1884 ◽  
Author(s):  
Chian-Jiun Liou ◽  
Ciao-Han Wei ◽  
Ya-Ling Chen ◽  
Ching-Yi Cheng ◽  
Chia-Ling Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Fatty Acid Synthase ◽  
Epididymal Adipose Tissue ◽  
Obese Mice ◽  
High Fat

Background/Aims: Fisetin is a naturally abundant flavonoid isolated from various fruits and vegetables that was recently identified to have potential biological functions in improving allergic airway inflammation, as well as anti-oxidative and anti-tumor properties. Fisetin has also been demonstrated to have anti-obesity properties in mice. However, the effect of fisetin on nonalcoholic fatty liver disease (NAFLD) is still elusive. Thus, the present study evaluated whether fisetin improves hepatic steatosis in high-fat diet (HFD)-induced obese mice and regulates lipid metabolism of FL83B hepatocytes in vitro. Methods: NAFLD was induced by HFD in male C57BL/6 mice. The mice were then injected intraperitoneally with fisetin for 10 weeks. In another experiment, FL83B cells were challenged with oleic acid to induce lipid accumulation and treated with various concentrations of fisetin. Results: NAFLD mice treated with fisetin had decreased body weight and epididymal adipose tissue weight compared to NAFLD mice. Fisetin treatment also reduced liver lipid droplet and hepatocyte steatosis, alleviated serum free fatty acid, and leptin concentrations, significantly decreased fatty acid synthase, and significantly increased phosphorylation of AMPKα and the production of sirt-1 and carnitine palmitoyltransferase I in the liver tissue. In vitro, fisetin decreased lipid accumulation and increased lipolysis and β-oxidation in hepatocytes. Conclusion: This study suggests that fisetin is a potential novel treatment for alleviating hepatic lipid metabolism and improving NAFLD in mice via activation of the sirt1/AMPK and β-oxidation pathway.

scholarly journals The Establishment of Transgenerational Epigenetic Inheritance in the C. elegans Germline is Mediated by Lipid Metabolism

2020 ◽  
Author(s):  
Dan Peng ◽  
Chen Wang ◽  
Kai-Le Li ◽  
Zhi-Xue Gan ◽  
Yong-Hao Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Epigenetic Inheritance ◽  
Transport Proteins ◽  
Model System ◽  
Epigenetic Changes ◽  
Acetyl Coa Carboxylase ◽  
Loss Of Function ◽  
Epigenetic Memory ◽  
Binding Partner ◽  
C Elegans

SUMMARYEnvironmental stress-induced epigenetic changes are inherited by germlines and profoundly affect the behavior and physiology of subsequent generations. However, the mechanisms by which acquired transgenerational epigenetic imprints are established in the parental germline remain poorly understood. In this study, we used Caenorhabditis elegans as a model system and demonstrated that a key node of metabolism-Pod-2, an acetyl-CoA carboxylase, together with vitellogenins (Vits), cholesterol-binding/transport proteins, guide establishment of the acquired transgenerational epigenetic modifications H3K27me3 in the parental germline. The loss of function of a Vit; its transporter or receptor; or its binding partner, pod-2, resulted in the loss of acquired epigenetic memory in the germline. Our findings indicate that lipid metabolism is a critical mediator for establishing transgenerational epigenetic imprints in the germline.

scholarly journals C. elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling

2017 ◽  
Author(s):  
JF Clark ◽  
M Meade ◽  
G Ranepura ◽  
DH Hall ◽  
C Savage-Dunn
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
Metabolic Disorders ◽  
Bmp Signaling ◽  
Lipid Homeostasis ◽  
Metabolic Homeostasis ◽  
C Elegans ◽  
Lipid Droplet Size ◽  
Lipid Stores

AbstractMetabolic homeostasis is coordinately controlled by diverse inputs, which must be understood to combat metabolic disorders. Here we introduce DBL-1, the C. elegans BMP2/4 homolog, as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL 1/BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling (IIS) in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through inter-organ signaling to IIS, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.

scholarly journals Absence of gravin-mediated signaling inhibits development of high-fat diet-induced hyperlipidemia and atherosclerosis

2019 ◽  
Vol 317 (4) ◽  
pp. H793-H810 ◽  
Author(s):  
Qiying Fan ◽  
Xing Yin ◽  
Abeer Rababa’h ◽  
Andrea Diaz Diaz ◽  
Cori S. Wijaya ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Protein Kinase ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Regulatory Element ◽  
Plaque Formation ◽  
High Fat ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

Gravin, an A-kinase anchoring protein, is known to play a role in regulating key processes that lead to inflammation and atherosclerosis development, namely, cell migration, proliferation, and apoptosis. We investigated the role of gravin in the development of high-fat diet (HFD)-induced atherosclerosis and hyperlipidemia. Five-week-old male wild-type (WT) and gravin-t/t mice were fed a normal diet or an HFD for 16 wk. Gravin-t/t mice showed significantly lower liver-to-body-weight ratio, cholesterol, triglyceride, and very low-density lipoprotein levels in serum as compared with WT mice on HFD. Furthermore, there was less aortic plaque formation coupled with decreased lipid accumulation and liver damage, as the gravin-t/t mice had lower levels of serum alanine aminotransferase and aspartate aminotransferase. Additionally, gravin-t/t HFD-fed mice had decreased expression of liver 3-hydroxy-3-methyl-glutaryl-CoA reductase, an essential enzyme for cholesterol synthesis and lower fatty acid synthase expression. Gravin-t/t HFD-fed mice also exhibited inhibition of sterol regulatory element binding protein-2 (SREBP-2) expression, a liver transcription factor associated with the regulation of lipid transportation. In response to platelet-derived growth factor receptor treatment, gravin-t/t vascular smooth muscle cells exhibited lower intracellular calcium transients and decreased protein kinase A- and protein kinase C-dependent substrate phosphorylation, notably involving the Erk1/2 signaling pathway. Collectively, these results suggest the involvement of gravin-dependent regulation of lipid metabolism via the reduction of SREBP-2 expression. The absence of gravin-mediated signaling lowers blood pressure, reduces plaque formation in the aorta, and decreases lipid accumulation and damage in the liver of HFD mice. Through these processes, the absence of gravin-mediated signaling complex delays the HFD-induced hyperlipidemia and atherosclerosis. NEW & NOTEWORTHY The gravin scaffolding protein plays a key role in the multiple enzymatic pathways of lipid metabolism. We have shown for the first time the novel role of gravin in regulating the pathways related to the initiation and progression of atherosclerosis. Specifically, an absence of gravin-mediated signaling decreases the lipid levels (cholesterol, triglyceride, and VLDL) that are associated with sterol regulatory element binding protein-2 downregulation.

scholarly journals Sinapine-enriched rapeseed oils reduced fatty liver formation in high-fat diet-fed C57BL/6J mice

RSC Advances ◽  
2020 ◽  
Vol 10 (36) ◽  
pp. 21248-21258
Author(s):  
Youdong Li ◽  
Jinwei Li ◽  
Peirang Cao ◽  
Yuanfa Liu
Keyword(s):  
Lipid Metabolism ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
High Fat ◽  
In Cells

Sinapine reduces lipid accumulation in cells and the liver by regulating lipid metabolism.

scholarly journals Effects of Metformin Combined with Lactoferrin on Lipid Accumulation and Metabolism in Mice Fed with High-Fat Diet

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1628 ◽  
Author(s):  
Qing-Qing Min ◽  
Li-Qiang Qin ◽  
Zhen-Zhen Sun ◽  
Wen-Ting Zuo ◽  
Lin Zhao ◽  
...  
Keyword(s):  
Body Weight ◽  
Lipid Metabolism ◽  
Protein Expression ◽  
Visceral Fat ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Control Group ◽  
Lipolytic Enzyme ◽  
High Fat ◽  
Hepatic Lipid

Metformin (Met) and lactoferrin (Lf) both exhibit beneficial effects on body weight management and lipid accumulation. However, the synergistical action of Met and Lf remains unclear. In this study, 64 mice were divided into five groups, namely, the control group, high-fat diet (HFD group), HFD with Met (Met group), Lf (Lf group), and a combination of Met and Lf (Met + Lf group). Met (200 mg/kg body weight) and Lf (2 g/100 mL) were administrated in drinking water. The experiment lasted for 12 weeks. Body weight, serum, and hepatic lipids were determined. Histology of the liver and perirenal fat was observed. Protein expression related to hepatic lipid metabolism was also measured. HFD significantly increased body weight, visceral fat weight, and lipid profiles, which lead to obesity and dyslipidemia in mice. Compared with the HFD group, the treatments significantly decreased body weight and Lee’s index (body mass index of mice) with the lowest values in the Met + Lf group. The treatments also decreased the weight of visceral fat, and improved circulating lipid profile and the ability for regulating glucose intake. The adipocyte size and serum TC level were significantly lower in the Met + Lf group as compared with those in the Met or Lf group. The treatments alleviated hepatic lipid accumulation, especially in the Met + Lf group. For protein expression, the p-AMPK/AMPK ratio, a key kinase-regulating cellular energy homeostasis, was significantly higher in the Met + Lf group than the ratio in the HFD group. Similarly, the treatments significantly downregulated the protein expression of lipogenic enzymes (FAS, ACC, and SREBP-1) and upregulated the protein expression of lipolytic enzyme (ATGL). The protein expression of HMGCoAR, which is an important rate limiting enzyme in cholesterol biosynthesis, was only significantly lower in the Met + Lf group than in the HFD group. In conclusion, Met and Lf, either alone or in combination, prevented HFD-induced obesity and improved lipid metabolism.

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