Lipopolysaccharide induces adipose differentiation-related protein expression and lipid accumulation in the liver through inhibition of fatty acid oxidation in mice

2007 ◽  
Vol 42 (12) ◽  
pp. 969-978 ◽  
Author(s):  
Masumi Ohhira ◽  
Wataru Motomura ◽  
Mitsuko Fukuda ◽  
Takayuki Yoshizaki ◽  
Nobuhiko Takahashi ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Protein Expression ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Acid Oxidation ◽  
Related Protein ◽  
Adipose Differentiation

scholarly journals Medium & long-chain acylcarnitine’s relation to lipid metabolism as potential predictors for diabetic cardiomyopathy: a metabolomic study

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Dan-meng Zheng ◽  
Zhen-ni An ◽  
Ming-hao Ge ◽  
Dong-zhuo Wei ◽  
Ding-wen Jiang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Expression ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Cardiomyocyte Hypertrophy ◽  
Acid Oxidation ◽  
Simple Type ◽  
Related Protein ◽  
Long Chain

Abstract Background Acylcarnitine is an intermediate product of fatty acid oxidation. It is reported to be closely associated with the occurrence of diabetic cardiomyopathy (DCM). However, the mechanism of acylcarnitine affecting myocardial disorders is yet to be explored. This current research explores the different chain lengths of acylcarnitines as biomarkers for the early diagnosis of DCM and the mechanism of acylcarnitines for the development of DCM in-vitro. Methods In a retrospective non-interventional study, 50 simple type 2 diabetes mellitus patients and 50 DCM patients were recruited. Plasma samples from both groups were analyzed by high throughput metabolomics and cluster heat map using mass spectrometry. Principal component analysis was used to compare the changes occurring in the studied 25 acylcarnitines. Multivariable binary logistic regression was used to analyze the odds ratio of each group for factors and the 95% confidence interval in DCM. Myristoylcarnitine (C14) exogenous intervention was given to H9c2 cells to verify the expression of lipid metabolism-related protein, inflammation-related protein expression, apoptosis-related protein expression, and cardiomyocyte hypertrophy and fibrosis-related protein expression. Results Factor 1 (C14, lauroylcarnitine, tetradecanoyldiacylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, arachidic carnitine, octadecanoylcarnitine, 3-hydroxypalmitoleylcarnitine) and factor 4 (octanoylcarnitine, hexanoylcarnitine, decanoylcarnitine) were positively correlated with the risk of DCM. Exogenous C14 supplementation to cardiomyocytes led to increased lipid deposition in cardiomyocytes along with the obstacles in adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathways and affecting fatty acid oxidation. This further caused myocardial lipotoxicity, ultimately leading to cardiomyocyte hypertrophy, fibrotic remodeling, and increased apoptosis. However, this effect was mitigated by the AMPK agonist acadesine. Conclusions The increased plasma levels in medium and long-chain acylcarnitine extracted from factors 1 and 4 are closely related to the risk of DCM, indicating that these factors can be an important tool for DCM risk assessment. C14 supplementation associated lipid accumulation by inhibiting the AMPK/ACC/CPT1 signaling pathway, aggravated myocardial lipotoxicity, increased apoptosis apart from cardiomyocyte hypertrophy and fibrosis were alleviated by the acadesine.

scholarly journals MON-672 Progesterone Receptor Membrane Component 1 Suppresses Lipid Accumulation and Lipotoxicity in Animal Model of Diabetic Cardiomyopathy (DCM)

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sang R Lee ◽  
Eui-ju Hong
Keyword(s):  
Fatty Acid ◽  
Progesterone Receptor ◽  
Fatty Acid Oxidation ◽  
Diabetic Cardiomyopathy ◽  
Mitochondrial Respiration ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Acid Oxidation ◽  
High Fat ◽  
Membrane Component

Abstract Diabetic cardiomyopathy (DCM) is one of the complications triggered by type II diabetes (T2D) (1). When free fatty acids (FFA) are abundant in insulin resistant pre-diabetic patients because of adipose lipolysis, FFA tends to move toward heart (2). Lipid accumulation can cause cardiac lipotoxicity and exacerbate DCM (3). In previous study, Pgrmc1 has been identified to associate with fatty acid synthesis (4). Therefore, we assumed that Pgrmc1 will associate with DCM. By feeding high-fat diet for 8 weeks and injecting streptozotocin (30mg/kg), T2D and DCM were induced. The lipid accumulation was exacerbated in T2D-induced Pgrmc1 KO heart, and FFA level was also high. Levels of lipid metabolic genes showed the tendency for lipid accumulation and lipotoxicity, and glycolysis was induced in T2D-induced Pgrmc1 KO heart. Though glycolysis presents higher efficiency for energy production in cardiomyopathy (5), it did not compensate the impairment of mitochondrial respiration in Pgrmc1 KO heart. High-fat diet and streptozotocin could not be the interfering factors, because suppression of fatty acid oxidation, induction of glycolysis, and impairment of mitochondrial respiration were observed similarly in post-prandial mice which were fed with normal chow. Insulin was excluded for interfering factor as cell line with serum starvation showed mitochondrial suppression and glycolytic induction in flux analyzer analysis in Pgrmc1 knockdown. Conversely, induction of fatty acid oxidation and suppression of glycolysis were observed in 72 h fasting of Pgrmc1 KO heart, suggesting the nutrition is closely associated with the metabolic modulation of Pgrmc1 on heart. This metabolic phenotype of Pgrmc1 KO heart consequently exacerbated DCM by showing high levels of fibrosis, inflammation, endoplasmic reticulum stress, and oxidative stress. References: (1) Jia G, Hill MA, Sowers JR. Diabetic Cardiomyopathy: An Update of Mechanisms Contributing to This Clinical Entity. Circulation research. 2018;122:624-38. (2) Noll C, Carpentier AC. Dietary fatty acid metabolism in prediabetes. Current opinion in lipidology. 2017;28:1-10. (3) Goldberg IJ, Trent CM, Schulze PC. Lipid metabolism and toxicity in the heart. Cell metabolism. 2012;15:805-12. (4) Lee SR, Kwon SW, Kaya P, Lee YH, Lee JG, Kim G, et al. Loss of progesterone receptor membrane component 1 promotes hepatic steatosis via the induced de novo lipogenesis. Scientific reports. 2018;8:15711. (5) Nagoshi T, Yoshimura M, Rosano GM, Lopaschuk GD, Mochizuki S. Optimization of cardiac metabolism in heart failure. Current pharmaceutical design. 2011;17:3846-53.

Kaempferol Isolated from Nelumbo nucifera Inhibits Lipid Accumulation and Increases Fatty Acid Oxidation Signaling in Adipocytes

2015 ◽  
Vol 18 (12) ◽  
pp. 1363-1370 ◽  
Author(s):  
Bonggi Lee ◽  
Misung Kwon ◽  
Jae Sue Choi ◽  
Hyoung Oh Jeong ◽  
Hae Young Chung ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Accumulation ◽  
Nelumbo Nucifera ◽  
Acid Oxidation

scholarly journals Berberine Reduces Lipid Accumulation by Promoting Fatty Acid Oxidation in Renal Tubular Epithelial Cells of the Diabetic Kidney

2022 ◽  
Vol 12 ◽  
Author(s):  
Qingfeng Rong ◽  
Baosheng Han ◽  
Yafeng Li ◽  
Haizhen Yin ◽  
Jing Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Epithelial Cells ◽  
Fatty Acid Oxidation ◽  
High Glucose ◽  
Lipid Accumulation ◽  
Diabetic Kidney Disease ◽  
Acid Oxidation ◽  
Tubular Epithelial Cells ◽  
Diabetic Kidney ◽  
Renal Tubular

Abnormal lipid metabolism in renal tubular epithelial cells contributes to renal lipid accumulation and disturbed mitochondrial bioenergetics which are important in diabetic kidney disease. Berberine, the major active constituent of Rhizoma coptidis and Cortex phellodendri, is involved in regulating glucose and lipid metabolism. The present study aimed to investigate the protective effects of berberine on lipid accumulation in tubular epithelial cells of diabetic kidney disease. We treated type 2 diabetic db/db mice with berberine (300 mg/kg) for 12 weeks. Berberine treatment improved the physical and biochemical parameters of the db/db mice compared with db/m mice. In addition, berberine decreased intracellular lipid accumulation and increased the expression of fatty acid oxidation enzymes CPT1, ACOX1 and PPAR-α in tubular epithelial cells of db/db mice. The mitochondrial morphology, mitochondrial membrane potential, cytochrome c oxidase activity, mitochondrial reactive oxygen species, and mitochondrial ATP production in db/db mice kidneys were significantly improved by berberine. Berberine intervention activated the AMPK pathway and increased the level of PGC-1α. In vitro berberine suppressed high glucose-induced lipid accumulation and reversed high glucose-induced reduction of fatty acid oxidation enzymes in HK-2 cells. Importantly, in HK-2 cells, berberine treatment blocked the change in metabolism from fatty acid oxidation to glycolysis under high glucose condition. Moreover, berberine restored high glucose-induced dysfunctional mitochondria. These data suggested that berberine alleviates diabetic renal tubulointerstitial injury through improving high glucose-induced reduction of fatty acid oxidation, alleviates lipid deposition, and protect mitochondria in tubular epithelial cells.

scholarly journals Acetate Affects the Process of Lipid Metabolism in Rabbit Liver, Skeletal Muscle and Adipose Tissue

Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 799 ◽  
Author(s):  
Lei Liu ◽  
Chunyan Fu ◽  
Fuchang Li
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Synthesis ◽  
Lipid Accumulation ◽  
Acid Synthesis ◽  
Control Group ◽  
Acid Oxidation ◽  
Signal Pathways ◽  
Peroxisome Proliferator ◽  
Acid Uptake

Short-chain fatty acids (SCFAs) (a microbial fermentation production in the rabbit gut) have an important role in many physiological processes, which may be related to the reduced body fat of rabbits. In the present experiment, we study the function of acetate (a major SCFA in the rabbit gut) on fat metabolism. Ninety rabbits (40 days of age) were randomly divided into three groups: a sham control group (injection of saline for four days); a group experiencing subcutaneous injection of acetate for four days (2 g/kg BM per day, one injection each day, acetate); and a pair-fed sham treatment group. The results show that acetate-inhibited lipid accumulation by promoting lipolysis and fatty acid oxidation and inhibiting fatty acid synthesis. Activated G protein-coupled receptor 41/43, adenosine monophosphate activated protein kinase (AMPK) and extracellular-signal-regulated kinase (ERK) 1/2 signal pathways were likely to participate in the regulation in lipid accumulation of acetate. Acetate reduced hepatic triglyceride content by inhibiting fatty acid synthesis, enhancing fatty acid oxidation and lipid output. Inhibited peroxisome proliferator-activated receptor α (PPARα) and activated AMPK and ERK1/2 signal pathways were related to the process in liver. Acetate reduced intramuscular triglyceride level via increasing fatty acid uptake and fatty acid oxidation. PPARα was associated with the acetate-reduced intracellular fat content.

scholarly journals Lipotoxic Palmitate Impairs the Rate of β-Oxidation and Citric Acid Cycle Flux in Rat Neonatal Cardiomyocytes

2016 ◽  
Vol 40 (5) ◽  
pp. 969-981 ◽  
Author(s):  
Taha Haffar ◽  
Ali Akoumi ◽  
Nicolas Bousette
Keyword(s):  
Fatty Acid ◽  
Citric Acid ◽  
Dehydrogenase Activity ◽  
Fatty Acid Oxidation ◽  
Isocitrate Dehydrogenase ◽  
Lipid Accumulation ◽  
Citric Acid Cycle ◽  
Acid Oxidation ◽  
Acid Cycle ◽  
Neonatal Cardiomyocytes

Background/Aims: Diabetic hearts exhibit intracellular lipid accumulation. This suggests that the degree of fatty acid oxidation (FAO) in these hearts is insufficient to handle the elevated lipid uptake. We previously showed that palmitate impaired the rate of FAO in primary rat neonatal cardiomyocytes. Here we were interested in characterizing the site of FAO impairment induced by palmitate since it may shed light on the metabolic dysfunction that leads to lipid accumulation in diabetic hearts. Methods: We measured fatty acid oxidation, acetyl-CoA oxidation, and carnitine palmitoyl transferase (Cpt1b) activity. We measured both forward and reverse aconitase activity, as well as NAD+ dependent isocitrate dehydrogenase activity. We also measured reactive oxygen species using the 2', 7'-Dichlorofluorescin Diacetate (DCFDA) assay. Finally we used thin layer chromatography to assess diacylglycerol (DAG) levels. Results: We found that palmitate significantly impaired mitochondrial β-oxidation as well as citric acid cycle flux, but not Cpt1b activity. Palmitate negatively affected net aconitase activity and isocitrate dehydrogenase activity. The impaired enzyme activities were not due to oxidative stress but may be due to DAG mediated PKC activation. Conclusion: This work demonstrates that palmitate, a highly abundant fatty acid in human diets, causes impaired β-oxidation and citric acid cycle flux in primary neonatal cardiomyocytes. This metabolic defect occurs prior to cell death suggesting that it is a cause, rather than a consequence of palmitate mediated lipotoxicity. This impaired mitochondrial metabolism can have important implications for metabolic diseases such as diabetes and obesity.

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