scholarly journals Concentration-dependent change in hypothalamic neuronal transcriptome by the dietary fatty acids: oleic and palmitic acids

2021 ◽  
Author(s):  
Fabiola Pacheco Valencia ◽  
Amanda F Marino ◽  
Christos Noutsos ◽  
Kinning Poon

Prenatal high-fat diet exposure increases hypothalamic neurogenesis events in embryos and programs offspring to be obesity-prone. The molecular mechanism involved in these dietary effects of neurogenesis are unknown. This study investigated the effects of oleic and palmitic acids, which are abundant in a high-fat diet, on the hypothalamic neuronal transcriptome and how these changes impact neurogenesis events. The results show differential effects of low and high concentrations of oleic or palmitic acid treatment on differential gene transcription. Gene ontology analysis uncovered significant gene enrichment in several cellular pathways involved in gene regulation and protein production, particularly with proliferation, migration, and cell survival. The enriched signaling pathways include Wnt, integrin, PDGF, and apoptosis, in addition endocrine function signaling pathways CCKR and GnRH. Further examination of proliferation and migration show low concentrations of oleic acid to stimulate proliferation and high concentrations of both oleic and palmitic acid to stimulate apoptosis. Oleic acid also reduced hypothalamic neuronal migration, with little effects by palmitic acid. The results show direct impact of the two most abundant fatty acids in a high fat diet to directly impact hypothalamic neuronal proliferation and migration. The results also uncovered signaling pathways affected by oleic and palmitic acid and suggest a mechanism of prenatal high-fat diet induced neurogenesis events is through these two abundant fatty acids.

Genes ◽  
2019 ◽  
Vol 10 (10) ◽  
pp. 751 ◽  
Author(s):  
Wu ◽  
Wei ◽  
Yang ◽  
Zhao ◽  
Luo

The autophagy-lysosome pathway, which involves many crucial genes and proteins, plays crucial roles in the maintenance of intracellular homeostasis by the degradation of damaged components. At present, some of these genes and proteins have been identified but their specific functions are largely unknown. This study was performed to clone and characterize the full-length cDNA sequences of nine key autolysosome-related genes (vps11, vps16, vps18, vps33b, vps41, lamp1, mcoln1, ctsd1 and tfeb) from yellow catfish Pelteobagrus fulvidraco. The expression of these genes and the transcriptional responses to a high-fat diet and fatty acids (FAs) (palmitic acid (PA) and oleic acid (OA)) were investigated. The mRNAs of these genes could be detected in heart, liver, muscle, spleen, brain, mesenteric adipose tissue, intestine, kidney and ovary, but varied with the tissues. In the liver, the mRNA levels of the nine autolysosome-related genes were lower in fish fed a high-fat diet than those fed the control, indicating that a high-fat diet inhibited formation of autolysosomes. Palmitic acid (a saturated FA) significantly inhibited the formation of autolysosomes at 12 h, 24 h and 48 h incubation. In contrast, oleic acid (an unsaturated FA) significantly induced the formation of autolysosomes at 12 h, but inhibited them at 24 h. At 48 h, the effects of OA incubation on autolysosomes were OA concentration-dependent in primary hepatocytes of P. fulvidraco. The results of flow cytometry and laser confocal observations confirmed these results. PA and OA incubation also increased intracellular non-esterified fatty acid (NEFA) concentration at 12 h, 24 h and 48 h, and influenced mRNA levels of fatty acid binding protein (fabp) and fatty acid transport protein 4 (fatp4) which facilitate FA transport in primary hepatocytes of P. fulvidraco. The present study demonstrated the molecular characterization of the nine autolysosome-related genes and their transcriptional responses to fat and FAs in fish, which provides the basis for further exploring their regulatory mechanism in vertebrates.


1999 ◽  
Vol 64 (7-8) ◽  
pp. 471-481 ◽  
Author(s):  
Alberto Gallegos-Infante ◽  
Ramiro Rico-Martinez

The crystallization of fatty acids is very important in industrial applications and biological systems. A comparison between theoretical models and experimental data helps in clarifying mechanistic aspects of these systems. In this contribution, we compare the performance of two models in fitting data from the crystallization of supersaturated solutions of palmitic acid in oleic acid. One of themodels was developed by Avrami and the other is based on considering diffusion as limiting (the D-model). The D-model fitted the data better than the Avrami model in all cases. The D-model has a low value of the regression coefficient (r2, lower than 0.9) in only three cases. For these points, the thermodynamic force was smaller. Differences in the parameter n (an index of dimensionality) were observed; these differences indicate that clusters were present previous to the crystallization process. Furthermore, there appears to be a difference in the mechanism of crystallization of pure solutions of palmitic acid and solutions with a small fraction of oleic acid. Thus, one is lead to the conclusion that the rate of crystallization of fatty acids at high concentrations is limited by diffusion.


Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Hiroki Matsui ◽  
Hiroaki Sunaga ◽  
Saki Anjo ◽  
Mas Rizky A Syamsunarno ◽  
Tatsuya Iso ◽  
...  

Introduction: Elovl6, the elongase of long chain fatty acids 6, is a rate-limiting enzyme catalyzing the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. Our recent study showed that Elovl6 is abundantly expressed in vascular smooth muscle cells (VSMC) and is dramatically induced in neointima in rat. Hypothesis: In this study, we tested the hypothesis that changes of fatty acid (FA) composition by Elovl6 affects the proliferation of VSMC and contributes to neointimal formation in vivo. Methods and Results: Abundant Elovl6 expression was observed in mice femoral artery at 2 weeks after wire-injury and in intimal thickening lesion of human coronary artery. Furthermore, Elovl6 mRNA expression in cultured human aortic SMC (HASMC) was significantly increased by platelet-derived growth factor-BB (2.4-fold, p<0.05) or hypoxic stress (6.7-fold, p<0.01) in a dose- or time-dependent manner. Furthermore, knockdown of Elovl6 expression in HASMC markedly suppressed cell proliferation (16%, relative to control, p<0.01) and migration, concomitantly induced the expression of p21 and phospholyration of AMP-activated protein kinase (p-AMPK) and suppressed mTOR expression. Consistent with in vitro data, Elovl6 deficient (Elovl6 -/-) mice at 2 weeks after injury showed markedly suppressed neointimal formation compared with wild-type (WT) mice (intima/media ratio: WT, 1.4 ± 0.6; Elovl6 -/-, 0.5 ± 0.2; Ki67-positive cells: 0.2 fold relative to WT mice; N=6-7, p<0.05). Of an importance, analysis of FA composition in SMC isolated from Elovl6 -/- mice showed that high levels of palmitic acid and low levels of oleic acid were detected as compared with that from WT mice. In accordance with these results, exogenous treatment of palmitic acid in SMC substantially suppressed cell proliferation (42%, relative to control, p<0.01) and migration, induced p21 and p-AMPK expressions. Conversely, these effects were blunted by adenovirus-mediated Elovl6-overexpression or exogenous oleic acid treatment. Conclusions: Collectively, our study demonstrates that proliferation of VSMC is tightly regulated by FA composition modulated by Elvlo6, offering a novel therapeutic target for arterial proliferative disease in which VSMC plays a key role.


2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Patricia G. Tremblay ◽  
Chloé Fortin ◽  
Marc-André Sirard

AbstractMaternal metabolic disorders such as obesity and diabetes are detrimental factors that compromise fertility and the success rates of medically assisted procreation procedures. During metabolic stress, adipose tissue is more likely to release free fatty acids (FFA) in the serum resulting in an increase of FFA levels not only in blood, but also in follicular fluid (FF). In humans, high concentrations of palmitic acid and stearic acid reduced granulosa cell survival and were associated with poor cumulus-oocyte complex (COC) morphology. Obesity and high levels of circulating FFA were also causatively linked to hampered insulin sensitivity in cells and compensatory hyperinsulinemia. To provide a global picture of the principal upstream signaling pathways and genomic mechanisms involved in this metabolic context, human granulosa-like tumor cells (KGN) were treated with a combination of palmitic acid, oleic acid, and stearic acid at the higher physiological concentrations found in the follicular fluid of women with a higher body mass index (BMI) (≥ 30.0 kg/m2). We also tested a high concentration of insulin alone and in combination with high concentrations of fatty acids. Transcription analysis by RNA-seq with a cut off for fold change of 1.5 and p-value 0.05 resulted in thousands of differentially expressed genes for each treatment. Using analysis software such as Ingenuity Pathway Analysis (IPA), we were able to establish that high concentrations of FFA affected the expression of genes mainly related to glucose and insulin homoeostasis, fatty acid metabolism, as well as steroidogenesis and granulosa cell differentiation processes. The combination of insulin and high concentrations of FFA affected signaling pathways related to apoptosis, inflammation, and oxidative stress. Taken together, our results provided new information on the mechanisms that might be involved in human granulosa cells exposed to high concentrations of FFA and insulin in the contexts of metabolism disorders.


2021 ◽  
Author(s):  
Jingda Li ◽  
Tianqi Wang ◽  
Panpan Liu ◽  
Fuyuan Yang ◽  
Xudong Wang ◽  
...  

Hesperetin as a major bioflavonoid in citrus fruits improves NAFLD by suppressing hepatic oxidative stress and inflammation.


2021 ◽  
Author(s):  
Xiaodan Lu ◽  
Rongbin Zhong ◽  
Ling Hu ◽  
Luyao Huang ◽  
Lijiao Chen ◽  
...  

Abstract Large yellow croaker roe phospholipids (LYCRPLs) has great nutritional value because of containing rich docosahexaenoic acid (DHA), which is a kind of n-3 polyunsaturated fatty acids (n-3 PUFAs). In...


2021 ◽  
Vol 12 (8) ◽  
Author(s):  
Heyun Zhang ◽  
Zhangyu Zheng ◽  
Rongqin Zhang ◽  
Yongcong Yan ◽  
Yaorong Peng ◽  
...  

AbstractHepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. SET and MYND domain-containing protein 3 (SMYD3) has been shown to promote the progression of various types of human cancers, including liver cancer; however, the detailed molecular mechanism is still largely unknown. Here, we report that SMYD3 expression in HCC is an independent prognostic factor for survival and promotes the proliferation and migration of HCC cells. We observed that SMYD3 upregulated sphingosine-1-phosphate receptor 1 (S1PR1) promoter activity by methylating histone 3 (H3K4me3). S1PR1 was expressed at high levels in HCC samples, and high S1PR1 expression was associated with shorter survival. S1PR1 expression was also positively correlated with SMYD3 expression in HCC samples. We confirmed that SMYD3 promotes HCC cell growth and migration in vitro and in vivo by upregulating S1PR1 expression. Further investigations revealed that SMYD3 affects critical signaling pathways associated with the progression of HCC through S1PR1. These findings strongly suggest that SMYD3 has a crucial function in HCC progression that is partially mediated by histone methylation at the downstream gene S1PR1, which affects key signaling pathways associated with carcinogenesis and the progression of HCC.


2017 ◽  
Vol 152 (5) ◽  
pp. S418
Author(s):  
Yuki Hirata ◽  
Shinji Fukuda ◽  
Kazuhiko Yamada ◽  
Kazuhide Higuchi ◽  
Yuki I. Kawamura ◽  
...  

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