scholarly journals Pyrroloquinoline Quinone Modifies Lipid Profile, but Not Insulin Sensitivity, of Palmitic Acid-Treated L6 Myotubes

2020 ◽  
Vol 21 (21) ◽  
pp. 8382
Author(s):  
Elżbieta Supruniuk ◽  
Agnieszka Mikłosz ◽  
Adrian Chabowski
Keyword(s):  
Fatty Acid ◽  
Palmitic Acid ◽  
Lipid Content ◽  
Fatty Acid Synthase ◽  
Citrate Synthase ◽  
Muscle Cells ◽  
Pyrroloquinoline Quinone ◽  
Sirtuin 1 ◽  
Fatty Acid Transport ◽  
L6 Myotubes

Pyrroloquinoline quinone (PQQ) is a novel stimulator of mitochondrial biogenesis and cellular energy metabolism. This is the first study investigating regulatory mechanisms and metabolic responses underlying PQQ’s action in palmitate-exposed L6 myotubes. Particularly, we assessed alterations in lipid content and composition, expression of metabolic enzymes, and changes in glucose transport. The experiments were conducted using muscle cells subjected to short (2 h) and prolonged (24 h) incubation with PQQ in a sequence of pre- and post-palmitic acid (PA) exposure. We demonstrated the opposite effects of 2 and 24 h treatments with PQQ on lipid content, i.e., a decline in the level of free fatty acids and triacylglycerols in response to short-time PQQ incubation as compared to increases in diacylglycerol and triacylglycerol levels observed after 24 h. We did not demonstrate a significant impact of PQQ on fatty acid transport. The analysis of metabolic enzyme expression showed that the vast majority of PQQ-dependent alterations cumulated in the PA/PQQ 24 h group, including elevated protein amount of peroxisome proliferator activated receptor γ co-activator 1α (PGC-1α), sirtuin-1 (SIRT1), phosphorylated 5′AMP-activated protein kinase (pAMPK), carnitine palmitoyltransferase I (CPT1), citrate synthase (CS), fatty acid synthase (FAS), and serine palmitoyltransferase, long chain base subunit 1 (SPT1). In conclusion, the results mentioned above indicate PQQ-dependent activation of both fatty acid oxidation and lipid synthesis in order to adapt cells to palmitic acid-rich medium, although PQQ did not attenuate insulin resistance in muscle cells.

scholarly journals Male Breast Cancer—Immunohistochemical Patterns and Clinical Relevance of FASN, ATF3, and Collagen IV

2021 ◽  
Vol 15 ◽  
pp. 117822342110024
Author(s):  
Saudade André ◽  
António E Pinto ◽  
Giovani L Silva ◽  
Fernanda Silva ◽  
Jacinta Serpa ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Disease Free Survival ◽  
Collagen Iv ◽  
Male Breast ◽  
Fatty Acid Transport ◽  
Valuable Insight ◽  
Activating Transcription Factor 3 ◽  
Stromal Fibroblasts ◽  
Prognostic Analysis

Background: Male breast carcinoma (male BC) is an uncommon neoplasia without individualized strategies for diagnosis and therapeutics. Low overall survival (OS) rates have been reported, mostly associated with patients’ advanced stage and older age. Intratumoral heterogeneity versus homogeneity of malignant epithelial cells seems to be an important factor to consider for the development of combination therapies with curative intention. Objective: In this preliminary study, we aim to provide valuable insight into the distinct clinicopathologic features of male BC. Material and methods: In a series of 40 male BC patients, we evaluated by immunohistochemistry androgen receptor; activating transcription factor 3 (ATF3); p16; cyclin D1; fatty acid synthase (FASN); fatty acid transport protein 1 (FATP1); β1, β3, β4, and β6 integrins; collagen I and collagen IV; and their interactions. Kaplan-Meier survival curves and log-rank tests were assessed for statistical analysis. Results: Homogeneous epithelial staining of p16, ATF3, β6 integrin, FASN, and FATP1 was found to be significantly intercorrelated, and associated with high Ki67. These markers also stained tumor stromal fibroblasts. The prognostic analysis showed statistically significant associations of FASN with disease-free survival (DFS) and OS, as well as of ATF3 with OS and collagen IV with DFS. Conclusions: This study highlights, as a novel finding, the relevance of FASN, ATF3, and collagen IV immunophenotypes, which may have innovative application in the clinical management of male BC.

scholarly journals Identification of the molecular regulation of differences in lipid deposition in dedifferentiated preadipocytes from different chicken tissues

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zheng Ma ◽  
Na Luo ◽  
Lu Liu ◽  
Huanxian Cui ◽  
Jing Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Lipid Content ◽  
Regulatory Network ◽  
Total Lipid Content ◽  
Fatty Acid Transport ◽  
Lipid Deposition ◽  
Ppar Signaling ◽  
The Difference

Abstract Background A body distribution with high intramuscular fat and low abdominal fat is the ideal goal for broiler breeding. Preadipocytes with different origins have differences in terms of metabolism and gene expression. The transcriptome analysis performed in this study of intramuscular preadipocytes (DIMFPs) and adipose tissue-derived preadipocytes (DAFPs) aimed to explore the characteristics of lipid deposition in different chicken preadipocytes by dedifferentiation in vitro. Results Compared with DAFPs, the total lipid content in DIMFPs was reduced (P < 0.05). Moreover, 72 DEGs related to lipid metabolism were screened, which were involved in adipocyte differentiation, fatty acid transport and fatty acid synthesis, lipid stabilization, and lipolysis. Among the 72 DEGs, 19 DEGs were enriched in the PPAR signaling pathway, indicating its main contribution to the regulation of the difference in lipid deposition between DAFPs and DIMFPs. Among these 19 genes, the representative APOA1, ADIPOQ, FABP3, FABP4, FABP7, HMGCS2, LPL and RXRG genes were downregulated, but the ACSL1, FABP5, PCK2, PDPK1, PPARG, SCD, SCD5, and SLC27A6 genes were upregulated (P < 0.05 or P < 0.01) in the DIMFPs. In addition, the well-known pathways affecting lipid metabolism (MAPK, TGF-beta and calcium) and the pathways related to cell communication were enriched, which may also contribute to the regulation of lipid deposition. Finally, the regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs was proposed based on the above information. Conclusions Our data suggested a difference in lipid deposition between DIMFPs and DAFPs of chickens in vitro and proposed a molecular regulatory network for the difference in lipid deposition between chicken DAFPs and DIMFPs. The lipid content was significantly increased in DAFPs by the direct mediation of PPAR signaling pathways. These findings provide new insights into the regulation of tissue-specific fat deposition and the optimization of body fat distribution in broilers.

scholarly journals miR-21-5p regulates mitochondrial respiration and lipid content in H9C2 cells

2019 ◽  
Vol 316 (3) ◽  
pp. H710-H721 ◽  
Author(s):  
Victoria L. Nasci ◽  
Sandra Chuppa ◽  
Lindsey Griswold ◽  
Kathryn A. Goodreau ◽  
Ranjan K. Dash ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Fatty Acid Oxidation ◽  
Lipid Content ◽  
Mitochondrial Respiration ◽  
Acid Oxidation ◽  
H9c2 Cells ◽  
Cellular Lipid ◽  
Transfected Cells

Cardiovascular-related pathologies are the single leading cause of death in patients with chronic kidney disease (CKD). Previously, we found that a 5/6th nephrectomy model of CKD leads to an upregulation of miR-21-5p in the left ventricle, targeting peroxisome proliferator-activated receptor-α and altering the expression of numerous transcripts involved with fatty acid oxidation and glycolysis. In the present study, we evaluated the potential for knockdown or overexpression of miR-21-5p to regulate lipid content, lipid peroxidation, and mitochondrial respiration in H9C2 cells. Cells were transfected with anti-miR-21-5p (40 nM), pre-miR-21-5p (20 nM), or the appropriate scrambled oligonucleotide controls before lipid treatment in culture or as part of the Agilent Seahorse XF fatty acid oxidation assay. Overexpression of miR-21-5p attenuated the lipid-induced increase in cellular lipid content, whereas suppression of miR-21-5p augmented it. The abundance of malondialdehyde, a product of lipid peroxidation, was significantly increased with lipid treatment in control cells but attenuated in pre-miR-21-5p-transfected cells. This suggests that miR-21-5p reduces oxidative stress. The cellular oxygen consumption rate (OCR) was increased in both pre-miR-21-5p- and anti-miR-21-5p-transfected cells. Levels of intracellular ATP were significantly higher in anti-mR-21-5p-transfected cells. Pre-miR-21-5p blocked additional increases in OCR in response to etomoxir and palmitic acid. Conversely, anti-miR-21-5p-transfected cells exhibited reduced OCR with both etomoxir and palmitic acid, and the glycolytic capacity was concomitantly reduced. Together, these results indicate that overexpression of miR-21-5p attenuates both lipid content and lipid peroxidation in H9C2 cells. This likely occurs by reducing cellular lipid uptake and utilization, shifting cellular metabolism toward reliance on the glycolytic pathway. NEW & NOTEWORTHY Both overexpression and suppression of miR-21-5p augment basal and maximal mitochondrial respiration. Our data suggest that reliance on glycolytic and fatty acid oxidation pathways can be modulated by the abundance of miR-21-5p within the cell. miR-21-5p regulation of mitochondrial respiration can be modulated by extracellular lipids.

scholarly journals Additive effects of dexamethasone and palmitate on hepatic lipid accumulation and secretion

2016 ◽  
Vol 57 (4) ◽  
pp. 261-273 ◽  
Author(s):  
Ewa Harasim-Symbor ◽  
Karolina Konstantynowicz-Nowicka ◽  
Adrian Chabowski
Keyword(s):  
Liquid Chromatography ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Combined Treatment ◽  
Protective Mechanism ◽  
Gas Liquid Chromatography ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Additive Effects ◽  
Extracellular Lipid

Synthetic and natural glucocorticoids are able to highly modify liver lipid metabolism, which is possibly associated with nonalcoholic fatty liver disease development. We have assessed the changes in lipid and sphingolipid contents in hepatocytes, lipid composition and saturation status as well as the expression of proteins involved in fatty acid transport after both dexamethasone and palmitate treatments. The experiments were conducted on primary rat hepatocytes, incubated with dexamethasone and/or palmitic acid during short (16 h) and prolonged (40 h) exposure. Intracellular and extracellular lipid and sphingolipid contents were assessed by gas liquid chromatography and high-performance liquid chromatography, respectively. The expression of selected proteins was estimated by Western blotting. Short and prolonged exposure to dexamethasone combined with palmitic acid resulted in increased expression of fatty acid transporters, which was subsequently reflected by excessive intracellular accumulation of triacylglycerols and ceramide. The expression of microsomal transfer protein and cassette transporter was also significantly increased after dexamethasone and palmitate treatment, which was in accordance with elevated extracellular lipid and sphingolipid contents. Our data showed additive effects of dexamethasone and palmitate on protein-dependent fatty acid uptake in primary hepatocytes, resulting in the increased accumulation of triacylglycerols and sphingolipids. Moreover, the combined treatment altered fatty acid composition and diminished triacylglycerols desaturation index. Importantly, we observed that additive effects on both increased microsomal transport protein expression as well as elevated export of triacylglycerols, which may be relevant as a liver protective mechanism.

scholarly journals Lipid Dynamics, Identification, and Expression Patterns of Fatty Acid Synthase Genes in an Endoparasitoid, Meteorus pulchricornis (Hymenoptera: Braconidae)

2020 ◽  
Vol 21 (17) ◽  
pp. 6228
Author(s):  
Jiao Wang ◽  
Li-Wei Shen ◽  
Xiao-Rong Xing ◽  
Yu-Qi Xie ◽  
Yi-Jiangcheng Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Content ◽  
Fatty Acid Synthase ◽  
Developmental Stages ◽  
Adult Stage ◽  
Expression Patterns ◽  
Lipid Synthesis ◽  
Open Reading Frames ◽  
Lipid Dynamics ◽  
Meteorus Pulchricornis

In insect parasitoids, fatty acid synthases (FASs) have received less attention and their roles associated with lipogenesis loss are far from clear. Meteorus pulchricornis is a solitary endoparasitoid wasp of many larvae of lepidopteran pests. The lipid content during developmental stages of M. pulchricornis was measured; it was higher in the larval and pupal stages but declined from six-day-old pupae. Lipid accumulation constantly decreased in the adult stage, even after feeding on honey solutions. To investigate the roles of FASs in lipid synthesis in M. pulchricornis, four FAS genes (MpulFAS1~4) were identified from the transcriptome database of M. pulchricornis. All FAS genes included full-length open reading frames and shared 72–79% similarity with the sequences of Microplitis demolitor. qRT-PCR validation showed that all four FASs had the highest expression after the adult wasps were fed on honey diets. MpulFAS1 and MpulFAS2 reached their expression peaks at the adult stage but MpulFAS3 and MpulFAS4 peaked at the larval stage. To further study the function of FASs, dsRNA injection knocked down the expression of four MpulFASs and resulted in a significant decline of lipid content at the adult stage in M. pulchricornis. Results from this study suggest that M. pulchricornis adults cannot accumulate lipid content effectively and FASs may still contribute to lipid synthesis in the adult stage. This broadens the knowledge on the ability of lipid synthesis in parasitoid wasps and provides insight into the roles of FASs in insects with parasitic life-history traits.

scholarly journals The Computational Analyses, Molecular Dynamics of Fatty-Acid Transport Mechanism to the CD36 Receptor: The Outcomes of the Mutation K164A on the Binding Domain, Structure and Function

2021 ◽  
Author(s):  
Jihane Akachar ◽  
Catherine Etchebest ◽  
Rachid Eljaoudi ◽  
Azeddine Ibrahimi
Keyword(s):  
Molecular Dynamics ◽  
Fatty Acids ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Conformational Changes ◽  
Structural Basis ◽  
Fatty Acid Transport ◽  
Acid Uptake ◽  
Wild Type ◽  
Cavity Structure

Abstract The transmembrane glycoprotein CD36, which is responsible of the metabolic disorders, and the elevated intake of fat induces lipid buildup, is a multifunctional scavenger receptor signaling those functions in high-affinity tissue uptake of long-chain fatty acids. In this study, we used series of molecular dynamics simulations of the wild type and mutants types K164A CD36 protein interacting with one Palmitic acid (PLM) besides simulations of the wild type interacting with the three PLM to find out the mechanism of the functioning of the complex CD36/Fatty acids and the unraveling of the role of the mutation. Additionally we determined whether Lys164, mostly exposed to protein surface, played important roles in fatty acid uptake. These simulations revealed, the conformational changes induced by Lys164 residue and the altered interactions induced by the mutagenesis of surface lysine that was badly influencing the folding, utility, solubility, and stability form of the variant. Furthermore, Lys164 residue provided the structural basis of forming an opening at the region of principal portal for the dissociation of palmitic acid. The results of our simulations revealed hole two fatty acids found in CD36 cavity structure and it was the most preferred to CD36 structure stabilization.

scholarly journals Dendrobium officinale Regulates Fatty Acid Metabolism to Ameliorate Liver Lipid Accumulation in NAFLD Mice

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Shan-Shan Lei ◽  
Ning-Yu Zhang ◽  
Fu-Chen Zhou ◽  
Xinglishang He ◽  
Hui-Ying Wang ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Coenzyme A ◽  
Liver Lipid ◽  
Dendrobium Officinale ◽  
Fatty Acid Transport ◽  
Related Protein ◽  
Shotgun Lipidomics ◽  
Nonalcoholic Fatty Liver ◽  
Underlying Mechanisms

Dendrobium officinale (DOF) is a traditional Chinese edible and officinal plant. Ultrafine DOF powder (DOFP) can regulate lipids and histopathology in the liver, but the underlying mechanisms of hepatic fatty acid (FA) metabolism, which is generally correlated with the development of nonalcoholic fatty liver disease (NAFLD), remain unclear. The purpose of the present study was to investigate whether DOFP treatment alters hepatic FA metabolism in NAFLD mice by using multidimensional mass spectrometry-based shotgun lipidomics (MDMS-SL) and analyse the underlying mechanisms. A 3-week DOFP treatment prevented lipid deposition and improved hepatic histopathology in NAFLD mice after withdrawal from the high-sucrose, high-fat (HSHF) diet, and it decreased triglyceride and FA content in the liver. Furthermore, the C16 : 0/C14 : 0 and C18 : 1/18 : 0 ratios in FAs were significantly decreased in the DOFP treatment group, and the C20 : 4/C20 : 3 and C22 : 4/C22 : 3 ratios were increased, and saturated FA was inhibited. Additionally, DOFP treatment significantly increased the content of two FA β-oxidation-related proteins (carnitine palmitoyltransferase 1-α and acyl-coenzyme A oxidase 1). It also decreased the content of a FA synthesis-related protein (fatty acid synthase), a FA desaturation-related protein (stearoyl-coenzyme A desaturase-1), and a FA uptake-related protein (fatty acid transport protein 2). Moreover, DOFP treatment improved dysregulated levels of major phospholipids in the livers of model mice. The results of this study confirm that DOFP treatment in NAFLD mice has liver recovery effects by regulating FA metabolism.

scholarly journals Identification of molecular regulation on difference of lipid deposition in dedifferentiated preadipocytes from different chicken tissues

2021 ◽  
Author(s):  
zheng ma ◽  
Na Luo ◽  
Lu Liu ◽  
Huanxian Cui ◽  
Jing Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Signaling Pathway ◽  
Lipid Content ◽  
Regulatory Network ◽  
Fatty Acid Transport ◽  
Lipid Deposition ◽  
Ppar Signaling ◽  
The Difference

Abstract Background: The body distribution with high intramuscular fat and low abdominal fat is ideal goal for broiler breeding. Preadipocytes with different origins have differences in metabolism and gene expression. This transcriptome analysis of intramuscular preadipocytes (DIMPs) and adipose tissue-derived preadipocytes (DAFPs) is aim to explore the characteristics in lipid deposition of different chicken preadipocytes by dedifferentiation in vitro. Results: Compared to DAFPs, the total lipid content was decreased (P <0.05) in DIMFPs after two days with 100% confluence. Moreover, 72 DEGs related to lipid metabolism were screened, which are involved in the adipocyte differentiation, fatty acid transport and fatty acid synthesis, lipid stabilization, and lipolysis. Among the 72 DEGs, 19 DEGs were enriched in the PPAR signaling pathway, indicating a main contribution to the regulation of the difference of lipid deposition between DAFPs and DIMFPs. Among these 19 genes, the representative APOA1, ADIPOQ, FABP3, FABP4, FABP7, HMGCS2, LPL and RXRG genes were down-regulated, but ACSL1, FABP5, PCK2, PDPK1, PPARG, SCD, SCD5, SLC27A6 genes were up-regulated (P < 0.05 or P < 0.01) in the DIMFPs. In addition, the well-known pathways affecting lipid metabolism (MAPK-, TGF beta-, Calcium-, PPAR signaling pathway) and the pathways related to cell communication were enriched, which may also contribute to the regulation of lipid deposition. Finally, the regulatory network for the difference of lipid deposition between chicken DAFPs and DIMFPs were proposed based on the above information.Conclusions: Our data suggested the difference of lipid deposition between DIMPs and DAFPs of chicken in vitro, and proposed the molecular regulatory network for the difference of lipid deposition between chicken DAFPs and DIMFPs. The lipid content was significantly increased in DAFPs by the direct mediation of PPAR signaling pathways. These findings provide new insights into the regulation of tissue-specific fat deposition and optimizing body fat distribution in broilers.

scholarly journals Sphingosine-1-phosphate analog FTY720 reverses obesity but not age-induced anabolic resistance to muscle contraction

2019 ◽  
Vol 317 (3) ◽  
pp. C502-C512
Author(s):  
Donato A. Rivas ◽  
Nicholas P. Rice ◽  
Yassine Ezzyat ◽  
Devin J. McDonald ◽  
Brittany E. Cooper ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acid ◽  
Palmitic Acid ◽  
Muscle Contraction ◽  
Chronic Inflammation ◽  
Muscle Atrophy ◽  
Muscle Cells ◽  
Skeletal Muscle Atrophy ◽  
Anabolic Resistance ◽  
Sphingosine 1 Phosphate

Sarcopenia, the age-associated loss of skeletal muscle mass and function, is coupled with declines in physical functioning leading to subsequent higher rates of disability, frailty, morbidity, and mortality. Aging and obesity independently contribute to muscle atrophy that is assumed to be a result of the activation of mutual physiological pathways. Understanding mechanisms contributing to the induction of skeletal muscle atrophy with aging and obesity is important for determining targets that may have pivotal roles in muscle loss in these conditions. We find that aging and obesity equally induce an anabolic resistance to acute skeletal muscle contraction as observed with decreases in anabolic signaling activation after contraction. Furthermore, treatment with the sphingosine-1-phosphate analog FTY720 for 4 wk increased lean mass and strength, and the anabolic signaling response to contraction was improved in obese but not older animals. To determine the role of chronic inflammation and different fatty acids on anabolic resistance in skeletal muscle cells, we overexpressed IKKβ with and without exposure to saturated fatty acid (SFA; palmitic acid), polyunsaturated fatty acid (eicosapentaenoic acid), and monounsaturated fatty acid (oleic acid). We found that IKKβ overexpression increased inflammation markers in muscle cells, and this chronic inflammation exacerbated anabolic resistance in response to SFA. Pretreatment with FTY720 reversed the inflammatory effects of palmitic acid in the muscle cells. Taken together, these data demonstrate chronic inflammation can induce anabolic resistance, SFA aggravates these effects, and FTY720 can reverse this by decreasing ceramide accumulation in skeletal muscle.

Abstract 801: Sensitivity of cell lines to Fatty Acid Synthase inhibitors depends on the lipid content in the cellular environment

2014 ◽  
Author(s):  
Karine A. Smans ◽  
Sabine D. Breucker ◽  
Norbert Esser ◽  
Erwin Fraiponts ◽  
Ron Gilissen ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Cell Lines ◽  
Lipid Content ◽  
Fatty Acid Synthase ◽  
Cellular Environment
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