Showing papers on "Fatty acid-binding protein published in 2019"
TL;DR: Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of F ABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review.
Abstract: Fatty acid-binding proteins (FABPs), a family of lipid chaperones, contribute to systemic metabolic regulation via several lipid signaling pathways. Fatty acid-binding protein 4 (FABP4), known as adipocyte FABP (A-FABP) or aP2, is mainly expressed in adipocytes and macrophages and plays important roles in the development of insulin resistance and atherosclerosis in relation to metabolically driven low-grade and chronic inflammation, referred to as 'metaflammation'. FABP4 is secreted from adipocytes in a non-classical pathway associated with lipolysis and acts as an adipokine for the development of insulin resistance and atherosclerosis. Circulating FABP4 levels are associated with several aspects of metabolic syndrome and cardiovascular disease. Ectopic expression and function of FABP4 in cells and tissues are also related to the pathogenesis of several diseases. Pharmacological modification of FABP4 function by specific inhibitors, neutralizing antibodies or antagonists of unidentified receptors would be novel therapeutic strategies for several diseases, including obesity, diabetes mellitus, atherosclerosis and cardiovascular disease. Significant roles of FABP4 as a lipid chaperone in physiological and pathophysiological conditions and the possibility of FABP4 being a therapeutic target for metabolic and cardiovascular diseases are discussed in this review.
136 citations
TL;DR: A thorough characterization of lipid receptors of the nervous system could provide a framework for a better understanding of their roles in neurophysiology and, potentially, help for the development of novel drugs against aging and neurodegenerative processes.
Abstract: Fatty acids (FAs) are typically associated with structural and metabolic roles, as they can be stored as triglycerides, degraded by β-oxidation or used in phospholipids' synthesis, the main components of biological membranes. It has been shown that these lipids exhibit also regulatory functions in different cell types. FAs can serve as secondary messengers, as well as modulators of enzymatic activities and substrates for cytokines synthesis. More recently, it has been documented a direct activity of free FAs as ligands of membrane, cytosolic, and nuclear receptors, and cumulative evidence has emerged, demonstrating its participation in a wide range of physiological and pathological conditions. It has been long known that the central nervous system is enriched with poly-unsaturated FAs, such as arachidonic (C20:4ω-6) or docosohexaenoic (C22:6ω-3) acids. These lipids participate in the regulation of membrane fluidity, axonal growth, development, memory, and inflammatory response. Furthermore, a whole family of low molecular weight compounds derived from FAs has also gained special attention as the natural ligands for cannabinoid receptors or key cytokines involved in inflammation, largely expanding the role of FAs as precursors of signaling molecules. Nutritional deficiencies, and alterations in lipid metabolism and lipid signaling have been associated with developmental and cognitive problems, as well as with neurodegenerative diseases. The molecular mechanism behind these effects still remains elusive. But in the last two decades, different families of proteins have been characterized as receptors mediating FAs signaling. This review focuses on different receptors sensing and transducing free FAs signals in neural cells: (1) membrane receptors of the family of G Protein Coupled Receptors known as Free Fatty Acid Receptors (FFARs); (2) cytosolic transport Fatty Acid-Binding Proteins (FABPs); and (3) transcription factors Peroxisome Proliferator-Activated Receptors (PPARs). We discuss how these proteins modulate and mediate direct regulatory functions of free FAs in neural cells. Finally, we briefly discuss the advantages of evaluating them as potential targets for drug design in order to manipulate lipid signaling. A thorough characterization of lipid receptors of the nervous system could provide a framework for a better understanding of their roles in neurophysiology and, potentially, help for the development of novel drugs against aging and neurodegenerative processes.
86 citations
TL;DR: A role for FABPs is increasingly being reported in tumor biology with elevated exogenous FABP expression being associated with tumor progression and invasiveness, however, a less clear role has been appreciated for dysregulated FABp expression during cell transformation and early expansion.
49 citations
TL;DR: This work shows that the abilities of FASN and MAGL to promote nuclear receptor activation and PCa metastasis are critically dependent upon co-expression of FABP5 in vitro and in vivo and suggests that disruption of lipid signaling via FABp5 inhibition may constitute a new avenue to treat metastatic PCa.
Abstract: Prostate cancer (PCa) is defined by dysregulated lipid signaling and is characterized by upregulation of lipid metabolism-related genes including fatty acid binding protein 5 (FABP5), fatty acid synthase (FASN), and monoacylglycerol lipase (MAGL). FASN and MAGL are enzymes that generate cellular fatty acid pools while FABP5 is an intracellular chaperone that delivers fatty acids to nuclear receptors to enhance PCa metastasis. Since FABP5, FASN, and MAGL have been independently implicated in PCa progression, we hypothesized that FABP5 represents a central mechanism linking cytosolic lipid metabolism to pro-metastatic nuclear receptor signaling. Here, we show that the abilities of FASN and MAGL to promote nuclear receptor activation and PCa metastasis are critically dependent upon co-expression of FABP5 in vitro and in vivo. Our findings position FABP5 as a key driver of lipid-mediated metastasis and suggest that disruption of lipid signaling via FABP5 inhibition may constitute a new avenue to treat metastatic PCa.
47 citations
TL;DR: It is supported that FABP4 contributed to RIF via promoting inflammation and lipid metabolism, which should be considered as one new drug target to treat RIF.
Abstract: Fatty acid binding protein 4 (FABP4), a subtype of fatty acid-binding protein family, shows critical roles in metabolism and inflammation. However, its roles on regulating renal interstitial fibrosis (RIF) remain unclear. In this work, LPS-stimulated in vitro models on NRK-52E and NRK-49F cells, and in vivo UUO models in rats and mice were established. The results showed that comparing with control groups or sham groups, the expression levels of α-SMA, COL1A, COL3A, IL-1β, IL-6, and TNF-α in LPS-stimulated cells or UUO animals were significantly increased. Meanwhile, the levels of TC, TG, and free fatty acid were also significantly increased as well as the obvious lipid droplets, and the serum levels of BUN, Cr were significantly increased with large amounts of collagen deposition in renal tissues. Further investigation showed that compared with control groups or sham groups, the expression levels of FABP4 in LPS-stimulated cells and UUO animals were significantly increased, resulting in down- regulating the expression levels of PPARγ, upregulating the levels of p65 and ICAM-1, and decreasing the expression levels of ACADM, ACADL, SCP-2, CPT1, EHHADH, and ACOX1. To deeply explore the mechanism of FABP4 in RIF, FABP4 siRNA and inhibitor interfered cell models, and UUO model on FABP4 knockout (KO) mice were used. The results showed that the expression levels of α-SMA, COL1A, and COL3A were significantly decreased, the deposition of lipid droplets decreased, and the contents of TC, TG, and free fatty acids were significantly decreased after gene silencing. Meanwhile, the expression levels of PPAR-γ, ACADM, ACADL, SCP-2, CPT1, EHHADH, and ACOX1 were upregulated, the levels of p65 and ICAM-1 were downregulated, and the mRNA levels of IL-1β, IL-6, and TNF-α were decreased. Our results supported that FABP4 contributed to RIF via promoting inflammation and lipid metabolism, which should be considered as one new drug target to treat RIF.
40 citations
TL;DR: It is shown that this metabolic phenotype was mediated by PPAR-α signaling, despite the lack of fatty acids in culture media, as Hs-FABP7 cells attempted to survive.
38 citations
TL;DR: It is suggested that adrenergic overdrive and resultant adipose tissue lipolysis induce cardiac AMPK-FGF21 feed-forward loop that potentially provides cardioprotection against ischemic damage.
Abstract: Fibroblast growth factor 21 (FGF21) is a metabolic hormone having anti-oxidative and anti-hypertrophic effects. However, the regulation of FGF21 expression during acute myocardial infarction (AMI) remains unclear. We tested blood samples from 50 patients with AMI and 43 patients with stable angina pectoris (sAP) for FGF21, fatty acid binding protein 4 (FABP4), a protein secreted from adipocytes in response to adrenergic lipolytic signal, and total and individual fatty acids. Compared with sAP patients, AMI patients had higher serum FGF21 levels on admission, which were significantly correlated with peak FABP4 and saturated fatty acids (SFAs) but not with peak levels of cardiac troponin T. In mice, myocardial ischemia rapidly induced FGF21 production by the heart, which accompanied activation of AMP-activated protein kinase (AMPK)-dependent pathway. Like AICAR, an activator of AMPK, catecholamines (norepinephrine and isoproterenol) and SFAs (palmitate and stearate) significantly increased FGF21 production and release by cardiac myocytes via AMPK activation. Recombinant FGF21 induced its own expression as well as members of down-stream targets of AMPK involved in metabolic homeostasis and mitochondrial biogenesis in cardiac myocytes. These findings suggest that adrenergic overdrive and resultant adipose tissue lipolysis induce cardiac AMPK-FGF21 feed-forward loop that potentially provides cardioprotection against ischemic damage.
30 citations
TL;DR: The multiple FakBs of S. pneumoniae permit the utilization of the entire spectrum of mammalian fatty acid structures to construct its membrane, and an expanded fatty acid-binding pocket within the hydrophobic interior of SpFakB3 that explains its ability to accommodate multiple cis double bonds.
30 citations
TL;DR: The results identify FABP4 as a molecule involved in diabetic/lipid-induced cardiomyopathy and indicate that this molecule may be an emerging biomarker for diabetic carduomyopathy-related disturbances, such as myocardial neutral lipid accumulation.
Abstract: Objective Fatty acid binding protein 4 (FABP4) is an intracellular lipid chaperone involved in the crosstalk between adipose and peripheral tissues, and it contributes to widespread insulin resistance in cells, including cardiac cells. However, the role of this adipokine in regulating cardiac metabolism and myocardial neutral lipid content in patients with type 2 diabetes has not been elucidated. Methods The impact of circulating FABP4 on the cardiac neutral lipid content was measured by proton magnetic resonance spectroscopy (1H-MRS) in patients with type 2 diabetes. Additionally, circulating FABP4 and the cardiac triglyceride content were analysed in high-fat diet (HFD)-fed mice, and the impact of the exogenous FABP4 was explored in HL-1 cardiac cells. Results Serum FABP4 levels were higher in type 2 diabetic patients compared to healthy individuals. Circulating FABP4 levels were associated with myocardial neutral lipid content in type 2 diabetic patients. In HFD-fed mice, both serum FABP4 and myocardial triglyceride content were increased. In FABP4-challenged HL-1 cells, extracellular FABP4 increased intracellular lipid accumulation, which led to impairment of the insulin-signalling pathway and reduced insulin-stimulated glucose uptake. However, these effects were partially reversed by FABP4 inhibition with BMS309403, which attenuated the intracellular lipid content and improved insulin signalling and insulin-stimulated glucose uptake. Conclusions Taken together, our results identify FABP4 as a molecule involved in diabetic/lipid-induced cardiomyopathy and indicate that this molecule may be an emerging biomarker for diabetic cardiomyopathy-related disturbances, such as myocardial neutral lipid accumulation. Additionally, FABP4 inhibition may be a potential therapeutic target for metabolic-related cardiac dysfunctions.
28 citations
TL;DR: It is shown that FABP4 is secreted from white, but not brown, adipose tissue in response to lipolytic stimulation in a sirtuin-1 (SIRT1)–dependent manner via a mechanism that requires some,but not all, autophagic components.
Abstract: Fatty acid binding protein 4 (FABP4) is a leaderless lipid carrier protein primarily expressed by adipocytes and macrophages that not only functions intracellularly but is also secreted. The secretion is mediated via unconventional mechanism(s), and in a variety of species, metabolic dysfunction is correlated with elevated circulating FABP4 levels. In diabetic animals, neutralizing antibodies targeting serum FABP4 increase insulin sensitivity and attenuate hepatic glucose output, suggesting the functional importance of circulating FABP4. Using animal and cell-based models, we show that FABP4 is secreted from white, but not brown, adipose tissue in response to lipolytic stimulation in a sirtuin-1 (SIRT1)-dependent manner via a mechanism that requires some, but not all, autophagic components. Silencing of early autophagic genes such as Ulk1/2, Fip200, or Beclin-1 or chemical inhibition of ULK1/2 or VPS34 attenuated secretion, while Atg5 knockdown potentiated FABP4 release. Genetic knockout of Sirt1 diminished secretion, and serum FABP4 levels were undetectable in Sirt1 knockout mice. In addition, blocking SIRT1 by EX527 attenuated secretion while activating SIRT1 by resveratrol-potentiated secretion. These studies suggest that FABP4 secretion from adipocytes is regulated by SIRT1 and requires early autophagic components.
28 citations
TL;DR: This review focuses on the expression and function of FABP7 in different tumors, and possible mechanisms of FAP7 in tumor proliferation and migration.
Abstract: Lipids are major molecules for the function of organisms and are involved in the pathophysiology of various diseases. Fatty acids (FAs) signaling and their metabolism are some of the most important pathways in tumor development, as lipids serve as energetic sources during carcinogenesis. Fatty acid binding proteins (FABPs) facilitate FAs transport to different cell organelles, modulating their metabolism along with mediating other physiological activities. FABP7, brain-typed FABP, is thought to be an important molecule for cell proliferation in healthy as well as diseased organisms. Several studies on human tumors and tumor-derived cell lines put FABP7 in the center of tumorigenesis, and its high expression level has been reported to correlate with poor prognosis in different tumor types. Several types of FABP7-expressing tumors have shown an up-regulation of cell signaling activity, but molecular mechanisms of FABP7 involvement in tumorigenesis still remain elusive. In this review, we focus on the expression and function of FABP7 in different tumors, and possible mechanisms of FABP7 in tumor proliferation and migration.
TL;DR: Study demonstrated that both mRNA and protein expression of hepatic OCTN2 (carnitine/organic cation transporter 2) were obviously down-regulated in male mice after 12-week olanzapine treatment, and Supplementation of L-Car is a promising strategy to attenuate olanZapine-induced simple steatosis.
TL;DR: It is demonstrated that FABP5 is upregulated in human ccRCC tissues and cell lines and is positively correlated with the progression ofccRCC, suggesting that F ABP5 may be a cancer-promoting protein in ccR CC.
TL;DR: The purpose of this review is to summarize recent findings regarding FABP functions and mechanisms of action, including their potential utilization as serum markers of tissue-specific metabolic diseases.
Abstract: Purpose of review Fatty acid-binding proteins (FABPs) are a family of small, abundant proteins with highly tissue-specific expression patterns whose different functions remain incompletely understood. The purpose of this review is to summarize recent findings regarding FABP functions and mechanisms of action, including their potential utilization as serum markers of tissue-specific metabolic diseases. Recent findings FABPs are important not only in their tissues of origin but also appear to influence the metabolism and function of tissues distal to their sites of expression. This may be secondary to metabolic changes in their primary tissues, and/or a result of FABP secretion from these tissues leading to effects on distal sites. Their levels in the circulation are increasingly explored as potential biomarkers for tissue-specific disease prognosis and progression. Summary The nine fatty acid-binding members of the FABP family have unique tissue-specific functions and important secondary effects on tissues in which they are not expressed. For many of the FABPs, circulating levels may be indicative of disease processes related to their primary tissues, and may influence physiological function in distal tissues.
TL;DR: A novel miR-34b-DCP1A axis that has a significant role in regulating milk fat synthesis is revealed and it is suggested that miR -34b may be used to improve the beneficial ingredients in milk.
Abstract: Milk fat is a main nutritional component of milk, and it has become one of the important traits of dairy cow breeding. Recently, there is increasing evidence that microRNAs (miRNA) play significant roles in the process of milk fat synthesis in the mammary gland. Primary bovine mammary epithelial cells (BMEC) were harvested from midlactation cows and cultured in DMEM/F-12 medium with 10% fetal bovine serum, 100 units/mL penicillin, 100 µg/mL streptomycin, 5 µg/mL bovine insulin, 1 µg/mL hydrocortisone, and 2 µg/mL bovine prolactin. We found that miR-34b mimic transfection in BMEC reduced the content of intracellular triacylglycerol (TAG) and lipid droplet accumulation via triacylglycerol assay and Oil Red O staining; meanwhile, overexpression of miR-34b inhibited mRNA expression of lipid metabolism-related genes such as peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FASN), fatty acid binding protein 4 (FABP4), and CCAAT enhancer binding protein alpha (C/EBPα). Whereas miR-34b inhibitor resulted in completely opposite results. Furthermore, q-PCR and western blot analysis revealed the mRNA and protein expression levels of DCP1A were downregulated in miR-34b mimic transfection group and upregulated in miR-34b inhibitor group. Moreover, luciferase reporter assays verified that DCP1A was the direct target of miR-34b and DCP1A gene silencing in BMEC-inhibited TAG accumulation and suppressed lipid droplet formation. In conclusion, these findings revealed a novel miR-34b-DCP1A axis that has a significant role in regulating milk fat synthesis and suggested that miR-34b may be used to improve the beneficial ingredients in milk.
TL;DR: Investigation of the relationship between I-FABP, I-BABP, LBP, and galectin-9 levels in MCI and AD and multivariate analysis revealed that increased I- BABP and galECTin- 9 levels were significantly associated with reduced mini-mental state examination (MMSE) score.
TL;DR: Ex-vivo study in isolated primary epididymal adipocytes revealed that C21 inhibits long chain fatty acid transporter, via a nitric oxide synthase/guanylate cyclase/protein kinase G-dependent pathway, and proposes pharmacological activation of AT2R regulates fatty acid metabolism and thermogenesis and prevents HFD-induced adiposity in mice.
Abstract: Recent studies on mice with null mutation of the angiotensin type 2 receptor (AT2R) gene have implicated the involvement of AT2R in regulating adipocyte size and obesity, a major risk factor for metabolic syndrome. However, the outcome from these studies remains inconclusive. Therefore, current study was designed to test whether pharmacological activation of AT2R regulates adiposity and lipid metabolism. Male mice (5-weeks old) were pre-treated with vehicle or AT2R agonist (C21, 0.3 mg/kg, i.p., daily, for 4 days) and fed normal diet (ND). Then these animals were subdivided into ND and high-fat diet (HFD) regimen and concomitantly treated with vehicle or C21 through day 14. Vehicle-treated HFD-fed mice demonstrated an increase in epididymal white adipose tissue (eWAT) weight and adipocyte size, which were associated with increased eWAT expression of the lipogenic regulators, fatty acid binding protein and fatty acid synthase, decreased expression of adipose triglyceride lipase and increased expression of hormone-sensitive lipase. Interestingly, C21 pre-treatment altered HFD-induced changes in lipogenic and lipolytic regulators. C21 pre-treatment prevented decrease in expression of uncoupler protein-1 in brown adipose in HFD-fed mice, which was associated with increased core temperature. In addition, C21 pre-treatment ameliorated plasma-free fatty acids, triglycerides, insulin and tumor necrosis factor-α in HFD-fed mice. Ex-vivo study in isolated primary epididymal adipocytes revealed that C21 inhibits long chain fatty acid transporter, via a nitric oxide synthase/guanylate cyclase/protein kinase G-dependent pathway. Collectively, we propose pharmacological activation of AT2R regulates fatty acid metabolism and thermogenesis and prevents HFD-induced adiposity in mice.
TL;DR: It is indicated that FABP1 may promote fat deposition by promoting the production and secretion of TAG and VLDL in steer liver by changing the expression patterns of mRNAs in liver tissue following castration.
Abstract: Castration is an important means of improving the beef quality via increasing fat deposition. However, little is known about the molecular mechanism underlying the fat deposition after castration. Here, the intramuscular fat (IMF) content of the steer group was shown to be much higher than the bull group. To understand transcriptional changes in the genes involved in fat deposition following castration, differential expression patterns of mRNAs in liver tissue were investigated in steers and bulls using RNA sequencing. In total, we obtained 58,282,367-54,918,002 uniquely mapped reads, which covered 90.13% of the currently annotated transcripts; 5,864 novel transcripts and optimized 9,088 known genes were determined. These results indicated that castration could change the expression patterns of mRNAs in liver tissue, and 282 differentially expressed genes (DEGs) were detected between steers and bulls. KEGG pathway analysis showed that the DEGs were mostly enriched in PPAR signaling pathway, steroid biosynthesis, steroid hormone biosynthesis, and biosynthesis of fatty acids. Furthermore, eight DEGs were corroborated via quantitative real-time PCR and we found that FABP1 gene knockdown in bovine hepatocytes prominently reduced intracellular triacylglycerol (TAG) synthesis and very low density lipoprotein (VLDL) secretion in culture medium. In summary, these results indicate that FABP1 may promote fat deposition by promoting the production and secretion of TAG and VLDL in steer liver.
TL;DR: Results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP‐activated protein kinase signal pathway.
Abstract: The aim of the present study was to investigate the effect of 5-bromo-3,4-dihydroxybenzaldehyde (BD) isolated from Polysiphonia morrowii on adipogenesis and differentiation of 3T3-L1 preadipocytes into mature adipocytes and its possible mechanism of action. Levels of lipid accumulation and triglyceride were significantly lower in BD treated cells than those in untreated cells. In addition, BD treatment reduced protein expression levels of peroxisome proliferator-activated receptor-γ, CCAAT/enhancer-binding proteins α, and sterol regulatory element-binding protein 1 compared with control (no treatment). It also reduced expression levels of adiponectin, leptin, fatty acid synthase, and fatty acid binding protein 4. AMP-activated protein kinase activation was found to be one specific mechanism involved in the effect of BD. These results demonstrate that BD possesses inhibitory effect on adipogenesis through activating AMP-activated protein kinase signal pathway.
19 Mar 2019
TL;DR: Manipulation of fatty acid binding protein orthologues in C. elegans suggest these proteins and their role in lipid regulation are important for mitochondrial function.
Abstract: It is accepted that smaller mammals with higher metabolic rates have shorter lifespans. The very few species that do not follow these rules can give insights into interesting differences. The recorded maximum lifespans of bats are exceptional - over 40 years, compared with the laboratory mouse of 4 years. We investigated the differences in the biochemical composition of mitochondria between bat and mouse species. We used proteomics and ultra-high-performance liquid chromatography coupled with high resolution mass spectrometry lipidomics, to interrogate mitochondrial fractions prepared from Mus musculus and Pipistrellus pipistrellus brain and skeletal muscle. Fatty acid binding protein 3 was found at different levels in mouse and bat muscle mitochondria and its orthologues were investigated in Caenorhabditis elegans knock-downs for LBP 4, 5 and 6. In the bat, high levels of free fatty acids and N-acylethanolamine lipid species together with a significantly greater abundance of fatty acid binding protein 3 in muscle (1.8-fold, p=0.037) were found. Manipulation of fatty acid binding protein orthologues in C. elegans suggest these proteins and their role in lipid regulation are important for mitochondrial function.
TL;DR: It is found that GW7647 binding causes little change in the FABP1 backbone, but solvent exposes several residues in the loops around the portal region, including Lys-57, Glu-77, and Lys-96.
TL;DR: The results indicate that STAT5A-dependent FABP5 expression plays a carcinogenic role in the tumorigenesis of gastric cancer cells via reprogramming intracellular fatty acid metabolism, which establishes a new mechanism for the tumorsigenic ability of gastrics cancer cells.
Abstract: Objective The aim of this study was to determine the underlying effect of STAT5A-mediated fatty acid metabolism on the tumorigenesis of gastric cancer cells. Materials and methods The expression patterns of STAT5A and FASN in gastric cancer were investigated based on the Cancer Genome Atlas (TCGA) database and compared between 40 pairs of cancer samples and adjacent tissues. The pathological significance of STAT5A in gastric cancer was explored by GESA assay, and the molecular mechanism of STAT5A-mediated FASN expression was investigated by Luciferase assay and ChIP-qPCR. Fatty acid metabolic change was explored by detecting the content of neutral lipid, triglycerides, and phospholipids in STAT5A silenced MKN28 and AGS cells. Furthermore, Cell Counting Kit-8 (CCK-8) assay, colony formation, and Mouse xenograft were used to detect the function of STAT5A-mediated fatty acid metabolism on tumorigenic ability of gastric cancer cells. Results Upregulated STAT5A in gastric cancer was found to be not only an unconventional risk for over survival of gastric cancer patients, but also associated with fatty acid metabolism signaling. Furthermore, STAT5A can regulate the expression of the fatty acid binding protein 5 (FABP5) by binding to the promoter of FABP5 in MKN28 and AGS cells. Functional studies have shown that STAT5A-dependent FABP5 expression promoted the proliferation and tumorigenesis of gastric cancer cells by reprogramming intracellular fatty acid metabolism. Conclusions Our results indicate that STAT5A-dependent FABP5 expression plays a carcinogenic role in the tumorigenesis of gastric cancer cells via reprogramming intracellular fatty acid metabolism, which establishes a new mechanism for the tumorigenesis of gastric cancer cells.
TL;DR: It is demonstrated that FABP is an essential element of skeletal muscle energy metabolism in vivo; its knockdown in locust flight muscle prevents extended flight activity.
Abstract: During migratory flight, desert locusts rely on fatty acids as their predominant source of energy. Lipids mobilized in the fat body are transported to the flight muscles and enter the muscle cells as free fatty acids. It has been postulated that muscle fatty acid binding protein (FABP) is needed for the efficient translocation of fatty acids through the aqueous cytosol towards mitochondrial β-oxidation. To assess whether FABP is required for this process, dsRNA was injected into freshly emerged adult males to knock down the expression of FABP. Three weeks after injection, FABP and its mRNA were undetectable in flight muscle, indicating efficient silencing of FABP expression. At rest, control and treated animals exhibited no morphological or behavioral differences. In tethered flight experiments, both control and treated insects were able to fly continually in the initial, carbohydrate-fueled phase of flight, and in both groups, lipids were mobilized and released into the hemolymph. Flight periods exceeding 30 min, however, when fatty acids become the main energy source, were rarely possible for FABP-depleted animals, while control insects continued to fly for more than 2 h. These results demonstrate that FABP is an essential element of skeletal muscle energy metabolism in vivo.
TL;DR: These novel finding contribute to the confirmation that edible fungi Pleurotus ostreatus and it's bioactive AQ is an adequate supplement for constraining the lipid and triglycerides in differentiated mature adipocytes by reversing the fat deposition.
TL;DR: 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.
Abstract: 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.
TL;DR: It is suggested that high glucose diet diminished the effects of LKO on the whole body and lipid phenotype of these mice.
TL;DR: PRL induced the lipid synthesis of organ‐cultured pigeon crops in a dose‐ and time‐dependent manner, which was related to the increased expression of genes involved in fatty acid transportation and lipogenesis.
TL;DR: Disruption of endothelial autophagy reduces cardiac fatty acid storage and dampens reliance on fatty acid oxidation as a cardiac fuel source and represents a novel target for designing new strategies aimed at resetting perturbed myocardial bioenergetics.
TL;DR: The first 1.3 Å high-resolution structure of LBP-8 was determined, which allowed us to identify a structurally conserved nuclear localization signal and amino acids involved in lipid binding and show that it binds to life-extending ligands in worms such as oleic acid and oleoylethanolamide with high affinity.
Abstract: The lysosome plays a crucial role in the regulation of longevity. Lysosomal degradation is tightly coupled with autophagy that is induced by many longevity paradigms and required for lifespan extension. The lysosome also serves as a hub for signal transduction and regulates longevity via affecting nuclear transcription. One lysosome-to-nucleus retrograde signaling pathway is mediated by a lysosome-associated fatty acid binding protein LBP-8 in Caenorhabditis elegans. LBP-8 shuttles lysosomal lipids into the nucleus to activate lipid regulated nuclear receptors NHR-49 and NHR-80 and consequently promote longevity. However, the structural basis of LBP-8 action remains unclear. Here, we determined the first 1.3 A high-resolution structure of this life-extending protein LBP-8, which allowed us to identify a structurally conserved nuclear localization signal and amino acids involved in lipid binding. Additionally, we described the range of fatty acids LBP-8 is capable of binding and show that it binds to life-extending ligands in worms such as oleic acid and oleoylethanolamide with high affinity.
TL;DR: In summary, Scp-2/Scp-x gene ablation in Fabp1 null (LKO) mice antagonized the impact of LKO and HFD on brain ARA and, subsequently, EC levels, indicating that both FABP1 and SCP-2 participate in regulating the EC system in the brain.
Abstract: Brain endocannabinoids (EC) such as arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol (2-AG) primarily originate from serum arachidonic acid (ARA), whose level is regulated in part by a cytosolic ARA-binding protein, that is, liver fatty acid binding protein-1 (FABP1), not expressed in the brain. Ablation of the Fabp1 gene (LKO) increases brain AEA and 2-AG by decreasing hepatic uptake of ARA to increase serum ARA, thereby increasing ARA availability for uptake by the brain. The brain also expresses sterol carrier protein-2 (SCP-2), which is also a cytosolic ARA-binding protein. To further resolve the role of SCP-2 independent of FABP1, mice ablated in the Scp-2/Scp-x gene (DKO) were crossed with mice ablated in the Fabp1 gene (LKO) mice to generate triple knock out (TKO) mice. TKO impaired the ability of LKO to increase brain AEA and 2-AG. While a high-fat diet (HFD) alone increased brain AEA, TKO impaired this effect. Overall, these TKO-induced blocks were not attributable to altered expression of brain proteins in ARA uptake, AEA/2-AG synthesis, or AEA/2-AG degrading enzymes. Instead, TKO reduced serum levels of free ARA and/or total ARA and thereby decreased ARA availability for uptake to the brain and downstream synthesis of AEA and 2-AG therein. In summary, Scp-2/Scp-x gene ablation in Fabp1 null (LKO) mice antagonized the impact of LKO and HFD on brain ARA and, subsequently, EC levels. Thus, both FABP1 and SCP-2 participate in regulating the EC system in the brain.