PPARγregulatesfabp4expression to increase DHA content in golden pompano (Trachinotus ovatus) hepatocytes

Lei, Chunyan; Fan, Bin; Tian, Jingjing; Li, Mengmeng; Li, Yuanyou

doi:10.1017/s0007114521000775

Cited by 8 publications

(6 citation statements)

References 48 publications

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“…However, previous studies have shown that DHA and EPA could be natural PPAR agonist to activate PPARG signaling [29,30]. In golden pompano hepatocytes, the overexpression of PPARG increased the DHA content, whereas suppression of PPARG expression diminished this effect, suggesting that PPARG play an active role in regulating DHA content [31]. Here, we conducted the correlation analysis between PPARG and individual DHA-and EPAcontaining glycerophospholipid rather than total DHA or EPA content.…”

Section: Discussionmentioning

confidence: 95%

Molecular regulation of differential lipid molecule accumulation in intramuscular fat and abdominal fat of chicken

Huang

Wu³

et al. 2022

Preprint

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Background Reducing abdominal fat (AF) accumulation and increasing the level of intramuscular fat (IMF) simultaneously is a major breeding goal in poultry industry. Results To explore the different molecular mechanisms between AF and IMF, gene expression profiles in the breast muscle (BM) and AF among three chicken breeds were analyzed. A total of 4737 shared DEGs were identified between BM and AF, of which 2602 DEGs were upregulated and 2135 DEGs were downregulated in the BM groups compared with that in AF groups. DEGs involved in glycerophospholipid metabolism and glycerolipid metabolism were potential regulators resulting in the difference of lipid metabolite accumulation in IMF and AF. PPAR signaling pathway was the most important pathway involved in tissue-specific lipid deposition. Correlation analysis showed that most representative DEGs enriched in PPAR signaling pathway, such as FABP5, PPARG, ACOX1, GK2, were negatively correlated with PUFA-enriched glycerophospholipid molecules. Most DEGs related to glycerophospholipid metabolism, such as GPD2, GPD1, PEMT, CRLS1 and GBGT1, were positively correlated with glycerophospholipid molecules, especially DHA- and arachidonic acid (ARA)- containing glycerophospholipid molecules. Conclusion This study elucidated the molecular mechanism of tissue-specific lipid deposition and poultry meat quality.

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Section: Discussionmentioning

confidence: 95%

Molecular regulation of differential lipid molecule accumulation in intramuscular fat and abdominal fat of chicken

Huang

Wu³

et al. 2022

Preprint

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“…Only FABP4 and FABP5 are expressed across various cancer types, suggesting that genetic amplification itself is necessary but not sufficient for their abnormal expression in cancer. Expression of FABP4 , as a major target of PPARγ[ 19 ], has been shown to be controlled by PPARγ[ 4 ], and FABP4 has been shown to negatively regulate PPARγ expression level, likely through a negative feedback signaling loop. In contrast to FABP4 , FABP5 has been shown to facilitate fatty-acid induced PPARγ activation and downstream signaling, and activated PPARγ in turn upregulates FABP5 expression levels in prostate cancer[ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Some of the family members including FABP4 , FABP5 , and FABP7 are abnormally expressed in cancer cells beyond tissue expression restriction and play important roles in cancer malignancy and progression[ 2 , 3 ]. FABP4 is normally expressed in adipocytes at high levels and its expression is controlled by peroxisome proliferator-activated receptor gamma (PPARγ)[ 4 ]. Accumulating evidence shows that FABP4 plays important roles in cancer progression in multiple cancer types, including breast cancer[ 5 ], ovarian cancer[ 6 ], and colon cancer[ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

Li,

Lee,

Zhao

et al. 2024

World J Clin Oncol

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BACKGROUND Hepatocellular carcinoma (HCC) is an aggressive subtype of liver cancer and is one of the most common cancers with high mortality worldwide. Reprogrammed lipid metabolism plays crucial roles in HCC cancer cell survival, growth, and evolution. Emerging evidence suggests the importance of fatty acid binding proteins (FABPs) in contribution to cancer progression and metastasis; however, how these FABPs are dysregulated in cancer cells, especially in HCC, and the roles of FABPs in cancer progression have not been well defined. AIM To understand the genetic alterations and expression of FABPs and their associated cancer hallmarks and oncogenes in contributing to cancer malignancies. METHODS We used The Cancer Genome Atlas datasets of pan cancer and liver hepatocellular carcinoma (LIHC) as well as patient cohorts with other cancer types in this study. We investigated genetic alterations of FABPs in various cancer types. mRNA expression was used to determine if FABPs are abnormally expressed in tumor tissues compared to non-tumor controls and to investigate whether their expression correlates with patient clinical outcome, enriched cancer hallmarks and oncogenes previously reported for patients with HCC. We determined the protein levels of FABP5 and its correlated genes in two HCC cell lines and assessed the potential of FABP5 inhibition in treating HCC cells. RESULTS We discovered that a gene cluster including five FABP family members (FABP4, FABP5, FABP8, FABP9 and FABP12 ) is frequently co-amplified in cancer. Amplification, in fact, is the most common genetic alteration for FABPs, leading to overexpression of FABPs. FABP5 showed the greatest differential mRNA expression comparing tumor with non-tumor tissues. High FABP5 expression correlates well with worse patient outcomes (P < 0.05). FABP5 expression highly correlates with enrichment of G2M checkpoint (r = 0.33, P = 1.1e-10), TP53 signaling pathway (r = 0.22, P = 1.7e-5) and many genes in the gene sets such as CDK1 (r = 0.56, P = 0), CDK4 (r = 0.49, P = 0), and TP53 (r = 0.22, P = 1.6e-5). Furthermore, FABP5 also correlates well with two co-expressed oncogenes PLK1 and BIRC5 in pan cancer especially in LIHC patients (r = 0.58, P = 0; r = 0.58, P = 0; respectively). FABP5high Huh7 cells also expressed higher protein levels of p53, BIRC5, CDK1, CDK2, and CDK4 than FABP5low HepG2 cells. FABP5 inhibition more potently inhibited the tumor cell growth in Huh7 cells than in HepG2 cells. CONCLUSION We discovered that FABP5 gene is frequently amplified in cancer, especially in HCC, leading to its significant elevated expression in HCC. Its high expression correlates well with worse patient outcome, enriched cancer hallmarks and oncogenes in HCC. FABP5 inhibition impaired the cell viability of FABP5high Huh7 cells. All these support that FABP5 is a novel therapeutic target for treating FABP5high HCC.

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“…Furthermore, FABP5 was higher in FO than in FLX placenta. FABPs have differential affinities to specific FAs: FABP5 binds to both DHA and AA, whereas FABP7 binds specifically to DHA [47,[52][53][54], and both FABP4 and FABP5 specifically increase the uptake of DHA [55][56][57][58]. Furthermore, although FABP3 was shown to bind preferentially to AA (n-6 FA) [54], it regulates both n-3 and n-6 FA transport in mouse trophoblasts [59].…”

Section: Maternal N-3 Fa Supplementation Affects the Placental Lipid ...mentioning

confidence: 99%

Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

dos Santos Silva,

Kra,

Butenko

et al. 2024

J Animal Sci Biotechnol

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Background The placenta plays a crucial role in supporting and influencing fetal development. We compared the effects of prepartum supplementation with omega-3 (n-3) fatty acid (FA) sources, flaxseed oil (FLX) and fish oil (FO), on the expression of genes and proteins related to lipid metabolism, inflammation, oxidative stress, and the endocannabinoid system (ECS) in the expelled placenta, as well as on FA profile and inflammatory response of neonates. Late-pregnant Holstein dairy cows were supplemented with saturated fat (CTL), FLX, or FO. Placental cotyledons (n = 5) were collected immediately after expulsion, and extracted RNA and proteins were analyzed by RT-PCR and proteomic analysis. Neonatal blood was assessed for FA composition and concentrations of inflammatory markers. Results FO increased the gene expression of fatty acid binding protein 4 (FABP4), interleukin 10 (IL-10), catalase (CAT), cannabinoid receptor 1 (CNR1), and cannabinoid receptor 2 (CNR2) compared with CTL placenta. Gene expression of ECS-enzyme FA-amide hydrolase (FAAH) was lower in FLX and FO than in CTL. Proteomic analysis identified 3,974 proteins; of these, 51–59 were differentially abundant between treatments (P ≤ 0.05, |fold change| ≥ 1.5). Top canonical pathways enriched in FLX vs. CTL and in FO vs. CTL were triglyceride metabolism and inflammatory processes. Both n-3 FA increased the placental abundance of FA binding proteins (FABPs) 3 and 7. The abundance of CNR1 cannabinoid-receptor-interacting-protein-1 (CNRIP1) was reduced in FO vs. FLX. In silico modeling affirmed that bovine FABPs bind to endocannabinoids. The FLX increased the abundance of inflammatory CD44-antigen and secreted-phosphoprotein-1, whereas prostaglandin-endoperoxide synthase 2 was decreased in FO vs. CTL placenta. Maternal FO enriched neonatal plasma with n-3 FAs, and both FLX and FO reduced interleukin-6 concentrations compared with CTL. Conclusion Maternal n-3 FA from FLX and FO differentially affected the bovine placenta; both enhanced lipid metabolism and modulated oxidative stress, however, FO increased some transcriptional ECS components, possibly related to the increased FABPs. Maternal FO induced a unique balance of pro- and anti-inflammatory components in the placenta. Taken together, different sources of n-3 FA during late pregnancy enhanced placental immune and metabolic processes, which may affect the neonatal immune system.

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PPARγregulatesfabp4expression to increase DHA content in golden pompano (Trachinotus ovatus) hepatocytes

Cited by 8 publications

References 48 publications

Molecular regulation of differential lipid molecule accumulation in intramuscular fat and abdominal fat of chicken

Molecular regulation of differential lipid molecule accumulation in intramuscular fat and abdominal fat of chicken

Fatty acid binding protein 5 is a novel therapeutic target for hepatocellular carcinoma

Maternal supplementation with n-3 fatty acids affects placental lipid metabolism, inflammation, oxidative stress, the endocannabinoid system, and the neonate cytokine concentrations in dairy cows

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