Decreased Expression of FADS1 Predicts a Poor Prognosis in Patients with Esophageal Squamous Cell Carcinoma

Du, Yong,Yan, Shu-Mei,Gu, Wan-Yi,He, Fan,Huang, Li-Yun,Li, Mei,Yuan, Yan,Chen, Ren-Hui,Zhong, Qian,Li, Man-Zhi,Li, Yong,Zeng, Mu-Sheng Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.12

FADS1 (fatty acid desaturase 1) plays a crucial role in fatty acid metabolism, and it was recently reported to be involved in tumorigenesis. However, the role of FADS1 expression in esophageal squamous cell carcinoma (ESCC) remains unknown. In the current study, we investigated the expression and clinical pathologic and prognostic significance of FADS1 in ESCC. Immunohistochemical analyses revealed that 58.2% (146/251) of the ESCC tissues had low levels of FADS1 expression, whereas 41.8% (105/251) exhibited high levels of FADS1 expression. In positive cases, FADS1 expression was detected in the cytoplasm of cells. Correlation analyses demonstrated that FADS1 expression was significantly correlated with tumor location (p=0.025) but not with age, gender, histological grade, tumor status, nodal status or TNM staging. Furthermore, patients with tumors expressing high levels of FADS1had a longer disease-free survival time (p<0.001) and overall survival time (p <0.001). Univariate and multivariate analyses revealed that, along with nodal status, FADS1 expression was an independent and significant predictive factor (p<0.001). In conclusion, our study suggested that FADS1 might be a valuable biomarker and potential therapeutic target for ESCC.

Linseed oil supplementation affects fatty acid desaturase 2, peroxisome proliferator activated receptor gamma, and insulin-like growth factor 1 gene expression in turkeys (Meleagris gallopavo)

Szalai Klaudia,Tempfli Károly,Zsédely Eszter,Lakatos Erika,Gáspárdy András,Bali Papp Ágnes 아세아·태평양축산학회 2021 Animal Bioscience Vol.34 No.4

Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated. Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (FADS2), peroxisome proliferator activated receptor gamma (PPARγ), and insulin-like growth factor 1 (IGF1) genes was analysed by means of quantitative reverse transcription polymerase chain reaction. Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic FADS2 levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The PPARγ expression was lower (p<0.05), whereas IGF1 was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in FADS2, PPARγ, and IGF1 gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control. Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased FADS2 expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased PPARγ expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased IGF1 expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group. Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated.Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (<i>FADS2</i>), peroxisome proliferator activated receptor gamma (<i>PPARγ</i>), and insulin-like growth factor 1 (<i>IGF1</i>) genes was analysed by means of quantitative reverse transcription polymerase chain reaction.Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic <i>FADS2</i> levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The <i>PPARγ</i> expression was lower (p<0.05), whereas <i>IGF1</i> was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in <i>FADS2</i>, <i>PPARγ</i>, and <i>IGF1</i> gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control.Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased <i>FADS2</i> expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased <i>PPARγ</i> expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased <i>IGF1</i> expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group.

식이지방에 첨가한 Conjugated Linoleic Acid가 지방산 조성, delta-5 Desaturase(D5D)와 Fatty Acid Desaturase2(FADS2) 유전자 발현에 미치는 영향

황윤희(Yun?Hee Hwang),강금지(Keum?Jee Kang) 한국식품영양과학회 2007 한국식품영양과학회지 Vol.36 No.10

본 연구에서 4주령 ICR 수컷 마우스에 쇠기름과 어유에 단독 또는 0.5% CLA를 첨가한 식이로 4주동안 사육하여 혈장과 간의 지방산 조성과 D5D와 FADS2의 유전자 발현을 관찰한 결과는 다음과 같다. CLA는 C18:2와 경쟁적으로 지방산의 elongation과 desaturation에 참가하며, CLA의 첨가는 BTC군에서 C20:4수준을 높여주는 효과가 있었다. 또, 지방산의 β-산화에 의해 생성되기도 하는 C22:6은 BTC군에서 간의 C22:6의 함량이 BT군보다 증가하였다. D5D와 FADS2는 쇠기름섭취군(BT, BTC)에서 발현이 유의적으로 증가하였는데, 특히 D5D의 발현은 BTC군이 다른 군보다 유의적으로 증가하였다. 이에 대한 지방산 전환 또한 BTC군이 C18:2로부터 C20:4로 불포화하고 elongation하는 비율이 혈장과 간 모두에서 가장 높았다. 결론적으로 BT에 CLA를 첨가한 경우에 지방산 조성의 변화와 FADS2와 D5D의 발현을 증가시켜 지방산의 불포화도를 높여서 eicosanoids 합성과 항상성에 영향을 미치는 것으로 나타났으나 FO에 CLA첨가시에는 영향을 미치지 않는 것으로 나타났다. We investigated the effects of conjugated linoleic acid (CLA) on the fatty acid composition in the plasma and liver, and the expressions of delta-5 desaturase (D5D) and fatty acid desaturase2 (FADS2) genes in ICR male mice using two different sources of fats in the diets. The experimental groups were divided into four groups: beef tallow (BT) and fish oil (FO), BT with CLA supplementation (BTC), and FO with CLA supplementation (FOC) groups. Ten mice in each group were fed with the experimental diets for 4 weeks. All mice were fed experimental diets containing 12% of total dietary fat (w/w) either with or without 0.5%CLA (w/w). Fatty acid compositions were analyzed in the plasma and liver using gas chromatography. The levels of D5D and FADS2 expression were analyzed by RT-PCR in the liver. The results showed that CLA participates competitively with C18:2 in the elongation and desaturation processes, leading to significant increase in the levels of C20:4 and C22:6 in BTC group (p<0.05). The expression levels of D5D and FADS2 were higher in BT and BTC group than those of FO and FOC group. In particular, the expression of D5D gene was greatly upregulated in BTC group. Furthermore, the conversion ratios from C18:2 to C20:4 in the liver were higher in BTC group than those in other groups. Thus our results suggest that increased expressions of D5D and FADS2 genes may be responsible for the enhanced CLA effects on the desaturation in the BT containing saturated fatty acids rather than the FO rich in n-3 PUFA.

FADS gene polymorphisms in Koreans: Association with ω6 polyunsaturated fatty acids in serum phospholipids, lipid peroxides, and coronary artery disease

Kwak, J.H.,Paik, J.K.,Kim, O.Y.,Jang, Y.,Lee, S.H.,Ordovas, J.M.,Lee, J.H. Elsevier Scientific Publ. Co 2011 Atherosclerosis Vol.214 No.1

Objective: We investigated the association of polymorphisms in FADS genes with polyunsaturated fatty acids (PUFAs) in serum phospholipids, lipid peroxides, and coronary artery disease (CAD) in Koreans. Methods: In this case-control study, CAD patients (n=756, 40-79 years) and healthy controls (n=890) were genotyped for rs174537 near FADS1 (FEN1 rs174537G>T), FADS2 (rs174575, rs2727270), and FADS3 (rs1000778). We calculated the odds ratios (ORs) for CAD risk and measured serum PUFA composition and lipid peroxide. Results: Among four SNPs, only rs174537G>T differed in allele frequencies between controls and CAD patients after adjustment for age, BMI, cigarette smoking, alcohol consumption, hypertension, diabetes mellitus, and hyperlipidemia (P=0.017). The minor T allele was associated with a lower risk of CAD [OR 0.75 (95%CI 0.61-0.92), P=0.006] after adjustment. rs174537T carriers had a significantly higher proportion of linoleic acid (LA, 18:2ω6), lower arachidonic acid (AA, 20:4ω6), and lower ratios of AA/dihomo-γ-linolenic acid (DGLA, 20:3ω6) and AA/LA than G/G subjects in both control and CAD groups. In the control group, 174537T carriers had significantly lower levels of total- and LDL-cholesterol, malondialdehyde, and ox-LDL. In CAD patients, rs174537T carriers showed a larger LDL particle size than G/G subjects. The proportion of AA in serum phospholipids positively correlated with LDL-cholesterol, ox-LDL, and malondialdehyde in controls and with 8-epi-prostaglandin F<SUB>2α</SUB> in both control and CAD groups. Conclusion: The rs174537T is associated with a lower proportion of AA in serum phospholipids and reduced CAD risk, in association with reduced total- and LDL-cholesterol and lipid peroxides.

Sexually Matured Female Mice showed Higher γ-Linolenic Acid (GLA) in the Muscle Tissue

Chang Seok Park,Sang-Rae Cho,Young Sik Park 한국수정란이식학회 2015 한국동물생명공학회지 Vol.30 No.2

The sexual maturation occurred by the changes of steroid hormones was known to sex-dependently and/or agedependently regulate the lipid metabolism in various animal species. Our current study demonstrates that lipid and its functional fatty acids can be changed depending on the status of sexual maturation. Of the functional fatty acids, γ- linolenic acid (GLA; 18:3n-6) is an important factor for maintaining human health. The purpose of our study was to investigate the level of GLA in mice with different stages of sexual maturation. To this end, the longissimus muscle (LM) of immature (3-week-old) and mature (7-week-old) female mice was analysed for the fatty acid composition by gas chromatography. Furthermore, both gene and protein level of Δ6 desaturase (FADS2) which is involved in GLA metabolism by real time PCR and Western blotting, respectively. Mature females showed greater (P<0.05) serum 17β -estradiol (E2) level and LM GLA contents than immature group. The mRNA and protein levels of FADS2, which converts precursor linoleic acid into GLA, were higher (P<0.05) in mature female mice than in immature mice. In conclusion, these results show that sexual maturation of female mice induces GLA and FADS2 contents in LM.

Sexual Maturation May Affect the Levels of n-6 PUFA in Muscle Tissues of Male Mice

Park, Chang Seok,Choi, Inho,Park, Young Sik Korean Society of Animal Sciences and Technology 2013 한국축산학회지 Vol.55 No.2

Lipid metabolism in mature male mice may be different from immature male mice, but the relationship of lipid metabolism, especially n-6 fatty acid metabolism, and sexual maturation is not clearly established. This study was carried out to elucidate whether sexual maturation may affect the metabolism of functional n-6 fatty acids of lipid components by investigating the composition of fatty acids in the longissimus muscle tissues of mature and immature male mice with GC and analyzing the expression of genes and proteins for synthesis of n-6 fatty acids with real-time PCR and western blotting, respectively. Mature male mice showed significantly higher testosterone level in the sera. Similarly, n-6 fatty acids, levels of linoleic acid (LA 18:2n-6) and total n-6 PUFA (Polyunsaturated fatty acids) were increased, but the levels of ${\gamma}$-linolenic acid (GLA; 18:3n-6), dihomo-${\gamma}$-linolenic acid (DGLA; 20:3n-6) and arachidonic acid (AA; 20:4 n-6) were decreased in the mature male mice. mRNA levels of ${\Delta}5$-desaturase (FASD1) and elongase (ELOVL5) genes related to n-6 fatty acid metabolism increased. However, the level of FADS1 protein only increased in mature male mice. In conclusion, this study suggested that sexual maturation of male mice affected n-6 fatty acid metabolism by stimulating the expression of enzyme FADS1 of n-6 PUFA metabolism.

Sexually Matured Female Mice showed Higher γ-Linolenic Acid (GLA) in the Muscle Tissue

박영식,조상리,박창석 사단법인 한국동물생명공학회 2015 한국동물생명공학회지 Vol.30 No.2

The sexual maturation occurred by the changes of steroid hormones was known to sex-dependently and/or agedependently regulate the lipid metabolism in various animal species. Our current study demonstrates that lipid and its functional fatty acids can be changed depending on the status of sexual maturation. Of the functional fatty acids, γ- linolenic acid (GLA; 18:3n-6) is an important factor for maintaining human health. The purpose of our study was to investigate the level of GLA in mice with different stages of sexual maturation. To this end, the longissimus muscle (LM) of immature (3-week-old) and mature (7-week-old) female mice was analysed for the fatty acid composition by gas chromatography. Furthermore, both gene and protein level of Δ6 desaturase (FADS2) which is involved in GLA metabolism by real time PCR and Western blotting, respectively. Mature females showed greater (P<0.05) serum 17β -estradiol (E2) level and LM GLA contents than immature group. The mRNA and protein levels of FADS2, which converts precursor linoleic acid into GLA, were higher (P<0.05) in mature female mice than in immature mice. In conclusion, these results show that sexual maturation of female mice induces GLA and FADS2 contents in LM.

Sexually Matured Female Mice showed Higher γ-Linolenic Acid (GLA) in the Muscle Tissue

Park, Chang Seok,Cho, Sang-Rae,Park, Young Sik The Korean Society of Embryo Transfer 2015 한국동물생명공학회지 Vol.30 No.2

The sexual maturation occurred by the changes of steroid hormones was known to sex-dependently and/or age-dependently regulate the lipid metabolism in various animal species. Our current study demonstrates that lipid and its functional fatty acids can be changed depending on the status of sexual maturation. Of the functional fatty acids, ${\gamma}$-linolenic acid (GLA; 18:3n-6) is an important factor for maintaining human health. The purpose of our study was to investigate the level of GLA in mice with different stages of sexual maturation. To this end, the longissimus muscle (LM) of immature (3-week-old) and mature (7-week-old) female mice was analysed for the fatty acid composition by gas chromatography. Furthermore, both gene and protein level of ${\Delta}6$ desaturase (FADS2) which is involved in GLA metabolism by real time PCR and Western blotting, respectively. Mature females showed greater (P<0.05) serum $17{\beta}$-estradiol (E2) level and LM GLA contents than immature group. The mRNA and protein levels of FADS2, which converts precursor linoleic acid into GLA, were higher (P<0.05) in mature female mice than in immature mice. In conclusion, these results show that sexual maturation of female mice induces GLA and FADS2 contents in LM.

Unsaturated Fatty Acids, Desaturases, and Human Health

이형재,박우정 한국식품영양과학회 2014 Journal of medicinal food Vol.17 No.2

With the increasing concern for health and nutrition, dietary fat has attracted considerable attention. The composition of fatty acids in a diet is important since they are associated with major diseases, such as cancers, diabetes, and cardiovascular disease. The biosynthesis of unsaturated fatty acids (UFA) requires the expression of dietary fat-associated genes, such as SCD, FADS1, FADS2, and FADS3, which encode a variety of desaturases, to catalyze the addition of a double bond in a fatty acid chain. Recent studies using new molecular techniques and genomics, as well as clinical trials have shown that these genes and UFA are closely related to physiological conditions and chronic diseases; it was found that the existence of alternative transcripts of the desaturase genes and desaturase isoforms might affect human health and lipid metabolism in different ways. In this review, we provide an overview of UFA and desaturases associated with human health and nutrition. Moreover, recent findings of UFA, desaturases, and their associated genes in human systems are discussed. Consequently, this review may help elucidate the complicated physiology of UFA in human health and diseases.

Others : Sexual Maturation May Affect the Levels of n-6 PUFA in Muscle Tissues of Male Mice

( Chang Seok Park ),( Inho Choi ),( Young Sik Park ) 한국동물자원과학회(구 한국축산학회) 2013 한국축산학회지 Vol.55 No.2

Lipid metabolism in mature male mice may be different from immature male mice, but the relationship of lipid metabolism, especially n-6 fatty acid metabolism, and sexual maturation is not clearly established. This study was carried out to elucidate whether sexual maturation may affect the metabolism of functional n-6 fatty acids of lipid components by investigating the composition of fatty acids in the longissimus muscle tissues of mature and immature male mice with GC and analyzing the expression of genes and proteins for synthesis of n-6 fatty acids with real-time PCR and western blotting, respectively. Mature male mice showed significantly higher testosterone level in the sera. Similarly, n-6 fatty acids, levels of linoleic acid (LA I 8:2n-6) and total n-6 PUFA (Polyunsaturated fatty acids) were increased, but the levels of γ-linolenic acid (GLA. 18:3n-6), dihomo-γ-linolenic acid (DGLA; 20:3n-6) and arachidonic acid (AA; 20:4 n-6) were decreased in the mature male mice mRNA levels of △5-desaturase (FASDI) and elongase (ELOVL5) genes related to n-6 fatty acid metabolism increased. However, the level of FADSI protein only increased in mature male mice. In conclusion, this study suggested that sexual maturation of male mice affected n-6 fatty acid metabolism by stimulating the expression of enzyme FADSI of n-6 PIJFA metabolism.