Novel Lipogenic Enzyme ELOVL7 Is Involved in Prostate Cancer Growth through Saturated Long-Chain Fatty Acid Metabolism

Takagi, Kenji; Makino, Asami; Hullin-Matsuda, Françoise; Kobayashi, Toshihide; Furihata, Mutsuo; Chung, Suyoun; Ashida, Shingo; Miki, Tsuneharu; Fujioka, Tomoaki; Shuin, Taro; Nakamura, Yusuke; Nakagawa, Hidewaki

doi:10.1158/0008-5472.can-09-0775

Cited by 178 publications

(162 citation statements)

References 36 publications

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“…3B). Elovl7 expression is regulated by lipogenic enzymes and the androgen pathway through SREBP (11). Only Elovl3 revealed a decreasing tendency in the HFD mice (Fig.…”

Section: Discussionmentioning

confidence: 89%

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

et al. 2011

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Abstract. Peroxisomes catalyze a range of essential metabolic functions, mainly related to lipid metabolism. However, their roles in obesity have yet to be clarified. The aim of this study was to investigate the correlation between obesity and peroxisomal lipid metabolism, particularly very long-chain fatty acid (VLCFA) metabolism, gene expression of peroxisomal β-oxidation enzymes, peroxisomal ATP-binding cassette (ABC) transporter adrenoleukodystrophy (ABCD1) gene and its related gene, ABCD2, the elongation of the VLCFA (ELOVL) gene family and the transcriptional factors involved in the regulation of these genes, including peroxisome proliferator-activated receptor α (PPARα) and sterol regulatory element-binding protein. These factors were analyzed in livers from mice fed a high-fat diet (HFD) or a regular diet (RD) for 20 weeks. Furthermore, the amounts of plasma saturated and unsaturated fatty acids, including VLCFAs, were measured. A HFD induced hepatic gene expression of not only hydroxysteroid 17-β dehydrogenase 4 (HSD17b4) and sterol carrier protein 2 (SCP2) in peroxisomal β-oxidation enzymes but also of ELOVL1, 2, 5 and 6, which are involved in the elongation of saturated and unsaturated VLCFAs. Furthermore, ABCD2 mRNA prominently increased in the HFD mice. The transcriptional regulator of these genes, PPARα, was also up-regulated in the HFD mice. VLCFA ratios including C24:0/ C22:0, C25:0/C22:0 and C26:0/C22:0 are the most significant diagnostic markers of inherited peroxisomal diseases. These ratios were found to be low in the plasma of the HFD mice compared with the RD mice. The results suggest that HFD activates hepatic peroxisomal VLCFA metabolism, and may provide useful fundamental information to explain the role of peroxisomal function in obesity and lifestyle-related diseases.

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“…3B). Elovl7 expression is regulated by lipogenic enzymes and the androgen pathway through SREBP (11). Only Elovl3 revealed a decreasing tendency in the HFD mice (Fig.…”

Section: Discussionmentioning

confidence: 89%

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

et al. 2011

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“…7) have been identified so far. 26,27) Of the 7 isoforms, rat liver expresses four isoforms: Elovl1, Elovl2, Elovl5 and Elovl6.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Fatty Acid Profile in the Liver of SHR/NDmcr-cp (cp/cp) Rats, a Model of the Metabolic Syndrome

Tanaka

Yagi

Yamazaki

et al. 2012

Biological & Pharmaceutical Bulletin

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The fatty acid profile of hepatic lipid in spontaneously hypertensive rats (SHR)/NDmcr-cp (cp/cp) rats (SHR/NDcp), which offer an animal model of the metabolic syndrome, was characterized by comparing those in Wistar Kyoto rats (WKY), SHR, stroke-prone spontaneously hypertensive rats (SHRSP) and SHR/ NDmcr-cp ( / ) rats (SHR/ND ) . Hierarchical clustering analysis revealed that SHR/NDcp and the other four strains and/or substrains of rats were clearly disparate in fatty acid profile of hepatic lipid and that the disparity observed was due to the drastic increases in the mass of monounsaturated fatty acids, especially palmitoleic acid and oleic acid, in the liver of SHR/NDcp. Activities of stearoyl-CoA desaturase (SCD) and palmitoyl-CoA chain elongase in hepatic microsomes of SHR/NDcp were markedly higher than those of WKY, SHR, SHRSP and SHR/ND . Activities of palmitoleoyl-CoA chain elongase in the liver of SHR/ NDcp were also higher, but to a lesser extent. mRNA levels of SCD1 and elongation of very long-chain fatty acids (Elovl6), but not Elovl5, in the liver of SHR/NDcp were remarkably higher than those of the other four groups of rats. These results suggest that the enhanced expressions of SCD1 and Elovl6 induced abnormalities in fatty acid profile in the liver of SHR/NDcp. Key words fatty acid profile; palmitoleic acid; oleic acid; liver; SHR/NDmcr-cp (cp/cp) rat Obesity, hypertension, hyperlipidemia and hyperglycemia are risk factors for cardiovascular diseases. Patients who have two or more of these risk factors are susceptible to cardiovascular diseases; these states are called the metabolic syndrome. To explore protection against and treatment of the metabolic syndrome, studies on the pathophysiology and metabolic consequences of the metabolic syndrome are required using pertinent animal models. Spontaneously hypertensive rats (SHR)/NDmcr-cp (cp/cp) rats (SHR/NDcp) spontaneously develop obesity and hypertension, and display dyslipidemia and hyperglycemia, the values of body weight, systolic blood pressure, serum triglyceride and blood glucose in SHR/NDcp being 1.43, 1.65, 25.4 and 1.25 times, respectively, compared with those in Wistar Kyoto rats (WKY) (control rats) at 19 or 20 weeks of age.1) Thus, they provide a useful model of the metabolic syndrome.2,3) Hypertensive rats that spontaneously developed as a colony from normotensive WKY, were named SHR.4) By crossing SHR with Sprague-Dawley (SD) rats, obese spontaneously hypertensive rats, Koletsky strain, were obtained; this strain of rats is heterozygous for the cp gene.5) To eliminate the noncorpulent genes of the Koletsky strain, the rats were mated with SHR, and a congenic rat strain (SHR/National Institutes of Health (NIH)-corpulent) was developed.6) SHR/NDcp are a substrain of SHR/NIHcorpulent rats. With regard to metabolic abnormalities as to hypertension, hyperinsulinemia and hyperglycemia in SHR/ NDcp, many studies have been conducted. On the other hand, information on dyslipidemia in SHR/NDcp is very limited.

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“…The clinical significance of the relationship between androgens and lipid metabolism is highlighted by reports that FASN, ELOVL7, and SREBP proteins are commonly overexpressed in human prostate tumors compared with normal or benign prostatic hypertrophic tissue (Swinnen et al 2002, Rossi et al 2003, Ettinger et al 2004, Tamura et al 2009, with the expression of SREBP1 in particular showing positive associations with disease progression and Gleason grade (Ettinger et al 2004. Consistent with their androgenic regulation, both FASN and SREBP levels are initially decreased in patients treated with ADT but re-emerge with a higher level of expression in CRPC (Rossi et al 2003, Ettinger et al 2004.…”

Section: Genes Involved In Lipid Metabolism Are Altered In Clinical Pmentioning

confidence: 99%

Androgen control of lipid metabolism in prostate cancer: novel insights and future applications

Butler

Centenera

Swinnen

2016

Endocrine-Related Cancer

107

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One of the most typical hallmarks of prostate cancer cells is their exquisite dependence on androgens, which is the basis of the widely applied androgen deprivation therapy. Among the variety of key cellular processes and functions that are regulated by androgens, lipid metabolism stands out by its complex regulation and its many intricate links with cancer cell biology. Here, we review our current knowledge on the links between androgens and lipid metabolism in prostate cancer, and highlight recent developments and insights into the links between key oncogenic stimuli and altered lipid synthesis and/or uptake that may hold significant potential for biomarker development and provide new vulnerabilities for therapeutic intervention.

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Novel Lipogenic Enzyme ELOVL7 Is Involved in Prostate Cancer Growth through Saturated Long-Chain Fatty Acid Metabolism

Cited by 178 publications

References 36 publications

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

Induction of peroxisomal lipid metabolism in mice fed a high-fat diet

Characterization of Fatty Acid Profile in the Liver of SHR/NDmcr-cp (cp/cp) Rats, a Model of the Metabolic Syndrome

Androgen control of lipid metabolism in prostate cancer: novel insights and future applications

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