Carnitine palmitoyltransferase gene upregulation by linoleic acid induces CD4+ T cell apoptosis promoting HCC development
Brown ZJ, Fu Q, Ma C, Kruhlak M, Zhang H, Luo J, Heinrich B, Yu SJ, Zhang Q, Wilson A, Shi ZD, Swenson R, Greten TF
Cell death & disease · 120 citas
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Animales
- Resultado principal
- Eventos clínicos como enfermedad o muerte
Quién lo pagó
- Financiación
- Financiación independiente
- Gobierno
- National Institutes of Health
- Gobierno
- National Cancer Institute
Según 2 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2018-05-23 · Cell Death Dis · vol. 9 · número 6 · pág. 620
- Editorial
- Springer Nature
- Citado
- 144 citas · más que el 97% de estudios similares · 6.1× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 45 trabajos
- Acceso
- Acceso abierto (revista) · CC-BY
- Áreas de investigación
- Liver Disease Diagnosis and Treatment · Peroxisome Proliferator-Activated Receptors · Cancer, Lipids, and Metabolism
- Palabras clave
- Downregulation and upregulation, Biology, Fatty liver, Beta oxidation, Endocrinology, Cancer research, Carnitine, Internal medicine, Apoptosis, Biochemistry, Medicine, Metabolism
- MeSH
- cd4-positive t-lymphocytes, 3t3 cells, mitochondria, animals, mice, inbred c57bl, humans, mice, carcinoma, hepatocellular, liver neoplasms, reactive oxygen species, perhexiline, carnitine o-palmitoyltransferase, linoleic acid, ppar alpha, enzyme inhibitors, apoptosis, up-regulation, models, biological, carcinogenesis, non-alcoholic fatty liver disease
13 autores
- Zachary J. Brown🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Qiong Fu🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Chi Ma🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Michael J. Kruhlak🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Haibo Zhang🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Ji Luo🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Bernd Heinrich🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Su Jong Yu🇺🇸🇰🇷National Institutes of Health; Seoul National University; National Cancer Institute; Center for Cancer Research
- Qianfei Zhang🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Andrew John Wilson🇺🇸National Institutes of Health; National Cancer Institute; Center for Cancer Research
- Zhendan Shi🇺🇸National Institutes of Health; National Heart, Lung, and Blood Institute
- Rolf E. Swenson🇺🇸National Institutes of Health; National Heart, Lung, and Blood Institute
- Tim F. Greten🇺🇸 · autor de correspondenciaNational Institutes of Health; National Cancer Institute; Center for Cancer Research
Resumen
El texto original del estudio, en el idioma en que se publicó.
Hepatocellular carcinoma (HCC) is a common cause of cancer-related death worldwide. As obesity and diabetes become more prevalent, the contribution of non-alcoholic fatty liver disease (NAFLD) to HCC is rising. Recently, we reported intrahepatic CD4+ T cells are critical for anti-tumor surveillance in NAFLD. Lipid accumulation in the liver is the hallmark of NAFLD, which may perturb T cell function. We sought to investigate how the lipid-rich liver environment influences CD4+ T cells by focusing on carnitine palmitoyltransferase (CPT) family members, which control the mitochondrial β-oxidation of fatty acids and act as key molecules in lipid catabolism. Linoleic acid (C18:2) co-localized within the mitochondria along with a corresponding increase in CPT gene upregulation. This CPT upregulation can be recapitulated by feeding mice with a high-C18:2 diet or the NAFLD promoting methionine-choline-deficient (MCD) diet. Using an agonist and antagonist, the induction of CPT genes was found to be mediated by peroxisome proliferator-activated receptor alpha (PPAR-α). CPT gene upregulation increased mitochondrial reactive oxygen species (ROS) and led to cell apoptosis. In vivo, using liver-specific inducible MYC transgenic mice fed MCD diet, blocking CPT with the pharmacological inhibitor perhexiline decreased apoptosis of intrahepatic CD4+ T cells and inhibited HCC tumor formation. These results provide useful information for potentially targeting the CPT family to rescue intrahepatic CD4+ T cells and to aid immunotherapy for NAFLD-promoted HCC.
Resumen vía Europe PMC. Los derechos de autor siguen siendo de los autores o la editorial (CC BY).
Confianza de la comunidad
Cargando…
¿Cuánto confías en los hallazgos de este estudio?
Comentarios
¿Algo está mal aquí?
Señala este estudio si su información, etiquetas o financiación parecen incorrectas. Un editor revisa cada señalamiento.
Información educativa sobre investigación publicada. No es consejo médico ni una recomendación para empezar o dejar nada.