Hypoxia is associated with a lower expression of genes involved in lipogenesis in visceral adipose tissue

• Published in: Journal of translational medicine Vol. 13; no. 1; p. 373
• Main Authors: García-Fuentes, Eduardo, Santiago-Fernández, Concepción, Gutiérrez-Repiso, Carolina, Mayas, María D., Oliva-Olivera, Wilfredo, Coín-Aragüez, Leticia, Alcaide, Juan, Ocaña-Wilhelmi, Luis, Vendrell, Joan, Tinahones, Francisco J., Garrido-Sánchez, Lourdes
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 30.11.2015; BioMed Central
• Subjects: Adipose tissues; Adult; Animals; Body fat; Female; Gene Expression Regulation; Genes; Genetic aspects; Genetic research; Humans; Hypoxia - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Insulin resistance; Intra-Abdominal Fat - metabolism; Lipogenesis - genetics; Male; Mice; Mice, Inbred C57BL; Middle Aged; Obesity; Obesity, Morbid - metabolism; RNA; RNA, Messenger - genetics
• ISSN: 1479-5876; 1479-5876
• DOI: 10.1186/s12967-015-0732-5

A key role for HIF-1α in the promotion and maintenance of dietary obesity has been proposed. We analyzed the association between hypoxia and de novo lipogenesis in human adipose tissue. We studied HIF-1α mRNA and protein expression in fasting status in visceral adipose tissue (VAT) from non-obese and morbidly obese subjects, and in VAT from wild-type and ob/ob C57BL6J mice in both fasting and feeding status. We also analyzed the effect of hypoxia on the VAT mRNA expression of genes involved in lipogenesis. HIF-1α was increased in VAT from morbidly obese subjects. In fasting status, C57BL6J ob/ob mice had a higher VAT HIF-1α mRNA expression than C57BL6J wild-type mice. In feeding status, VAT HIF-1α mRNA expression significantly increased in C57BL6J wild-type, but not in C57BL6J ob/ob mice. In humans, HIF-1α mRNA expression correlated positively with body mass index and insulin resistance. VAT HIF-1α mRNA expression correlated negatively with ACC1, PDHB and SIRT3 mRNA expression, and positively with PPAR-γ. VAT explants incubated in hypoxia showed reduced SIRT3 and increased PPAR-γ, SREBP-1c, ACLY, ACC1 and FASN mRNA expression. Morbidly obese subjects have a higher level of VAT HIF-1α. Postprandial status is associated with an increase in HIF-1α mRNA expression in C57BL6J wild-type mice. Hypoxia alters the mRNA expression of genes involved in de novo lipogenesis in human VAT.