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
Department of Endocrinology and Nutrition, Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital, Malaga, Spain.
CIBEROBN, Institute of Health Carlos III, Malaga, Spain.
J Transl Med. 2015 Nov 30;13:373. 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.
有人提出HIF-1α在饮食性肥胖的促进和维持中起关键作用。我们分析了人类脂肪组织中缺氧与从头脂肪生成之间的关联。
我们研究了非肥胖和病态肥胖受试者内脏脂肪组织（VAT）在空腹状态下的HIF-1α mRNA和蛋白表达，以及野生型和ob/ob C57BL6J小鼠在空腹和进食状态下的VAT中的表达。我们还分析了缺氧对参与脂肪生成的基因在VAT中的mRNA表达的影响。
病态肥胖受试者的VAT中HIF-1α增加。在空腹状态下，C57BL6J ob/ob小鼠的VAT HIF-1α mRNA表达高于C57BL6J野生型小鼠。在进食状态下，C57BL6J野生型小鼠的VAT HIF-1α mRNA表达显著增加，而C57BL6J ob/ob小鼠则没有。在人类中，HIF-1α mRNA表达与体重指数和胰岛素抵抗呈正相关。VAT HIF-1α mRNA表达与ACC1、PDHB和SIRT3 mRNA表达呈负相关，与PPAR-γ呈正相关。在缺氧条件下培养的VAT外植体显示SIRT3减少，PPAR-γ、SREBP-1c、ACLY、ACC1和FASN mRNA表达增加。
病态肥胖受试者的VAT中HIF-1α水平较高。餐后状态与C57BL6J野生型小鼠中HIF-1α mRNA表达增加有关。缺氧改变了人类VAT中参与从头脂肪生成的基因的mRNA表达。
