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

Abstract

BackgroundA 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.MethodsWe 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.ResultsHIF-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.ConclusionsMorbidly 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.

Effects of acute hypoxia on human adipose tissue lipoprotein lipase activity and lipolysis

“…These observations confirm that the potential for lipid uptake of differentiated human preadipocytes is sensitive to an acute decrease in oxygen availability. It also complements recent evidence indicating that hypoxia impedes expression level of genes involved in de novo lipogenesis in human visceral adipose tissue [ 22 ].…”

ACLY (ATP Citrate Lyase) Mediates Radioresistance in Head and Neck Squamous Cell Carcinomas and is a Novel Predictive Radiotherapy Biomarker

“…It has previously been described that ACLY is overexpressed in malignant tissues as compared to normal tissues, which could provide for an optimal therapeutic window, yet the cause of overexpression of ACLY in HNSCC patients has not been investigated [23]. Experiments performed in visceral adipose tissue suggest that ACLY levels could be elevated as a result of an hypoxic environment, and that ACLY could be a possible target gene of the hypoxia-inducible factor 1α (HIF-1α) [24]. In that case, ACLY could correlate with the occurrence of hypoxic tumors, and the observed poor treatment response could be also partially attributed to the lack of oxygen required for effective irradiation.…”

BNIP3 induction by hypoxia stimulates FASN-dependent free fatty acid production enhancing therapeutic potential of umbilical cord blood-derived human mesenchymal stem cells

“…SREBP1 consists of two isoforms of SREBF1 gene, such as SREBP1a and SREBP1c. Previous reports presented that SREBP1c expression is responsible under hypoxic condition, which is associated with de novo lipogenesis [63], [64]. Although both SREBP1a and SREBP1c are involved in lipid metabolism [65], [66], most of previous studies present a SREBP-1c as a major regulator of FASN expression [67], [68].…”