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

Eduardo García-Fuentes,Wilfredo Oliva-Olivera,María D Mayas,Juan Alcaide,Joan Vendrell,Luis Ocaña-Wilhelmi,Carolina Gutiérrez-Repiso,Lourdes Garrido-Sánchez,Francisco J Tinahones,Concepción Santiago-Fernández,Leticia Coín-Aragüez

doi:10.1186/s12967-015-0732-5

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.

Highlights

A key role for hypoxia-inducible factor (HIF)-1α in the promotion and maintenance of dietary obesity has been proposed
Since hypoxia could be related to adipocyte lipid synthesis, we studied the relationship between HIF-1α, a marker of hypoxia, and the mRNA expression of genes involved in lipogenesis in human visceral adipose tissue (VAT)
In the present study we analyzed the association between VAT HIF-1α and several obesity-related variables and the mRNA expression of genes involved in lipogenesis

Summary

Methods

Subjects We evaluated 30 morbidly obese subjects, 15 with low insulin resistance [homeostasis model assessment of insulin resistance index (HOMA-IR) 8) [24]. Biopsy samples were immediately washed in physiological saline and frozen in liquid nitrogen after being obtained from the subject, and stored at −80 °C until analysis Another VAT sample from the non-obese subjects was placed in phosphate buffered saline (PBS) supplemented with 5 % bovine serum albumin (BSA) to perform adipose tissue explant cultures. Human adipose tissue culture VAT explants from non-obese subjects were prepared by cutting samples into 5 mg portions, which were subsequently incubated for 30 min in PBS + 5 % BSA (3 ml/g) [26]. Malonyl‐CoA in human adipose tissue Malonyl-CoA concentration was analyzed by a commercial kit (BlueGene Biotech, Shanghai, China) in fresh biopsies of VAT from morbidly obese (n = 5) and nonobese subjects (n = 5), and in VAT explant cultures from non-obese subjects (in normoxic and hypoxic conditions) (n = 3) according to manufacturer’s instructions. The results are given as the mean ± SD, and as the mean ± SEM in figures

Results

Background

Discussion