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. 2015 Nov 30:13:373.
doi: 10.1186/s12967-015-0732-5.

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

Eduardo García-Fuentes  1   2   3 , Concepción Santiago-Fernández  4 , Carolina Gutiérrez-Repiso  5 , María D Mayas  6 , Wilfredo Oliva-Olivera  7   8 , Leticia Coín-Aragüez  9   10 , Juan Alcaide  11   12 , Luis Ocaña-Wilhelmi  13 , Joan Vendrell  14   15 , Francisco J Tinahones  16   17 , Lourdes Garrido-Sánchez  18   19
Affiliations

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

Eduardo García-Fuentes et al. J Transl Med. .

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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Figures

Fig. 1
Fig. 1
HIF-1α expression in visceral adipose tissue (VAT) in non-obese and morbidly obese subjects with low (MO-low-IR) and high insulin resistance (MO-high-IR) in fasting condition. a HIF-1α mRNA and b representative immunoblot from non-obese and morbidly obese subjects (n = 4 per group). The results are given as the mean ± SEM. aP < 0.05 significant differences respect to the non-obese group. A.U. arbitrary units
Fig. 2
Fig. 2
mRNA expression of SIRT3, PPAR-γ, SREBP-1c, ACLY, FASN, ACC1, ACSS2 and PDHB in visceral adipose tissue explants culture incubated for 24 h at 37 °C in normoxic conditions (filled square) or placed in a hypoxic chamber for 24 h at 37 °C in hypoxic conditions (open square) (n = 5 per group). Results are shown as a percentage of the normoxic condition. The results are given as the mean ± SEM. *P < 0.05 significant differences between normoxic and hypoxic condition
Fig. 3
Fig. 3
HIF-1α expression in visceral adipose tissue from wild-type C57BL6J (WT) and ob/ob C57BL6J mice (Ob/Ob) in fasting (filled square) (n = 17 in WT and n = 17 in Ob/Ob mice) and feeding status (open square) (n = 17 in WT and n = 17 in Ob/Ob mice). a HIF-1α mRNA and b representative immunoblot (n = 4 per group). The results are given as the mean ± SEM. A.U. arbitrary units
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