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

García-Fuentes E, Santiago-Fernández C, Gutiérrez-Repiso C, Mayas MD, Oliva-Olivera W, Coín-Aragüez L, Alcaide J, Ocaña-Wilhelmi L, Vendrell J, Tinahones FJ, Garrido-Sánchez L - J Transl Med (2015)

Bottom Line: We also analyzed the effect of hypoxia on the VAT mRNA expression of genes involved in lipogenesis.VAT explants incubated in hypoxia showed reduced SIRT3 and increased PPAR-γ, SREBP-1c, ACLY, ACC1 and FASN mRNA expression.Hypoxia alters the mRNA expression of genes involved in de novo lipogenesis in human VAT.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Nutrition, Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital, Malaga, Spain. edugf1@gmail.com.

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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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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Fig3: 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

Mentions: As humans are in a feeding status most of the day, we wanted to test whether this state produces a change in HIF-1α mRNA expression. We used C57BL6J wild-type mice and obese C57BL6J ob/ob mice, given the impossibility of accessing human VAT in a feeding status. In the fasting status, the behavior of VAT HIF-1α mRNA expression in C57BL6J mice was similar to human VAT. In fasting status, C57BL6J ob/ob mice had a higher HIF-1α mRNA expression than C57BL6J wild-type mice (p < 0.001) (Fig. 3a). In feeding status, C57BL6J wild-type mice had a similar HIF-1α mRNA expression than C57BL6J ob/ob mice (p = 0.091) (Fig. 3a). C57BL6J wild-type mice showed a significant increase in the expression of HIF-1α mRNA expression in feeding status respect to fasting status (p < 0.0001), and C57BL6J ob/ob mice did not show a significant change in the expression of HIF-1α mRNA expression in feeding status respect to fasting status (p = 0.535) (Fig. 3b). These results were confirmed by western blot analysis (n = 4 per group) (Fig. 3b).Fig. 3


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

García-Fuentes E, Santiago-Fernández C, Gutiérrez-Repiso C, Mayas MD, Oliva-Olivera W, Coín-Aragüez L, Alcaide J, Ocaña-Wilhelmi L, Vendrell J, Tinahones FJ, Garrido-Sánchez L - J Transl Med (2015)

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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4663723&req=5

Fig3: 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
Mentions: As humans are in a feeding status most of the day, we wanted to test whether this state produces a change in HIF-1α mRNA expression. We used C57BL6J wild-type mice and obese C57BL6J ob/ob mice, given the impossibility of accessing human VAT in a feeding status. In the fasting status, the behavior of VAT HIF-1α mRNA expression in C57BL6J mice was similar to human VAT. In fasting status, C57BL6J ob/ob mice had a higher HIF-1α mRNA expression than C57BL6J wild-type mice (p < 0.001) (Fig. 3a). In feeding status, C57BL6J wild-type mice had a similar HIF-1α mRNA expression than C57BL6J ob/ob mice (p = 0.091) (Fig. 3a). C57BL6J wild-type mice showed a significant increase in the expression of HIF-1α mRNA expression in feeding status respect to fasting status (p < 0.0001), and C57BL6J ob/ob mice did not show a significant change in the expression of HIF-1α mRNA expression in feeding status respect to fasting status (p = 0.535) (Fig. 3b). These results were confirmed by western blot analysis (n = 4 per group) (Fig. 3b).Fig. 3

Bottom Line: We also analyzed the effect of hypoxia on the VAT mRNA expression of genes involved in lipogenesis.VAT explants incubated in hypoxia showed reduced SIRT3 and increased PPAR-γ, SREBP-1c, ACLY, ACC1 and FASN mRNA expression.Hypoxia alters the mRNA expression of genes involved in de novo lipogenesis in human VAT.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology and Nutrition, Institute of Biomedical Research of Malaga (IBIMA), Regional University Hospital, Malaga, Spain. edugf1@gmail.com.

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.

Show MeSH
Related in: MedlinePlus