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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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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
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Fig2: 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

Mentions: Hypoxia produced a significant reduction in the mRNA expression of SIRT3 (p = 0.033) (Fig. 2). However, hypoxia produced a significant increase in ACC1 (p = 0.011), ACLY (p = 0.020), PPAR-γ (p = 0.017), FASN (p = 0.011) and SREBP-1c mRNA expression (p = 0.034). The measure of the enzymatic activity confirmed the results of mRNA expression of ACLY (hypoxia: 0.064 ± 0.005 vs. normoxia: 0.029 ± 0.003 U/mg VAT, p = 0.002), ACCS (hypoxia: 0.0081 ± 0.0007 vs. normoxia: 0.0071 ± 0.0008 U/mg VAT, p = 0.186) and PDH (hypoxia: 1.4 × 10−8 ± 0.50 × 10−8 vs. normoxia: 1.6 × 10−8±1.0 × 10−8 U/mg VAT, p = 0.480). The ACC1 mRNA expression was confirmed by the analysis of malonyl-CoA concentration in VAT (hypoxia: 0.127 ± 0.010 vs. normoxia: 0.085 ± 0.003 ng/mg VAT, p = 0.012).Fig. 2


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)

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
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: 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
Mentions: Hypoxia produced a significant reduction in the mRNA expression of SIRT3 (p = 0.033) (Fig. 2). However, hypoxia produced a significant increase in ACC1 (p = 0.011), ACLY (p = 0.020), PPAR-γ (p = 0.017), FASN (p = 0.011) and SREBP-1c mRNA expression (p = 0.034). The measure of the enzymatic activity confirmed the results of mRNA expression of ACLY (hypoxia: 0.064 ± 0.005 vs. normoxia: 0.029 ± 0.003 U/mg VAT, p = 0.002), ACCS (hypoxia: 0.0081 ± 0.0007 vs. normoxia: 0.0071 ± 0.0008 U/mg VAT, p = 0.186) and PDH (hypoxia: 1.4 × 10−8 ± 0.50 × 10−8 vs. normoxia: 1.6 × 10−8±1.0 × 10−8 U/mg VAT, p = 0.480). The ACC1 mRNA expression was confirmed by the analysis of malonyl-CoA concentration in VAT (hypoxia: 0.127 ± 0.010 vs. normoxia: 0.085 ± 0.003 ng/mg VAT, p = 0.012).Fig. 2

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