Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1555-1565 |
| Journal | Molecular and Cellular Biology |
| Volume | 32 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2012 |
| MoE publication type | A1 Journal article-refereed |
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Peroxisome Proliferator-Activated Receptor γ-Dependent Regulation of Lipolytic Nodes and Metabolic Flexibility. / Rodriguez-Cuenca, Sergio; Carobbio, Stefania; Velagapudi, Vidya; Barbarroja, Nuria; Moreno-Navarrete, Jose Maria; Tinahones, Francisco Jose; Fernandez-Real, Jose Manuel; Orešič, Matej; Vidal-Puig, Antonio.
In: Molecular and Cellular Biology, Vol. 32, No. 8, 2012, p. 1555-1565.Research output: Contribution to journal › Article › Scientific › peer-review
TY - JOUR
T1 - Peroxisome Proliferator-Activated Receptor γ-Dependent Regulation of Lipolytic Nodes and Metabolic Flexibility
AU - Rodriguez-Cuenca, Sergio
AU - Carobbio, Stefania
AU - Velagapudi, Vidya
AU - Barbarroja, Nuria
AU - Moreno-Navarrete, Jose Maria
AU - Tinahones, Francisco Jose
AU - Fernandez-Real, Jose Manuel
AU - Orešič, Matej
AU - Vidal-Puig, Antonio
PY - 2012
Y1 - 2012
N2 - Optimal lipid storage and mobilization are essential for efficient adipose tissue. Nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) regulates adipocyte differentiation and lipid deposition, but its role in lipolysis and dysregulation in obesity is not well defined. This investigation aimed to understand the molecular impact of dysfunctional PPARγ on the lipolytic axis and to explore whether these defects are also confirmed in common forms of human obesity. For this purpose, we used the P465L PPARγ mouse as a model of dysfunctional PPARγ that recapitulates the human pparγ mutation (P467L). We demonstrated that defective PPARγ impairs catecholamine-induced lipolysis. This abnormal lipolytic response is exacerbated by a state of positive energy balance in leptin-deficient ob/ob mice. We identified the protein kinase A (PKA) network as a PPARγ-dependent regulatory node of the lipolytic response. Specifically, defective PPARγ is associated with decreased basal expression of prkaca (PKAcatα) and d-akap1, the lipase genes Pnplaz (ATGL) and Lipe (HSL), and lipid droplet protein genes fsp27 and adrp in vivo and in vitro. Our data indicate that PPARγ is required for activation of the lipolytic regulatory network, dysregulation of which is an important feature of obesity-induced insulin resistance in humans.
AB - Optimal lipid storage and mobilization are essential for efficient adipose tissue. Nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) regulates adipocyte differentiation and lipid deposition, but its role in lipolysis and dysregulation in obesity is not well defined. This investigation aimed to understand the molecular impact of dysfunctional PPARγ on the lipolytic axis and to explore whether these defects are also confirmed in common forms of human obesity. For this purpose, we used the P465L PPARγ mouse as a model of dysfunctional PPARγ that recapitulates the human pparγ mutation (P467L). We demonstrated that defective PPARγ impairs catecholamine-induced lipolysis. This abnormal lipolytic response is exacerbated by a state of positive energy balance in leptin-deficient ob/ob mice. We identified the protein kinase A (PKA) network as a PPARγ-dependent regulatory node of the lipolytic response. Specifically, defective PPARγ is associated with decreased basal expression of prkaca (PKAcatα) and d-akap1, the lipase genes Pnplaz (ATGL) and Lipe (HSL), and lipid droplet protein genes fsp27 and adrp in vivo and in vitro. Our data indicate that PPARγ is required for activation of the lipolytic regulatory network, dysregulation of which is an important feature of obesity-induced insulin resistance in humans.
U2 - 10.1128/MCB.06154-11
DO - 10.1128/MCB.06154-11
M3 - Article
VL - 32
SP - 1555
EP - 1565
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
SN - 0270-7306
IS - 8
ER -