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Peroxisome prolifer...
Peroxisome proliferator-activated receptor γ-dependent regulation of lipolytic nodes and metabolic flexibility
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- Rodriguez-Cuenca, Sergio (författare)
- Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
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- Carobbio, Stefania (författare)
- Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
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- Velagapudi, Vidya R. (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland
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- Barbarroja, Nuria (författare)
- VTT Technical Research Centre of Finland, Espoo, Finland; Hospital Virgen de la Victoria, CIBERobn Fisiopatología de la Obesidad y Nutrición, Malaga, Spain
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- Moreno-Navarrete, Jose Maria (författare)
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, Girona, Spain; CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain
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- Tinahones, Francisco Jose (författare)
- Hospital Virgen de la Victoria, CIBERobn Fisiopatología de la Obesidad y Nutrición, Malaga, Spain
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- Fernandez-Real, Jose Manuel (författare)
- Department of Diabetes, Endocrinology and Nutrition, Institut d'Investigació Biomédica de Girona, Girona, CIBERobn Fisiopatología de la Obesidad y Nutrición, Girona, Spain
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- Oresic, Matej, 1967- (författare)
- Örebro universitet,Institutionen för medicinska vetenskaper,VTT Technical Research Centre of Finland, Espoo, Finland
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- Vidal-Puig, Antonio (författare)
- Department of Clinical Biochemistry, Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom
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(creator_code:org_t)
- American Society for Microbiology, 2012
- 2012
- Engelska.
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Ingår i: Molecular and Cellular Biology. - : American Society for Microbiology. - 0270-7306 .- 1098-5549. ; 32:8, s. 1555-1565
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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