Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis
Objective: Peroxisome Proliferator-Activated Receptors (PPARs) are nuclear receptors involved in the control of lipid metabolism. The PPARα isoform is highly expressed in brown adipose tissue (BAT). However, its precise role in BAT remains unclear. Here, we aimed to investigate the role of PPARα in...
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| Language: | English |
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Elsevier
2025-08-01
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| Series: | Molecular Metabolism |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877825000912 |
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| author | Pierre-Louis Batrow Sylvie Caspar-Bauguil Nathalie Rochet Nadine Gautier Anne-Sophie Rousseau Marielle Maret Samah Rekima Etienne Mouisel Emmanuel Van Obberghen Christian H. Roux Hervé Guillou Catherine Postic Christian Wolfrum Dominique Langin Ez-Zoubir Amri Isabelle Mothe-Satney |
| author_facet | Pierre-Louis Batrow Sylvie Caspar-Bauguil Nathalie Rochet Nadine Gautier Anne-Sophie Rousseau Marielle Maret Samah Rekima Etienne Mouisel Emmanuel Van Obberghen Christian H. Roux Hervé Guillou Catherine Postic Christian Wolfrum Dominique Langin Ez-Zoubir Amri Isabelle Mothe-Satney |
| author_sort | Pierre-Louis Batrow |
| collection | DOAJ |
| description | Objective: Peroxisome Proliferator-Activated Receptors (PPARs) are nuclear receptors involved in the control of lipid metabolism. The PPARα isoform is highly expressed in brown adipose tissue (BAT). However, its precise role in BAT remains unclear. Here, we aimed to investigate the role of PPARα in BAT of high fat diet-induced obese mice in a thermoneutral environment. Methods: We used tamoxifen-inducible-BAT specific PPARα knockout mice (PPARαBATKO) that were housed at thermoneutrality to minimize BAT basal activation, fed a high-fat diet for 20 weeks and challenged with a β3-adrenergic agonist (CL316,243) during the last week. Both male and female mice were studied. Results: Body weight and glucose tolerance tests were similar in both sexes and genotypes. However, BAT morphology was altered in PPARαBATKO mice, with more unilocular and larger lipid droplets compared to control mice, suggesting BAT impaired function. Indeed, when treated with CL316,243, both male and female mice had increased De Novo Lipogenesis (DNL), reflected by an increased expression of ChREBPβ and lipogenic enzymes ACLY, ACC1, FASN and SCD1. These changes were accompanied by an increase in fatty acids in triglycerides, and thus an increase in lipid storage. Moreover, lipid profiles in phospholipids were different, suggesting a modification in the membrane content with an increase of palmitoleate. Conclusions: Altogether, our results reveal a key role for PPARα in DNL in BAT and in the regulation of lipid metabolism in HFD-induced obesity. |
| format | Article |
| id | doaj-art-6f55fd36feb14dde9cb0f836f5ab4832 |
| institution | Kabale University |
| issn | 2212-8778 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj-art-6f55fd36feb14dde9cb0f836f5ab48322025-08-20T03:28:14ZengElsevierMolecular Metabolism2212-87782025-08-019810218410.1016/j.molmet.2025.102184Deletion of PPARα in mouse brown adipocytes increases their De Novo LipogenesisPierre-Louis Batrow0Sylvie Caspar-Bauguil1Nathalie Rochet2Nadine Gautier3Anne-Sophie Rousseau4Marielle Maret5Samah Rekima6Etienne Mouisel7Emmanuel Van Obberghen8Christian H. Roux9Hervé Guillou10Catherine Postic11Christian Wolfrum12Dominique Langin13Ez-Zoubir Amri14Isabelle Mothe-Satney15Université Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, FranceInstitute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, Inserm, Toulouse III University - Paul Sabatier (UPS), Toulouse, France; Department of Medical Biochemistry, Toulouse University Hospitals, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, FranceUniversité Côte d’Azur, CNRS, Inserm, IRCAN, Nice, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, FranceInstitute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, Inserm, Toulouse III University - Paul Sabatier (UPS), Toulouse, FranceUniversité Côte d’Azur, CNRS, Laboratoire de PhysioMédecine Moléculaire (LP2M), Laboratories of Excellence Ion Channel Science and Therapeutics, Nice, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, France; Rheumatology Department, Hospital Pasteur 2 CHU, Adipocible Research Study Group, 06000, Nice, FranceToxalim (Research Centre in Food Toxicology), Université de Toulouse, INRAE, ENVT, INP-Purpan, UPS, Toulouse, FranceUniversité Paris Cité, Institut Cochin, CNRS, Inserm, Paris, FranceLaboratory of Translational Nutrition Biology, Institute of Food, Nutrition and Health, ETH Zurich, Schwerzenbach, SwitzerlandInstitute of Metabolic and Cardiovascular Diseases, I2MC, University of Toulouse, Inserm, Toulouse III University - Paul Sabatier (UPS), Toulouse, France; Department of Medical Biochemistry, Toulouse University Hospitals, France; Institut Universitaire de France (IUF), Paris, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, FranceUniversité Côte d’Azur, CNRS, Inserm, Adipocible Research Study Group, Institut de Biologie Valrose (iBV), Nice, France; Corresponding author. Institut de Biologie Valrose, Université Côte d’Azur, CNRS UMR 7277, Inserm U1091, Tour Pasteur, Faculté de Médecine, 28, Avenue de Valombrose, 06107, Nice, France.Objective: Peroxisome Proliferator-Activated Receptors (PPARs) are nuclear receptors involved in the control of lipid metabolism. The PPARα isoform is highly expressed in brown adipose tissue (BAT). However, its precise role in BAT remains unclear. Here, we aimed to investigate the role of PPARα in BAT of high fat diet-induced obese mice in a thermoneutral environment. Methods: We used tamoxifen-inducible-BAT specific PPARα knockout mice (PPARαBATKO) that were housed at thermoneutrality to minimize BAT basal activation, fed a high-fat diet for 20 weeks and challenged with a β3-adrenergic agonist (CL316,243) during the last week. Both male and female mice were studied. Results: Body weight and glucose tolerance tests were similar in both sexes and genotypes. However, BAT morphology was altered in PPARαBATKO mice, with more unilocular and larger lipid droplets compared to control mice, suggesting BAT impaired function. Indeed, when treated with CL316,243, both male and female mice had increased De Novo Lipogenesis (DNL), reflected by an increased expression of ChREBPβ and lipogenic enzymes ACLY, ACC1, FASN and SCD1. These changes were accompanied by an increase in fatty acids in triglycerides, and thus an increase in lipid storage. Moreover, lipid profiles in phospholipids were different, suggesting a modification in the membrane content with an increase of palmitoleate. Conclusions: Altogether, our results reveal a key role for PPARα in DNL in BAT and in the regulation of lipid metabolism in HFD-induced obesity.http://www.sciencedirect.com/science/article/pii/S2212877825000912Peroxisome proliferator-activated receptor alphaBrown adipose tissueInducible UCP1-CREHigh fat diet-induced obesityβ3-adrenergic stimulationLipid metabolism |
| spellingShingle | Pierre-Louis Batrow Sylvie Caspar-Bauguil Nathalie Rochet Nadine Gautier Anne-Sophie Rousseau Marielle Maret Samah Rekima Etienne Mouisel Emmanuel Van Obberghen Christian H. Roux Hervé Guillou Catherine Postic Christian Wolfrum Dominique Langin Ez-Zoubir Amri Isabelle Mothe-Satney Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis Molecular Metabolism Peroxisome proliferator-activated receptor alpha Brown adipose tissue Inducible UCP1-CRE High fat diet-induced obesity β3-adrenergic stimulation Lipid metabolism |
| title | Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis |
| title_full | Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis |
| title_fullStr | Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis |
| title_full_unstemmed | Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis |
| title_short | Deletion of PPARα in mouse brown adipocytes increases their De Novo Lipogenesis |
| title_sort | deletion of pparα in mouse brown adipocytes increases their de novo lipogenesis |
| topic | Peroxisome proliferator-activated receptor alpha Brown adipose tissue Inducible UCP1-CRE High fat diet-induced obesity β3-adrenergic stimulation Lipid metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S2212877825000912 |
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