P G Blanchard1, V Turcotte1, M Côté1, Y Gélinas1, S Nilsson2, G Olivecrona2, Y Deshaies1, W T Festuccia3. 1. Department of Medicine, Faculty of Medicine, Quebec Heart and Lung Institute, Laval University, Quebec, QC, Canada. 2. Department of Medical Biosciences/Physiological Chemistry, Umeå University, Umeå, Sweden. 3. Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Abstract
AIM: Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood. METHODS: We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg(-1) day(-1) , 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding. RESULTS: Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF. CONCLUSIONS: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.
AIM: Peroxisome proliferator-activated receptor (PPAR) γ activation is associated with preferential lipoprotein lipase (LPL)-mediated fatty acid storage in peripheral subcutaneous fat depots. How PPARγ agonism acts upon the multi-level modulation of depot-specific lipid storage remains incompletely understood. METHODS: We evaluated herein triglyceride-derived lipid incorporation into adipose tissue depots, LPL mass and activity, mRNA levels and content of proteins involved in the modulation of LPL activity and fatty acid transport, and the expression/activity of enzymes defining adipose tissue lipogenic potential in rats treated with the PPARγ ligand rosiglitazone (30 mg kg(-1) day(-1) , 23 days) after either a 10-h fasting period or a 17-h fast followed by 6 h of ad libitum refeeding. RESULTS:Rosiglitazone stimulated lipid accretion in subcutaneous fat (SF) ~twofold and significantly reduced that of visceral fat (VF) to nearly half. PPARγ activation selectively increased LPL mass, activity and the expression of its chaperone LMF1 in SF. In VF, rosiglitazone had no effect on LPL activity and downregulated the mRNA levels of the transendothelial transporter GPIHBP1. Overexpression of lipid uptake and fatty acid transport proteins (FAT/CD36, FATP1 and FABP4) and stimulation of lipogenic enzyme activities (GPAT, AGPAT and DGAT) upon rosiglitazone treatment were of higher magnitude in SF. CONCLUSIONS: Together these findings demonstrate that the depot-specific transcriptional control of LPL induced by PPARγ activation extends to its key interacting proteins and post-translational modulators to favour subcutaneous lipid storage.
Authors: Maynara L Andrade; Gustavo R Gilio; Luiz A Perandini; Albert S Peixoto; Mayara F Moreno; Érique Castro; Tiago E Oliveira; Thayna S Vieira; Milene Ortiz-Silva; Caroline A Thomazelli; Adriano B Chaves-Filho; Thiago Belchior; Patricia Chimin; Juliana Magdalon; Rachael Ivison; Deepti Pant; Linus Tsai; Marcos Y Yoshinaga; Sayuri Miyamoto; William T Festuccia Journal: Biochim Biophys Acta Mol Cell Biol Lipids Date: 2021-05-15 Impact factor: 5.228
Authors: Laura J den Hartigh; Shari Wang; Leela Goodspeed; Tomasz Wietecha; Barbara Houston; Mohamed Omer; Kayoko Ogimoto; Savitha Subramanian; G A Nagana Gowda; Kevin D O'Brien; Karl J Kaiyala; Gregory J Morton; Alan Chait Journal: PLoS One Date: 2017-02-28 Impact factor: 3.240