PPARγ signaling and metabolism: the good, the bad and the future
Maryam Ahmadian,Jae Myoung Suh,Nasun Hah,Christopher Liddle,Annette R. Atkins,Michael Downes,Ronald M. Evans +6 more
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TLDR
This review highlights key advances in understanding PPARγ signaling in energy homeostasis and metabolic disease and also provides new explanations for adverse events linked to TZD-based therapy.Abstract:
Thiazolidinediones (TZDs) are potent insulin sensitizers that act through the nuclear receptor peroxisome proliferator-activated receptor-γ (PPARγ) and are highly effective oral medications for type 2 diabetes. However, their unique benefits are shadowed by the risk for fluid retention, weight gain, bone loss and congestive heart failure. This raises the question as to whether it is possible to build a safer generation of PPARγ-specific drugs that evoke fewer side effects while preserving insulin-sensitizing potential. Recent studies that have supported the continuing physiologic and therapeutic relevance of the PPARγ pathway also provide opportunities to develop newer classes of molecules that reduce or eliminate adverse effects. This review highlights key advances in understanding PPARγ signaling in energy homeostasis and metabolic disease and also provides new explanations for adverse events linked to TZD-based therapy.read more
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Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal.
TL;DR: This review focuses on biochemical concepts of lipidPeroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting geneexpression and promoting cell death.
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What We Talk About When We Talk About Fat
TL;DR: New perspective is gained on the roles played by adipocyte in a variety of homeostatic processes and on the mechanisms used by adipocytes to communicate with other tissues and how these relationships are altered during metabolic disease and how they might be manipulated to restore metabolic health.
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Macrophages, Immunity, and Metabolic Disease
TL;DR: The pathophysiological link between macrophages, obesity, and insulin resistance is discussed, highlighting the dynamic immune cell regulation of adipose tissue inflammation and the new therapeutic targets that have emerged.
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Natural product agonists of peroxisome proliferator-activated receptor gamma (PPARγ): a review.
Limei Wang,Birgit Waltenberger,Eva-Maria Pferschy-Wenzig,Martina Blunder,Xin Liu,Clemens Malainer,Tina Blazevic,Stefan Schwaiger,Judith M. Rollinger,Elke H. Heiss,Daniela Schuster,Brigitte Kopp,Rudolf Bauer,Hermann Stuppner,Verena M. Dirsch,Atanas G. Atanasov +15 more
TL;DR: A significant research effort has recently been undertaken to explore the PPARγ-activating potential of a wide range of natural products originating from traditionally used medicinal plants or dietary sources.
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Regulation of metabolism by the innate immune system
TL;DR: The roles of innate immune cells involved in secreting inflammatory factors in the obese state, including proinflammatory adipose tissue macrophages and natural killer cells are reviewed.
References
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Charles F. Burant,Seamus Sreenan,Ken-Ichi Hirano,Tzu Ann C. Tai,Jeffrey J. Lohmiller,John N. Lukens,Nicholas O. Davidson,Susan R. Ross,Reed A. Graves +8 more
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TL;DR: This work has employed DNase I hypersensitive site analysis to investigate the genome‐wide changes in chromatin structure that accompany the binding of adipogenic transcription factors and demonstrates that C/EBPβ marks a large number of transcription factor ‘hotspots’ before induction of differentiation and chromatin remodelling and is required for their establishment.
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Compensation by Fibroblast Growth Factor 1 (FGF1) Does Not Account for the Mild Phenotypic Defects Observed in FGF2 Null Mice
TL;DR: The results suggest that the relatively mild defects in FGF2 knockout animals are not a consequence of compensation by FGF1 and suggest highly restricted roles for both factors under normal developmental and physiological conditions.
Journal ArticleDOI
Collecting duct-specific deletion of peroxisome proliferator-activated receptor γ blocks thiazolidinedione-induced fluid retention
Hui Zhang,Aihua Zhang,Aihua Zhang,Donald E. Kohan,Raoul D. Nelson,Frank J. Gonzalez,Tianxin Yang +6 more
TL;DR: A PPARgamma-dependent pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention is demonstrated.
Journal ArticleDOI
Cardiomyocyte expression of PPARγ leads to cardiac dysfunction in mice
Ni-Huiping Son,Tae-Sik Park,Haruyo Yamashita,Masayoshi Yokoyama,Lesley Ann Huggins,Kazue Okajima,Shunichi Homma,Matthias Szabolcs,Li-Shin Huang,Ira J. Goldberg +9 more
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