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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Mechanistic elucidation guided by covalent inhibitors for the development of anti-diabetic PPARγ ligands.
Hwan Bae,Jun Young Jang,Sun-Sil Choi,Jae-Jin Lee,Heejun Kim,Ala Jo,Kong-Joo Lee,Jang Hyun Choi,Se Won Suh,Seung Bum Park +9 more
TL;DR: The X-ray structure of PPARγ co-crystallized with SR1664 bound to the alternate binding site ofPPARγ is revealed and it is confirmed that this blocks the phosphorylation of Ser273.
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PEGylated Curcumin Derivative Attenuates Hepatic Steatosis via CREB/PPAR- γ /CD36 Pathway.
TL;DR: Findings suggest that Curc-mPEG454 reverses HFD-induced hepatic steatosis via the activation of CREB inhibition of the hepatic PPAR-γ/CD36 pathway, which may be an effective therapeutic for high-fat-diet-induced NAFLD.
Journal ArticleDOI
PPARγ deacetylation dissociates thiazolidinedione’s metabolic benefits from its adverse effects
Michael J Kraakman,Qiongming Liu,Jorge Postigo-Fernandez,Ruiping Ji,Ning Kon,Delfina Larrea,Maria Namwanje,Lihong Fan,Michelle Chan,Estela Area-Gomez,Wenxian Fu,Remi J. Creusot,Li Qiang +12 more
TL;DR: It is shown that targeted PPAR&ggr; mutations resulting in constitutive deacetylation increased energy expenditure and protected from visceral adiposity and diet-induced obesity by augmenting brown remodeling of white adipose tissues, and appears to fulfill the goal of dissociating the metabolic benefits of PPAR; activation from its adverse effects.
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Arid5a, an RNA-Binding Protein in Immune Regulation: RNA Stability, Inflammation, and Autoimmunity.
Kishan Kumar Nyati,Kishan Kumar Nyati,Mohammad Mahabub-Uz Zaman,Praveen Sharma,Tadamitsu Kishimoto +4 more
TL;DR: Current research on Arid5a is reviewed, which has focused attention towards the therapeutic potential of this factor in the putative treatment of inflammatory and autoimmune disorders, including experimental autoimmune encephalomyelitis and sepsis in mice.
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