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
Reads0
Chats0
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
Citations
More filters
Journal ArticleDOI
Adipocyte-specific Repression of PPAR-gamma by NCoR Contributes to Scleroderma Skin Fibrosis
Benjamin D. Korman,Roberta Goncalves Marangoni,Gabriel Lord,Jerrold M. Olefsky,Warren G. Tourtellotte,John Varga +5 more
TL;DR: The results implicate, for the first time, to the knowledge, deregulated NCoR/PPAR-γ pathways in SSc, and they support a role of adipocyte modulation of skin fibrosis.
Journal ArticleDOI
QSAR studies in the discovery of novel type-II diabetic therapies.
Areej Abuhammad,Mutasem O. Taha +1 more
TL;DR: This review focuses on drug targets that raised recent scientific interest and/or led to successful antidiabetic agents in the market and special emphasis has been made on studies that led to the identification of novel antidi diabetic scaffolds.
Journal ArticleDOI
The Myofibroblast: TGFβ-1, A Conductor which Plays a Key Role in Fibrosis by Regulating the Balance between PPARγ and the Canonical WNT Pathway
TL;DR: This review focuses on the contractile properties of myofibroblasts and on the TGF-β1 conductor which regulates the antagonism between PPARγ and the canonical WNT/β-catenin pathway.
Journal ArticleDOI
Bone-Derived Factors: A New Gateway to Regulate Glycemia.
TL;DR: This review proposes emerging perspectives for several bone-derived factors that may regulate glycemia through the activation or inhibition of bone remodeling or directly by regulating function of key organs such as pancreatic beta cell proliferation, insulin expression and secretion, storage and release of glucose from the liver, skeletal muscle contraction, and browning of the adipose tissue.
References
More filters
Journal ArticleDOI
Brown Adipose Tissue: Function and Physiological Significance
Barbara Cannon,Jan Nedergaard +1 more
TL;DR: The development of brown adipose tissue with its characteristic protein, uncoupling protein-1 (UCP1), was probably determinative for the evolutionary success of mammals, as its thermogenesis enhances neonatal survival and allows for active life even in cold surroundings.
Journal ArticleDOI
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Steven E. Nissen,Kathy Wolski +1 more
TL;DR: Patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes mellitus as well as the availability of outcome data for myocardial infarction and death from cardiovascular causes.
Journal ArticleDOI
An Antidiabetic Thiazolidinedione Is a High Affinity Ligand for Peroxisome Proliferator-activated Receptor γ (PPARγ)
Jürgen M. Lehmann,Linda B. Moore,Tracey Smith-Oliver,William O. Wilkison,Timothy M. Willson,Steven A. Kliewer +5 more
TL;DR: It is reported that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor γ (PPARγ), a member of the nuclear receptor superfamily recently shown to function in adipogenesis, and raised the intriguing possibility that PPARγ is a target for the therapeutic actions of this class of compounds.
Journal ArticleDOI
Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor.
TL;DR: The results suggest that the physiologic role of PPAR gamma 2 is to regulate development of the adipose lineage in response to endogenous lipid activators and that this factor may serve to link the process of adipocyte differentiation to systemic lipid metabolism.
Journal ArticleDOI
A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus–induced lung injury
Keiji Kuba,Yumiko Imai,Shuan Rao,Hong Gao,Feng Guo,Bin Guan,Yi Huan,Peng Yang,Yanli Zhang,Wei Deng,Linlin Bao,Binlin Zhang,Guang Liu,Zhong Wang,Mark C. Chappell,Yanxin Liu,Dexian Zheng,Andreas Leibbrandt,Teiji Wada,Arthur S. Slutsky,Depei Liu,Chuan Qin,Chengyu Jiang,Josef M. Penninger +23 more
TL;DR: A molecular explanation why SARS-CoV infections cause severe and often lethal lung failure and suggest a rational therapy for SARS and possibly other respiratory disease viruses is provided.
Related Papers (5)
Effect of Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes
Steven E. Nissen,Kathy Wolski +1 more