scholarly journals 3-Phosphoinositide-Dependent Protein Kinase-1 Activates the Peroxisome Proliferator-Activated Receptor-γ and Promotes Adipocyte Differentiation

2006 ◽  
Vol 20 (2) ◽  
pp. 268-278 ◽  
Author(s):  
Yuzhi Yin ◽  
Hongyan Yuan ◽  
Chenguang Wang ◽  
Nagarajan Pattabiraman ◽  
Mahadev Rao ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Adipocyte Differentiation ◽  
Peroxisome Proliferator ◽  
Dependent Protein Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Protein

scholarly journals Deletion of CaMKK2 from the Liver Lowers Blood Glucose and Improves Whole-Body Glucose Tolerance in the Mouse

2012 ◽  
Vol 26 (2) ◽  
pp. 281-291 ◽  
Author(s):  
Kristin A. Anderson ◽  
Fumin Lin ◽  
Thomas J. Ribar ◽  
Robert D. Stevens ◽  
Michael J. Muehlbauer ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Protein Kinase ◽  
Glucose Tolerance ◽  
Glucose Intolerance ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Dependent Protein Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Dependent Protein

Abstract Ca2+/calmodulin-dependent protein kinase kinase 2 (CaMKK2) is a member of the Ca2+/CaM-dependent protein kinase family that is expressed abundantly in brain. Previous work has revealed that CaMKK2 knockout (CaMKK2 KO) mice eat less due to a central nervous system -signaling defect and are protected from diet-induced obesity, glucose intolerance, and insulin resistance. However, here we show that pair feeding of wild-type mice to match food consumption of CAMKK2 mice slows weight gain but fails to protect from diet-induced glucose intolerance, suggesting that other alterations in CaMKK2 KO mice are responsible for their improved glucose metabolism. CaMKK2 is shown to be expressed in liver and acute, specific reduction of the kinase in the liver of high-fat diet-fed CaMKK2floxed mice results in lowered blood glucose and improved glucose tolerance. Primary hepatocytes isolated from CaMKK2 KO mice produce less glucose and have decreased mRNA encoding peroxisome proliferator-activated receptor γ coactivator 1-α and the gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, and these mRNA fail to respond specifically to the stimulatory effect of catecholamine in a cell-autonomous manner. The mechanism responsible for suppressed gene induction in CaMKK2 KO hepatocytes may involve diminished phosphorylation of histone deacetylase 5, an event necessary in some contexts for derepression of the peroxisome proliferator-activated receptor γ coactivator 1-α promoter. Hepatocytes from CaMKK2 KO mice also show increased rates of de novo lipogenesis and fat oxidation. The changes in fat metabolism observed correlate with steatotic liver and altered acyl carnitine metabolomic profiles in CaMKK2 KO mice. Collectively, these results are consistent with suppressed catecholamine-induced induction of gluconeogenic gene expression in CaMKK2 KO mice that leads to improved whole-body glucose homeostasis despite the presence of increased hepatic fat content.

scholarly journals A Cistanches Herba Fraction/β-Sitosterol Causes a Redox-Sensitive Induction of Mitochondrial Uncoupling and Activation of Adenosine Monophosphate-Dependent Protein Kinase/Peroxisome Proliferator-Activated ReceptorγCoactivator-1 in C2C12 Myotubes: A Possible Mechanism Underlying the Weight Reduction Effect

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Hoi Shan Wong ◽  
Jihang Chen ◽  
Pou Kuan Leong ◽  
Hoi Yan Leung ◽  
Wing Man Chan ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Weight Reduction ◽  
Uncoupling Protein ◽  
Adenosine Monophosphate ◽  
C2c12 Myotubes ◽  
Metabolic Enzyme ◽  
Peroxisome Proliferator ◽  
Mitochondrial Uncoupling ◽  
Dependent Protein Kinase ◽  
Dependent Protein

Previous studies have demonstrated that HCF1, a semipurified fraction of Cistanches Herba, causes weight reduction in normal diet- and high fat diet-fed mice. The weight reduction was associated with the induction of mitochondrial uncoupling and changes in metabolic enzyme activities in mouse skeletal muscle. To further investigate the biochemical mechanism underlying the HCF1-induced weight reduction, the effect of HCF1 and its active component,β-sitosterol (BSS), on C2C12 myotubes was examined. Incubation with HCF1/BSS caused a transient increase in mitochondrial membrane potential (MMP), possibly by fluidizing the mitochondrial inner membrane. The increase in MMP was paralleled to an increase in mitochondrial reactive oxygen species (ROS) production. Mitochondrial ROS, in turn, triggered a redox-sensitive induction of mitochondrial uncoupling by uncoupling protein 3 (UCP3). Biochemical analysis indicated that HCF1 was capable of activating an adenosine monophosphate-dependent protein kinase/peroxisome proliferator-activated receptorγcoactivator-1 pathway and thereby increased the expression of cytochrome c oxidase and UCP3. Animal studies using mitochondrial recoupler also confirmed the role of mitochondrial uncoupling in the HCF1-induced weight reduction. In conclusion, a HCF1/BSS causes the redox-sensitive induction of mitochondrial uncoupling and activation of AMPK/PGC-1 in C2C12 myotubes, with resultant reductions in body weight and adiposity by increased energy consumption.

scholarly journals Cyclic AMP (cAMP)-Mediated Stimulation of Adipocyte Differentiation Requires the Synergistic Action of Epac- and cAMP-Dependent Protein Kinase-Dependent Processes

2008 ◽  
Vol 28 (11) ◽  
pp. 3804-3816 ◽  
Author(s):  
Rasmus Koefoed Petersen ◽  
Lise Madsen ◽  
Lone Møller Pedersen ◽  
Philip Hallenborg ◽  
Hanne Hagland ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Cellular Response ◽  
Adipocyte Differentiation ◽  
Rho Kinase ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein ◽  
Dependent Processes ◽  
Stimulation Of

ABSTRACT Cyclic AMP (cAMP)-dependent processes are pivotal during the early stages of adipocyte differentiation. We show that exchange protein directly activated by cAMP (Epac), which functions as a guanine nucleotide exchange factor for the Ras-like GTPases Rap1 and Rap2, was required for cAMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of cAMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response.

scholarly journals Calreticulin inhibits commitment to adipocyte differentiation

2008 ◽  
Vol 182 (1) ◽  
pp. 103-116 ◽  
Author(s):  
Eva Szabo ◽  
Yuanyuan Qiu ◽  
Shairaz Baksh ◽  
Marek Michalak ◽  
Michal Opas
Keyword(s):  
Transcriptional Activation ◽  
Calcium Concentration ◽  
Adipocyte Differentiation ◽  
Embryonic Stem ◽  
Feedback Mechanism ◽  
Peroxisome Proliferator ◽  
Cellular Functions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Negative Feedback Mechanism ◽  
Dependent Protein

Calreticulin, an endoplasmic reticulum (ER) resident protein, affects many critical cellular functions, including protein folding and calcium homeostasis. Using embryonic stem cells and 3T3-L1 preadipocytes, we show that calreticulin modulates adipogenesis. We find that calreticulin-deficient cells show increased potency for adipogenesis when compared with wild-type or calreticulin-overexpressing cells. In the highly adipogenic crt−/− cells, the ER lumenal calcium concentration was reduced. Increasing the ER lumenal calcium concentration led to a decrease in adipogenesis. In calreticulin-deficient cells, the calmodulin–Ca2+/calmodulin-dependent protein kinase II (CaMKII) pathway was up-regulated, and inhibition of CaMKII reduced adipogenesis. Calreticulin inhibits adipogenesis via a negative feedback mechanism whereby the expression of calreticulin is initially up-regulated by peroxisome proliferator–activated receptor γ (PPARγ). This abundance of calreticulin subsequently negatively regulates the expression of PPARγ, lipoprotein lipase, CCAAT enhancer–binding protein α, and aP2. Thus, calreticulin appears to function as a Ca2+-dependent molecular switch that regulates commitment to adipocyte differentiation by preventing the expression and transcriptional activation of critical proadipogenic transcription factors.

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