scholarly journals Laforin, a dual specificity phosphatase involved in Lafora disease, regulates insulin response and whole-body energy balance in mice

2011 ◽  
Vol 20 (13) ◽  
pp. 2571-2584 ◽  
Author(s):  
Santiago Vernia ◽  
Miguel Heredia ◽  
Olga Criado ◽  
Santiago Rodriguez de Cordoba ◽  
Pablo M. Garcia-Roves ◽  
...  
2015 ◽  
Vol 55 (8) ◽  
pp. 988 ◽  
Author(s):  
A. F. Koontz ◽  
D. H. Kim ◽  
K. R. McLeod ◽  
J. L. Klotz ◽  
D. L. Harmon

This study was designed to examine alteration of ruminal kinetics, as well as N and energy balance during fescue toxicosis. Six ruminally cannulated Holstein steers (bodyweight (BW) = 217 ± 7 kg) were weight matched into pairs and pair fed throughout a crossover design experiment with a 2×2 factorial treatment structure. Factors were endophyte (infected, E+ vs. uninfected, E−) and feeding level (1100 (L) or 1800 (H) kJ/kG BW.75). During each period, after 8 days of feeding level adaptation, animals were ruminally dosed twice daily with ground fescue seed for the remainder of the period. One steer per pair was dosed with ground endophyte infected fescue seed (E+), the other with ground endophyte free fescue seed. In situ degradation of ground alfalfa was determined on Days 13–16. Total faecal and urinary collections were performed on Days 17–21, with animals placed into indirect calorimetry head-boxes during Days 20 and 21. Heat production (HP) was calculated using the Brower equation. Retained energy (RE) was calculated as intakeE – (faecalE + urinaryE + gaseousE + HP). Liquid and particulate passage rates were evaluated using Cr:EDTA and iADF respectively on Days 22 and 23. There was no difference (P > 0.9) in dry matter intake (DMI)/kg.75 between endophyte treatments, and DMI/kg.75 was different (P < 0.01) between H and L intake by design. Animals on H feeding had higher (P < 0.01) water, N and energy intakes. Energy and N excretion, as well as retained DE, ME, RE, and HP were higher (P < 0.03) for H versus L. There was no difference in retained N, DE, ME, or HP (P > 0.15) between endophyte treatments. Neither rate nor extent of in situ degradation was altered by intake level or endophyte treatment (P > 0.3). DM percentage and DM weight of rumen contents were increased (P < 0.01) by E+ dosing. Particulate passage increased (P = 0.0002) during H intake and decreased (P = 0.02) with E+ dosing. Ruminal liquid passage decreased (P < 0.03) with H feeding, while liquid flow rate tended to be reduced (P < 0.14) with E+ dosing. Total VFA concentration increased with both H feeding (P < 0.01) and E+ dosing (P < 0.0001). Despite these differences, the N and energy balance data indicate that the reductions in weight gain and productivity seen during fescue toxicosis are primarily due to reduced intake.


2013 ◽  
Vol 37 (7) ◽  
pp. 1033-1047 ◽  
Author(s):  
Mardi S. Byerly ◽  
Muhannad Al Salayta ◽  
Roy D. Swanson ◽  
Kiwook Kwon ◽  
Jonathan M. Peterson ◽  
...  

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e43962 ◽  
Author(s):  
Su-Hyoun Chon ◽  
John D. Douglass ◽  
Yin Xiu Zhou ◽  
Nashmia Malik ◽  
Joseph L. Dixon ◽  
...  

2011 ◽  
Vol 439 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Carlos Romá-Mateo ◽  
Maria del Carmen Solaz-Fuster ◽  
José Vicente Gimeno-Alcañiz ◽  
Vikas V. Dukhande ◽  
Jordi Donderis ◽  
...  

Lafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). In the present study, we demonstrate that laforin is a phosphoprotein, as indicated by two-dimensional electrophoresis, and we identify Ser25 as the residue involved in this modification. We also show that Ser25 is phosphorylated both in vitro and in vivo by AMPK. Lastly, we demonstrate that this residue plays a critical role for both the phosphatase activity and the ability of laforin to interact with itself and with previously established binding partners. The results of the present study suggest that phosphorylation of laforin-Ser25 by AMPK provides a mechanism to modulate the interaction between laforin and malin. Regulation of this complex is necessary to maintain normal glycogen metabolism. Importantly, Ser25 is mutated in some LD patients (S25P), and our results begin to elucidate the mechanism of disease in these patients.


2016 ◽  
Vol 12 (7) ◽  
pp. 421-432 ◽  
Author(s):  
Miguel López ◽  
Rubén Nogueiras ◽  
Manuel Tena-Sempere ◽  
Carlos Diéguez

2011 ◽  
Vol 12 (3) ◽  
pp. 127-140 ◽  
Author(s):  
Pablo Blanco Martínez de Morentin ◽  
Carmen R. González ◽  
Asisk K. Saha ◽  
Luís Martins ◽  
Carlos Diéguez ◽  
...  

2016 ◽  
Vol 104 (4) ◽  
pp. 398-411 ◽  
Author(s):  
Ismael González-García ◽  
Johan Fernø ◽  
Carlos Diéguez ◽  
Rubén Nogueiras ◽  
Miguel López

2011 ◽  
Vol 10 (1) ◽  
pp. 99 ◽  
Author(s):  
Mandy So ◽  
Mandeep P Gaidhu ◽  
Babak Maghdoori ◽  
Rolando B Ceddia

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e24040 ◽  
Author(s):  
Vikas V. Dukhande ◽  
Devin M. Rogers ◽  
Carlos Romá-Mateo ◽  
Jordi Donderis ◽  
Alberto Marina ◽  
...  

2013 ◽  
Vol 14 (4) ◽  
pp. 377-386 ◽  
Author(s):  
Min-Seon Kim ◽  
Wenying Quan ◽  
Myung-Shik Lee

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