Phospholipid methylation regulates muscle metabolic rate through Ca2+ transport efficiency.

Phospholipid methylation regulates muscle metabolic rate through Ca2+ transport efficiency.

Nature metabolism (2020-05-15)

Anthony R P Verkerke, Patrick J Ferrara, Chien-Te Lin, Jordan M Johnson, Terence E Ryan, J Alan Maschek, Hiroaki Eshima, Christopher W Paran, Brenton T Laing, Piyarat Siripoksup, Trevor S Tippetts, Edward J Wentzler, Hu Huang, Espen E Spangenburg, Jeffrey J Brault, Claudio J Villanueva, Scott A Summers, William L Holland, James E Cox, Dennis E Vance, P Darrell Neufer, Katsuhiko Funai

PMID32405618

ABSTRACT

The biophysical environment of membrane phospholipids affects structure, function, and stability of membrane-bound proteins.1,2 Obesity can disrupt membrane lipids, and in particular, alter the activity of sarco/endoplasmic reticulum (ER/SR) Ca2+-ATPase (SERCA) to affect cellular metabolism.3-5 Recent evidence suggests that transport efficiency (Ca2+ uptake / ATP hydrolysis) of skeletal muscle SERCA can be uncoupled to increase energy expenditure and protect mice from diet-induced obesity.6,7 In isolated SR vesicles, membrane phospholipid composition is known to modulate SERCA efficiency.8-11 Here we show that skeletal muscle SR phospholipids can be altered to decrease SERCA efficiency and increase whole-body metabolic rate. The absence of skeletal muscle phosphatidylethanolamine (PE) methyltransferase (PEMT) promotes an increase in skeletal muscle and whole-body metabolic rate to protect mice from diet-induced obesity. The elevation in metabolic rate is caused by a decrease in SERCA Ca2+-transport efficiency, whereas mitochondrial uncoupling is unaffected. Our findings support the hypothesis that skeletal muscle energy efficiency can be reduced to promote protection from obesity.

MATERIALI

N° Catalogo

Marchio

Descrizione del prodotto

N6876

Sigma-Aldrich

Blu nitrotetrazolo cloruro, ≥90.0% (HPLC)

RTHYMAG-30K

Millipore

Gruppo di microsfere magnetiche per tiroide di ratto MILLIPLEX^® - saggio endocrino multiplex, The analytes available for this multiplex kit are: TSH, T3, T4.