Regulation of the PI3K/AKT Pathway and Fuel Utilization During Primate Torpor in the Gray Mouse Lemur, Microcebus murinus
10.1016/j.gpb.2015.03.006
- Author:
Tessier N SHANNON
1
;
Zhang JING
;
Biggar K KYLE
;
Wu CHENG-WEI
;
Pifferi FABIEN
;
Perret MARTINE
;
F Kenneth B Storey
Author Information
1. Institute of Biochemistry&Department of Biology
- Keywords:
Insulin signaling pathway;
PI3K/AKT;
mTOR;
GSK3;
Pyruvate dehydrogenase;
Metabolic rate depression
- From:
Genomics, Proteomics & Bioinformatics
2015;(2):91-102
- CountryChina
- Language:Chinese
-
Abstract:
Gray mouse lemurs (Microcebus murinus) from Madagascar present an excellent model for studies of torpor regulation in a primate species. In the present study, we analyzed the response of the insulin signaling pathway as well as controls on carbohydrate sparing in six different tissues of torpid versus aroused gray mouse lemurs. We found that the relative level of phospho-insulin receptor substrate (IRS-1) was significantly increased in muscle, whereas the level of phospho-insulin receptor (IR) was decreased in white adipose tissue (WAT) of torpid animals, both suggesting an inhibition of insulin/insulin-like growth factor-1 (IGF-1) signaling during torpor in these tissues. By contrast, the level of phospho-IR was increased in the liver. Interestingly, muscle,WAT, and liver occupy central roles in whole body homeostasis and each displays regulatory con-trols operating at the plasma membrane. Changes in other tissues included an increase in phospho-glycogen synthase kinase 3a (GSK3a) and decrease in phospho-ribosomal protein S6 (RPS6) in the heart, and a decrease in phospho-mammalian target of rapamycin (mTOR) in the kidney. Pyruvate dehydrogenase (PDH) that gates carbohydrate entry into mitochondria is inhibited via phosphory-lation by pyruvate dehydrogenase kinase (e.g., PDK4). In the skeletal muscle, the protein expres-sion of PDK4 and phosphorylated PDH at Ser 300 was increased, suggesting inhibition during torpor. In contrast, there were no changes in levels of PDH expression and phosphorylation in other tissues comparing torpid and aroused animals. Information gained from these studies high-light the molecular controls that help to regulate metabolic rate depression and balance energetics during primate torpor.
