Effects of different exercise intensities on clusterin metabolism and its interference on insulin signaling in rodents

Abstract

Clusterin, or apolipoprotein J (Apo B) through its membrane receptor (LRP2) acts on insulin signaling pathway potentiating its effects on peripheral tissues (skeletal muscle, liver and adipose tissue) and also the hypothalamus. These findings have been described as physiological data, however as pilot data already brought all the insulin signaling pathway in liver clusterin knockouts mice liver and we found that when there is a deletion of clusterin in the liver the phosphorilation of key proteins responsible for insulin signlaing transduction is decreased, resulting in increased of insulin resistance in the liver. Therefore, from these results we initially suggest the liver as an important secretory organ of clusterin and also its important role in the insulin signaling (see pilot data). However, the expression of this protein in peripheral tissues and its mechanisms of action are not fully understood. It is known that physical exercise is able to regulate crucial proteins involved in insulin signaling and promotes metabolic improvements in diabetic animals and humans. However, its effects in the regulation of clusterin and hence glucose homeostasis have not been elucidated. Therefore, this research proposal aims to initially know the metabolism of clusterin throughout the day and evaluate the nutritional effect of the organism in clusterin secretion and also assess the circadian cycle of this apoprotein (secretion over 24hrs with analyzes in each 2 hours). Later, we will evaluate its role in insulin signaling in the liver of lean and obese animals subjected to different exercise protocols (moderate and heavy intensities) and trying to understand its mechanistic we will do a silencing of LRP2 in the liver and try to elucidate how occurs this cross-talk between clusterin and insulin pathways. (AU)