Caloric Restriction Increases Parkin Recruitment in Hearts of Obese Insulin‐Resistant Rats

Abstract

Mitochondria provide energy to the cells, making the task of mitochondrial recycling highly important. Impairments in mitochondrial number and function can lead to dysregulation of cellular metabolism and disrupted capacity to maintain homeostasis. The Parkin gene codes for the protein, Parkin, which is a component of the Parkin/PINK1 pathway that helps regulate mitophagy. An impairment in the Parkin gene may also results in nonfunctional mitochondria, potentially leading to many diseases such as type two diabetes mellitus and cardiovascular disease. Recent studies suggest that Parkin expression is downregulated during insulin resistance. To address the hypothesis that insulin resistance downregulates Parkin in the heart, a piece of the left ventricle of the hearts of 4 groups of rats were extracted: (1) Long Evans Tokushima Otsuka (LETO), (2) Otsuka Long‐Evans Tokushima Fatty (OLETF), (3) LETO with caloric restriction, and (4) OLETF with caloric restriction. Extracted Parkin from the hearts of each group was measured by Western blot. Because Parkin expression is downregulated with insulin resistance, we anticipated lower levels of express in the insulin resistant, OLETF rats compared to LETO, and that caloric restriction would restore Parkin expression in the OLETF rats. Parkin protein expression was 71% lower in OLETF than LETO. While the 16% increase in expression in caloric restricted LETO group was not statistically significant, the expression increased nearly 7.5‐fold with caloric restriction in OLETF group compared to the ad lib OLETF group. The data suggest that the benefits of CR on CV function and health go beyond the potential benefits of mass loss (usually adiposity) but include cellular energetics and metabolism in the heart of insulin resistant rats.Support or Funding InformationThe STRIDE Fellowship is supported by the American Physiological Society and a grant from the National Heart, Lung and Blood Institute (NHLBI; 1 R25 HL115473‐01).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.