# A Single Intraperitoneal Secreted Protein Acidic and Rich in Cysteine Injection in Mice Is Towards an Exercise-like Phenotype

## TL;DR

Injecting SPARC in mice mimics some benefits of exercise, like improved metabolism and muscle development, potentially offering therapy for those unable to exercise.

## Contribution

This study demonstrates acute metabolic and muscle-related benefits of a single SPARC injection in mice.

## Key findings

- SPARC injection improves glucose metabolism and mitochondrial biogenesis in mice muscles.
- SPARC reduces muscle protein degradation and promotes myogenesis and extracellular matrix remodeling.
- No significant changes in glycemia were observed following SPARC injection.

## Abstract

Many individuals with health problems or conditions (disabilities, aging, etc.) are not able to perform the physical activity they need as therapy. In this context, the molecule SPARC, which is produced by muscles during exercise, has been pointed out by previous studies as producing/mediating the effects of exercise (such as metabolic benefits). In this study, we injected SPARC into mice and found that it improves the metabolic functions in the muscles (mainly glucose and proteins). These results highlight SPARC as a potential therapeutic agent that would produce exercise-like effects, therefore, providing options for individuals who need exercise benefits but are unable to perform the required physical activity.

Secreted protein acidic and rich in cysteine (SPARC) is a protein widely expressed in various tissues. The metabolic and functional exploration of SPARC indicated it as a mediator of the exercise-induced effects. Furthermore, SPARC overexpression mimics exercise effects (including anti-aging phenotype), whereas its knockout both reduces the exercise-induced phenotype and increases aging. Each of these previous studies has been carried out for weeks and, therefore, indicates chronic effects of SPARC. To complete the puzzle, there is a need to explore the acute effects of SPARC. Thus, this study reports results of selected molecular and metabolic explorations of mice following a single injection of SPARC. Following both a validation of the Western blot as a detection method of SPARC in the serum and the optimization of the post-injection sacrifice time, mice (male and female) were injected with either SPARC or saline and sacrificed after 4 h. Body weight, selected tissues weights, and glycemia were measured. Muscle (tibialis anterior)—that was also harvested after the sacrifice and frozen—was used to measure the expression of selected proteins related to metabolism, protein hemostasis, and muscle development. Briefly, the results indicate a protein expression pattern towards improved glucose metabolism, oxidative phosphorylation, mitochondrial biogenesis, extracellular matrix remodeling, myogenesis, and protein synthesis. On the other hand, the expression of other proteins is towards decreased muscle protein degradation. There were no significant effects of SPARC injection on glycemia. These findings represent an important step towards developing a pharmacology based on injecting SPARC to achieve therapeutic effects that basically mimic exercise benefits, including anti-aging, metabolic enhancement, and muscle development. This is of particular importance for individuals who are unable to perform the required physical activity due to physical disabilities, aging, or hospitalization.