Secreted Protein Acidic and Rich in Cysteine (SPARC)—Mediated Exercise Effects: Illustrative Molecular Pathways against Various Diseases

Abstract

The strong benefits of exercise, in addition to the development of both the therapeutic applications of physical activity and molecular biology tools, means that it has become very important to explore the underlying molecular patterns linking exercise and its induced phenotypic changes. Within this context, secreted protein acidic and rich in cysteine (SPARC) has been characterized as an exercise-induced protein that would mediate and induce some important effects of exercise. Herein, we suggest some underlying pathways to explain such SPARC-induced exercise-like effects. Such mechanistic mapping would not only allow us to understand the molecular processes of exercise and SPARC effects but would also highlight the potential to develop novel molecular therapies. These therapies would be based on mimicking the exercise benefits via either introducing SPARC or pharmacologically targeting the SPARC-related pathways to produce exercise-like effects. This is of a particular importance for those who do not have the ability to perform the required physical activity due to disabilities or diseases. The main objective of this work is to highlight selected potential therapeutic applications deriving from SPARC properties that have been reported in various publications.

Exploring exercise-driven exerkines: unraveling the regulation of metabolism and inflammation

“…Exerkines may alleviate the degree of inflammation in adipose tissue. SPARC is an exerkine that can induce the “browning” of WAT, converting it into metabolically active beige adipose tissue ( Ghanemi, Yoshioka & St-Amand, 2023 ). This transformation not only enhances lipid metabolism but also reduces inflammation through mechanisms like AMPK activation and downregulation of NF-κB signaling.…”

Obesity and Bone Mineral Density Protection Paradox in Chronic Kidney Disease: Secreted Protein Acidic and Rich in Cysteine as a Piece of the Puzzle?

“…The importance of highlighting such an obesity paradox derives from the fact that obesity represents the epidemic of our era, which is expected to continue increasing [71]. Finally, such mechanistic links can represent starting points towards developing therapies based on SPARC or on the molecular targeting of SPARCrelated pathways, as we have already suggested in diverse pathological contexts [72][73][74]. However, the gap is still large, as further experiments are required to investigate the hypothesis of obesity and the bone mineral density protection paradox involving SPARC as the link among other biomolecules.…”

Secreted Protein Acidic and Rich in Cysteine (SPARC) to Manage Coronavirus Disease-2019 (COVID-19) Pandemic and the Post-COVID-19 Health Crisis

“…According to the different pathways at the molecular and cellular levels linking SPARC to exercise, the resulting phenotypic changes will involve increasing myogenesis, the extracellular matrix and muscle glucose transporter expression, as well as decreasing adipogenesis and mitochondrial dysfunction [ 88 ]. The exploration of such pathways represents a starting point towards the development of novel therapeutic options for COVID-19 and its complications, which are urgently required, especially with the risk of the emergence of COVID-19 variants [ 89 , 90 , 91 , 92 ].…”