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The Effects of Capsaicinoids on Skeletal Muscle Metabolism and Function: A Translational Study from Cells to Humans
Secondary Supervisor(s): Dr Mark Turner
University of Registration: Coventry University
BBSRC Research Themes: Integrated Understanding of Health (Ageing, Diet and Health)
Project Outline
Skeletal muscle mass and function are essential for overall health and quality of life, comprising 30-40% of body mass and playing key roles in metabolism, endocrine signalling, and health maintenance (PMID:26791164Link opens in a new window). This is particularly important in aging populations, as the loss of muscle mass, known as sarcopenia, is associated with increased disability and mortality (PMID:38086772Link opens in a new window). Furthermore, several clinical conditions can lead to a reduction in skeletal muscle mass and function, which may result in diminished functional capacity and worsened disease prognosis (PMID: 37596181Link opens in a new window).
In efforts to enhance muscle mass and function, bioactive substances such as capsaicin, the primary capsaicinoid found in chilli peppers, have attracted significant attention. Capsaicin is readily absorbed upon ingestion and binds to the TRPV1 receptor, which is widely expressed in skeletal muscle, adipose tissue, and the central nervous system. It has been shown to boost energy expenditure and fat oxidation and improving physical performance in both animal models and humans (PMID:33383571Link opens in a new window). A pilot study from our research group found that acute capsaicin treatment in isolated skeletal muscles from adult rats led to an increase in power output, using the work loop model (Figure 1). There is a need to further investigate this, for example, by testing different protocols of electrostimulation, varying doses, and using aged mice.
Figure 1: The effects of capsaicin on the work loop power of isolated mouse soleus (A) and EDL (B) muscles * P<0.05 vs control (unpublished data).
Although studies have investigated capsaicin's influence on performance and body composition, its direct effects and underlying mechanisms on skeletal muscle mass and function remain poorly understood. This highlights the need for further research to fully grasp its therapeutic potential, especially in conditions where skeletal muscle structure and function are impaired, such as ageing.
Aim
Using a translational approach with in vitro, animal, and human models, this project aims to investigate the therapeutic potential of capsainoids on skeletal muscle metabolism and function, as well as their anti-atrophic potential.
Objective 1: To investigate the effects of capsaicin on skeletal muscle metabolism using an in vitro approach, under both basal and atrophic (induced by dexamethasone treatment) conditions.
Objective 2: To determine whether capsaicin can act directly on skeletal muscle by stimulating contractility (i.e., force and power output) in a work loop model using isolated muscle from mice.
Objective 3: To investigate the effects of acute and chronic capsiate supplementation on muscle function and functional in older adults.
Methods
The project will adopt a translational approach to determine the impact of capsaicin on skeletal muscle structure and function. Initially, cells will be treated with capsaicin under basal conditions, alongside co-treatment with dexamethasone. By employing molecular biology and histology techniques (e.g., PCR, immunoblotting, immunohistochemistry), the activation of TRPV1 will be examined for its effects on muscle protein synthesis and degradation pathways, as well as morphological changes, to evaluate its effects on normal and atrophic conditions.
Subsequently, the direct effects of capsaicin on skeletal muscle contractility will be investigated using isolated mouse muscles, applying the work-loop model.
Finally, older adults of both sexes will be supplemented with a capsaicin analogue (capsiate), and its acute and chronic effects on muscle function and overall functional capacity will be measured through isokinetic dynamometry and the Senior Fitness Test, respectively.
Using this translational approach, the project will generate a holistic and mechanistic understanding of the effects of capsaicinoids (and potentially other TRPV1 agonists) on muscle function, as well as their potential use in promoting skeletal muscle health.
