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Updated: Jul 10, 2026

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Measuring Skeletal Muscle Thermogenesis in Mice and Rats
Published on: July 27, 2022
Sarcolipin-SERCA uncoupling as a plausible heat source for sustaining fever
1Department of Kinesiology & Health Sciences, University of Waterloo, Waterloo, ON, Canada.
Frontiers in Physiology
|July 9, 2026
Summary
Skeletal muscle may be a key heat producer during fever, contributing to elevated body temperature. This study investigates non-shivering thermogenesis in muscle, potentially involving sarcolipin, to understand fever mechanisms.
Area of Science:
- Physiology
- Mammalian Thermoregulation
- Host Defense Mechanisms
Background:
- Fever elevates core body temperature and metabolic rate as a host defense mechanism.
- The primary tissue responsible for heat production during fever in adult mammals is not fully understood.
- Classical models emphasize brown adipose tissue (BAT) and shivering, but these have limitations in adult mammals.
Purpose of the Study:
- To investigate the role of skeletal muscle as a thermogenic tissue during fever.
- To differentiate between shivering and non-shivering thermogenesis in skeletal muscle during febrile responses.
- To explore the potential contribution of sarcolipin-mediated sarcoplasmic/endoplasmic reticulum Ca2+-ATPase (SERCA) uncoupling to fever.
Main Methods:
- Utilizing integrated calorimetry and electromyography to measure heat production and muscle activity.
- Employing tissue-specific perturbation approaches in translational models.
- Analyzing the expression of uncoupling proteins (UCPs) and sarcolipin (SLN) in response to inflammatory challenges.
Main Results:
- Febrile responses are observed in UCP1-deficient models, suggesting alternative thermogenic pathways.
- Disruption of UCP3 attenuates lipopolysaccharide (LPS)-induced hyperthermia, indicating a role for muscle in fever.
- Evidence suggests sarcolipin-mediated SERCA uncoupling as a potential mechanism for scalable heat production in skeletal muscle during inflammation.
Conclusions:
- Skeletal muscle is a significant contributor to febrile hypermetabolism, particularly during the maintenance phase of fever.
- Sarcolipin-mediated SERCA uncoupling presents a plausible mechanism for non-shivering thermogenesis in skeletal muscle during fever.
- Further research is needed to fully elucidate the contribution of skeletal muscle to fever and its underlying molecular mechanisms.
Related Concept Videos
Methods of reducing fever
The signs and symptoms of fever include hot and dry skin, flushed face, thirst, muscle aches, anorexia, headache, tachycardia, tachypnea, and fatigue. Elevated body temperature is reduced using two methods: pharmacological and nonpharmacological. Proper identification and treatment of the root cause of a fever is of utmost importance.
Pharmacological Methods of Reducing Fever:
Pharmacological Methods of Reducing Fever:
Increased Body Temperature
A body temperature above 38°C (100.4 °F) is known as fever or pyrexia, and a person with fever is termed 'febrile.' Typically, the hypothalamus, a part of the brain that acts as the body's thermostat, regulates body temperature through a thermoregulatory setpoint. It receives signals from cold and warm thermal receptors throughout the body and adjusts the body's temperature accordingly. Fever occurs when this hypothalamic setpoint is altered, usually in response to an infection or illness.
Decreased Body Temperature
A decreased body temperature can occur in patients with hypothermia and frostbite. Heat loss with extended cold exposure overpowers the body's ability to create heat, resulting in hypothermia. Core temperature readings help classify hypothermia. Mild hypothermia is temperatures between 32 °C (89.6 °F) and 35°C (95 °F) and is caused by impaired thermoregulation. Moderate hypothermia is temperatures between 28 C (82.4 °F) and 32 °C (89.6 °F) caused by sustained extreme cold exposure, and severe...
Homeostatic Imbalances in Body Temperature
Hyperthermia occurs when the body's temperature becomes unusually high, often due to heat exposure, intense physical activity, or certain illnesses. This condition can create a dangerous cycle where elevated body temperature increases the metabolic rate, generating more heat and potentially leading to organ failure and brain damage. A severe form of hyperthermia, called heat stroke, can raise body temperature to life-threatening levels. Fever, on the other hand, is a controlled form of...
Types of Fever
Fever can be triggered by several factors, including infections, nervous system disorders, certain cancers, blood diseases like leukemia, embolism, thrombosis, heatstroke, dehydration, surgical trauma, crushing injuries, and allergic reactions.
Here are the different types of fever:
Here are the different types of fever:
Body Temperature
The body's temperature, measured in degrees, is determined by the balance between heat production and dissipation to the surrounding environment. For instance, if exercising vigorously, the body will produce more heat, causing sweat and dissipating that heat. Despite extreme environmental conditions and physical exertion, the human temperature-control system maintains a constant core body temperature (the temperature of deep tissues, which are the tissues located beneath the skin and other...

