What is Metabolism?

Metabolism is the intricate set of chemical processes that occur within living organisms to maintain life. From breathing to digesting food, metabolism encompasses all the biochemical reactions that sustain cells and enable organisms to grow, reproduce, and respond to their environment. Understanding metabolism is crucial for comprehending energy balance, nutrient utilization, and overall health. Indirect calorimetry, a method used to measure metabolism, offers valuable insights into how organisms utilize energy.

Metabolic Processes

Metabolic pathways are sequences of chemical reactions that convert molecules from one form to another. Key metabolic pathways include glycolysis, the citric acid cycle (Krebs cycle), and oxidative phosphorylation. In glycolysis, glucose is broken down into pyruvate, generating ATP and NADH. The citric acid cycle completes the oxidation of glucose-derived pyruvate, producing more ATP and reducing equivalents. Oxidative phosphorylation, occurring in the mitochondria, utilizes the reducing equivalents to generate ATP through the electron transport chain.

Anabolism and Catabolism

Anabolism refers to the series of metabolic pathways that involve the synthesis of complex molecules from simpler ones. It requires energy input, typically in the form of adenosine triphosphate (ATP) and reducing equivalents such as nicotinamide adenine dinucleotide phosphate (NADPH). Anabolic processes are responsible for building and maintaining cellular structures, storing energy in the form of macromolecules, and facilitating growth and repair. Catabolism involves the breakdown of complex molecules into simpler ones, resulting in the release of energy. This energy is often captured in the form of ATP and NADH, which can be used to drive cellular processes. Catabolic pathways play a vital role in providing cells with the energy needed to carry out various metabolic activities.

Metabolic Phenotyping

Metabolic phenotyping is a powerful tool for assessing metabolic function by measuring gas exchange, including oxygen consumption and carbon dioxide production. This non-invasive method provides valuable insights into energy metabolism, substrate utilization, and overall metabolic health in living organisms. By analyzing respiratory gases, researchers can quantify metabolic rate, energy expenditure, and nutrient metabolism, facilitating the study of metabolic phenotypes in health and disease. Columbus Instruments' CLAMS (Comprehensive Laboratory Animal Monitoring System) is a system that integrates advanced sensing for metabolic phenotyping studies in research settings. CLAMS provides a comprehensive view of a subject’s metabolic profile, by having the ability to track subject activity, consumption, and body weight while accounting for environmental conditions.

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Indirect Calorimetry for Studying Metabolism

How it Works

Indirect calorimetry is a non-invasive method used to estimate metabolic rate by measuring the exchange of respiratory gases, primarily oxygen and carbon dioxide. This method relies on the principle that the body's consumption of oxygen and production of carbon dioxide correlate with energy expenditure. By analyzing the ratio of oxygen consumption (VO2) to carbon dioxide production (VCO2), indirect calorimetry provides valuable insights into metabolic processes.

Negative Ventilation

In indirect calorimetry systems, ventilation plays a crucial role in maintaining appropriate airflow within metabolic chambers or cages where subjects are housed during metabolic studies. Negative ventilation is an approach used to regulate airflow and ensure the accuracy of metabolic measurements. In a negative ventilation system, fresh air is drawn from the surrounding environment into the metabolic cage or chamber. This airflow circulates throughout the chamber, ensuring adequate ventilation and mixing of gases.

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Applications

Energy Metabolism

Indirect calorimetry is a pivotal method for studying energy metabolism in laboratory rodents, offering insights into resting metabolic rate (RMR), energy expenditure during activity, substrate utilization, thermogenesis, and metabolic flexibility. RMR measurements provide baseline information on energy requirements for essential physiological functions, while assessments of energy expenditure during activity elucidate how animals allocate energy resources across different behaviors. Indirect calorimetry also reveals the relative contribution of carbohydrates and fats to energy metabolism, aiding in understanding substrate utilization patterns. To better understand energy contribution, Clambake is a newly developed method to evaluate contributing factors to individual energy expenditure.

Clambake was developed by the Jon Brestoff Lab at Washington University in St. Louis to better understand energy expenditure. Through parameters outputted by the Comprehensive Lab Animal Monitoring System (CLAMS) on subject activity, consumption, and respiration exchange, Clambake can categorize energy expenditure between adaptive thermogenesis, thermic effect of food, activity-induced energy expenditure, and basal metabolic rate (BMR).

Cold Snap

Cold Snap events, characterized by sudden and significant drops in temperature, can have notable impacts on metabolic phenotyping studies. This can have profound effects on overall health and disease risk. Exposure to cold temperatures may influence metabolic parameters such as energy expenditure, glucose metabolism, and lipid metabolism, which are linked to the development of metabolic disorders such as obesity, diabetes, and cardiovascular disease. These events disrupt environmental conditions and physiological responses, influencing metabolic parameters. Studying cold snaps is important to analyze the body’s metabolic response to conserve energy. Understanding the relationship between environmental factors and metabolic health outcomes is valuable in researching seasonal change, hibernation, and homeostasis. CLAMS utilizes an environmental controller to simulate these temperature drops. By drying the sampled air of each chamber through a desiccant, chilling effects on humidity are reduced, and accurate metabolic responses can be more easily measured.

Nutrition and Obesity

Indirect calorimetry is widely employed in nutritional studies using laboratory rodents to investigate the metabolic effects of different diets, nutrient compositions, and feeding regimens. Researchers can assess energy balance, nutrient utilization, and metabolic responses to dietary interventions, such as calorie restriction, high-fat diets, or specific nutrient supplements. It contributes to our understanding of dietary influences on metabolic health and disease risk.

Pharmacology

Indirect calorimetry is valuable for assessing the metabolic effects of drugs and pharmacological compounds in laboratory rodents. Researchers can evaluate the impact of drug treatments on energy metabolism, thermogenesis, and substrate utilization, providing insights into drug mechanisms of action and potential metabolic side effects. It aids in drug discovery and the development of novel therapeutics for metabolic disorders and other health conditions.