How is thermogenesis measured?

How is thermogenesis measured?

Thermogenesis is measured in research settings primarily by indirect calorimetry, which determines energy expenditure from the rates of oxygen consumption (VO2) and carbon dioxide production (VCO2). This method calculates heat production indirectly via the Weir equation, using the respiratory quotient (RQ) to estimate substrate oxidation. In animal studies, indirect calorimetry is often combined with telemetry to monitor core body temperature and activity, providing a comprehensive assessment of energy balance. For tissue-specific thermogenesis, researchers use molecular markers such as uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) and beige adipocytes, measured by Western blotting, immunohistochemistry, or qPCR. In vitro models, including differentiated 3T3-L1 adipocytes, allow direct measurement of oxygen consumption rates using Seahorse extracellular flux analyzers. Human studies frequently employ ventilated hood systems or whole-room indirect calorimeters to assess diet-induced thermogenesis (DIT) and 24-hour energy expenditure under controlled conditions.

The work on thermogenesis centers on the sympathetic nervous system and its regulation of adipose tissue, particularly the beta-adrenergic signaling pathway that activates UCP1-mediated uncoupling in mitochondria.

Research Studies

FSTL1 and white adipose tissue browning in male mice

Follistatin-like 1 (FSTL1) is an adipokine that has been implicated in white adipose tissue (WAT) browning and thermogenesis. In male mice at ambient room temperature, overexpression of FSTL1 induced WAT browning, enhanced energy metabolism, and promoted glucose uptake. Mice with FSTL1 deficiency exhibited cold intolerance and were prone to obesity, while WAT-specific overexpression prevented metabolic dysfunction in diet-induced obesity. The study reported that FSTL1 cannot directly induce thermogenesis in adipocytes, suggesting an indirect mechanism involving sympathetic nerve crosstalk [2].

Sulforaphane and obesity-related metabolic dysfunction

Sulforaphane, an isothiocyanate derived from cruciferous vegetables, has been evaluated for its antioxidant, anti-inflammatory, and metabolic regulatory properties in the context of obesity. A narrative review critically assessed preclinical and clinical evidence, noting that sulforaphane may influence thermogenesis through mitochondrial dysfunction and oxidative stress pathways. However, the review highlighted limitations in current data, including variability in bioavailability and study designs [3].

GIPR agonism and antagonism in obesity pharmacotherapy

Glucagon-like peptide-1 receptor (GLP-1R) agonists have transformed obesity treatment, but their efficacy is limited by gastrointestinal side effects. The recent success of dual GLP-1R/GIP receptor agonists has renewed interest in GIPR-targeted therapies. This review discusses how GIPR agonism and antagonism represent opposite approaches to enhance weight loss and tolerability, with potential implications for thermogenesis regulation [4].

Systemic vibration therapy and thermogenesis in adults with obesity

A clinical trial evaluated the effects of systemic vibration therapy (SVT) on thermogenesis, cardiovascular parameters, endocrine-inflammatory markers, and physical-functional performance in adults with obesity. The study compared vertical and side-alternating vibrating platforms to a placebo group with a simulated sound but no vibration. The primary outcomes included changes in thermogenesis and physical performance, aiming to determine if vibration-induced mechanical stimuli could enhance energy expenditure [5].

Increasing caloric intake and diet-induced thermogenesis

Diet-induced thermogenesis (DIT) refers to the energy expended for digesting, absorbing, and metabolizing nutrients. A clinical trial investigated how different diets varying in protein, fat, carbohydrate, and total calories affect DIT and 24-hour energy expenditure in healthy adults. Participants resided in a clinic for 35 days and consumed eight different diets, with DIT measured using indirect calorimetry. The study aimed to elucidate the impact of macronutrient composition on thermogenesis [6].

Postprandial gut hormone responses and meal-induced thermogenesis in type 1 diabetes

A study compared postprandial responses to a test meal between subjects with type 1 diabetes and healthy controls, focusing on gut hormone levels, meal-induced thermogenesis, hunger, and satiety. The findings aimed to characterize differences in thermogenic responses and their relationship with glycemic control and appetite regulation [7].

Long-term weight loss effects on postprandial gut hormones and meal-induced thermogenesis

Another study examined long-term effects of weight loss on postprandial gut hormone secretion, meal-induced thermogenesis, and fasting metabolomic/lipidomic indices in surgically managed obese individuals compared to conservatively managed patients. The research sought to determine whether sustained weight loss alters thermogenic responses to meals and associated metabolic parameters [8].

Canagliflozin and adipocyte thermogenesis in 3T3-L1 cells

Canagliflozin, an SGLT2 inhibitor, exhibits anti-obesity effects in clinical practice, but its direct effects on adipocytes are not fully understood. In 3T3-L1 preadipocytes, canagliflozin promoted differentiation and enhanced lipid mobilization and thermogenesis through AMPK/autophagy-dependent pathways. This in vitro study provides mechanistic insights into how canagliflozin may modulate adipose tissue remodeling [9].

Forskolin and de novo beige adipogenesis in adipose stem cells

Forskolin, a cAMP activator, has been investigated for its ability to induce browning of white adipose tissue. A study using adipose stem cell-targeted local delivery of forskolin demonstrated de novo beige adipogenesis and adipose tissue browning in mice, offering a potential strategy to combat obesity with reduced off-target effects. The research focused on the differentiation of adipose-derived stromal/stem cells into beige adipocytes [10].

EGCG and BAT-independent thermogenic switch in subcutaneous adipose tissue

Epigallocatechin gallate (EGCG), a green tea catechin, has anti-obesity effects, but its impact on thermogenesis is not fully understood. A study found that EGCG triggered a BAT-independent thermogenic switch and remodeled the immune microenvironment in subcutaneous adipose tissue of mice. This suggests that EGCG may promote thermogenesis through mechanisms independent of classical brown fat activation [11].

Time-restricted feeding and HIIT effects on thermogenesis-related proteins in diabetic rats

A study evaluated the independent and combined effects of time-restricted feeding (TRF) and high-intensity interval training (HIIT) on thermogenesis-related protein abundance in white adipose tissue of diabetic rats. The results indicated that both interventions modulated proteins involved in thermogenesis, with potential implications for managing diabetes-related metabolic dysfunction [12].

Mazdutide in type 2 diabetes and nonalcoholic fatty liver disease

Mazdutide, a dual GLP-1R/glucagon receptor agonist, is being evaluated in a clinical trial for patients with type 2 diabetes mellitus and moderate-to-severe nonalcoholic fatty liver disease who were previously treated with semaglutide. The study aims to assess the efficacy and safety of switching to mazdutide, with secondary outcomes including changes in visceral fat and metabolic parameters that may relate to thermogenesis [1].

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Sources

• [1] Efficacy and Safety of Mazdutide in Patients With Type 2 Diabetes Mellitus and Moderate to Severe Nonalcoholic Fatty Liver Disease Previously Treated With Semaglutide
• [2] The Adipose-Sympathetic Nerve Crosstalk: FSTL1 as an Adipocyte-Derived Neurotrophic Factor for WAT Browning.
• [3] Sulforaphane and Broccoli-Derived Preparations in Obesity and Obesity-Related Metabolic Dysfunction: Mechanistic Insights, Preclinical Evidence, and Clinical Perspectives.
• [4] One receptor, two opposite approaches: efficacy and tolerability of GIPR agonism and antagonism in obesity pharmacotherapy.
• [5] Evaluation of the Effects of Systemic Vibration Therapy on Thermogenesis, Cardiovascular Parameters, Endocrine-inflammatory Markers, and Physical-functional Performance in Adults With Obesity.
• [6] The Effects of Increasing Caloric Intake on Diet-Induced Thermogenesis and 24h Energy Expenditure
• [7] Postprandial Gut Hormone Responses in Patients With Type 1 Diabetes Mellitus
• [8] Long Term Effects of Weight Loss on Post-prandial Gut Hormone Responses and Meal Induced Thermogenesis
• [9] AMPK/Autophagy-Dependent Pro-Adipogenic Effect Coupled With Enhanced Lipid Mobilization and Thermogenesis Underlies the Dual Action of Canagliflozin Against Obesity.
• [10] Adipose stem cell-targeted local delivery of forskolin induces de novo beige adipogenesis and adipose tissue browning to combat obesity.
• [11] EGCG combats obesity by triggering a BAT-independent thermogenic switch and remodeling the immune microenvironment in subcutaneous adipose tissue.
• [12] Effects of time-restricted feeding and high-intensity interval training on thermogenesis-related protein abundance in white adipose tissue of diabetic rats.