Substrate Utilization by Brown Adipose Tissue: What’s Hot and What’s Not?

• Published in: Frontiers in endocrinology (Lausanne) Vol. 11; p. 571659
• Main Authors: McNeill, Ben T., Morton, Nicholas M., Stimson, Roland H.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 25.09.2020
• Subjects: Adipose Tissue, Brown - metabolism; brown adipose tissue; Diabetes Mellitus, Type 2 - metabolism; Dyslipidemias - metabolism; Endocrinology; Energy Metabolism - physiology; Fatty Acids - metabolism; Glucose - metabolism; Humans; metabolism; obesity; Obesity - metabolism; positron emission tomography (PET); substrate; thermogenesis; Thermogenesis - physiology; Triglycerides - metabolism; glucose; lipids; thermogenesis; brown adipose tissue; positron emission tomography (PET); metabolism; obesity; substrate
• ISSN: 1664-2392; 1664-2392
• DOI: 10.3389/fendo.2020.571659

Our understanding of brown adipose tissue (BAT) function in humans has increased rapidly over the past 10 years. This is predominantly due to the development of powerful non-invasive imaging techniques such as positron emission tomography that can quantify BAT mass and function using metabolic tracers. Activation of BAT during cold-induced thermogenesis is an effective way to dissipate energy to generate heat and requires utilization of multiple energy substrates for optimal function. This has led to interest in the activation of BAT as a potential therapeutic target for type 2 diabetes, dyslipidaemia, and obesity. Here, we provide an overview of the current understanding of BAT substrate utilization in humans and highlight additional mechanisms found in rodents, where BAT more prominently contributes to energy expenditure. During thermogenesis, BAT demonstrates substantially increased glucose uptake which appears to be critical for BAT function. However, glucose is not fully oxidized, with a large proportion converted to lactate. The primary energy substrate for thermogenesis is fatty acids, released from brown adipocyte triglyceride stores. Active BAT also sequesters circulating lipids to sustain optimal thermogenesis. Recent evidence reveals that metabolic intermediates from the tricarboxylic acid cycle and glycolytic pathways also play a critical role in BAT function. Understanding the role of these metabolites in regulating thermogenesis and whole body substrate utilization may elucidate novel strategies for therapeutic BAT activation.