Abstract
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.
Highlights
The incidence of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease has increased globally over the last 50 years and interventions to curb obesity have been unsuccessful [1]
Recent work has highlighted that Brown adipose tissue (BAT) thermogenesis utilizes a more complex substrate range than merely glucose and fatty acids [12, 13]
Internal triglyceride stores and free fatty acids (FFA) are clearly defined as substrates with key roles in BAT thermogenesis, there is emerging evidence that other substrates contribute to BAT function
Summary
The incidence of obesity, type 2 diabetes mellitus (T2DM) and cardiovascular disease has increased globally over the last 50 years and interventions to curb obesity have been unsuccessful [1]. Substrate Utilization by BAT opportunity to address this imbalance as BAT activation increases energy expenditure through oxidation of energy substrates [4]. Recent work has highlighted that BAT thermogenesis utilizes a more complex substrate range than merely glucose and fatty acids [12, 13]. This complexity raises important questions regarding the mechanisms regulating BAT activation. In order to target BAT therapeutically, it is essential to understand the key pathways involved in thermogenesis In this mini-review, we will discuss our understanding of the role and importance of substrate utilization by human BAT and highlight the key remaining questions
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