Origins and early development of the concept that brown adipose tissue thermogenesis is linked to energy balance and obesity

Sep 14, 2016Biochimie

Early ideas about how heat production in brown fat relates to energy use and obesity

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Abstract

Brown adipose tissue (BAT) is associated with thermogenic activity, which is significantly reduced in obesity.

BAT was established as a key site for non-shivering thermogenesis in cold-acclimated rats.
The mechanism for heat production in BAT involves uncoupling oxidative phosphorylation through a pathway regulated by UCP1.
Obese ob/ob mice exhibit decreased thermogenic activity in BAT, suggesting a link between BAT function and obesity.
Diet-induced thermogenesis has been observed in rats when overfed, indicating activation of brown fat.
Indices of BAT activity, such as mitochondrial content and UCP1 levels, show reduced thermogenesis in obesity.
BAT activation has been linked to physiological states like lactation and fasting.

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Brown adipose tissue (BAT) was identified as a thermogenic organ in 1961, and in 1978 shown to be the major site of thermoregulatory non-shivering thermogenesis in rats acclimated to the cold. Investigations in the mid-late 1970s established the uncoupling of oxidative phosphorylation through a proton conductance pathway across the mitochondrial inner membrane as the mechanism for heat production in BAT, this being regulated by UCP1 which was first discovered as a 32,000 Mcold-inducible protein. These developments came when those concerned with nutritional energetics were proposing that thermogenesis is a significant factor in energy balance and the aetiology of obesity. A link with BAT was first demonstrated in obese ob/ob mice, which were shown to have decreased thermogenic activity in the tissue, and in rats exhibiting diet-induced thermogenesis (DIT) during overfeeding on a cafeteria diet where an activation of brown fat was evident. These pioneering observations led to extensive studies on BAT in different animal models of obesity, both genetic (particularly ob/ob and db/db mice, fa/fa rats) and experimentally-induced. In each case, indices of BAT activity and capacity (mitochondrial content, GDP binding, amount of UCP1) indicated that the tissue plays a role in DIT and that obesity is characterised by reduced thermogenesis. Links between BAT and whole-body energetics were also made in physiological situations such as lactation and fasting. Studies in the 1980s also provided clear evidence for the presence of BAT in adult humans, particularly through the detection of UCP1, and its activation in patients with phaeochromocytoma. Interest in BAT in energetics and obesity waned by the 1990s; the current major renewal of interest has undoubtedly been contingent on the pioneering developments that emerged some 40 years ago. r

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Origins and early development of the concept that brown adipose tissue thermogenesis is linked to energy balance and obesity

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