Functional characterization of human brown adipose tissue metabolism

Abstract

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

Loss of α-actinin-3 during human evolution provides superior cold resilience and muscle heat generation

“…Second, BAT constitutes a significant heat source in human infants. 43,46 We here show expression of Actn3 in BAT of adult mice following acute cold exposure. Although we could not detect any physiologically relevant Actn3 genotype-specific difference in BAT properties after acute cold exposure, our data do not exclude the possibility of an a-actinin-3-dependent effect on BAT thermogenesis in human infants.…”

“…43 Adult humans have little BAT (<5% of total fat mass 44 ) and it is difficult to assess its importance as a heat generator. 45,46 We therefore utilized the welldefined Actn3 KO mouse model to examine the impact of BAT activation as a mechanism for improved heat generation in a-actinin-3-deficient individuals. 4 Adult wild-type (WT) and Actn3 KO mice were kept in a cold (4 C) room for 5 h and core body temperature was measured at regular intervals using a rectal probe.…”

Beige Fat Maintenance; Toward a Sustained Metabolic Health

“…In humans, BAT was initially thought to exist only in the neck and shoulder of infants (23). However, later studies found active BAT in the paracervical and supraclavicular as well as in the anterior neck regions of adult humans (23)(24)(25)(26)(27).…”

Metabolic Improvement via Enhancing Thermogenic Fat-Mediated Non-shivering Thermogenesis: From Rodents to Humans

“…Increasing BAT mass and BAT activity could be potential mechanistic targets to induce an upregulation of BAT-mediated NST. BAT mass can be quantified using PET/CT ( 24 ). Specifically, 18 F-FDG positive adipose tissue with an SUV mean threshold ≥ 1.5 is considered BAT.…”

“…Using direct PET/CT scan with [ 15 O]O 2 and [ 15 O]H 2 O, it has been shown that a short-time mild cold exposure could cause a BAT-mediated oxygen consumption, which is as 0.1–0.6% of whole-body oxygen consumption in humans ( 30 – 33 ). Following a chronic cold exposure for 4 weeks, the contribution of BAT to whole-body oxygen consumption in humans further increases to 0.5–2.3% ( 24 , 34 ). However, in mice, their oxygen consumption is increased by 38–60% after a mild cold exposure ( 35 , 36 ).…”