Beige Adipocytes Are a Distinct Type of Thermogenic Fat Cell in Mouse and Human

Abstract

Summary Brown fat defends against hypothermia and obesity through thermogenesis mediated by mitochondrial UCP1. Recent data suggest that there are two distinct types of brown fat: classical brown fat derived from a myf-5 cellular lineage and UCP1-positive cells that emerge in white fat from a non-myf-5 lineage. Here we report the cloning of “beige” cells from murine white fat depots. Beige cells resemble white fat cells in having extremely low basal expression of UCP1, but like classical brown fat, they respond to cyclic AMP stimulation with high UCP1 expression and respiration rates. Beige cells have a gene expression pattern distinct from either white or brown fat and are preferentially sensitive to the polypeptide hormone irisin. Finally, we show that deposits of brown fat previously observed in adult humans are composed of beige adipose cells. These data illustrate a new cell type with therapeutic potential in mouse and human.

Autophagy at the crossroads of catabolism and anabolism

“…BAT is composed of specialized multilocular adipocytes that have higher numbers of mitochondria than unilocular white adipocytes; the multilocular adipocytes are involved in dissipating energy as heat during cold-or diet-induced thermogenesis by promoting the β-oxidation of fatty acids 79 . Recently, a third type of adipocyte was identified; called beige or brite adipocytes, these are brown-like adipocytes that are found in WAT 80 . These beige cells mimic white fat cells in the basal state, but function in a similar manner to brown fat cells by upregulating the expression of thermogenic genes in response to thermogenic stimuli.…”

“…These beige cells mimic white fat cells in the basal state, but function in a similar manner to brown fat cells by upregulating the expression of thermogenic genes in response to thermogenic stimuli. Interestingly, beige cells possess a gene expression pattern distinct from either white or brown fat cells 80 .…”

Obesity and related consequences to ageing

“…Brown adipose tissue cells contain uncoupling protein 1 (UCP1), localized in the inner mitochondrial membrane where it dissipates the membrane potential generated by respiration fuelled by beta-oxidation of fatty acids to produce heat (Ricquier 2011) (reviewed by Cannon andNedergaard 2004 (Cannon andNedergaard 2004)). Additionally, brown adipocytes, also called brite or beige cells, can be induced in WAT depots upon cold stimulation (Cannon and Nedergaard 2004;Wu et al 2012).…”

“…Although novel findings have led to a consensus that metabolically active BAT is present in most children and many adult humans (Virtanen et al 2009;Cypess et al 2009), BAT deposits are often undetectable in people who live at thermoneutrality (23°C) (Seale and Lazar 2009). Recent studies suggest that adult human BAT presents the molecular characteristics of rodent beige cells rather than classical BAT (Wu et al 2012). Animal studies showed relatively stable Ucp1 mRNA levels in adult mice (Xue et al 2005;Chabowska-Kita et al 2015); nonetheless, BAT activity was shown to diminish in ageing (Seale and Lazar 2009).…”

Exercise regulation of adipose tissue

“…The amount of BAT in humans has been shown to vary with age, BMI, and gender, compounding the complexity of these studies. [11][12][13] Beige adipocytes are found interspersed within the WAT, [14][15][16] specifically the subcutaneous WAT (scWAT), in response to various stimuli including cold exposure and b-adrenergic stimulation. Beige cells come from a Myf5-lineage distinguishing them from BAT, but can, upon stimulation, express high levels of UCP1 and contribute to non-shivering thermogenesis.…”