Both proliferation and lipogenesis of brown adipocytes contribute to postnatal brown adipose tissue growth in mice

Abstract

Brown adipose tissue (BAT) is the primary non-shivering thermogenesis organ in mammals, which plays essential roles in maintaining the body temperature of infants. Although the development of BAT during embryogenesis has been well addressed in rodents, how BAT grows after birth remains unknown. Using mouse interscapular BAT (iBAT) as an example, we studied the cellular and molecular mechanisms that regulate postnatal BAT growth. By analyzing the developmental dynamics of brown adipocytes (BAs), we found that BAs size enlargement partially accounts for iBAT growth. By investigating the BAs cell cycle activities, we confirmed the presence of proliferative BAs in the neonatal mice. Two weeks after birth, most of the BAs exit cell cycle, and the further expansion of the BAT was mainly due to lipogenesis-mediated BAs volume increase. Microscopy and fluorescence-activated cell sorting analyses suggest that most BAs are mononuclear and diploid. Based on the developmental dynamics of brown adipocytes, we propose that the murine iBAT has two different growth phases between birth and weaning: increase of BAs size and number in the first two weeks, and BAs size enlargement thereafter. In summary, our data demonstrate that both lipogenesis and proliferation of BAs contribute to postnatal iBAT growth in mice.

Strategies for Hypothermia Compensation in Altricial and Precocial Newborn Mammals and Their Monitoring by Infrared Thermography

“…In contrast, altricial species are born with little or no BAT, whose deposition increases when exposed to low temperatures during the first weeks of birth [ 75 ], and they are the primary source of metabolic heat [ 66 ]. In mice ( Mus musculus ), this happens at approximately two weeks of birth [ 76 ]. Analysis from days 0 to 120 after birth has reported that the interscapular BAT’s weight increases from approximately 10 mg to almost 60 mg, respectively, to be replaced later by WAT [ 77 ].…”

Global Adipose Tissue Remodeling During the First Month of Postnatal Life in Mice

“…Immediately at birth, pups have to be able to defend body temperature. After birth, brown adipose tissue still grows, mainly due to proliferation until postnatal day 14 and thereafter by storing more lipid ( 20 ), a transition suggestively synchronous to the observed whitening ( 14 ).…”

“…As plausible as this interpretation sounds, it fails to explain a simultaneous whitening of brown adipose tissues, if these two transitions are in fact causally connected. Both types of adipose tissue undergo postnatal developmental stages possibly accounting for the observed remodeling events: although functional at birth, BAT continues growth by an initial postnatal phase of rapid precursor proliferation and subsequent terminal differentiation including triglyceride loading ( 20 ). At the turning point, these events may be misinterpreted as whitening of existing brown adipocytes.…”

Brown Adipose Tissue: New Challenges for Prevention of Childhood Obesity. A Narrative Review

“…At 1 month, and later in life, buccal fat pad is instead made of WAT, characterized by larger adipocytes [ 65 ]. It remains unclear whether brown cells transform into white adipocytes or the WAT develops in the empty spaces once the BAT disappeared at the level of buccal fat pad, but it has been demonstrated that in mice BAT growth at the level of the inter scapular region in the first two weeks of life is due to both proliferation and lipogenesis, while later in infancy BAT grows mainly via lipogenesis [ 67 ]. While BAT develops in embryos, BeAT is induced from WAT during postnatal life [ 68 ].…”