Transcriptional Landscaping Identifies a Beige Adipocyte Depot in the Newborn Mouse

Abstract

The present study sought to identify gene networks that are hallmarks of the developing inguinal subcutaneous adipose tissue (iWAT) and the interscapular brown adipose tissue (BAT) in the mouse. RNA profiling revealed that the iWAT of postnatal (P) day 6 mice expressed thermogenic and lipid catabolism transcripts, along with the abundance of transcripts associated with the beige adipogenesis program. This was an unexpected finding, as thermogenic BAT was believed to be the only site of nonshivering thermogenesis in the young mouse. However, the transcriptional landscape of BAT in P6 mice suggests that it is still undergoing differentiation and maturation, and that the iWAT temporally adopts thermogenic and lipolytic potential. Moreover, P6 iWAT and adult (P56) BAT were similar in their expression of immune gene networks, but P6 iWAT was unique in the abundant expression of antimicrobial proteins and virus entry factors, including a possible receptor for SARS-CoV-2. In summary, postnatal iWAT development is associated with a metabolic shift from thermogenesis and lipolysis towards fat storage. However, transcripts of beige-inducing signal pathways including β-adrenergic receptors and interleukin-4 signaling were underrepresented in young iWAT, suggesting that the signals for thermogenic fat differentiation may be different in early postnatal life and in adulthood.

Co-Evolution of Breast Milk Lipid Signaling and Thermogenic Adipose Tissue

“…To illustrate this, extrapolating the average daily fat intake of a breastfed infant to an adult would result in a non-physiological and a hardly-possible degree of fat consumption (Figure 1C) [12][13][14][15][16]. Moreover, newborns are capable of heat generation from lipids, a trait which declines by adulthood (Figure 1D), especially in obese individuals [17]. Restoring this ability of the adipocyte is considered today as a possible mechanism to reduce obesity [18].…”

“…The graph shows the weight of various food items which provide the daily fat intake of a breastfed infant (e.g., fat content of ~1250g chocolate is equivalent with the daily fat intake of a breastfed infant). (D) Histology of the subcutaneous adipose tissue after birth and in adulthood in the mouse [17]. Notably, the infant adipose tissue is rich in multilocular ("beige") adipocytes, contains PAS + glycogen granules, and expresses UCP1 protein.…”

“…In turn, the adult adipose tissue is built up from unilocular adipocytes, which do not store glycogen, nor express UCP1. Postnatal development of the subcutaneous adipose tissue is associated with a shift from lipid catabolism and thermogenesis to lipid storage and thermal insulation [17]. H&E, hematoxylin and eosin; PAS, periodic acid Schiff (staining glycogen); UCP1, uncoupling protein 1 (immunohistochemistry); lp, lipid droplet.…”

“…In humans, the adipose tissue primordia begins its expansion during the latter part of gestation, and maternal ketone bodies and glucose constitute the main lipogenic substrates for the fetus [1]. Approximately 70% of fetal glucose is converted into fat before birth [53,54], and primordial fat cells contain glycogen and neutral lipids [17,[55][56][57]. At birth, these energy reserves account for 1% and 16% of the body weight, respectively [2].…”

“…Brite adipose tissue was initially observed in the subcutaneous adipose tissue of rodents exposed to cold, and consists of both brown and white adipocytes. Beige adipocytes may develop without a cold stress, and are prevalent in some subcutaneous fat depots in the young [12,17] and in the adult mouse [102]. It is considered as a transitional form between white and brown adipose tissue, and its cells are often termed beige adipocytes [103].…”