Comprehensive Analysis of the Characteristics and Differences in Adult and Newborn Brown Adipose Tissue (BAT): Newborn BAT Is a More Active/Dynamic BAT

Abstract

Brown adipose tissue (BAT) plays an essential role in maintaining body temperature and in treating obesity and diabetes. The adult BAT (aBAT) and neonatal BAT (neBAT) vary greatly in capacity, but the characteristics and differences between them on the molecular level, as well as the related features of BAT as it develops post-delivery, have not yet been fully determined. In this study, we examined the morphological features of aBAT and neBAT of mice by using hematoxylin-eosin (H&E) staining, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). We found that neBAT contains a smaller number and size of lipid droplets, as well as more abundant mitochondria, compared with aBAT. The dynamic morphological changes revealed that the number and size of lipid droplets increase, but the number of mitochondria gradually decrease during the post-delivery development, which consisted of some differences in RNA or protein expression levels, such as gradually decreased uncoupling protein 1 (UCP1) expression levels and mitochondrial genes, such as mitochondrial transcription factor A (Tfam). The adipocyte differentiation-related genes, such as transcription factor CCAAT enhancer-binding protein β (CEBPβ), were also continuously upregulated. Additionally, the different features of aBAT and neBAT were analyzed from the global transcription (RNA-Seq) level, which included messenger RNA (mRNA), microRNA, long non-coding RNA (lncRNA), circRNA, and DNA methylation, as well as proteins (proteomics). Differentially methylated region (DMR) analysis identified 383 hyper- and 503 hypo-methylated genes, as well as 1221 new circRNA in ne-BAT and 1991 new circRNA in a-BAT, with significantly higher expression of circRNA in aBAT compared with neBAT. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that mitochondrial activity, protein synthesis, and cell life activity levels were higher in neBAT, and pathways related to ribosomes, spliceosomes, and metabolism were significantly activated in neBAT compared to aBAT. Collectively, this study describes the dynamic changes occurring throughout post-delivery development from the morphological, molecular and omics perspectives. Our study provides information that may be utilized in improving BAT functional activity through gene regulation and/or epigenetic regulation.

Is Upregulation of Sarcolipin Beneficial or Detrimental to Muscle Function?

“…We found that gradual cold adaptation of neonatal mice prevents programmed developmental downregulation of SLN expression in adult quadriceps and gastrocnemius, glycolytic muscles ( Pant et al, 2015a ). Neonatal mice have significant amounts of BAT with very high UCP1 expression ( Cannon and Nedergaard, 2004 ; Harris et al, 2020 ; Liu et al, 2020 ) and, therefore, it can be argued that the thermogenic demand of neonatal mice is met by BAT based NST. The finding that UCP1 −/− neonates are able to survive at 22°C (below thermoneutrality of 28°C) and can be gradually cold adapted to 4°C suggests the existence of additional NST components ( Enerback et al, 1997 ).…”

Uncovering the Role of Glycogen in Brown Adipose Tissue

“…Is the same process repeated after the first exposure to cold at birth? The number and size of LDs increase during postnatal development in BAT (38) and the presence of glycogen has been described in the BAT of neonates (26,27). We can hypothesize that after the first cold exposure at birth, glycogen accumulates and is involved in the replenishment of LD in BAT.…”

Long non-coding RNAs in regulation of adipogenesis and adipose tissue function

“…A recent analysis compared adult and newborn BAT in mice. Several morphological and molecular differences were identified, including lncRNA expression ( Liu et al, 2020 ). For example, neonatal BAT—which seems to be more physiologically plastic and active compared to adult BAT—expresses NONMMUG024827 lncRNA.…”