Adipose tissue development during early life: novel insights into energy balance from small and large mammals

Abstract

Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.

Cord blood irisin at the extremes of fetal growth

“…In order to survive, the newborn must accelerate heat production via non-shivering thermogenesis in BAT, mediated by the expression of BAT tissuespecific UCP1 [29]. Thus, BAT is essential for ensuring effective postnatal adaptation and its growth during gestation is largely dependent on glucose supply from the mother to the fetus [29]. Therefore, it may be assumed that BAT depots are probably diminished in the IUGR fetus, secondary to both reduced glucose supply by the mother and irisin deficiency.…”

“…Since the discovery of BAT in adult humans, there has been a dramatic resurgence in research interest regarding its role in the defense against obesity and obesityassociated disorders [29][30][31]. Furthermore, a reduction in early BAT has been proposed to perpetuate through the life cycle, leading to suppression of energy expenditure and ultimately to obesity and impaired glucose homeostasis [32].…”

The Ontogeny of Brown Adipose Tissue

“…It is only well after birth that fat starts to appear around the stomach, and the visual and structural appearances of this fat are very different from those of depots present in the newborn, as illustrated in Figure 5. During early postnatal life, adipose tissue is usually the most rapid growing organ reflecting, in part, the substantial increase in available lipid derived from the mother's milk (120). This postnatal period of adipose tissue growth normally coincides with the time of peak milk production of the mother.…”

“…Intriguingly, it is highly abundant in the newborn infant (3) and is the depot that retains the highest amount of UCP1 mRNA in juvenile sheep (121). One thermogenic stimulus to this depot in children is feeding (110,120), suggestive of a direct involvement of BAT in dietary-induced thermogenesis (DIT).…”

Innate Hypothermia after Hypoxic Ischaemic Delivery

“…The normal adaptive response to cold air exposure after birth is associated with a rise in oxygen consumption [7] from the activation of brown adipose tissue [8,9]. Brown adipose tissue is rich in mitochondria which consume oxygen, generating metabolic heat through uncoupled aerobic respiration - non-shivering thermogenesis.…”