Alagal, Reham
(2018)
Nutritional programming of brown adipose tissue.
PhD thesis, University of Nottingham.
Abstract
Maintenance of functional brown adipose tissue (BAT) beyond the newborn period, through its role in expending energy in thermogenesis, provides a potential target to prevent childhood obesity. As the body’s fat distribution can be programmed by nutrition in early life, this study investigated whether modifying the maternal diet in the immediate newborn period increases the thermogenic potential of major brown fat depots. In humans and sheep, UCP1 decreases after birth, thus, BAT gradually transitions to be white adipose tissue (WAT). Three major adipose tissue depots in sheep (sternal, perirenal and epicardial) were studied which are all populated with brown adipocytes in early postnatal life, and then undergo a transition to WAT by the end of first month of life. Heat production in BAT is mediated by uncoupling protein (UCP)1 and fatty acids have the potential to increase the amount of UCP1. The aim of this thesis was, therefore, to determine whether maternal fatty acid supplementation with a readily available short-chain fatty acid (i.e. canola or sunflower oil) modifies milk fatty acid profile and thus the development of adipose tissue in the offspring.
Ewes, that each reared twin lambs, were fed a control diet or one supplemented with either 3% canola or sunflower oil from the day of delivery throughout lactation. Milk samples, ewe and lamb weights were taken at 7 and 28 days and offspring underwent tissue and blood sampling at either 7 or 28 days of age. The mRNA expression of regulatory genes associated with thermogenesis and fatty acid metabolism was measured. The abundance of UCP1 and other mitochondrial proteins was determined by immunohistochemistry and immunoblotting. Finally, microarray datasets were subjected to multi-region bioinformatics analysis in order to obtain biologically meaningful information about the examined adipose tissue depots.
Supplementation of the maternal diet with canola oil, and to lesser extent, sunflower oil, resulted in decreased medium-chain saturated fatty acids and increased monounsaturated fatty acids content of milk. Omega-6 polyunsaturated fatty acids was also increased in milk of ewes that received the sunflower oil supplement.
Although maternal fatty acid supplementation did not alter the mRNA expression of UCP1 in suckling lambs, tissue morphology (histology and microscopy) and protein abundance showed an increased UCP1 in adipose tissue located in the perirenal at 28 days of age compared with controls, suggesting canola oil delayed the rate of BAT loss. Microarray analysis indicate that each depot exhibited a distinct profile of gene expression and contained a small number of unique modules of co-expressed genes associated with distinct biological processes. Compared to other adipose tissue depots, perirenal showed a greater capability to respond to changes in the maternal diet. It was the most responsive adipose depot to maternal supplementation with canola oil causing an increase in the expression of some genes associated with the modulation of thermogenesis in BAT. With regards to genes involved in fatty acid metabolism, the epicardial depot appeared to be the primary site of unsaturated fatty acid synthesis in the first week of age, whilst this was dominant in the perirenal depot by day 28 of age when BAT is mostly converted into WAT.
In conclusion, manipulating the fatty acid profile of milk ingested by the newborn may delay, or even prevent, UCP1 loss in early life. In addition, the recognition of the different characteristics of adipose tissue depots in early life expands the current understanding of adipose tissue development and the variations of their response to dietary intervention.
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