Abstract

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the first month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confirmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life.

Highlights

  • Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)[1] and rapid fat growth

  • The maternal diet was modified to cause a shift in the fatty acid (FA) composition of maternal milk achieved through feeding the mothers a supplement of canola oil

  • To establish which fat depots could be classified as being brown and whether the rate of loss of brown adipocytes occurs at similar rates in those depots, we first examined the distribution of UCP1 by immunohistochemistry

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Summary

Introduction

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)[1] and rapid fat growth. We employed a machine learning (ML) algorithm followed by a weighted gene co-expression network analysis in order to find biologically meaningful associations in microarray datasets from the five major fat depots in sheep at 7 (when brown characteristics can dominate) and 28 (when brown fat is scarce) days of age. These measures enabled us to elucidate the distribution of cellular plasticity in response to a nutritional intervention between depots. The inclusion of canola in dairy ruminants feed has been reported to reduce the omega-6/omega-3 FA ratio and conjugated linoleic acid (CLA) in milk, both which are properties that have been found to up-regulate UCP genes in adipose tissue[9]

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