Grant: Master's Award: Canada Graduate Scholarships

Maternal high-saturated fat diet (mHFD) consumption during gestation and lactation is associated with chronic proinflammation and metabolic dysfunction in offspring. Metabolic issues present as an accumulation of white adipose tissue (energy storage) and a lower volume of brown adipose tissue (energy expenditure). These variations in adipose tissue are due to impaired uncoupling proteins (UCP) function. UCPs aid in energy homeostasis and can reduce white adipose tissue accumulation and proinflammation in the central nervous system (CNS). Prolonged breastfeeding attenuates mHFD-induced metabolic problems by promoting UCP1 function. Although, what component(s) of breastmilk confer these effects and how are unknown. A component found in breast milk; milk-derived extracellular vesicles (MEV) are able to reduce proinflammation. I hypothesize that increased MEV transfer, and prolonged breastfeeding will attenuate metabolic dysfunction in offspring with perinatal mHFD exposure. A rescue effect during postnatal development. The methods are split into in vivo and in vitro streams. For the in vivo work, adult female rats will be fed a high-fat diet or a control diet for 4 weeks before mating until pups are weaned. Pups will be supplemented with MEVs twice daily until culled at postnatal day (PND) 21 (standard lactation period) or PND 28 (extended lactation period), and CNS and endocrine tissues collected. For the in vitro work, UCP transcripts will be silenced using siRNA before proinflammatory priming of microglia cells. After priming, microglia will be treated with MEVs and harvested. Transcript and protein abundance of UCPs will be assessed in both approaches. This study aims to understand the role of UCPs in the CNS and the pro-survival role of milk during early development.