Judith Simcox

As a postdoctoral fellow, I discovered that acylcarnitines are necessary for maintaining body temperature during cold exposure (Figure 1). Cold exposure triggers the release of free fatty acids from white adipocytes, which then go to the liver to where they are substrates for acylcarnitine production and secretion into circulation. These excess acylcarnitines are then taken up by the brown adipose tissue and used to fuel thermogenesis.

The Simcox laboratory will focus on two unanswered questions:

1) How are liver-produced lipids taken up & metabolized in brown adipocytes?
Brown adipocytes increase uptake of circulating lipids 12-fold during cold exposure, but the contribution of the various lipid species to thermogenesis remains elusive. We will use heavy isotope and fluorescently labeled lipids to identify lipid importers, assess metabolic pathways of uptake, and characterize the functional importance of various lipid species in isolated brown adipocytes (Figure 2).

2) How is hepatic lipid processing regulated in cold exposure?
Hepatic lipid processing is required for mice to maintain their body temperature in response to cold exposure. In untargeted lipidomic analysis we identified several hundred hepatic lipids that are altered in cold exposure and correlate with changes in circulating lipids. We will functionally characterize the role of these lipids in cold exposure and identify the transcriptional programs that regulate their production and clearance.