The accumulation of
lipids is a hallmark of human
clear cell renal cell carcinoma (ccRCC). Advanced ccRCC
tumors frequently show increased
lipid biosynthesis, but the regulation of lipid metabolism in early stage ccRCC
tumors has not been studied. Here, we performed combined transcriptomics and metabolomics on a previously characterized transgenic mouse model (TRAnsgenic
Cancer of the Kidney, TRACK) of early stage ccRCC. We found that in TRACK kidneys, HIF1α activation increases transcripts of
lipid receptors (Cd36, ACVRL1),
lipid storage genes (Hilpda and Fabp7), and intracellular levels of
essential fatty acids, including linoleic acid and
linolenic acid. Feeding the TRACK mice a high-fat diet enhances
lipid accumulation in the kidneys. These results show that HIF1α increases the uptake and storage of dietary
lipids in this early stage ccRCC model. By then analyzing early stage human ccRCC specimens, we found similar increases in CD36 transcripts and increases in linoleic and
linolenic acid relative to normal kidney samples. CD36
mRNA levels decreased, while FASN transcript levels increased with increasing ccRCC
tumor stage. These results suggest that an increase in the
lipid biosynthesis pathway in advanced ccRCC
tumors may compensate for a decreased capacity of these advanced ccRCCs to scavenge extracellular
lipids.