) Moreover, in the
Pemt−/− mice, plasma ALT (a marker for liver disease) was 10-fold
higher than in Pemt+/+ mice (71.2 units/l compared to 7.2 units/l).
Howdoes the lack of PEMT protect against obesity and insulin resistance
(type 2 diabetes)? One possible explanation that was considered
was that the lower level of hepatic PC in Pemt−/− mice (57 nmol/mg
protein) compared to 76 nmol/mg protein in Pemt+/+ mice might
lead to decreased obesity and increased insulin sensitivity.
Hence, we
determined if reduction of hepatic PC biosynthesis in liver-specific
CTα knockout (LCTαKO)mice also protected mice from obesity/insulin
resistance.
Thiswas a tenable hypothesis since the CT pathway accounts
for ~70% of hepatic PC biosynthesis. Hepatic CT activity was decreased
by 85% in LCTαKO mice compared to control mice [76].