Hibernation increases cholesterol and apolipoprotein A‐I levels in ground squirrels

Abstract

Studies in two ground squirrel species suggest expression of ApoA‐I increases in gut and liver during hibernation. Since ApoA‐I is the major lipoprotein in HDL particles, we hypothesized that hibernation alters cholesterol metabolism. To test this idea we measured cholesterol and lipoprotein levels, and changes in expression of genes that regulate their metabolism in summer (SUM) and hibernating (HIB) 13‐lined ground squirrels. Plasma cholesterol was ~2‐fold greater in HIB squirrels during torpor (T) (474.6 ± 44.8 mg/dl) and interbout arousal (IBA) (436.1 ± 56.2 mg/dl) than in SUM (219.1 ± 12.8 mg/dl, P<0.01); VLDL‐, LDL‐, and HDL‐cholesterol showed the same trend. ApoA‐I mRNA levels in liver and gut, and protein levels in plasma, liver and gut were greater in HIB (P<0.05 for all). Liver mRNA levels of ApoB, LXR, SREBP2 and the rate limiting enzyme in cholesterol synthesis (HMGR) were similar in SUM and HIB, but SREBP1c expression was lower in T compared with SUM and IBA (P<0.001). Protein expression of CYP7A1 (bile acid synthesis) was lower in HIB ((P<0.05). ABCA1 mRNA levels rose 13‐fold in gut of HIB, suggesting altered cholesterol processing in gut during hibernation. These results confirm significant seasonal changes in cholesterol and lipoprotein dynamics in ground squirrels. Understanding their causes and functional significance will shed light on adaptations to the lipid‐centric metabolism of hibernation.