Figure 5.

Increasing PGC-1α expression in the liver down-regulates endogenous hepatic XBP1s activity. (A–E) Eight week-old lean male mice were infected with Ad-LacZ (n = 4) or Ad-PGC-1α (1.2 × 10⁸ PFU/g, n = 4) via tail-vein injection; 5 days later, the mice were fasted for 24 h, then re-fed for 1 h. (A) PGC-1α mRNA (Ppargc1a) levels and (B) Xbp1s mRNA levels in the liver determined by qPCR. (C) Levels of endogenous XBP1s and tubulin protein in total liver extracts, and levels of nuclear XBP1s, flag-PGC-1α, and lamin A/C protein levels in nuclear extracts from the liver. (D, E) Quantitation of XBP1s protein levels in C. (D) XBP1s protein amounts in total liver lysates normalized with tubulin and (E) XBP1s protein amounts in the nuclear fraction normalized with Lamin A/C. (F–H) Eight week-old lean male mice were infected with Ad-LacZ or Ad-XBP1s (4 × 10⁷ PFU/g) via tail-vein injection. 5 days later, 4 h-fasted mice received either saline or glucagon (500 μg/kg) by intraperitoneal injection. The liver was collected 2 h after the treatment. (F) Xbp1s mRNA levels in the liver (n = 5 for each). (G) Levels of XBP1s, PGC-1α, and actin proteins in the liver. (H) Quantified XBP1s protein levels in G. Each experiment was independently repeated in three independent cohorts (A–H). Values are means ± s.e.m. Significance was determined by Student's t test or one-way ANOVA with Bonferroni post hoc test (F, H). *P < 0.05, **P < 0.01, ***P < 0.001. N/S – not significant.