Figure 2.

Intermittent starvation maintains hepatocyte function and activates AMPK. (A) Albumin and (B) urea secretions, and (C) CYP3A4 enzyme activity in starved (as described in Figure 1B) and nonstarved cultures over time. (D) Functional bile canaliculi in PHHs within starved and nonstarved micropatterned cocultures (MPCCs) as assessed by the excretion of the CDF dye. Left: images of representative bile canaliculi in PHH islands within the 2 conditions. Right: relative area of excreted CDF in PHH islands within starved versus nonstarved MPCCs after 6 weeks of culture. Data are normalized to the nonstarved controls. (E) p-AMPK per mg of protein in MPCC lysates following 2 starvation periods. Scale bars on images represent 400 µm. *p < .05, **p ≤ .01, ***p ≤ .001, and ****p ≤ .0001. Abbreviations: p-AMPK, phosphorylated adenosine monophosphate-activated protein kinase; PHH, primary human hepatocyte.