Figure 6 : Sestrin2 is an endogenous attenuator of steatohepatitis progression.

From: Hepatoprotective role of Sestrin2 against chronic ER stress

Figure 6

(a,b) Livers from WT and Sesn2−/− mice kept on HFD (HFD panels) or Lepob/ob/Sesn2+/− (Con) and Lepob/ob/Sesn2−/− mice kept on LFD (Lepob panels) were subjected to anti-F4/80 staining to visualize macrophage infiltration (a). F4/80-positive areas were quantified (b). (ch) Livers from obese Sesn2−/− mice transduced with AAV-Con (n=4) or AAV-Sesn2 (n=3) (c,d) or injected with PBS (n=4) or TUDCA (n=5) (e,f) or PBS (n=6) or AICAR (n=5) (g,h) were analysed with anti-F4/80 staining (c,e,g). F4/80-positive areas were quantified (d,f,h). Nuclei were visualized with haematoxylin (a,c,e,g). (i,j) Working model of how Sestrin2-mediated UPR attenuates NAFLD progression. In the WT liver, Sestrin2 is induced during obesity through the PERK–c/EBPβ pathway to attenuate protein translation and thereby relieve ER stress (i). In Sesn2−/− liver, persistent mTORC1 activity elevates protein synthesis and subsequently aggravates ER stress, leading to facilitated NAFLD progression (j). Scale bars, 200 μm. All data are shown as the mean±s.e.m. P values are from Student’s t-test.