Skip to main content
. Author manuscript; available in PMC: 2026 Aug 7.
Published in final edited form as: Cell. 2025 Aug 7;188(21):6044–6063.e24. doi: 10.1016/j.cell.2025.07.016

Figure 4: Right cervical vagotomy preserves liver metabolism during cancer cachexia.

Figure 4:

A. Left: A representative western blot demonstrating decreased HNF4α and OTC protein expression in cachectic LLC mice livers, compared to those from control mice injected with PBS (WT). Right: A quantification of blot intensity (N=5 for each group). B. 5μM acetylcholine supplementation in THLE-2 for 48 hours decreases HNF4α at the protein (upper) and RNA (lower) levels in primary human hepatocytes as evaluated by western blot and RT-PCR, respectively. C-D. Wildtype mice injected with shHNF4α compared to shLUCIFERASE. C. Decreased liver expression of HNF4α protein levels (upper panel) and a decrease in RNA expression of HNF4α, OTC, and albumin (lower panels), in wildtype mice injected with shHNF4α compared to shLUCIFERASE-injected mice (shLUCIFERASE: N=4, shHNF4α: N=5). D. Weight measurements and NMR body composition analyses measuring % of initial weight, fat, and lean body mass of mice injected with shHNF4α demonstrate a significant loss of weight, fat, and lean body mass compared to control mice injected with shLUCIFERASE (shLUCIFERASE: N=4, shHNF4α: N=5). E. RT PCR measurements show an increase in LCN2 levels in livers of mice with LLC (left) and mice injected with AAV-shHNF4α (right). F. RT-PCR measurements demonstrate an increase in HNF4α and OTC RNA levels in the livers of mice with LLC treated with vagotomy, compared to LLC mice treated with a sham procedure. G. VetScan analysis of liver lysate demonstrates an increase in albumin levels in LLC mice treated with vagotomy (LLC+sham: N=5, LLC+vagotomy: N=4). H. Mass spectrometry analysis of CAC-associated amino acid relative levels in livers of mice with LLC demonstrates preservation of amino acid levels following vagotomy. Heatmap represents an average of relative values per metabolite per treatment. (For WT sham, n-5, WT+vagotomy n=5, LLC sham n=2, LLC + vagotomy n=4). *All statistical analyses were performed using Student t-test; For all box plots, dots represent data collected from unique mice. For all tests, * represents p<0.05, ** represents p<0.005, *** represents p<0.0005, **** represents p<0.0005. See also Figure S5.