Fig. 5

Arg2 deficiency suppresses obesity-associated mouse PDA and results in ammonia accumulation. a DNA gel confirming the genotypes of KPC cells with wild-type (WT) expression or knockout (KO) of Arg2. b Proliferation curves of cells in a (n = 6). Data are representative of three independent experiments. c Volumes of orthotopic PDA tumors from cells in b injected (250,000 per mouse) in lean or obese 11–13 week old male C57BL/6J-129 svJae mice and grown for 2 weeks (n = 6 except for Obese-Arg2^+/+ n = 5). d ¹⁵N₄,¹³C₆ enrichment in plasma arginine in mice from c infused with ¹⁵N₄,¹³C₆-arginine (n = 3). e, Schematic showing that Arg2 knockdown in obese PDA causes shunting of arginine away from the urea cycle and towards creatine biosynthesis, along with transfer of nitrogen into glutamate, aspartate, glutamine, and ammonia in Arg2 ^−/− KPC tumors of obese mice. Red arrows indicate increases in ¹⁵N-labeling, of indicated metabolites in Arg2 ^−/− tumors of obese mice. Gamt, Guanidinoacetate N-Methyltransferase. f Relative abundance of total pool of the indicated metabolites from tumors in c. g Relative abundance of the indicated labeled isotopomers in tumors from c. h Relative abundance (left) and fractional labeling (right) of derivatized ¹⁵N-ammonia. Data represent the mean ± s.e.m. in b, or mean ± s.d. in c, d, f–h. * P ≤ 0.05, **P ≤ 0.01 and *** P ≤ 0.001, **** P ≤ 0.0001, by two-way ANOVA in b, and one-way ANOVA in c, f–h, followed by Tukey test