Streptozotocin (stz)

Streptozotocin (AdipoGen Life Sciences, AG-CN2-0046) was administered on postnatal day 2 (0.4mg/mouse, subcutaneous) and male mice were weaned to a 60% lard diet (TD.06414, Envigo) (23 (link)). Blood glucose was checked at 6 and 9 weeks of age (Glucocard Vital glucometer) and animals with consistently low glucose (<400mg/dL) were excluded. Tissue and serum were collected at 12 or 18 weeks of age following a 4h fast and 2h after injection of BrdU (200μl/IP, 18mg/ml bromodeoxyuridine, 1.8mg/ml fluorodeoxyuridine). DEN/TFF: Male mice were injected with diethyl nitrosamine (DEN, #N0258, Sigma-Aldrich) at P14 (25mg/kg, IP) (24 (link)) and fed high transfat, fructose diet (TFF TD.06303, Envigo) (25 (link)). Serum and tissue were collected at 4 or 7 months of age and 2h after injection of BrdU. In some studies, mice were injected with AAV at 2–4 weeks of age (IP) as indicated. For all HCC studies, animals were weighed weekly and monitored for signs of distress.
Additional reagent information and experimental protocols including details of dietary studies, electron microscopy, histological assessment and untargeted lipidomics are provided in Supplemental Methods.

To induce diabetes mellitus, C57BL/6 male mice (4-week-old) were injected i.p. with streptozotocin (Adipogen, San Diego, CA, USA) at 80 mg/kg/dose in 200 μL of 0.1 M citrate buffer daily for 4 days (Patras et al., 2020 ). Control mice received 4 daily treatments of 200 μL of 0.1 M citrate buffer. Mice were weighed weekly thereafter. The concentration of blood glucose 7-week-old mice was determined 24 h prior to infection. Sample glucose was determined using an AimStrip Plus blood glucose meter kit (Germaine Labs, Indianapolis, IN, USA).