Mouse models

All mouse experiments were approved by the Animal Ethics Committee of Kangwon National University (approval numbers KW-190425-5, KW-190723-1, KW-190819-1, and KW-190819-1). All experiments were conducted adhering to the NIH Guide for the Care and Use of Laboratory Animals. Male C57BL/6, ob/ob, and db/db mice were obtained from Orient Bio Inc. (Sungnam, South Korea). Redd1^+/− mice were bred and maintained in the animal facility at Kangwon National University and intercrossed to obtain Redd1^−/− and WT littermates as previously described⁴³. Redd1^flox/flox (Redd1^fl/fl) and Redd1^{Lys219Ala/Lys220Ala} knock-in (Redd1^KKAA) mice were generated using CRISPR/Cas9 in C57BL/6 zygotes (ToolGen Inc. Seoul, South Korea), and their genotypes were confirmed by PCR analysis and genomic DNA sequencing (Supplementary Figs. ¹⁴ and ¹⁵). Adipoq-Cre and LysM-Cre mice were purchased from the Jackson Laboratories (Bar Harbor, ME, USA). Redd1^fl/fl mice were crossed with Adipoq-Cre or LysM-Cre mice to generate mice with adipocyte- (Redd1^ΔAdipoq) or myeloid-specific deletion of Redd1 (Redd1^ΔLysM), respectively. Mice were housed in a specific pathogen-free facility (12 h light/dark cycle) that was maintained at 18–24 °C and 30–50% humidity. Six-week-old male mice were fed either NC (10% calories as fat, #D12450B, JA BIO, Inc., Suwon, South Korea) or HFD (60% calories as fat, #D12492, JA BIO, Inc.) for 10 weeks to analyze expression levels of adipogenic genes Pparg, Cebpa, and aP2 or for 16 weeks to examine obesity and metabolic complications. Food consumption was monitored daily and body weight was recorded weekly.