C57bl 6j mice

C57BL/6J and C57BL/6N male mice were obtained from OrientBio (Kyounggido, Korea). Mice were housed at the animal facility of the Lee Gil Ya Cancer and Diabetes Institute (CACU, Gachon University, Incheon, Korea), in accordance with “Guidelines and Animal for Users”. Six week-old male C57BL/6J mice were fed an HFD (60% fat primarily from lard, Research Diets, Inc., New Brunswick, NJ, USA, #D12492). After 10 weeks (at 16 weeks of age), mice were randomly divided into two groups: the PBS-treated HFD group (HFD + PBS; n = 5) and the phloroglucinol-treated HFD group (HFD + phloroglucinol; n = 5). Phloroglucinol (100 mg/kg in PBS) or PBS was administered by oral intubation daily for 9 weeks. Body weight and food consumption were measured weekly.

Male C57BL/6 J mice were purchased from Janvier Labs at an age of 6-8 weeks. Upon arrival, mice were group-housed and kept in a constant environment with the ambient temperature set to 22 ± 2 °C with constant humidity (45–65%) and a 12 hrs/12 hrs light/dark cycle. Murine AdEVs were isolated from the adipocyte fraction of the epididymal white adipose tissue (eWAT) of male C57BL/6 J mice fed with high fat diet (HFD, #D12332, Research Diets Inc) or chow (Altromin #1310) for 4–6 months. Murine eWAT processing and subsequent AdEV isolations by SEC or dUC, as well as the isolation of AdEVs and SVF-EVs from human liposuction samples are described in the supplementary information.

Six to 8 weeks old female heterozygous Hsd: Athymic Nude-Foxn1nu/Foxn1⁺ mice were purchased from Envigo (Indianapolis, IN). Six to 8-weeks-old male C57BL/6J mice were purchased from Jackson Laboratories (Bar Harbor, ME). Mice were housed at the Mayo Clinic animal care facility, which is accredited by the Association for Assessment and Accreditation of Laboratory and Animal Care International (AAALACI). Aging was induced in two separate cohorts of C57BL/6J mice [fed with regular diet or high-fat diet (D12492, Research diets)] by keeping them in-housed for 24 months (24 mo) at the Mayo Clinic animal care facility, i.e., a small cohort of 5 mice, 2 months old was maintained for 22 months fed throughout on regular diet to obtain an aged mice group (24 mo), and, another cohort of 5 mice (2 months old) was fed on high-fat-diet (HFD) to induce obesity and continued on HFD for 22 months to obtain an aged-obese mice group (24 mo). All animal procedures were performed with proper animal handling, adhering to the National Institutes of Health (NIH) guidelines and protocols approved by the Institutional Animal Care and Use Committee (IACUC) at Mayo Clinic, Rochester.