Fig 2: Ginsenoside Rd had no effect on inflammatory levels in SIRT6-deficient MPHs. (A and B) In OA&PA-incubated SIRT6-deficient MPHs, the ginsenoside Rd treatment lowered nuclear NF?b-p65 levels, as exhibited by IF (A) and WB (B). (C) After OA&PA therapy, ginsenoside Rd has no effect on genes associated with inflammation in SIRT6-deficient MPHs. The mean ± SD of three independent experiments is used to present all data.

Fig 3: Energy expenditure in high-fat diet-fed mice with Sirt6 deficiency in microglia. A Images of brown fat and UCP1 immunohistochemical staining. B Serum NE content. n = 7–8/group. C Body core temperature of mice during acute cold exposure. n = 7 /group. D Oxygen consumption of mice exposed to acute cold temperature. n = 5–6/group. E CO2 production of mice exposed to acute cold temperature. n = 5–6/group. F Heat production of mice exposed to acute cold temperature. n = 5–6/group. Data are presented as mean ± SEM, * p < 0.05, ** p < 0.01, *** p < 0.001

Fig 4: Ginsenoside Rd has no effect on the lipid metabolism’s abnormality caused by OA&PA in SIRT6-deficient MPHs. (A) SIRT6 deficiency eliminates the therapeutic benefits of ginsenoside Rd on lipid accumulation in MPHs. (B) Treatment with ginsenoside Rd fails to lower TG levels in MPHs that are generated by SIRT6-deficient mice. (C) Ginsenoside Rd administration has little effect on SIRT6-deficient MPHs’ fatty acid oxidation genes. (D) Ginsenoside Rb therapy has no effect on hepatic lipid accumulation (BODIPY 493/503), lipoperoxidation (BODIPY 581/591), or ROS levels in SIRT6-deficient MPHs treated with OA&PA. In OA&PA-incubated SIRT6-deficient MPHs, ginsenoside Rd administration had no effect on the mitochondrial structure (E) or biogenesis (F). The mean ± SD of three independent experiments is used to show all data. ***P < 0.001.

Fig 5: Sirt6 deficiency in microglia exacerbates high-fat diet-induced hypothalamic inflammation. A Immunofluorescent localization of Iba1 (red) and TNF-α (green) in hypothalamus. Arrowheads indicate representative cells showing co-localization. Scale bars: 100 μm. B TNF-α positive microglia counting from mice on a HFD for 12 weeks. n = 5–6/group. C mRNA expression of inflammatory factors in the hypothalamus of male mice on a HFD for 8 weeks. n = 8–12/group. Data are presented as mean ± SEM, * p < 0.05, ** p < 0.01