NOX-6-18 (dihydrocholide)

Wild-type (WT), Gpr132fl/fl, Lyz2-cre+/−Gpr132fl/fl (male, female, high-fat diet induced Type 2 diabetes mellitus)^[1]

25 ng per gram body weight

i.p.; every other day; 4-6 weeks or 12-14 weeks

Significantly reduced HFD-induced weight gain in male and female WT mice after 12-14 week treatment.
Improved glucose tolerance in male and female HFD-fed mice after 12-14 week treatment.
Improved insulin tolerance in male HFD-fed mice after 12-14 week treatment.
Reduced fasting plasma glucose and insulin levels in HFD-fed mice after 12-14 week treatment.
Reduced refeeding plasma glucose levels and increased refeeding insulin levels in HFD-fed mice after 12-14 week treatment.
Reduced liver and white adipose tissue (WAT) weight, hepatic steatosis, and hepatic triglyceride levels in HFD-fed mice after 12-14 week treatment.
Reduced CD11c+ islet cell numbers in pancreatic islets of HFD-fed mice after 12-14 week treatment.
Downregulated mRNA levels of inflammatory markers Il1b, Tnf, Ccl2, and Cxcl1 in CD11c+ Ly6C− F4/80lo islet-resident macrophages from HFD-fed mice after 12-14 week treatment.
Downregulated inflammatory cytokine mRNA levels in F4/80+ macrophages from liver and WAT of HFD-fed mice after 12-14 week treatment.
Partially reversed reduced energy expenditure and respiratory quotient in HFD-fed mice after 12-14 week treatment.
Significantly reduced HFD-induced weight gain after 4-6 week treatment.
Improved glucose tolerance in HFD-fed mice after 4-6 week treatment.
Downregulated mRNA levels of inflammatory markers Ccl2 and Cxcl1 in CD11c+ Ly6C− F4/80lo islet-resident macrophages from HFD-fed mice after 4-6 week treatment.
Reduced CD11c+ islet cell numbers in pancreatic islets of HFD-fed mice after 4-6 week treatment.