Tgfb1lox/lox mice, Tgfbr2lox/lox mice, Tgfb1+/− mice, GFAP-Cre mice, and Tlr4−/− mice on C57BL/6 were obtained from Jackson32 (link),61 (link)-64 (link) and continued to be maintained on C57BL/6. CMV-lox-stop-lox-Tgfb1 mice30 (link) obtained from Jackson were backcrossed into C57BL/6. POMC-Cre mice maintained on C57BL/6 were used in our previous research20 (link),65 (link). All mice were housed in standard, pathogen-free animal facility with 12h/12h light and darkness cycles, and adult male mice were used in experiments of this work. Mice were maintained on normal chow since weaning, and for some experiments involving HFD feeding, a HFD (45% kcal fat, Research Diets, Inc.) was used when mice were two to three months old. Food intake and body weight of mice were measured using a laboratory scale. GTT was performed in mice through intraperitoneal (i.p.) injection of glucose at 2g/kg body weight. ITT was performed in mice through i.p. injection of human recombinant insulin (Nova Nordisk) at the dose of 0.7U/kg body weight. Blood glucose levels during GTT and ITT were measured with LifeScan® blood glucose monitoring system. All procedures were approved by the Institutional Animal Care and Use Committee of Albert Einstein College of Medicine.