a, Schematic describing the generation of ROSA26-IC7Fc mice. The panel shows (1) ROSA26 wild-type locus; (2) ROSA26-IC7Fc targeting vector; and (3) ROSA26 locus after homologous recombination. b–d, Eight-week-old male mice that overexpress liver-specific IC7Fc (IC7FcAlb-cre) and littermate controls (IC7FcWT) were killed in the fed state. IC7Fc expression was determined by western blots in different tissues (b) and circulating IC7Fc levels in plasma were detected by ELISA (c); n = 4 (WT), n = 9 (Alb). d, STAT3 phosphorylation in liver tissues from IC7FcAlb-cre mice. e–i, Eight-week-old IC7FcAlb-cre and control (IC7FcWT) mice fed a chow diet until 19 weeks of age. e, Growth curve as change in total body mass (left), fat mass (middle) and lean mass (right) of chow-fed IC7FcAlb-cre mice (n = 9) and littermate controls (n = 5). f, Fasting blood glucose (left) and insulin levels (right) in 8-week-old mice; left, n = 10 and 12, and right, n = 5 and 9 for WT and Alb mice, respectively. g, Glucose levels during an OGTT shown as time course (left) and expressed as iAUC (right) in fasted mice; n = 5 (WT), n = 8 (Alb). h, i, Plasma levels of NEFA and glucagon in 19-week-old transgenic mice; n = 5 and 9 (h) and n = 8 and 19 (i) for WT and Alb mice, respectively. j–t, Differences between 7-week-old male IC7FcMCK-cre mice (MCK, n = 8)—which predominantly overexpress muscle-specific IC7Fc (mice were kept at 30 °C holding temperature)—and littermate control mice (WT, n = 5), before the start of diet intervention. j, Total body mass, fat mass and lean mass. k, Fasting blood glucose. l, Glucose levels during an OGTT shown as time course (left) and expressed as iAUC (right). m, Fasting insulin levels after a 4-week HFD in IC7FcMCK-cre mice (n = 6) and littermate controls (n = 5). n–t, Eight-week-old IC7FcMCK-cre mice (n = 5) and littermate controls (n = 7) fed a HFD for 6 weeks. Total body mass (n), fat mass (o) and lean mass (p). Fasting blood glucose levels (q, left), insulin levels (q, right), glucose during an OGTT (r) and plasma insulin (s) after a HFD. t, Difference in weight of tibialis anterior (TA) of mice at cull at 14 weeks of age. u, Normal chow-fed 26-week-old male IC7FcMCK-cre and littermate mice were kept at 22 °C holding temperature (n = 4 per genotype) and femurs were analysed as follows: Percentage of BV/TV (left) and quantification of trabecular number (right). Data are mean ± s.e.m. P values determined by: Student’s two-tailed unpaired t-test (c, f (right), g–m, q (right), r, t, u); two-tailed unpaired Mann–Whitney U-test (f (left) and q (left)); two-way ANOVA with Sidak’s multiple comparisons test (e, g, l, n–p, r, s). Source data