Monosaccharide-induced lipogenesis regulates the human hepatic sex hormone–binding globulin gene
J. Clin. Invest. David M. Selva, et al. 117:3979 doi:10.1172/JCI32249 [
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Figure 1Hepatic production of SHBG in mice expressing human
SHBG transgenes (
21) is reduced after feeding diets with high monosaccharide content or increasing blood glucose levels by streptozotocin treatment.
(
A and
B) Mice were fed high-sucrose or isocaloric basal diets for 7 days (3 per group), and the diets were then reversed in two 7-day cycles. Serum SHBG levels are expressed as mean ± SEM relative to pretreatment levels to compensate for between-animal variability (
A). At day 21, human SHBG mRNA abundance was determined in relation to 18S RNA (mean ± SEM) in liver and kidney; **
P < 0.01 compared with basal diet values (
B). (
C) Serum SHBG levels in mice expressing a human
SHBG transgene lacking a USF-binding site in the promoter (
24) were reduced by feeding a high-sucrose diet. Animals (3 per group) were fed a basal diet (squares) or a high-sucrose diet (diamonds) for 7 days, and diets were then reversed for 7 days. Serum SHBG measurements (mean ± SEM) are expressed relative to pretreatment levels. (
D) Serum SHBG levels (mean ± SEM) were reduced relative to pretreatment levels in human
SHBG transgenic mice (3–4 per group) fed equicaloric diets containing high glucose, sucrose, or fructose, when compared with a basal diet. (
E) Human
SHBG transgenic mice treated with streptozotocin were maintained on a basal diet for 11 days, followed by a high-sucrose diet (phase I) and the basal diet (phase II). Serum SHBG levels (mean ± SEM) are expressed relative to pretreatment values.