Figure 3.

Liver ChREBP loss- and gain-of-function models increase and decrease hepatocellular G6P and glycogen levels, respectively but produce overlapping phenotypes with respect to systemicfuel metabolism.A, liver ChREBP KO reduces the expression of enzymes involved in glycolysis, glucose production, lipogenesis, and VLDL packaging and secretion, which increases hepatocellular G6P and glycogen with variable effects on liver fat content. Through unknown mechanisms, this also reduces body weight and insulin resistance. B, liver ChREBP overexpression increases the expression of enzymes involved in glycolysis, glucose production, lipogenesis, and VLDL packaging and secretion, which reduces hepatocellular G6P and glycogen levels with variable effects on liver fat content. ChREBP overexpression also markedly increases circulating FGF21, which has pleiotropic metabolic effects including enhancing browning of white adipose tissue, which may enhance systemic fuel metabolism. Enzymes noted in red are ChREBP transcriptional targets.