Fig. 3.

Changes in fructose metabolism associated with protection from high-fat, high-fructose (HFHF) diet–induced NAFLD in the HIF-P4H-2-deficient mice. Wild-type (wt) and Hif-p4h-2^gt/gt (gt/gt) males after e–g 6 or c, h–k 8 weeks on a HFHF diet (n = 8–10/group). a, b¹⁴C-fructose uptake test. After 2 weeks on the HFHF diet and a 12-h fast, wt and gt/gt females received ¹⁴C-fructose orally and were sacrificed after 15 min and tissue samples were measured for ¹⁴C radioactivity as disintegration/min/mg (DPM) (n = 12/group). a DPM per mg of tissue in indicated tissues. b Sum radioactivity detected in all tissues measured including and excluding the small intestine. c qPCR analysis of the mRNA levels of glucose and fructose transporters and metabolizing enzymes in the small intestine of the gt/gt mice relative to wt. Gene expression was studied relative to β-actin mRNA. d Ketohexokinase activity in the small intestine of females after 4 weeks on a HFHF diet (n = 6–8/group). e Oral glucose tolerance test (GTT). The value for 0 min was determined after a 12-h fast. f Serum insulin levels determined from the 0-min GTT samples. g HOMA-IR scores determined from the 0-min values. h Serum uric acid levels. i Blood lactate levels. j Blood lactate-to-glucose ratio. k qPCR analysis of liver mRNA levels of glucose and fructose transporters and metabolizing enzymes in gt/gt mice relative to wt, studied relative to TATA-box-binding protein mRNA. Data are means ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001. The p value for d was calculated from log-transformed values. b, blood; BAT, brown adipose tissue; HOMA-IR, homeostatic model assessment-insulin resistance; KHK, ketohexokinase; s, serum; SLC2A 1-5, solute carrier family-2 member 1-5; WAT, white adipose tissue