title: SGLT5 reabsorbs fructose in the kidney but its deficiency paradoxically exacerbates hepatic steatosis induced by fructose.
abstract: Although excessive fructose intake is epidemiologically linked with dyslipidemia, obesity, and diabetes, the mechanisms regulating plasma fructose are not well known. Cells transfected with sodium/glucose cotransporter 5 (SGLT5), which is expressed exclusively in the kidney, transport fructose in vitro; however, the physiological role of this transporter in fructose metabolism remains unclear. To determine whether SGLT5 functions as a fructose transporter in vivo, we established a line of mice lacking the gene encoding SGLT5. Sodium-dependent fructose uptake disappeared in renal brush border membrane vesicles from SGLT5-deficient mice, and the increased urinary fructose in SGLT5-deficient mice indicated that SGLT5 was the major fructose reabsorption transporter in the kidney. From this, we hypothesized that urinary fructose excretion induced by SGLT5 deficiency would ameliorate fructose-induced hepatic steatosis. To test this hypothesis we compared SGLT5-deficient mice with wild-type mice under conditions of long-term fructose consumption. Paradoxically, however, fructose-induced hepatic steatosis was exacerbated in the SGLT5-deficient mice, and the massive urinary fructose excretion was accompanied by reduced levels of plasma triglycerides and epididymal fat but fasting hyperinsulinemia compared with fructose-fed wild-type mice. There was no difference in food consumption, water intake, or plasma fructose between the two types of mice. No compensatory effect by other transporters reportedly involved in fructose uptake in the liver and kidney were indicated at the mRNA level. These surprising findings indicated a previously unrecognized link through SGLT5 between renal fructose reabsorption and hepatic lipid metabolism.
authors: Research Division, Chugai Pharmaceutical Co, Ltd, Gotemba, Shizuoka, Japan.
authors: Taku
authors: T
authors: Fukuzawa
authors: Masanori
authors: M
authors: Fukazawa
authors: Otoya
authors: O
authors: Ueda
authors: Hideaki
authors: H
authors: Shimada
authors: Aki
authors: A
authors: Kito
authors: Mami
authors: M
authors: Kakefuda
authors: Yosuke
authors: Y
authors: Kawase
authors: Naoko A
authors: NA
authors: Wada
authors: Chisato
authors: C
authors: Goto
authors: Naoshi
authors: N
authors: Fukushima
authors: Kou-Ichi
authors: K
authors: Jishage
authors: Kiyofumi
authors: K
authors: Honda
authors: George L
authors: GL
authors: King
authors: Yoshiki
authors: Y
authors: Kawabe
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism*; D005632:Fructose / Q000378:metabolism* / Q000633:toxicity; D005838:Genotype; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051247:Sodium-Glucose Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051247:Sodium-Glucose Transport Proteins; D005632:Fructose