title: Sex differences in renal and metabolic responses to a high-fructose diet in mice.
abstract: High fructose intake has been associated with increased incidences of renal disease and hypertension, among other pathologies. Most fructose is cleared by the portal system and metabolized in the liver; however, systemic levels of fructose can rise with increased consumption. We tested whether there were sex differences in the renal responses to a high-fructose diet in mice. Two-month-old male and female C57BL6/129/SV mice (n = 6 mice per sex per treatment) were randomized to receive control or high-fructose (65% by weight) diets as pelleted chow ad libitum for 3 mo. Fructose feeding did not significantly affect body weight but led to a 19% and 10% increase in kidney weight in male and female mice, respectively. In male mice, fructose increased the expression (∼50%) of renal cortical proteins involved in metabolism, including glucose transporter 5 (facilitative fructose transporter), ketohexokinase, and the insulin receptor (β-subunit). Female mice had lower basal levels of glucose transporter 5, which were unresponsive to fructose. However, female mice had increased urine volume and plasma K(+) and decreased plasma Na(+) with fructose, whereas male mice were less affected. Likewise, female mice showed a two- to threefold reduction in the expression Na(+)-K(+)-2Cl(-) cotransporter 2 in the thick ascending limb and aquaporin-2 in the collecting duct with fructose relative to female control mice, whereas male mice had no change. Overall, our results support greater proximal metabolism of fructose in male animals and greater distal tubule/collecting duct (electrolyte homeostasis) alterations in female animals. These sex differences may be important determinants of the specific nature of pathologies that develop in association with high fructose consumption.
authors.affiliation: Division of Endocrinology and Metabolism, Georgetown University, Washington, District of Columbia; and.
authors.forename: Nikhil
authors.initials: N
authors.lastname: Sharma
authors.affiliation: Division of Endocrinology and Metabolism, Georgetown University, Washington, District of Columbia; and Center for the Study of Sex Differences in Health, Aging, and Disease, Department of Medicine, Georgetown University, Washington, District of Columbia.
authors.forename: Lijun
authors.initials: L
authors.lastname: Li
authors.affiliation: Division of Endocrinology and Metabolism, Georgetown University, Washington, District of Columbia; and Center for the Study of Sex Differences in Health, Aging, and Disease, Department of Medicine, Georgetown University, Washington, District of Columbia ecelbarc@georgetown.edu.
authors.forename: C M
authors.initials: CM
authors.lastname: Ecelbarger
mesh_terms: D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D004573:Electrolytes / Q000097:blood / Q000652:urine; D005260:Female; D005632:Fructose / Q000009:adverse effects* / Q000378:metabolism; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D051296:Glucose Transporter Type 5; D006984:Hypertrophy; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D012727:Sex Characteristics; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D064466:Solute Carrier Family 12, Member 1 / Q000378:metabolism; D013549:Sweetening Agents / Q000009:adverse effects*; D014527:Uric Acid / Q000378:metabolism
chemical_list: C496024:Aqp2 protein, mouse; D051399:Aquaporin 2; D004573:Electrolytes; D051246:Glucose Transport Proteins, Facilitative; D051296:Glucose Transporter Type 5; C578715:Slc12a1 protein, mouse; C465351:Slc2a5 protein, mouse; D064466:Solute Carrier Family 12, Member 1; D013549:Sweetening Agents; D014527:Uric Acid; D005632:Fructose; D000254:Sodium-Potassium-Exchanging ATPase
keywords: aquaporin-2; electrolyte; glucose transporter 5; ketohexokinase; proximal tubule