Specific Adaptive Mechanisms in Water‐Sodium Regulation in a Desert Rodent Fed With Salty Diets

Abstract

High‐salt diets (HSD) are known to cause renal injury and hypertension in mice, rats, or even humans. Desert rodents have evolved an ability to adapt to water scarcity and concentrated electrolytes in vegetation over a long evolutionary period. However, how the desert rodent species adapt to salty diets remains rarely studied. In this study, we revealed the different adaptive mechanisms in water‐sodium regulation using Mongolian gerbils (Meriones unguiculatus) and C57BL/6J mice fed with HSD (containing 4% and 8% NaCl concentrations) as models. The HSD mice showed concentration‐dependent reductions in body mass and solute‐free water clearance, and increases in total solute excretion, associated with increased nocturnal blood pressure and daily energy expenditure compared with the control mice. In contrast, the HSD gerbils maintained the same body mass and blood pressure as the control gerbils, and adjusted urine osmolality and food intake to achieve water and sodium balance. Transcriptomic and qPCR analysis revealed differential expression of genes related to water and sodium balance, with downregulation of Slc14a2, Nos1, and Corin, and upregulation of Sgk1, Cyp4a14, and Cyp4a10, and upregulation in antioxidative response genes including Gsta1, Gsta2, Gstm3, and Hmgcs2 in mice. However, a small number of differential genes were observed in Mongolian gerbils, with increased Gjb6 and decreased Aqp4 expression related to water‐balance regulation, and increased expression of the fibrosis‐suppressing gene Grem2. Our study uncovers the unique renal adaptive mechanisms in desert mammals through upregulation of Gjb6 and downregulation of Aqp4 expression for coping with high‐salt and arid environments.

The Renal Function of the Wild Rodent Cerradomys goytaca Reveals Adaptations in the Mechanisms of Urinary Concentration and Solute Excretion

“…The ability to excrete higher amounts of sodium and potassium while simultaneously conserving water suggests a finely regulated renal adaptation in C. goytaca. Similar physiological strategies have been described in desert rodents, which exhibit enhanced mechanisms for water conservation and tolerance to elevated electrolyte intake from vegetation (Rocha et al 2021b) For example, Meriones unguiculatus consumes a diet rich in high-salt plants and dry seeds throughout the year (Nouri et al 2020), while maintaining water balance despite a high-protein diet (43.3%) containing 2% saline (Edwards et al 1983Yang et al 2025;).…”

The Renal Function of the Wild Rodent Cerradomys goytaca Reveals Adaptations in the Mechanisms of Urinary Concentration and Solute Excretion

“…The ability to excrete higher amounts of sodium and potassium while simultaneously conserving water suggests a finely regulated renal adaptation in C. goytaca. Similar physiological strategies have been described in desert rodents, which exhibit enhanced mechanisms for water conservation and tolerance to elevated electrolyte intake from vegetation (Rocha et al 2021b) For example, Meriones unguiculatus consumes a diet rich in high-salt plants and dry seeds throughout the year (Nouri et al 2020), while maintaining water balance despite a high-protein diet (43.3%) containing 2% saline (Edwards et al 1983Yang et al 2025;).…”

Multiomic Analyses Reveal the Molecular Mechanisms of Arid Adaptation in a Desert Rodent Species

“…During water deprivation, Aqp4 was upregulated, while Aqp3 was downregulated, accompanied by no changes in Aqp1 or Aqp2 in the kidneys of the O. sibirica . However, upregulation of Aqp2 was observed in the kidneys under water restriction conditions for the production of highly concentrated urine in some other small mammals, such as in the Lepus yarkandensis ( Zhang et al 2013 ), Rattus norvegicus ( Dantzler et al 2011 ), M. unguiculatus ( Xu and Wang 2016 ), and M. musculus ( Fenton and Knepper 2007 ; Esteva-Font et al 2012 ), and downregulation of renal Aqp4 expression associated with reduced urine osmolality was observed in M. unguiculatus fed with high salt diets ( Yang et al 2025 ). The production of highly concentrated urine in the large mammal C. bactrianus is achieved by an increase in sodium excretion, and water is effectively stored in the kidney to cope with high-salt and water-deficient environments ( Benlamlih et al 1992 ; Goumi et al 1993 ).…”

The Renal Function of the Wild Rodent Cerradomys goytaca Reveals Adaptations in the Mechanisms of Urinary Concentration and Solute Excretion

“…The ability to excrete higher amounts of sodium and potassium while simultaneously conserving water suggests a finely regulated renal adaptation in C. goytaca. Similar physiological strategies have been described in desert rodents, which exhibit enhanced mechanisms for water conservation and tolerance to elevated electrolyte intake from vegetation (Rocha et al 2021b) For example, Meriones unguiculatus consumes a diet rich in high-salt plants and dry seeds throughout the year (Nouri et al 2020), while maintaining water balance despite a high-protein diet (43.3%) containing 2% saline (Edwards et al 1983Yang et al 2025;).…”

Multiomic Analyses Reveal the Molecular Mechanisms of Arid Adaptation in a Desert Rodent Species

“…During water deprivation, Aqp4 was upregulated, while Aqp3 was downregulated, accompanied by no changes in Aqp1 or Aqp2 in the kidneys of the O. sibirica . However, upregulation of Aqp2 was observed in the kidneys under water restriction conditions for the production of highly concentrated urine in some other small mammals, such as in the Lepus yarkandensis ( Zhang et al 2013 ), Rattus norvegicus ( Dantzler et al 2011 ), M. unguiculatus ( Xu and Wang 2016 ), and M. musculus ( Fenton and Knepper 2007 ; Esteva-Font et al 2012 ), and downregulation of renal Aqp4 expression associated with reduced urine osmolality was observed in M. unguiculatus fed with high salt diets ( Yang et al 2025 ). The production of highly concentrated urine in the large mammal C. bactrianus is achieved by an increase in sodium excretion, and water is effectively stored in the kidney to cope with high-salt and water-deficient environments ( Benlamlih et al 1992 ; Goumi et al 1993 ).…”

The Renal Function of the Wild Rodent Cerradomys goytaca Reveals Adaptations in the Mechanisms of Urinary Concentration and Solute Excretion

“…The ability to excrete higher amounts of sodium and potassium while simultaneously conserving water suggests a finely regulated renal adaptation in C. goytaca. Similar physiological strategies have been described in desert rodents, which exhibit enhanced mechanisms for water conservation and tolerance to elevated electrolyte intake from vegetation (Rocha et al 2021b) For example, Meriones unguiculatus consumes a diet rich in high-salt plants and dry seeds throughout the year (Nouri et al 2020), while maintaining water balance despite a high-protein diet (43.3%) containing 2% saline (Edwards et al 1983Yang et al 2025;).…”

Multiomic Analyses Reveal the Molecular Mechanisms of Arid Adaptation in a Desert Rodent Species

“…During water deprivation, Aqp4 was upregulated, while Aqp3 was downregulated, accompanied by no changes in Aqp1 or Aqp2 in the kidneys of the O. sibirica . However, upregulation of Aqp2 was observed in the kidneys under water restriction conditions for the production of highly concentrated urine in some other small mammals, such as in the Lepus yarkandensis ( Zhang et al 2013 ), Rattus norvegicus ( Dantzler et al 2011 ), M. unguiculatus ( Xu and Wang 2016 ), and M. musculus ( Fenton and Knepper 2007 ; Esteva-Font et al 2012 ), and downregulation of renal Aqp4 expression associated with reduced urine osmolality was observed in M. unguiculatus fed with high salt diets ( Yang et al 2025 ). The production of highly concentrated urine in the large mammal C. bactrianus is achieved by an increase in sodium excretion, and water is effectively stored in the kidney to cope with high-salt and water-deficient environments ( Benlamlih et al 1992 ; Goumi et al 1993 ).…”