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Tryptophan Depletion through a Low Protein Diet Alters Renal Structure and Function in Young Male Mice
Author(s) -
Irsik Debra L.,
Xu Jianrui,
Kang Baolin,
Zhong Qing,
Ding Kehong,
McGee-Lawrence Meghan,
Bollag Wendy B.,
Isales Carlos M.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05720
Subject(s) - kynurenine , endocrinology , medicine , low protein diet , tryptophan , albuminuria , renal function , kidney , chemistry , metabolite , amino acid , biochemistry
Low protein diets have been used in patients with chronic kidney disease to decrease uremic burden, but its use is controversial due to concerns about malnutrition. Long term use of a low‐protein diet may also impact bone health through reduction of the essential amino acid, tryptophan. We have previously shown that feeding a low‐protein diet with increased levels of its metabolite, kynurenine (a change that also occurs in aging) to adult mice leads to bone loss. The kidney regulates many important factors for bone health such as Vitamin D, and in conjunction with parathyroid hormone, phosphate and calcium. Since aging is known to also impact the kidney, we hypothesized that alterations in the normal ratio of tryptophan to kynurenine would impact kidney structure and function. We fed 3‐mo‐old male mice one of four diets [normal 18% protein (NP) or low 8% protein (LP) with or without kynurenine added] for 8 weeks. Mice were housed in metabolic cages for baseline measurements and again at the end of the feeding for 24‐hr urine collection. At sacrifice, kidneys were weighed to detect changes in renal mass, frozen for Western blotting or formalin‐fixed for histological analysis. As expected, we found decreased albuminuria with LP; however, there was a further reduction with KYN treatment in LP mice. There was significant diuresis (2.2±0.31 vs. 0.8±0.1 ml/day) in LP compared to NP mice that was attenuated in KYN mice (1.0±0.2ml/day); this effect may be due in part to a reduction in AQP2 levels. Natriuresis followed a similar trend but did not reach significance (0.12±0.01 vs. 0.08±0.01 mmol/day). Renal mass alone (0.17±0.00 vs. 0.20±0.01 g) and kidney weight/body weight (0.0055±0.0001 vs. 0.0059±0.0001) was decreased in LP mice with no further impact of KYN. Thus, while changes in the tryptophan to kynurenine ratio seem to impact the kidney, the changes vary with the renal parameter investigated. Support or Funding Information AG036675