Dietary methionine restriction modulates renal response and attenuates kidney injury in mice

Abstract

Methionine restriction (MR) extends the lifespan across several species, such as rodents, fruit flies, roundworms, and yeast. MR studies have been conducted on various rodent organs, such as liver, adipose tissue, heart, bones, and skeletal muscle, to elucidate its benefits to the healthspan; however, studies of the direct effect of MR on kidneys are lacking. To investigate the renal effects of MR, we used young and aged unilateral nephrectomized and 5/6 nephrectomized (5/6Nx) mice. Our studies indicated that MR mice experienced polydipsia and polyuria compared with control-fed counterparts. Urine albumin, creatinine, albumin-to-creatinine ratio, sulfur amino acids, and electrolytes were reduced in MR mice. Kidneys of MR mice up-regulated genes that are involved in ion transport, such as Aqp2, Scnn1a, and Slc6a19, which indicated a response to maintain osmotic balance. In addition, we identified renoprotective biomarkers that are affected by MR, such as clusterin and cystatin C. Of importance, MR attenuated kidney injury in 5/6Nx mice by down-regulating inflammation and fibrosis mechanisms. Thus, our studies in mice show the important role of kidneys during MR in maintaining osmotic homeostasis. Moreover, our studies also show that the MR diet delays the progression of kidney disease.-Cooke, D., Ouattara, A., Ables, G. P. Dietary methionine restriction modulates renal response and attenuates kidney injury in mice. FASEB J. 32, 693-702 (2018). www.fasebj.org

Sulfur amino acid restriction–induced changes in redox‐sensitive proteins are associated with slow protein synthesis rates

“…A). Plasma 2 H 2 O reached maximal levels earlier in SAAR than in CD rats, likely due to higher intake of water, as shown in other studies . In order to compare rates of synthesis of 2 H‐Ala, it is important that both CD and SAAR rats have similar levels of precursor (i.e., 2 H 2 O).…”

Methyl Donor Nutrients in Chronic Kidney Disease: Impact on the Epigenetic Landscape

“…Folate is the term used to describe a range of forms of the water-soluble vitamin B-9 that occurs naturally in foods (Table 1) (41,45). Dietary folate has an important role in the formation of SAM, and can be a limiting factor in the associated pathway.…”

“…Additionally, Met restriction may delay the progression of CKD by down-regulating inflammatory and fibrotic processes. This results in lower expression of urinary biomarkers normally elevated during kidney disease(41).Correspondingly therefore, a high Met diet may induce elevated levels of oxidative stress and elevate renal damage in kidneys with tubular hypertrophy(42,43). Surprisingly therefore, , Amaral et al(44) have reported that a high Met diet is not deleterious to kidney cells in Wistar rats.…”

“…Met restriction is particularly pertinent to renal biology. Indeed, Cooke et al(41) recently showed that kidneys in 5/6 nephrectomized mice play an important role in maintaining osmotic balance during Met restriction diet, by up-regulating genes involved with ion transport. Additionally, Met restriction may delay the progression of CKD by down-regulating inflammatory and fibrotic processes.…”

A Low-Protein Diet for Diabetic Kidney Disease: Its Effect and Molecular Mechanism, an Approach from Animal Studies

“…Several studies have shown that a methionine restriction (MR) extends lifespans in several species, such as rodents, fruit flies, roundworms, and yeast, possibly through an increased oxidative stress capacity and hydrogen sulfate (H 2 S) production [ 66 , 67 , 68 , 69 ]. Cooke et al recently reported that an MR attenuated a kidney injury in 5/6 nephlectomy mice by down-regulating inflammation and fibrosis mechanisms [ 70 ]. Therefore, we suspect that the reno-protective effect of a VLPD on DKD in type 2 diabetes and obesity rats in our previous studies may be exerted through methionine or other amino acid restriction.…”