Renoprotective mechanisms of soy protein intake in the obese Zucker rat.
We previously showed that long-term consumption of a soy protein diet (SoyP) reduces renal damage in obese Zucker (ObeseZ) rats by restoring urinary NO2 and NO3 excretion (UNO2/NO3V), suggesting that nitric oxide (NO) deficiency may contribute to the renal progression observed in this model. In addition, there is compelling evidence that hyperleptinemia produced deleterious effects on the kidney through its interaction with the short leptin receptor (ObRa). This study was designed to evaluate the contribution of the NO/endothelial NO synthase (eNOS) system, renal oxidative stress, and ObRa expression to the renoprotection conferred by the consumption of a SoyP in ObeseZ rats. Ten lean and ten male ObeseZ rats were included. One-half of each group was fed with a 20% SoyP and the other half with a 20% casein protein diet (CasP) over the course of 160 days. eNOS protein levels and phosphorylation, renal lipoperoxidation (rLPO), and antioxidant enzyme activity were assessed. In addition, renal ObRa, TGF-beta, and kidney injury molecule (Kim-1) mRNA levels, as well as urinary Kim-1 levels, were measured. Renal injury observed in ObeseZ rats fed with CasP was not associated with changes in eNOS expression or phosphorylation. However, this group did present with increased rLPO, reduced catalase activity, and upregulation of ObRa, TGF-beta1, and Kim-1. In contrast, ObeseZ rats fed with a SoyP exhibited a reduction in NOS-Thr495 phosphorylation and rLPO, as well as an enhanced catalase activity. These findings were associated with a significant reduction of ObRa, TGF-beta1, and Kim-1 mRNA levels and urinary Kim-1 protein. Our results show that renoprotection by SoyP in ObeseZ rats is in part mediated by increased NO availability secondary to a reduction in eNOS-T495 phosphorylation and oxidative stress, together with a significant reduction in ObRa and TGF-beta expression.
Trujillo
Joyce
J
Molecular Physiology Unit, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico.
Cruz
Cristino
C
Tovar
Armando
A
Vaidya
Vishal
V
Zambrano
Elena
E
Bonventre
Joseph V
JV
Gamba
Gerardo
G
Torres
Nimbe
N
Bobadilla
Norma A
NA
D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D002364:Caseins / Q000008:administration & dosage / Q000494:pharmacology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism / Q000652:urine; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009765:Obesity / Q000150:complications*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker; D054411:Receptors, Leptin / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D030262:Soybean Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000235:genetics
D000975:Antioxidants; D002364:Caseins; D015815:Cell Adhesion Molecules; D004044:Dietary Proteins; D020738:Leptin; D052250:Nitric Oxide Synthase Type III; D054411:Receptors, Leptin; D030262:Soybean Proteins; D016212:Transforming Growth Factor beta; C110936:Havcr1 protein, rat; C496316:Nos3 protein, rat