title: A low-protein diet concomitant with high calorie intake preserves renal function and structure in diabetic OLETF rats.
abstract: BACKGROUND
  Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a spontaneous type 2 diabetes model, were used to clarify whether and how a low-protein diet prevents progressive diabetic nephropathy, in terms of functional and structural parameters.
  
  
  METHODS
  A low-protein diet (LPD) with 11% protein content, was compared to the normal 24% protein diet (NPD) without keeping isocaloric conditions. Daily food intake, body weight, and blood and urine chemistry were serially measured in rats from 10 through 60 weeks of age, and renal clearance studies and histological evaluations were performed at 40 and 60 weeks of age.
  
  
  RESULTS
  Daily calorie intake was higher in the OLETF rats fed on the LPD than in those fed on the NPD throughout the experiment. Due to this hyperphagia, fasting blood glucose and hemoglobin (Hb)A1c were dramatically increased in the LPD-fed OLETF rats at 30 weeks and thereafter, whereas urinary protein excretion was decreased by more than half after 26 weeks in the LPD group. Plasma concentrations of total cholesterol and triglyceride were decreased in the LPD-fed OLETF rats at 40 and 60 weeks. Inulin clearance in the LPD group was higher only at 60 weeks of age. The glomerular sclerosis index (GSI) and tubulointerstitial index (TII) were preserved in the LPD group. The LPD induced a decrease in tubulointerstitial macrophage infiltration as compared with the NPD at both 40 and 60 weeks of age, but glomerular macrophage infiltration was not alleviated.
  
  
  CONCLUSIONS
  A low-protein diet, despite the worsening hyperglycemia caused by hyperphagia, not only reduced proteinuria but also ameliorated hyperlipidemia in OLETF rats, thereby preserving renal function and structure in diabetic nephropathy, probably via a macrophage-mediated mechanism.
authors.affiliation: Kagawa Nutrition University, 3-9-21 Chiyoda, Sakado, Saitama 350-0288, Japan. smatsuda@eiyo.ac.jp
authors.forename: Sanae
authors.initials: S
authors.lastname: Matsuda
authors.forename: Kazuko
authors.initials: K
authors.lastname: Iwata
authors.forename: Kazushi
authors.initials: K
authors.lastname: Takahashi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Homma
authors.forename: Yoshifuru
authors.initials: Y
authors.lastname: Tamura
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Kanda
authors.forename: Taketoshi
authors.initials: T
authors.lastname: Inokami
authors.forename: Hitonari
authors.initials: H
authors.lastname: Nosaka
authors.forename: Mitsumasa
authors.initials: M
authors.lastname: Nagase
authors.forename: Shunya
authors.initials: S
authors.lastname: Uchida
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D003920:Diabetes Mellitus / Q000378:metabolism / Q000473:pathology; D004032:Diet; D004044:Dietary Proteins; D002149:Energy Intake; D007668:Kidney / Q000166:cytology* / Q000502:physiology*; D008297:Male; D051381:Rats; D020334:Rats, Inbred OLETF; D014280:Triglycerides / Q000097:blood; D014556:Urine / Q000737:chemistry
chemical_list: D001786:Blood Glucose; D004044:Dietary Proteins; D014280:Triglycerides; D002784:Cholesterol