title: Functional and structural changes in the kidney in the early stages of obesity.
abstract: The purpose of this study was to examine the histologic and functional changes that occur in the kidney in the early stages of obesity caused by a high-fat diet. Lean dogs (n = 8) were fed a standard kennel ration, and obese dogs (n = 8) were fed the standard kennel ration plus a supplement of cooked beef fat each day for 7 to 9 wk or 24 wk. Body weights were 58 +/- 5% greater and kidney weights were 31 +/- 7% greater in obese dogs, compared with the average values for lean dogs. Plasma renin activity and insulin concentrations were both 2.3-fold greater in obese dogs, compared with lean dogs. Obesity was associated with a mean arterial pressure increase of 12 +/- 3 mmHg, a 38 +/- 6% greater GFR, and a 61 +/- 7% higher renal plasma flow, compared with lean dogs. The glomerular Bowman's space area was significantly greater (+41 +/- 7%) in dogs fed the high-fat diet, compared with lean animals, mainly because of expansion of Bowman's capsule (+22 +/- 7%). There was also increased mesangial matrix and thickening of the glomerular and tubular basement membranes and the number of dividing cells (proliferating cell nuclear antigen-stained) per glomerulus was 36 +/- 8% greater in obese dogs, compared with lean dogs. There was also a trend for glomerular transforming growth factor-beta1 expression, as estimated by semiquantitative immunohistochemical analysis, to be elevated with the high-fat diet. Therefore, a high-fat diet caused increased arterial pressure, hyperinsulinemia, activation of the renin-angiotensin system, glomerular hyperfiltration, and structural changes in the kidney that may be the precursors of more severe glomerular injury associated with prolonged obesity.
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi.|Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Henegar
authors.affiliation: Department of Pathology, University of Mississippi Medical Center, Jackson, Mississippi.|Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Bigler
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.|Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Lisa K
authors.initials: LK
authors.lastname: Henegar
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.|Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: Suresh C
authors.initials: SC
authors.lastname: Tyagi
authors.affiliation: Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi.|Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi.
authors.forename: John E
authors.initials: JE
authors.lastname: Hall
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D004041:Dietary Fats / Q000008:administration & dosage / Q000009:adverse effects; D004285:Dogs; D006439:Hemodynamics; D007124:Immunoenzyme Techniques; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000098:blood supply / Q000473:pathology* / Q000503:physiopathology*; D009765:Obesity / Q000473:pathology*; D011863:Radioimmunoassay; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D007328:Insulin; D016212:Transforming Growth Factor beta; D012964:Sodium; D012083:Renin