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.
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Early in development of obesity and even in obese children, there is often interstitial fibrosis, microalbuminuria or proteinuria, expansion of mesangial matrix, glomerulomegaly, focal segmental glomerular sclerosis, and podocyte disorder associated with glomerular hyperfiltration.
“Early in development of obesity and even in obese children, there is often interstitial fibrosis, microalbuminuria or proteinuria, expansion of mesangial matrix, glomerulomegaly, focal segmental glomerular sclerosis, and podocyte disorder associated with glomerular hyperfiltration142–144.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [144]
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- Authors
- HENEGAR, J. R., BIGLER, S. A., HENEGAR, L. K., TYAGI, S. C., & HALL, J. E.
- Affiliations
- University of Mississippi Medical Center (US)
- Corresponding author
- HENEGAR, JEFFREY R.
- BIGLER, STEVEN A.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2001-06
- Volume
- 12
- Issue
- 6
- Pages
- 1211-1217
- ISSN
- 1046-6673 (ISSN-L)
- OpenAlex
- W2119741758
- Cited by
- 549
- References
- 28
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 14 · 2023: 13 · 2022: 24 · 2021: 20 · 2020: 19 · 2019: 17 · 2018: 29 · 2017: 51 · 2016: 35 · 2015: 21 · 2014: 27 · 2013: 26 · 2012: 38
- FWCI
- 7.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of the American Society of Nephrology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL51991)
- Topics
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Renal and Vascular Pathologies
- Keywords
- obesity, high-fat diet, kidney histology, glomerular hyperfiltration, renal plasma flow, mesangial matrix, glomerular basement membrane thickening, tubular basement membrane thickening, hyperinsulinemia, plasma renin activity, renin-angiotensin system, hypertension, proliferating cell nuclear antigen, glomerular cell proliferation, TGF-β1, canine model, early renal damage
- MeSH terms
- Analysis of Variance, Animals, Blood Pressure, Dietary Fats, Dogs, Hemodynamics, Immunoenzyme Techniques, Insulin, Kidney, Obesity, Radioimmunoassay, Renin, Sodium, Transforming Growth Factor beta
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