Glomerular structural and functional changes in a high-fat diet mouse model of early-stage Type 2 diabetes

P. Wei, P. H. Lane, J. T. Lane, B. J. Padanilam, S. C. Sansom

Research output: Contribution to journalArticle

58 Citations (Scopus)

Abstract

Aims/hypothesis. Type 2 diabetes often results in diabetic nephropathy, which is preceded by an elevated glomerular filtration rate (GFR). This study was designed to develop a mouse model of Type 2 diabetes and to elucidate the glomerular events in the early stages of diabetic nephropathy. Methods. Four-week-old mice were fed a normal or high-fat (42% of total calories from fat) diet, and body weight, blood glucose, insulin, leptin, lipids and GFR were monitored from 9 to 21 weeks or longer after the feeding programme. Mesangial cell dedifferentiation was accessed by alpha-smooth muscle actin staining. Glomerular hypertrophy was determined using image analysis with haematoxylin-eosin staining. Matrix deposition was determined by type IV collagen staining. Results. After 9 weeks, mice fed a high-fat diet weighed more than mice fed a normal diet (30.5±1.2 vs 22.3±0.5 g, p<0.05), and mice fed a high-fat diet were hyperinsulinaemic (283.9±69.7 vs 102.9±36.4 pmol/l, p<0.05), hyperglycaemic (8.0±0.6 vs 6.5±0.2 mmol/l, p<0.05) and their leptin levels were increased six-fold (1.48±0.45 vs 0.25±0.03 ng/ml, p<0.05). After 13 weeks, mice fed a high-fat diet showed hyperfiltration (GFR; 440±60 vs 210±10 μl/min, p<0.05). During the early stages of diabetic nephropathy, mesangial cell dedifferentiation was evident, shown by increased expression of alpha-smooth muscle actin in the glomeruli. After 9 weeks, mice fed a high-fat diet already demonstrated increased type IV collagen deposition. After 13 weeks, they developed enlarged glomerular tufts compared with those of their age-matched controls. Conclusions/interpretation. The results of this study suggest that collagen IV deposition precedes the hyperfiltration and enlargement of glomeruli in early-stage diabetic nephropathy. Dedifferentiation of mesangial cells may be associated with collagen IV deposition.

Original languageEnglish (US)
Pages (from-to)1541-1549
Number of pages9
JournalDiabetologia
Volume47
Issue number9
DOIs
StatePublished - Sep 1 2004

Fingerprint

High Fat Diet
Type 2 Diabetes Mellitus
Diabetic Nephropathies
Mesangial Cells
Cell Dedifferentiation
Glomerular Filtration Rate
Collagen Type IV
Staining and Labeling
Leptin
Smooth Muscle
Actins
Collagen
Fats
Diet
Hematoxylin
Eosine Yellowish-(YS)
Hypertrophy
Blood Glucose
Body Weight
Insulin

Keywords

  • Diabetic nephropathy
  • GFR
  • Glomerulopathy
  • High-fat diet
  • Hyperfiltration
  • Hyperglycaemia
  • Hyperinsulinaemia
  • Leptin
  • Mice
  • Obesity
  • Type 2 diabetes
  • Type IV collagen

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Glomerular structural and functional changes in a high-fat diet mouse model of early-stage Type 2 diabetes. / Wei, P.; Lane, P. H.; Lane, J. T.; Padanilam, B. J.; Sansom, S. C.

In: Diabetologia, Vol. 47, No. 9, 01.09.2004, p. 1541-1549.

Research output: Contribution to journalArticle

@article{85efda3f5e3141e9b9f35fe76e1a0da0,
title = "Glomerular structural and functional changes in a high-fat diet mouse model of early-stage Type 2 diabetes",
abstract = "Aims/hypothesis. Type 2 diabetes often results in diabetic nephropathy, which is preceded by an elevated glomerular filtration rate (GFR). This study was designed to develop a mouse model of Type 2 diabetes and to elucidate the glomerular events in the early stages of diabetic nephropathy. Methods. Four-week-old mice were fed a normal or high-fat (42{\%} of total calories from fat) diet, and body weight, blood glucose, insulin, leptin, lipids and GFR were monitored from 9 to 21 weeks or longer after the feeding programme. Mesangial cell dedifferentiation was accessed by alpha-smooth muscle actin staining. Glomerular hypertrophy was determined using image analysis with haematoxylin-eosin staining. Matrix deposition was determined by type IV collagen staining. Results. After 9 weeks, mice fed a high-fat diet weighed more than mice fed a normal diet (30.5±1.2 vs 22.3±0.5 g, p<0.05), and mice fed a high-fat diet were hyperinsulinaemic (283.9±69.7 vs 102.9±36.4 pmol/l, p<0.05), hyperglycaemic (8.0±0.6 vs 6.5±0.2 mmol/l, p<0.05) and their leptin levels were increased six-fold (1.48±0.45 vs 0.25±0.03 ng/ml, p<0.05). After 13 weeks, mice fed a high-fat diet showed hyperfiltration (GFR; 440±60 vs 210±10 μl/min, p<0.05). During the early stages of diabetic nephropathy, mesangial cell dedifferentiation was evident, shown by increased expression of alpha-smooth muscle actin in the glomeruli. After 9 weeks, mice fed a high-fat diet already demonstrated increased type IV collagen deposition. After 13 weeks, they developed enlarged glomerular tufts compared with those of their age-matched controls. Conclusions/interpretation. The results of this study suggest that collagen IV deposition precedes the hyperfiltration and enlargement of glomeruli in early-stage diabetic nephropathy. Dedifferentiation of mesangial cells may be associated with collagen IV deposition.",
keywords = "Diabetic nephropathy, GFR, Glomerulopathy, High-fat diet, Hyperfiltration, Hyperglycaemia, Hyperinsulinaemia, Leptin, Mice, Obesity, Type 2 diabetes, Type IV collagen",
author = "P. Wei and Lane, {P. H.} and Lane, {J. T.} and Padanilam, {B. J.} and Sansom, {S. C.}",
year = "2004",
month = "9",
day = "1",
doi = "10.1007/s00125-004-1489-1",
language = "English (US)",
volume = "47",
pages = "1541--1549",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "9",

}

TY - JOUR

T1 - Glomerular structural and functional changes in a high-fat diet mouse model of early-stage Type 2 diabetes

AU - Wei, P.

AU - Lane, P. H.

AU - Lane, J. T.

AU - Padanilam, B. J.

AU - Sansom, S. C.

PY - 2004/9/1

Y1 - 2004/9/1

N2 - Aims/hypothesis. Type 2 diabetes often results in diabetic nephropathy, which is preceded by an elevated glomerular filtration rate (GFR). This study was designed to develop a mouse model of Type 2 diabetes and to elucidate the glomerular events in the early stages of diabetic nephropathy. Methods. Four-week-old mice were fed a normal or high-fat (42% of total calories from fat) diet, and body weight, blood glucose, insulin, leptin, lipids and GFR were monitored from 9 to 21 weeks or longer after the feeding programme. Mesangial cell dedifferentiation was accessed by alpha-smooth muscle actin staining. Glomerular hypertrophy was determined using image analysis with haematoxylin-eosin staining. Matrix deposition was determined by type IV collagen staining. Results. After 9 weeks, mice fed a high-fat diet weighed more than mice fed a normal diet (30.5±1.2 vs 22.3±0.5 g, p<0.05), and mice fed a high-fat diet were hyperinsulinaemic (283.9±69.7 vs 102.9±36.4 pmol/l, p<0.05), hyperglycaemic (8.0±0.6 vs 6.5±0.2 mmol/l, p<0.05) and their leptin levels were increased six-fold (1.48±0.45 vs 0.25±0.03 ng/ml, p<0.05). After 13 weeks, mice fed a high-fat diet showed hyperfiltration (GFR; 440±60 vs 210±10 μl/min, p<0.05). During the early stages of diabetic nephropathy, mesangial cell dedifferentiation was evident, shown by increased expression of alpha-smooth muscle actin in the glomeruli. After 9 weeks, mice fed a high-fat diet already demonstrated increased type IV collagen deposition. After 13 weeks, they developed enlarged glomerular tufts compared with those of their age-matched controls. Conclusions/interpretation. The results of this study suggest that collagen IV deposition precedes the hyperfiltration and enlargement of glomeruli in early-stage diabetic nephropathy. Dedifferentiation of mesangial cells may be associated with collagen IV deposition.

AB - Aims/hypothesis. Type 2 diabetes often results in diabetic nephropathy, which is preceded by an elevated glomerular filtration rate (GFR). This study was designed to develop a mouse model of Type 2 diabetes and to elucidate the glomerular events in the early stages of diabetic nephropathy. Methods. Four-week-old mice were fed a normal or high-fat (42% of total calories from fat) diet, and body weight, blood glucose, insulin, leptin, lipids and GFR were monitored from 9 to 21 weeks or longer after the feeding programme. Mesangial cell dedifferentiation was accessed by alpha-smooth muscle actin staining. Glomerular hypertrophy was determined using image analysis with haematoxylin-eosin staining. Matrix deposition was determined by type IV collagen staining. Results. After 9 weeks, mice fed a high-fat diet weighed more than mice fed a normal diet (30.5±1.2 vs 22.3±0.5 g, p<0.05), and mice fed a high-fat diet were hyperinsulinaemic (283.9±69.7 vs 102.9±36.4 pmol/l, p<0.05), hyperglycaemic (8.0±0.6 vs 6.5±0.2 mmol/l, p<0.05) and their leptin levels were increased six-fold (1.48±0.45 vs 0.25±0.03 ng/ml, p<0.05). After 13 weeks, mice fed a high-fat diet showed hyperfiltration (GFR; 440±60 vs 210±10 μl/min, p<0.05). During the early stages of diabetic nephropathy, mesangial cell dedifferentiation was evident, shown by increased expression of alpha-smooth muscle actin in the glomeruli. After 9 weeks, mice fed a high-fat diet already demonstrated increased type IV collagen deposition. After 13 weeks, they developed enlarged glomerular tufts compared with those of their age-matched controls. Conclusions/interpretation. The results of this study suggest that collagen IV deposition precedes the hyperfiltration and enlargement of glomeruli in early-stage diabetic nephropathy. Dedifferentiation of mesangial cells may be associated with collagen IV deposition.

KW - Diabetic nephropathy

KW - GFR

KW - Glomerulopathy

KW - High-fat diet

KW - Hyperfiltration

KW - Hyperglycaemia

KW - Hyperinsulinaemia

KW - Leptin

KW - Mice

KW - Obesity

KW - Type 2 diabetes

KW - Type IV collagen

UR - http://www.scopus.com/inward/record.url?scp=5644263762&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=5644263762&partnerID=8YFLogxK

U2 - 10.1007/s00125-004-1489-1

DO - 10.1007/s00125-004-1489-1

M3 - Article

C2 - 15338127

AN - SCOPUS:5644263762

VL - 47

SP - 1541

EP - 1549

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 9

ER -