A high-fat diet aggravates tubulointerstitial but not glomerular lesions in obese Zucker rats

Abstract

A high-fat diet aggravates tubulointerstitial but not glomerular density lipoprotein (LDL) [1]. Although many studies lesions in obese Zucker rats.have evaluated the effects of dietary fat on glomerular Background. Despite a large body of evidence that manipulesions, limited information is available regarding its eflation of dietary fat alters glomerular lesions, reports regarding fects on tubulointerstitial lesions. To examine whether a the effects of dietary fat on tubulointerstitial lesions are limited. high-fat diet aggravates glomerular and tubulointerstitialObese Zucker rats (OZR) spontaneously develop glomerular and tubulointerstitial lesions in association with hyperlipidlesions, we administered a high (20%)-or low (1%)-fat emia. We sought to elucidate the effects of dietary fat on diet to OZR and lean Zucker rats (LZR) for 30 weeks. glomerular and tubulointerstitial lesions in OZR versus leanIn this study, the high-fat diet aggravated tubulointer-Zucker rats (LZR) and to assess the involvement of macrostitial but not glomerular injury in OZR, whereas the phages in the development of these lesions.Methods. We fed LZR and OZR either a low-(1%) or opposite occurred in LZR. We also evaluated whether high-fat (20%) diet. After 30 weeks of the specified diet, the macrophages are involved in the development of dietary creatinine clearance (C Cr ) and renal histology as well as plasma fat-induced tubulointerstitial and glomerular lesions in lipid concentrations were examined. For morphological evaluathese rats.tion, glomerular sclerosis (GSI) and tubulointerstitial indices (TII) were each determined by a point-counting method. Infiltrating macrophages were stained immunohistochemically us- METHODSing an avidin-biotin complex technique. Results. The high-fat diet increased the plasma low-densityFive-week-old male LZR and OZR were purchased lipoprotein concentration in OZR. Both low-and high-fat OZR from Charles River Laboratories (Kingston, NY, USA).groups had higher GSI and TII than LZR receiving either diet.Rats had free access to food. LZR and OZR were eachThe high-fat diet aggravated TII but not GSI or C Cr in OZR;divided into two groups according to dietary fat content:conversely, high fat intake worsened GSI and C Cr but not TII in LZR. Tubulointerstitial macrophages were most prominent low-fat LZR (N ϭ 9), high-fat LZR (N ϭ 7), low-fat in the high-fat OZR group, followed by the low-fat OZR group.OZR (N ϭ 6), and high-fat OZR (N ϭ 8). Low-fat rats Glomerular macrophages were similar in number in all groups.were given a daily diet with 1% fat (corn oil, 0.5%; lard,Conclusions. The manipulation of dietary fat has diverse 0.5%). The high-fat diet included 20% fat (corn oil, 10%;effects on the kidney. A high-fat diet aggravated macrophagemediated tubulointerstitial lesions in OZR, whereas in LZR, lard, 10%). The rats' body weight was measured every the diet induced glomerulosclerosis.

The high-fat-fed lean Zucker rat: a spontaneous isocaloric model of fat-induced insulin resistance associated with muscle GSK-3 overactivity

“…1). This observation is consistent with the findings of a previous study using male lean Zucker rats, in which a less pronounced high-fat diet (20% of calories derived from fat) was provided over 30 wk (30). However, it is clear that the proportion of consumed calories derived from fat was markedly higher in the HFF group (Fig.…”

“…For example, Matsuda et al (30) fed male lean Zucker rats a 20% fat diet for 30 wk and reported a greater body weight gain, increased plasma triglycerides, and enhanced plasma thiobarbituric acid-reacting substrates, an index of oxidative stress. Maher et al (28) fed male lean Zucker rats a 48% fat diet for 6 wk and observed an enhanced body weight gain, but no effects on plasma glucose or insulin.…”

“…Rats undergoing high-fat feeding (HFF) (ϳ50% of calories derived from fat for more than 3 wk) display marked metabolic dysfunctions (14,16,25), including large increases in body weight gain. However, only a limited number of investigations have pursued a long-term (Ͼ3 wk) HFF regimen in lean Zucker rats (24,27,28,30). These previous HFF studies utilized male lean Zucker rats, and none of these investigations have adequately addressed the potential metabolic consequences of a long-term high-fat diet in the lean Zucker rats, including an assessment of skeletal muscle insulin signaling.…”

Saturated-fat diet induces moderate diabetes and severe glomerulosclerosis in hamsters

“…Concurrently, the widening of the mesangial area occurred, and led eventually to renal failure, the main cause of increased mortality recorded in hamsters fed with saturated-fat diets. Our data corroborate and extend the findings of previous studies showing that obesity and high-fat diets are linked with kidney dysfunction in rats [6,8] and dogs [12]. The exact mechanism of this has not been defined but could involve input from non-esterified fatty acids [39].…”

Hyperlipidemia aggravates renal disease in B6.ROP Os/+ mice

“…Lipids have been shown to induce glomerular expression of chemoattractants such as MCP-1, monocyte-colony-stimulating factor (M-CSF), migration inhibitory factor (MIF), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) [47][48][49] and various animal models of hyperlipidemia-induced renal disease have demonstrated increased influx of macrophages into glomeruli [28,30,34,50] and into the tubulointerstitium [23,29,51,52] of affected animals. The functional importance of macrophages in mediating renal injury in hyperlipidemic states is highlighted by work done by Pesek-Diamond et al [51] showing that depletion of macrophages resulted in an amelioration of renal function impairment and reduction of glomerulosclerosis and matrix expansion in hyperlipidemic rats with acute puromycin aminonucleoside nephrosis.…”