Abstract
BackgroundObesity is a risk factor for chronic kidney disease (CKD). While the exact mechanisms remain unclear, inflammation may be a consequence of obesity that directly impacts the kidneys. The aim of this study was to examine the inflammatory status of the kidneys and potential ongoing renal damage, i.e., tubular damage and fibrosis after long-term obesity maintained through persistent consumption of a high-fat diet (HFD).ResultsTwenty-four-week-old male Long-Evans (LEV) rats were continuously fed a control diet (CD) or HFD for 51 weeks. The mean body weight was higher in HFD-fed rats than in control diet-fed rats and markedly elevated during the last 24 weeks. Blood analyses revealed no substantial alterations in renal functional parameters by HFD consumption but a substantial increase in creatine kinase, a muscle loss marker. Magnetic resonance imaging (MRI) was utilized to quantify rat quadriceps muscle mass. The data showed that HFD-induced obesity in LEV rats was accompanied by minor decreases in muscle mass and strength at 75 weeks of age. Rat kidney inflammatory status was evaluated using histological and immunohistological techniques. The number of foci with immune cell infiltrates and infiltrating monocytes/macrophages was significantly increased in HFD-fed rat kidneys at week 75. Renal fibrosis parameters, including glomerulosclerosis and tubular damage, were also markedly increased in renal tissues from HFD-fed rats compared to the controls. The significant increase in tubular protein casts in HFD-fed rat tissues indicated that renal function was already disturbed. Rat kidney inflammatory status was further evaluated using the simultaneous profiling of twenty-two inflammatory markers in kidney tissue extracts. Consistently, MCP-1 and eotaxin (CCL11) levels were elevated in obese LEV rat kidneys.ConclusionsCompared to CD-fed rats, HFD-fed obese LEV rats show significant damage of renal structures with aging. These subtle changes may sensitize the kidneys to the development of progressive CKD.
Highlights
Obesity is a risk factor for chronic kidney disease (CKD)
Long-term high-fat diet (HFD) leads to obesity and impairment of muscle function in aging rats To investigate the effect of long-term HFD in aging LEV rats, we measured food intake and body weight of eight HFD-fed and eight control diet (CD)-fed male rats between 23 and 75 weeks of age
Magnetic resonance imaging (MRI)-based examination of the musculus vastus lateralis cross-sectional area showed a slight but significant decrease in the relative cross-sectional area in the HFD group, which was consistent with the results from the grip strength test (Fig. 1d, left panel)
Summary
Obesity is a risk factor for chronic kidney disease (CKD). While the exact mechanisms remain unclear, inflammation may be a consequence of obesity that directly impacts the kidneys. Controlled animal studies revealed that a few weeks of rapid weight gain leads to structural changes in the kidneys, including enlargement of Bowman’s space, increased glomerular cell proliferation, thicker mesangial matrix and basement membranes [9]. These early renal changes occurred with no evidence for initial renal malfunction; if progressive, they could eventually impact the glomerular lumen, reduce the filtration surface area and lead to kidney injury. This slowly developing vicious cycle may be accelerated in the setting of metabolic derangements induced by obesity, such as inflammation or oxidative stress
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