Structural and functional changes in the kidneys of high-fat diet-induced obese mice

Abstract

Metabolic syndrome has been reported to be associated with chronic kidney disease, but the mechanisms remain unclear. Although feeding of a high-fat diet (HFD) to C57BL/6 mice is reported to induce systemic metabolic abnormalities and subsequent renal injuries, such as albuminuria, similar to human metabolic syndrome, alterations in HFD-induced renal injuries have not been fully elucidated in detail. We therefore investigated the structural and functional changes in the kidneys of C57BL/6 mice on a HFD. Six-week-old mice were fed a low-fat diet (LFD; 10% of total calories from fat) or a HFD (60% fat) for 12 wk. Mice fed a HFD showed significant increases in body weight, systolic blood pressure, plasma insulin, glucose, and triglycerides compared with those on a LFD. Accompanying these systemic changes, mice on a HFD showed albuminuria, an increase in glomerular tuft area, and mesangial expansion. These systemic and renal alterations in mice on a HFD were prevented by body weight control with the dietary restriction of feeding a HFD. Furthermore, mice on a HFD showed renal pathophysiological alterations including renal lipid accumulation, an increased accumulation of type IV collagen in glomeruli, an increase in macrophage infiltration in the renal medulla, an increase in urinary 8-hydroxy-2'-deoxyguanosine excretion, and impaired sodium handling. In conclusion, this study suggests that local metabolic alterations in the kidney play important roles in the development of renal injury associated with metabolic syndrome in addition to systemic metabolic changes and an increase in body weight.

Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice

“…Clinical factors, including hypertension, diabetes mellitus, obesity, abnormal lipid levels and vitamin deficiency, as well as tissue factors such as increased activity of the renin-angiotensin-aldosterone system, increased levels of advanced glycation end products, oxidative stress, decreased nitric oxide, TGF-β, have been associated with increasing renal aging (Choudhury & Levi 2011). In addition, HFD-induced obese mice showed pathophysiological changes including albuminuria, increase in glomerular tuft area, mesangial expansion, renal lipid accumulation, increased collagen in glomeruli, increased macrophage infiltration in medulla, and impaired sodium handling (Deji et al 2009). Therefore, we could suppose that aging combined with HFD feeding are considered to further increase the risk of development or progression of renal injury.…”

“…In addition, HFD feeding in mice has been known to induce characteristics of metabolic syndrome including obesity, hyperglycemia, hyperinsulinemia, dyslipidemia, and hypertension. These systemic changes combined with local alterations in the kidney with aging are considered to further increase the risk of development or progression of chronic kidney disease (Deji et al 2009). However, the effect of aging on HFD-induced renal injury has not been determined.…”

Mechanisms of obesity-induced hypertension

“…31 The primary histologic features are relatively few lesions of focalsegmental glomerulosclerosis, profound glomerulomegaly because of glomerular hyalinosis and fibrosis, as well as lipid accumulation in the glomeruli and adhesion to Bowman's capsule. 32,33 Some studies suggest that lipid accumulation is a result of alterations in fat metabolism.…”

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

“…Metformin Reduces Renal Inflammation, Apoptosis, and Fibrosis-Clinical and experimental studies highlighted the association of high fat diet with inflammation and apoptosis (24,25). Hence, we also checked the molecular markers of renal inflammation, apoptosis, and fibrosis.…”