High-fat-diet-induced obesity causes an inflammatory and tumor-promoting microenvironment in the rat kidney

Abstract

SUMMARYObesity and concomitant comorbidities have emerged as public health problems of the first order. For instance, obese individuals have an increased risk for kidney cancer. However, direct mechanisms linking obesity with kidney cancer remain elusive. We hypothesized that diet-induced obesity (DIO) promotes renal carcinogenesis by inducing an inflammatory and tumor-promoting microenvironment. We compared chow-fed lean Wistar rats with those that were sensitive (DIOsens) or partially resistant (DIOres) to DIO to investigate the impact of body adiposity versus dietary nutrient overload in the development of renal preneoplasia and activation of tumor-promoting signaling pathways. Our data clearly show a correlation between body adiposity, the severity of nephropathy, and the total number and incidence of preneoplastic renal lesions. However, similar plasma triglyceride, plasma free fatty acid and renal triglyceride levels were found in chow-fed, DIOres and DIOsens rats, suggesting that lipotoxicity is not a critical contributor to the renal pathology. Obesity-related nephropathy was further associated with regenerative cell proliferation, monocyte infiltration and higher renal expression of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-6, IL-6 receptor and leptin receptor. Accordingly, we observed increased signal transducer and activator of transcription 3 (STAT3) and mammalian target of rapamycin (mTOR) phosphorylation in tubules with preneoplastic phenotypes. In summary, our results demonstrate that high body adiposity induces an inflammatory and proliferative microenvironment in rat kidneys that promotes the development of preneoplastic lesions, potentially via activation of the STAT3 and mTOR signaling pathways.

Gold-quercetin nanoparticles prevent metabolic endotoxemia-induced kidney injury by regulating TLR4/NF-kB signaling and Nrf2 pathway in high fat diet fed mice

“…[43][44][45] Particularly, pervious researches have suggested that excess intake of fat-rich diet may cause hyperlipemia and intestinal endotoxemia, resulting in blood lipid metabolism disorder and systemic inflammation, ultimately contributing to the development of CKD and NAFLD. [46][47][48] Thus, kidney disease caused by eating habits has widely received enough attention by the researchers. HFD-induced metabolic abnormalities would change kidney-related gene expression …”

“…48 Therefore, inhibition of metabolic disorder at an early stage is considered a feasible strategy for curing chronic renal disease. Recently, quercetin, a beneficial bioflavonoid thought to promote health, has been shown to aid in the prevention of cancer, hepatitis, atherosclerosis, organic lesions, and other diseases.…”

The emerging role of the endocannabinoid system in the pathogenesis and treatment of kidney diseases

“…glomerular hypertrophy, glomerular basement membrane thickening, mesangial matrix expansion, and increased tubular inflammation) [83,84]. Together with renal inflammation [85] and oxidative stress [86], these changes may lead to decreased renal function and ultimately glomerulosclerosis and tubulointerstitial fibrosis [78,[87][88][89].…”

A High-Fat Diet Increases Oxidative Renal Injury and Protein Glycation in D-Galactose-Induced Aging Rats and Its Prevention by Korea Red Ginseng

“…d-Galactose has been used to induce oxidative stress in vivo to mimic the natural aging process in rats and mice (17)(18)(19)(20). In addition, a high-fat diet (HFD) was found to be a significant risk factor for kidney disease (21)(22)(23). HFD-induced obesity may expedite the aging process (24).…”