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Sterol O-Acyltransferase Inhibition Ameliorates High-Fat Diet-Induced Renal Fibrosis and Tertiary Lymphoid Tissue Maturation after Ischemic Reperfusion Injury

Ariyasu, Yuki 京都大学 DOI:10.14989/doctor.k24795

2023.05.23

概要

There is a substantial and increasing burden of obesity on public health worldwide.
Obesity is a major risk factor for several pathological conditions, including hypertension,
diabetes, cardiovascular diseases, and chronic kidney disease (CKD). Importantly, several
clinical studies have demonstrated that obesity is a major risk factor for the development
of end-stage renal disease (ESRD), which is independent of diabetes and hypertension [1].
Hsu et al. reported that, in the general population, obese patients (BMI > 30 kg/m2 )
had a 3.57-fold higher risk of developing ESRD compared with normal weight patients
(BMI: 18.5–24.9 kg/m2 ) [2]. Experimental studies utilizing a high-fat diet (HFD)-induced
obesity model also demonstrated an association between obesity and CKD. In the kidneys of HFD-fed mice, lipid dysregulation, such as accumulation of non-esterified fatty
acids and/or cholesterol, was observed, along with increased pro-inflammatory cytokines,
oxidative stress, and fibrosis [3–5], which are major hallmarks of chronic inflammation.
However, despite its clinical significance, the mechanisms by which obesity promotes
chronic inflammation remain elusive, and the molecular details of lipid dysregulation in
obesity-related kidney disease remain unclear. ...

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