Liver X receptor activation induces podocyte injury via inhibiting autophagic activity

Podocyte injury plays a key role in the occurrence and development of kidney diseases. Decreased autophagic activity in podocyte is closely related to its injury and the occurrence of proteinuria. Liver X receptors (LXRs), as metabolic nuclear receptors, participate in multiple pathophysiological processes and express in several tissues, including podocytes. Although the functional roles of LXRs in the liver, adipose tissue and intestine are well established; however, the effect of LXRs on podocytes function remains unclear. In this study, we used mouse podocytes cell line to investigate the effects of LXR activation on podocytes autophagy level and related signaling pathway by performing Western blotting, RT-PCR, GFP-mRFP-LC3 transfection, and immunofluorescence staining. Then, we tested this effect in STZ-induced diabetic mice. Transmission electron microscopy and immunohistochemistry were employed to explore the effects of LXR activation on podocytes function and autophagic activity. We found that LXR activation could inhibit autophagic flux through blocking the formation of autophagosome in podocytes in vitro which was possibly achieved by affecting AMPK, mTOR, and SIRT1 signaling pathways. Furthermore, LXR activation in vivo induced autophagy suppression in glomeruli, leading to aggravated podocyte injury. In summary, our findings indicated that activation of LXRs induced autophagy suppression, which in turn contributed to the podocyte injury.

     

Inverse Relationship between Serum Lipoxin A4 Level and the Risk of Metabolic Syndrome in a Middle-Aged Chinese Population

Metabolic syndrome (MetS) has been identified to be associated with a state of chronic, low-grade inflammation in adipose tissue. Lipoxins are endogenously generated from arachidonic acid, and exhibit anti-inflammatory actions. Currently, there is no available cohort study identifying the association between serum lipoxins level and MetS. Here we investigate the relationship between serum lipoxin A4 (LXA4) level and the risk of incident MetS in a middle-aged Chinese population. A total 624 participants aged 40–65 years were enrolled at baseline, with 417 (including 333 MetS absence) of them were followed up at 2.5 years. Abdominal visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) were determined using MRI. Serum lipoxin A4 levels were measured by ELISA. At baseline, serum LXA4 levels were significantly correlated with a cluster of traditional MetS risk factors related to obesity (P≤0.05). A higher incidence of new Mets was found in the participants of the lowest tertile of LXA4 levels as compared with that in participants of the highest tertile (P = 0.025). Low serum LXA4 levels [OR 2.607(1.151–5.909), P = 0.022] and high VFA [OR 2.571(1.176–5.620), P = 0.018] were associated with an increased incident Mets, respectively, which remained statistically significant after adjustment for age, gender, current smoking, and alcohol drinking status. Logistic regression analysis suggested a combination of low serum LXA4 levels and high WC/VFA might optimize the prediction of incident Mets in middle-aged Chinese population [OR 4.897/4.967, P = 0.009/0.003]. Decrease in serum LXA4 level and increase in VFA are independent predictors of incident Mets in a population-based cohort, and a combination of them enhances the prognostic value of incident Mets. Taken together, our data suggest that serum LXA4 levels might be useful for early detection and prevention of Mets.