Adropin Carried by Reactive Oxygen Species-Responsive Nanocapsules Ameliorates Renal Lipid Toxicity in Diabetic Mice

Abstract

Diabetic kidney disease (DKD) is a common diabetes complication mainly caused by lipid toxicity characterized by oxidative stress. Studies have shown that adropin (Ad) regulates energy metabolism and may be an effective target to improve DKD. This study investigated the effect of exogenous Ad encapsulated in reactive oxygen species (ROS)-responsive nanocapsules (Ad@Gel) on DKD. HK2 cells were induced with high glucose (HG) and intervened with Ad@Gel. A diabetes mouse model was established using HG and high-fat diet combined with streptozotocin and treated with Ad@Gel to observe its effects on renal function, pathological damage, lipid metabolism, and oxidative stress. Results showed that Ad@Gel could protect HK2 from HG stimulation in vitro. It also effectively controls blood glucose and lipid levels, improves renal function, inhibits excessive production of ROS, protects mitochondria from damage, improves lipid deposition in renal tissues, and downregulates the expression of lipogenic proteins SEBP-1 and ADRP in DKD mice. In HG-induced HK2 cells or the kidney of DKD patients, the low expression of neuronatin (Nnat) and high expression of translocator protein (TSPO) were observed. Knockdown Nnat or overexpression of TSPO significantly reversed the effect of Ad@Gel on improving mitochondrial damage. In addition, knockdown Nnat also significantly reversed the effect of Ad@Gel on lipid metabolism. The results suggest that the effect of Ad on DKD may be achieved by activating Nnat to improve lipid metabolism and inhibit TSPO activity, thereby enhancing mitochondrial function.

The impact of oxidative stress-induced mitochondrial dysfunction on diabetic microvascular complications

“…In addition, other researchers found that Nox4 knockdown reduced NADPH oxidase activity, accompanied by reduction in high-glucose-induced superoxide, yet mitochondrial Nox4 expression was increased in the renal cortex of diabetic rats, demonstrating the role for Nox4 in the regulation of mitochondrial function ( 144 ). Adropin improved lipid metabolism and renal function in diabetic mice, regulated blood glucose and lipids, inhibited ROS production, improved lipid deposition and down-regulated lipoprotein expression ( 145 ). G Protein-Coupled Bile Acid Receptor TGR5 improved indicators of renal injury in db/db mice, upregulated regulators of mitochondrial biogenesis, reduced lipid accumulation and H 2 O 2 production and increased SOD2 activity; similarly, similar results were observed in high glucose-induced podocytes ( 146 ).…”

Role of adropin in arterial stiffening associated with obesity and type 2 diabetes

“…This would indicate that presence of adropin may be required for priming the phosphorylation of eNOS and the production of NO through Akt activation, which is Ca 2+ -independent, to elicit augmented endothelial-dependent vasodilation. Alternatively, adropin has been reported to decrease reactive oxygen species (228), which could result in the increased bioavailability of NO and endothelial function of aged arteries. Third, the receptor for adropin-mediated effects on endothelial cells remains to be fully elucidated and controversial.…”

Mechanism of Cytotoxic Action of Gold Nanorods Photothermal Therapy for A549 Cell

“…Cancer cells use lipid metabolism to obtain energy, biofilm components, and signaling molecules needed for proliferation, survival, invasion, metastasis, tumor response, and cancer treatment. Numerous studies showed that lipid metabolism disorders play a key role in the progression of NPs exposure toxicity. ,− In this experimental group, 18-hydroxyoleate and 9,10-epoxystearic acid were up-regulated and phosphocholine was downregulated, while the levels of the remaining metabolites did not change significantly. Both metabolites in the GNR group were significantly up-regulated, implying that these may help in clearing cancer cells.…”