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.