Hypolipidemic and Antioxidant Properties of Oryzanol Concentrate in Reducing Diabetic Nephropathy via SREBP1 Downregulation Rather than β-Oxidation.

Scope: Diabetic nephropathy (DN) is a micro-vascular complication of
chronic diabetes. Sterol regulatory element binding protein1 (SREBP1)
participation in the development of DN is reported. Oryzanol concentrate
(OC) at 0.1% and 0.3% is tested for its antioxidant and hypolipidemic effects.
The aim of the work is to study the involvement of OC in the amelioration of
DN in STZ-induced diabetic animal model.
Methods and results: Animals were grouped into starch, high-fat, and
OC-treated control/diabetic groups (SFC/SFD, HFC/HFD, OFC/OFD). The
markers of DN, increased glomerular filtration rate and kidney weight, were
evident in HFD and reduced in OFD group by �1.09 and �1.3 fold,
respectively. The amelioration of defensive antioxidant enzyme activities and
lipid peroxidation, expressions of lipid-associated biomolecules (SREBP1 and
FAS) were also observed. HFD showed increased ECM accumulation of
glycoproteins, particularly Type IV collagen, fibronectin. SREBP1-associated
gene transforming growth factor-β (TGF-β) was reduced on treatment (OFD
� 1.3 fold) as to HFD (�2.7 fold).
Conclusion: Oryzanol concentrate, having hypolipidemic and antioxidant
properties, also downregulated the lipid biosynthesis through reduced
SREBP1–TGF-β interactions (EMSA) and could effectively ameliorate DN.
Gene (ACC2, Cpt1, and ACOX) expression studies showed that β-oxidation
was not involved in reducing DN.