Gamma Oryzanol Treats Obesity‐Induced Kidney Injuries by Modulating the Adiponectin Receptor 2/PPAR‐α Axis

Abstract

The kidney is an important organ in the maintenance of body homeostasis. Dietary compounds, reactive metabolites, obesity, and metabolic syndrome (MetS) can affect renal filtration and whole body homeostasis, increasing the risk of chronic kidney disease (CKD) development. Gamma oryzanol (γOz) is a compound with antioxidant and anti-inflammatory activity that has shown a positive action in the treatment of obesity and metabolic diseases. Aim. To evaluate the effect of γOz to recover renal function in obese animals by high sugar-fat diet by modulation of adiponectin receptor 2/PPAR-α axis Methods. Male Wistar rats were initially randomly divided into 2 experimental groups: control and high sugar-fat diet (HSF) for 20 weeks. When proteinuria was detected, HSF animals were allocated to receive γOz or maintain HSF for more than 10 weeks. The following were analyzed: nutritional and biochemical parameters, systolic blood pressure, and renal function. In the kidney, the following were evaluated: inflammation, oxidative stress, and protein expression by Western blot. Results. After 10 weeks of γOz treatment, γOz was effective to improve inflammation, increase antioxidant enzyme activities, increase the protein expression of adiponectin receptor 2 and PPAR-α, and recover renal function. Conclusion. These results permit us to confirm that γOz is able to modulate PPAR-α expression, inflammation, and oxidative stress pathways improving obesity-induced renal disease.

CD36-Mediated Lipid Accumulation and Activation of NLRP3 Inflammasome Lead to Podocyte Injury in Obesity-Related Glomerulopathy

“…SREBP-1 is responsible for fatty acid synthesis, and PPAR α regulates lipid oxidation utilization [3]. It has been reported that the expression of PPAR α in kidney tissue is downregulated in the mouse model of high-fat diet and cases of stage IV of diabetic nephropathy [30, 31], which is inconsistent with our results. One of the possible reasons for inconsistency may be that the modeling time of ORG mice is about 12 weeks and the renal lesion seems to maintain in the early stage.…”

Gamma-oryzanol as a potential modulator of oxidative stress and inflammation via PPAR-y in adipose tissue: a hypothetical therapeutic for cytokine storm in COVID-19?

“…Body weight was measured weekly. After euthanasia, the fat deposits (visceral (VAT), epididymal (EAT) and retroperitoneal (RAT) were used to calculate the adiposity index (AI) by the following formula: [(VAT + EAT + RAT)/FBW] x100 [ 21 ].…”

“…Natural compounds as γOz, the main bioactive from rice bran and germ, is a compound with anti-inflammatory and antioxidant activities [ 18 ]. Studies have shown that the γOz has a positive action in the treatment of some obesity- related comorbidities and attenuation of proinflammatory cytokines [ [19] , [20] , [21] , [22] ]. However, little is known about the γOz action as a possible agonist of PPAR-γ.…”

Adiponectin in renal fibrosis

“…Previous studies have reported that the AGING APN-mediated prostacyclin-PPARα-heme oxygenase-1 signaling pathway protects against renal ischemia/ reperfusion injury [55]. Furthermore, it has recently been shown that γ-oryzanol improves obesity-induced nephropathy by regulating the AdipoR2/PPAR-α axis [56]. Recent evidence has shown that AdipoR2-induced activation of PPARα upregulates the genes involved in fatty acid transport and binding and also activates peroxisomal and mitochondrial fatty acid β-oxidation, thereby promoting fatty acid catabolism.…”