Cold Press Pomegranate Seed Oil Attenuates Dietary-Obesity Induced Hepatic Steatosis and Fibrosis through Antioxidant and Mitochondrial Pathways in Obese Mice

Abstract

Aim: Obesity is associated with metabolic syndrome, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), and type 2 diabetes. In this study, we investigated whether the dietary supplementation of pomegranate seed oil (PSO) exerted a protective effect on liver lipid uptake, fibrosis, and mitochondrial function in a mouse model of obesity and insulin resistance. Method: In this in vivo study, eight-week-old C57BL/6J male mice were fed with a high fat diet (HFD) for 24 weeks and then were divided into three groups as follows: group (1) Lean; group (n = 6) (2) HF diet; group (n = 6) (3) HF diet treated with PSO (40 mL/kg food) (n = 6) for eight additional weeks starting at 24 weeks. Physiological parameters, lipid droplet accumulation, inflammatory biomarkers, antioxidant biomarkers, mitochondrial biogenesis, insulin sensitivity, and hepatic fibrosis were determined to examine whether PSO intervention prevents obesity-associated metabolic syndrome. Results: The PSO group displayed an increase in oxygen consumption, as well as a decrease in fasting glucose and blood pressure (p < 0.05) when compared to the HFD-fed mice group. PSO increased both the activity and expression of hepatic HO-1, downregulated inflammatory adipokines, and decreased hepatic fibrosis. PSO increased the levels of thermogenic genes, mitochondrial signaling, and lipid metabolism through increases in Mfn2, OPA-1, PRDM 16, and PGC1α. Furthermore, PSO upregulated obesity-mediated hepatic insulin receptor phosphorylation Tyr-972, p-IRB tyr1146, and pAMPK, thereby decreasing insulin resistance. Conclusions: These results indicated that PSO decreased obesity-mediated insulin resistance and the progression of hepatic fibrosis through an improved liver signaling, as manifested by increased insulin receptor phosphorylation and thermogenic genes. Furthermore, our findings indicate a potential therapeutic role for PSO in the prevention of obesity-associated NAFLD, NASH, and other metabolic disorders.

Natural Product Heme Oxygenase Inducers as Treatment for Nonalcoholic Fatty Liver Disease

“…N. sativa oil and TQ are potent inducers of HO-1 in the lung, heart, liver, and cell lines such as HaCaT cells derived from human keratinocytes [ 75 , 76 , 105 , 106 , 107 ]. Recent studies have demonstrated that supplementation of TQ alone or given in combination with fish oil omega-3 prevents the development of dietary obesity-induced NAFLD [ 75 , 76 ]. TQ alone or in combination, also alleviated other dietary-induced obesity complications such as hypertension, decreases in oxygen consumption, and insulin resistance [ 75 , 76 ].…”

“…Recent studies have demonstrated that supplementation of TQ alone or given in combination with fish oil omega-3 prevents the development of dietary obesity-induced NAFLD [ 75 , 76 ]. TQ alone or in combination, also alleviated other dietary-induced obesity complications such as hypertension, decreases in oxygen consumption, and insulin resistance [ 75 , 76 ]. The ability of TQ supplementation to lower blood pressure in dietary-induced obesity is similar to a previous study demonstrating the antihypertensive actions of TQ supplementation in a model of nitric oxide deficient hypertension [ 106 ].…”

“…The ability of TQ supplementation to lower blood pressure in dietary-induced obesity is similar to a previous study demonstrating the antihypertensive actions of TQ supplementation in a model of nitric oxide deficient hypertension [ 106 ]. TQ supplementation also restored the levels of important markers of mitochondrial functions such as mitofusin-1 (MFN-1), MFN-2, and OPA1 in the liver [ 75 , 76 ]. Dietary obesity also induced hepatic fibrosis and inflammation, both of which were significantly reversed by TQ supplementation [ 75 , 76 ].…”

“…TQ supplementation also restored the levels of important markers of mitochondrial functions such as mitofusin-1 (MFN-1), MFN-2, and OPA1 in the liver [ 75 , 76 ]. Dietary obesity also induced hepatic fibrosis and inflammation, both of which were significantly reversed by TQ supplementation [ 75 , 76 ]. TQ supplementation also increased hepatic Akt signaling leading to alterations in insulin receptor phosphorylation and liver insulin resistance improvements [ 76 ].…”

“…Dietary obesity also induced hepatic fibrosis and inflammation, both of which were significantly reversed by TQ supplementation [ 75 , 76 ]. TQ supplementation also increased hepatic Akt signaling leading to alterations in insulin receptor phosphorylation and liver insulin resistance improvements [ 76 ]. Rashidmayvan et al recently tested the effectiveness of N. sativa oil in NAFLD patients in an eight week randomized, double-blind, placebo-controlled clinical trial [ 77 ].…”