RESUMO
Red rice bran extract (RRBE) is rich in phytonutrients and has been shown to have anti-diabetic, anti-inflammatory, and antioxidant properties. However, its anti-hepatic steatosis and anti-dyslipidemic properties have not been thoroughly investigated. This study examined the aforementioned properties of RRBE, the underlying mechanism by which it alleviated non-alcoholic fatty liver disease in high-fat diet (HFD)-fed mice, and its major bioactive constituents. The mice were divided into four groups based on their diet: (1) low-fat diet (LFD), (2) LFD with high-dose RRBE (1 g/kg/day), (3) HFD, and (4) HFD with three different doses of RRBE (0.25, 0.5, and 1 g/kg/day). The administration of RRBE, especially at medium and high doses, significantly mitigated HFD-induced hepatosteatosis and concomitantly improved the serum lipid profile. Further, RRBE modified the level of expression of lipid metabolism-related genes (adipose triglyceride lipase (ATGL), cluster of differentiation 36 (CD36), lipoprotein lipase (LPL), liver X receptor alpha (LXRα), sterol regulatory element-binding protein-1c (SREBP-1c), SREBP-2, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), and carnitine palmitoyltransferase 1A (CPT1A)) in hepatic or adipose tissues and improved the expression of hepatic high-density lipoprotein cholesterol (HDL-C) cmetabolism-related genes (hepatic lipase (HL) and apolipoprotein A-Ç (ApoA-Ç)). RRBE also attenuated markers of liver injury, inflammation, and oxidative stress, accompanied by a modulated expression of inflammatory (nuclear factor-kappa B (NF-κB) and inducible nitric oxide synthase (iNOS)), pro-oxidant (p47phox), and apoptotic (B-cell lymphoma protein 2 (Bcl-2)-associated X and Bcl-2) genes in the liver. High-performance liquid chromatography analyses indicated the presence of protocatechuic acid, γ-oryzanol, vitamin E, and coenzyme Q10 in RRBE. Our data indicate that RRBE alleviates HFD-induced hepatosteatosis, dyslipidemia, and their pathologic complications in part by regulating the expression of key genes involved in lipid metabolism, inflammation, oxidative stress, and apoptosis.
Assuntos
Dislipidemias , Hepatopatia Gordurosa não Alcoólica , Oryza , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Dieta Hiperlipídica/efeitos adversos , Fígado/metabolismo , Metabolismo dos Lipídeos , Inflamação/metabolismo , Dislipidemias/etiologia , Dislipidemias/complicações , Anti-Inflamatórios/metabolismo , Camundongos Endogâmicos C57BLRESUMO
Red rice bran extract (RRBE) has been reported to have the potential for in vitro metabolic modulation and anti-inflammatory properties. However, little is known about the molecular mechanisms of these potentials in adipose tissue. This study aimed to evaluate the in vivo anti-adipogenic, anti-hypertrophic, and anti-inflammatory activities of RRBE and its major bioactive compounds in mice. After six weeks of consuming either a low-fat diet or a high-fat diet (HFD), 32 mice with initial body weights of 20.76 ± 0.24 g were randomly divided into four groups; the four groups were fed a low-fat diet, a HFD, a HFD plus 0.5 g/kg of RRBE, or a HFD plus 1 g/kg of RRBE, respectively. The 6-week treatment using RRBE reduced HFD-induced adipocyte hypertrophy, lipid accumulation, and inflammation in intra-abdominal epididymal white adipose tissue (p < 0.05) without causing significant changes in body and adipose tissue weight, which reductions were accompanied by the down-regulated expression of adipogenic and lipid metabolism genes, including CCAAT/enhancer-binding protein-alpha, sterol regulatory element-binding protein-1c, and hormone-sensitive lipase (p < 0.05), as well as inflammatory genes, including macrophage marker F4/80, nuclear factor-kappa B p65, monocyte chemoattractant protein-1, tumor necrosis factor-alpha, and inducible nitric oxide synthase (p < 0.05), in adipose tissue. Furthermore, RRBE significantly decreased serum tumor necrosis factor-alpha levels (p < 0.05). Bioactive compound analyses revealed the presence of phenolics, flavonoids, anthocyanins, and proanthocyanidins in these extracts. Collectively, this study demonstrates that RRBE effectively attenuates HFD-induced pathological adipose tissue remodeling by suppressing adipogenesis, lipid dysmetabolism, and inflammation. Therefore, RRBE may emerge as one of the alternative food products to be used against obesity-associated adipose tissue dysfunction.