RESUMEN
Chronic inflammation and insulin resistance lead to metabolic syndrome and there is an urgent need to establish effective treatments and prevention methods. Our previous study reported that obese model Zucker (fa/fa) rats fed with ozonated olive oil alleviated fatty liver and liver damage by suppressing inflammatory factors. However, differences among animal species related to the safety and efficacy of ozonated olive oil administration remain unclear. Therefore, this study investigated the effects of oral intake of ozonated olive oil on lipid metabolism in normal mice and mice in the obesity model. C57BL/6J and db/db mice were fed the following AIN-76 diets for four weeks: the mice were either fed a 0.5% olive oil diet (Control diet) or 0.5% ozonated olive oil diet (Oz-Olive diet) in addition to 6.5% corn oil. The results indicated that four weeks of Oz-Olive intake did not adversely affect growth parameters, hepatic lipids or serum parameters in normal C57BL/6J mice. Subsequent treatment of db/db mice with Oz-Olive for four weeks reduced the levels of hepatic triglycerides, serum alkaline phosphatase, and serum insulin. These effects of Oz-Olive administration might be due to suppression of fatty acid synthesis activity and expression of lipogenic genes, as well as suppression of inflammatory gene expression. In conclusion, this study confirmed the safety of Oz-Olive administration in normal mice and its ability to alleviate hepatic steatosis by inhibiting fatty acid synthesis and inflammation in obese mice.
Asunto(s)
Hígado Graso , Ratones , Ratas , Animales , Aceite de Oliva/farmacología , Aceite de Oliva/uso terapéutico , Aceite de Oliva/metabolismo , Ratones Endogámicos C57BL , Ratas Zucker , Hígado Graso/metabolismo , Hígado/metabolismo , Ratones Endogámicos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Ácidos Grasos/metabolismo , Inflamación/metabolismo , Ratones ObesosRESUMEN
MAIN CONCLUSION: A novel gene belonging to the aldo-keto reductase 13 family is involved in isoliquiritigenin biosynthesis in dahlia. The yellow pigments of dahlia flowers are derived from 6'-deoxychalcones, which are synthesized via a two-step process, involving the conversion of 3-malonyl-CoA and 4-coumaloyl-CoA into isoliquiritigenin in the first step, and the subsequent generation of butein from isoliquiritigenin. The first step reaction is catalyzed by chalcone synthase (CHS) and aldo-keto reductase (AKR). AKR has been implicated in the isoflavone biosynthesis in legumes, however, isolation of butein biosynthesis related AKR members are yet to be reported. A comparative RNA-seq analysis between two dahlia cultivars, 'Shukuhai' and its butein-deficient lateral mutant 'Rinka', was used in this study to identify a novel AKR gene involved in 6'-deoxychalcone biosynthesis. DvAKR1 encoded a AKR 13 sub-family protein with significant differential expression levels, and was phylogenetically distinct from the chalcone reductases, which belongs to the AKR 4A sub-family in legumes. DNA sequence variation and expression profiles of DvAKR1 gene were correlated with 6'-deoxychalcone accumulation in the tested dahlia cultivars. A single over-expression analysis of DvAKR1 was not sufficient to initiate the accumulation of isoliquiritigenin in tobacco, in contrast, its co-overexpression with a chalcone 4'-O-glucosyltransferase (Am4'CGT) from Antirrhinum majus and a MYB transcription factor, CaMYBA from Capsicum annuum successfully induced isoliquiritigenin accumulation. In addition, DvAKR1 homologous gene expression was detected in Coreopsideae species accumulating 6'-deoxychalcone, but not in Asteraceae species lacking 6'-deoxychalcone production. These results not only demonstrate the involvement of DvAKR1 in the biosynthesis of 6'-deoxychalcone in dahlia, but also show that 6'-deoxychalcone occurrence in Coreopsideae species developed evolutionarily independent from legume species.
Asunto(s)
Chalconas , Dahlia , Aldehído Reductasa/metabolismo , Aldo-Ceto Reductasas/genética , Aldo-Ceto Reductasas/metabolismo , Chalconas/metabolismo , Coenzima A/metabolismo , Dahlia/genéticaRESUMEN
Excessive lipid accumulation in organs and adipocytes results in chronic inflammation. This causes irreversible organ dysfunction and the development of metabolic syndrome, atherosclerosis, and cancer. Ozonated olive oil shows anti-inflammatory effects when applied directly to the skin; however, there are no reports on its effects on lipid metabolism through its oral administration in rats. Hence, this study investigates the effects of oral ingestion of ozonated olive oil on the pathologies of obese model rats. Obese model Zucker (fa/fa) rats were fed one of the following AIN-76 diets for four weeks: control diet: 6.5% corn oil + 0.5% olive oil, low ozonated oil diet: 6.5% corn oil + 0.45% olive oil + 0.05% ozonated olive oil, high ozonated oil diet: 6.5% corn oil + 0.5% ozonated olive oil. Control diet fed-Zucker lean rats were used as the reference. Growth parameters, hepatic lipids, hepatic enzyme activities, and serum parameters were determined. As the results, there was a dose-dependent improvement of hepatomegaly, fatty liver and elevated levels of hepatic injury markers in Zucker (fa/fa) rat upon ozonated olive oil consumption. Activities of hepatic enzymes related to lipid synthesis and lipid degradation were not affected by ozonated olive oil intake. On the other hand, there was a dose-dependent elimination of hepatic lipid secretion deficiency and suppression of inflammatory factors upon ozonated olive oil consumption. In conclusion, ozonated olive oil intake by Zucker (fa/fa) rats alleviates hepatic steatosis through the inhibition of triglyceride accumulation in the liver and suppression of inflammatory factors.
Asunto(s)
Hígado Graso , Animales , Hígado Graso/metabolismo , Hígado/metabolismo , Obesidad/complicaciones , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Aceite de Oliva/metabolismo , Aceite de Oliva/farmacología , Aceite de Oliva/uso terapéutico , Ratas , Ratas ZuckerRESUMEN
Heating milk fat leads to lactone formation. Hydroxy fatty acids, esterified in triacylglycerol (TAG), are likely precursors of lactones in milk fat, but respective hydroxy TAG isomers have not been directly detected for several decades. In this study, we separated hydroxy TAG isomers-1,2-dipalmitoyl-3-(5-hydroxy decanoyl)-rac-glycerol (PP(C10-5OH)-TAG), 1,2-dipalmitoyl-3-(5-hydroxy dodecanoyl)-rac-glycerol (PP(C12-5OH)-TAG), 1,2-dipalmitoyl-3-(5-hydroxy tetradecanoyl)-rac-glycerol (PP(C14-5OH)-TAG), and 1,2-dipalmitoyl-3-(4-hydroxy dodecanoyl)-rac-glycerol-by using liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with an octacocyl silylation column. This method revealed the presence of PP(C10-5OH)-TAG, PP(C12-5OH)-TAG, and PP(C14-5OH)-TAG in butter oil, whereas no hydroxy TAG isomers were detected in heat-treated butter oil. Furthermore, a heating test of hydroxy TAG standards showed a decrease in hydroxy TAG levels and an increase in the corresponding lactone levels. These changes were stimulated by adding a small amount of water. This is the first reported analysis of respective hydroxy TAG isomers in milk fat using LC-ESI-MS/MS.