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The Effect of Olive Leaf Extract on Hepatic Fat Accumulation in Sprague-Dawley Rats Fed a High-fat Diet
Abstract and Figures
Oleuropein, the active constituent of olive leaf extract, possesses anti-oxidant, hypoglycemic, and hypolipidemic activities. We aimed to assess whether the effect of olive leaf extract on hepatic fat accumulation is preventive or therapeutic. Sprague-Dawley (SD) rats were fed a high-fat diet with (ODOD group) or without (HDHD group) olive leaf extract (1,000 mg/kg diet) for 38 weeks. Another group of rats were fed a high-fat diet for 23 weeks, followed by a high-fat diet with olive leaf extract (1,000 mg/kg diet) for 15 weeks (HDOD group). Serology, histopathology, anti-oxidative activity, and liver fatty acid synthesis were compared to those fed a standard diet (LDLD group) at 26 and 41 weeks of age. The serum levels of total cholesterol, triglyceride and aspartate aminotransferase tended to be lower in the ODOD group as compared to the HDHD and HDOD groups, although there were no significant differences. Histopathologically, hepatic steatosis tended to be less evident in the HDOD and ODOD groups as compared to the HDHD group, and lobular inflammation was not observed in the ODOD group at 26 weeks of age. Hepatic thioredoxin-1 staining tended to be less evident in the ODOD group than in the HDHD and HDOD groups at 41 weeks of age. There were no significant differences in hepatic lipogenic enzyme activities between the ODOD group and HDHD/HDOD groups. Our data suggest that olive leaf extract had a preventive, rather than therapeutic, effect on hepatic steatohepatitis in SD rats fed a high-fat diet
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... Improved coronary blood flow in the isolated rabbit heart treated with oleuropein suggested antiarrhythmic and antispasmodic effects (Esmailidehaj et al., 2016). In the high-fat-fed rats, the anti-fibrotic effect of oleuropein has been indicated by its protection against hepatic fibrosis in the course of steatohepatitis (Omagari et al., 2010). According to the above-mentioned information and potent anti-oxidants and anti-fibrotic effects of olive leaves and especially its component, oleuropein, we hypothesized that olive leaf extract (OLE) could modulate DCM-induced cardiac remodeling pathways with an emphasis on fibrosis and hypertrophy, in order to restore heart function. ...
The key role of fibrosis and hypertrophy processes in developing diabetes‐induced heart injury has been demonstrated. Considering the known hypoglycemic effects of olive leaf extract (OLE), we decided to investigate its potential effect and associated mechanisms on cardiac fibrosis and myocardial hypertrophy in streptozotocin (STZ)‐induced diabetic rats. Eight groups were included in this study: control, diabetic, diabetic‐OLEs (100, 200 and 400 mg/kg), diabetic‐metformin (300 mg/kg), diabetic‐valsartan (30 mg/kg), and diabetic‐metformin/valsartan (300/30 mg/kg). After a treatment period of 6 weeks, echocardiography was used to assess cardiac function. Heart‐to‐body weight ratio (HW/BW) and fasting blood sugar (FBS) were measured. Myocardial histology was examined by Masson's trichrome staining. Gene expressions of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), β–myosin heavy chain (β‐MHC), TGF‐β1, TGF‐β3, angiotensin II type 1 receptor (AT1), alpha‐smooth muscle actin (α‐SMA), and collagen were evaluated by the quantitative real‐time PCR in heart tissue. A reduction in the FBS level and HW/BW ratio in the extract groups was obvious. The improvement of left ventricular dysfunction, cardiac myocytes hypertrophy, and myocardial interstitial fibrosis was also observed in treated groups. A lowering trend in the expression of all hypertrophic and fibrotic indicator genes was evident in the myocardium of OLE treated rats. Our data indicated that OLE could attenuate fibrosis and reduce myocardial hypertrophy markers, thus improving the cardiac function and structure in the STZ‐induced diabetic rats.
Practical applications
This study demonstrates that olive leaf extract in addition to lowering blood glucose levels and the heart‐to‐body weight ratio (HW/BW) may also improve cardiac function and reduce cardiac hypertrophy and fibrosis in cardiac tissue, which leads to inhibition of diabetic heart damage. Thus it is possible that including olive leaf extracts in the diets of individuals with diabetes may assist in lowering cardiovascular disease risk factors.
Traditional Persian medicine (TPM) is a holistic approach to medicine, and treatment of various diseases originates from humoral medicine. The base of TPM is prevention from illness. Therefore several remedies have been recommended for staying healthy. Olive is a highly used medicinal plant in TPM. In this setting, olive and olive-derived products were prescribed for the treatment of several diseases, including neurological disorders, oral cavity problems, gastrointestinal diseases, cardiovascular diseases, respiratory system disorders, skin diseases, urinary system disorders, obstetrics, and gynecology conditions. Many recent studies support the traditional medicinal use of olives. In this chapter, the authors try to describe the medicinal use of olives in TPM and to allude to evidence-based studies on this subject in conventional medicine.
Liver and kidney organelles from rat and pig were separated by isopycnic sucrose density gradient centrifugation and located
by marker enzymes. Carnitine palmitoyltransferase was shown to be exclusively a mitochondrial enzyme. In liver, approximately
52% of carnitine acetyltransferase activity was mitochondrial, 14% peroxisomal, and 34% located in a lipid-rich membranous
fraction. Microsomes were a component of this last fraction and, when isolated by differential centrifugation, contained carnitine
acetyltransferase activity. This enzyme has not previously been reported to be in peroxisomes. The specific activity of carnitine
acetyltransferase in liver peroxisomes was two to three times greater than in the mitochondria or microsomes. Partial fractionation
of broken rat liver peroxisomes into core, membranes, and the soluble matrix indicated that carnitine acetyltransferase had
a similar distribution to the matrix enzyme, catalase. In gradients of rat and pig kidney, carnitine acetyltransferase was
found primarily in the mitochondrial fractions. This enzyme was also not detected in microbodies, mitochondria, or microsomes
from plants.
Carnitine acetyltransferase activity in liver fractions was confirmed by three separate assays—an 1(-)-carnitine-dependent
release of coenzyme A (CoA) from acetyl-CoA, identification of the 14C-labeled reaction product acetylcarnitine, and the 1(-)-acetylcarnitine-dependent formation of acetyl-CoA from CoA. Carnitine
acyltransferase activity for octanoyl-CoA in hepatic peroxisomes and microsomes was about equal to activity for acetyl-CoA.
In the mitochondria, activity for octanoyl-CoA was six times greater than for acetyl-CoA.
Non-alcoholic fatty liver disease (NAFLD) is an increasingly recognized pathology with a high prevalence and a possible evolution to its inflammatory counterpart (non-alcoholic steatohepatitis, or NASH). The pathophysiology of NAFLD and NASH has many links with the metabolic syndrome, sharing a causative factor in insulin resistance. According to a two-hit hypothesis, increased intrahepatic triglyceride accumulation (due to increased synthesis, decreased export, or both) is followed by a second step (or “hit”), which may lead to NASH. The latter likely involves oxidative stress, cytochrome P450 activation, lipid peroxidation, increased inflammatory cytokine production, activation of hepatic stellate cells and apoptosis. However, both “hits” may be caused by the same factors. The aim of this article is to overview the biochemical steps of fat regulation in the liver and the alterations occurring in the pathogenesis of NAFLD and NASH.
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of liver damage and alteration of hepatic enzymes. NAFLD is strongly associated with metabolic syndrome and obesity. It is characterized by fat accumulation in the liver that may progress throughout hepatic steatosis and inflammation (non-alcoholic steatohepatitis [NASH]) toward cirrhosis and liver failure. In the last decade several studies suggested that NAFLD is an independent cardiovascular risk factor that increases cardiovascular mortality. At present, several studies investigating possible therapeutic approaches are ongoing. The present review is focused on the current and promising treatments of NAFLD.
The clinical implications of non-alcoholic fatty liver diseases (NAFLD) derive from their potential to progress to fibrosis and cirrhosis. Inappropriate dietary fat intake, excessive intake of soft drinks, insulin resistance and increased oxidative stress results in increased free fatty acid delivery to the liver and increased hepatic triglyceride (TG) accumulation. An olive oil-rich diet decreases accumulation of TGs in the liver, improves postprandial TGs, glucose and glucagon-like peptide-1 responses in insulin-resistant subjects, and upregulates glucose transporter-2 expression in the liver. The principal mechanisms include: decreased nuclear factor-kappaB activation, decreased low-density lipoprotein oxidation, and improved insulin resistance by reduced production of inflammatory cytokines (tumor necrosis factor, interleukin-6) and improvement of jun N-terminal kinase-mediated phosphorylation of insulin receptor substrate-1. The beneficial effect of the Mediterranean diet is derived from monounsaturated fatty acids, mainly from olive oil. In this review, we describe the dietary sources of the monounsaturated fatty acids, the composition of olive oil, dietary fats and their relationship to insulin resistance and postprandial lipid and glucose responses in non-alcoholic steatohepatitis, clinical and experimental studies that assess the relationship between olive oil and NAFLD, and the mechanism by which olive oil ameliorates fatty liver, and we discuss future perspectives.
Cardiovascular diseases are the main cause of death worldwide at the turn of the XXI century [1]. Although it has been projected that by 2020, 71% of deaths due to ischaemic heart disease (IHD), will occur in developing countries [2], developed countries currently continue to exhibit unacceptable high absolute rates of cardiovascular mortality. Interestingly, IHD has a surprisingly low incidence in some developed countries such as France, Spain, Greece, Italy or Portugal, leading to a higher life expectancy in Mediterranean areas as compared with Northern European countries or the USA [3]. Diet and lifestylerelated factors may be responsible for this advantage. The role of diet on IHD has been studied during almost a century, and substantial evidence about the protection by some nutrients and food items is cur
Male rats of the Wistar strain were given oleuropein for 3 weeks at a dose of 25 or 50 mg/kg of body weight. Heart samples were analyzed for the lipid composition by the Iatroscan technique and for the fatty acid profile of neutral and polar lipids by the capillary gas chromatography. In addition, the oleuropein, α- and β-tocopherol content in the total heart lipids were also determined. Oleuropein treatment increased the level of cholesteryl esters, but it decreased the level of triacylglycerols, in the heart of animals. Sphingomyelin and lysophosphatidylcholine levels were only higher in the 50 mg oleuropein group. There was also a significant reduction in the linoleic acid content in the heart polar lipids of oleuropein-treated animals. As consequence of treatment, oleuropein was incorporated into the heart of animals in a concentration-dependent manner, whereas the α- and β-tocopherol content decreased. Oleuropein may therefore act as a substitute of the natural antioxidants in heart, with minor changes in the unsaturated lipids.
Obesity is associated with an increased risk of nonalcoholic fatty liver disease (NAFLD). Steatosis, the hallmark feature of NAFLD, occurs when the rate of hepatic fatty acid uptake from plasma and de novo fatty acid synthesis is greater than the rate of fatty acid oxidation and export (as triglyceride within very low-density lipoprotein). Therefore, an excessive amount of intrahepatic triglyceride (IHTG) represents an imbalance between complex interactions of metabolic events. The presence of steatosis is associated with a constellation of adverse alterations in glucose, fatty acid, and lipoprotein metabolism. It is likely that abnormalities in fatty acid metabolism, in conjunction with adipose tissue, hepatic, and systemic inflammation, are key factors involved in the development of insulin resistance, dyslipidemia, and other cardiometabolic risk factors associated with NAFLD. However, it is not clear whether NAFLD causes metabolic dysfunction or whether metabolic dysfunction is responsible for IHTG accumulation, or possibly both. Understanding the precise factors involved in the pathogenesis and pathophysiology of NAFLD will provide important insights into the mechanisms responsible for the cardiometabolic complications of obesity.
Oxidative stress may play an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Oleuropein, the active constituent of olive leaf, possesses anti-oxidant, hypoglycaemic, and hypolipidaemic activities. We aimed to investigate the preventive effects of olive leaf extract on hepatic fat accumulation in a rat model of NASH.
Spontaneously hypertensive/NIH-corpulent rats were fed a diet of AIN-93G with or without olive leaf extract (500, 1000, 2000 mg/kg diet, and control; 5 rats each) for 23 weeks. Serological and histopathological findings, anti-oxidative activity, and the alteration of fatty acid synthesis in the liver were evaluated.
Histopathologically, a diet of AIN-93G containing more than 1000 mg/kg olive leaf extract had a preventive effect for the occurrence of NASH. Thioredoxin-1 expression in the liver was more evident in rats fed this diet, and 4-hydroxynonenal expression in the liver was less evident in these rats. There were no significant differences in the activities of hepatic carnitine palmitoyltransferase, fatty acid synthase, malic enzyme, and phosphatidic acid phosphohydrolase among the groups.
Our data suggest that olive leaf extract may help prevent NASH, presumably through its anti-oxidative activity.
Unlabelled:
Nonalcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease in the western world. It is now recognized that these patients have myriad of important co-morbidities (e.g., diabetes, hypothyroidism and metabolic syndrome). The workup of patients with suspected NAFLD should consist of excluding competing etiologies and systemic evaluation of metabolic comorbidities. NAFLD is histologically categorized into steatosis and steatohepatitis, two states with fairly dichotomous natural history. While significant progress has been made in terms of noninvasively predicting advanced fibrosis, insufficient progress has been made in predicting steatohepatitis. Currently, liver biopsy remains the gold standard for the histological stratification of NAFLD. While sustained weight loss can be effective to treat NASH, it is often difficult to achieve. Foregut bariatric surgery can be quite effective in improving hepatic histology in selected patients without liver failure or significant portal hypertension. Thiazolidinediones have shown promise and the results from the ongoing, large multicenter study should become available soon. Large multicenter studies of CB, receptor anatagonists are also underway but their results will not be available for several years. Several recent studies have highlighted that cardiovascular disease is the single most important cause of morbidity and mortality in this patient population.
Conclusion:
Health care providers should not only focus on liver disease but also concentrate on aggressively modifying and treating their cardiovascular risk factors.