Zecharia Madar

Hebrew University of Jerusalem | HUJI · Robert H. Smith Institute of Plant Sciences and Genetics in Agriculture

This study aimed to investigate the effects of two types of peanuts, regular Hanoch (HN) and a new high-oleic cultivar., Hanoch-Oleic (HO), on metabolic parameters and gut microbiota composition. Male C57BL/6 mice were fed with a normal diet (ND) or ND supplemented with HN (NDh) or HO (NDo). Following 18 weeks of diet regimen, the NDo group exhibit...

Non-alcoholic fatty liver disease (NAFLD) has become an epidemic with increasing prevalence. Limited treatment options and poor adherence emphasize the urgent need for novel therapies for the treatment and/or prevention of NAFLD. Bioactive natural compounds found in medicinal plants are promising as novel therapeutic agents for NAFLD. Chiliadenus i...

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver abnormalities and has been linked with metabolic syndrome hallmarks. Unfortunately, current treatments are limited. This work aimed to elucidate the effects of three cannabis extracts on metabolic alteration and gut microbiota composition in a mouse model of NAFLD and obesit...

A new Israeli-developed peanut cultivar, “Hanoch-Oleic” (HO), uniquely contains enlarged oleic acid contents and was designed to confer additional beneficial effects over the traditional cultivar, “Hanoch” (HN). This work elucidates metabolic changes and microbiota adaptations elicited by HO addition to a high-fat diet (HFD). Male C57BL/6 mice were...

Background Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis and its phytocannabinoids may potentially be beneficial for treating metabolic disorder...

Background: Nonalcoholic fatty-liver disease (NAFLD) is a global health problem associated with gut dysbiosis and intestinal permeability. Broccoli is a natural source of bioactive phytochemicals, characterized by health-promoting properties. Objective: This study evaluated the effect of broccoli florets and stalks on liver fat accumulation, inflam...

Nonalcoholic fatty liver disease (NAFLD) is linked to obesity, type 2 diabetes, hyperlipidemia, and gut dysbiosis. Gut microbiota profoundly affects the host energy homeostasis, which, in turn, is affected by a high-fat diet (HFD) through the liver-gut axis, among others. Broccoli contains beneficial bioactive compounds and may protect against seve...

Objective Broccoli a "functional food", which contains bioactive compounds and phytochemicals have beneficial health promoting effects. This study aimed at investigating the effects of broccoli consumption on lipid and glucose metabolism and gut microbiota. Design Male C57BL/6J mice 7-8 weeks old were fed ad libitum with a normal diet supplemented...

Background: Oleic-acid consumption can possibly prevent or delay metabolic diseases. In Israel, a Virginia-type peanut cultivar with a high content of oleic acid has been developed. Objective: This study examined the effect of consuming high oleic peanuts (D7) on the development of fatty liver compared to the standard HN strain. Design: The tw...

Introduction: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic syndrome, which often includes obesity, diabetes, and dyslipidemia. Several studies in mice and humans have implicated the involvement of the gut microbiome in NAFLD. While cannabis may potentially be beneficial for treating metabolic disorders such as NAFLD, the ef...

Quantification of fatty vacuoles in the liver, with differentiation from lumina of liver blood vessels and bile ducts, is an example where the traditional semiquantitative pathology assessment can be enhanced with artificial intelligence (AI) algorithms. Using glass slides of mice liver as a model for nonalcoholic fatty liver disease, a deep learni...

Nonalcoholic steatohepatitis (NASH) is currently one of the most common liver diseases worldwide. The toxic effects of lipids and bile acids contribute to NASH. The regenerative pathway in response to damage to the liver includes activation of the inflammatory process and priming of hepatocytes to proliferate to restore tissue homeostasis. However,...

Background: Adipokines such as ghrelin, leptin, resistin and adiponectin have been proposed as being involved in energetic balance and bone turnover. There is scarce knowledge as to adipokine activity in hip fractured elderly patients in acute settings. We evaluated whether active nutritional support may reflect on adipokines levels and affect outc...

Scope Galactomannan and citrus pectin are considered ‘super fibers’ known for altering gut microbiota composition and improving glucose and lipid metabolism. This study aimed to investigate the fiber's effect on a non‐alcoholic steatohepatitis (NASH) model Methods and results Two feeding experiments were carried out using groups of 7–8 week‐old ma...

Objective: Galactomannans derived from fenugreek confer known health benefits; however, there is little information regarding health benefits of citrus pectin (CP) and its association with gut microbiome metabolites. The aim of this study was to examine links between galactomannan and CP consumption, microbiota development, and glucose metabolism....

Green tea polyphenol extracts (GTE) are sold commercially as cholesterol-reducing agents and for weight reduction however, they have also been reported to be hepatotoxic. Our results from both in vitro and in vivo studies indicate that green tea polyphenols can potentiate liver injury after and during treatment with high cholesterol diet to induce...

Nonalcoholic liver diseases (NAFLD) is one of the most common chronic liver disease in Western countries. Oxygen is a central component of the cellular microenvironment, which participate in the regulation of cell survival, differentiation, functions and energy metabolism. Accordingly, sufficient oxygen supply is an important factor for tissue dura...

Scope: This study investigated the potential deleterious impact of dietary supplementation with green tea extract (GTE) on the progression of fatty liver disease, in a mouse model of cholesterol-induced steatohepatitis, that represents chronic liver injury. Methods and results: Male C57BL mice (n = 32, eight weeks old) were fed for 6 weeks with...

Scope: Hyperglycemia is associated with oxidative stress, which accelerates cardiovascular complications. This study investigates the potential of glabridin to regulate paraoxonase 2 (PON2) levels, in vivo, and explores the glabridin protective effect on PON2 through tryptophan-fluorescence quenching and mass spectrometry. Methods and results: A...

New evidance highlights the importance of food timing. Recently, we showed that a low-calorie diet with carbohydrates eaten mostly at dinner changed diurnal hormone secretion and led to greater weight loss and improved metabolic status in obese people. Herein, we set out to test whether concentrated-carbohydrates diet (CCD), in which carbohydrates...

In females, hyperglycemia abolishes estrogen-vascular protection, leading to inflammation and oxidative stress that are related to diabetes-associated cardiovascular complications. Such knowledge led us to examine the potential of glabridin, as a replacement of estrogen anti-inflammatory activity under high glucose conditions. In macrophage-like ce...

The use of Web-based apps to promote a healthy lifestyle is increasing, although most of these programs were not assessed using suitable epidemiological methods. We evaluated the effectiveness of a newly developed Web-based app in promoting a healthy lifestyle and educating adults on such lifestyles. We also analyzed predictors for success in acqui...

Effective nutritional guidelines for reducing abdominal obesity and metabolic syndrome are urgently needed. Over the years, many different dietary regimens have been studied as possible treatment alternatives. The efficacy of low-calorie diets, diets with different proportions of fat, protein, and carbohydrates, traditional healthy eating patterns,...

The circadian clock influences nearly all aspects of metabolism. However, little is known regarding the effect of the energy status on circadian rhythms. Our aim was to test the effect of two opposing energy situations, metformin and lipid emulsion (LE), on clock and metabolic circadian expression in differentiated C2C12 myotubes. Metformin treatme...

Our goal was to evaluate the effect of breakfast size and composition on body weight, glycemic control, and metabolic markers in adults with type 2 diabetes mellitus (T2DM). 59 overweight/obese adults with T2DM were randomized to one of two isocaloric diabetic diets for 3 months; big breakfast (BB), breakfast was rich in fat and protein and provide...

Hypoxia inducible factor‐1 (HIF‐1) and cholesterol have been separately implicated in the development of several liver pathologies. The aim of the present study was to investigate possible activation of HIF‐1 pathway by cholesterol in AML12‐hepatocytes. Increased HIF‐1α protein accumulation was evident in hepatocytes after 2h of incubation with cho...

Cholesterol and chronic activation of hypoxia inducible factor-1 (HIF-1) have been separately implicated in the pathogenesis and progression of liver diseases. In AML12-hepatocytes increased HIF-1α protein accumulation was evident after 2h of incubation with cholesterol, while enhanced HIF-1 transcriptional activity was observed after 6h. Investiga...

Sustained weight reduction is needed in order to end the "vicious cycle" of abdominal obesity-a known risk factor for diabetes and coronary heart disease. However, most obese subjects fail to maintain long-term diets; they regain lost body weight and develop metabolic syndrome. Adipose tissue itself contributes to weight cycling and metabolic patho...

Glucocorticoids induce circadian gene expression in cultured cells and change the phase of circadian gene expression in vivo. In addition, glucocorticoids induce differentiation of preadipocyte to adipocytes. We set out to test the effect of dexamethasone, a glucocorticoid receptor agonist, on circadian rhythms in 3T3-L1 differentiated adipocytes....

Aims: The current study aim was to elucidate the antihypoglycemic role and mechanism of inducible nitric oxide synthase (iNOS) under inflammatory stress. Methods: Liver inflammatory stress was induced in wild-type (WT) and iNOS-knockout (iNOS(-/-)) mice by lipopolysaccharide (LPS) (5 mg/kg) with and without the background of nonalcoholic steatoh...

Background & aims: Optimizing nutritional intake has been recommended for geriatric patients undergoing hip-fracture surgery. Whether nutritional support guided by repeated measurements of resting energy requirements (REE) improves outcomes in these patients is not known. Methods: A randomized, controlled, unblinded, prospective, cohort study co...

The aim of the study was to evaluate the effect of Nitric oxide (NO) on redox changes and fat accumulation in hepatocytes. AML-12 hepatocytes were exposed to the NO donor Diethylenetriamine-NONOate (DETA-NO). DETA-NO led to a dose- and time-dependent increase in lipid accumulation in the cells, measured by Nile red fluorescence. Exposure of the cel...

Metformin is a commonly-used treatment for type 2 diabetes, whose mechanism of action has been linked, in part, to activation of AMP-activated protein kinase (AMPK). However, little is known regarding its effect on circadian rhythms. Our aim was to evaluate the effect of metformin administration on metabolism, locomotor activity and circadian rhyth...

Background and aims: Our recently published randomised clinical trial evaluated the effect of a low-calorie diet with carbohydrates eaten at dinner. This dietary pattern led to lower hunger scores, and better anthropometric, biochemical and inflammatory outcomes compared to a standard low-calorie diet. In the same study, changes in diurnal secreti...

Hepatic gluconeogenesis tightly controls blood glucose levels in healthy individuals, yet disorders of fatty acids (FAs) oxidation are characterized by hypoglycemia. We studied the ability of free-FAs to directly inhibit gluconeogenesis, as a novel mechanism that elucidates the hypoglycemic effect of FAs oxidation defects. Primary rat hepatocytes w...

Disruption of circadian rhythms leads to obesity and metabolic disorders. Timed restricted feeding (RF) provides a time cue and resets the circadian clock, leading to better health. In contrast, a high-fat (HF) diet leads to disrupted circadian expression of metabolic factors and obesity. We tested whether long-term (18 wk) clock resetting by RF ca...

Olive tree (Olea europaea L.) leaves have been widely used in traditional remedies in European and Mediterranean countries as extracts, herbal teas, and powder. They contain several potentially bioactive compounds that may have hypoglycemic properties. To examine the efficacy of 500 mg oral olive leaf extract taken once daily in tablet form versus...

Steatosis increases the sensitivity of hepatocytes to hypoxic injury. Thus, this study was designed to elucidate the role of hypoxia-inducible factor-1α (HIF1α) in steatotic hepatocytes during hypoxia. AML12 hepatocytes and isolated rat hepatocytes were treated with a free fatty acid mixture of oleate and palmitate (2:1, 1 mM) for 18 h, which gener...

Chiliadenus iphionoides (Boiss. & Blanche) Brullo (Asteraceae), a small aromatic shrub found throughout Israel, is used traditionally in the treatment of diabetes mellitus. In this study, Chiliadenus iphionoides anti-diabetic activity was characterized using cellular and animal models. Pancreatic β cells, adipocytes, and skeletal myotubes were trea...

This study was designed to investigate the effect of a low-calorie diet with carbohydrates eaten mostly at dinner on anthropometric, hunger/satiety, biochemical, and inflammatory parameters. Hormonal secretions were also evaluated. Seventy-eight police officers (BMI >30) were randomly assigned to experimental (carbohydrates eaten mostly at dinner)...

Accumulating evidence indicates that mitochondria have a key role in non-alcoholic fatty liver disease (NAFLD). C57BL/6J mice were fed a choline-deficient, ethionine-supplemented (CDE) diet. Histological studies demonstrated accumulation of fat vacuoles in up to 90% of hepatocytes in mice fed the CDE diet for 14 days. In addition, a decrease in mit...

To determine whether nutritional support guided by repeated measurements of resting energy requirements improves the outcome of critically ill patients. This was a prospective, randomized, single-center, pilot clinical trial conducted in an adult general intensive care (ICU) unit. The study population comprised mechanically ventilated patients (n =...

The primary objective of this study was to investigate the impact of lipid oversupply on the AMPK pathway in skeletal muscle, liver, and adipose tissue. Male Wistar rats were infused with lipid emulsion (LE) or phosphate-buffered saline for 5 h/day for 6 days. Muscles exposed to LE for 6 days exhibited increased AMPK and acetyl-CoA carboxylase (ACC...

The risk of death from cardiovascular diseases (CVDs), which are exacerbated by oxidative stress, is higher in diabetic women. This phenomenon has been attributed to the loss of estradiol-vascular protection. Such knowledge led us to examine the potential of glabridin, a phytoestrogen, to substitute estradiol up-regulation of antioxidant enzymes un...

This study hypothesized that upregulation of inducible nitric oxide synthase (iNOS) would preserve the metabolic status of the liver under conditions of steatosis and acute inflammation. Wild-type C57BL/6J and C57BL/6 iNOS-knockout (-/-) mice were fed a choline-deficient ethionine-supplemented diet (CDE). Mice were also injected with 5 mg/kg lipopo...

The circadian clock controls energy homeostasis by regulating circadian expression of proteins involved in metabolism. Disruption of circadian rhythms leads to obesity and metabolic disorders. Little is known regarding the control of the biological clock over adiponectin signaling pathway in adipose tissue, the adiponectin producer, and muscle, an...

The aim of this study was to detect mitochondrial alterations in J774.2 macrophages and mouse peritoneal macrophages (MPM) foam cells. J774.2 and MPM cells were exposed to triacylglycerol (TG) emulsion (1 mg/ml) for induction of fat accumulation. Impairment of mitochondrial function was reflected by reduced cellular ATP production and decreased exp...

Background & aims Fatty liver, inflammation, fibrosis and cirrhosis are associated with portal hypertension. Nitric oxide (NO) is a universal messenger molecule that plays diverse and essential physiological roles in multiple organ systems. A decrease in NO production can lead to disruption in blood flow and portal hypertension. We therefore sought...

Red microalgae contain functional sulfated polysaccharides (containing dietary fibers), polyunsaturated fatty acids, zeaxanthin, vitamins, minerals, and proteins. Studies in rat models support the therapeutic properties of algal biomass and isolated polysaccharides. Algal products incorporated into rat diets were found to significantly improve tota...

Mitochondrial dysfunction and hepatocyte cell death have been reported in fatty liver and non-alcoholic steatohepatitis. Our aim in this study was to evaluate whether direct exposure of hepatocytes to extracellular fat could facilitate such deleterious effects. FaO hepatic cells treated with fat was used as an in vitro model for steatosis. FaO hepa...

The circadian clock controls energy homeostasis by regulating circadian expression and/or activity of enzymes involved in metabolism. Disruption of circadian rhythms may lead to obesity and metabolic disorders. We tested whether the biological clock controls adiponectin signaling pathway in the liver and whether fasting and/or high-fat (HF) diet af...

The susceptibility of larvae ofThaumetopoea solitaria Freyer (Lepidoptera; Notodontidae, Thaumetopoeinae), fed on treated pistachio foliage, to three commercial control products derived fromBacillus thuringiensis (Bt), was evaluated in the laboratory. Both Dipel DF and Delfin WG were highly effective against 1 st and 2 nd instar larvae at relativel...

Accumulation of fat in the liver, also known as steatosis, may lead to inflammation and tissue damage. Kupffer cells (KCs) are the resident macrophages of the liver and have an important role in inflammatory reactions. The inflammatory response of isolated rat KCs to endotoxin in the presence of lipids was investigated in this study. KCs were treat...

Caveolin-1, a component of caveolae, regulates signaling pathway compartmentalization by interacting with tyrosine (Tyr) kinase receptors and their substrates. Perturbations in caveolae lipid composition have been shown in vitro to displace proteins from lipid microdomains, thereby altering their functionality and subsequent downstream signaling. T...

Many infections are associated with diabetes, as the ability of the body to fight pathogens is impaired. Recently, low levels of defensins have been found in diabetic rodents. However, whether hyperglycemia and/or insulin deficiency/insensitivity is the reason for the reduced defensin levels is still unknown. To study the functionality of the innat...

Triacylglycerols (TGs) are being considered as an independent risk factor in atherosclerosis and metabolic syndrome, acting by dysregulation of the TG/high-density lipoprotein axis. Accumulation of lipids in subendothelial space attracts macrophages, leading to atherosclerotic plaque formation and increased plaque instability due to formation of fo...

Four parasitoids emerged from leaves galled by the waspOphelimus maskelli (Ashmead) that were collected in Wagga Wagga, NSW, Australia:Closterocerus chameleon (Girault) and an unidentified Tetrastichinae species (Eulophidae); andStethynium ophelimi Huber andStethynium breviovipositor (Huber (Mymaridae).C. chamaeleon andS. ophelimi were released in...

The foliage resin composition of Cupressus sempervirens var. pyramidalis showed significant differences between healthy trees and trees infested with Diplodia pinea f. sp. cupressi and/or Seiridium cardinale. However, no relationship was found between the resin composition and the specific pathogen.

Many infections are associated with diabetes, as the ability of the body to fight pathogens is impaired. Recently, altered levels of defensins and polymorphism in Toll-like receptors (TLRs), two crucial components of the innate immune system, have been associated with diabetes. To study the functionality of the innate immune system during diabetes,...

This study was designed to test whether adiponectin plays a role in diet-induced obesity and insulin resistance and acts as a mediator to induce or inhibit specific metabolic pathways involved in lipid metabolism Forty C57BL/6J male mice were fed either a high-fat (HF) or control diet for 4 months, and adiponectin, its receptors, and enzyme express...

The effects of natural antioxidants on nitric oxide (NO) modulation and oxidative status were determined in rat epithelial lung cells (L-2). Cells were stimulated with cytokines and treated with one of the following: resveratrol, soybean saponin group B (SSB), quercetin, genistein, olive leaf polyphenol concentrate (OLPC), or N-acetyl-L-cystein (NA...

Interventional studies have shown that increased intake of fruit and vegetables reduces blood pressure (BP). However, the contribution of specific dietary components has not been evaluated. The aim of the present study was to determine, in patients with stage I hypertension, the antihypertensive effect of juice of the so-called sweetie fruit (a hyb...

This study was designed to evaluate the effects of triacylglycerol (TG) on nitric oxide (NO) production, expression of endothelial (e) and inducible (i) nitric oxide synthase (NOS) and variables related to oxidative stress in rat isolated hepatocytes. Hepatocytes were isolated and exposed to TG in the form of a lipid emulsion (0.01-0.1% LE). Exposu...

The aim of this study was to elucidate death pathways in macrophages resulting from exposure to triacylglycerols (TG), mechanisms which may be relevant to the development of atherosclerosis. A commercial TG emulsion (lipid emulsion, LE; 0.1-1.5 mg lipids/ml) was added to J774.2 cells in culture. Within the first 24 h after TG treatment, cellular re...