Zecharia Madar

Olive Oil as a Functional Food: Epidemiology and Nutritional Approaches

Olive oil is an integral ingredient of the Mediterranean diet and accumulating evidence suggests that it may have health benefits that include reduction of risk factors of coronary heart disease, prevention of several varieties of cancers, and modification of immune and inflammatory responses. Olive oil appears to be an example of a functional food, with varied components that may contribute to its overall therapeutic characteristics. Olive oil is known for its high levels of monounsaturated fatty acids and is also a good source of phytochemicals including polyphenolic compounds, squalene, and alpha-tocopherol.

Timed high-fat diet resets circadian metabolism and prevents obesity

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 can attenuate the disruptive effects of diet‐induced obesity. Analyses included liver clock gene expression, locomotor activity, blood glucose, metabolic markers, lipids, and hormones around the circadian cycle for a more accurate assessment. Compared with mice fed the HF diet ad libitum, the timed HF diet restored the expression phase of the clock genes Clock and Cry1 and phase‐advanced Per1, Per2, Cry2, Bmal1, Rorα, and Rev‐erbα. Although timed HF‐diet‐fed mice consumed the same amount of calories as ad libitum low‐fat diet‐fed mice, they showed 12% reduced body weight, 21% reduced cholesterol levels, and 1.4‐fold increased insulin sensitivity. Compared with the HF diet ad libitum, the timed HF diet led to 18% lower body weight, 30% decreased cholesterol levels, 10% reduced TNF‐α levels, and 3.7‐fold improved insulin sensitivity. Timed HF‐diet‐fed mice exhibited a better satiated and less stressed phenotype of 25% lower ghrelin and 53% lower corticosterone levels compared with mice fed the timed low‐fat diet. Taken together, our findings suggest that timing can prevent obesity and rectify the harmful effects of a HF diet.—Sherman, H., Genzer, Y., Cohen, R., Chapnik, N., Madar, Z., Froy, O. Timed high‐fat diet resets circadian metabolism and prevents obesity. FASEB J. 26, 3493–3502 (2012). www.fasebj.org

The effect of an ethanol extract derived from fenugreek (Trigonella foenum-graecum) on bile acid absorption and cholesterol levels in rats

The hypocholesterolaemic properties of an ethanol extract from defatted fenugreek (Trigonella foenum-graecum) seeds were investigated. Purification of the crude extract by dialysis produced an isolated component with haemolytic properties. The dialysate was also found to contain saponins demonstrated by thin-layer chromatography. Experiments in vitro employing the everted-sac technique showed that the ethanol extract had the ability to inhibit taurocholate and deoxycholate absorption in a dose-dependent manner. In two separate feeding experiments, hypercholesterolaemic rats were fed on 30 or 50 g ethanol extract/kg for a 4-week period. Reductions in plasma cholesterol levels ranged from 18 to 26% and a tendency for lower concentrations of liver cholesterol was observed. These results indicate that the ethanol extract from fenugreek seeds contained hypocholesterolaemic components which appear to be saponins that interact with bile salts in the digestive tract.

High-Fat Diet Delays and Fasting Advances the Circadian Expression of Adiponectin Signaling Components in Mouse Liver

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 affects this control. Mice were fed low-fat or HF diet and fasted on the last day. The circadian expression of clock genes and components of adiponectin metabolic pathway in the liver was tested at the RNA, protein, or enzyme activity level. In addition, serum levels of glucose, adiponectin, and insulin were measured. Under low-fat diet, adiponectin signaling pathway components exhibited circadian rhythmicity. However, fasting and HF diet altered this circadian expression; fasting resulted in a phase advance, and HF diet caused a phase delay. In addition, adenosine monophosphate-activated protein kinase levels were high during fasting and low during HF diet. Changes in the phase and daily rhythm of clock genes and components of adiponectin signaling pathway as a result of HF diet may lead to obesity and may explain the disruption of other clock-controlled output systems, such as blood pressure and sleep/wake cycle, usually associated with metabolic disorders.

Apoptosis cascade proteins are regulated in vivo by high intracolonic butyrate concentration: correlation with colon cancer inhibition.

The present study was aimed at evaluating the effect of high intracolonic butyrate concentrations, either through fermentation of a soluble fiber-enriched diet or via intracolonic butyrate instillation, on colon cancer in a chemically induced (dimethylhydrazine) rat model. The effects were tested in four groups of dimethylhydrazine-treated rats: (i) rats fed a standard diet, (ii) rats fed a diet enriched with 15% citrus pectin, a soluble fiber that ferments and produces a high concentration of intracolonic butyrate, (iii) rats fed a standard diet and intrarectally instilled with a sodium butyrate solution (50 mM), (iv) rats fed a standard diet and intrarectally instilled with sodium butyrate vehicle solution (100 mM NaCl). The apoptotic index in the distal colon of rats fed pectin was higher than in colonic tissue from rats fed a standard diet. The expression of caspase-1, a cysteine protease implicated in the regulation of programmed cell death, as detected by both Northern and Western analysis, showed the highest mRNA and protein levels in colonic tissue from rats intrarectally instilled with butyrate. Immunohistology confirmed the Western blot findings. Expression of the cleaved poly(ADP-ribose) polymerase product, a downstream nuclear substrate for caspase-3 in the apoptotic pathway, was elevated in both the pectin-fed and butyrate-instilled groups. Expression of the antiapoptotic protein Bcl-2 was significantly reduced following pectin feeding as well as butyrate instillation. The highest expression of Bcl-2 was observed in tumor tissue. A marked reduction in aberrant crypt number was observed in colonic tissue obtained from both the pectin-fed and butyrate-instilled groups relative to rats from the standard diet group. The average tumor volume per rat in both the pectin-fed and butyrate-instilled groups was significantly lower than in rats from the standard diet and the sodium butyrate vehicle-instilled groups. We conclude that high butyrate levels, either instilled or obtained following fermentation of soluble dietary fibers, inhibit early and late events in colon tumorigenesis by controlling the transcription expression and activity of key proteins involved in the apoptotic cascade.

A High‐Fat Diet Has a Tissue‐Specific Effect on Adiponectin and Related Enzyme Expression

Objective: 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

New legume sources as therapeutic agents

This review evaluates the potential health benefits of three legume sources that rarely appear in Western diets and are often overlooked as functional foods. Fenugreek (Trigonella foenum graecum) and isolated fenugreek fractions have been shown to act as hypoglycaemic and hypocholesterolaemic agents in both animal and human studies. The unique dietary fibre composition and high saponin content in fenugreek appears to be responsible for these therapeutic properties. Faba beans (Vicia faba) have lipid-lowering effects and may also be a good source of antioxidants and chemopreventive factors. Mung beans (Phaseolus aureus, Vigna radiatus) are thought to be beneficial as an antidiabetic, low glycaemic index food, rich in antioxidants. Evidence suggests that these three novel sources of legumes may provide health benefits when included in the daily diet.

Binding sites of human growth hormone and ovine and bovine prolactins in the mammary gland and the liver of lactating dairy cow.

Membrane preparations and Triton X-100 solubilized fractions from the mammary gland and liver of the lactating dairy cow were capable of specific binding of [125I]hGH and [125I]oPRL. The specific binding of the latter was significantly lower and could not be increased by higher receptor levels. Displacement studies of [125I]hGh by hGH, bPRL and oPRL revealed that the two latter hormones have a 20-40-fold lower affinity for the receptor than hGH, although strong indications exist that they all bind or the same sites. This feature is unique for cows and does not exist or is much less pronounced in rodents.

Olive Leaf Extract as a Hypoglycemic Agent in Both Human Diabetic Subjects and in Rats

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 matching placebo in improving glucose homeostasis in adults with type 2 diabetes (T2DM). In this controlled clinical trial, 79 adults with T2DM were randomized to treatment with 500 mg olive leaf extract tablet taken orally once daily or matching placebo. The study duration was 14 weeks. Measures of glucose homeostasis including Hba1c and plasma insulin were measured and compared by treatment assignment. In a series of animal models, normal, streptozotocin (STZ) diabetic, and sand rats were used in the inverted sac model to determine the mechanism through which olive leaf extract affected starch digestion and absorption. In the randomized clinical trial, the subjects treated with olive leaf extract exhibited significantly lower HbA1c and fasting plasma insulin levels; however, postprandial plasma insulin levels did not differ significantly by treatment group. In the animal models, normal and STZ diabetic rats exhibited significantly reduced starch digestion and absorption after treatment with olive leaf extract compared with intestine without olive leaf treatment. Reduced digestion and absorption was observed in both the mucosal and serosal sides of the intestine. Though reduced, the decline in starch digestion and absorption did not reach statistical significance in the sand rats. Olive leaf extract is associated with improved glucose homeostasis in humans. Animal models indicate that this may be facilitated through the reduction of starch digestion and absorption. Olive leaf extract may represent an effective adjunct therapy that normalizes glucose homeostasis in individuals with diabetes.

Soluble polysaccharide and biomass of red microalga Porphyridium sp. alter intestinal morphology and reduce serum cholesterol in rats

The present study investigated the effects of the red microalga Porphyridium sp. on gastrointestinal physiology and lipid metabolism in male Sprague-Dawley rats. Diets containing dietary fibre from pelleted red microalgal cells (biomass) or their sulfated polysaccharide, pectin or cellulose (control) were fed to rats for a period of 30 d. All three fibre-supplemented diets increased the length of both the small intestine and colon, with a significantly greater effect in rats fed the algal polysaccharide. The polysaccharide also increased mucosa and muscularis cross-sectional area of the jejunum, and caused hypertrophy in the muscularis layer. The algal biomass significantly lowered gastrointestinal transit time by 44% in comparison with the control rats. Serum and mucosal cholecystokinin levels were lower in rats on the pectin and polysaccharide diets, while cholecystokinin levels in rats fed algal biomass were not different from those in the control animals. In comparison with the control diet, all the experimental diets significantly lowered serum cholesterol levels (22-29%). Feeding of non-fermentable algal polysaccharide or biomass significantly increased faecal weight and bile acid excretion compared with pectin-fed or control rats. The algal polysaccharide and biomass were thus shown to be potent hypocholesterolaemic agents active at low concentrations in the diet. Both metabolic and morphological changes were observed following consumption of algae, suggesting several possible mechanisms by which the alga affects lipid metabolism. The results presented in the present study encourage the use of red microalga as a functional food.