A review on differential effects of dietary fatty acids on weight, appetite and energy expenditure.

The association between weight and chronic diseases is well defined. The quality and quantity of dietary fatty acids is an important external factor and appetite and energy expenditure, are important internal factors in determining body weight. On the other hand, dietary fatty acids composition can modulate appetite and energy metabolism, but not all fats are equal in producing metabolic responses.Given the accumulating evidence for differential effects of various dietary fatty acids, one important area of investigation is to scrutinize their roles in weight, appetite and energy expenditure modulation. There is substantial evidence to suggest that saturated fatty acids have a greater effect on appetite control, although in the long run may result in more weight gain than unsaturated fatty acids due to a weaker stimulation of energy expenditure. In contrast, mono-unsaturated fats do not have much effects on appetite control, but they can be beneficial in weight control over the long term due to stimulatory effects on energy expenditure. Interestingly, in case of poly unsaturated fats, including n-3 and n-6, their effect on increasing energy expenditure is aligned, but they act differently in controlling weight and appetite.

Threshold protective effect of deuterated polyunsaturated fatty acids on peroxidation of lipid bilayers.

Autoxidation of polyunsaturated fatty acids (PUFAs) damages lipid membranes and generates numerous toxic by-products implicated in neurodegeneration, aging, and other pathologies. Abstraction of bis-allylic hydrogen atoms is the rate-limiting step of PUFA autoxidation, which is inhibited by replacing bis-allylic hydrogens with deuterium atoms (D-PUFAs). In cells, the presence of a relatively small fraction of D-PUFAs among natural PUFAs is sufficient to effectively inhibit lipid peroxidation (LPO). Here, we investigate the effect of various D-PUFAs on the stability of liposomes under oxidative stress conditions. The permeability of vesicle membranes to fluorescent dyes was measured as a proxy for bilayer integrity, and the formation of conjugated dienes was monitored as a proxy for LPO. Remarkably, both approaches reveal a similar threshold for the protective effect of D-PUFAs in liposomes. We show that protection rendered by D-PUFAs depends on the structure of the deuterated fatty acid. Our findings suggest that protection of PUFAs against autoxidation depends on the total level of deuterated bi-sallylic (CD2 ) groups present in the lipid bilayer. However, the phospholipid containing 6,6,9,9,12,12,15,15,18,18-d10 -docosahexaenoic acid exerts a stronger protective effect than should be expected from its deuteration level. These findings further support the application of D-PUFAs as preventive/therapeutic agents in numerous pathologies that involve LPO.

Effect of long-chain polyunsaturated fatty acid supplementation during pregnancy or lactation on infant and child body composition: a systematic review.

BACKGROUND: n-3 (omega-3) Long-chain polyunsaturated fatty acids (LC-PUFAs) inhibit fat cell differentiation and fat storage in adults, and this has led to the hypothesis that maternal n-3 LC-PUFA supplementation may reduce fat mass in children. OBJECTIVE: The objective of this systematic review was to evaluate the effect of n-3 LC-PUFA supplementation in pregnancy or lactation on infant and child body composition in randomized controlled trials. DESIGN: MEDLINE and EMBASE databases were searched for relevant articles. Human trials that supplemented the maternal diet with n-3 LC-PUFAs during pregnancy or lactation and assessed either body fat mass or body mass index in children were included. Trials had to be randomized in design. The quality of all included studies was assessed against set criteria, and results of eligible trials were compared. RESULTS: There were only 3 human trials (4 publications) that met our inclusion criteria. There was considerable disparity in study design and trial quality. The results were variable and showed positive, negative, or neutral effects of maternal n-3 LC-PUFA supplementation on body fat mass in children. CONCLUSIONS: This systematic review highlights the paucity of robust data from human studies to evaluate the effect of increased n-3 LC-PUFA exposure during the perinatal period on body fat mass in offspring. Further studies are required in which the intervention is confined to the perinatal period and that are sufficiently powered, have appropriate controls, have adequate blinding of participants and investigators, and have high retention rates.

In vitro assessment of P450 induction potential of novel chemopreventive agents SR13668, 9-cis-UAB30, and pentamethychromanol in primary cultures of human hepatocytes.

Several compounds, including 2,10-dicarbethoxy-6-methoxy-5,7-dihydroindolo[2,3-b]carbazole (SR13668), (2E,4E,6Z,8E)-8-(3',4'-dihydro-1'(2'H)-napthalen-1'-ylidene)-3,7-dimethyl-2,4,6-octatrienoic acid (9-cis-UAB30), and 2,2,5,7,8-pentamethyl-6-chromanol (PMCol), were selected as promising chemopreventive agents and have entered preclinical trials for cancer prevention. The potential for adverse drug events resulting from interactions with other administered drugs, food components, or food additives presents an important question. Among the most important drug-drug interactions (DDI) is the potential of a new chemical entity (NCE) to induce cytochrome P450 enzymes (P450). Drug induction of P450 enzymes can lead to adverse drug interactions by increasing the metabolism of other drugs that are substrates for the induced isoform. Currently, sandwich cultured primary human hepatocytes are the standard for predicting human P450 enzyme induction in vitro as these cells retain the ability to respond to prototypical P450 inducers with the same specificity and potency exhibited in vivo. Therefore, a select panel of inducible P450 target genes (CYP1A2, CYP2B6, and CYP3A4) and their induction activity (measured by LC-MS/MS of respective marker substrate metabolites) were monitored in cultured hepatocytes following treatment with SR13668, 9-cis-UAB30, or PMCol to predict clinically significant drug-induced expression. The concentration ranges of the NCE used were selected to maximize the clinical relevance of these results. All responses were evaluated according to major prototypical P450 inducers (i.e., 3-methylcholanthrene, 3-MC; phenobarbital, PB; rifampicin, RIF) and increases > or = 40% of the respective positive control(s) were considered an indication of demonstrable induction. Herein, we report that there is low potential for DDI with SR13668 and PMCol due to enzyme induction of CYP1A2, CYP2B6, and CYP3A4 expression at the concentrations examined. Similarly, the study results suggested that 9-cis-UAB30 has low potential to induce CYP1A2 and CYP3A4 expression at the concentrations examined. However, 9-cis-UAB30 was shown to significantly induce CYP2B6 enzyme activity at 10 microM suggesting the potential for DDI as a result.

[Fish oil supplementation in rheumatoid arthritis]. / La supplementazione dietetica con olio di pesce nell'artrite reumatoide.

The beneficial properties of fish oil are well known and are related to its fatty acid composition rich in omega-3 polyunsaturated fatty acids. In the last years a variety of epidemiological and clinical studies have demonstrated the efficacy of fish oil supplementation in the rheumatic diseases, in particular in rheumatoid arthritis. The anti-inflammatory effects of fish oil are linked to the production of alternative eicosanoids, to the reduction of proinflammatory cytokines, to the inhibition of the activation of T lymphocytes and of catabolic enzymes. Fish oil supplementation could represent a valuable support to the traditional pharmacological treatment of rheumatoid arthritis.

New insect system for testing antibiotics.

New and efficient methods to screen antibiotics are needed to counter increased antibiotic resistance in pathogens and the emergence of new diseases. Here we report a new insect model for screening antibiotics in vivo using the grasshopper Romalea microptera. The system is inexpensive, efficient, and flexible, avoids animal-welfare problems, and can be used to test against most major pathogenic groups. We employed this system to test 11 commercial antibiotics against a pathogenic Encephalitozoon species (Microsporidia). Oral treatment with fumagillin or thiabendazole significantly reduced pathogen spore counts, whereas spore counts of grasshoppers fed with albendazole, ampicillin, chloramphenicol, griseofulvin, metronidazole, sulfadimethoxine, or tetracycline were not significantly different from the infected controls. Quinine produced a distinct, but nonsignificant, reduction in spores, and streptomycin a nonsignificant increase in spores. Although 2 antibiotics significantly reduced spore counts, in no case was the pathogen totally eliminated. This study demonstrates the validity of this system as a method to screen antibiotics. It also corroborates the difficulty researchers and physicians have had in treating microsporidia infections, and suggests that quinine and related alkaloid compounds should be further examined as possible therapeutic agents against this group of ubiquitous pathogens. In addition, streptomycin and related compounds should be tested to determine if this widely used antibiotic enhances microsporidiosis.

A nutritional strategy to improve oxygenation and decrease morbidity in patients who have acute respiratory distress syndrome.

Enteral nutrition is increasingly becoming the standard of care for critically ill patients with the goal of providing nutritional support that prevents nutritional deficiencies and reduces morbidity. Furthermore, the development of nutritional strategies that dampen inflammation is an encouraging advance in the management of patients who have acute respiratory distress syndrome. This article discusses evidence from randomized, controlled studies that the use of a specialized nutritional formula containing eicosapentaenoic acid plus gamma-linolenic acid and elevated antioxidants offer physiologic and anti-inflammatory benefits over standard formulas.

Effects of different dietary fat types on postprandial appetite and energy expenditure.

OBJECTIVE: Observational studies suggest that monounsaturated (MUFA) and trans fatty acids (TRANS) are more fattening than polyunsaturated fatty acids (PUFA). Therefore, the aim of this study was to investigate the acute effect of intake of PUFA, MUFA, or TRANS on appetite and energy expenditure (EE). RESEARCH METHODS AND PROCEDURES: Three test meals were randomly given in a cross-over design to 19 overweight (BMI: 26.8 +/- 0.4 kg/m2), young (25.2 +/- 0.7 years) men. The fat-rich breakfasts (0.8 g fat/kg body weight, 60% energy from fat) varied only in the source of C:18-fat. EE was measured continuously in a respiration chamber, and appetite sensations were rated by visual analog scales before and every 30 minutes, for 5 hours, after the meal. After 5 hours, an ad libitum meal was served, and energy intake was registered. Sensory evaluations of all meals were given using visual analog scales. Data were analyzed by two-way ANOVA. RESULTS: There were no differences in basal or postprandial values of appetite ratings and EE, in subsequent ad libitum energy intake, or in the sensory evaluation of the test meals among the 3 test days. DISCUSSION: Giving acutely large amounts of MUFA, PUFA, or TRANS did not impose any differences in appetite and EE in overweight humans. However, studies with extended protocols and other subject groups are warranted to investigate the long-term effect of dietary fat quality on the regulation of energy balance and body weight.

In vitro and in vivo assessment of lipid peroxidation of infant nutrient preparations: effect of nutrition on oxygen toxicity.

Commercial infant formulas, human milk, and lipid emulsions were analyzed for evidence of naturally occurring lipid peroxidation and for susceptibility to an in vitro oxidative challenge using neonatal rat lung, liver, or intestine homogenates. Peroxidation was assessed by quantitation of TBA reactants, diene conjugates, lipid peroxides, and ethane and pentane hydrocarbons. The peroxidation of commercial formulas and human milk was influenced by the nutrient composition, as PUFA and iron enhanced while vitamin E inhibited one or more of the peroxidation pathways. Formulas and lipid emulsions differed in their response to a biological oxidant challenge. Neither neonatal rat lung nor liver tissue were effective in peroxidizing the formula or human milk in vitro, but both formula and human milk were peroxidized by exposure to neonatal rat intestinal tissue. The lipid emulsion was readily peroxidized by neonatal rat lung, liver, and intestinal tissue. The influence of nutrition on survival in hyperoxia was also studied by exposing newborn rat pups to either air or greater than 95% oxygen in the course of feeding Ringer's lactate, Similac 24 + iron, human milk, or Intralipid 10%. The survival of newborn rat pups exposed to air or greater than 95% oxygen was affected by the type of diet received.

Assessment of the pyrogenic potency of the thromboxane A2-mimetics, SQ26655 and U46619, and thromboxane B2 by intrapreoptic injection in the cat.

Using bilateral injection into the anterior hypothalamic/preoptic region of the conscious, indomethacin pretreated cat as an assay system, the pyrogenic activity of two thromboxane A2-mimetics (SQ26655 and U46619) and thromboxane B2 was assessed. PGE2 was used as a reference pyrogenic agent. Thromboxane B2 and both of the thromboxane A2-mimetics were at least 5263 times less potent than PGE2. The results do not support the putative role of thromboxanes as mediators of fever.