Administration of Linoleoylethanolamide Reduced Weight Gain, Dyslipidemia, and Inflammation Associated with High-Fat-Diet-Induced Obesity

Acylethanolamides (NAEs) are bioactive lipids derived from diet fatty acids that modulate important homeostatic functions, including appetite, fatty acid synthesis, mitochondrial respiration, inflammation, and nociception. Among the naturally circulating NAEs, the pharmacology of those derived from either arachidonic acid (Anandamide), oleic acid (OEA), and palmitic acid (PEA) have been extensively characterized in diet-induced obesity. For the present work, we extended those studies to linoleoylethanolamide (LEA), one of the most abundant NAEs found not only in plasma and body tissues but also in foods such as cereals. In our initial study, circulating concentrations of LEA were found to be elevated in overweight humans (body mass index (BMI, Kg/m) > 25) recruited from a representative population from the south of Spain, together with AEA and the endocannabinoid 2-Arachidonoyl glycerol (2-AG). In this population, LEA concentrations correlated with the circulating levels of cholesterol and triglycerides. In order to gain insight into the pharmacology of LEA, we administered it for 14 days (10 mg/kg i.p. daily) to obese male Sprague Dawley rats receiving a cafeteria diet or a standard chow diet for 12 consecutive weeks. LEA treatment resulted in weight loss and a reduction in circulating triglycerides, cholesterol, and inflammatory markers such as Il-6 and Tnf-alpha. In addition, LEA reduced plasma transaminases and enhanced acetyl-CoA-oxidase (Acox) and Uncoupling protein-2 (Ucp2) expression in the liver of the HFD-fed animals. Although the liver steatosis induced by the HFD was not reversed by LEA, the overall data suggest that LEA contributes to the homeostatic signals set in place in response to diet-induced obesity, potentially contributing with OEA to improve lipid metabolism after high fat intake. The anti-inflammatory response associated with its administration suggests its potential for use as a nutrient supplement in non-alcoholic steatohepatitis.Juan Decara holds a “Miguel Servet” (CP21/00021) research contract from the Ministerio de Ciencia e Innovación, Instituto de Salud Carlos III (ISCIII), cofunded by European Social Fund, “Investing in your future”, Gobierno de España. The present work was funded by Instituto de Salud Carlos III (ISCIII), Ministerio de Ciencia e Innovación; European Regional Development Funds Euro- pean Union (ERDF-EU) grants “Proyectos de Investigación en Salud” PI19/01577 and PI22/00427; Proyectos de investigación en salud (PI-0139-2018) Consejería de Salud y Familias, Junta de An- dalucía, Proyecto de Investigación en Salud; grant for international postdoctoral stay “Jose Castillejo” Program (Grant CAS15/00257), Ministerio de Educación Cultura y Deporte, Gobierno de España. The funders had no role in the design of the study; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication

Latin America's Nitrogen Challenge

Latin America (LA) has many social indicators similar to those of highly developed economies but most frequently falls midway between least developed countries and industrialized regions. To move forward, LA must address uncontrolled urbanization, agricultural production, social inequity, and destruction of natural resources. We discuss these interrelated challenges in terms of human impact on the nitrogen (N) cycle. Human activity has caused unprecedented changes to the global N cycle; in the past century; total global fixation of reactive N (Nr) has at least doubled (1). Excess Nr leaked into the environment negatively affects soils, atmosphere, and water resources in temperate zones (1). In addition to N excess from human impact, mining of natural soil N creates N deficits in some regions (2, 3).Fil: Austin, Amy Theresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura; ArgentinaFil: Bustamante, M. M. C.. Universidade Do Brasilia; BrasilFil: Nardoto, G. B.. Universidade Do Brasilia; BrasilFil: Mitre, S. K.. Universidade Do Brasilia; BrasilFil: Pérez, T.. Instituto Venezolano de Investigaciones Cientificas; VenezuelaFil: Ometto, J. P. H. B.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Ascarrunz, N. L.. Instituto Boliviano de Investigación Forestal; BoliviaFil: Forti, M. C.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Longo, K.. Centro de Previsao de Tempo e Estudos Climaticos. Instituto Nacional de Pesquisas Espaciais; BrasilFil: Gavito, M. E.. Universidad Nacional Autónoma de México; MéxicoFil: Enrich Prast, A.. Universidade Federal do Rio de Janeiro; BrasilFil: Martinelli, L. A.. Universidade de Sao Paulo; Brasi

Agronomic Management of Indigenous Mycorrhizas

Many of the advantages conferred to plants by arbuscular mycorrhiza (AM) are associated to the ability of AM plants to explore a greater volume of soil through the extraradical mycelium. Sieverding (1991) estimates that for each centimetre of colonized root there is an increase of 15 cm3 on the volume of soil explored, this value can increase to 200 cm3 depending on the circumstances. Due to the enhancement of the volume of soil explored and the ability of the extraradical mycelium to absorb and translocate nutrients to the plant, one of the most obvious and important advantages resulting from mycorrhization is the uptake of nutrients. Among of which the ones that have immobilized forms in soil, such as P, assume particular significance. Besides this, many other benefits are recognized for AM plants (Gupta et al, 2000): water stress alleviation (Augé, 2004; Cho et al, 2006), protection from root pathogens (Graham, 2001), tolerance to toxic heavy metals and phytoremediation (Audet and Charest, 2006; Göhre and Paszkowski, 2006), tolerance to adverse conditions such as very high or low temperature, high salinity (Sannazzaro et al, 2006), high or low pH (Yano and Takaki, 2005) or better performance during transplantation shock (Subhan et al, 1998). The extraradical hyphae also stabilize soil aggregates by both enmeshing soil particles (Miller e Jastrow, 1992) and producing a glycoprotein, golmalin, which may act as a glue-like substance to adhere soil particles together (Wright and Upadhyaya, 1998). Despite the ubiquous distribution of mycorrhizal fungi (Smith and Read, 2000) and only a relative specificity between host plants and fungal isolates (McGonigle and Fitter, 1990), the obligate nature of the symbiosis implies the establishment of a plant propagation system, either under greenhouse conditions or in vitro laboratory propagation. These techniques result in high inoculum production costs, which still remains a serious problem since they are not competitive with production costs of phosphorus fertilizer. Even if farmers understand the significance of sustainable agricultural systems, the reduction of phosphorus inputs by using AM fungal inocula alone cannot be justified except, perhaps, in the case of high value crops (Saioto and Marumoto, 2002). Nurseries, high income horticulture farmers and no-agricultural application such as rehabilitation of degraded or devegetated landscapes are examples of areas where the use of commercial inoculum is current. Another serious problem is quality of commercial available products concerning guarantee of phatogene free content, storage conditions, most effective application methods and what types to use. Besides the information provided by suppliers about its inoculum can be deceiving, as from the usually referred total counts, only a fraction may be effective for a particular plant or in specific soil conditions. Gianinazzi and Vosátka (2004) assume that progress should be made towards registration procedures that stimulate the development of the mycorrhizal industry. Some on-farm inoculum production and application methods have been studied, allowing farmers to produce locally adapted isolates and generate a taxonomically diverse inoculum (Mohandas et al, 2004; Douds et al, 2005). However the inocula produced this way are not readily processed for mechanical application to the fields, being an obstacle to the utilization in large scale agriculture, especially row crops, moreover it would represent an additional mechanical operation with the corresponding economic and soil compaction costs. It is well recognized that inoculation of AM fungi has a potential significance in not only sustainable crop production, but also environmental conservation. However, the status quo of inoculation is far from practical technology that can be widely used in the field. Together a further basic understanding of the biology and diversity of AM fungi is needed (Abbott at al, 1995; Saito and Marumoto, 2002). Advances in ecology during the past decade have led to a much more detailed understanding of the potential negative consequences of species introductions and the potential for negative ecological consequences of invasions by mycorrhizal fungi is poorly understood. Schwartz et al, (2006) recommend that a careful assessment documenting the need for inoculation, and the likelihood of success, should be conducted prior to inoculation because inoculations are not universally beneficial. Agricultural practices such as crop rotation, tillage, weed control and fertilizer apllication all produce changes in the chemical, physical and biological soil variables and affect the ecological niches available for occupancy by the soil biota, influencing in different ways the symbiosis performance and consequently the inoculum development, shaping changes and upset balance of native populations. The molecular biology tools developed in the latest years have been very important for our perception of these changes, ensuing awareness of management choice implications in AM development. In this context, for extensive farming systems and regarding environmental and economic costs, the identification of agronomic management practices that allow controlled manipulation of the fungal community and capitalization of AM mutualistic effect making use of local inoculum, seem to be a wise option for mycorrhiza promotion and development of sustainable crop production

Exploring Linkages between Supporting, Regulating, and Provisioning Ecosystem Services in Rangelands in a Tropical Agro-Forest Frontier

Rangeland management in former tropical rainforest areas may affect ecosystem services. We hypothesized that management practices like burning and overgrazing reduce supporting (soil quality) and consequently also provisioning (forage productivity and quality) and regulating (nutrient cycling) ecosystem services. We established 31 exclosures in two landscape categories (alluvial soils, low-hills), documented management practices, and assessed 18 soil quality indicators, litter decomposition as a proxy for nutrient cycling, and forage quantity and quality during one year in grasslands of the Lacandon region, southeast Mexico. Path analysis was used to explore direct and indirect effects of livestock management practices on soil-based ecosystem services. Landscape position had direct effects on management practices, and direct and indirect effects on soil properties. Altitude (a proxy for the soil catena, ranging from alluvial soils along the Lacantún river to Cambisols and Acrisols in the low-hills) was the variable showing most significant negative relations with soil quality and forage production. Decomposition rate was site-specific and had no relation with landscape position and management. Our study suggests that position on the landscape, which relates to nutrient and water availability, had stronger effects than management practices on forage productivity and quality and drives farmers management practices. View Full-Tex

(13)C Incorporation into Signature Fatty Acids as an Assay for Carbon Allocation in Arbuscular Mycorrhiza

The ubiquitous arbuscular mycorrhizal fungi consume significant amounts of plant assimilated C, but this C flow has been difficult to quantify. The neutral lipid fatty acid 16:1ω5 is a quantitative signature for most arbuscular mycorrhizal fungi in roots and soil. We measured carbon transfer from four plant species to the arbuscular mycorrhizal fungus Glomus intraradices by estimating (13)C enrichment of 16:1ω5 and compared it with (13)C enrichment of total root and mycelial C. Carbon allocation to mycelia was detected within 1 day in monoxenic arbuscular mycorrhizal root cultures labeled with [(13)C]glucose. The (13)C enrichment of neutral lipid fatty acid 16:1ω5 extracted from roots increased from 0.14% 1 day after labeling to 2.2% 7 days after labeling. The colonized roots usually were more enriched for (13)C in the arbuscular mycorrhizal fungal neutral lipid fatty acid 16:1ω5 than for the root specific neutral lipid fatty acid 18:2ω6,9. We labeled plant assimilates by using (13)CO(2) in whole-plant experiments. The extraradical mycelium often was more enriched for (13)C than was the intraradical mycelium, suggesting rapid translocation of carbon to and more active growth by the extraradical mycelium. Since there was a good correlation between (13)C enrichment in neutral lipid fatty acid 16:1ω5 and total (13)C in extraradical mycelia in different systems (r(2) = 0.94), we propose that the total amount of labeled C in intraradical and extraradical mycelium can be calculated from the (13)C enrichment of 16:1ω5. The method described enables evaluation of C flow from plants to arbuscular mycorrhizal fungi to be made without extraction, purification and identification of fungal mycelia

“DEPRESSION AND ANXIETY AS OBESITY-RELATED COMORBIDITIES: POSSIBLE PROTECTIVE EFFECTS OF ACYLETHANOLAMIDES”

Obesity, whose primary cause is overconsumption of high-palatable caloric-dense food, has been linked to increased risk of depression and anxiety disorders. Indeed, diet restriction and abstinence from high-palatable food exacerbate these comorbidities. Considering the biological functions of endocannabinoids, such as anandamide, and related lipid signals, such as oleoylethanolamide and palmitoylethanolamide in the modulation of the reward system and mood tone; they might play a key role in modulating all the neurobehavioral components of this scenario. The aim of this study was to explore whether the abstinence from a palatable diet, after a long-term ad libitum consumption of high palatable food, might produce alterations of the emotional reactivity and mood tone and whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH) by PF-3845 treatment (which causes an increase of acylethanolamide tone) could ameliorate such alterations. We used a rat model of diet-induced obesity based on hedonic overfeeding of a cafeteria-style diet (consisting of bacon, sausage, chocolate, cookies, etc) for 40 days. A control group of rats with ad libitum access only to standard chow and water was maintained. After the first 40 days of cafeteria diet, rats underwent an abstinence period of 28 days, with no longer access to the cafeteria diet but still ad libitum access to standard chow. During the abstinence period, animals were treated either with the FAAH inhibitor PF-3845 (10 mg/kg, sc.) or its vehicle administered every other day. At the end of the abstinence period, half of the rats were subjected to behavioral analyses such as the open field test, the elevated plus maze and the forced swimming test. The second half were sacrificed, their brains collected and micro-dissected for HPLC analyses of monoamines, western blot analysis of different proteins involved in the synthesis and degradation of acylethanolamides (monoacylglicerol lipase or MAGL; N-acyl phosphatidylethanolamine-specific phospholipase D or NAPE-PLD; diacylglycerol lipase alpha and beta or DAGL-α, DAGL-β; FAAH) and linked to inflammatory processes (cyclooxygenase 2 or COX2, CX3C chemokine receptor 1 or CX3CR1, allograft inflammatory factor 1or IBA-1, glial fibrillary acidic protein or GFAP). The preliminary results obtained from the behavioural studies showed that the prolonged abstinence from the cafeteria-diet was associated to anxiety-like behaviour in both the open-field and the elevated-plus-maze tests and depressive-like behaviour in the forced-swimming-test. The pharmacological treatment with PF-3845 was able to revert the depressive-like phenotype and to dampen the anxiety-like behaviour. Interestingly the altered behaviour was accompanied by modifications of monoaminergic tissue levels in key brain areas regulating eating; the treatment with PF-3845 was able to ameliorate such alterations. The results obtained from the western blotting analyses showed that the abstinence from the cafeteria diet reduced the expression of DAGL-β in the hypothalamus, NAPE-PLD and GFAP in medial prefrontal cortex. The treatment with PF-3845 was able to decrease the expression of CB1, NAPE-PLD and DAGL-α within the hypothalamus and reduce the expression of GFAP in medial prefrontal cortex. Overall the results obtained from the present study further support the role of the endocannabinoid system as a valid pharmacological target for the development of treatments for the neurofunctional alterations related to obesity

Possible protective effects of FAAH inhibition on depressive-like and anxiety-like neurofunctional alterations induced by the abstinence from a high-caloric-high-palatable diet causing obesity

The aim of this study was to explore whether the abstinence from a high-fat-high-palatable diet, causing obesity development, could produce in rodents alterations of emotional reactivity and mood tone and whether the pharmacological inhibition of fatty acid amide hydrolase (FAAH), which increase brain acylethanolamide tone, could ameliorate such alterations. We used a rat model of diet-induced obesity based on a cafeteria-style diet. After the first 40 days of cafeteria diet, rats underwent an abstinence period of 28 days; during this period, half of the animals were chronically treated with the FAAH inhibitor PF-3845 (10 mg/kg, intraperitoneally). At the end of the abstinence, rats were subjected to behavioral tests such as the open field test, the elevated plus maze and the forced swimming test, then sacrificed. Brains were collected, microdissected and selected regions were subjected to HPLC analysis of monoammines and western blot analysis for the expression of proteins of the endocannabinoid system and inflammation were performed. Rats, after cafeteria diet abstinence, revealed an anxiety-like behaviour; PF-3845 was able to exert an anxiolytic-like and antidepressant-like effect. Moreover, numerous alterations of the monoaminergic transmission were detected in selected brain areas and such alterations were partially recovered by the pharmacological treatment. Abstinence was able to alter the expression of proteins involved in neuroinflammation and those affecting the endocannabinoid system. PF-3845 treatment was able to partially restore these alterations. The results support the hypothesis that FAAH might be a possible target for the treatment of psychiatric alterations associated to obesity and food dependence