Dietary Plant Lectins Appear to Be Transported from the Gut to Gain Access to and Alter Dopaminergic Neurons of Caenorhabditis elegans, a Potential Etiology of Parkinson's Disease.

Lectins from dietary plants have been shown to enhance drug absorption in the gastrointestinal tract of rats, be transported trans-synaptically as shown by tracing of axonal and dendritic paths, and enhance gene delivery. Other carbohydrate-binding protein toxins are known to traverse the gut intact in dogs. Post-feeding rhodamine- or TRITC-tagged dietary lectins, the lectins were tracked from gut to dopaminergic neurons (DAergic-N) in transgenic Caenorhabditis elegans (C. elegans) [egIs1(Pdat-1:GFP)] where the mutant has the green fluorescent protein (GFP) gene fused to a dopamine transport protein gene labeling DAergic-N. The lectins were supplemented along with the food organism Escherichia coli (OP50). Among nine tested rhodamine/TRITC-tagged lectins, four, including Phaseolus vulgaris erythroagglutinin (PHA-E), Bandeiraea simplicifolia (BS-I), Dolichos biflorus agglutinin (DBA), and Arachis hypogaea agglutinin (PNA), appeared to be transported from gut to the GFP-DAergic-N. Griffonia Simplicifolia and PHA-E, reduced the number of GFP-DAergic-N, suggesting a toxic activity. PHA-E, BS-I, Pisum sativum (PSA), and Triticum vulgaris agglutinin (Succinylated) reduced fluorescent intensity of GFP-DAergic-N. PHA-E, PSA, Concanavalin A, and Triticum vulgaris agglutinin decreased the size of GFP-DAergic-N, while BS-I increased neuron size. These observations suggest that dietary plant lectins are transported to and affect DAergic-N in C. elegans, which support Braak and Hawkes' hypothesis, suggesting one alternate potential dietary etiology of Parkinson's disease (PD). A recent Danish study showed that vagotomy resulted in 40% lower incidence of PD over 20 years. Differences in inherited sugar structures of gut and neuronal cell surfaces may make some individuals more susceptible in this conceptual disease etiology model.

Using Caenorhabditis elegans as a Model for Obesity Pharmacology Development.

The Caenorhabditis elegans model is a rapid and inexpensive method to address pharmacologic questions. We describe the use of C. elegans to explore 2 pharmacologic questions concerning candidate antiobesity drugs and illustrate its potential usefulness in pharmacologic research: (1) to determine a ratio of betahistine-olanzapine that blocks the olanzapine-induced intestinal fat deposition (IFD) as detected by Nile red staining and (2) to identify the mechanism of action of a pharmaceutical candidate AB-101 that reduces IFD. Olanzapine (53 µg/mL) increased the IFD (12.1 ± 0.1%, P < 0.02), which was blocked by betahistine (763 µg/mL, 39.3 ± 0.01%, P < 0.05) in wild-type C. elegans (N2). AB-101 (1.0%) reduced the IFD in N2 (P < 0.05), increased the pharyngeal pumping rate (P < 0.05), and reversed the elevated IFD induced by protease inhibitors atazanavir and ritonavir (P < 0.05). AB-101 did not affect IFD in a ACS null mutant strain acs-4(ok2872) III/hT2[bli-4(e937) let-?(q782) qIs48](I;III) suggesting an involvement of the lipid oxidation pathway and an upregulation of CPT-1. Our studies suggest that C. elegans may be used as a resource in pharmacologic research. This article is intended to stimulate a greater appreciation of its value in the development of new pharmaceutical interventions.

Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model.

Prowashonupana barley (PWB) is high in ß-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and ß-glucans may benefit hyperglycaemia-impaired lipid metabolism.

Effects of three intense sweeteners on fat storage in the C. elegans model.

Beverages sweetened with caloric sweeteners (CS), glucose, sucrose or high-fructose corn syrup, are associated with weight gain. Beverages sweetened with intense sweeteners (IS) are marketed as low-calorie substitutes to prevent beverages-associated weight gain. Using Caenorhabditis elegans, the effects on intestinal fat deposition (IFD) and pharyngeal pumping rate (PPR) of cola beverages sweetened with glucose, aspartame, or aspartame plus acesulfame-potassium (AceK) were compared. Control groups received Escherichia coli (OP50) only. Study I: the nematodes received additional glucose- or IS-sweetened beverages. Study II: the nematodes received additional glucose, aspartame, or aspartame plus AceK (AAK). Beverages containing CS or IS (aspartame or AAK) did not alter IFD in wild type (N2) or in daf-16 deficiency. The CS cola increased IFD in sir-2.1 deficiency (P<0.05). The AAK-cola increased IFD in daf-16/daf-2 deficiency and sir-2.1 deficiency (P<0.05). Glucose increased IFD in N2 and daf-16 deficiency (P<0.05). Aspartame showed a tendency towards reduced IFD in N2 and decreased IFD in daf-16/daf-2 deficiency (P<0.05). AAK increased IFD in daf-16 deficiency and sir-2.1 deficiency (P<0.05), and reversed the aspartame-induced reduction in IFD. The aspartame-sweetened cola increased the PPR in daf-16/daf-2 deficiency and daf-16 deficiency (P<0.05); similar results were obtained in N2 with both IS (P<0.05). AAK increased the PPR in daf-16/daf-2, daf-16, and sir-2.1 deficiencies (P<0.05). Thus, IS increased the PPR, a surrogate marker of lifespan. Aspartame may have an independent effect in reducing IFD to assist humans desiring weight loss. AceK may increase IFD in presence of insulin resistance.