Effects of Free Linoleic Acid and Oleic Acid in Sesame Meal Extract as Pancreatic Lipase Inhibitors on Postprandial Triglyceridemia: A Randomized, Double-Blind, Placebo-Controlled, Crossover Study in Healthy Volunteers.

A great number of chemically diverse pancreatic lipase (PL) inhibitors have been identified to tackle obesity; however, very few of them have entered clinical studies. The ethanolic extract of sesame meal is a potent PL inhibitor, and its activity hinges exclusively on two free fatty acids: linoleic acid and oleic acid, which were proven to reduce postprandial triglyceride excursion in rats. Herein, to investigate the clinical efficacy of the sesame meal extract, in a crossover trial, 30 healthy volunteers were randomized to receive the sesame meal extract containing experimental food or placebo along with a high-fat meal. Treatment with the sesame meal extract significantly lowered the incremental postprandial serum triglyceride concentration and reduced the incremental area under the curve (iAUC) by 16.8% (p-value = 0.03) compared to placebo. Significant decreases in postprandial remnant-like lipoprotein particle cholesterol and low-density lipoprotein particles were also observed, whereas high-density lipoprotein cholesterol was increased. These results suggest that treatment with the sesame meal extract significantly reduced the postprandial excursion of triglycerides and improved the lipidemic profile after high dietary fat intake in healthy individuals, indicating the substantial potential of free linoleic acid and oleic acid and natural products rich in these compounds for the management of obesity and related conditions.

Free Linoleic Acid and Oleic Acid Reduce Fat Digestion and Absorption In Vivo as Potent Pancreatic Lipase Inhibitors Derived from Sesame Meal.

Pancreatic lipase catalyzes the cleavage of triacylglycerols at the oil-water interface, and is known as the dominant determiner of dietary fat digestion. Reducing dietary fat digestion and absorption by modulating the activity of pancreatic lipase has become a favorable strategy to tackle obesity. Orlistat is, at present, the only pancreatic lipase inhibitor approved for the treatment of obesity; however, an array of gastrointestinal adverse effects associated with orlistat limits its tolerability. As a safe alternative to orlistat, a number of natural product-derived compounds with varying degrees of pancreatic lipase inhibitory activity have been reported. We herein reported that bioactivity-guided fractionation of sesame meal led to the identification of free linoleic acid and oleic acid as potent inhibitors of porcine pancreatic lipase in vitro with an IC50 of 23.1 µg/mL (82.4 µM) and 11.7 µg/mL (41.4 µM), respectively. In rats, a single oral dose of the mixture of these fatty acids significantly suppressed the elevation of blood triacylglycerol level following fat intake. These results substantiate the role of free linoleic acid and oleic acid as a novel class of natural product-derived functional molecules that act as pancreatic lipase inhibitors, and their potential for healthy, routine-based weight management.

Triterpenes induced by young apple fruits in response to herbivore attack.

Apples Malus domestica, known as a rich source of triterpene acids, induced more variety and quantity of triterpene acids in response to herbivory or mechanical damage. There were 3 major induced compounds: pomaceic acid and euscaphic acid, both of which are known apple triterpene acids, and 2α,19α-dihydroxy-3-oxours-12-en-28-oic acid (named eriobotoric acid), which was first identified in apples. In this study, the 3 compounds' induction curves after damage, varietal differences in induction amounts, and physiological roles against pest insects were further investigated. Eriobotoric acid showed clear antifeedant activity against lepidopteran insect Spodoptera litura but not against apple pests.

Plant volatile eliciting FACs in lepidopteran caterpillars, fruit flies, and crickets: a convergent evolution or phylogenetic inheritance?

Fatty acid amino acid conjugates (FACs), first identified in lepidopteran caterpillar spit as elicitors of plant volatile emission, also have been reported as major components in gut tracts of Drosophila melanogaster and cricket Teleogryllus taiwanemma. The profile of FAC analogs in these two insects was similar to that of tobacco hornworm Manduca sexta, showing glutamic acid conjugates predominantly over glutamine conjugates. The physiological function of FACs is presumably to enhance nitrogen assimilation in Spodoptera litura larvae, but in other insects it is totally unknown. Whether these insects share a common synthetic mechanism of FACs is also unclear. In this study, the biosynthesis of FACs was examined in vitro in five lepidopteran species (M. sexta, Cephonodes hylas, silkworm, S. litura, and Mythimna separata), fruit fly larvae and T. taiwanemma. The fresh midgut tissues of all of the tested insects showed the ability to synthesize glutamine conjugates in vitro when incubated with glutamine and sodium linolenate. Such direct conjugation was also observed for glutamic acid conjugates in all the insects but the product amount was very small and did not reflect the in vivo FAC patterns in each species. In fruit fly larvae, the predominance of glutamic acid conjugates could be explained by a shortage of substrate glutamine in midgut tissues, and in M. sexta, a rapid hydrolysis of glutamine conjugates has been reported. In crickets, we found an additional unique biosynthetic pathway for glutamic acid conjugates. T. taiwanemma converted glutamine conjugates to glutamic acid conjugates by deaminating the side chain of the glutamine moiety. Considering these findings together with previous results, a possibility that FACs in these insects are results of convergent evolution cannot be ruled out, but it is more likely that the ancestral insects had the glutamine conjugates and crickets and other insects developed glutamic acid conjugates in a different way.

Conversion of 3-oxo steroids into ecdysteroids triggers molting and expression of 20E-inducible genes in Drosophila melanogaster.

Ecdysteroids, steroid hormones in insects, coordinate major developmental transitions. During postembryonic development, ecdysone is biosynthesized from dietary cholesterol in the prothoracic gland (PG). Despite extensive studies, the initial conversion process, the so-called "Black Box", has not been characterized. A cytochrome P450 enzyme, Spookier (Spok), is speculated as a rate limiting enzyme in the Black Box during larval-pupal transitions in Drosophila melanogaster. RNAi mediated knockdown of spok expression in the PG results in arrest of molting. Because the developmental arrest can be rescued by application of an appropriate intermediate, we examined potential activities of candidate intermediates in the RNAi-treated larvae. We found that two 3-oxo steroids, cholesta-4,7-diene-3,6-dione-14α-ol (Δ(4)-diketol) and 5ß [H]cholesta-7-ene-3,6-dione-14α-ol (diketol), triggered molting of the RNAi-treated larvae. We also detected an enhancement of the amounts of ecdysteroids in the RNAi-treated larvae by feeding the Δ(4)-diketol or diketol, indicating that the dietary 3-oxo steroids were incorporated and converted into ecdysteroids in vivo. Furthermore, 20-hydroxyecdysone inducible genes were induced in the RNAi-treated larvae by feeding the Δ(4)-diketol or diketol. These results indicate that Δ(4)-diketol and diketol are components of the ecdysteroid biosynthetic pathway and lie downstream of a step catalyzed by Spok.