AbstractType 2 immunity plays an essential role in the maintenance of metabolic homeostasis and its disruption during obesity promotes meta-inflammation and insulin resistance. Infection with the helminth parasite Schistosoma mansoni and treatment with its soluble egg antigens (SEA) can induce a type 2 immune response in metabolic organs and improve insulin sensitivity and glucose tolerance in obese mice, yet a causal relationship remains unproven. Here, we investigated the effects and underlying mechanisms of the T2 ribonuclease omega-1 (ω1), one of the major S. mansoni immunomodulatory glycoproteins, on metabolic homeostasis. Male C57Bl6/J mice were fed a high-fat diet for 12 weeks followed by bi-weekly injection of SEA, ω1 or vehicle for 4 additional weeks. Whole-body metabolic homeostasis and energy expenditure were assessed by glucose/insulin tolerance tests and indirect calorimetry, respectively. Tissue-specific immune cell phenotypes were determined by flow cytometry. We show that treatment of obese mice with plant-produced recombinant ω1, harboring similar glycan motifs as present on the native molecule, decreased body fat mass and improved systemic insulin sensitivity and glucose tolerance in a time-and dose-dependent manner. This effect was associated with an increase in white adipose tissue (WAT) type 2 T helper cells, eosinophils and alternatively-activated macrophages, without affecting type 2 innate lymphoid cells. In contrast to SEA, the metabolic effects of ω1 were still observed in obese STAT6-deficient mice with impaired type 2 immunity, indicating that its metabolic effects are independent of the type 2 immune response. Instead, we found that ω1 inhibited food intake, without affecting locomotor activity, WAT thermogenic capacity or whole-body energy expenditure, an effect also occurring in leptin receptor-deficient obese and hyperphagic db/db mice. Altogether, we demonstrate that while the helminth glycoprotein ω1 can induce type 2 immunity, it improves whole-body metabolic homeostasis in obese mice by inhibiting food intake via a STAT6-independent mechanism.Author summaryThe obesity-induced chronic low-grade inflammation, notably in adipose tissue, contributes to insulin resistance and increased risk of type 2 diabetes. We have previously shown that infection with parasitic helminth worms was associated with protection against obesity-related metabolic dysfunctions both in mice and humans. We have also reported that treatment of obese mice with an extract of Schistosoma mansoni eggs (SEA) improves insulin sensitivity and glucose tolerance, a beneficial effect that was associated with a helminth-specific type 2 immune response in metabolic organs. Here, we studied the effects of omega-1 (ω1), a single immunomodulatory molecule from SEA, on metabolic health in obese mice, and investigated the role of the host immune response elicited. We found that ω1 induced a helminth-characteristic type 2 immune response in adipose tissue and improved both insulin sensitivity and glucose tolerance in obese mice. Yet, in contrast to SEA, ω1’s immunomodulatory properties were dispensable for its metabolic effects. Instead, we show that ω1 inhibited food intake, a feature accounting for most of the improvements in metabolic health. Together, our findings indicate that helminth molecules may improve metabolic health through multiple distinct mechanisms, and further characterization of such molecules could lead to new therapeutic strategies to combat obesity.

Is paper WS selected for presentation by an SPE Program committee following review of information cnntained in an abstract submitted by the author(s). Contents of the paper, as presented, have not been revtewed by the S@ety of Petroleum Englneera and are subject to mrretion by the author(s). The material, as presented, does not neceaearlly reflect anỹ ition of the society of Petroleum Engineers, ita ofricera, w members. Papers presented at SPE meetings are subject to pubK@tion retiew by Editorial Committees of the Scdety of Petroleum Englneara. Electronic reproduction, distribution, or storage of any part of this paper for mmmerdal pu~ee tithwt the written mnsent of the Sdety of Petroleum Engineers Is prohibited. Permission to raproduce In print is restricted to an absbad of not more than 300 wurds; illustrations may not be mpied.The abstrad must mntsln wnsplcuous atiowledgment of Mere and by whom the paper was preeented. Write Librartan, SPE, P.O. Mx 833636, Ritiardson, TX 7S0S3-3836, U.SA., fax 01 -972-952-%3S. AbstractFor oil production under high water cut conditions the efforts needed for de-oiling of the production water are mainly determined by the oil-droplet-size distribution of this water. This distribution is predominantly the result of droplet breakup in the choke valve. To determine the effect of the choke valve on the droplet-size distribution, we have conducted laboratory experiments in which we used a circular orifice in a circular pipe. With the help of theory on droplet break-up in turbulent flow and with knowledge of the flow field inside an orifice, a prediction of the distribution after break-up can be made. It is shown that the droplets increase in size with increasing oil viscosity and Mermore it appears that, for the description of the break-up process, the distribution of the turbulence over the orifice zone is an important factor.