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Zande, H.J.P. van der; Gonzalez, M.A.; Ruiter, K. de; Wilbers, R.H.P.; Garcia-Tardon, N.; Huizen, M. van; ... ; Guigas, B. (2021)

The helminth glycoprotein omega-1 improves metabolic homeostasis in obese mice through type 2 immunity-independent inhibition of food intake

Article / Letter to editor
Type 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) 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 (omega 1), one of the major S mansoni immunomodulatory glycoproteins, on metabolic homeostasis. We show that treatment of obese mice with plant-produced recombinant omega 1, 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,...Show moreType 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) 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 (omega 1), one of the major S mansoni immunomodulatory glycoproteins, on metabolic homeostasis. We show that treatment of obese mice with plant-produced recombinant omega 1, 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 omega 1 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 omega 1 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 omega 1 can induce type 2 immunity, it improves whole-body metabolic homeostasis in obese mice by inhibiting food intake via a STAT6-independent mechanism.Show less
helminths
immunometabolism
insulin sensitivity
macrophages
type 2 immunity
All authors
Zande, H.J.P. van der; Gonzalez, M.A.; Ruiter, K. de; Wilbers, R.H.P.; Garcia-Tardon, N.; Huizen, M. van; Noort, K. van; Pelgrom, L.R.; Lambooij, J.M.; Zawistowska-Deniziak, A.; Otto, F.; Ozir-Fazalalikhan, A.; Willigen, D. van; Welling, M.; Poles, J.; Leeuwen, F. van; Hokke, C.H.; Schots, A.; Yazdanbakhsh, M.; Loke, P.; Guigas, B.
Date
2021-02-01
Journal
FASEB Journal
Volume
35
Issue
2
DOI
doi:10.1096/fj.202001973R
Link
https://faseb.onlinelibrary.wiley.com/doi/10.1096/fj.202001973R