Immunomodulatory glycan LNFPIII alleviates hepatosteatosis and insulin resistance through direct and indirect control of metabolic pathways
| Autor: | Chih-Hao Lee, Lingling Dai, David Jacobi, Kristopher J. Stanya, Sihao Liu, Donald A. Harn, Changlin Li, Matthew R. Gangl, Prerna Bhargava |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Glycan
Adipose tissue Mice Obese Receptors Cytoplasmic and Nuclear Inflammation Diet High-Fat General Biochemistry Genetics and Molecular Biology Article Diabetes Mellitus Experimental 03 medical and health sciences Mice 0302 clinical medicine Insulin resistance Polysaccharides medicine Animals Humans 030304 developmental biology 0303 health sciences biology Macrophages Fatty liver Amino Sugars General Medicine Dendritic Cells Hep G2 Cells medicine.disease 3. Good health Interleukin-10 Fatty Liver Interleukin 10 Metabolic pathway Adipose Tissue Liver Immunology biology.protein medicine.symptom Signal transduction Insulin Resistance Metabolic Networks and Pathways 030215 immunology Signal Transduction |
| Zdroj: | Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | Parasitic worms express host-like glycans to attenuate the immune response of human hosts. The therapeutic potential of this immunomodulatory mechanism in controlling the metabolic dysfunction that is associated with chronic inflammation remains unexplored. We demonstrate here that administration of lacto-N-fucopentaose III (LNFPIII), a Lewis(X)-containing immunomodulatory glycan found in human milk and on parasitic helminths, improves glucose tolerance and insulin sensitivity in diet-induced obese mice. This effect is mediated partly through increased interleukin-10 (Il-10) production by LNFPIII-activated macrophages and dendritic cells, which reduces white adipose tissue inflammation and sensitizes the insulin response of adipocytes. Concurrently, LNFPIII treatment upregulates nuclear receptor subfamily 1, group H, member 4 (Fxr-α, also known as Nr1h4) to suppress lipogenesis in the liver, conferring protection against hepatosteatosis. At the signaling level, the extracellular signal-regulated kinase (Erk)-activator protein 1 (Ap1) pathway seems to mediate the effects of LNFPIII on both inflammatory and metabolic pathways. Our results suggest that LNFPIII may provide new therapeutic approaches to treat metabolic diseases. |
| Databáze: | OpenAIRE |
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