Lgals9 deficiency ameliorates obesity by modulating redox state of PRDX2
| Autor: | Jun Eguchi, Jun Wada, Satoshi Yamaguchi, Toshiro Niki, Atsuko Nakatsuka, Akihiro Katayama, Sanae Teshigawara, Tomokazu Nunoue |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Immunoprecipitation Molecular biology Science Metabolic disorders Adipose tissue Adipokine Inflammation Diseases medicine.disease_cause Article Medical research Internal medicine medicine Protein disulfide-isomerase Gene knockdown Multidisciplinary Chemistry Health care Experimental models of disease Endocrinology Apoptosis Medicine medicine.symptom Oxidative stress |
| Zdroj: | Scientific Reports, Vol 11, Iss 1, Pp 1-12 (2021) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | The adipose tissue is regarded as an endocrine organ and secretes bioactive adipokines modulating chronic inflammation and oxidative stress in obesity. Gal-9 is secreted out upon cell injuries, interacts with T-cell immunoglobulin-3 (Tim-3) and induces apoptosis in activated Th1 cells. Gal-9 also binds to protein disulfide isomerase (PDI), maintains PDI on surface of T cells, and increases free thiols in the disulfide/thiol cycles. To explore the molecular mechanism of obesity, we investigated Gal-9−/− and Gal-9wt/wt C57BL/6J mice fed with high fat-high sucrose (HFHS) chow. Gal-9−/− mice were resistant to diet-induced obesity associated with reduction of epididymal and mesenteric fat tissues and improved glucose tolerance compared with Gal-9wt/wt mice. However, the number of M1, M2 macrophages, and M1/M2 ratio in epididymal fat were unaltered. Under HFHS chow, Gal-9−/− mice receiving Gal-9−/− or Gal-9wt/wt bone marrow-derived cells (BMCs) demonstrated significantly lower body weight compared with Gal-9wt/wt mice receiving Gal-9−/− BMCs. We identified the binding between Gal-9 and peroxiredoxin-2 (PRDX2) in sugar chain-independent manner by nanoLC-MS/MS, immunoprecipitation, and pull-down assay. In 3T3L1 adipocytes, Gal-9 knockdown shifts PRDX2 monomer (reduced form) dominant from PRDX2 dimer (oxidized form) under oxidative stress with H2O2. The inhibition of Gal-9 in adipocytes may be a new therapeutic approach targeting the oxidative stress and subsequent glucose intolerance in obesity. |
| Databáze: | OpenAIRE |
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