2023-03-09 バーミンガム大学
この研究は、肥満に伴う低レベルの炎症反応と、それによって引き起こされる膵臓の変化と糖尿病の発症の間に、adiponectin-PEPITEMパスウェイがあることを示しています。
PEPITEMは、天然由来ペプチドであり、肥満関連疾患の原因に対処するための新しい薬剤を提供する可能性があります。今後は、これらの結果を人間に応用するための治療薬につなげることが必要です。
<関連情報>
- https://www.birmingham.ac.uk/news/2023/naturally-occurring-peptide-may-tackle-the-root-cause-of-obesity-related-conditions
- https://academic.oup.com/cei/advance-article/doi/10.1093/cei/uxad022/7073686?login=false
PEPITEMは白血球の輸送を調節して肥満による炎症を抑制する PEPITEM modulates leukocyte trafficking to reduce obesity-induced inflammation
Laleh Pezhman, Sophie J Hopkin, Jenefa Begum, Silke Heising, Daniela Nasteska, Mussarat Wahid, G Ed Rainger, David J Hodson, Asif J Iqbal, Myriam Chimen,Helen M McGettrick
Clinical and Experimental Immunology Published:09 March 2023
DOI:https://doi.org/10.1093/cei/uxad022
Abstract
Dysregulation of leukocyte trafficking, lipid metabolism, and other metabolic processes are the hallmarks that underpin and drive pathology in obesity. Current clinical management targets alternations in lifestyle choices (e.g. exercise, weight loss) to limit the impact of the disease. Crucially, re-gaining control over the pathogenic cellular and molecular processes may offer an alternative, complementary strategy for obese patients. Here we investigate the impact of the immunopeptide, PEPITEM, on pancreas homeostasis and leukocyte trafficking in mice on high-fed obesogenic diet (HFD). Both prophylactic and therapeutic treatment with PEPITEM alleviated the effects of HFD on the pancreas, reducing pancreatic beta cell size. Moreover, PEPITEM treatment also limited T-cell trafficking (CD4+ T-cells and KLRG1+ CD3+ T-cells) to obese visceral, but not subcutaneous, adipose tissue. Similarly, PEPITEM treatment reduced macrophage numbers within the peritoneal cavity of mice on HFD diet at both 6 and 12 weeks. By contrast, PEPITEM therapy elevated numbers of T and B cells were observed in the secondary lymphoid tissues (e.g. spleen and inguinal lymph node) when compared to the untreated HFD controls. Collectively our data highlights the potential for PEPITEM as a novel therapy to combat the systemic low-grade inflammation experienced in obesity and minimize the impact of obesity on pancreatic homeostasis. Thus, offering an alternative strategy to reduce the risk of developing obesity-related co-morbidities, such as type 2 diabetes mellitus, in individuals at high risk and struggling to control their weight through lifestyle modifications.
