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Type 2 and type 1 diabetes have opposing effects on the systemic murine complement alternative pathway

Colineau, Lucie LU ; Kolodziej, Olga LU ; Ajona, Daniel ; Pio, Ruben ; Blom, Anna M. LU orcid and King, Ben C. LU orcid (2026) In iScience 29(7).
Abstract

Complement factor D (FD) (adipsin), is an adipokine essential for the activation of the complement alternative pathway (AP), contributing to inflammation but also to metabolic homeostasis through C3a production. We investigated the metabolic regulation of Cfd expression in mouse models. A diet-induced model of insulin resistance reduced expression of key AP components, including adipose Cfd, hepatic C3, and factor B. In contrast, two independent type 1 diabetes (T1D) models increased adipose Cfd and hepatic C3 expression, leading to elevated ex vivo serum AP activation, and increased serum C3b, indicating enhanced complement activation in vivo. Across models, adipose Cfd expression showed a strong negative correlation with serum insulin... (More)

Complement factor D (FD) (adipsin), is an adipokine essential for the activation of the complement alternative pathway (AP), contributing to inflammation but also to metabolic homeostasis through C3a production. We investigated the metabolic regulation of Cfd expression in mouse models. A diet-induced model of insulin resistance reduced expression of key AP components, including adipose Cfd, hepatic C3, and factor B. In contrast, two independent type 1 diabetes (T1D) models increased adipose Cfd and hepatic C3 expression, leading to elevated ex vivo serum AP activation, and increased serum C3b, indicating enhanced complement activation in vivo. Across models, adipose Cfd expression showed a strong negative correlation with serum insulin levels, and insulin treatment in T1D mice restored Cfd to baseline. These findings reveal opposing regulation of adipose Cfd and liver C3 in type 1 versus type 2 diabetes models, with corresponding effects on systemic complement activity, highlighting a link between insulin, complement regulation, and metabolic disease.

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author
; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
biological sciences, health sciences, molecular biology
in
iScience
volume
29
issue
7
article number
116359
publisher
Elsevier
external identifiers
  • scopus:105041542749
  • pmid:42325578
ISSN
2589-0042
DOI
10.1016/j.isci.2026.116359
language
English
LU publication?
yes
id
95c2237f-5560-4c69-9cab-140dc8d49a43
date added to LUP
2026-07-03 09:51:56
date last changed
2026-09-25 16:38:36
@article{95c2237f-5560-4c69-9cab-140dc8d49a43,
  abstract     = {{<p>Complement factor D (FD) (adipsin), is an adipokine essential for the activation of the complement alternative pathway (AP), contributing to inflammation but also to metabolic homeostasis through C3a production. We investigated the metabolic regulation of Cfd expression in mouse models. A diet-induced model of insulin resistance reduced expression of key AP components, including adipose Cfd, hepatic C3, and factor B. In contrast, two independent type 1 diabetes (T1D) models increased adipose Cfd and hepatic C3 expression, leading to elevated ex vivo serum AP activation, and increased serum C3b, indicating enhanced complement activation in vivo. Across models, adipose Cfd expression showed a strong negative correlation with serum insulin levels, and insulin treatment in T1D mice restored Cfd to baseline. These findings reveal opposing regulation of adipose Cfd and liver C3 in type 1 versus type 2 diabetes models, with corresponding effects on systemic complement activity, highlighting a link between insulin, complement regulation, and metabolic disease.</p>}},
  author       = {{Colineau, Lucie and Kolodziej, Olga and Ajona, Daniel and Pio, Ruben and Blom, Anna M. and King, Ben C.}},
  issn         = {{2589-0042}},
  keywords     = {{biological sciences; health sciences; molecular biology}},
  language     = {{eng}},
  number       = {{7}},
  publisher    = {{Elsevier}},
  series       = {{iScience}},
  title        = {{Type 2 and type 1 diabetes have opposing effects on the systemic murine complement alternative pathway}},
  url          = {{http://dx.doi.org/10.1016/j.isci.2026.116359}},
  doi          = {{10.1016/j.isci.2026.116359}},
  volume       = {{29}},
  year         = {{2026}},
}