Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse.
10.11817/j.issn.1672-7347.2025.240619
- Author:
Kexin LONG
1
,
2
,
3
;
Wangqing CHEN
1
;
Manyun MAO
1
,
4
;
Wu ZHU
1
,
5
Author Information
1. Department of Dermatology, Xiangya Hospital, Central South University, Changsha
2. long_kx@
3. com.
4. maomanyun@yeah.net.
5. zhuwuxy@csu.edu.cn.
- Publication Type:Journal Article
- Keywords:
acitretin;
glucose and lipid metabolism;
lipogenesis;
psoriasis
- MeSH:
Acitretin/therapeutic use*;
Psoriasis/drug therapy*;
Animals;
Imiquimod;
Humans;
Glucose/metabolism*;
Homeostasis/drug effects*;
Mice;
Lipid Metabolism/drug effects*;
Mice, Inbred BALB C;
Female;
Hep G2 Cells;
Disease Models, Animal
- From:
Journal of Central South University(Medical Sciences)
2025;50(3):344-357
- CountryChina
- Language:English
-
Abstract:
OBJECTIVES:Psoriasis is a chronic inflammatory skin disease often accompanied by comorbidities such as hyperglycemia, insulin resistance, and obesity. Acitretin, as a second-generation retinoid, is used in the treatment of psoriasis. This study aims to explore the role of acitretin on glucose and lipid metabolism in psoriasis.
METHODS:HepG2 cells were treated with acitretin under high- or low-glucose conditions. mRNA and protein expression levels of glucose transport-related genes were evaluated using real-time reverse transcription PCR (real-time RT-PCR) and Western blotting. Glucose uptake was analyzed by flow cytometry, and intracellular lipid droplet formation was assessed via Oil Red O staining. Healthy adult female BALB/C mice were randomly divided into 3 groups: a control group, an imiquimod (IMQ)-induced psoriasis model group (IMQ group), and an acitretin treatment group. Skin lesions and inflammatory markers were examined, along with changes in body weight, plasma glucose/lipid levels, and transcription of metabolic genes. Islets were isolated from normal and psoriasis-induced mice, and the effect of acitretin on insulin secretion was evaluated in vitro.
RESULTS:Acitretin treatment increased glucose uptake and lipid droplet synthesis of HepG2 in high-glucose environment, with elevated transcription levels of glucose transport-related genes GLUT1 and GLUT4. Transcription of gluconeogenesis-related gene G6pase decreased, while transcription levels of glycogen synthesis-related genes AKT1 and GSY2 increased (all P<0.05), while acitretin inhibits glucose uptake and promotes gluconeogenesis in low-glucose environment. In vivo experiments revealed that compared with the control group, the blood glucose level in the IMQ group was significantly decreased (P<0.05), while acitretin treatment partially restored glucose homeostasis and alleviated weight loss. Ex vivo culture of islets from psoriatic mice revealed that acitretin reduced elevated insulin secretion and downregulated PDX-1 expression, while upregulating glucose homeostasis gene SIRT1 and insulin sensitivity gene PPARγ (all P<0.05). These findings suggest that acitretin plays a critical role in improving islet function and restoring islet homeostasis.
CONCLUSIONS:Acitretin helps maintain the balance between hepatic glycogenesis and gluconeogenesis, enhances insulin sensitivity, and improves pancreatic islet function, thereby promoting systemic and cellular glucose homeostasis.
