Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse.

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.