Insulin resistance impairs cutaneous wound healing in mice

• Published in: Wound repair and regeneration Vol. 21; no. 3; pp. 464 - 472
• Main Authors: Otranto, Marcela, Nascimento, Adriana Paulino do, Monte-Alto-Costa, Andréa
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.05.2013
• Subjects: Animals; Disease Models, Animal; Follow-Up Studies; Glucose Tolerance Test; Hydroxyproline - metabolism; Immunoblotting; Immunohistochemistry; Insulin Resistance - physiology; Male; Mice; Mice, Inbred C57BL; Nitric Oxide Synthase Type II - metabolism; Skin - injuries; Skin - metabolism; Skin - pathology; Wound Healing - physiology; Wounds and Injuries - metabolism; Wounds and Injuries - pathology
• ISSN: 1067-1927; 1524-475X; 1524-475X
• DOI: 10.1111/wrr.12042

Obesity is associated with significant changes in skin combined with metabolic alterations such as insulin resistance. Our aim was to investigate the effects of insulin resistance induced by a high‐fat diet on cutaneous wound healing. Male C57BL/6 mice were fed standard chow (SC group) or high‐fat chow (HFC group) for 30 weeks. On day 0 (28th week), an excisional wound was performed. After 14 days (30th week), the mice were euthanized. Starting from the 8th week, the HFC group had a higher body weight. The HFC group became intolerant to glucose, resistant to insulin, and presented increased plasma cholesterol and triglyceride levels. The wound area was greater in the HFC group. The inflammatory infiltrate and the amount of “fibroblast‐like” cells increased in superficial regions of the lesions in the HFC group. The collagen fibers were more organized and denser in the SC group. Hydroxyproline levels were lower in the HFC group. The nitric oxide synthase‐2‐positive cells were higher in the HFC group. Lipid peroxidation and protein carbonyl levels were higher in the HFC group. The expression levels of alpha‐smooth muscle actin and transforming growth factor‐β were higher in the HFC group. These findings support the hypothesis that insulin resistance leads to delayed cutaneous wound healing.