Could lithospemic acid-B attenuate transdifferentiation from brown adipocyte to white adipocyte in high-fat diet mice?

Abstract

Background: Obesity is becoming a global epidemic in both children and adults, and energy balance is important for developing obesity. Brown adipose tissue (BAT) contributes to the control of body temperature and energy expenditure, and recently a new concept of transdifferentiation of two kinds of adipocytes – brown adipocytes and white adipocytes – induced by physiologic stimuli to meet different energy partitioning biological demands. Lithospermic acid-B (LAB), tetramer of caffeic acid, the most abundant component in aqueous extracts of the Salvia species and recently is known to have antioxidative and antifibrotic effects. However, little is known about the effect of LAB on brown adipose tissue. The present study was undertaken to examine the effects of LAB treatment on the transdifferentiation of brown adipocyte to white adipocyte-like cell in high-fat diet mice and the further protective effect against diet-induced obesity. Materials and Methods: Male C57BL/6 mice (n = 18) were separated into three groups: (1) fed with chow diet and vehicle treated; (2) fed with high-fat diet and vehicle treated; (3) fed with high-fat diet and LAB (20mg/kg/day) treated. Body weights and food intakes were measured weekly and random glucose levels were checked every 4 weeks. After 16 weeks, fasting plasma glucose, leptin and adiponectin levels were measured in the morning after an overnight fast and insulin tolerance test was done. Histological examination and morphometric analysis of brown adipose tissues were performed. Immunohistochemistry, immunofluorescence, western blot analysis and RT-PCR for UCP-1 expression were performed. Results: After 16wks, LAB treatment did not affect HFD-associated alterations in body weight, food intake, fasting glucose level, and insulin resistance. However, we observed the morphometric changes indicating preservation of characteristics of brown adioicytes in LAB treated group. And LAB attenuates the transdifferentiation of brown adipocyte to white adipocyte-like cell and maintains the expression of UCP-1 at both protein and mRNA levels in mice fed a high-fat diet. However, the serum levels of leptin and adiponectin were not different. Conclusions: These results suggest that the effect of LAB to inhibit the transdifferentiation of brown adipocyte in animal fed high-fat diet, is associated with the pathophysiology of obesity and related to therapeutic strategies of anti-obesity and/or anti-diabetic drugs.