sphingosine kinase 2 knockout mice resist hfd-induced obesity through increasing energy expenditure

Background: it has been reported that sphingosine kinase (sk) 2 plays a role in maintaining metabolism and glucose homeostasis. however, the mechanism remains uncertain. objectives: the present research aimed to further investigate the effect of sk2 knockout on high-fat diet (hfd)-induced obesity and metabolic regulation. methods: male sk2−/− and wild-type (wt) control mice were challenged with hfd for 8 weeks. then, body composition, inguinal white adipose tissue (iwat) histology, intraperitoneal glucose tolerance tests (ipgtt), and metabolic parameters were examined, and expression levels of uncoupling protein 1 (ucp1), a key molecular marker of thermogenesis, in iwat were determined. results: after 8 weeks of hfd challenge, compared with wt mice, sk2−/− mice displayed decreased whole body, epididymal white adipose tissue (ewat) and iwat weights, reduced fat/lean body mass ratios and inguinal adipocytes size; also, sk2-/- mice exhibited improved intraperitoneal glucose tolerance. next, elevated energy expenditure was observed in sk2−/− mice compared with wt mice; however, neither food intake nor physical activity showed obvious difference between sk2-/- and wt mice. furthermore, we found that the expressions of ucp1 was markedly increased in iwat from sk2-/- mice. conclusions: sk2-/- mice may resist hfd-induced obesity through increasing energy expenditure by promoting thermogenesis in the beige adipose tissue.