Objective: To investigate the effect of silent mating type information regulation 2 homolog 1 (SIRT1) deficiency on function of brown adipose tissue (BAT) in high-fat diet (HFD)-induced obese mice.
Methods: Male SIRT1 deficient heterozygous (SIRT1(+ /-)) mice and their wild-type (WT) littermates were challenged with a HFD diet for 16 weeks to induce obesity model.Energy metabolic cages were used to measure oxygen consumption and heat production, and cold tolerance test was to evaluate the adaptive thermogenic function.With brown fat collected after the diet intervention, determination techniques were adopted included HE staining for morphologic changes, immunohistochemical staining and Western blotting for uncoupling protein 1 (UCP1) expression, quantitative real-time PCR for relative content of mitochondria DNA (mtDNA).
Results: Compared to WT controls, SIRT1(+ /-) mice displayed significant decreases in both oxygen consumption and heat production[(2 681±297) vs (3 017±313) ml·kg(-1)·h(-1,) (19.05±2.40) vs (21.15±2.49) kcal·kg(-1)·h(-1,) both P<0.05)], as well as an impairment in maintaining their body temperature during the cold challenge.HE staining revealed the accumulation of larger lipid droplets in BAT of SIRT1(+ /-) mice, and both immunohistochemical staining and Western blotting indicated an obvious reduction in expression of UCP1 (P<0.05). Quantitative real-time PCR showed a significant decrease in the relative mtDNA content in BAT of SIRT1(+ /-) mice (0.38±0.10 vs 1.00±0.40, P<0.05).
Conclusion: SIRT1 deficiency promotes BAT dysfunction, meaning that whitening in obese mice.