Division of Gastroenterology and Hepatology, Department of Internal Medicine, Maastricht University Medical Centre, Maastricht, The Netherlands.
School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands.
Horm Metab Res. 2020 Dec;52(12):869-876. doi: 10.1055/a-1301-2378. Epub 2020 Dec 1.
Brown adipose tissue (BAT) might be a beneficial mediator in the development and treatment of nonalcoholic steatohepatitis (NASH). We aim to evaluate the gene expression of BAT activity-related genes during the development and the dietary and surgical treatment of NASH. BAT was collected from male mice that received a high fat-high sucrose diet (HF-HSD) or a normal chow diet (NCD) for 4 and 20 weeks (n=8-9 per dietary group and timepoint) and from mice that underwent dietary intervention (return to NCD) (n=8), roux-en-y gastric bypass (RYGB) (n=6), or sham procedure (n=6) after 12 weeks HF-HSD. Expression of BAT genes involved in lipid metabolism (Cd36 and Cpt1b; p<0.05) and energy expenditure (Ucp1 and Ucp3; p<0.05) were significantly increased after 4 weeks HF-HSD compared with NCD, whereas in the occurrence of NASH after 20 weeks HF-HSD no difference was observed. We observed no differences in gene expression regarding lipid metabolism or energy expenditure at 8 weeks after dietary intervention (no NASH) compared with HF-HSD mice (NASH), nor in mice that underwent RYGB compared with SHAM. However, dietary intervention and RYGB both decreased the BAT gene expression of inflammatory cytokines (Il1b, Tnf-α and MCP-1; p<0.05). Gene expression of the neuregulin 4 was significantly decreased after 20 weeks HF-HSD (p<0.05) compared with NCD, but was restored by dietary intervention and RYGB (p<0.05). In conclusion, BAT is hallmarked by dynamic alterations in the gene expression profile during the development of NASH and can be modulated by dietary intervention and bariatric surgery.
棕色脂肪组织（BAT）可能是非酒精性脂肪性肝炎（NASH）发生和治疗的有益介质。我们旨在评估 BAT 活性相关基因在 NASH 发生和饮食及手术治疗过程中的基因表达情况。雄性小鼠接受高脂肪高蔗糖饮食（HF-HSD）或正常饮食（NCD）4 周和 20 周（每组和每个时间点 8-9 只），以及经过饮食干预（恢复 NCD）、胃旁路手术（RYGB）或假手术（SHAM）12 周 HF-HSD 后，收集 BAT。与 NCD 相比，HF-HSD 4 周后，BAT 参与脂质代谢（Cd36 和 Cpt1b；p<0.05）和能量消耗（Ucp1 和 Ucp3；p<0.05）的基因表达显著增加，而在 20 周 HF-HSD 后发生 NASH 时则无差异。与 HF-HSD 小鼠（NASH）相比，饮食干预 8 周后（无 NASH），或与 RYGB 相比，SHAM 手术中，脂质代谢或能量消耗的基因表达均无差异。然而，饮食干预和 RYGB 均降低了 BAT 炎性细胞因子（Il1b、Tnf-α 和 MCP-1；p<0.05）的基因表达。与 NCD 相比，HF-HSD 20 周后神经调节蛋白 4 的基因表达显著降低（p<0.05），但通过饮食干预和 RYGB 可恢复（p<0.05）。总之，BAT 在 NASH 发生过程中的基因表达谱呈现动态变化，并可通过饮食干预和减重手术来调节。
