Ahmadieh Samah, Goo Brandee, Zarzour Abdalrahman, Kim David, Shi Hong, Veerapaneni Praneet, Chouhaita Ronnie, Yiew Nicole K H, Dominguez Gonzalez Carla, Chakravartty Akash, Pennoyer James, Hassan Nazeera, Benson Tyler W, Ogbi Mourad, Fulton David J, Lee Richard, Rice Robert D, Hilton Lisa R, Lei Yun, Lu Xin-Yun, Chen Weiqin, Kim Ha Won, Weintraub Neal L
Department of Medicine, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.
Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, Georgia, USA.
Obesity (Silver Spring). 2024 Jan;32(1):107-119. doi: 10.1002/oby.23924. Epub 2023 Oct 23.
Impaired adipogenic differentiation exacerbates metabolic disease in obesity. This study reported that high-fat diet (HFD)-fed mice housed at thermoneutrality exhibited impaired adipogenic differentiation, attributed to increased expression of histone deacetylase 9 (HDAC9). However, the impact of HFD on adipogenic differentiation is reportedly variable, possibly reflecting divergent environmental conditions such as housing temperature.
C57BL/6J (wild-type [WT]) mice were housed at either thermoneutral (28-30°C) or ambient (20-22°C) temperature and fed HFD or chow diet (CD) for 12 weeks. For acute exposure experiments, WT or transient receptor potential cation channel subfamily M member 8 (TRPM8) knockout mice housed under thermoneutrality were acutely exposed to ambient temperature for 6 to 24 h.
WT mice fed HFD and housed at thermoneutrality, compared with ambient temperature, gained more weight despite reduced food intake. They likewise exhibited increased inguinal adipose tissue HDAC9 expression and reduced adipogenic differentiation in vitro and in vivo compared with CD-fed mice. Conversely, HFD-fed mice housed at ambient temperature exhibited minimal change in adipose HDAC9 expression or adipogenic differentiation. Acute exposure of WT mice to ambient temperature reduced adipose HDAC9 expression independent of sympathetic β-adrenergic signaling via a TRPM8-dependent mechanism.
Adipose HDAC9 expression is temperature sensitive, regulating adipogenic differentiation in HFD-fed mice housed under thermoneutrality.
脂肪生成分化受损会加剧肥胖中的代谢性疾病。本研究报道，在热中性环境下饲养的高脂饮食（HFD）喂养小鼠表现出脂肪生成分化受损，这归因于组蛋白去乙酰化酶9（HDAC9）表达增加。然而，据报道，HFD对脂肪生成分化的影响是可变的，这可能反映了不同的环境条件，如饲养温度。
将C57BL/6J（野生型[WT]）小鼠饲养在热中性（28 - 30°C）或环境温度（20 - 22°C）下，并给予HFD或普通饮食（CD）12周。对于急性暴露实验，将在热中性环境下饲养的WT或瞬时受体电位阳离子通道亚家族M成员8（TRPM8）基因敲除小鼠急性暴露于环境温度6至24小时。
与环境温度相比，在热中性环境下饲养并给予HFD的WT小鼠尽管食物摄入量减少，但体重增加更多。与给予CD的小鼠相比，它们在体外和体内同样表现出腹股沟脂肪组织HDAC9表达增加以及脂肪生成分化减少。相反，在环境温度下饲养的HFD喂养小鼠的脂肪HDAC9表达或脂肪生成分化变化最小。通过TRPM8依赖性机制，将WT小鼠急性暴露于环境温度可降低脂肪HDAC9表达，且与交感β-肾上腺素能信号无关。
脂肪HDAC9表达对温度敏感，在热中性环境下饲养的HFD喂养小鼠中调节脂肪生成分化。
