Recruitment of Muscle Genes as an Effect of Brown Adipose Tissue Ablation in Cold-Acclimated Brandt's Voles ( Lasiopodomys brandtii ).
Min LiuXue-Ying ZhangChen-Zhu WangDe-Hua WangPublished in: International journal of molecular sciences (2022)
Skeletal muscle-based nonshivering thermogenesis (NST) plays an important role in the regulation and maintenance of body temperature in birds and large mammals, which do not contain brown adipose tissue (BAT). However, the relative contribution of muscle-based NST to thermoregulation is not clearly elucidated in wild small mammals, which have evolved an obligate thermogenic organ of BAT. In this study, we investigated whether muscle would become an important site of NST when BAT function is conditionally minimized in Brandt's voles ( Lasiopodomys brandtii ). We surgically removed interscapular BAT (iBAT, which constitutes 52%~56% of total BAT) and exposed the voles to prolonged cold (4 °C) for 28 days. The iBAT-ablated voles were able to maintain the same levels of NST and body temperature (~37.9 °C) during the entire period of cold acclimation as sham voles. The expression of uncoupling protein 1 (UCP1) and its transcriptional regulators at both protein and mRNA levels in the iBAT of cold-acclimated voles was higher than that in the warm group. However, no difference was observed in the protein or mRNA levels of these thermogenesis-related markers except for PGC-1α in other sites of BAT (including infrascapular region, neck, and axilla) between warm and cold groups either in sham or iBAT-ablated voles. The iBAT-ablated voles showed higher UCP1 expression in white adipose tissue (WAT) than sham voles during cold acclimation. The expression of sarcolipin ( SLN ) and sarcoplasmic endoplasmic reticulum Ca 2+ -dependent adenosine triphosphatase ( SERCA ) in skeletal muscles was higher in cold than in warm, but no alteration in phospholamban ( PLB ) and phosphorylated-PLB (P-PLB) was observed. Additionally, there was increased in iBAT-ablated voles compared to that in the sham group in cold. Moreover, these iBAT-ablated voles underwent extensive remodeling of mitochondria and genes of key components related with mitochondrial metabolism. These data collectively indicate that recruitment of skeletal muscle-based thermogenesis may compensate for BAT impairment and suggest a functional interaction between the two forms of thermogenic processes of iBAT and skeletal muscle in wild small mammals for coping cold stress.
Keyphrases
- skeletal muscle
- adipose tissue
- insulin resistance
- binding protein
- poor prognosis
- high fat diet
- endoplasmic reticulum
- oxidative stress
- squamous cell carcinoma
- long non coding rna
- metabolic syndrome
- type diabetes
- double blind
- clinical trial
- amino acid
- transcription factor
- early stage
- genome wide
- small molecule
- protein kinase
- machine learning
- high resolution
- sentinel lymph node
- deep learning
- stress induced
- atomic force microscopy
- lymph node
- single molecule
- atrial fibrillation
- catheter ablation
- genome wide identification