Codon-optimized FAM132b prevents diet-induced obesity by modulating adrenergic response and insulin action [article]

Zhengtang Qi, Jie Xia, Xiangli Xue, Wenbin Liu, Zhuochun Huang, Xue Zhang, Yong Zou, Jianchao Liu, Jiatong Liu, Xingtian Li, Lu Cao, Lingxia Li (+5 others)
2020 bioRxiv   pre-print
FAM132b has been identified as a exercise-induced myokine. It is a secreted protein precursor that belongs to the adipolin/erythroferrone family, and has hormone activity in circulation to regulate cellular iron homeostasis and lipid metabolism via unknown receptors. Here, adeno-associated viral vectors (AAV9) were engineered to induce overexpression of FAM132b with 2 codon mutations (A136T and P159A). Treatment of mice under high-fat diet feeding with FAM132b gene transfer resulted in marked
more » ... ductions in body weight, fat depot, adipocytes size, glucose intolerance and insulin resistance. Moreover, FAM132b overproduction reduced glycemic response to epinephrine (EPI) in whole body and increased lipolytic response to EPI in adipose tissues. This adrenergic response of adipose tissue led to the result that gene transfer reduced glycogen utilization and increased fat consumption in skeletal muscle during exercise. FAM132b knockdown by shRNA significantly increased glycemic response to EPI in vivo and reduced adipocytes response to EPI and adipose tissue browning. Structural analysis suggested that FAM132b mutants delivered by AAV9 may form a weak bond with ADRB2, and potentially bind to insulin against insulin receptor.
doi:10.1101/2020.08.31.275503 fatcat:jkquyfk7svcodlqyi4lj2y4l5u