RT Journal Article
SR Electronic
T1 Sustained anti-obesity effects of life-style change and anti-inflammatory interventions after conditional inactivation of the activin receptor ALK7
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.28.224881
DO 10.1101/2020.07.28.224881
A1 Raj Kamal Srivastava
A1 Ee-Soo Lee
A1 Eunice Sim
A1 New Chih Sheng
A1 Carlos F. Ibáñez
YR 2020
UL http://biorxiv.org/content/early/2020/07/30/2020.07.28.224881.abstract
AB Life-style change and anti-inflammatory interventions have only transient effects in obesity. It is not clear how benefits obtained by these treatments can be maintained longer term, specially during sustained high caloric intake. Constitutive ablation of the activin receptor ALK7 in adipose tissue enhances catecholamine signaling and lipolysis in adipocytes, and protects mice from diet-induced obesity. Here, we investigated the consequences of conditional ALK7 ablation in adipocytes of adult mice with pre-existing obesity. Although ALK7 deletion had little effect on its own, it synergized strongly with a transient switch to low-fat diet (life-style change) or anti-inflammatory treatment (Na-salicylate), resulting in enhanced lipolysis, increased energy expenditure, and reduced adipose tissue mass and body weight gain, even under sustained high caloric intake. By themselves, diet-switch and salicylate had only a temporary effect on weight gain. Mechanistically, combination of ALK7 ablation with either treatment strongly enhanced the levels of β3-AR, the main adrenergic receptor for catecholamine stimulation of lipolysis, and C/EBPα, an upstream regulator of β3-AR expression. These results suggest that inhibition of ALK7 can be combined with simple interventions to produce longer-lasting benefits in obesity.