Cthrc1 controls adipose tissue formation, body composition, and physical activity

Abstract

Objective This study investigated the effects of loss of Cthrc1 on adipogenesis, body composition, metabolism, physical activity and muscle physiology. Methods Complete metabolic and activity monitoring as well as grip strength measurements and muscle myography were performed in Cthrc1 null and wildtype mice. Results Compared to wildtypes, Cthrc1 null mice had similar body weights but significantly reduced energy expenditure, decreased lean mass and increased fat mass, especially visceral fat. In vitro studies demonstrated that Cthrc1 inhibited adipocyte differentiation as well as PPAR and CREB reporter activity, while preadipocytes isolated from Cthrc1 null mice exhibited enhanced adipogenic differentiation. Voluntary physical activity in Cthrc1 null mice as assessed by wheel running was reduced to approximately half the distance covered by wildtypes. Reduced grip strength was observed in Cthrc1 null mice at the age of 15 weeks or older with reduced performance and mass of fast twitch muscle. In the brain, Cthrc1 expression was most prominent in neurons of thalamic and hypothalamic nuclei with evidence for secretion into the circulation in the median eminence. Conclusions Our data indicate that Cthrc1 regulates body composition through inhibition of adipogenesis. In addition, central Cthrc1 may be a mediator of muscle function and physical activity.

ColXV promotes adipocyte differentiation via inhibiting DNA methylation and cAMP/PKA pathway in mice

“…CREB is a well-documented transcription factor involved in adipocyte differentiation and lipid metabolism. Previous study has shown collagen triple helix repeat containing 1 (Cthrc1) inhibits adipocyte differentiation by inhibiting PPARγ signaling and activating CREB [ 32 ], which is consistent with our findings CREB as a negative regulator in ColXV promoted adipocyte differentiation. Although some reports indicated that CREB participates in adipogenesis via positive transcriptional regulating C/EBPβ and PPARγ at early state [ 33 , 34 ], we found CREB suppressed adipocyte differentiation dependent on ColXV.…”

Human gingiva transcriptome during wound healing

“…) and adipose tissue metabolism (Stohn et al. ). The exact function of synaptotagmin 16, which is the product of SYT16 (Fukuda ), and which was down‐regulated in healing gingiva, remains unknown; there are no previous reports of SYT16 expression in the gingiva.…”

RNA-seq and metabolomic analyses of Akt1-mediated muscle growth reveals regulation of regenerative pathways and changes in the muscle secretome

“…Cthrc1 encodes for a secreted protein that was first identified to increase bone mass by regulating osteoblast proliferation and differentiation [ 75 ]. Recent studies also show that this factor has a metabolic function, as whole-body Cthrc1 deficiency will promote liver steatosis and increased subcutaneous fat mass [ 76 , 77 ]. Another example is biglycan (encoded by Bgn ) that is induced 11-fold by Akt1 in muscle.…”