Calsyntenin 3β Is Dynamically Regulated by Temperature in Murine Brown Adipose and Marks Human Multilocular Fat

Abstract

Activation of thermogenic adipose tissue is linked to improved metabolic outcomes in mice and humans. Dissipation of energy as heat during thermogenesis relies on sufficient innervation of fat by sympathetic nerve fibers, a process recently proposed to be regulated by the adipose-specific calsyntenin3b (Clstn3b)-S100b axis. Here we aimed 1) to assess enrichment patterns of CLSTN3b, S100b as well as the previously annotated neuronal CLSTN3a in perirenal brown and subcutaneous white human fat specimens, and 2) to investigate if the novel Clstn3b is dynamically regulated by changes in environmental temperatures and nutritional stress in thermogenic adipose tissues in mice. We provide evidence for CLSTN3b enrichment in multilocular perirenal fat located anatomically in the proximity to both the adrenal gland and sympathetic nerve bundles innervating the kidney in humans. Moreover, transcript levels of CLSTN3b, but not S100b or CLSTN3a, positively correlate with uncoupling protein 1 (UCP1) expression in human adipose tissue. Our results further show that Clsnt3b is preferentially expressed in brown adipocytes and is highly responsive to changes in environmental temperature and obesity state in mice. Collectively, this brief communication highlights CLSTN3b as a hallmark of thermogenic adipose depots in mice and humans.

CLSTN3β enforces adipocyte multilocularity to facilitate lipid utilization

“…10b). CLSTN3 was previously identified as the most significantly enriched gene in human multilocular versus unilocular adipose tissue 46,47 . To validate this finding, we analysed gene expression in periadrenal adipose tissue from control participants and patients with pheochromocytoma.…”

CLSTN3 gene variant associates with obesity risk and contributes to dysfunction in white adipose tissue

“…Moreover, due to the shared sequence homology between Clstn3b and Clstn3 genes, their total transcripts have been identified in transcriptomic datasets of mouse and human fat [ 26 , 45 ]. Furthermore, the adipose-specificity of both Clstn3 and Clstn3b transcripts has been assessed separately in adipose depots of mice and humans under environmental cues [ 46 ]. In the current study, we observed that the expression pattern of CLSTN3 gene in human adipose tissue is different from that in mice.…”

Full activation of thermogenesis in brown adipocytes requires Basigin action

“…Mice were first acclimated to 29 °C in climate chambers (Memmert HPP750Life) for 21 days and subsequently transitioned to 5 °C for 3, 7 or 21 days. The mice used are previously described [28]. For BAT deactivation experiment, mice were housed at 5 °C for 21 days and then transitioned to 29 °C for either 3 or 7 days.…”

“…For cold exposure experiments, 10 weeks old C57BL/6 male mice (Taconic, Germantown, NY, USA) were used and given a chow diet (1310; Altromin, Lage, Germany), as previously described [28]. Ob/ob male mice (Jackson Laboratories, Bar Harbor, ME, USA, Cat.000632) were fed the control diet (D12450B, Research Diets, Inc., New Brunswick, NJ, USA).…”