A neurogenic signature involving monoamine Oxidase-A controls human thermogenic adipose tissue development

Abstract

Mechanisms that control 'beige/brite' thermogenic adipose tissue development may be harnessed to improve human metabolic health. To define these mechanisms, we developed a species-hybrid model in which human mesenchymal progenitor cells were used to develop white or thermogenic/beige adipose tissue in mice. The hybrid adipose tissue developed distinctive features of human adipose tissue, such as larger adipocyte size, despite its neurovascular architecture being entirely of murine origin. Thermogenic adipose tissue recruited a denser, qualitatively distinct vascular network, differing in genes mapping to circadian rhythm pathways, and denser sympathetic innervation. The enhanced thermogenic neurovascular network was associated with human adipocyte expression of THBS4, TNC, NTRK3 and SPARCL1, which enhance neurogenesis, and decreased expression of MAOA and ACHE, which control neurotransmitter tone. Systemic inhibition of MAOA, which is present in human but absent in mouse adipocytes, induced browning of human but not mouse adipose tissue, revealing the physiological relevance of this pathway. Our results reveal species-specific cell type dependencies controlling the development of thermogenic adipose tissue and point to human adipocyte MAOA as a potential target for metabolic disease therapy.

Wnt signaling preserves progenitor cell multipotency during adipose tissue development

“…6a ) and generate a functional human/mouse hybrid adipose depot (Fig. 6b ) 33 . Analysis of human transcript-specific reads in adipose tissue formed 8 weeks after implantation revealed expected expression of human adipocyte genes, as well as expression of mesenchymal progenitor markers and canonical Wnt target genes (Fig.…”

“…Methods for the collection and culture of adipose tissue explants were previously published 33 . In brief, ~10 7 passage 3 human adipose tissue derived progenitor cells were thawed into 150-mm plate and after 72 h they were split 1:2 at a dense seeding density of ~8 × 10 6 cells per 150-mm plate.…”

Network Pharmacology Prediction and Metabolomics Validation of the Novel Targets of Morus alba L. against High-Fat Diet-Induced Diabetes Mellitus in C57/6J Mice

“…An et al [31] discovered that regardless of genetic and other clinical factors, methylation variation in the MAOA gene promoter is related to fasting plasma glucose. Solivan-Rivera et al [32] identifed mechanisms that regulate the formation of thermogenic adipose tissue and suggested that human adipocyte MAOA could serve as a potential therapeutic target for metabolic disorders. Our molecular docking analysis of eugenol and MAOA refected that the hypoglycemic mechanism may be bound up with inhibiting MAOA by eugenol after a high-fat diet.…”

Involution of brown adipose tissue through a Syntaxin 4 dependent pyroptosis pathway

“…It is well established that humans are born with classical brown adipose tissue localized to the interscapular and perirenal regions 49 with the interscapular depot regressing in the first and second decade of life 17,20 and the perirenal depot slowly transforming into a white adipose tissue depot 50 . Since thermogenic adipose tissue increases insulin sensitivity and energy expenditure to suppress the development of diabetes and obesity, there are currently numerous efforts to find therapeutic approaches to induce the formation of beige adipose tissue [51][52][53] . However, an alternative approach would be to prevent the regression of brown adipocytes that are present at birth.…”