Teneurin-2 (TENM2) deficiency induces UCP1 expression in differentiating human fat cells

Mol Cell Endocrinol. 2017 Mar 5:443:106-113. doi: 10.1016/j.mce.2017.01.015. Epub 2017 Jan 11.

Abstract

Under certain conditions UCP1 expressing adipocytes arise in white adipose tissue depots of both mice and humans. It is still not fully understood whether these cells differentiate de novo from specific progenitor cells or if they transdifferentiate from mature white adipocytes. Performing expression pattern analysis comparing adipocyte progenitor cells from deep and subcutaneous neck adipose tissue, we recently identified teneurin-2 (TENM2) enriched in white adipocyte progenitor cells. Here we tested whether TENM2 deficiency in adipocyte progenitor cells would lead to a brown adipocyte phenotype. By targeting TENM2 in SGBS preadipocytes using siRNA, we demonstrate that TENM2 knockdown induces both UCP1 mRNA and protein expression upon adipogenic differentiation without affecting mitochondrial mass. Furthermore, TENM2 knockdown in human SGBS adipocytes resulted in increased basal and leak mitochondrial respiration. In line with our previous observation these data suggest that TENM2 deficiency in human adipocyte precursors leads to induction of brown adipocyte marker genes upon adipogenic differentiation.

Keywords: Adipogenesis; Brown adipose tissue; Obesity; TENM2.

MeSH terms

  • Adipocytes, Brown / cytology*
  • Adipocytes, Brown / metabolism*
  • Adipocytes, White / cytology
  • Adipocytes, White / metabolism
  • Adipogenesis / genetics
  • Adipose Tissue, White / cytology
  • Arrhythmias, Cardiac / pathology
  • Biomarkers / metabolism
  • Cell Differentiation / genetics*
  • Cell Respiration / genetics
  • Gene Knockdown Techniques
  • Genetic Diseases, X-Linked / pathology
  • Gigantism / pathology
  • Heart Defects, Congenital / pathology
  • Humans
  • Intellectual Disability / pathology
  • Membrane Proteins / deficiency*
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism
  • Nerve Tissue Proteins / deficiency*
  • Nerve Tissue Proteins / metabolism
  • RNA, Small Interfering / metabolism
  • Stem Cells / metabolism
  • Uncoupling Protein 1 / genetics*
  • Uncoupling Protein 1 / metabolism

Substances

  • Biomarkers
  • Membrane Proteins
  • Nerve Tissue Proteins
  • RNA, Small Interfering
  • TENM2 protein, human
  • UCP1 protein, human
  • Uncoupling Protein 1

Supplementary concepts

  • Simpson-Golabi-Behmel syndrome