Peijs, L. | Search bioRxiv

bioRxiv2020

Thermogenic genes are blunted whereas brown adipose tissue identity is preserved in human obesity

Obesity associates with a reduction in cold-induced glucose tracer uptake in brown adipose tissue in humans, suggesting loss of thermogenic capacity. We therefore hypothesized that a whitening of BAT occurs in obesity and assessed the molecular characteristics of deep neck BAT in a cohort of 24 normal weight, 24 overweight and 22 obese individuals in comparison with subcutaneous abdominal white adipose tissue (WAT). We found that the major marker of BAT thermogenesis, UCP1, was associated with central but not general obesity. We performed transcriptomic analysis of BAT in a cohort of 27 individuals classified as normal weight, over-weight or obese, and additionally four subjects with type 2 diabetes (T2DM), dispersed among the 3 BMI groups. We identified 3204 differentially expressed genes between BAT and WAT in samples from normal weight individuals, including genes involved in thermogenesis, but also revealing differences in developmental and immune system related genes. In BAT from individuals with overweight or obesity, 202 genes were downregulated and 66 of these were involved in cellular respiratory pathways, likely reflecting previously observed reduction in thermogenic function with obesity. Importantly, most BAT selective genes were not affected, and isolated adipose progenitors differentiated into thermogenic adipocytes with equal frequency regardless of BMI group. In conclusion, our data suggest a retained BAT identity, with a selective reduction of thermogenic genes, in human obesity.

cell biology↗

bioRxiv2018

Proteomics-based comparative mapping of the human brown and white adipocyte secretome reveals EPDR1 as a novel batokine

Secreted proteins from adipose tissue play a role in metabolic cross-talk and homeostasis. We performed high sensitivity mass spectrometry-based proteomics on the cell media of in vitro differentiated, non-immortalized brown adipocytes derived from supraclavicular adipose of adult humans and white adipocytes derived from subcutaneous adipose of adult humans. We identified 471 potentially secreted proteins covering interesting protein categories such as hormones, growth factors, growth factor binding proteins, cytokines, extracellular matrix proteins, and proteins of the complement system, which were differentially regulated in brown and white adipocytes. A total of 101 proteins were exclusively quantified in brown adipocytes, among these ependymin-related protein 1 (EPDR1). Ablation of EPDR1 impaired the induction of thermogenic transcripts in response to norepinephrine in brown adipocytes, while EPDR1-treated mice increased their energy consumption, suggesting a role in brown fat commitment and activation. Our work reveals substantial differences between the secretomes of brown and white human adipocytes and identifies novel candidate batokines.

physiology↗