Loureiro, J. J. | bioRxiv Science

bioRxiv2026

Rapid Remodeling of Human White Adipose Tissue Following Bariatric Surgery

Bariatric surgery induces profound weight loss and improvement of obesity-associated metabolic dysfunction. Recent studies have shown that adipose tissue undergoes remodeling after weight loss, characterized by a reduction in proinflammatory immune cells, increased vascularization, and a shift in the adipocyte transcriptome, but these studies focused on time points long after surgery. We performed single nucleus RNA-seq (snRNA-seq) in subcutaneous white adipose tissue (SAT) samples from subjects with obesity undergoing bariatric surgery, collected at baseline and at one, six, and twelve months after surgery. We identify profound remodeling of SAT within the first month after surgery, characterized by a surge in lipid-associated macrophages and sharp reductions in specific populations of adipocytes, adipose stromal and progenitor cells (ASPCs), and endothelial cells. Transcriptional profiles strongly suggest that some adipocytes undergo apoptosis soon after surgery, while new adipocytes are generated by de novo differentiation. Mechanistically, the data are consistent with a model whereby coordinated early loss of a hedgehog signaling axis between endothelial cells and an anti-adipogenic population of ASPCs known as adipose regulatory cells (Aregs; ASPCPTCH2) enables a transient burst of adipogenesis to occur. Interestingly, very few of these early features seen in human subjects are represented in a mouse model of surgical weight loss.

physiology↗

bioRxiv2026

The impact of low-frequency genetic variants on serum protein levels

The mapping of protein quantitative trait loci (pQTLs) can provide molecular links between genotype and phenotype. Most such studies focus on common variants, but the effects of low-frequency (LF) variants remain underexplored. Focusing on cis-pQTLs, we integrated serum measurements of 7,596 proteins with genomic data, including LF variants (minor allele frequency [MAF] 0.1-1%), in 5,291 Icelanders to identify independent cis-pQTLs for 2,166 SOMAmers. Incorporating LF variants increased the number of detected genetic signals per protein, demonstrating widespread allelic heterogeneity in cis-acting regulation of serum proteins. LF pQTLs were enriched for coding variants in the respective protein-encoding gene, but also among distal secondary signals, revealing additional regulatory layers not captured by common variants alone. Proteins affected by common variant cis-pQTLs were more often secreted and exhibited tissue-specific expression, whereas proteins exclusively affected by LF variants were primarily from more constrained and biologically essential pathways. Expanding both protein coverage and the allele-frequency spectrum reveals a more complex and heterogeneous cis-regulatory architecture of circulating proteins.

genomics↗