bims-mimead 2026-04-26 papers

Issue of 2026–04–26
two papers selected by
Rachel M. Handy, University of Guelph

Nat Commun. 2026 Apr 20.

Adipose single cell epigenome and transcriptome localize genetic risk for cardiometabolic disease and accelerated aging.

Seung Hyuk T Lee, Asha Kar, Kyla Z Gelev, Zeyuan Johnson Chen, Sankha Subhra Das, Sini Heinonen, Tuure Saarinen, Maija Vaittinen, Dorota Kaminska, Hilkka Peltoniemi, Chongyuan Luo, Anne Juuti, Ville Männistö, Jussi Pihlajamäki, Minna U Kaikkonen, Kirsi H Pietiläinen, Brunilda Balliu, Päivi Pajukanta.

Obesity impairs subcutaneous adipose tissue function, which predisposes to chronic cardiometabolic comorbidities and accelerated biological aging. However, regulatory variants, their target genes and epigenomic landscape underlying this predisposition in each subcutaneous adipose tissue cell-type remain elusive. Our subcutaneous adipose tissue cell-type level cis-expression quantitative trait and colocalization analyses reveal cis-expression quantitative trait locus variants, regulating 279 genes for 33 cardiometabolic disease and aging traits. Most of these genes are cell-type-specific (90%), led by adipocytes (55%), and missed in previous bulk tissue colocalization studies. Conducting subcutaneous adipose tissue cell-type level epigenome analysis, we discover that the vast majority (81%) of these colocalized cardiometabolic disease and aging risk variants map to the active chromatin compartments that comprise only 45% of the human genome, revealing three-dimensional epigenome in the center of cardiometabolic disease and aging risk. These findings uncover genetic and epigenomic regulation of genes underlying 33 cardiometabolic disease and aging traits in subcutaneous adipose tissue cell-types and offer critical insights into the principal role of three-dimensional chromatin in disease risk.

DOI: https://doi.org/10.1038/s41467-026-72248-4

Aging Cell. 2026 May;25(5): e70509

The Mitochondrial NAD Transporter SLC25A51 in Adipocytes Regulates Adipose Tissue Mitochondrial Function and Systemic Metabolism During Aging.

Nicotinamide adenine dinucleotide (NAD) is a classical coenzyme regulating cellular energy metabolism. Emerging evidence demonstrates the causal relationship between defective NAD metabolism and various age-associated diseases. The major purpose of the present study was to investigate the role of adipocyte mitochondrial NAD biology in age-associated metabolic diseases. To this end, we focused on solute carrier family 25 member 51 (SLC25A51), a recently identified mitochondrial NAD transporter. We found that aging was associated with decreased adipose tissue SLC25A51 expression in both humans and mice. We next generated and analyzed novel knockout and overexpression models, which we have named adipocyte-specific Slc25a51 knockout (ASKO) and Slc25a51 overexpressing (ASLO) mice. ASKO mice had a marked decrease in adipose tissue mitochondrial NAD levels and exhibited age-associated systemic metabolic complications, such as obesity, glucose intolerance, insulin resistance, hyperinsulinemia, metabolic inflexibility, dyslipidemia, and hepatosteatosis. Mechanistically, loss of Slc25a51 reduced mitochondrial respiratory function, fatty acid oxidation capacity, and adiponectin production in adipose tissue, likely contributing to the development of systemic metabolic complications. Conversely, ASLO mice were protected from obesity and insulin resistance caused by aging. In conclusion, our results provide novel mechanistic and therapeutic insights into understanding the critical role of adipocyte mitochondrial NAD transporter SLC25A51 in the pathophysiology of age-associated metabolic diseases, particularly obesity and insulin resistance.

Keywords: NAD; adipocyte; aging; insulin resistance; obesity

DOI: https://doi.org/10.1111/acel.70509