Immune system’s role in metabolic disease detailed in tissue atlasOct. 25, 2023, 2:29 PM
by Paul Govern
Researchers at Vanderbilt University Medical Center have published the largest single-site adipose tissue atlas known to date. A tissue atlas is a comprehensive, detailed map of the cells, structures and molecules within a specific tissue or organ, designed to support open-ended study.
The research team’s Human Adipose Tissue Atlas is based on subcutaneous fat specimens gathered from 59 VUMC research participants living with HIV. The team used single-cell RNA sequencing to identify cell types and gene expression patterns.
The team reports findings from the atlas in a recent issue of Frontiers in Immunology. The study was led by infectious diseases specialists Celestine Wanjalla, MD, PhD, assistant professor of Medicine, Samuel Bailin, MD, assistant professor of Medicine, and John Koethe, MD, associate professor of Medicine.
Subcutaneous white adipose tissue has emerged as a critical regulator of systemic metabolic homeostasis, and it happens to be easily enough collected using liposuction. The atlas covers the gamut of insulin sensitivity in people living with HIV, including specimens from 20 subjects without diabetes, 19 with prediabetes, and 20 with diabetes.
The report reads like a compendium, appearing to leave no stone unturned. Among the highlighted findings, the researchers found that glucose intolerance is accompanied by a rise in lipid-associated macrophages and effector memory T cells, and a reduction in the macrophages found in small spaces around blood vessels. As
glucose intolerance increased, the team observed a rise in expression of genes related to inflammation and lipid processing in multiple cell types. In analyzing how cells communicate with each other, the study found increased signaling related to proinflammatory responses and the formation of fibrous connective tissue.
Persons with HIV have higher rates of cardiometabolic diseases compared to HIV-negative persons with similar traditional risk profiles, note the study’s authors.
“People with treated human immunodeficiency infection provide an important model for studying the role of the innate and adaptive immune system in the development of cardiovascular and metabolic diseases,” said Koethe.
Bailin adds, “These data highlight a central role of adipose tissue in metabolic disease and the complexity of cell interactions and gene expression changes that give rise to functional differences in adipose tissue in persons with HIV with metabolic disease. Some of the changes are shared with HIV-negative individuals with metabolic diseases.”
Wanjalla notes, “With the atlas available online, it serves as a valuable shared reference for future studies investigating adipose tissue-related mechanism of metabolic disease and therapeutic interventions.”
Others on the study include Jonathan Kropski, MD, Rama Gangula, MS, LaToya Hannah, NP, Joshua Simmons, Mona Mashayekhi, MD, PhD, Fei Ye, PhD, MSPH, Run Fan, PhD, Simon Mallal, MBBS, Christian Warren, Spyros Kalams, MD, and Curtis Gabriel MD, PhD.
The study was supported by National Institutes of Health grants R01DK112262, R01DK131529, R01HL145372, K23HL156759 and K23DK135414.