Multi-omics profiling reveals molecular features of visceral adiposity in autonomous cortisol secretion
Abstract
Autonomous cortisol secretion (ACS) from adrenal adenomas increases cardiometabolic risk. Visceral adiposity is a hallmark of ACS. We characterized ACS-associated visceral adiposity using multi-omics profiling of periadrenal adipose tissue and plasma. ACS exhibited higher visceral-to-subcutaneous fat ratio (VSR), adipocyte hypertrophy, and inflammation-related pathway enrichment than non-functioning adrenal tumors. RNA-seq deconvolution and immunohistochemistry indicated increased macrophage infiltration. Plasma steroid metabolomics identified 11-deoxycorticosterone (11-DOC), a mineralocorticoid metabolite, as positively associated with VSR in premenopausal ACS women independent of cortisol. The 11-DOC-associated gene module correlated with inflammation-related pathways, notably macrophage activation. Lipidomics identified ceramides as ACS discriminators, with Cer(d18:1/16:0) most strongly associated with inflammation- and lipid metabolism-related pathways. Mendelian randomization showed genetically predicted plasma Cer(d18:1/16:0) was positively associated with trunk fat mass. These findings identify circulating 11-DOC and adipose ceramide accumulation as molecular features associated with adipose inflammation and visceral adiposity in ACS, providing hypothesis-generating insights that require functional validation.
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BibTeX
@article{nakao2026multiomics,
title = {{Multi-omics profiling reveals molecular features of visceral adiposity in autonomous cortisol secretion}},
author = {Hiroshi Nakao and Maki Yokomoto-Umakoshi and Masamichi Fujita and Kohta Nakatani and Yuya Kitamura and Ryo Ogasawara and Hiroki Kaneko and Norifusa Iwahashi and Yui Nakano and Tazuru Fukumoto and Tatsuki Ogasawara and Hiroki Takayanagi and Takashi Matsumoto and Yoshihiro Izumi and Masatoshi Eto and Takeshi Bamba and Hironobu Umakoshi and Yoshihiro Ogawa},
journal = {iScience},
year = {2026},
month = oct,
doi = {10.1016/j.isci.2026.117776},
url = {https://www.cell.com/iscience/fulltext/S2589-0042(26)03157-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Multi-omics profiling reveals molecular features of visceral adiposity in autonomous cortisol secretion
AU - Hiroshi Nakao
AU - Maki Yokomoto-Umakoshi
AU - Masamichi Fujita
AU - Kohta Nakatani
AU - Yuya Kitamura
AU - Ryo Ogasawara
AU - Hiroki Kaneko
AU - Norifusa Iwahashi
AU - Yui Nakano
AU - Tazuru Fukumoto
AU - Tatsuki Ogasawara
AU - Hiroki Takayanagi
AU - Takashi Matsumoto
AU - Yoshihiro Izumi
AU - Masatoshi Eto
AU - Takeshi Bamba
AU - Hironobu Umakoshi
AU - Yoshihiro Ogawa
PY - 2026
DA - 2026/10/08
JO - iScience
DO - 10.1016/j.isci.2026.117776
UR - https://www.cell.com/iscience/fulltext/S2589-0042(26)03157-3
AB - Autonomous cortisol secretion (ACS) from adrenal adenomas increases cardiometabolic risk. Visceral adiposity is a hallmark of ACS. We characterized ACS-associated visceral adiposity using multi-omics profiling of periadrenal adipose tissue and plasma. ACS exhibited higher visceral-to-subcutaneous fat ratio (VSR), adipocyte hypertrophy, and inflammation-related pathway enrichment than non-functioning adrenal tumors. RNA-seq deconvolution and immunohistochemistry indicated increased macrophage infiltration. Plasma steroid metabolomics identified 11-deoxycorticosterone (11-DOC), a mineralocorticoid metabolite, as positively associated with VSR in premenopausal ACS women independent of cortisol. The 11-DOC-associated gene module correlated with inflammation-related pathways, notably macrophage activation. Lipidomics identified ceramides as ACS discriminators, with Cer(d18:1/16:0) most strongly associated with inflammation- and lipid metabolism-related pathways. Mendelian randomization showed genetically predicted plasma Cer(d18:1/16:0) was positively associated with trunk fat mass. These findings identify circulating 11-DOC and adipose ceramide accumulation as molecular features associated with adipose inflammation and visceral adiposity in ACS, providing hypothesis-generating insights that require functional validation.
SN - 2589-0042
ER -