Inflammation in Fat Depots: Clues to the Cardio-Kidney-Metabolic Connection

It is increasingly recognized that not all fat is the same. While excess or dysfunctional adipose tissue contributes to cardio-kidney-metabolic (CKM) syndrome, the specific inflammatory signals coming from different fat depots – subcutaneous, visceral, hepatic, or even intramuscular – remain poorly understood. A new analysis we performed in the Dallas Heart Study and presented at #AHA25 helps shed light on this. Using a highly sensitive proteomic platform (NULISA™), we measured 248 circulating inflammatory proteins in more than 100 community participants who also underwent whole-body MRI to quantify fat in different regions.

We found that ectopic fat depots have their own inflammatory “fingerprint.” Intramuscular fat showed the greatest number of overall and unique associations, while visceral and liver fat showed similar inflammatory profiles and subcutaneous fat did not display prominent proinflammatory characteristics. Importantly, several of these proteins were also tied to features of CKM syndrome – including insulin resistance, elevated blood pressure, metabolic syndrome, and impaired kidney function – and to lower cardiorespiratory fitness, as reflected by peak VO₂.

These findings highlight that “fat inflammation” is not uniform across the body and that its biochemical profile may help explain why some patients develop metabolic and renal complications before overt cardiovascular disease. In the future, circulating inflammatory proteins may serve as early biomarkers to identify high-risk individuals or even as therapeutic targets in the spectrum of CKM syndrome.