# Region-specific variation in the properties of skeletal adipocytes reveals regulated and constitutive marrow adipose tissues

## TL;DR

This study reveals that marrow adipose tissue varies by region, with distinct properties and behaviors that could impact bone health and metabolism.

## Contribution

The paper identifies two distinct types of marrow adipose tissue with unique regulatory and developmental characteristics.

## Key findings

- Proximal marrow adipose tissue is regulated and lost under cold exposure, while distal tissue is constitutive and preserved.
- Distal marrow adipocytes show higher monounsaturated fatty acids and specific gene expression patterns.
- Human distal marrow fat also shows increased unsaturation, suggesting conserved biological mechanisms.

## Abstract

Marrow adipose tissue (MAT) accumulates in diverse clinical conditions but remains poorly understood. Here we show region-specific variation in MAT adipocyte development, regulation, size, lipid composition, gene expression, and genetic determinants. Early MAT formation in mice is conserved, while later development is strain dependent. Proximal, but not distal, MAT is lost with 21-day cold exposure. Rat MAT adipocytes from distal sites have an increased proportion of monounsaturated fatty acids and expression of Scd1/Scd2, Cebpa and Cebpb. Humans also have increased distal marrow fat unsaturation. We define proximal ‘regulated’ MAT (rMAT) as single adipocytes interspersed with active hematopoiesis, whereas distal ‘constitutive’ MAT (cMAT) has low hematopoiesis, contains larger adipocytes, develops earlier, and remains preserved upon systemic challenges. Loss of rMAT occurs in mice with congenital generalized lipodystrophy type 4, whereas both rMAT and cMAT are preserved in mice with congenital generalized lipodystrophy type 3. Consideration of these MAT subpopulations may be important for future studies linking MAT to bone biology, hematopoiesis and whole-body metabolism.