# Adipocyte-specific deletion of Dbc1 does not recapitulate healthy obesity phenotype but suggests regulation of inflammation signaling

## TL;DR

Deleting Dbc1 in fat cells does not prevent obesity-related metabolic issues but shows increased inflammation, suggesting other cells in fat tissue are responsible for the protective effects seen in whole-body Dbc1 deletions.

## Contribution

The study reveals a novel role for Dbc1 in inflammation signaling within adipocytes during obesity.

## Key findings

- Dbc1 deletion in mature adipocytes did not prevent weight gain or metabolic dysregulation.
- Dbc1 KO adipocytes showed increased inflammation-related gene expression during obesity.
- The protective 'healthy obesity' phenotype is likely due to Dbc1 function in non-adipocyte cells.

## Abstract

The protein Deleted in Breast Cancer 1 (Dbc1) is an important regulator of various transcription factors and epigenetic modulators, significantly influencing metabolism, obesity, and aging-related processes. Knockout mice lacking Dbc1 exhibit severe obesity but remain protected from liver steatosis, insulin resistance, and atherosclerosis. We hypothesized that this phenotype of “healthy obesity” results from adipose tissue expansion, which prevents free fatty acid spillover and subsequent metabolic damage to peripheral tissues. To further investigate the putative role of Dbc1 in adipose cells during obesity and its effects on metabolic dysregulation, we generated conditional Dbc1 knockout (KO) mice by backcrossing with AdipoQ-CRE transgenic mice to selectively abrogate Dbc1 expression in all mature adipocytes (Dbc1LoxP/LoxP;CRE). These mice demonstrated effective deletion of Dbc1 in mature adipocytes across various fat depots. We assessed the impact of Dbc1 deletion on metabolic regulation in male and female mice fed standard chow and high-fat diets. Our findings revealed that Dbc1 knockout in mature adipocytes did not influence weight gain, glucose tolerance, or other metabolic dysregulation markers, irrespective of sex. However, Dbc1 KO adipocytes exhibited an mRNA expression profile indicative of heightened inflammation during obesity. These results suggest that the protective phenotype observed in whole-body Dbc1 KO obese mice is not attributable to Dbc1’s function within mature adipocytes but likely involves other cell types in adipose tissue. Moreover, the specific deletion of Dbc1 in mature adipocytes unveils a novel role of Dbc1 in inflammation signaling during obesity.