This study investigates the role of neutrophils in visceral adipose tissue (VAT) inflammation and metabolic disorders associated with obesity. Key findings include: 1. **Neutrophil Recruitment in Obesity**: VAT from obese individuals contains more neutrophils compared to lean individuals, and this increase is associated with a distinct bacterial community. The presence of neutrophils in VAT is influenced by both the donor's microbiome and the recipient's diet. 2. **Mechanism of Recruitment**: In a mouse model, gavaging microbiome-depleted mice with stool from obese individuals, followed by a high-fat diet, led to an increase in VAT neutrophils. This recruitment was dependent on the donor's BMI and the recipient's diet. 3. **Inflammatory Effects**: The increase in VAT neutrophils was followed by an increase in pro-inflammatory CD4+ Th1 cells and a decrease in regulatory T cells (Tregs). Depleting neutrophils with an antibody prevented these changes, suggesting that neutrophils play a crucial role in VAT inflammation. 4. **Transcriptomic Analysis**: VAT neutrophils exhibit a distinct gene expression profile compared to peripheral blood (PB) neutrophils, with higher expression of genes related to inflammation, chemotaxis, and extracellular matrix production. These neutrophils also show increased expression of genes involved in bactericidal activity and LPS induction. 5. **VAT Neutrophils in Other Tissues**: A custom-signature tool was developed to identify VAT-isolated neutrophil (VIN) signatures in bulk transcriptome datasets. This tool revealed that VIN-type neutrophils are widespread in various tissues, including colon adenocarcinoma, where their abundance correlated with overall survival. 6. **Clinical Implications**: The study suggests that VAT neutrophils may be a novel therapeutic target for treating inflammatory-driven complications of obesity, such as insulin resistance and colon cancer. The findings highlight the importance of VAT neutrophils in obesity-related inflammation and provide insights into potential therapeutic strategies for managing obesity-related metabolic disorders.This study investigates the role of neutrophils in visceral adipose tissue (VAT) inflammation and metabolic disorders associated with obesity. Key findings include: 1. **Neutrophil Recruitment in Obesity**: VAT from obese individuals contains more neutrophils compared to lean individuals, and this increase is associated with a distinct bacterial community. The presence of neutrophils in VAT is influenced by both the donor's microbiome and the recipient's diet. 2. **Mechanism of Recruitment**: In a mouse model, gavaging microbiome-depleted mice with stool from obese individuals, followed by a high-fat diet, led to an increase in VAT neutrophils. This recruitment was dependent on the donor's BMI and the recipient's diet. 3. **Inflammatory Effects**: The increase in VAT neutrophils was followed by an increase in pro-inflammatory CD4+ Th1 cells and a decrease in regulatory T cells (Tregs). Depleting neutrophils with an antibody prevented these changes, suggesting that neutrophils play a crucial role in VAT inflammation. 4. **Transcriptomic Analysis**: VAT neutrophils exhibit a distinct gene expression profile compared to peripheral blood (PB) neutrophils, with higher expression of genes related to inflammation, chemotaxis, and extracellular matrix production. These neutrophils also show increased expression of genes involved in bactericidal activity and LPS induction. 5. **VAT Neutrophils in Other Tissues**: A custom-signature tool was developed to identify VAT-isolated neutrophil (VIN) signatures in bulk transcriptome datasets. This tool revealed that VIN-type neutrophils are widespread in various tissues, including colon adenocarcinoma, where their abundance correlated with overall survival. 6. **Clinical Implications**: The study suggests that VAT neutrophils may be a novel therapeutic target for treating inflammatory-driven complications of obesity, such as insulin resistance and colon cancer. The findings highlight the importance of VAT neutrophils in obesity-related inflammation and provide insights into potential therapeutic strategies for managing obesity-related metabolic disorders.