New England Surgical Society

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Blood Gene Expression Profiles Support Early Changes in Immunometabolism in Patients Following Sleeve Gastrectomy
*Tammy Lo1, *Keyvan Heshmati1, Ali Tavakkoli1, *Damien C Croteau-Chonka2, Eric G Sheu1
1Brigham and Women's Hospital, Boston, MA;2Channing Division of Network Medicine, Boston, MA

Objective: To characterize immunologic changes induced by surgical weight loss that promote improvements in metabolic disease.
Design:
: Longitudinal, prospective human cohort study.
Setting: Single academic tertiary care hospital.
Patients: Adult, morbidly obese patients undergoing LSG without a history of immunologic disease, (N=20; 75% female; mean age = 45.9 years; mean body mass index (BMI) = 44.07.2 kg/m2).
Interventions: Laparoscopic sleeve gastrectomy (LSG).
Main Outcome Measures: Parameters of weight, co-morbidities, and trends in blood biomarkers were observed from pre-operative baseline to 1 year in 3-monthly interval follow-ups. Adipose tissue biopsies and whole blood leukocytes were collected peri-operatively and blood again every 3 months to facilitate RNA-sequencing. Paired-sample univariate differential gene expression analyses were performed using DESeq2. For this study, we focused on the early post-operative changes at 3 months.
Results: LSG led to a significant reduction in mean total body weight loss (18.124.34%). Improvements in biomarkers such as adiponectin (P<0.05), resistin (P<0.05), C reactive protein, and interleukin-6 were also observed after LSG. Total white blood cell counts were reduced, but white cell composition was also altered after LSG, with a significant decrease in neutrophil percentage and increase in lymphocytes percentage. In a subset of six subjects, gene set enrichment analyses demonstrated that by 3 months LSG also induced significant blood gene expression changes in several key metabolic pathways in leukocytes (Fig. 1).
Conclusions: LSG induces significant changes in the function and metabolism of leukocytes as early as 3 months post-operatively.


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