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 1 Brigham and Women's Hospital, Boston, MA, USA 2 Channing Division of Network Medicine, Boston, MA, USA
Background:
Laparoscopic sleeve gastrectomy (LSG) is an effective weight loss procedure and has a positive impact on obesity-related co-morbidities. We hypothesize that the effects of LSG are caused by and reflected in the immune-metabolic changes.
Methods:
Prospective data has been collected from enrolled human subjects from a single institution. Parameters of weight, co-morbidities and trends in blood biomarkers are observed from pre-operative baseline to 1 year in 3-monthly interval follow ups. Leukocytes were collected and isolated every 3 months for RNA sequencing.
Results:
20 patients were enrolled (M: F, 5:15; mean age, 45.9 years-old; mean BMI 44.0±7.2 Kg/m2). LSG led to a significant reduction in mean total body weight loss (18.12±4.34%). Improvements in biomarkers such as adiponectin, resistin, 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. Changes in neutrophil and lymphocyte fraction were reduced in patients with metabolic diseases (P<0.01). 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.
Conclusion:
LSG induces significant changes in the function and metabolism of leukocytes as early as 3 months post-operatively. The improvement in CRP and white cells composition alteration interacts closely with weight loss; suggesting that immune response plays an important role in LSG.
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