SFEBES2021 Oral Poster Presentations Metabolism, Obesity and Diabetes (4 abstracts)
3 mg Liraglutide ameliorates inflammation and improves hypothalamic regulation of energy homeostasis by modulation of Sphingosine-1-Phosphate signalling in super-responders
Lewis Spencer 1 , Georgios K Dimitriadis 2,3 , Aparna Duggirala 1 , Danielle Bate 4 , Allan Davasgaium 4 , Wiaam Al-Hasani 3 , Alexander D Miras 5 , Carel Le Roux 6 , Royce P Vincent 3,2 , Harpal S Randeva 4,7 & Gyanendra Tripathi 1
1Human Sciences Research Centre, University of Derby, Derby, United Kingdom; 2King’s College London, London, United Kingdom; 3King’s College Hospital NHS Foundation Trust, London, United Kingdom; 4University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom; 5Imperial College London, London, United Kingdom; 6University College Dublin, Dublin, Ireland; 7University of Warwick, Coventry, United Kingdom
Background: Growing evidence suggests that hypothalamic lipid sensing plays a key role in controlling food intake, fat deposition and energy balance and that its dysregulation could lead to obesity and type 2 diabetes (T2D). Recent investigations reported that sphingosine-1-phosphate (S1P) is involved in the hypothalamic control of energy homeostasis. Intra-cerebroventricular administration of S1P decreased food intake and increased energy expenditure in rodents.
Methods: We conducted a 24-week, open-label real-world study involving 62 participants with a BMI >30kg/m2, without T2D. Patients received once-daily subcutaneous liraglutide 3.0 mg, alongside a reduced calorie diet based on individual estimated basic metabolic rate. The primary outcome was change in body-weight. Secondary outcomes included changes in anthropometrics, proinflammatory cytokines (IL1b, IL6, IL-8 and TNFa) and plasma metabolome using Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS) providing untargeted study of water-soluble metabolites (HILIC-LCMS) and lipid metabolites (C18 reversed-phase LCMS).
Results: Participants were aged 38.6±9.8 years (mean ± SD) and 87.1% of participants were women. They weighed 117.5±24.5kg with BMI of 41.33±6.9kg/m2. At week 24, participants had lost 12.85±8.4 kg or 9.9±5.8 % body weight (P < 0.001). 55.1% of participants lost 5-10% and 18.4% lost >10% body weight (P < 0.001). According to weight loss (WL) response, participants were divided into non-responders (<5% WL,n = 21), good responders (5-10% WL,n = 19) and super-responders (>10% WL,n = 9). At week 24, oxidised lysoglycerophospholipid metabolic pathway was heavily enriched. Metabolites phosphatidylcholine and triglycerides were significantly (P < 0.001) downregulated, and S1P was upregulated (P < 0.005) comparing super-responders to non-responders. IL-6 had significant positive correlation (r=0.732, P < 0.001) with WL. In all super-responders, IL-6 concentration was significantly decreased and S1P expression was significantly higher.
Conclusions: In this study, administration of liraglutide was associated with upregulation of S1P and reduction of IL-6 in super-responders. S1P signalling may be key in determining response to treatment with liraglutide.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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