Impact of short‐ and long‐term weight loss on the inflammatory profile of metabolically healthy and unhealthy obese patients
Authors: Clark Madison , Barrenäs Fredrik , Rajan Meenu , Sotak Matus , Wallenius Ville , Borgeson Emma 
Published: June 2021

Study Objective

Obesity is a predisposing factor for cardiometabolic and kidney disease. Inflammation has been identified as an underlying risk factor. However, studies report conflicting results on the impact of short‐ and long‐term weight loss on obesity‐related inflammation. Here we investigate levels of inflammation in lean, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO) patients, and the impact of short‐ and long‐term weight loss, using multiplex arrays and bioinformatics analysis.

Methods

Obese patients scheduled to undergo gastric bypass surgery were age‐ and sex‐matched to lean controls (ClinicalTrials.gov NCT02322073), and sub‐classified as metabolically healthy (MHO: n=4) or unhealthy (MUO: n=7) using International Diabetes Guidelines (i.e. metabolically unhealthy is defined as having more than two cardiometabolic risk factors: central adiposity, hyperglycemia, elevated triglycerides, decrease HDL‐cholesterol, elevated blood pressure). Gender was not a part off inclusion/exclusion criteria, thus three patients were male and eight were female. Plasma was collected at baseline and following short‐ and long‐term weight loss. The short‐term weight loss consisted of a 3‐week diet regime, which takes place before surgery and resulted in 8.7 kg weight loss. The long‐term weight loss was measured 1‐year post‐surgery, at which time the patients had lost on average 46.7 kg. A multiplex array of 96 inflammation‐related plasma proteins (Olink Inflammation Panel) was analyzed using R‐studio program software version 1.1.38 and Graph Pad Prism.

Results

Inflammation (measured as C‐reactive protein) was higher in both MHO and MUO patients than in lean controls, although multivariate analysis of the multiplex array identified 11 proteins that were significantly different between the MHO/MUO groups at baseline. Hierarchal cluster analysis further revealed that the MHO group clustered together at baseline and after short‐term dieting, but not after long‐term weight loss. Both MHO and MUO groups presented with higher levels of macrophage inflammatory protein (MIP)‐1α, C‐C motif chemokine (CCL)‐4, oncostatin‐M and TNSF‐14, as compared to lean controls. CCL‐4 was not affected by weight loss, but oncostatin‐M and TNSF‐14 were significantly lowered by long‐term weight loss in both obese groups. MIP‐1α was further elevated by short‐term dieting, but reduced following long‐term weight loss. IL‐8 and CDCP1 were only increased in the MUO group, while IL‐18 and the anti‐inflammatory LAP TGF‐β1 were only increased in the MHO group; none of these proteins were attenuated by weight loss. Surprisingly, CCL25 and Fractalkine (chemotactics for T‐cells and monocytes) were not elevated in MHO or MUO groups at baseline compared to lean controls, but they were significantly higher 1‐year post‐surgery.

Conclusion

In summary, our study revealed that although obesity increases inflammatory markers, these may be differently regulated in MHO versus MUO patients and by short‐ and long‐term weight loss. Currently ongoing investigations are delineating the specific pathways involved.

Support or Funding Information

The Borgeson lab is supported by the Knut & Alice Wallenberg Foundation, Wallenberg Centre for Molecular & Translational Medicine, the Swedish Research Council, (no. 2016/82), the Swedish Society for Medical Research (no. S150086), Ake Wiberg's Foundation (no. M15‐0058), Konrad & Helfrid Johansson's foundation.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.