Association of circulating levels of apolipoprotein M and adiponectin with insulin sensitivity in overweight subjects and obese patients with weight loss surgery

Background Most adipokines are up-regulated with obesity and promote metabolic dysfunction, while few, like adiponectin, are down-regulated during adipose tissue expansion and probably protect against obesity-related disorders. High adiponectin is linked to low inflammation and insulin sensitivity. Similarly, apolipoprotein M (apoM) was recently identified as an adipokine for which the expression in adipose tissue is positively associated with metabolic health. Our aim was to compare circulating levels of apoM to those of adiponectin in overweight and obese individuals with respect to metabolic parameters and insulin sensitivity. Methods Adiponectin and apoM were measured in a cross-sectional study including 169 overweight men and in a surgery-induced weight loss program including 13 obese patients of both sexes who underwent sleeve gastrectomy. Correlations between the homeostasis model assessment of insulin resistance (HOMA-IR) index, bioclinical parameters, adiponectin and apoM levels, and lifestyle habits were assessed using Spearman correlation coefficients. Multiple regression analyses of HOMA-IR were performed. Results In overweight men, plasma adiponectin and apoM were lower in participants with diabetes. The apoM level did not correlate with that of adiponectin and was higher in individuals with dyslipidemia. Similar to adiponectin, apoM was negatively associated with HOMA-IR (r = −0.29), hs-CRP (r = −0.28) and HDL markers (HDL-C, r = 0.32; apoA-I, r = 0.32). Unlike adiponectin, apoM did not correlate with triglyceride levels but was positively associated with LDL markers (LDL-C, r = 0.27; apoB100, r = 0.20) and negatively with fat mass (r = −0.26) and age (r = −0.25). In multiple regression models, apoM was the only negative determinant of HOMA-IR, while adiponectin did not contribute to HOMA-IR variability. Accordingly, while sleeve gastrectomy improved insulin sensitivity, change in HOMA-IR at one year of follow-up was strongly negatively associated with change in the level of circulating apoM (r = -0.71) but not with change in the adiponectin level. Conclusions Both circulating apoM and adiponectin are negatively correlated with bioclinical variables associated with obesity, inflammation, and insulin resistance. Unexpectedly, apoM, but not adiponectin, was a negative determinant of HOMA-IR. We identified for the first time circulating apoM as a novel biomarker of insulin sensitivity. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was funded by the Region Occitanie Pyrenees-Mediterranee (GRAINE HEPATOCARE, Reference number 19014226). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocols were approved by the local ethics committee: Comite de protection des personnes, Toulouse/Sud-Ouest, file #1-99-48, Feb 2000; and the the Research Ethics Board of Aix-Marseille University ([NCT01277068][1] and [NCT02332434][2]). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes The datasets analyzed during the current study are not publicly available but are available from the corresponding authors on reasonable request. * AT : adipose tissue apoA-I : apolipoprotein A-I apoB100 : apolipoprotein B100 apoC-III : apolipoprotein C-III apoM : apolipoprotein M BMI : body mass index bpm : beats per minute CAD : coronary artery disease γ -GT : gamma-glutamyltransferase HDL-C : high-density lipoprotein cholesterol HOMA-IR : Homeostasis Model Assessment of Insulin Resistance hs-CRP : high-sensitivity C-Reactive Protein LDL-C : low-density lipoprotein cholesterol T2D : type 2 diabetes. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT01277068&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F10%2F2023.02.09.23285709.atom [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02332434&atom=%2Fmedrxiv%2Fearly%2F2023%2F02%2F10%2F2023.02.09.23285709.atom