IMPACT OF VITAMIN D DEFICIENCY, DYSLIPIDEMIA AND OBESITY ON SERUM LIPIDOMIC PROFILE. SEARCH FOR NEW BIOMARKERS AS EARLY PREDICTORS OF OBESITY-ASSOCIATED COMORBIDITIES.

Research studies indicate that up to 58% of the world adult population will be overweight or obese by 2030 [1]. Obesity is not only related to food intake, but factors such as lifestyle and genetic background contribute to its onset [3–5]. This disease [2] is commonly associated with vitamin D (Vit. D) deficiency [6,7], and genetic associations have been identified to explain this link [8]; however, differences in dietary intake, sun exposure, or Vit. D metabolism are also involved [9]. Moreover, along with Vit. D deficiency, lipids, and particularly sphingolipids (SLs) as ceramides (Cers) and sphingomyelins (SMs) have been described as involved, not only in increasing inflammation [10,11], but also in the development of cardiovascular disease and type two diabetes [12–14], two common conditions observed in obese subjects. Given the pivotal role of SLs in obesity associated co-morbidities and the association of Vit. D, dyslipidemia and obesity, our study was aimed at profiling circulating SLs in human subjects under these conditions, in order to provide hints for the identification of new biomarkers to be introduced in clinical settings. To define human SLs profile in obesity, dyslipidemia, and Vit. D associated deficiency, sera from 23 normal-weight normolipidemic (NWNL), 46 normal-weight, dyslipidemic, Vit. D deficient (NWDL) and 60 obese dyslipidemic, Vit. D deficient (ODL) Saudi Arabian subjects were analyzed with a dual approach, characterized by the use of two complementary techniques: the HPTLC-Primuline profiling and the LC-MS analysis. Furthermore, to define SLs profiles in the context of human adaptation to high altitude hypoxia, sera from 59 Vit. D deficient dyslipidemic children living at high altitude were analyzed by LC-MS. Children were grouped based on their BMI percentiles in 7 underweight (UW), 30 normal-weight (NW), 13 overweight (OW) and 9 obese (O). SLs profile analysis of NWNL and ODL Saudi Arabian subjects displayed differences in total Cer and total SM caused by dyslipidemia and vitamin D deficiency, whereas specific Cers, and SMs acyl chains characterize obese subjects, only. Gender differences were found in SLs profiles independently from dyslipidemia and Vit. D status. Obesity-associated Cers, SMs, and dihydrosphingomyelins (dhSMs) specific acyl chains were identified in the NWDL vs. ODL comparison independently from dyslipidemia and Vit D status, and are thought to be drivers of increased risk of developing obesity-associated morbidities. The analysis of SLs profiles from dyslipidemic children with Vit. D deficiency allowed to confirm the results of Saudi Arabian subjects regarding SLs association with dyslipidemia and associated Vit. D deficiency. Furthermore, SLs profile analysis led to the identification of a characteristic SLs portraits associated with BMI and related to hypoxia metabolic adaptation.