Predictors of Subclinical Inflammatory Obesity: Plasma Levels of Leptin, Very Low-Density Lipoprotein Cholesterol and CD14 Expression of CD16+ Monocytes

Abstract

Objective: Predictors of subclinical inflammatory obesity (SIO) can be important tools for early therapeutic interventions in obesity-related comorbidities. Waist circumference (WC) and BMI have different SIO sensitivity. We aimed to i) identify SIO predictors and ii) investigate whether CD16+ monocytes are associated with BMI- (generally) or WC-defined (centrally) obesity. Methods: Anthropometric and metabolic/endocrine (namely catecholamines, adrenaline and noradrenaline) parameters were evaluated, and CD16+ monocytes were studied by flow cytometry in the peripheral blood from 63 blood donors, and compared and correlated to each other. Multiple linear regression analysis was performed to identify variables that best predict SIO. Results: CD16+ monocyte counts were similar in BMI and WC groups. CD16+ monocytes from centrally obese (CO) showed a more inflammatory pattern, as compared to non-CO subjects. WC was sensitive to lipidemia and, in CO subjects, lipidemia was associated with a more inflammatory phenotype of CD16+ monocytes. These differences were not noticed between BMI groups. Adrenaline was correlated with CD16+ monocyte expansion with a lower inflammatory pattern. Leptin, very low-density lipoprotein cholesterol (VLDL-C), and CD14 expression of CD16+ monocytes were found to be CO predictors. Conclusions: WC-, but not BMI-defined obesity, was associated with a more inflammatory pattern of CD16+ monocytes, without monocyte expansion, suggesting that a monocyte maturation process rather than an independent arise of CD16+ monocytes occurs in CO. Thus, in a population with low cardiovascular risk, leptin, VLDL-C, and CD14 expression of CD16+ monocytes predict CO, constituting a putative tool for screening of SIO.

Dopaminergic pathways in obesity-associated immuno-metabolic depression

“…Moreover, higher leptin was associated with hyperphagia, independently from weight (Milaneschi et al , 2017). We found that plasma levels of leptin, very-low-density lipoprotein-cholesterol and CD14 expression in monocyte subsets are predictors of subclinical inflammatory obesity (Leite et al ., 2017 a ), which can constitute an important tool for early therapeutic interventions in obesity-related comorbidities, namely depression.…”

Bioinformatics Analysis of Key Genes and Pathways for Obesity Associated Type 2 Diabetes Mellitus as a Therapeutic Target

“…ERBB2 [36], DACT1 [37], ARAP1 [38], MYH9 [39], INPPL1 [40], SARM1 [41], NOTCH1 [42], ROBO1 [43], MAPK8IP1 [44], ANK1 [45], SARM1 [46], SREBF2 [47], SIK1 [48], PASK (PAS domain containing serine/threonine kinase) [49], NOS2 [50], OAS3 [51], KL (klotho) [52], PECAM1 [53], S100A12 [54], S100P [55], BATF3 [56], PLEK (pleckstrin) [57], ALOX5 [58], ARG1 [59], CXCL8 [60], CXCR1 [61], PTAFR (platelet activating factor receptor) [62], PYGL (glycogen phosphorylase L) [63], TCF4 [64], CAMP (cathelicidin antimicrobial peptide) [65], RUNX2 [66], PLA2G2A [67], GCG (glucagon) [68], RARRES2 [69] and HAP1 [70] were involved in the genesis of type 2 diabetes mellitus. Recent studies have reported that ACHE (acetylcholinesterase) [71], FGFR3 [72], VLDLR (very low density lipoprotein receptor) [73], SHC1 [74], HDAC6 [75], CHRNA2 [76], CASR (calcium sensing receptor) [77], ELK1 [78], TYK2 [79], CIITA (class II major histocompatibility complex transactivator) [80], ZAP70 [81], GPT (glutamic--pyruvic transaminase) [82], CHI3L1 [83], AIF1 [84], MMP9 [85], ITGB2 [86], CFD (complement factor D) [87], C3AR1 [88], LGALS1 [89], CD14 [90], TIMP1 [91], TLR2 [92], LTF (lactotransferrin) [93], BRCA2 [94] and IGFBP3 [95] promotes the development of obesity. Sun et al [96] found that TRPM2 was significantly associated in obesity associated type 2 diabetes mellitus.…”

“…LGALS1 [89], CD14 [90], TIMP1 [91], TLR2 [92], LTF (lactotransferrin) [93], BRCA2 [94] and IGFBP3 [95] promotes the development of obesity. Sun et al [96] found that TRPM2 was significantly associated in obesity associated type 2 diabetes mellitus.…”

Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms)

“…In general, the role of individual circulating monocyte subpopulations in obesity remains to be elucidated [4]. It is not known when monocytes are activated: before they invade tissues or during differentiation into macrophages in obesity and T2DM.…”

“…Obesity is associated with an increase in circulating monocytes [3] and their recruitment to inflamed adipose tissue (AT) in animals and humans [4]. Insulin resistance associated with obesity develops against the background of an increase in the number of tissue macrophages (in adipose, muscle, and liver tissues) and their enhanced pro-inflammatory effects.…”