High-Density Lipoprotein-Associated miR-223 Is Altered after Diet-Induced Weight Loss in Overweight and Obese Males

Abstract

Background and AimsmicroRNAs (miRNAs) are small, endogenous non-coding RNAs that regulate metabolic processes, including obesity. The levels of circulating miRNAs are affected by metabolic changes in obesity, as well as in diet-induced weight loss. Circulating miRNAs are transported by high-density lipoproteins (HDL) but the regulation of HDL-associated miRNAs after diet-induced weight loss has not been studied. We aim to determine if HDL-associated miR-16, miR-17, miR-126, miR-222 and miR-223 levels are altered by diet-induced weight loss in overweight and obese males.MethodsHDL were isolated from 47 subjects following 12 weeks weight loss comparing a high protein diet (HP, 30% of energy) with a normal protein diet (NP, 20% of energy). HDL-associated miRNAs (miR-16, miR-17, miR-126, miR-222 and miR-223) at baseline and after 12 weeks of weight loss were quantified by TaqMan miRNA assays. HDL particle sizes were determined by non-denaturing polyacrylamide gradient gel electrophoresis. Serum concentrations of human HDL constituents were measured immunoturbidometrically or enzymatically.ResultsmiR-16, miR-17, miR-126, miR-222 and miR-223 were present on HDL from overweight and obese subjects at baseline and after 12 weeks of the HP and NP weight loss diets. The HP diet induced a significant decrease in HDL-associated miR-223 levels (p = 0.015), which positively correlated with changes in body weight (r = 0.488, p = 0.032). Changes in miR-223 levels were not associated to changes in HDL composition or size.ConclusionHDL-associated miR-223 levels are significantly decreased after HP diet-induced weight loss in overweight and obese males. This is the first study reporting changes in HDL-associated miRNA levels with diet-induced weight loss.

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

“…Some studies reported that the contents of miR-486 and miR-92a in HDL are reduced in vulnerable CVD patients [68]. HDL-associated miR-223 levels are decreased after high-protein diet-induced weight loss in overweight and obese males [69]. Intestinal lymphatic HDL-associated miR-223 is reduced during insulin resistance and is restored by niacin in rats [70].…”

Non-Exosomal and Exosomal Circulatory MicroRNAs: Which Are More Valid as Biomarkers?

“…For example, in a study where the most abundant miRNA transported by HDL, miR-223 (up to 10,000 copies per microgram of HDL), was transported to Huh7 cells showed a significant reduction of miR-223 target gene expression (Vickers et al, 2011). In addition to that, in this review, two studies (Niculescu et al, 2015;Tabet et al, 2016) involving human samples also shown evidence for miRNA transportation via HDL.…”

“…A biomarker can thus provide impartial information regarding the current physiological state of living organisms (Gill et al, 2017). Biomarkers exist in the form of antibodies (Dardari et al, 2000: IgG-ZEBRA as a biomarker in young patients with nasopharyngeal carcinoma), microbes (Shah et al, 2018: the fecal microbiome as a biomarker of colorectal cancer), DNA (Teo et al, 2019: sequencing of circulating cell-free DNA [cfDNA] from human blood plasma as a noninvasive methodology to study age-associated changes in the epigenome in vivo), RNA/miRNA (as tabulated in this review), lipids (Seow et al, 2019: the lipid fraction of the solid nonenhancing region showed potential as a novel prognostic biomarker of survival outcome in glioma), metabolites [Lou et al, 2019: a urinary metabolite of polycyclic aromatic hydrocarbons, 8hydroxy-2′-deoxyguanosine (8-OHdG), can be a biomarker of oxidative stress in pregnant women], and/or protein [Xu et al, 2019: serum protein, the insulin-like growth factor-binding protein miR-19, miR-21, miR-132, miR-133, miR-146, miR-155, miR-223, miR-377, miR-451, miR-641, miR-887, miR-1246, and miR-4284 CAD miRNAs were associated with MP-containing plasma compared to MP-free plasma of CAD patients Tabet et al, 2016 HDL -serum PEG-6000 method Qiazol miRNA-easy kits f Weight loss Downregulation in HP patient vs. normal protein diet miR-16 and According to previous study: downregulation in gastric bypass bariatric surgery patients -548c-5p, miR-638, miR-5787, miR-8975, and miR-6869-5p Involved in the process of glucose metabolism in CRC Ostenfeld et al, 2016 Pooled (IGFBP-1), as a biomarker for the early detection of gastrointestinal cancer]. Alteration in biomarker concentration, structure, function, or action can be associated with the onset, progression, or even regression of a particular disorder as a result of how the body responds to it (Gill et al, 2017).…”

microRNAs in lipoprotein and lipid metabolism: from biological function to clinical application

“…Tabet et al showed a mild decrease in HDL-carried miR-223-3p concentration following a 12-week diet rich in proteins and that this change in HDL-miR-223-3p level was associated with a diet-induced weight loss in overweight and obese men (Table 3) [137]. Our group reported an increased concentration of HDL-carried miR-223-3p and miR-135a-3p, which was associated with an overall worsening of the cardiovascular disease (CVD) risk profile (e.g.…”