2023 Volume 70 Issue 6 Pages 581-589
Adipocyte apoptosis is a key initial event that contributes to macrophage infiltration into adipose tissue (AT) and thus triggers AT inflammation in obesity. MicroRNA-27a (miR-27a) was shown to mediate the pathological processes of many metabolic disorders; however, whether miR-27a is involved in adipocyte apoptosis of obese AT remains unknown. The present study aimed to investigate the alteration of miR-27a in obese individuals and its antiapoptotic function in adipocytes. In vivo, serum samples and omental adipose tissue from humans as well as epididymal fat pads from mice were collected to detect miR-27a expression. In vitro, 3T3-L1 preadipocytes and mature adipocytes were treated with TNF-α to induce apoptosis and transfected with a mimic for overexpressing miR-27a-3p. The results showed that miR-27a was markedly decreased in the serum and AT of obese human patients and in the AT of high-fat diet-fed mice. Regression analyses revealed that the serum level of miR-27a was correlated with metabolic parameters in human obesity. Notably, TNF-α induced cell apoptosis in both preadipocytes and mature adipocytes, as evidenced by the upregulation of cleaved caspase 3 and cleaved caspase 8 and the ratio of Bax to Bcl-2, while these effects were partly diminished by miR-27a overexpression. In addition, TUNEL and Hoechst 33258 staining verified that miR-27a overexpression markedly inhibited the apoptosis of adipocytes under TNF-α stimulation. Thus, miR-27a was downregulated in the AT of obese subjects with proapoptotic status, and overexpression of miR-27a exerted an antiapoptotic effect on preadipocytes, providing a novel potential target for preventing AT dysfunction.
OVER THE PAST DECADES, obesity has been accepted as one of the major health hazards worldwide and is associated with type 2 diabetes, liver steatosis and other metabolic disorders [1, 2]. In obesity, inflammation characterized by macrophage infiltration has been described as the core feature in adipose tissue (AT) [3]. Apoptosis of adipocytes is an initial event for the induction of immune cell aggregation and AT inflammation [4-6]. Apoptotic adipocytes trigger the localization and infiltration of macrophages into AT with massive inflammatory cytokine secretion, which further induces more apoptosis of adipocytes, thereby accelerating the inflammatory processes in AT.
Evidence has confirmed that inhibition of adipocyte apoptosis protects obese animals against macrophage recruitment and insulin resistance [7, 8]. Thus, searching for new targets to prevent adipocyte apoptosis may be a novel therapeutic strategy for the treatment of obesity-related metabolic disorders.
MicroRNAs (miRNAs) are an evolutionarily conserved class of small endogenous noncoding RNAs (22 nt) that regulate gene expression and thus mediate multiple biological processes in various diseases [9]. Recently, miRNAs have been investigated in research on obesity and metabolic syndrome [10, 11]. miR-27a was dysregulated in the AT of individuals with obesity and type 2 diabetes [12-14]. Kim et al. revealed that miR-27a expression was reduced during adipocyte differentiation, and ectopic expression of miR-27a repressed adipocyte differentiation by targeting PPAR-λ [15], indicating that miR-27a may play an important role in AT dysfunction.
miRNAs can also be readily detected in human serum and serve as novel diagnostic and/or prognostic markers in metabolic disorders, including obesity [11, 16]. However, to date, there is no report about the circulating level of miR-27a in obesity, and whether miR-27a is involved in the regulation of adipocyte apoptosis is unknown.
Male C57BL/6J mice were maintained under a 12-h light/dark cycle with free access to food and drinking water. After 2 weeks of adaptive feeding, six-week-old male C57BL/6J littermates were randomly assigned to receive a chow diet (CD, n = 8) (15% fat, Harlan, Kentucky, USA) or a high-fat diet (HFD, n = 8) (45% fat, Harlan) for 8 weeks. At termination, the body weights were obtained. After the animals were sacrificed by an overdose of pentobarbital sodium (150 mg/kg) injected intraperitoneally, epididymal fat pads were harvested as previously described [17]. Animal care and experimental procedures were performed with approval from the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University.
SubjectsThe harvest of human adipose tissues was approved by the Ethics Committee of the First Affiliated Hospital of Chongqing Medical University Ethical Committee, and informed consent was obtained from all participants. Human omental adipose tissues were obtained from 21 lean and 14 obese subjects who underwent laparoscopic cholecystectomy. Serum samples were obtained from another cohort with 23 lean and 23 obese subjects. Participants in the lean and obese groups of each cohort were sex- and age-matched. Obesity was defined as BMI ≥25 kg/m2 based on the criteria of the World Health Organization (WHO, 1998) adapted for Asian adults [18].
The following anthropometric measurements were acquired from each subject: height, weight, waist circumference (WC), hip circumference (HC), systolic blood pressure (SBP) and diastolic blood pressure (DBP). Body mass index (BMI) was calculated as weight (kilograms)/height (meters)2. The biochemical parameters, including total cholesterol (TC), triglycerides (TG), high-density-lipoprotein cholesterol (HDL-c), low-density-lipoprotein cholesterol (LDL-c), glycosylated hemoglobin (HbAlc), fasting plasma glucose (FPG), 2-hour postload glucose (2hPG), fasting insulin (FINS) and high-sensitivity C-reactive protein (hs-CRP), were measured as previously described [19].
Serum adiponectin concentration was determined by a commercial ELISA kit (R&D, Minnesota, USA). Homeostasis model assessment for insulin resistance (HOMA-IR) and homeostasis model assessment for insulin sensitivity (HOMA-IS) were used to estimate insulin resistance and insulin sensitivity according to the following formulas: FPG (mmol/L) × FINS (mIU/L)/22.5 and 1/FPG (mmol/L) × FINS (mIU/L), respectively.
Cell cultureMurine 3T3-L1 cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM) (Gibco, California, USA) containing 10% FBS (Gibco) and 1% antibiotics (HyClone, Logan, USA). At confluence (Day 0), differentiation of preadipocytes was induced by the addition of medium containing 100 nmol/L insulin, 0.5 mM 3-isobutyl-1-methyulxanthine and 0.25 mM dexamethasone (all from Sigma-Aldrich, Bornem, Belgium). After 48 h, the cells were cultured in DMEM containing 100 nmol/L insulin and 10% FBS for another 2 days, and then, the medium was replaced with DMEM with 10% FBS. On Day 8, cells were fully differentiated and confirmed by Oil Red O staining.
Transfection of miR-27a-3p mimic in 3T3-L1 adipocytesFirst, 3T3-L1 preadipocytes or differentiated adipocytes were treated with 50 nM miR-27a-3p mimics (Qiagen, Hilden, Germany) or miR-mimic negative control (Qiagen) with HiPerFect Transfection Reagent (Qiagen) for 24 h according to the manufacturer’s protocol as previously mentioned [20]. The transfection efficiency was shown by over 100-fold overexpression of miR-27a compared with that of the control cells. The medium was replaced with fresh medium 24 h after transfection of miR-mimic or negative control, and then, the cells were treated with or without 50 ng/mL recombinant TNF-α (PeproTech, USA) for another 24 h to induce apoptosis.
Real-time quantitative PCRFor adipocytes or adipose tissue, total RNA, including miRNA, was extracted using a miRNeasy Mini kit (Qiagen) according to the manufacturer’s protocol. For serum samples, total RNA, including miRNA, was isolated using the miRNeasy Serum/Plasma kit (Qiagen). To correct the variations in RNA isolation, we spiked in a nonhuman (Caenorhabditis elegans) synthetic miRNA, e.g., cel-miR-39 miRNA mimic (Qiagen), into the sample before nucleic acid isolation. For mRNA and miRNA quantification, 1 μg RNA was reverse-transcribed by using the miScript Reverse Transcription kit (Qiagen), and RT‒qPCR was performed with the designated primers as previously described [21, 22]. GAPDH or RNU6B (Qiagen) was used as the internal control. Data were analyzed by the relative quantification (ΔΔCt) method.
Western blot analysisProteins were extracted from adipocytes or adipose tissue using lysis buffer containing 0.1% protease inhibitor cocktail (Roche Diagnostics, Indiana, USA), and protein concentrations were determined using the BCA protein assay kit (Beyotime, Shanghai, China). Equal amounts of protein from different groups were subjected to SDS‒PAGE and transferred onto PVDF membranes. Nonspecific binding was blocked with 5% BSA. Then, the membranes were incubated with the following specific primary antibodies: mouse monoclonal anti-cleaved caspase 3 (1:1000; Cell Signaling Technology, Boston, USA), mouse monoclonal anti-cleaved caspase 8 (1:2000; Cell Signaling), rabbit polyclonal anti-Bax (1:2000; Santa Cruz, California, USA), rabbit polyclonal anti-Bcl2 (1:1000; Sigma, Bornem, Belgium) and mouse monoclonal anti-β-actin (1:5000; ZSGB-BIO, Beijing, China) overnight at 4°C. The membranes were washed with Tris-buffered saline with Tween (TBST) and incubated with the following peroxidase-conjugated secondary antibodies: goat anti-rabbit IgG (1:5000; ZSGB-BIO) and goat anti-mouse IgG (1:5000; ZSGB-BIO) for 1 hour at room temperature. Protein bands were detected using the Western Bright ECL substrate (Advansta, California, USA) and visualized with the Vilber Fusion image system (Torcy, France). Finally, the band intensities were quantitatively analyzed using Fushion FX software (Torcy, France). The relative expression levels of proteins were normalized to β-actin.
Apoptosis assaysCell apoptosis was analyzed by TUNEL assays (Roche) and Hoechst 33258 staining (Beyotime, Jiangsu, China) after miR-27a-3p mimic transfection and TNF-α treatment. For the TUNEL assay, cells were fixed with 4% (v/v/) paraformaldehyde for 30 min at room temperature, permeabilized with 0.1% Triton X-100 on ice for 2 min and stained with the TUNEL fluorochrome. Cells stained with TUNEL were observed by fluorescence microscopy. For Hoechst 33258 staining, cells were fixed for 10 min in 4% formaldehyde solution, and the nuclei were stained with Hoechst 33258 for 5 min. Then, the cells were examined by fluorescence microscopy.
Statistical analysisData were acquired from 6 repeated experiments and are expressed as the mean ± SE unless otherwise indicated. Student’s t test (unpaired, two-tailed) was used to compare the two groups. Data involving more than 2 groups were assessed by one-way ANOVA followed by the Newman‒Keuls test. Pearson’s correlation analysis was performed using the statistical software SPSS 19.0. The statistical significance of differences was considered at values of p < 0.05.
After 8 weeks, the mice in the HFD group showed a much higher body weight (g) (34.51 ± 1.55 vs. 25.30 ± 1.38, p < 0.001) and epididymal fat pad weight (g) (1.55 ± 0.31 vs. 0.48 ± 0.06, p < 0.001) than the CD mice. To confirm the presence of AT apoptosis, we first examined the expression of caspase 8 (a critical initiation caspase) and caspase 3, a key effector caspase that executes the apoptotic program [23]. By Western blot analysis, we found that the protein levels of cleaved caspase 3 and cleaved caspase 8 were significantly increased in the epididymal AT of the obese mice compared with the CD mice (Fig. 1A–1C). In addition, compared with that of the CD mice, the ratio of Bax and Bcl2, as a marker of apoptotic sensitivity [24, 25], was significantly increased in the AT of the obese mice (Fig. 1D), suggesting that obesity induced apoptosis in the AT of mice. Similarly, the induction of apoptosis was also noted in omental AT from obese human subjects (Fig. 1E–1G).
Detection of miR-27a and apoptosis-related proteins in the fat depots of mice and human subjects. C57 L/6J mice were fed either a chow diet (CD) or a high-fat diet (HFD) for 8 weeks. Omental AT was obtained from lean control (Lean, n = 21) and obese subjects (Obese, n = 14) undergoing laparoscopic cholecystectomy. Apoptosis-related proteins, including cleaved caspase 3, cleaved caspase 8, Bax, Bcl2 and miR-27a, were detected in epididymal AT and human subjects. (A) Western blot detection of the protein levels of apoptosis-related proteins in epididymal AT of mice. (B–D) Semiquantitative analysis of cleaved caspase 3 (B), cleaved caspase 8 (C), and the ratio of Bax/Bcl2 (D) in each group. (E) Western blot detection of apoptosis-related proteins in omental AT of human subjects. (F–G) Semiquantitative analysis of cleaved caspase 3 (F) and the ratio of Bax/Bcl2 (G) in each group. (H–I) Expression of miR-27a in the fat depots of mice (H) and human subjects (I) was quantified by RT‒qPCR. Corresponding densitometric analyses were normalized to β-actin or Bcl2. Values were normalized to β-actin or U6 and are presented as relative expression compared to that of the CD mice or lean subjects. Data are presented as the mean ± SEM. * p < 0.05 and ** p < 0.01 vs. the CD or lean group. AT, adipose tissue. CD, chow diet. HFD, high-fat diet.
The expression of miR-27a in the epididymal AT of mice was determined by RT‒qPCR. Compared to that of the CD mice, miR-27a was significantly downregulated in the AT of the obese mice (Fig. 1H). We further verified the expression of miR-27a in omental AT from obese subjects and lean controls, which were well matched in terms of age (y) (54.38 ± 10.68 vs. 49.45 ± 9.69, p = 0.171) and sex (7/7 vs. 10/11 men/women per group). As expected, obese human subjects also displayed significantly lower expression of miR-27a in omental AT (Fig. 1I).
miR-27a was downregulated in apoptotic adipocytesTo clarify whether the downregulation of miR-27a was associated with apoptosis, we challenged adipocytes with 50 ng/mL TNF-α, a widely used proapoptotic stimulant to induce adipocyte apoptosis [26]. As expected, TNF-α sharply elevated the protein levels of cleaved caspase 3 and cleaved caspase 8 and the ratio of Bax/Bcl-2 in both preadipocytes (Fig. 2A–2D) and mature adipocytes (Fig. 2E–2H), which mimicked the apoptotic status of AT in human obesity. Intriguingly, miR-27a expression was significantly downregulated in TNF-induced apoptotic adipocytes compared with that of the control group (Fig. 2I, 2J).
Induction of apoptosis and downregulation of miR-27a in 3T3-L1 preadipocytes and differentiated mature adipocytes under TNF-α stimulation. Preadipocytes or differentiated adipocytes were treated with or without 50 ng/mL TNF-α for 24 h. (A) Western blot detection of the protein expression of apoptosis-related proteins in adipocytes. (B–D) Semiquantitative analysis of cleaved caspase 3 (B), cleaved caspase 8 (C), and the ratio of Bax/Bcl2 (D). (E) Western blot detection of the protein expression of apoptosis-related proteins in mature adipocytes. (F–H) Semiquantitative analysis of cleaved caspase 3 (F), cleaved caspase 8 (G), and the ratio of Bax/Bcl2 (H). (I–J) Expression of miR-27a in adipocytes (I) and mature adipocytes (J) was quantified by RT‒qPCR. Values were normalized to β-actin or U6 and are presented as relative expression compared to the CTRL. * p < 0.05 vs. the CTRL. CTRL, control.
To gain insight into whether miR-27a was involved in regulating adipocyte apoptosis, we transfected preadipocytes and mature 3T3-L1 adipocytes with 50 nM miR-27a mimic followed by TNF-α treatment. miR-27a overexpression obviously suppressed the TNF-α-induced elevation of cleaved caspase 3, cleaved caspase 8 and the Bax/Bcl2 ratio in preadipocytes (Fig. 3A); however, in differentiated adipocytes, the antiapoptotic effect of miR-27a overexpression was much less pronounced, which only significantly inhibited cleaved caspase 3 expression but not cleaved caspase 8 expression (Fig. 3B). Furthermore, both the TUNEL apoptosis assay and Hoechst 33258 staining showed that the percentage of apoptotic adipocytes was notably decreased by miR-27a overexpression in 3T3-L1 preadipocytes (Fig. 3C).
Overexpression of miR-27a inhibited TNF-α-induced apoptosis in adipocytes. First, 3T3-L1 preadipocytes or differentiated mature adipocytes were transfected with 50 nM miR-27a mimic (MIMIC) or negative control (CTRL) oligos. Then, the cells were incubated with or without 50 ng/mL TNF-α for 24 h. (A and B) Western blot detection and semiquantitative analysis of the protein expression of cleaved caspase 3, cleaved caspase 8, Bax and Bcl2 in preadipocytes (A) and mature adipocytes (B). Corresponding densitometric analyses were normalized to β-actin. (C) Apoptotic cells were observed by TUNEL and Hoechst 33258 staining. Red arrows indicate positive apoptotic cells (stained in bright blue; magnification, ×100). * p < 0.05 vs. the CTRL, # p < 0.05 vs. TNF. CTRL, control.
Given that miRNAs can be secreted into circulation [27], we thus detected alterations in the circulating level of miR-27a between 23 obese and 23 lean subjects. Compared to the lean subjects, the obese patients displayed marked metabolic abnormalities, characterized by higher levels of BMI, WC, HC, SBP, DBP, FPG, FINS, 2hPG, HbA1c, TG, and hs-CRP and lower HDL-c and adiponectin (Table 1).
| Variables | Lean (n = 23) | Obese (n = 23) | p value |
|---|---|---|---|
| Age (years) | 50.30 ± 10.12 | 46.83 ± 10.89 | 0.268 |
| Sex (men/women) | 11/12 | 13/10 | 0.555 |
| BMI (kg/m2) | 21.87 ± 1.07 | 30.79 ± 2.33 | <0.001 |
| WC (cm) | 81.30 ± 6.21 | 99.22 ± 8.42 | <0.001 |
| HC (cm) | 91.04 ± 3.64 | 106.17 ± 7.22 | <0.001 |
| SBP (mmHg) | 111.22 ± 14.21 | 120.36 ± 15.27 | 0.043 |
| DBP (mmHg) | 70.87 ± 10.95 | 79.78 ± 11.38 | 0.010 |
| TC (mmol/L) | 4.49 ± 0.81 | 4.52 ± 1.01 | 0.911 |
| TG (mmol/L) | 1.56 ± 0.81 | 2.35 ± 1.46 | 0.031 |
| HDL-c (mmol/L) | 1.34 ± 0.40 | 0.92 ± 0.23 | <0.001 |
| LDL-c (mmol/L) | 2.53 ± 0.42 | 2.89 ± 0.69 | 0.068 |
| HbA1c (%) | 5.70 ± 0.33 | 6.08 ± 0.65 | 0.017 |
| FPG (mmol/L) | 5.19 ± 0.39 | 5.60 ± 0.43 | 0.002 |
| FINS(mIU/L) | 5.69 ± 3.56 | 12.06 ± 5.08 | <0.001 |
| 2hPG (mmol/L) | 6.82 ± 0.62 | 8.74 ± 1.31 | <0.001 |
| HOMA-IR | 1.18 ± 0.75 | 3.06 ± 1.38 | <0.001 |
| HOMA-IS | 0.05 ± 0.03 | 0.02 ± 0.01 | <0.001 |
| ApN (ug/mL) | 18.79 ± 10.80 | 12.09 ± 4.88 | 0.032 |
| hs-CRP (mg/L) | 0.54 ± 0.53 | 2.16 ± 2.28 | 0.009 |
Data are presented as mean ± SD and analyzed by independent sample t test or χ2 test. BMI: body mass index; WC: waist circumference; HC: hip circumference; SBP: systolic blood pressure; DBP: diastolic blood pressure; TC: total cholesterol; TG: triglycerides; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; FINS: fasting insulin; HOMA-IR: homeostasis model assessment for insulin resistance; HOMA-IS: homeostasis model assessment for insulin sensitivity; 2hPG: 2-hour post-load plasma glucose; hs-CRP: high-sensitivity C-reactive protein.
In addition, serum miR-27a levels were significantly decreased by 55.2% in the obese subjects compared with the lean controls (p < 0.05, Fig. 4) and showed negative correlations with BMI (r = –0.375, p = 0.012), WC (r = –0.324, p = 0.032), HC (r = –0.306, p = 0.043), 2hPG (r = –0.410, p = 0.006), hs-CRP (r = –0.366, p = 0.033), FINS (r = –0.372, p = 0.030), and HOMA-IR (r = –0.370, p = –0.034) and positive correlations with adiponectin (r = 0.374, p = 0.042) and HOMA-IS (r = 0.459, p = 0.006, Table 2).
Expression of miR-27a in human serum. Human serum was obtained from 23 lean controls (Lean) and 23 obese subjects (Obese). The expression of miR-27a in serum was quantified by RT‒qPCR. Values were normalized to U6 and are presented as relative expression compared to lean subjects. ** p < 0.01 vs. lean.
| miR-27a | ||
|---|---|---|
| r | p | |
| Age | –0.181 | 0.245 |
| BMI | –0.375 | 0.012 |
| WC | –0.324 | 0.032 |
| HC | –0.306 | 0.043 |
| SBP | –0.058 | 0.716 |
| DBP | –0.190 | 0.221 |
| TC | –0.180 | 0.274 |
| TG | –0.213 | 0.180 |
| HDL-c | 0.144 | 0.175 |
| LDL-c | –0.261 | 0.135 |
| HbA1c | –0.211 | 0.175 |
| FPG | –0.222 | 0.153 |
| 2hPG | –0.410 | 0.006 |
| FINS | –0.372 | 0.030 |
| HOMA-IR | –0.370 | 0.034 |
| HOMA-IS | 0.459 | 0.006 |
| hs-CRP | –0.366 | 0.033 |
| Adiponectin | 0.374 | 0.042 |
BMI: body mass index; WC: waist circumference; HC: hip circumference; SBP: systolic blood pressure; DBP: diastolic blood pressure; TC: total cholesterol; TG: triglycerides; HDL-c: high-density lipoprotein cholesterol; LDL-c: low-density lipoprotein cholesterol; FPG: fasting plasma glucose; FINS: fasting insulin; HOMA-IR: homeostasis model assessment for insulin resistance; HOMA-IS: homeostasis model assessment for insulin sensitivity; 2hPG: 2-hour post-load plasma glucose; hs-CRP: high-sensitivity C-reactive protein.
In the present study, we showed that miR-27a was obviously downregulated both in serum and omental AT of human obesity, and serum miR-27a presented notable associations with metabolic parameters. In addition, we indicated that miR-27a had a protective role in preventing TNF-α-induced apoptosis in 3T3-L1 preadipocytes.
Increased apoptosis in AT is associated with obesity in both rodents and humans and may represent one of the early mechanisms involved in the development of systemic subclinical inflammation and impaired insulin sensitivity by causing macrophage infiltration [7]. In our study, adipose tissue from mice with diet-induced obesity and obese humans displayed a proapoptotic phenotype, as evidenced by increased protein levels of cleaved caspase 3 and cleaved caspase 8 and an increased Bax/Bcl2 ratio, which was in accordance with previous studies [5, 28]. Conversely, miR-27a expression was obviously downregulated in the AT of both mouse and human obesity, which is consistent with previous results from an obese mouse model [15]. Although Collares et al. [29] reported reverse miR-27a expression patterns in the omentum of morbidly obese patients (average BMI 47.46 kg/m2), contrasting with our obese subjects (average BMI 30.79 kg/m2), we consider this finding may be due to the difference in the race and degree of obesity, suggesting that morbid obesity displayed much more complicated metabolic disorders in AT [30].
miRNAs have been widely investigated in AT dysfunction [31, 32], while the concrete role of miRNAs in adipocyte apoptosis is poorly explored. As a well-known cytokine, TNF-α is a major proapoptotic stimulant in adipocytes and has been shown to induce apoptosis in human adipocytes [33]; thus, we induced adipocyte apoptosis with TNF-α. We observed that as the expression of apoptotic proteins was elevated by TNF-α stimulation, miR-27a was correspondingly downregulated. Moreover, a gain-of-function study further showed that miR-27a overexpression significantly diminished these elevated apoptotic proteins and the percentage of apoptotic adipocytes induced by TNF-α in preadipocytes but not in mature adipocytes, suggesting a critical antiapoptotic effect of miR-27a in preadipocytes. The discrepant antiapoptotic role of miR-27a in preadipocytes and mature adipocytes might be attributed to the following two aspects. On the one hand, although apoptosis often occurs in both preadipocytes and differentiated adipocytes, higher sensitivity to apoptotic stimuli was found in preadipocytes than in mature adipocytes [34]. On the other hand, in obesity, oversized adipocytes were the predominant cell type by mass; however, preadipocytes greatly outnumber mature adipocytes [35], which highlighted the antiapoptotic role of miR-27a in preadipocytes.
In recent years, altered circulating miRNA profiles have already been linked to metabolic disease states, including obesity. The detection of circulating miRNAs in patients has been considered a novel method for evaluating the progression of metabolic disorders [36-38]. In our study, for the first time, we found that miR-27a was markedly downregulated in the serum of obese subjects, and it was negatively related to BMI, WC, HC, 2hPG, hs-CRP, FINS and HOMA-IR but positively related to adiponectin and HOMA-IS. These linear associations further revealed that miR-27a may serve as a potential predictive biomarker of obesity and insulin resistance.
Collectively, our study supports that miR-27a, which is downregulated in human obesity, can prevent preadipocyte apoptosis, and miR-27a may be a novel target for the treatment of AT dysfunction and obesity-related metabolic disorders.
We are very grateful to the Department of Hepatobiliary of the First Affiliated Hospital of Chongqing Medical University for the collection of human adipose tissue.
The authors declare that they have no competing interests.
This work was supported by grants from the National Natural Science Foundation of China (81370954), the National Key Clinical Specialties Construction Program of China, and the Chongqing Science and Technology Committee (cstc2015jcyjB0111).
