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. 2017 Oct;23:225-234.
doi: 10.2119/molmed.2017.00067. Epub 2017 Aug 23.

Adipose Tissue and Serum CCDC80 in Obesity and Its Association With Related Metabolic Disease

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Free PMC article

Adipose Tissue and Serum CCDC80 in Obesity and Its Association With Related Metabolic Disease

O Osorio-Conles et al. Mol Med. .
Free PMC article

Abstract

Coiled-coil domain-containing 80 (CCDC80) is an adipocyte-secreted protein that modulates glucose homeostasis in response to diet-induced obesity in mice. The objective of this study is to analyze the link between human CCDC80 and obesity. CCDC80 protein expression was assessed in paired visceral (VAT) and subcutaneous (SAT) adipose tissue from 10 subjects (BMI range 22.4-38.8 kg/m2). Circulating CCDC80 levels were quantified in serum samples from two independent cross-sectional cohorts comprising 33 lean and 15 obese (cohort 1) and 32 morbid obese (cohort 2) male subjects. Insulin sensitivity, insulin secretion and blood neutrophil count were quantified in serum samples from both cohorts. Additionally, circulating free IGF-1 levels and oral glucose tolerance tests (OGTT) were assessed in cohort 1 whereas C-reactive protein levels and degree of atherosclerosis and hepatic steatosis were studied in cohort 2. In lean subjects, total CCDC80 protein content assessed by immunoblotting was lower in VAT than in SAT. In obese patients, CCDC80 was increased in VAT (P<0.05), but equivalent in SAT compared with lean counterparts. In cohort 1, serum CCDC80 correlated negatively with the acute insulin response to glucose and IGF1 levels, and positively with blood neutrophil count, independently of BMI, but not with insulin sensitivity. In cohort 2, serum CCDC80 was positively linked to the inflammatory biomarker C-reactive protein (r=0.46; P=0.009), atherosclerosis (carotid intima-media thickness, r=0.62; P<0.001) and hepatic steatosis (ANOVA P=0.025). Overall, these results suggest for the first time that CCDC80 may be a component of the obesity-altered secretome in VAT and could act as an adipokine whose circulant levels are linked to glucose tolerance derangements and related to inflammation-associated chronic complications.

Keywords: Adipokines; CCDC80; Obesity; Subcutaneous Adipose Tissue; Visceral Adipose Tissue.

Conflict of interest statement

DISCLOSURE

The authors declare that they have no competing interests as defined by Molecular Medicine, or other interests that might be perceived to influence the results and discussion reported in this paper.

Figures

Figure 1.
Figure 1.
Analysis of CCDC80 and CD14 protein content in SAT and VAT depots from lean and obese patients and CCDC80 protein in human plasma. (A) Western blot analysis of SAT and VAT extracts (20 μg protein). Membranes were hybridized with antibodies against CCDC80, CD14 and FAA. A representative blot is shown. Bands were quantified and the ratio of intensities between CCDC80 or CD14 and control FAA was calculated. (B) Relative CCDC80 protein content. Data are expressed in arbitrary units and are means ± SEM from 5 samples. #P < 0.05 between different depots in lean patients; *P < 0.05 between VAT depots in obese versus lean patients. (C) Western blot analysis of 1 μl of human plasma and 0.8 ng of purified CCDC80 protein (50 kDa fragment). The membrane was hybridized with an antibody against CCDC80. (D) Relative CD14 protein content. Data are expressed in arbitrary units and are means ± SEM from 5 samples. #P < 0.05 between different depots in obese patients; *P < 0.05 between VAT depots in obese versus lean patients.
Figure 2.
Figure 2.
CCDC80 protein expression in human SGBS adipocytes during differentiation. (A) Western blot analysis of CCDC80 protein content in SGBS cell extracts of confluent preadipocytes (d 0), differentiating adipocytes (d 1–8) and mature adipocytes (d 14). (B) Confluent preadipocytes incubated with or without 25 nM dexamethasone, 0.5 mM IBMX and 2 μM rosiglitazone for 16 h. In A and B, a representative image is shown. Ratios of intensity of CCDC80 bands compared with intensity of GAPDH are expressed as a percentage of (untreated) confluent preadipocyte values and are means ± standard error of the mean from two experiments performed in triplicate. *P < 0.05 and **P < 0.01 vs untreated preadipocytes. (C) CCDC80 mRNA levels relative to 18S rRNA were measured in confluent preadipocytes, differentiating adipocytes (4 d post-differentiation) and mature adipocytes (14 d post-differentiation). Data are means ± standard error of the mean of 2ΔCp × 103 from two experiments performed in triplicate. *P < 0.001 to preadipocytes; #P < 0.01 to differentiating adipocytes.
Figure 3.
Figure 3.
Serum CCDC80 protein levels in a cohort with different degrees of obesity in association with insulin secretion and inflammation parameters. Bivariate correlation analysis showing association of CCDC80 levels with (A) acute insulin response to glucose (AIRg values, which were logarithmically transformed to normalize values), r = –0.35, P = 0.02; (B) with serum glucose levels 30 min post-OGTT, r = –0.34, P = 0.02; (C) circulating IGF1 levels, r = –0.43, P = 0.01; and (D) blood neutrophil count, r = 0.26, P = 0.07.
Figure 4.
Figure 4.
Serum CCDC80 protein levels in a cohort of morbidly obese patients in association with liver steatosis and carotid atherosclerosis. (A) Box plots showing CCDC80 levels (median value and 25th and 75th percentiles) according to degree of hepatic steatosis in consecutive morbidly obese patients without steatosis (n = 11) compared with slight (n = 10), moderate (n = 5) and severe (n = 2) steatosis. (B) Bivariate correlation analysis between serum CCDC80 protein levels and internal carotid intima-media thickness.

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