Lower zinc-alpha2-glycoprotein production by adipose tissue and liver in obese patients unrelated to insulin resistance.
BACKGROUND
Zinc-alpha2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays.


OBJECTIVE
The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored.


METHODS
This was a case-control study.


METHODS
The study was conducted at a university referral center.


METHODS
Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures.


RESULTS
Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 +/- 10.45 vs. 63.26 +/- 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = -0.65, P < 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = -0.68, P < 0.001) and VAT were detected (r = -0.64, P < 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro.


CONCLUSIONS
A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance.
Selva
David M
DM
Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, Instituto de Salud Carlos III, Universitat Autònoma de Barcelona, Barcelona, Spain.
Lecube
Albert
A
Hernández
Cristina
C
Baena
Juan A
JA
Fort
José M
JM
Simó
Rafael
R
D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D006528:Carcinoma, Hepatocellular; D002460:Cell Line; D045744:Cell Line, Tumor; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D015390:Gastric Bypass; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000601:surgery; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D029589:Seminal Plasma Proteins / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000090203:Zn-Alpha-2-Glycoprotein
D017931:DNA Primers; D012333:RNA, Messenger; D029589:Seminal Plasma Proteins; D000090203:Zn-Alpha-2-Glycoprotein