Leptin and adiponectin DNA methylation levels in adipose tissues and blood cells are associated with BMI, waist girth and LDL-cholesterol levels in severely obese men and women.
BACKGROUND
Leptin (LEP) and adiponectin (ADIPOQ) genes encode adipokines that are mainly secreted by adipose tissues, involved in energy balance and suspected to play a role in the pathways linking adiposity to impaired glucose and insulin homeostasis. We have thus hypothesized that LEP and ADIPOQ DNA methylation changes might be involved in obesity development and its related complications. The objective of this study was to assess whether LEP and ADIPOQ DNA methylation levels measured in subcutaneous (SAT) and visceral adipose tissues (VAT) are associated with anthropometric measures and metabolic profile in severely obese men and women. These analyses were repeated with DNA methylation profiles from blood cells obtained from the same individuals to determine whether they showed similarities.


METHODS
Paired SAT, VAT and blood samples were obtained from 73 severely obese patients undergoing a bioliopancreatic diversion with duodenal switch. LEP and ADIPOQ DNA methylation and mRNA levels were quantified using bisulfite-pyrosequencing and qRT-PCR respectively. Pearson's correlation coefficients were computed to determine the associations between LEP and ADIPOQ DNA methylation levels, anthropometric measures and metabolic profile.


RESULTS
DNA methylation levels at the ADIPOQ gene locus in SAT was positively associated with BMI and waist girth whereas LEP DNA methylation levels in blood cells were negatively associated with body mass index (BMI). Fasting LDL-C levels were found to be positively correlated with DNA methylation levels at LEP-CpG11 and -CpG17 in blood and SAT and with ADIPOQ DNA methylation levels in SAT (CpGE1 and CpGE3) and VAT (CpGE1).


CONCLUSIONS
These results confirm that LEP and ADIPOQ epigenetic profiles are associated with obesity. We also report associations between LDL-C levels and both LEP and ADIPOQ DNA methylation levels suggesting that LDL-C might regulate their epigenetic profiles in adipose tissues. Furthermore, similar correlations were observed between LDL-C and LEP blood DNA methylation levels suggesting a common regulatory pathway of DNA methylation in both adipose tissues and blood.
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada. andree-anne.houde@usherbrooke.ca.|ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, QC, Canada. andree-anne.houde@usherbrooke.ca.
Andrée-Anne
AA
Houde
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada. cecilia.legare@usherbrooke.ca.|ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, QC, Canada. cecilia.legare@usherbrooke.ca.
Cécilia
C
Légaré
Quebec Heart and Lung Institute, Quebec, Canada. simon.biron@chg.ulaval.ca.|Department of Surgery, Laval University, Quebec, Canada. simon.biron@chg.ulaval.ca.
Simon
S
Biron
Quebec Heart and Lung Institute, Quebec, Canada. odette.lescelleur@criucpq.ulaval.ca.|Department of Surgery, Laval University, Quebec, Canada. odette.lescelleur@criucpq.ulaval.ca.
Odette
O
Lescelleur
Quebec Heart and Lung Institute, Quebec, Canada. laurentbiertho@gmail.com.|Department of Surgery, Laval University, Quebec, Canada. laurentbiertho@gmail.com.
Laurent
L
Biertho
Quebec Heart and Lung Institute, Quebec, Canada. simon.marceau@ssss.gouv.qc.ca.|Department of Surgery, Laval University, Quebec, Canada. simon.marceau@ssss.gouv.qc.ca.
Simon
S
Marceau
Quebec Heart and Lung Institute, Quebec, Canada. andre.tchernof@criucpq.ulaval.ca.|Axe Endocrinologie et Néphrologie, Centre de recherche du CHU de Québec, Quebec, QC, Canada. andre.tchernof@criucpq.ulaval.ca.|Department of Food Science and Nutrition, Laval University, Québec, QC, Canada. andre.tchernof@criucpq.ulaval.ca.
André
A
Tchernof
Axe Endocrinologie et Néphrologie, Centre de recherche du CHU de Québec, Quebec, QC, Canada. marie-claude.vohl@fsaa.ulaval.ca.|Department of Food Science and Nutrition, Laval University, Québec, QC, Canada. marie-claude.vohl@fsaa.ulaval.ca.|Institute of Nutrition & Functional Foods, Université Laval, Quebec, QC, Canada. marie-claude.vohl@fsaa.ulaval.ca.
Marie-Claude
MC
Vohl
Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, QC, Canada. marie-france.hivert@usherbrooke.ca.|Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, MA, USA. marie-france.hivert@usherbrooke.ca.|General Medicine Division, Massachusetts General Hospital, Boston, MA, USA. marie-france.hivert@usherbrooke.ca.
Marie-France
MF
Hivert
Department of Biochemistry, Université de Sherbrooke, Sherbrooke, QC, Canada. luigi.bouchard@usherbrooke.ca.|ECOGENE-21 and Clinical Research Center and Lipid Clinic, Chicoutimi Hospital, Saguenay, QC, Canada. luigi.bouchard@usherbrooke.ca.
Luigi
L
Bouchard
D052242:Adiponectin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D015992:Body Mass Index; D049628:Body Size; D008078:Cholesterol, LDL / Q000097:blood*; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D020738:Leptin / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism; D055105:Waist Circumference; D055815:Young Adult
D052242:Adiponectin; D008078:Cholesterol, LDL; D020738:Leptin; D012333:RNA, Messenger