PMID- 29540272
OWN - NLM
STAT- MEDLINE
DCOM- 20190501
LR  - 20190501
IS  - 1879-0739 (Electronic)
IS  - 0271-5317 (Linking)
VI  - 50
DP  - 2018 Feb
TI  - Association of low dietary folate intake with lower CAMKK2 gene methylation, 
      adiposity, and insulin resistance in obese subjects.
PG  - 53-62
LID - S0271-5317(17)30437-2 [pii]
LID - 10.1016/j.nutres.2017.11.007 [doi]
AB  - Folate deficiency has been putatively implicated in the onset of diverse 
      metabolic abnormalities, including insulin resistance, by altering epigenetic 
      processes on key regulatory genes. The calcium/calmodulin-dependent protein 
      kinase kinase 2 (CAMKK2) is involved in the regulation of critical metabolic 
      processes such as adiposity and glucose homeostasis. This study hypothesized 
      associations between low folate intakes and lower methylation levels of the 
      CAMKK2 gene, with the presence of metabolic alterations in subjects with obesity. 
      A cross-sectional ancillary study was conducted in obese subjects (n=47) from the 
      RESMENA study (Spain). Fat mass was measured by dual-energy x-ray absorptiometry. 
      Dietary intake and metabolic profile were assessed by validated methods. DNA 
      methylation and gene expression in peripheral white blood cells were analyzed by 
      microarray approaches. A total of 51 cytosine-phosphate-guanine sites were 
      associated with folate intake (false discovery rate values < 0.0001), including 
      one located in the 5' untranslated region of the CAMKK2 gene (Illumina ID, 
      cg16942632), which was selected and separately analyzed. Subjects with total 
      folate intake lower than 300mug/d showed more fat mass (especially trunk fat), as 
      well as statistically higher levels of glucose, insulin, homeostatic model 
      assessment-insulin resistance (HOMA-IR) index, cortisol, and plasminogen 
      activator inhibitor-1 than those consuming at least or more than 300mug/d. Of 
      note, folate deficiency was related to lower CAMKK2 methylation. Interestingly, 
      CAMKK2 methylation negatively correlated with the HOMA-IR index. Furthermore, 
      CAMKK2 expression directly correlated with HOMA-IR values. In summary, this study 
      suggests associations between low folate intakes, lower CAMKK2 gene methylation, 
      and insulin resistance in obese individuals.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - Ramos-Lopez, Omar
AU  - Ramos-Lopez O
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain.
FAU - Samblas, Mirian
AU  - Samblas M
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain.
FAU - Milagro, Fermin I
AU  - Milagro FI
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain; Biomedical Research Centre 
      Network in Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, 
      Spain.
FAU - Zulet, M Angeles
AU  - Zulet MA
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain; Biomedical Research Centre 
      Network in Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, 
      Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain.
FAU - Mansego, Maria L
AU  - Mansego ML
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain.
FAU - Riezu-Boj, Jose I
AU  - Riezu-Boj JI
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain; Navarra Institute for Health 
      Research (IdiSNA), Pamplona, Spain.
FAU - Martinez, J Alfredo
AU  - Martinez JA
AD  - Department of Nutrition, Food Science and Physiology, and Center for Nutrition 
      Research, University of Navarra, Pamplona, Spain; Biomedical Research Centre 
      Network in Physiopathology of Obesity and Nutrition (CIBERobn), ISCIII, Madrid, 
      Spain; Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; Madrid 
      Institute of Advanced Studies (IMDEA Food), Madrid, Spain. Electronic address: 
      jalfmtz@unav.es.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171205
PL  - United States
TA  - Nutr Res
JT  - Nutrition research (New York, N.Y.)
JID - 8303331
RN  - 0 (Blood Glucose)
RN  - 0 (Insulin)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 935E97BOY8 (Folic Acid)
RN  - EC 2.7.11.17 (CAMKK2 protein, human)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Kinase)
RN  - WI4X0X7BPJ (Hydrocortisone)
SB  - IM
MH  - Adipose Tissue/metabolism
MH  - Adiposity
MH  - Adult
MH  - Blood Glucose/metabolism
MH  - Body Composition
MH  - Calcium-Calmodulin-Dependent Protein Kinase Kinase/*metabolism
MH  - Cross-Sectional Studies
MH  - *DNA Methylation
MH  - *Diet
MH  - Feeding Behavior
MH  - Female
MH  - Folic Acid/*administration & dosage
MH  - Folic Acid Deficiency/*complications/metabolism
MH  - Humans
MH  - Hydrocortisone/blood
MH  - Insulin/blood
MH  - *Insulin Resistance
MH  - Male
MH  - Middle Aged
MH  - Nutritional Status
MH  - Obesity/*complications/metabolism
MH  - Plasminogen Activator Inhibitor 1/blood
OTO - NOTNLM
OT  - Adiposity
OT  - CAMKK2
OT  - Folate
OT  - Insulin resistance
OT  - Obesity
EDAT- 2018/03/16 06:00
MHDA- 2019/05/02 06:00
CRDT- 2018/03/16 06:00
PHST- 2017/05/16 00:00 [received]
PHST- 2017/08/22 00:00 [revised]
PHST- 2017/11/30 00:00 [accepted]
PHST- 2018/03/16 06:00 [entrez]
PHST- 2018/03/16 06:00 [pubmed]
PHST- 2019/05/02 06:00 [medline]
AID - S0271-5317(17)30437-2 [pii]
AID - 10.1016/j.nutres.2017.11.007 [doi]
PST - ppublish
SO  - Nutr Res. 2018 Feb;50:53-62. doi: 10.1016/j.nutres.2017.11.007. Epub 2017 Dec 5.