CCNG2 and CDK4 is associated with insulin resistance in adipose tissue.
BACKGROUND
The involvement of cyclin G2 (CCNG2) and cyclin-dependent kinase-4 (CDK4), cell cycle regulatory proteins, in adipose tissue metabolism and insulin resistance is still unknown. The objective of this study was to analyze CCNG2 and CDK4 levels in visceral (VAT) and subcutaneous adipose tissue (SAT) from nonobese and morbidly obese patients and their relationship with insulin resistance.


METHODS
We studied the mRNA and protein levels of CCNG2 and CDK4 in VAT and SAT from 12 nonobese and 23 morbidly obese patients (11 with low [MO-L-IR] and 12 with high insulin resistance [MO-H-IR]).


RESULTS
The nonobese patients had a significantly greater CCNG2 expression in VAT (P = .004) and SAT (P<.001) than the MO-L-IR and MO-H-IR patients. The MO-H-IR patients had a significantly lower CDK4 expression in VAT than the MO-L-IR (P = .026), but similar to the nonobese patients. CDK4 and CCNG2 expression correlated significantly in VAT (r = 0.511, P<.001) and SAT (r = .535, P = .001). In different multiple regression analysis models, CCNG2 and CDK4 expression in VAT was mainly predicted by glucose (P = .047 and P = .008, respectively), and CCNG2 expression in SAT was mainly predicted by body mass index (P = .041). No significant associations were found with CDK4 expression in SAT. Moreover, VAT CCNG2 expression was the main determinant of the improvement in the homeostasis model assessment of insulin resistance index at 3 months after bariatric surgery (B = -271.7, P = .026).


CONCLUSIONS
Our data show for the first time that the human CCNG2 and CDK4 expression of VAT are inversely associated with glucose and insulin resistance.
CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN), Málaga, Spain; Unidad de Gestion Clinica de Endocrinologia y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clinico Virgen de la Victoria, Málaga, Spain.
Lourdes
L
Garrido-Sánchez
Unidad de Gestion Clinica de Endocrinologia y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clinico Virgen de la Victoria, Málaga, Spain.
Maria del Mar
Mdel M
Roca-Rodríguez
Endocrinology and Diabetes Unit, Joan XXIII University Hospital, IISPV, Universitat Rovira i Virgili, Tarragona, Spain; CIBER of Diabetes and Associated Metabolic Disorders (CIBERDEM), Tarragona, Spain.
Sonia
S
Fernández-Veledo
Endocrinology and Diabetes Unit, Joan XXIII University Hospital, IISPV, Universitat Rovira i Virgili, Tarragona, Spain; CIBER of Diabetes and Associated Metabolic Disorders (CIBERDEM), Tarragona, Spain.
Joan
J
Vendrell
Lipids and Atherosclerosis Unit, IMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN), Cordoba, Spain.
Elena María
EM
Yubero-Serrano
Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clinico Virgen de la Victoria, Málaga, Spain.
Luis
L
Ocaña-Wilhelmi
CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN), Málaga, Spain; Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigaciones Biomédicas de Málaga (IBIMA), Hospital Regional Universitario, Málaga, Spain. Electronic address: edugf1@gmail.com.
Eduardo
E
García-Fuentes
CIBER of Physiopathology, Obesity and Nutrition (CIBEROBN), Málaga, Spain; Unidad de Gestion Clinica de Endocrinologia y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Clinico Virgen de la Victoria, Málaga, Spain. Electronic address: fjtinahones@hotmail.com.
Francisco Jose
FJ
Tinahones
D000328:Adult; D050110:Bariatric Surgery; D015992:Body Mass Index; D016022:Case-Control Studies; D056767:Cyclin G2 / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000502:physiology*; D050152:Intra-Abdominal Fat / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000378:metabolism* / Q000601:surgery; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D050151:Subcutaneous Fat / Q000378:metabolism*
D056767:Cyclin G2; D012333:RNA, Messenger; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4
Adipogenesis; Adipose tissue; Cyclin G2; Cyclin-dependent kinases 4; Insulin resistance; Morbid obesity