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Published on: February 17, 2023
CCNG2 and CDK4 is associated with insulin resistance in adipose tissue
Lourdes Garrido-Sánchez1, Maria del Mar Roca-Rodríguez2, Sonia Fernández-Veledo3
1CIBER 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.
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).
Conclusion:
Our data show for the first time that the human CCNG2 and CDK4 expression of VAT are inversely associated with glucose and insulin resistance.
Insights
Cyclin G2 (CCNG2) and cyclin-dependent kinase-4 (CDK4) expression in visceral adipose tissue is inversely linked to insulin resistance. Lower CCNG2 and CDK4 levels in obese patients correlate with higher insulin resistance, with CCNG2 predicting improvements post-surgery.
Area of Science:
- Metabolic research
- Obesity studies
- Cell cycle regulation
Background:
- The roles of cyclin G2 (CCNG2) and cyclin-dependent kinase-4 (CDK4) in adipose tissue metabolism and insulin resistance remain unclear.
- Investigating these cell cycle proteins is crucial for understanding metabolic dysfunction.
Purpose of the Study:
- To analyze CCNG2 and CDK4 expression levels in visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT).
- To compare these levels between nonobese and morbidly obese individuals with varying degrees of insulin resistance.
- To determine the relationship between CCNG2/CDK4 expression and insulin resistance.
Main Methods:
- Studied mRNA and protein levels of CCNG2 and CDK4 in VAT and SAT.
- Included 12 nonobese and 23 morbidly obese patients (stratified by insulin resistance).
Main Results:
- Nonobese patients exhibited significantly higher CCNG2 expression in both VAT and SAT compared to obese patients.
- Morbidly obese patients with high insulin resistance (MO-H-IR) showed significantly lower CDK4 expression in VAT.
- CCNG2 and CDK4 expression correlated significantly in both VAT and SAT; VAT expression was predicted by glucose levels, and SAT CCNG2 by BMI.
- VAT CCNG2 expression was a key determinant of insulin resistance improvement after bariatric surgery.
Conclusions:
- Human CCNG2 and CDK4 expression in visceral adipose tissue are inversely associated with glucose and insulin resistance.
- These findings highlight a novel link between cell cycle regulators and metabolic health in adipose tissue.
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