Differential NADP-Dependent Isocitrate Dehydrogenases Expression in Metabolically Healthy Obesity vs Metabolic...

Nicotinamide adenine dinucleotide phosphate (NADP)-dependent isocitrate dehydrogenases, isocitrate dehydrogenase enzyme (IDH)1 and IDH2, are crucial to normal glucose and lipid metabolism and to oxidative species handling. This study aimed to assess the probability of utilizing NADP-dependent isocitrate dehydrogenases deficiency as a biomarker of the progression of metabolically healthy obesity (MHO) to metabolic syndrome (MetS).

The study enrolled 120 participants. We investigated IDH1 and IDH2 mRNA expression in peripheral whole blood samples collected from 40 MetS patients, 40 individuals with MHO, and 40 healthy controls, in relation to serum NADP-dependent isocitrate dehydrogenases activity, serum leptin, adiponectin, high-sensitivity C-reactive protein (hs-CRP), and calculated Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).

IDH1 mRNA expression was significantly lower in MetS patients compared to MHO in whom the transcript levels were indifferent from the controls. IDH2 was more deficient in MetS than MHO, and both were lower than controls. Serum NADP-dependent IDH enzyme activity was remarkably lower in the MetS group compared to the MHO group as well as to controls (2.83 ± 0.47 mU/mL, 4.58 ± 0.67 and 6.09 ± 0.93, respectively, P < 0.001). Both transcripts showed strong negative correlations to HOMA-IR, adiposity biomarkers, and hs-CRP. Regression analysis demonstrated that for every 10% decrease in IDH1 and IDH2 transcription, the odds of developing obesity-associated MetS increases by 4.9- and 6.3-fold, respectively.

In contrast to MHO, both IDH1 and IDH2 are deficient in MetS. Their deficiency coincides with chronic inflammation, adipose tissue dysfunction, and insulin resistance. Our preliminary data support the potential use of NADP- dependent IDH as a predictive biomarker of obesity-related MetS.