L mitochondrial regulation.Table 1 Demographic and metabolic characteristics of participantsCharacteristics Sex (male/female) Age (years) BMI (kg/m2) Fasting glucose (mg/dL) Fasting insulin (U/mL) HOMA-IR Triglyceride (mg/dL) HDL (mg/dL) LDL (mg/dL) VLDL (mg/dL) LDL/HDL ratio Total Cynaroside web cholesterol (mg/dL) Total cholesterol/HDL HbA1c ( ) Lean (n = 8) 2/6 28.1 ?4.5 23.1 ?0.6 83.9 ?1.9 9.4 ?1.6 1.94 ?0.32 94.9 ?16.6 59.8 ?4.1 94.4 ?8.3 19.0 ?3.3 1.7 ?0.2 173.2 ?7.5 3.0 ?0.3 5.4 ?0.1 Obese (n = 32) 8/24 49.5 ?2.4** 36.6 ?1.2*** 95.9 ?2.4* 21.8 ?2.5* 5.31 ?0.68* 145.8 ?20.5 53.8 ?2.1 115.6 ?4.8* 29.2 ?4.1 2.2 ?0.1* 195.2 ?6.2 3.8 ?0.2* 5.7 ?0.Mean ?SE; *p < 0.05; **p < 0.001; ***p < 0.Moreover, the plasma LDL level (115.6 ?4.8 vs. 94.4 ?8.3, p < 0.05), low-density lipoprotein (LDL)/high-density lipoprotein (HDL) ratio (2.2 ?0.1 vs. 1.7 ?0.2, p < 0.05), and total cholesterol/HDL ratio (3.8 ?0.2 vs. 3.0 ?0.3, p < 0.05) all showed significant elevation. These findings suggest that the obese group had impairment in insulin signaling, concurrent with aberrant glucose and lipid metabolism.mtDNAn was reduced in obese subjectsResultsMetabolic changes in obese subjectsAmong the 40 participants, 32 people had a BMI greater than 30 (mean value = 36.6; referred to later as obese group) and 8 showed BMI below 25 (mean value = 23.1; referred to later as lean group), with the difference between the two groups being significant (p < 0.0001). As shown in Table 1 and Additional file 1: Figure S1, the obese group showed a significant impairment in fasting glucose (95.9 ?2.4 vs. 83.9 ?1.9 in the lean group, p < 0.05), and fasting insulin levels dramatically increased (21.8 ?2.5 vs. 9.4 ?1.6 in the lean group, p < 0.05), suggestive of impaired insulin sensitivity or development of insulin resistance [37, 38]. Insulin resistance was further confirmed by the HOMA-IR value, which was 2.7-fold (p < 0.05) higher in the obese group than in the lean one.The mitochondrial genome or mtDNA encodes 13 protein components of the respiration chain that underpin mitochondrial function [39, 40]. We found that the mtDNAn in the obese group was 6.9-fold lower (delta log-mtDNAn = 0.84, p < 0.001) when compared with their lean counterparts (Fig. 1). Given the significant age difference shown in Table 1 and Additional file 1: Figure S1, we conducted an age-matched analysis of mtDNAn, which indicated an mtDNAn tenfold lower (delta log-mtDNAn = 0.99, p < 0.05) in obese the group than in the lean group (Additional file 2: Figure S2). This is consistent with a previous report showing lower mitochondrial content in the skeletal muscle and adipose tissues from obese individuals [7?, 11]. Because changes in mtDNAn can affect the integrity, assembly, and operation of the mitochondrial respiratory chain [41, 42], it is conceivable that the mitochondrial function or capacity is impaired in obese subjects.Alteration of mtDNAn was associated with insulin resistanceTo examine how mtDNAn alteration was associated with the metabolic changes in obese subjects, we compared the mtDNAn in the insulin-sensitive (InS) groupZheng et al. Clinical Epigenetics (2015) 7:Page 3 ofless than 125 mg/DL indicates impaired fasting glucose (IFG) [46]. In the IFG group, the fasting glucose level was 111 mg/dL on average, significantly higher than that of the NFG group (86 mg/dL on average, p < 0.0001). However, the mtDNAn values of these two groups showed no significant PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27864321 difference (Fig. 3). In addition, mtDNAn did not c.