Abstract
The liver plays a central role in the glucose and lipid metabolism. Studies performed on animal models have shown an important role of lipid accumulation in the induction of insulin resistance. We sought to explain whether in obese humans, the insulin resistance is associated with hepatic ceramide accumulation. The experiments were conducted on obese men and women. Each gender was divided into three groups: Normal glucose tolerance group (NGT), Impaired glucose tolerance group (IGT), and Type 2 diabetic subjects (T2D). Ceramide (Cer) content was analyzed with the use of LC/MS/MS. An oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1c), percentage body fat (FAT%), and body mass index (BMI) was also measured. Total hepatic ceramide was significantly higher in T2D females as compared to NGT females (p < 0.05), whereas in males, total ceramide was significantly higher in IGT and T2D as compared to NGT (p < 0.05). In both, men and women, the highest increase in T2D subjects, was observed in C16:0-Cer, C18:0:-Cer, C22:0-Cer, and C24:0-Cer (p < 0.05) as compared to NGT group. Interestingly, glucose (at 0′ and at 120′ in OGTT) and HbA1c positively correlated with the ceramide species that most increased in T2D patients (C16:0-Cer, C18:0-Cer, C22:0-Cer, and C24:0-Cer). In men glucose and HbA1c significantly correlated with only C22:0-Cer. This is one of the few studies comparing hepatic ceramide content in severely obese patients. We found that, ceramide content increased in diabetic patients, both in men and women, and the content of ceramide correlated with glycemic parameters. These data indicate ceramide contribution to the induction of hepatic insulin resistance.
Highlights
Obesity is defined as an excess of body fat
Inclusion criteria for Normal glucose tolerance group (NGT), Impaired glucose tolerance group (IGT), and type 2 diabetes (T2D) groups were applied according to American Diabetes Association guidelines: NGT group—HbA1c < 5.7, one-point oral glucose tolerance test (OGTT) at 120 min < 140 mg/dL; IGT group—5.7 < HbA1c < 6.5, 140 mg/dL < OGTT at 120 min < 200 mg/dL, no T2D diagnosis and no prior medication; T2D group HbA1C > 6.5, OGTT at 120 min > 200 mg/dL, prior T2D diagnosis and medication
Within females and males groups, there were no significant differences in percentage body fat (%FAT) between NGT vs. IGT vs. T2D (Table 1)
Summary
Obesity is defined as an excess of body fat This state is associated with lipids accumulation in adipose tissue, and in other tissues, such as skeletal muscle and the liver. In some works, both short- and long-term feeding with a high fat diet did not lead to an increase of ceramides in the liver, despite the induction of insulin resistance [15,16,17]. The objective of the present study was to determine whether hepatic ceramide content is implicated in development of glucose metabolism disorders, including insulin resistance and T2D in obese men and woman with different levels of glucose metabolism disturbances. Our secondary goal was to observe any gender-specific differences between metabolic disturbances and hepatic ceramides
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