In this study, we have clearly established that TG48 is a SFA-rich TG species. Since SFAs are inflammatory 
, their increased levels reflect increased inflammation in renal patients. The association between SFAs and inflammation and their mechanisms has been well studied. SFAs inhibit the activation of insulin receptor substrate 1, which causes insulin resistance and contributes to metabolic syndrome 
. This inhibition could occur in insulin-sensitive cells like white adipose tissue, muscle, heart and liver 
. SFAs cause the activation of the mitogen-activated protein kinases and subsequent induction of inflammatory genes in white adipose tissue, immune cells, and mitotubes. SFAs decrease adiponectin production, which decreases the oxidation of glucose and fatty acids 
. SFAs cause recruitment of immune cells, such as macrophages, neutrophils, and bone marrow-derived dendritic cells to white adipose tissue and muscle. Palmitate but not linoleate activates macrophages 
which lead to the production of cytokine interleukin-6 in coronary artery endothelial cells and coronary artery smooth muscle cells 
. Excess palmitate causes white adipose tissue dysregulation 
. It also increases inflammation and apoptosis through oxidative or endoplasmic reticulum stress and generation of reactive oxygen species. Oleate co-supplementation blocks palmitate-mediated suppression of β-oxidation, insulin sensitivity, and DG accumulation. These experiments suggest that SFAs are inflammatory, while the unsaturated fatty acids are not 
. Furthermore, higher polyunsaturated fatty acids, such as eicosapentaenoic and docosahexaenoic, have anti-inflammatory effects by inhibiting cyclooxygenase 2 and demonstrate the ability to reduce plasma concentrations of C-reactive protein (CRP), tumor necrotizing factor-α and interleukin-6 
. Interestingly, the carbon flux from a carbohydrate diet is converted to palmitate in the liver during endogenous lipogenesis 
. Thus, a diet rich in carbohydrates can also be inflammatory.
As shown in , TG increased in patients with HD and CKD relative to levels in control subjects. TG48 also increased from controls to HD and to CKD. However, TG48/TG ratios (or TG48%/TG) are not the same for the three groups. TG48%/TG significantly (p<0.0005) increased from controls (1.7%±2.9%) to HD (4.2%±2.6%) and to CKD (5.2%±3.2%). This means that when TG is increased, TG48 is disproportionately increased. This results in the longer-chain TG species (TG50+TG52+TG54+TG56), increased less proportionally, because the sum of TG48+TG50+TG52+TG54+TG56 equals TG.
As shown by Byrdwell 
, the longer the carbon chain length of the fatty acids, the higher the unsaturation of the TG. Thus, TG48 possesses relatively higher number of SFAs than those of TG50, TG52, TG54 and TG56. Therefore, increasing TG results in increasing more of TG48, thus, increasing more of SFAs and concomitantly increasing inflammation.
We observed that subjects with increased TG without renal disease also have increased TG48 (unpublished data). So the presence of measurable TG48 by GC is not a unique marker for renal disease. It is actually a reflection of the increased SFAs, therefore a reflection of increased inflammation. Indeed, hypertriglyceridemia is also known to be associated with increased inflammation.
The presently established link between OS/inflammation and apoC-III bound to apoB-containing lipoproteins is further enhanced by the recently reported findings 
that apoC-III, or its corresponding apoB-containing lipoproteins, were also proinflammatory as demonstrated by increasing endothelial cell expression of vascular and intercellular cell adhesion molecules and recruitment of monocytic cell. It is not surprising to see that TG48 is well correlated with apoC-III. Is there a cause- effect relationship between apoC-III and TG48? We are not certain. We may rationalize that when apoC-III is increased, TG would increase, since over expression of apoC-III
gene could cause hypertriglyceridemia 
. Our data indicate that when TG is increased, TG48 is increased more than the other TG molecular species. This implies that increased apoC-III could cause the increase of TG48 and thus increased levels of SFA. On the other hand, a diet rich in SFAs might increase TG. Would increased TG cause the increase of apoC-III? There might be such a possibility. However, more research is needed to answer this question unequivocally.
Inflammation causes the generation of reactive oxygen species 
. This may be why inflammation is closely associated with OS and vice versa. Several studies support a link between OS and inflammation in atherogenesis 
. Our data showing that OS index R2 correlated with TG48 may support this notion.
A number of studies have suggested that increased OS in association with inflammation contributes significantly to the accelerated kidney dysfunction and its consequential cardiovascular morbidity and mortality 
. Most of the previously described procedures to access OS are rather complicated and time consuming 
; however, our presently described method does not require treatment with chemical reagents, monoclonal antibodies, incubation, isolation of lipid classes or transesterification and therefore, provide a direct and very useful simplification. The main advantage of the GC method besides simplicity and speed is high reproducibility. R2 values have shown that a combination of OS and the levels of apoC-III in a binary system predict the risk for atherosclerosis in normolipidemic and hypertriglyceridemic subjects 
. Cholesteryl ester ratio method has also been successfully used to monitor the delay of OS recovery in patients with diabetic ketoacidosis after correction of ketoacidosis with insulin 
. Inflammation levels have been most frequently measured by CRP 
and interleukin-6 
. Both of these proteins are the results of inflammation. In contrast, SFAs measured by TG48 are the causes of inflammation.
Our data show that the inflammation measured by TG48 is correlated with TG, not CE. Since TG48 is part of the total TG, in general, the higher the TG, the higher the TG48, thus the higher the SFA and the higher the inflammation. Indeed, higher TG is associated with higher OS, as also shown by the CE-ratio method, but TG alone does not represent TG48 because the TG48/TG ratio is not a constant among different subjects.
Abnormalities of lipid and apolipoprotein profiles of CKD and HD patients confirmed and extended the results of our previous studies 
. Moreover, based on correlation coefficients between R2 and especially, TG48 and lipid, apolipoprotein, and lipoprotein-cholesterol levels, it was established that inflammation is highly correlated with the concentrations of TG and VLDL-C, moderately correlated with apoC-III bound to apoB-containing lipoproteins, and weakly with apoC-III, but not with TC, LDL-C nor with HDL-C. These results suggest that the high inflammation of renal patients stems more from TG-rich lipoproteins, not CE-rich apoB lipoproteins. The highly selective correlation of inflammation with TG or apoC-III-containing apoB lipoproteins, but not with cholesterol-rich apoB lipoproteins, was confirmed by the results of multivariate regression analysis showing a stronger relationship between TG48 and VLDL-C over LDL-C (15 times stronger for VLDL-C than that for LDL-C as shown by the equation #1).
Results from our study and those of other laboratories have already shown the significant role played by apoC-III bound to apoB-containing lipoproteins in the formation and progression of atherosclerotic lesion 
. Specifically, renal insufficiency resulting in elevated apoC-III, or LpB:C-III, presumably via insulin resistance triggers the chain of inflammatory events 
. Taken together, findings of the present study suggest that TG-rich apoC-III-containing apoB lipoproteins are linked to inflammation, while TC-rich apoB lipoproteins are not. It remains to be determined whether there are differences in the degree of inflammation between apolipoprotein-defined apoC-III-containing lipoproteins, including LpB:C, LpB:C:E and LpA-II:B:C:D:E particles.
The use of the TG48 marker revealed that HD patients had significantly lower inflammation and partially reduced levels of lipoprotein variables than CKD patients, suggesting a beneficial effect of haemodialysis that alleviates the uremic intoxication but cannot eliminate the underlying metabolic disturbance that persists during dialysis.
It has been observed that increased OS is already prevalent in CKD patients before dialysis 
. Our findings on increased OS/inflammation in renal patients are in agreement with the literature reports 
. This is the first report using TG48 for measuring SFAs and inflammation. This is also the first report to relate SFAs and inflammation with lipids and lipoproteins, and particularly, with apoC-III and apoC-III-containing apoB lipoproteins.
The major finding of this study is the recognition of TG48 as a new inflammatory factor characterized by the occurrence of inflammatory saturated fatty acids. The levels of TG48 had been found to be elevated in patients with chronic renal disease in comparison with those of normolipidemic subjects. The TG48 levels were correlated with the levels of TG, VLDL-C, apoC-III and apoC-III bound to apoB-containing lipoprotein subclasses, but not with TC, LDL-C and HDL-C in kidney patients. Furthermore TG48 is also correlated with oxidative stress. The well established dual role of apoC-III in inflammation and atherogenesis in combination with oxidative stress and inflammatory TG48 should be considered as severe risk factors for atherogenesis in chronic kidney disease. Further studies are needed to establish the occurrence of similar risk factors for atherogenesis in other dyslipoproteinemics.