The global rise in
prediabetes and diabetes, with
type 2 diabetes (T2DM) being predominant, highlights the association between T2DM and
hypertriglyceridemia (HTG). Patients with both abnormal
glucose levels and HTG require increased attention due to higher risks of complications and mortality. Therefore, this study aimed to find the key
long non-coding RNA (
lncRNA) of HTG in the abnormal
glucose metabolism patients. We collected blood samples for
RNA sequencing experiments and blood samples for validation in population. We have conducted
RNA sequencing, weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR) in a 82-vs-82-sample-size population and
insulin induced HepG2,
RNA- Fluorescence in situ hybridization (FISH) and Cell Counting Kit-8 (CCK-8). We also explored lipid metabolism related
transcription factor and the related
protein expression and processed key
lncRNA by both interference expression and overexpression, and the related consequences were rescued by its target
mRNA. ENST00000540317.5 (LINC317.5) was lower in HTG with abnormal
glucose metabolism and was found in both cytoplasm and nucleus in HepG2, inversely regulating the accumulation of TG and its target
mRNA TKFC. Relative expression of
peroxisome proliferator-activated receptor alpha (PPARĪ±) and
peroxisome proliferator-activated receptor gamma (PPARĪ³) were decreasing, and
SREBP-1c (
sterol regulatory element-binding protein-1c) was increasing of the interference expression of LINC317.5. Interference expression of LINC317.5 significantly decreased the
protein expression of ACADM and CPT1A, whereas increased the
protein expression of FAS and ACC1. TKFC partly reduced the
triglyceride (TG) accumulation of LINC317.5. In conclusion, we suggested LINC317.5-TKFC as a key for TG accumulation in the HepG2-insulin resistant (IR). These might provide information of non-invasive
biomarkers for the HTG with abnormal
glucose.