N-acetylcysteine (NAC) possesses a strong capability to ameliorate high-fat diet (HFD)-induced
non-alcoholic fatty liver disease (
NAFLD) in mice, but the underlying mechanism is still unknown. Our study aimed to clarify the involvement of
long non-coding RNA (
lncRNA) in the beneficial effects of NAC on HFD-induced
NAFLD. C57BL/6J mice were fed a normal-fat diet (10 % fat), a HFD (45 % fat) or a HFD plus NAC (2 g/l). After 14-week of intervention, NAC rescued the deleterious alterations induced by HFD, including the changes in body and liver weights, hepatic TAG, plasma
alanine aminotransferase, plasma
aspartate transaminase and liver histomorphology (haematoxylin and
eosin and
Oil red O staining). Through whole-transcriptome sequencing, 52 167 (50 758 known and 1409 novel) hepatic
lncRNA were detected. Our cross-comparison data revealed the expression of 175
lncRNA was changed by HFD but reversed by NAC. Five of those
lncRNA, lncRNA-NONMMUT148902·1 (NO_902·1),
lncRNA-XR_001781798·1 (XR_798·1), lncRNA-NONMMUT141720·1 (NO_720·1),
lncRNA-XR_869907·1 (XR_907·1), and lncRNA-ENSMUST00000132181 (EN_181), were selected based on an absolute log2 fold change value of greater than 4, P-value < 0·01 and P-adjusted value < 0·01. Further qRT-PCR analysis showed the levels of
lncRNA-NO_902·1,
lncRNA-XR_798·1, and
lncRNA-EN_181 were decreased by HFD but restored by NAC, consistent with the
RNA sequencing. Finally, we constructed a
ceRNA network containing
lncRNA-EN_181, 3
miRNA, and 13
mRNA, which was associated with the NAC-ameliorated
NAFLD. Overall,
lncRNA-EN_181 might be a potential target in NAC-ameliorated
NAFLD. This finding enhanced our understanding of the biological mechanisms underlying the beneficial role of NAC.