A mouse model of short‐term, diet‐induced fatty liver with abnormal cardiolipin remodeling via downregulated Tafazzin gene expression

Abstract

Background Cardiolipin (CL) helps maintain mitochondrial structure and function. Here we investigated whether a high carbohydrate diet (HCD) fed to mice for a short period (5 days) could modulate the CL level, including that of monolysoCL (MLCL) in the liver. Results Total CL in the HCD group was 22% lower than that in the normal chow diet (NCD) group (P < 0.05). The CL72:8 level strikingly decreased by 93% (P < 0.0001), whereas total nascent CLs (CLs other than CL72:8) increased (P < 0.01) in the HCD group. The total MLCL in the HCD group increased by 2.4‐fold compared with that in the NCD group (P < 0.05). Tafazzin expression in the HCD group was significantly downregulated compared with that in the NCD group (P < 0.05). A strong positive correlation between nascent CL and total MLCL (r = 0.955, P < 0.0001), and a negative correlation between MLCL and Tafazzin expression (r = −0.593, P = 0.0883) were observed. Conclusion A HCD modulated the fatty acid composition of CL and MLCL via Tafazzin in the liver, which could lead to mitochondrial dysfunction. This model may be useful for elucidating the relationship between fatty liver and mitochondrial dysfunction. © 2021 Society of Chemical Industry

Food-Derived β-Carboline Alkaloids Ameliorate Lipid Droplet Accumulation in Human Hepatocytes

“…After 24 h, the cells were treated with PBS, 0.25 mM OA only, 0.25 mM OA plus 200 and 400 μM compound 2 , or 0.25 mM OA plus 200 and 400 μM compound 4 . After another 24 h, RNA extraction and complementary DNA synthesis were performed, according to the manufacturer’s instructions and a previous study [ 49 ]. The sequences of the primers used are shown in the Supplementary Materials, Table S1 : adipose triglyceride lipase ( ATGL ), diacylglycerol O-acyltransferase 1 ( DGAT1 ), sterol regulatory element-binding protein 1 ( SREBP1 ), fatty acid synthase ( FASN ), stearoyl-CoA desaturase 1 ( SCD1 ), and glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ).…”

Kaempferol Improves Cardiolipin and ATP in Hepatic Cells: A Cellular Model Perspective in the Context of Metabolic Dysfunction-Associated Steatotic Liver Disease

“…CL is a lipid necessary for mitochondrial energy metabolism [ 8 ]. CL72:8, which contains four LA molecules, is the mature and functional form, and CL72:8 is the major component of hepatocytes in vivo [ 37 ]. In cultured C3A cells, the concentration of CL72:8 was only approximately 0.30% of the total concentration.…”

Identification of a β-Carboline Alkaloid from Chemoselectively Derived Vanilla Bean Extract and Its Prevention of Lipid Droplet Accumulation in Human Hepatocytes (HepG2)

“…This partially suggests the cleavage of glucoside metabolites to form aglycone metabolites and the appearance of new metabolites, including 34. The GNPS molecular network generated the data of ion parent detected from the BE initial sample (in green color), BE derivatized sample (purple), and a combination of both extract samples, leading to the identification of 16 molecules (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50), including the unknown ion parent predicted to be β-carboline alkaloid 34 (Figure 3). The ion parents are represented by nodes in the molecular network (MN), with chemically related metabolites clustered together.…”

“…The classical MN workflow using the GNPS platform was performed as described in Section 3.3.2.B. Metabolite dereplication revealed that 33 parent ions matched known metabolites (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50)(51) in the GNP library. The parent ions from liquid chromatography with tandem mass spectrometry (LC-MS/MS) analysis of the modified extracts were dereplicated as follows: β-carboline alkaloids compound (34), L -5-hydroxy-tryptophan (35), L -Kynurenine (36), hypnophilin (37), L-tryptophan (38), isocitrate| (39), 13a-Hydroxylupanin (40), MoNA:2488524 2 (41), ethylene Thiourea (42), N-Hydroxytetraadecanoylleucine (43), putrescine (44), 13-Docosenamide (45), 1-Hexadecanoyl-sn-glycerol (46), abrine (47), DL -Indole-3-lactic acid (48), MoNA:2488004 (49), and N-Acetylhistidine (50).…”

“…Gene expression analysis was performed using real-time PCR to investigate how supplementation of compound 34 during LDA in HepG2 cells affects lipolysis and lipogenesis. After another 24 h, RNA extraction and complementary DNA synthesis were performed according to the manufacturer's instructions as previously reported [15,49,50] and detailed in the Supplementary Information (Materials and Methods).…”