Curcumin represses lipid accumulation through inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis in porcine subcutaneous preadipocytes

Abstract

Objective: Excessive lipid accumulation in adipocytes results in prevalence of obesity and metabolic syndrome. Curcumin (CUR), a naturally phenolic active ingredient, has been shown to have lipid-lowering effects. However, its underlying mechanisms have remained largely unknown. Therefore, the study aims to determine the effect of CUR on cellular lipid accumulation in porcine subcutaneous preadipocytes (PSPA) and to clarify novel mechanisms.Methods: The PSPA were cultured and treated with or without CUR. Both cell counting Kit-8 and lactate dehydrogenase release assays were used to examine cytotoxicity. Intracellular lipid contents were measured by oil-red-o staining extraction and triglyceride quantification. Apoptosis was determined by flow cytometry and the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-nick end labelling assay. Adipogenic and apoptosis genes were analyzed by quantitative polymerase chain reaction and Western blot.Results: The CUR dose-dependently reduced the proliferation and lipid accumulation of PSPA. Noncytotoxic doses of CUR (10 to 20 μM) significantly inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and expression of adipogenic genes peroxisome proliferation-activity receptor-γ (PPAR-γ), CCAAT/enhancer binding protein-α, sterol regulatory element-binding protein-1c, adipocyte protein-2, glucose transporter-4 as well as key lipogenic enzymes fatty acid synthase and acetyl-CoA carboxylase, while ERK1/2 activation significantly reversed CUR-reduced lipid accumulation by increasing PPAR-γ. Furthermore, compared with differentiation induced media treated cells, higher dose of CUR (30 μM) significantly decreased the expression of AKT and B-cell lymphoma-2 (BCL2), while increased the expression of BCL-2-associated X (BAX) and the BAX/BCL-2 expression ratio, suggesting triggered apoptosis by inactivating AKT and increasing BAX/BCL-2 ratio and Caspase-3 expression. Moreover, AKT activation significantly rescued CUR inhibiting lipid accumulation via repressing apoptosis.Conclusion: These results demonstrate that CUR is capable of suppressing differentiation by inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis via decreasing AKT and subsequently increasing BAX/BCL-2 ratio and Caspase-3, suggesting that CUR provides an important method for the reduction of porcine body fat, as well as the prevention and treatment of human obesity.

Childhood obesity and curcumin: a possible effective anti-obesity adjunct

“…Hassan et al 36 who conducted a recent mechanistic study concluded curcumin does have the ability to exert potent antitoxic, anti-oxidant, tissue-protective, and anti-obesity effects, hence they recommended curcumin be added to various dietary regimens to prevent or delay organ dysfunction among obese people. Tsuda et al 37 similarly agree that curcumin has anti-obesity/anti-adipogenic and anti-diabetes biological properties among others, as also observed by Labban et al 38 and can be seen to have a high probability of preventing or reducing the magnitude of various obesity states through well defined biochemical signaling pathways and others that may be active even on preadipocytes, 39 as well as in reversing or modulating age and obesity associated metabolic diseases. 16,40 Most noteworthy is that it has also been shown that curcumin is a bioactive compound that may not only have multiple beneficial health and anti-oxidative effects, 41 but a beneficial effect on the course of SARS-CoV-2 infection and that might hence be helpful in the prevention of long-COVID complications-and others that are closely associated with cardiovascular diseases and obese states.…”

The effect of curcumin supplementation on circulating adiponectin and leptin concentration in adults: a GRADE-assessed systematic review and meta-analysis of randomised controlled trials

“…Various studies have pointed out the inhibitory effects of curcumin on NF- κ B signalling pathways as the main regulatory switcher of inflammatory pathways in cells (79,80) . Another possible effect of curcumin on adipokines can be related to transcription factors such as peroxisome proliferator-activated receptor- γ (PPAR γ ) (81) , sterol regulatory element-binding transcription factor 1 (82) , and CCAAT/enhancer-binding protein (C/EBP) (83) which affect the secretion of adipokines (84) . These transcription factors have various functions in the body including regulation of lipid metabolism, insulin sensitivity, inflammation and adipocyte differentiation.…”

Identification of Candidate Genes and Regulatory Competitive Endogenous RNA (ceRNA) Networks Underlying Intramuscular Fat Content in Yorkshire Pigs with Extreme Fat Deposition Phenotypes

“…Novel DEMiR-target genes have also been reported to be important for lipid metabolism and fat deposition ( Supplementary File S9 ), including novel-m0048-3p ( LEP , LEPR , LPL , CYB5R1 , VLDLR , CPT1A , PPARD ), novel-m0050-3p ( ACACA , PLIN1 , THRSP ), and novel-m0104-5p ( FFAR4 , PPARA , APOE ) [ 60 , 61 , 62 ]. Furthermore, KEGG and GO analyses revealed that the target genes of 36 DEMiRs were significantly enriched for terms and pathways related to fat cell differentiation, fatty acid biosynthesis, and lipid metabolism, such as the PPAR signaling pathway [ 63 ], PI3K–Akt signaling pathway [ 64 ], mTOR signaling pathway [ 65 ], and Wnt signaling pathway [ 66 ].…”