Diallyl Trisulfide Prevents Adipogenesis and Lipogenesis by Regulating the Transcriptional Activation Function of KLF15 on PPARγ to Ameliorate Obesity

Hu, Yanzhou; Xu, Jia; Gao, Ruxin; Xu, Ye; Huangfu, Bingxin; Asakiya, Charles; Huang, Xiao Ping; Zhang, Feng; Huang, Kunlun; He, Xiaoyun; Luo, Yunbo

doi:10.1002/mnfr.202200173

Cited by 7 publications

(3 citation statements)

References 52 publications

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“…Previous studies reported that KLF15 was involved in regulating adipogenesis (Fan et al, 2022;Hu et al, 2022;Raza et al, 2022). In high-fat feeding, KLF15 −/− mice were resistant to hepatic insulin resistance and fatty liver and responded to pharmacological induction of endoplasmic reticulum stress.…”

Section: Klf15 and Lipidmentioning

confidence: 95%

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

Chen

Li²,

Du³

2023

Front. Pharmacol.

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Liver diseases, characterized by metabolic disorder, have become a global public health problem with high morbidity and mortality. Krüppel-like factor 15 (KLF15) is a zinc-finger transcription factor mainly enriched in liver. Increasing evidence suggests that hepatic KLF15 is activated rapidly during fasting, and contributes to the regulation of gluconeogenesis, lipid, amino acid catabolism, bile acids, endobiotic and xenobiotic metabolism. This review summarizes the latest advances of KLF15 in metabolic reprogramming, and explore the function of KLF15 in acute liver injury, hepatitis B virus, and autoimmune hepatitis. which aims to evaluate the potential of KLF15 as a therapeutic target and prognostic biomarker for liver diseases.

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Section: Klf15 and Lipidmentioning

confidence: 95%

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

Chen

Li²,

Du³

2023

Front. Pharmacol.

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“…Six hours post-transfection, the medium was replaced with fresh medium containing 5 μmol/L of SFN or DMSO. Cells were harvested 48 h after transfection, and the luciferase activity was measured using a dual-luciferase reporter assay kit (DL101-01, Vazyme, Nanjing, China) and enzyme labeling instrument (Thermo Fisher, USA) [30], following manufacturer's instructions.…”

Section: Dual-luciferase Reporter Assaymentioning

confidence: 99%

Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization

Huang,

Xu,

et al. 2024

Food Science and Human Wellness

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Non-alcoholic fatty liver disease (NAFLD) has become a global issue and a severe threat to public health. However, to date, no approved therapeutic drugs have been developed. Dietary interventions with natural products have shown promise in preventing and treating NAFLD. Sulforaphane (SFN) is a phytocompound with antioxidant and anti-inflammatory properties, and previous research has demonstrated that SFN can ameliorate hepatic lipid accumulation and inflammation. However, the molecular mechanisms underlying these beneficial effects remain unclear. In this study, we confirmed the protective effects of SFN on excessive lipid accumulation and inflammatory injury in a high-fat, high-fructose diet-induced non-alcoholic steatohepatitis (NASH) mouse model. We found that SFN attenuates the inflammatory injury in a macrophage cell line and the liver of NASH mice, owing to the promotion of M1-type macrophage polarization toward the M2-type and the regulation of inflammatory mediators. Further analysis demonstrated that this SFN-induced macrophage M2-type polarization occurs in a Krüppel-like factor 4 (KLF4)-dependent manner. In summary, we uncovered a new mechanism of action underlying SFN activity and provide evidence that dietary intervention with SFN might be protective against NASH.

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“…When garlic is chopped or crushed, alliin is released and then hydrolyzed into allicin by allicinase. Allicin in vitro breaks down into a variety of fat-soluble organosulfur compounds, including diallyl trisulfide (DATS), diallyl disulfide (DADS), and diallyl sulfide (DAS) (5)(6)(7). The high permeability of allicin through cell membranes and rapid reaction with free thiol groups promote its diverse biological and therapeutic functions (8).…”

Section: Introductionmentioning

confidence: 99%

Effects of allicin on human Simpson-Golabi-Behmel syndrome cells in mediating browning phenotype

Ali

Wabitsch²,

Tews³

et al. 2023

Front. Endocrinol.

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IntroductionObesity is a major health problem because it is associated with increased risk of cardiovascular disease, diabetes, hypertension, and some cancers. Strategies to prevent or reduce obesity focus mainly on the possible effects of natural compounds that can induce a phenotype of browning adipocytes capable of releasing energy in the form of heat. Allicin, a bioactive component of garlic with numerous pharmacological functions, is known to stimulate energy metabolism.MethodsIn the present study, the effects of allicin on human Simpson-Golabi-Behmel Syndrome (SGBS) cells were investigated by quantifying the dynamics of lipid droplets (LDs) and mitochondria, as well as transcriptomic changes after six days of differentiation.ResultsAllicin significantly promoted the reduction in the surface area and size of LDs, leading to the formation of multilocular adipocytes, which was confirmed by the upregulation of genes related to lipolysis. The increase in the number and decrease in the mean aspect ratio of mitochondria in allicin-treated cells indicate a shift in mitochondrial dynamics toward fission. The structural results are confirmed by transcriptomic analysis showing a significant arrangement of gene expression associated with beige adipocytes, in particular increased expression of T-box transcription factor 1 (TBX1), uncoupling protein 1 (UCP1), PPARG coactivator 1 alpha (PPARGC1A), peroxisome proliferator-activated receptor alpha (PPARA), and OXPHOS-related genes. The most promising targets are nuclear genes such as retinoid X receptor alpha (RXRA), retinoid X receptor gamma (RXRG), nuclear receptor subfamily 1 group H member 3 (NR1H3), nuclear receptor subfamily 1 group H member 4 (NR1H4), PPARA, and oestrogen receptor 1 (ESR1).DiscussionTranscriptomic data and the network pharmacology-based approach revealed that genes and potential targets of allicin are involved in ligand-activated transcription factor activity, intracellular receptor signalling, regulation of cold-induced thermogenesis, and positive regulation of lipid metabolism. The present study highlights the potential role of allicin in triggering browning in human SGBS cells by affecting the LD dynamics, mitochondrial morphology, and expression of brown marker genes. Understanding the potential targets through which allicin promotes this effect may reveal the underlying signalling pathways and support these findings.

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Diallyl Trisulfide Prevents Adipogenesis and Lipogenesis by Regulating the Transcriptional Activation Function of KLF15 on PPARγ to Ameliorate Obesity

Cited by 7 publications

References 52 publications

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

Krüppel-like factor 15 in liver diseases: Insights into metabolic reprogramming

Sulforaphane ameliorates non-alcoholic steatohepatitis by KLF4-mediated macrophage M2 polarization

Effects of allicin on human Simpson-Golabi-Behmel syndrome cells in mediating browning phenotype

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