Peroxisome proliferator-activated receptor A/G reprogrammes metabolism associated with lipid accumulation in macrophages

Ye, Guozhu; Gao, Han; Lin, Yi; Ding, Dongxiao; Liao, Xu; Zhang, Han; Chi, Yulang; Dong, Shuang

doi:10.1007/s11306-019-1485-6

Cited by 9 publications

(4 citation statements)

References 42 publications

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“…Other studies suggest that higher levels of arachidonoylglycerophosphocholine are linked to thyroid and colon tumors. Oleate is known for its extensive physiological regulatory functions, stimulating fatty acid transport protein 1-mediated fatty acid uptake and inhibiting ATP-binding cassette transporters ABCA1/G1-mediated cholesterol efflux, leading to accumulation of neutral lipids, fatty acids, total cholesterol, and cholesterol esters in macrophages, thus influencing disease progression [ 43 – 45 ]. Our study’s findings echo recent research emphasizing the importance of metabolic reprogramming in LC progression.…”

Section: Discussionmentioning

confidence: 99%

The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data

Wu,

Liu,

Shi

et al. 2024

BMC Cancer

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Background Metabolic dysregulation is recognized as a significant hallmark of cancer progression. Although numerous studies have linked specific metabolic pathways to cancer incidence, the causal relationship between blood metabolites and lung cancer risk remains unclear. Methods Genomic data from 29,266 lung cancer patients and 56,450 control individuals from the Transdisciplinary Research in Cancer of the Lung and the International Lung Cancer Consortium (TRICL-ILCCO) were utilized, and findings were replicated using additional data from the FinnGen consortium. The analysis focused on the associations between 486 blood metabolites and the susceptibility to overall lung cancer and its three major clinical subtypes. Various Mendelian randomization methods, including inverse-variance weighting, weighted median estimation, and MR-Egger regression, were employed to ensure the robustness of our findings. Results A total of 19 blood metabolites were identified with significant associations with lung cancer risk. Specifically, oleate (OR per SD = 2.56, 95% CI: 1.51 to 4.36), 1-arachidonoylglyceropholine (OR = 1.79, 95% CI: 1.22 to 2.65), and arachidonate (OR = 1.67, 95% CI: 1.16 to 2.40) were associated with a higher risk of lung cancer. Conversely, 1-linoleoylglycerophosphoethanolamine (OR = 0.57, 95% CI: 0.40 to 0.82), ADpSGEGDFXAEGGGVR, a fibrinogen cleavage peptide (OR = 0.60, 95% CI: 0.47 to 0.77), and isovalerylcarnitine (OR = 0.62, 95% CI: 0.49 to 0.78) were associated with a lower risk of lung cancer. Notably, isoleucine (OR = 9.64, 95% CI: 2.55 to 36.38) was associated with a significantly higher risk of lung squamous cell cancer, while acetyl phosphate (OR = 0.11, 95% CI: 0.01 to 0.89) was associated with a significantly lower risk of small cell lung cancer. Conclusion This study reveals the complex relationships between specific blood metabolites and lung cancer risk, highlighting their potential as biomarkers for lung cancer prevention, screening, and treatment. The findings not only deepen our understanding of the metabolic mechanisms of lung cancer but also provide new insights for future treatment strategies.

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Section: Discussionmentioning

confidence: 99%

The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data

Wu,

Liu,

Shi

et al. 2024

BMC Cancer

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“…In our experiment, ACO, CPT1a, PPARα, and PPARδ were upregulated while SCD1 was downregulated under hypothermia, which was consistent with the study on Larimichthys Crocea [ 61 ]. Additionally, as a possible biomarker, glycine may be able to evaluate lipid accumulation as well as the lipid-lowering effects of PPARA/G in oleate-treated macrophages [ 21 ]. The activation of the PPAR pathway can also inhibit insulin sensitivity, thus could reduce glucose content [ 62 ], which was also confirmed in our study, evidenced by the decreased glucose and upregulated PPAR related genes.…”

Section: Discussionmentioning

confidence: 99%

“…PPARs play a significant role in adipogenesis, lipid metabolism, as well as maintenance of metabolic homeostasis, and are associated with a variety of metabolic related diseases, such as diabetes [ 17 , 18 , 19 ]. Additionally, it has been reported that PPARα also plays a role in in regulating the oxidation of fatty acids and amino acid metabolism [ 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

PPAR Signaling Maintains Metabolic Homeostasis under Hypothermia in Freshwater Drum (Aplodinotus grunniens)

Chen

Xue

et al. 2023

Metabolites

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Aplodinotus grunniens, known as freshwater drum, is a kind of eurythermal freshwater fish that is widely distributed in North America. In 2019, our research group reached a milestone on its artificial breeding and cultivation and have investigated its physiological adaption to the environment, providing a breakthrough and prospects for aquaculture. However, its adaptability and metabolic homeostasis to hypothermia is not fully understood. In this experiment, cold stress was conducted at 18 °C (LT18) and 10 °C (LT10) with 25 °C as control (Con) for 8 days to explore the effects of short-term hypothermia on the physiology and metabolism of freshwater drum. From the results, the level of free essential amino acids in LT18 and LT10 decreased significantly after 2 days cold stress compared with Con. Furthermore, plasma total triglyceride (TG) content and lipase (LPS) activity were decreased at LT10 for 2d. With RNA-seq in the liver, metabolic-related signaling, especially amino acid synthesis and lipid metabolism, was inhibited by hypothermia. Specifically, the PPAR signaling pathway is correlated with the inhibition of lipid and amino acid metabolism induced by hypothermia. These data confirmed that PPAR signaling maintains lipid and amino acid metabolic homeostasis during cold stress. These results give a theoretical foundation for hypothermia resistance in the area of metabolic homeostasis for freshwater drum.

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“…In addition, peroxisome proliferator-activated receptors is an essential roles in glucose and lipid metabolic processes. 29) Easily binding polyunsaturated fatty acids, PPAR-α accelerates β-oxidation of adipocytes in islet β cells and the clearance of fat in insulin-sensitive organs, resulting in increased insulin secretion under glucose stimulation. 30,31) It reported that the protection of mice with macrophage-specific JNK deficiency against insulin resistance was associated with reduced tissue infiltration by macrophages.…”

Section: Discussionmentioning

confidence: 99%

<i>Dendrobium officinale</i> Attenuates Myocardial Fibrosis <i>via</i> Inhibiting EMT Signaling Pathway in HFD/STZ-Induced Diabetic Mice

Zeng

et al. 2020

Biological & Pharmaceutical Bulletin

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Cardiac fibrosis is a major contributor for diabetic cardiomyopathy and Dendrobium officinale possessed therapeutic effects on hyperglycemia and diabetic cardiomyopathy. To further investigate the possible mechanisms of the Dendrobium officinale on diabetic myocardial fibrosis in mice. Water-soluble extracts of Dendrobium officinale (DOE) from dry stem was analyzed by HPLC and phenol-sulfuric acid method. Diabetic mice were induced by intraperitoneal injection of streptozotocin (STZ) (30 mg/kg) for 4 consecutive days after intragastric administration of a high-fat diet (HFD) for 2 weeks. The groups were as follows: control group, model group, DOE low, medium, high dose group (75, 150, 300 mg/kg) and Metformin positive group (125 mg/kg). The results showed that DOE dose-dependently lower serum insulin, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and grew the high-density lipoprotein cholesterol (HDL-C) after 12 weeks of daily administration with DOE. Hematoxylin-eosin staining and Sirius red staining showed obvious amelioration of cardiac injury and fibrosis. In addition, the result of immunoblot indicated that DOE increased the expression of peroxisome proliferator activated receptor-α (PPAR-α), phosphorylation of insulin receptor substrate 1 (p-IRS1) and E-cadherin and repressed the expression of transforming growth factor β1 (TGF-β1), phosphorylation of c-Jun N-terminal kinase (p-JNK), Twist, Snail1 and Vimentin. The present findings suggested that DOE ameliorated HFD/STZ-induced diabetic cardiomyopathy (DCM). The possible mechanism mainly associated with DOE accelerating lipid transport, inhibiting insulin resistant and suppressing fibrosis induced by epithelial mesenchymal transition (EMT).

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Peroxisome proliferator-activated receptor A/G reprogrammes metabolism associated with lipid accumulation in macrophages

Cited by 9 publications

References 42 publications

The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data

The associations between dysregulation of human blood metabolites and lung cancer risk: evidence from genetic data

PPAR Signaling Maintains Metabolic Homeostasis under Hypothermia in Freshwater Drum (Aplodinotus grunniens)

<i>Dendrobium officinale</i> Attenuates Myocardial Fibrosis <i>via</i> Inhibiting EMT Signaling Pathway in HFD/STZ-Induced Diabetic Mice

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