Si–Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation

Li, Jianchao; Wu, Kaiyi; Kuang, Jiangying; Huang, Nana; Guo, Xin; Du, Hang; Guo, Chong; Li, Rongrong; Zhu, Xiaomin; Zhang, Tianyu; Gong, Liping; Sheng, Lisong; Sun, Rong

doi:10.1016/j.jep.2022.115892

Cited by 4 publications

(3 citation statements)

References 57 publications

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“…AMP-activated protein kinase (AMPK) is a widely distributed serine/threonine protein kinase involved in a range of metabolic processes that play a vital role in energy metabolism and catabolism in WAT [ 28 , 35 , 36 ]. GLUT-4 is a key glucose transporter that promotes the use of extracellular glucose by insulin-sensitive cells to maintain blood glucose homeostasis [ 37 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice

et al. 2023

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Chitooligosaccharide (COS) is a natural product from the ocean, and while many studies have reported its important role in metabolic diseases, no study has systematically elaborated the anti-obesity effect and mechanism of COS. Herein, COSM (MW ≤ 3000 Da) was administered to diet-induced obese mice by oral gavage once daily for eight weeks. The results show that COSM administration reduced body weight; slowed weight gain; reduced serum Glu, insulin, NEFA, TC, TG, and LDL-C levels; increased serum HSL and HDL-C levels; improved inflammation; and reduced lipid droplet size in adipose tissue. Further lipidomic analysis of adipose tissue revealed that 31 lipid species are considered to be underlying lipid biomarkers in COS therapy. These lipids are mainly enriched in pathways involving insulin resistance, thermogenesis, cholesterol metabolism, glyceride metabolism and cyclic adenosine monophosphate (cAMP), which sheds light on the weight loss mechanism of COS. The Western blot assay demonstrated that COSM intervention can improve insulin resistance, inhibit de novo synthesis, and promote thermogenesis and β-oxidation in mitochondria by the AMPK pathway, thereby alleviating high-fat diet-induced obesity. In short, our study can provide a more comprehensive direction for the application of COS in obesity based on molecular markers.

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Section: Discussionmentioning

confidence: 99%

Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice

et al. 2023

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“…From the 5th week of the experiment, the rats of the SNS-L, SNS-H, and MET groups were orally given SNS (2 or 4 g/kg) or metformin (150 mg/kg) for 4 weeks, 15 , 19 and the rats in the CON and MOD groups received isovolumetric normal saline during this time, respectively. The low dose of SNS was determined by comparing the body surface area index between humans and rats.…”

Section: Methodsmentioning

confidence: 99%

“… 14 Network pharmacology-based analysis demonstrates that SNS significantly improves lipid accumulation in obesity through AMPK mediated lipolysis. 15 Our previous study revealed that SNS could improve lipid deposition in MAFLD rats induced by a high-fat and high-cholesterol diet (HFHCD). 16 However, whether this effect was through activating AMPK/SIRT1 signaling pathway or not remains unknown.…”

Section: Introductionmentioning

confidence: 99%

Si-Ni-San Reduces Hepatic Lipid Deposition in Rats with Metabolic Associated Fatty Liver Disease by AMPK/SIRT1 Pathway

Zhang,

Liu,

Wang

et al. 2023

DDDT

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Background Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood. Purpose The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways. Methods The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot. Results SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition. Conclusion SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.

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CTRP9 alleviates diet induced obesity through increasing lipolysis mediated by enhancing autophagy-initiation complex formation.

Lei,

Li,

Zuo

et al. 2024

The Journal of Nutritional Biochemistry

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Si–Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation

Cited by 4 publications

References 57 publications

Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice

Anti-Obesity Effect and Mechanism of Chitooligosaccharides Were Revealed Based on Lipidomics in Diet-Induced Obese Mice

Si-Ni-San Reduces Hepatic Lipid Deposition in Rats with Metabolic Associated Fatty Liver Disease by AMPK/SIRT1 Pathway

CTRP9 alleviates diet induced obesity through increasing lipolysis mediated by enhancing autophagy-initiation complex formation.

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