Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates insulin resistance and hepatic steatosis via PI3K/Akt/GSK3β pathway

Zheng, Xiaoya; Zhao, Mengge; Jiang, Cuihua; Sheng, Xueping; Yang, Huimin; Liu, Yao; Yao, Xiaoming; Zhang, Jian; Yin, Zhiqi

doi:10.1016/j.phymed.2019.153130

Cited by 40 publications

(33 citation statements)

References 30 publications

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“…Excessive lipid accumulation in hepatocytes is the hallmark of NAFLD (Bechmann et al., 2012). The results indicated that PA remarkably induces lipid accumulation in HepG2 cells, which was consistent with earlier studies (Zang et al., 2018; Zheng et al., 2020), while CA supplementation reversed the changes. Then, the lipid‐lowering mechanism of CA in HepG2 cells was explored.…”

Section: Resultssupporting

confidence: 91%

“…The oversupply of plasma FFAs to the liver leads to hepatic lipid accumulation, insulin resistance, glycogen reduction, and steatohepatitis with mitochondrial dysfunction, endoplasmic reticulum stress, and the release of reactive oxygen species (Buzzetti et al., 2016; Leamy, Egnatchik, & Young, 2013). PA is the most abundant saturated fatty acid in the liver and plasma of both normal and NAFLD subjects and can induce lipid and glucose metabolism disorders in human and rat liver cells (Araya et al., 2004; Zang, Fan, Chen, Huang, & Qin, 2018; Zheng et al., 2020). The HepG2 cells display most of the functional characteristics of normal human hepatocytes (Donato, Tolosa, & Gómez‐Lechón, 2015).…”

Section: Resultsmentioning

confidence: 99%

“…The HepG2 cells display most of the functional characteristics of normal human hepatocytes (Donato, Tolosa, & Gómez‐Lechón, 2015). In addition, HepG2 cells form part of an immortalized cell line with extended replicative capacity and stable phenotypes and are commonly used in the NAFLD model in vitro (Kanuri & Bergheim, 2013; Ren et al., 2018; Zang et al., 2018; Zheng et al., 2020). Therefore, in the study, PA was used in HepG2 cells to establish a cellular model in vitro .…”

Section: Resultsmentioning

confidence: 99%

“…An increase in glucose uptake causes a corresponding rise in intracellular glucose‐6‐phosphate to allosterically activate GS and subsequently promote glycogen synthesis. Phosphorylated AKT can also phosphorylate and inactivate GSK3β, leading to GS activation and glycogen synthesis (Ren et al., 2018; Yan et al., 2016; Zheng et al., 2020). Therefore, it was speculated that AKT was also likely to be targeted by CA, necessitating further research to confirm the additional CA mechanisms responsible for regulating lipid and glucose metabolism.…”

Section: Resultsmentioning

confidence: 99%

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Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Gai

Zhou

Zhang

et al. 2020

Journal of Food Science

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Impaired lipid and glucose metabolism in the liver is a crucial characteristic of nonalcoholic fatty liver disease (NAFLD). Coniferaldehyde (CA), a kind of phenolic compound found in many edible plants, has multiple biological and pharmacological functions. However, since the effect and molecular mechanism of CA on hepatic lipid and glucose metabolism disorders in NAFLD remain unknown, this study investigated its impact on the lipid and glucose metabolism of palmitic acid (PA)‐induced HepG2 cells. Compared with the HepG2 cells treated only with PA, supplementation with 25, 50, and 100 µM CA reduced the levels of intracellular triglyceride (by 7.11%, 19.62%, and 31.57%) and total cholesterol (by 8.46%, 23.32%, and 27.17%), and enhanced glucose uptake (by 40.91%, 57.49%, and 61.32%) and intracellular glycogen content (by 12.75%, 41.27%, and 53.77%). Moreover, CA supplementation downregulated the expression of sterol regulatory element‐binding protein‐1, fatty acid synthase, and stearoyl‐CoA desaturase 1 related to lipogenesis while upregulating the expression of carnitine palmitoyltransferase 1α related to fatty acid oxidation. CA supplementation also upregulated the glucose transporter 2 protein expression and phosphorylation of glycogen synthase kinase 3β while downregulating the phosphorylation of glycogen synthase. Most importantly, most of these effects of CA were reversed by pretreatment with AMP‐activated protein kinase (AMPK) inhibitor and small interfering RNA‐liver kinase B1 (LKB1). In conclusion, CA ameliorated the lipid and glucose metabolism in PA‐induced HepG2 cells via the LKB1/AMPK signaling pathway. Practical Application In this study, coniferaldehyde appeared to be effective in ameliorating hepatic lipid and glucose metabolism disorders in nonalcoholic fatty liver disease by reducing the levels of intracellular triglyceride and total cholesterol and enhancing glucose uptake and intracellular glycogen content via the LKB1/AMPK signaling pathway in vitro. Therefore, our findings provide new evidence in support of that supplementation with coniferaldehyde or food rich in coniferaldehyde might be considered as a viable dietary intervention strategy for preventing and treating nonalcoholic fatty liver disease.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 2 more Smart Citations

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Gai

Zhou

Zhang

et al. 2020

Journal of Food Science

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“…Because of the absence of an established pharmacotherapy, current recommendations for the treatment of NAFLD emphasize the management of lifestyle, including physical exercise and dietary modifications [11]. Functional fruits and vegetables with natural bioactive ingredients often possess strong anti-obesity, antioxidant and anti-inflammatory abilities, which may be ideal treatments for NAFLD and related metabolic disorders [12,13].…”

Section: Introductionmentioning

confidence: 99%

Dietary Platycodon grandiflorus Attenuates Hepatic Insulin Resistance and Oxidative Stress in High-Fat-Diet Induced Non-Alcoholic Fatty Liver Disease

Wang

Zhou

et al. 2020

Nutrients

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The root of Platycodon grandiflorus (PG), with hepatoprotective and anti-oxidation effects, has a long history of being used as food and herbal medicine in Asia. However, the mechanism of PG against non-alcoholic fatty liver disease (NAFLD) is still not clear. The aim of this study was to investigate the mechanism of PG suppressing the development of NAFLD induced by a high-fat diet (HFD) in mice. Male C57BL/6J mice were fed with either a standard chow diet or a HFD, either supplemented with or without PG, for 16 weeks. Serum lipids, liver steatosis, oxidative stress and insulin sensitivity were determined. Expressions or activities of hepatic enzymes in the related pathways were analyzed to investigate the mechanisms. PG significantly reduced HFD-induced hepatic injury and hyperlipidemia, as well as hepatic steatosis via regulating phosphorylation of acetyl-CoA carboxylase (p-ACC) and expression of fatty acid synthase (FAS). In addition, PG ameliorated oxidative stress by restoring glutathione (GSH) content and antioxidant activities, and improved insulin sensitivity by regulating the PI3K/Akt/GSK3β signaling pathway. Our data showed that dietary PG have profound effects on hepatic insulin sensitivity and oxidative stress, two key factors in the pathogenesis of NAFLD, demonstrating the potential of PG as a therapeutic strategy for NAFLD.

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In Vitro Propagation and Biotechnological Improvement Strategies of Plants with High-Intensity Sweetener and Anti-Diabetic Activities

Kairuz

Rivero-Aragón

Angenon

2021

Biotechnology of Anti-Diabetic Medicinal Plants

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Triterpenic acids-enriched fraction from Cyclocarya paliurus attenuates insulin resistance and hepatic steatosis via PI3K/Akt/GSK3β pathway

Cited by 40 publications

References 30 publications

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Coniferaldehyde ameliorates the lipid and glucose metabolism in palmitic acid‐induced HepG2 cells via the LKB1/AMPK signaling pathway

Dietary Platycodon grandiflorus Attenuates Hepatic Insulin Resistance and Oxidative Stress in High-Fat-Diet Induced Non-Alcoholic Fatty Liver Disease

In Vitro Propagation and Biotechnological Improvement Strategies of Plants with High-Intensity Sweetener and Anti-Diabetic Activities

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