Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS

Song,Hong-Mao; Li,Xiang; Liu,Yuan-Yuan; Lu,Wei-Ping; Cui,Zhao-Hui; Zhou,Li; Yao,Di; Zhang,Hong-Man

doi:10.3892/ijmm.2018.3593

Carnosic acid protects mice from high-fat diet-induced NAFLD by regulating MARCKS

Authors:
- Hong-Mao Song
- Xiang Li
- Yuan-Yuan Liu
- Wei-Ping Lu
- Zhao-Hui Cui
- Li Zhou
- Di Yao
- Hong-Man Zhang
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of Clinical Laboratory, Huai'an Hospital Affiliated to Xuzhou Medical University, Huai'an, Jiangsu 223300, P.R. China, Department of Endocrinology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, Jiangsu 223300, P.R. China
Published online on: March 27, 2018 https://doi.org/10.3892/ijmm.2018.3593
Pages: 193-207
Copyright: © Song et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage characterized by abnormal hepatic fat accumulation and inflammatory response. Although the molecular mechanisms responsible for the disease are not yet fully understood, the pathogenesis of NAFLD likely involves multiple signals. The identification of effective therapeutic strategies to target these signals is of utmost importance. Carnosic acid (CA), as a phenolic diterpene with anticancer, anti-bacterial, anti-diabetic and neuroprotective properties, is produced by many species of the Lamiaceae family. Myristoylated alanine-rich C-kinase substrate (MARCKS) is a major protein kinase C (PKC) substrate in many different cell types. In the present study, wild-type C57BL/6 and MARCKS-deficient mice were randomly divided into the normal chow- or high-fat (HF) diet-fed groups. The HF diet increased the fasting glucose and insulin levels, and promoted glucose intolerance in the wild-type mice. MARCKS deficiency further upregulated intolerance, fasting glucose and insulin. The HF diet also promoted hepatic steatosis, serum alanine transaminase (ALT) and aspartate transaminase (AST) activity, inflammation and lipid accumulation in the wild-type mice. These responses were accelerated in the MARCKS-deficient mice. Importantly, increased inflammation and lipid accumulation were associated with phosphoinositide 3-kinase (PI3K)/AKT, NLR family pyrin domain containing 3 (NLRP3)/nuclear factor-κB (NF-κB) and sterol regulatory element binding protein-1c (SREBP-1c) signaling pathway activation. The mice treated with CA exhibited a significantly improved glucose and insulin tolerance. The production of pro-inflammatory cytokines and lipid accumulation were suppressed by CA. Significantly, MARCKS was reduced in mice fed the HF diet. CA treatment upregulated MARCKS expression compared to the HF group. Furthermore, the activation of the PI3K/AKT, NLRP3/NF-κB and SREBP-1c signaling pathways was inhibited by CA. Taken together, our data suggest that CA suppresses inflammation and lipogenesis in mice fed a HF diet through MARCKS regulation. Thus, CA may be prove to be a useful anti-NAFLD agent.

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