Morroniside Delays NAFLD Progression in Fructose-Fed Mice by Normalizing Lipid Metabolism and Inhibiting the Inflammatory Response

Chronic fructose consumption is becoming one leading risk factor for NAFLD due to its hazard on cellular lipid metabolism, which plays an essential role in the pathogenesis of NAFLD. Morroniside, an iridoid glycoside from Cornus officinalis, has been suggested to have potent in regulating cellular glucolipid metabolism. However, the effect and mechanism of morroniside on improving fructose-induced hepatic steatosis and retarding NAFLD progression remain ambiguous. In this study, we illustrate the efficacy of morroniside in alleviating fructose-triggered hepatic steatosis in mice. Mechanically, morroniside suppressed de novo lipogenesis and promoted β-oxidation by inhibiting the activation of PGC1β. Additionally, morroniside was found to work in attenuating hepatic inflammation in response to long-term fructose intake. Taken together, the current study reveals that morroniside is a promising food and medicinal therapy for NAFLD treatment and is effective in delaying the progression of NAFLD to NASH, especially in subtypes caused by excessive carbohydrate intake.

[1]  Ying Wu,et al.  Cornus officinalis vinegar reduces body weight and attenuates hepatic steatosis in mouse model of nonalcoholic fatty liver disease. , 2022, Journal of food science.

[2]  Seon-Yong Jeong,et al.  Anti-Obesity Effects of Combined Cornus officinalis and Ribes fasciculatum Extract in High-Fat Diet-Induced Obese Male Mice , 2021, Animals : an open access journal from MDPI.

[3]  M. Febbraio,et al.  "Sweet death": Fructose as a metabolic toxin that targets the gut-liver axis. , 2021, Cell metabolism.

[4]  M. Birnbaum,et al.  Molecular aspects of fructose metabolism and metabolic disease. , 2021, Cell metabolism.

[5]  Peng Liu,et al.  Morroniside Promotes PGC-1α-Mediated Cholesterol Efflux in Sodium Palmitate or High Glucose-Induced Mouse Renal Tubular Epithelial Cells , 2021, BioMed research international.

[6]  I. Rowe,et al.  A Systematic Review of Animal Models of NAFLD Finds High‐Fat, High‐Fructose Diets Most Closely Resemble Human NAFLD , 2021, Hepatology.

[7]  S. Friedman,et al.  Mechanisms and disease consequences of nonalcoholic fatty liver disease , 2021, Cell.

[8]  Jeonghyung Kim,et al.  Efficacy and Safety of Combined Extracts of Cornus officinalis and Ribes fasciculatum for Body Fat Reduction in Overweight Women , 2020, Journal of clinical medicine.

[9]  Christian M. Metallo,et al.  Fructose stimulated de novo lipogenesis is promoted by inflammation , 2020, Nature Metabolism.

[10]  C. Stave,et al.  Global prevalence, incidence, and outcomes of non-obese or lean non-alcoholic fatty liver disease: a systematic review and meta-analysis. , 2020, The lancet. Gastroenterology & hepatology.

[11]  J. Rabinowitz,et al.  Dietary fructose feeds hepatic lipogenesis via microbiota-derived acetate , 2020, Nature.

[12]  C. Kahn,et al.  Dietary Sugars Alter Hepatic Fatty Acid Oxidation via Transcriptional and Post-translational Modifications of Mitochondrial Proteins. , 2019, Cell metabolism.

[13]  Z. Younossi.  Non-alcoholic fatty liver disease - A global public health perspective. , 2019, Journal of hepatology.

[14]  B. Neuschwander‐Tetri,et al.  Mechanisms of NAFLD development and therapeutic strategies , 2018, Nature Medicine.

[15]  K. Nadeau,et al.  Fructose and sugar: A major mediator of non-alcoholic fatty liver disease. , 2018, Journal of hepatology.

[16]  G. Shulman,et al.  Nonalcoholic Fatty Liver Disease as a Nexus of Metabolic and Hepatic Diseases. , 2018, Cell metabolism.

[17]  M. Serlie,et al.  Fructose Consumption, Lipogenesis, and Non-Alcoholic Fatty Liver Disease , 2017, Nutrients.

[18]  M. Herman,et al.  The Sweet Path to Metabolic Demise: Fructose and Lipid Synthesis , 2016, Trends in Endocrinology & Metabolism.

[19]  A. Moschetta,et al.  Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1β , 2016, Cellular and Molecular Life Sciences.

[20]  C. Kahn,et al.  Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease , 2016, Digestive Diseases and Sciences.

[21]  Meng Li,et al.  Reactive oxygen species-induced TXNIP drives fructose-mediated hepatic inflammation and lipid accumulation through NLRP3 inflammasome activation. , 2015, Antioxidants & redox signaling.

[22]  W. Ling,et al.  Retinol binding protein 4 stimulates hepatic sterol regulatory element‐binding protein 1 and increases lipogenesis through the peroxisome proliferator‐activated receptor‐γ coactivator 1β‐dependent pathway , 2013, Hepatology.

[23]  Jack A. Taylor,et al.  Critical evaluation of KCNJ3 gene product detection in human breast cancer: mRNA in situ hybridisation is superior to immunohistochemistry , 2016, Journal of Clinical Pathology.

[24]  D. W. Foster.  Malonyl-CoA: the regulator of fatty acid synthesis and oxidation. , 2012, The Journal of clinical investigation.

[25]  J. Kim,et al.  Evaluation of morroniside, iridoid glycoside from Corni Fructus, on diabetes-induced alterations such as oxidative stress, inflammation, and apoptosis in the liver of type 2 diabetic db/db mice. , 2011, Biological & pharmaceutical bulletin.

[26]  Da-Young Jung,et al.  Hepatoprotective and Antioxidative Activities of Cornus officinalis against Acetaminophen-Induced Hepatotoxicity in Mice , 2011, Evidence-based complementary and alternative medicine : eCAM.

[27]  J. Noh,et al.  Evaluation of loganin, iridoid glycoside from Corni Fructus, on hepatic and renal glucolipotoxicity and inflammation in type 2 diabetic db/db mice. , 2010, European journal of pharmacology.

[28]  J. Schwarz,et al.  The role of fructose in the pathogenesis of NAFLD and the metabolic syndrome , 2010, Nature Reviews Gastroenterology &Hepatology.

[29]  J. Noh,et al.  Effects of morroniside isolated from Corni Fructus on renal lipids and inflammation in type 2 diabetic mice , 2010, The Journal of pharmacy and pharmacology.

[30]  J. Noh,et al.  The beneficial effects of morroniside on the inflammatory response and lipid metabolism in the liver of db/db mice. , 2009, Biological & pharmaceutical bulletin.

[31]  O. Cummings,et al.  Design and validation of a histological scoring system for nonalcoholic fatty liver disease , 2005, Hepatology.

[32]  Christoph Handschin,et al.  Hyperlipidemic Effects of Dietary Saturated Fats Mediated through PGC-1β Coactivation of SREBP , 2005, Cell.

[33]  J. McGarry,et al.  A possible role for malonyl-CoA in the regulation of hepatic fatty acid oxidation and ketogenesis. , 1977, The Journal of clinical investigation.

[34]  G. Svegliati-Baroni,et al.  Nonalcoholic Fatty Liver Disease: Basic Pathogenetic Mechanisms in the Progression From NAFLD to NASH , 2019, Transplantation.

[35]  Zhao-hua Li,et al.  Alpinetin improved high fat diet-induced non-alcoholic fatty liver disease (NAFLD) through improving oxidative stress, inflammatory response and lipid metabolism. , 2018, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[36]  L. Tappy,et al.  Metabolic effects of fructose and the worldwide increase in obesity. , 2010, Physiological reviews.