Madecassoside ameliorates hepatic steatosis in high-fat diet-fed mice through AMPK/autophagy-mediated suppression of ER stress

Choi, Sung Woo; Cho, Wonjun; Oh, Heeseung; Abd El-Aty, A.M.; Hong, Soon Auck; Hong, Mineui; Jeong, Ji Hoon; Jung, Tae Woo

doi:10.1016/j.bcp.2023.115815

Cited by 6 publications

(2 citation statements)

References 31 publications

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“…AMPK has ameliorated ER stress in various experimental conditions (Choi et al, 2023; Li et al, 2014; Park et al, 2022). Consequently, we proceeded to assess whether IL‐38 influences AMPK phosphorylation in hepatocytes.…”

Section: Resultsmentioning

confidence: 99%

Interleukin‐38 alleviates hepatic steatosis through AMPK/autophagy‐mediated suppression of endoplasmic reticulum stress in obesity models

Sun,

Cho,

et al. 2024

Journal Cellular Physiology

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Interleukin‐38 (IL‐38), recently recognized as a cytokine with anti‐inflammatory properties that mitigate type 2 diabetes, has been associated with indicators of insulin resistance and nonalcoholic fatty liver disease (NAFLD). This study investigated the impact of IL‐38 on hepatic lipid metabolism and endoplasmic reticulum (ER) stress. We assessed protein expression levels using Western blot analysis, while monodansylcadaverine staining was employed to detect autophagosomes in hepatocytes. Oil red O staining was utilized to examine lipid deposition. The study revealed elevated serum IL‐38 levels in high‐fat diet (HFD)‐fed mice and IL‐38 secretion from mouse keratinocytes. IL‐38 treatment attenuated lipogenic lipid accumulation and ER stress markers in hepatocytes exposed to palmitate. Furthermore, IL‐38 treatment increased AMP‐activated protein kinase (AMPK) phosphorylation and autophagy. The effects of IL‐38 on lipogenic lipid deposition and ER stress were nullified in cultured hepatocytes by suppressing AMPK through small interfering (si) RNA or 3‐methyladenine (3MA). In animal studies, IL‐38 administration mitigated hepatic steatosis by suppressing the expression of lipogenic proteins and ER stress markers while reversing AMPK phosphorylation and autophagy markers in the livers of HFD‐fed mice. Additionally, AMPK siRNA, but not 3MA, mitigated IL‐38‐enhanced fatty acid oxidation in hepatocytes. In summary, IL‐38 alleviates hepatic steatosis through AMPK/autophagy signaling‐dependent attenuation of ER stress and enhancement of fatty acid oxidation via the AMPK pathway, suggesting a therapeutic strategy for treating NAFLD.

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Section: Resultsmentioning

confidence: 99%

Interleukin‐38 alleviates hepatic steatosis through AMPK/autophagy‐mediated suppression of endoplasmic reticulum stress in obesity models

Sun,

Cho,

et al. 2024

Journal Cellular Physiology

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“…Furthermore, ER stress and autophagy are also correlated, since autophagy is activated under ER stress conditions; so-called ER stress-mediated autophagy includes the degradation of protein aggregates, damaged organelles, and misfolded proteins. A new branch of macroautophagy is ER-phagy in which the autophagosome membrane selectively includes parts of the ER membrane [43,[46][47][48].…”

Section: Hepatic Er Stress and Unfolded Protein Response In Insulin R...mentioning

confidence: 99%

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Vesković,

Šutulović,

Hrnčić

et al. 2023

CIMB

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The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation in the liver. On the other side, triglyceride and free fatty acid accumulation in hepatocytes promotes insulin resistance via oxidative stress, endoplasmic reticulum stress, lipotoxicity, and the increased secretion of hepatokines. Cytokines and adipokines cause insulin resistance, thus promoting lipolysis in adipose tissue and ectopic fat deposition in the muscles and liver. Free fatty acids along with cytokines and adipokines contribute to insulin resistance in the liver via the activation of numerous signaling pathways. The secretion of hepatokines, hormone-like proteins, primarily by hepatocytes is disturbed and impairs signaling pathways, causing metabolic dysregulation in the liver. ER stress and unfolded protein response play significant roles in insulin resistance aggravation through the activation of apoptosis, inflammatory response, and insulin signaling impairment mediated via IRE1/PERK/ATF6 signaling pathways and the upregulation of SREBP 1c. Circadian rhythm derangement and biological clock desynchronization are related to metabolic disorders, insulin resistance, and NAFLD, suggesting clock genes as a potential target for new therapeutic strategies. This review aims to summarize the mechanisms of hepatic insulin resistance involved in NAFLD development and progression.

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Interleukin-27 as a novel player in alleviating hepatic steatosis: Mechanistic insights from an in vitro analysis

Cho,

Oh,

Abd El-Aty

et al. 2024

Biochemical and Biophysical Research Communications

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Madecassoside ameliorates hepatic steatosis in high-fat diet-fed mice through AMPK/autophagy-mediated suppression of ER stress

Cited by 6 publications

References 31 publications

Interleukin‐38 alleviates hepatic steatosis through AMPK/autophagy‐mediated suppression of endoplasmic reticulum stress in obesity models

Interleukin‐38 alleviates hepatic steatosis through AMPK/autophagy‐mediated suppression of endoplasmic reticulum stress in obesity models

The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Interleukin-27 as a novel player in alleviating hepatic steatosis: Mechanistic insights from an in vitro analysis

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