The Crosstalk between Fat Homeostasis and Liver Regional Immunity in NAFLD

Ma, Minjuan; Duan, Rui; Zhong, Hong; Liang, Tingming; Guo, Li

doi:10.1155/2019/3954890

Cited by 24 publications

(18 citation statements)

References 119 publications

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“…A vicious cycle is formed due to excessive production of FFA in body and leads to the increase of liver TG. 23 The accumulation of FFA in muscle and liver induced by increased lipolysis in turn interferes insulin's utilization, glucose metabolism and causing IR. 24 The peripheral tissue glucose uptake and utilization capacity are decreased by IR, 25 and excess glucose reaches the liver through blood circulation and deposits in the form of TG.…”

Section: Discussionmentioning

confidence: 99%

<p>Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway</p>

Gong²,

Wang³

et al. 2020

DDDT

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Purpose: Nonalcoholic fatty liver disease (NAFLD) has become a predictor of death in many diseases. This study was carried out to investigate the therapeutic effect of Radix Polygoni Multiflori Preparata (RPMP) and its main component emodin on egg yolk powderinduced NAFLD in zebrafish. Further investigation was performed to explore whether emodin was the main component of RPMP for the treatment of NAFLD as well as the underlying therapeutic mechanism of RPMP and emodin. Methods: Zebrafish were divided into control group, egg yolk powder group, RPMP group and emodin group. The obesity of zebrafish was evaluated by body weight, body length and BMI. The content of lipid was detected by triglyceride (TG), total cholesterol (TC) reagent kit and the fatty acid was detected by nonesterified free fatty acids (NEFA) reagent kit. HE staining was used to detect the histological structure of liver. Whole-mount Oil red O staining and Frozen oil red O staining were carried out to investigate the lipid accumulation in liver. KEGG and STRING databases were performed to analyze the potential role of AMPK between insulin resistance (IR) and fatty acid oxidation. Western blot and RT-qPCR were carried out for mechanism research. Results: RPMP and emodin significantly reduced zebrafish weight, body length and BMI. Both RPMP and emodin treatment could reduce the lipid deposition in zebrafish liver. RPMP significantly reduced the content of TG. However, emodin significantly reduced the contents of TG, TC and NEFA in zebrafish with NAFLD. The protein interaction network indicated that AMPK participated in both IR and fatty acid oxidation. Further investigation indicated that RPMP and emodin reduced hepatic lipogenesis via up-regulating the expressions of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT2), amp-activated protein kinase alpha (AMPKα), proliferator-activated receptor alpha (PPARα), carnitine palmitoyl transferase 1a (CPT-1a) and acyl-coenzyme A oxidase 1 (ACOX1). Conclusion: These findings suggest that emodin is the main component of RPMP for the treatment of NAFLD, which is closely related to the regulation of AMPK signaling pathway which increases IR and fatty acid oxidation.

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Section: Discussionmentioning

confidence: 99%

<p>Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway</p>

Gong²,

Wang³

et al. 2020

DDDT

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“…On the one hand, upper body fat accumulation resulted in increased free fatty acid release [22,23] and increased cytokines and adipocytokines production [24], which played an important role in the pathogenesis of NAFLD, namely, the "two hits" theory. Furthermore, the activation of carbohydrate response element binding protein and sterol regulatory element binding protein-1c upregulated glycolytic enzymes and fatty acid synthase to promote hepatic lipogenesis in obesity [25]. In addition, there was complex crosstalk between fat homeostasis and the liver regional immune system.…”

Section: Men Womenmentioning

confidence: 99%

Neck Circumference is an Effective Supplement for Nonalcoholic Fatty Liver Disease Screening in a Community-Based Population

Jian

et al. 2020

International Journal of Endocrinology

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Background. Accumulating evidence has shown that neck circumference (NC) is associated with obesity-related metabolic abnormalities. Nonalcoholic fatty liver disease (NAFLD) is regarded as a liver manifestation of metabolic syndrome. This study aimed to investigate the relationship between NC and liver fat content (LFC) and NAFLD. Methods. A total of 1698 subjects (577 men and 1121 women) from the Shanghai community were enrolled. All the subjects underwent NC measurement and biochemical measurements. LFC was calculated using the parameters from abdominal ultrasound images. Elevated NC was defined as NC ≥38.5 cm in men and NC ≥34.5 cm in women. Results. Subjects with NAFLD based on the LFC measurement had higher values of NC, liver enzyme profiles, homoeostasis model assessment-insulin resistance index, and LFC than those without NAFLD (all P<0.05), irrespective of sex. NC showed an upward trend with the increase of LFC in both men and women (both P<0.05). An elevated NC could identify 55.22% of men and 50.29% of women with NAFLD based on quantitative ultrasonography. The positive correlation between NC and LFC remained significant even after adjustment for central obesity (both P<0.05). After adjusting for confounding factors, the risk of NAFLD in subjects with an elevated NC was 1.52-fold higher in men (P=0.036) and 2.31-fold higher in women (P<0.001). Conclusions. There was a significant and positive correlation between NC and LFC. The risk of NAFLD increased significantly in subjects with an elevated NC.

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“…Thus, it becomes imperative to study the initiation and the progression of NAFLD through its various phenotypic stages to devise efficient and robust intervention measures to control the spread of this epidemic. Multiple studies have shown the importance of various key regulators and genetic alterations for the development and the progression of NAFLD [67,68]. However, there are only a few attempts to analyze NAFLD from a systems biology perspective, i.e., decoding how these different regulators interact in the context of NAFLD [17,[69][70][71][72].…”

Section: Discussionmentioning

confidence: 99%

Emergent Properties of the HNF4α-PPARγ Network May Drive Consequent Phenotypic Plasticity in NAFLD

Sahoo

Singh

Chakraborty

et al. 2020

JCM

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Non-alcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease in adults and children. It is characterized by excessive accumulation of lipids in the hepatocytes of patients without any excess alcohol intake. With a global presence of 24% and limited therapeutic options, the disease burden of NAFLD is increasing. Thus, it becomes imperative to attempt to understand the dynamics of disease progression at a systems-level. Here, we decoded the emergent dynamics of underlying gene regulatory networks that were identified to drive the initiation and the progression of NAFLD. We developed a mathematical model to elucidate the dynamics of the HNF4α-PPARγ gene regulatory network. Our simulations reveal that this network can enable multiple co-existing phenotypes under certain biological conditions: an adipocyte, a hepatocyte, and a “hybrid” adipocyte-like state of the hepatocyte. These phenotypes may also switch among each other, thus enabling phenotypic plasticity and consequently leading to simultaneous deregulation of the levels of molecules that maintain a hepatic identity and/or facilitate a partial or complete acquisition of adipocytic traits. These predicted trends are supported by the analysis of clinical data, further substantiating the putative role of phenotypic plasticity in driving NAFLD. Our results unravel how the emergent dynamics of underlying regulatory networks can promote phenotypic plasticity, thereby propelling the clinically observed changes in gene expression often associated with NAFLD.

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The Crosstalk between Fat Homeostasis and Liver Regional Immunity in NAFLD

Cited by 24 publications

References 119 publications

<p>Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway</p>

<p>Radix Polygoni Multiflori and Its Main Component Emodin Attenuate Non-Alcoholic Fatty Liver Disease in Zebrafish by Regulation of AMPK Signaling Pathway</p>

Neck Circumference is an Effective Supplement for Nonalcoholic Fatty Liver Disease Screening in a Community-Based Population

Emergent Properties of the HNF4α-PPARγ Network May Drive Consequent Phenotypic Plasticity in NAFLD

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