Zinc reduces hepatic lipid deposition and activates lipophagy via Zn2+/MTF‐1/PPARα and Ca2+/CaMKKβ/AMPK pathways

Wei, Chuan-Chuan; Luo, Zhi; Högstrand, Christer; Xu, Yi-Huan; Wu, Lixiang; Pan, Ya–Xiong; Song, Yong

doi:10.1096/fj.201800463

Cited by 115 publications

(137 citation statements)

References 41 publications

(63 reference statements)

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“…In the livers of hepatic steatosis mice, zinc has been considered to be closely related to the DNA-binding activity of PPAR-α [117]. Therefore, zinc deficiency may result in a decline of PPAR-α function, thereby facilitating a detrimental alteration of lipid peroxidation, ultimately exacerbating hepatic steatosis [177]. Sugino et al [178] investigated the effect of zinc (polaprezinc) in a NASH mouse model.…”

Section: Zincmentioning

confidence: 99%

Trace Elements, PPARs, and Metabolic Syndrome

Shi

Zou

Shen

et al. 2020

IJMS

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Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of Ppar-α; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of Ppar-γ, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs' expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs' actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.

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Section: Zincmentioning

confidence: 99%

Trace Elements, PPARs, and Metabolic Syndrome

Shi

Zou

Shen

et al. 2020

IJMS

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“…76 Administration of minerals such as zinc, with known proautophagy properties, has been shown to promote hepatic lipophagy and reduce liver steatosis. 77 Even alcohol, at least when administered acutely, appears to upregulate lipophagy in both livers of mice as well as cultured hepatocyte cell models, likely as a cytoprotective mechanism geared toward the removal of accumulated LDs. 78,79 Other aspects related to the progression of fatty liver disease may also be aided by a better understanding of lipophagy.…”

Section: Roles For Lipophagy In Fatty Liver Diseasementioning

confidence: 99%

Lipid Droplet Formation and Lipophagy in Fatty Liver Disease

Schulze

McNiven

2019

Semin Liver Dis

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Lipid droplets (LDs) are key sites of neutral lipid storage that can be found in all cells. Metabolic imbalances between the synthesis and degradation of LDs can result in the accumulation of significant amounts of lipid deposition, a characteristic feature of hepatocytes in patients with fatty liver disease, a leading indication for liver transplant in the United States. In this review, the authors highlight new literature related to the synthesis and autophagic catabolism of LDs, discussing key proteins and machinery involved in these processes. They also discuss recent findings that have revealed novel genetic risk factors associated with LD biology that contribute to lipid retention in the diseased liver.

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“…Proteins for Western blot were extracted from transfected HepG2 cells using RIPA lysis and extraction buffer (Thermo Fisher Scientific), and the protocols followed these described in our recent studies (22) . Protein concentration was measured using the Pierce BCA protein assay kit (Thermo Fisher Scientific).…”

Section: Mrna and Protein Expression Of Grass Carp Nsrebp-1 In Hepg2 mentioning

confidence: 99%

Novel insights for SREBP-1 as a key transcription factor in regulating lipogenesis in a freshwater teleost, grass carp Ctenopharyngodon idella

Tan

et al. 2019

Br J Nutr

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Disturbances in lipid metabolism are at the core of several health issues facing modern society, including fatty liver and obesity. The sterol regulatory element-binding protein 1 (SREBP-1) is one important transcription factor regulating lipid metabolism, but the relevant mechanism still remains unknown. The present study determined the transcriptional regulation of SREBP-1 and its target genes (including acetyl-CoA carboxylase α (accα), fatty acid synthase (fas) and stearoyl-CoA desaturase 1 (scd1)) in a freshwater teleost, grass carp Ctenopharyngodon idella. We cloned and characterised the 1988 bp, 2043 bp, 1632 bp and 1889 bp sequences of srebp-1, accα, scd1 and fas promoters, respectively. A cluster of putative binding sites of transcription factors, such as specific protein, yin yang 1, nuclear factor Y, sterol response elements (SRE) and enhancer box (E-box) element, were predicted on their promoter regions. Overexpression of nSREBP-1 reduced srebp-1 promoter activity, increased scd1 and fas promoter activity but did not influence accα promoter activity. The site-mutation and electrophoretic mobility shift assay analysis indicated that srebp-1, fas and scd1 promoters, but not accα promoter, possessed SRE. In Ctenopharyngodon idella kidney (CIK) cells of grass carp, nSREBP-1 overexpression significantly reduced srebp-1 mRNA expression and up-regulated miR-29 mRNA expression. The 3′UTR of srebp-1 possessed the potential miR-29 binding site and miR-29 up-regulated the luciferase activity of srebp-1 3′UTR and srebp-1 mRNA expression, implying a self-activating loop of SREBP-1 and miR-29 in grass carp. Based on the above-mentioned results, we found two novel transcriptional mechanisms for SREBP-1 in grass carp: (1) the auto-regulation sited on the SREBP-1 promoter regions was suppressive and (2) there was a self-activating loop of SREBP-1 and miR-29.

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Zinc reduces hepatic lipid deposition and activates lipophagy via Zn²⁺/MTF‐1/PPARα and Ca²⁺/CaMKKβ/AMPK pathways

Cited by 115 publications

References 41 publications

Trace Elements, PPARs, and Metabolic Syndrome

Trace Elements, PPARs, and Metabolic Syndrome

Lipid Droplet Formation and Lipophagy in Fatty Liver Disease

Novel insights for SREBP-1 as a key transcription factor in regulating lipogenesis in a freshwater teleost, grass carp Ctenopharyngodon idella

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