Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content

Zheng, Xiao‐Yan; Zhao, Shui‐Ping; Yu, Bo; Wu, Chenlu; Liu, Ling

doi:10.1515/hsz-2011-0259

Cited by 26 publications

(36 citation statements)

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“…Interestingly, apoA5 in hepatocytes is also localized on the surface of cytoplasmic LDs (Shu et al, 2007) and has proved to be an important modulator in cellular TG and lipoprotein metabolism (Shu et al, 2010). As expected, after incubation of human adipocytes with recombinant human apoA5 proteins, we observed an obvious reduction in cellular TG content (Zheng et al, 2012). As expected, after incubation of human adipocytes with recombinant human apoA5 proteins, we observed an obvious reduction in cellular TG content (Zheng et al, 2012).…”

Section: (2) Apoa5supporting

confidence: 68%

Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non‐alcoholic fatty liver disease

Zhao

2014

Biological Reviews

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Exchangeable apolipoproteins play an important role in systemic lipid metabolism, especially for lipoproteins with which they are associated. Recently, emerging evidence has suggested that exchangeable apolipoproteins, such as apolipoprotein A4 (apoA4), apolipoprotein A5 (apoA5), apolipoprotein C3 (apoC3) and apolipoprotein E (apoE), also exert important effects on intracellular lipid homeostasis. There is a close link between lipid metabolism in adipose tissue and liver because the latter behaves as the metabolic sensor of dysfunctional adipose tissue and is a main target of lipotoxicity. Given that the energy balance between these two major lipogenic organs is intimately involved in the pathogenesis of obesity and non-alcoholic fatty liver disease (NAFLD), we here review recent findings concerning the intracellular function of exchangeable apolipoproteins in triglyceride metabolism in adipocytes and hepatocytes. These apolipoproteins may act as mediators of crosstalk between adipose tissue and liver, thus influencing development of obesity and hepatosteatosis. This review provides new insights into the physiological role of exchangeable apolipoproteins and identifies latent targets for therapeutic intervention of obesity and its related disorders.

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Section: (2) Apoa5supporting

confidence: 68%

Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non‐alcoholic fatty liver disease

Zhao

2014

Biological Reviews

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“…Studies have shown that plasma levels of ApoA5 are reduced in obese subjects and inversely correlated with measures of insulin resistance [53]. In hepatocytes and adipocytes, ApoA5 localizes on the surface of cytoplasmic lipid droplets, and incubation with ApoA5 has been shown to reduce cellular triglyceride content in human adipocytes [54,55]. ApoM overexpression has been shown to improve insulin sensitivity in rats [56] and ApoM was found to be upregulated by all berries, except açai, which downregulated ApoM.…”

Section: Lingonberries Blackcurrants Bilberries and Açai Exert Theimentioning

confidence: 99%

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Heyman-Lindén

Seki

Storm

et al. 2016

The Journal of Nutritional Biochemistry

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The liver is a critical organ for regulation of energy homeostasis and fatty liver disease is closely associated with obesity and insulin resistance. We have previously found that lingonberries, blackcurrants and bilberries prevent, whereas açai berries exacerbate, the development of hepatic steatosis and obesity in the high-fat (HF)-fed C57BL/6J mouse model. In this follow-up study, we investigated the mechanisms behind these effects. Genome-wide hepatic gene expression profiling indicates that the protective effects of lingonberries and bilberries are accounted for by several-fold downregulation of genes involved in acute-phase and inflammatory pathways (e.g. Saa1, Cxcl1, Lcn2). In contrast, açai-fed mice exhibit marked upregulation of genes associated with steatosis (e.g. Cfd, Cidea, Crat) and lipid and cholesterol biosynthesis, which is in line with the exacerbation of HF-induced hepatic steatosis in these mice. In silico transcription factor analysis together with immunoblot analysis identified NF-κB, STAT3 and mTOR as upstream regulators involved in mediating the observed transcriptional effects. To gain further insight into mechanisms involved in the gene expression changes, the HELP-tagging assay was used to identify differentially methylated CpG sites. Compared to the HF control group, lingonberries induced genome-wide hypermethylation and specific hypermethylation of Ncor2, encoding the corepressor NCoR/SMRT implicated in the regulation of pathways of metabolic homeostasis and inflammation. We conclude that the beneficial metabolic effects of lingonberries and bilberries are associated with downregulation of inflammatory pathways, whereas for blackcurrants, exerting similar metabolic effects, different mechanisms of action appear to dominate. NF-κB, STAT3 and mTOR are potential targets of the health-promoting effects of berries.

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“…These results suggest that ApoA5 might induce a decrease in VLDL associated TG levels by both decreasing hepatic VLDL synthesis and increasing VLDL clearance. Besides, a recent study showed that ApoA5 may be absorbed by human adipocytes and may play a role in TG storage regulation [21]. …”

Section: Introductionmentioning

confidence: 99%

Association of two common polymorphisms of apolipoprotein A5 gene with metabolic syndrome indicators in a North Iranian population, a cross-sectional study

Halalkhor

Jalali

Hajian‐Tilaki

et al. 2014

J Diabetes Metab Disord

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BackgroundMetabolic syndrome is an obesity dependent disorder with a worldwide high prevalence. Regarding the high prevalence of Metabolic syndrome in Iran we analyzed the influence of -1131T>C (rs662799) and c.56C>G (S19W, rs3135506) polymorphisms of the novel apolipoprotein gene, ApoA5, on some Metabolic Syndrome indicators in population from north of Iran.Methods199 volunteers from Babol city-Iran were divided in two groups of low (N = 99, TG ≤ 103 mg/dl) and high (N = 100, TG ≥ 150 mg/dl) serum levels of Triglycerides (TG). We amplified the gene fragments containing -1131T>C and c.56C>G polymorphisms by PCR method and revealed the polymorphisms by RFLP analysis.ResultsWe found a significant association (p = 0.016, Independent t-test) between high levels of TG and -1131T>C polymorphism but not between this polymorphism and serum HDL-C concentrations. Carriers of the C allele had a 1.97 times higher odds ratio to be in the high-TG group than those of the TT genotype (95%, CI = 1.05-3.68). We observed no association between -1131T>C polymorphism with either Waist-to-Hip Ratio (WHR) or Body-Mass-Index (BMI). In the case of c.56C>G polymorphism, although it showed a significant relationship with WHR (p = 0/040, Independent t-test), but failed to correlate with either levels of TG (p = 0.594) or HDL-C (p = 0.640) in serum.ConclusionOur study confirms that ApoA5 gene polymorphisms, -1131T>C and c.56C>G are associated with the two criteria of Metabolic Syndrome, TG and WHR, respectively.

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Apolipoprotein A5 internalized by human adipocytes modulates cellular triglyceride content

Cited by 26 publications

References 0 publications

Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non‐alcoholic fatty liver disease

Intracellular role of exchangeable apolipoproteins in energy homeostasis, obesity and non‐alcoholic fatty liver disease

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet

Association of two common polymorphisms of apolipoprotein A5 gene with metabolic syndrome indicators in a North Iranian population, a cross-sectional study

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