Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

Xepapadaki, Eva; Maulucci, Giuseppe; Constantinou, Caterina; Karavia, Eleni A.; Zvintzou, Evangelia; Daniel, Bareket; Sasson, Shlomo; Kypreos, Kyriakos E.

doi:10.1016/j.bbadis.2019.02.003

Cited by 19 publications

(23 citation statements)

References 49 publications

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“…The basis of the improved glycaemic control in these individuals was attributed to increased secretion of insulin from β-cells and enhanced glucose uptake into skeletal muscle [62]. This result is consistent with what has been reported for apoA-I knockout mice that have impaired glucose tolerance, in mice that overexpress human apoA-I and have improved glucose tolerance, and in in vitro studies of cultured skeletal muscle cells where incubation with lipid-free apoA-I has been reported to increase glucose uptake in an insulin-dependent and -independent manner by increasing glycolysis and mitochondrial respiration [27,28,[68][69][70]. Some of these studies are particularly important because they suggest that apoA-I-and HDL-based therapies may improve glycaemic control in patients with T2D that have complete loss of β-cell function and are refractory to many of the currently available antidiabetic therapies [28,71].…”

Section: Apolipoprotein A-i and Apolipoprotein A-iisupporting

confidence: 85%

High Density Lipoproteins and Diabetes

Cochran

Manandhar

Rye

2021

Cells

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Epidemiological studies have established that a high plasma high density lipoprotein cholesterol (HDL-C) level is associated with reduced cardiovascular risk. However, recent randomised clinical trials of interventions that increase HDL-C levels have failed to establish a causal basis for this relationship. This has led to a shift in HDL research efforts towards developing strategies that improve the cardioprotective functions of HDLs, rather than simply increasing HDL-C levels. These efforts are also leading to the discovery of novel HDL functions that are unrelated to cardiovascular disease. One of the most recently identified functions of HDLs is their potent antidiabetic properties. The antidiabetic functions of HDLs, and recent key advances in this area are the subject of this review. Given that all forms of diabetes are increasing at an alarming rate globally, there is a clear unmet need to identify and develop new approaches that will complement existing therapies and reduce disease progression as well as reverse established disease. Exploration of a potential role for HDLs and their constituent lipids and apolipoproteins in this area is clearly warranted. This review highlights focus areas that have yet to be investigated and potential strategies for exploiting the antidiabetic functions of HDLs.

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Section: Apolipoprotein A-i and Apolipoprotein A-iisupporting

confidence: 85%

High Density Lipoproteins and Diabetes

Cochran

Manandhar

Rye

2021

Cells

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“…The results for the functional enrichment of the DEGs showed that some genes were enriched to pathways related to glucose and lipid metabolism. In addition, these pathways were confirmed to be related to lipid metabolism in previous studies, including APOA1 [41] and STARD3 [42] . Chen identified 581 putative lincRNAs related to pig muscle growth and fat deposition, and their target genes were involved in fat deposition-related processes such as the lipid metabolic process and fatty acid degradation [43] .…”

Section: Discussionsupporting

confidence: 68%

Identification of Long Non-Coding RNAs Involved in Fat Deposition in Pigs Using Two High-Throughput Sequencing Methods

Liu¹,

Hong²,

Zhang³

et al. 2020

Preprint

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Background: Adipose is an important body tissue in pigs, and fatty traits are critical in pig production. The function of long non-coding RNA (lncRNA) in fat deposition and metabolism has been proven in previous studies. In this study, we focused on lncRNAs associated with fattening traits in pigs. The adipose tissue of six Landrace pigs with either extremely-high or -low backfat thickness ( n high = 3, n low = 3) was collected, after which we performed strand-specific RNA sequencing using biological replicates and pooling methods. Results: A total of 19,631 genes and 2,013 lncRNAs were identified using the coding potential calculator, coding-non-coding index, and Pfam database, including 334 known transcripts and 1,679 novel transcripts. Using edgeR, we determined that 220 lncRNAs and 1,512 genes were differentially expressed (|Fold Change| > 2 and false discovery rate < 0.05) between the two groups in biological replicate RNA sequencing (RNA-seq), and 127 lncRNAs and 2,240 genes were differently expressed in pooling RNA-seq. Further Kyoto Encyclopedia of Genes and Genomes and Gene Ontology enrichment analysis of the differentially expressed genes found that some of the genes were involved in several key pathways related to fat development. After targeting gene prediction, we determined that some cis-target genes of the differentially expressed lncRNAs play an important role in fat deposition. For example, ACSL3 is cis-targeted by lncRNA TCONS-00052400, and it can activate the conversion of long-chain fatty acids. In addition, lncRNA TCONS_00041740 was up-regulated in the high backfat thickness group, and its cis-target gene ACACB was also up-regulated in this group. It has been reported that ACACB is the rate-limiting enzyme in fatty acid oxidation. Conclusions: Since these genes have necessary functions in fat metabolism, the results imply that the lncRNAs detected in our study may affect fat deposition in pigs through regulation of their target genes. In summary, our study explored the regulation of lncRNA and their target genes on fat deposition in pigs and provided new insights for further investigation of the biological functions of lncRNA.

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“…The direct causative relationship between HDL structure and type 2 diabetes was investigated in a study evaluating the role of ApoA-1 and LCAT deficiency in diet-induced obesity and glucose homeostasis in mice [87]. ApoA-1 deficiency results in lack of classical ApoA-1-HDL, while LCAT deficiency results in mainly discoidal HDL particles, both of which constitute drastic changes in HDL structure and composition.…”

Section: Cell Lipotoxicity Apoptosismentioning

confidence: 99%

HDL and type 2 diabetes: the chicken or the egg?

et al. 2021

Self Cite

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HDL is a complex macromolecular cluster of various components, such as apolipoproteins, enzymes and lipids. Quality evidence from clinical and epidemiological studies led to the principle that HDL-cholesterol (HDL-C) levels are inversely correlated with the risk of CHD. Nevertheless, the failure of many cholesteryl ester transfer protein inhibitors to protect against CVD casts doubts on this principle and highlights the fact that HDL functionality, as dictated by its proteome and lipidome, also plays an important role in protecting against metabolic disorders. Recent data indicate that HDL-C levels and HDL particle functionality are correlated with the pathogenesis and prognosis of type 2 diabetes mellitus, a major risk factor for CVD. Hyperglycaemia leads to reduced HDL-C levels and deteriorated HDL functionality, via various alterations in HDL particles' proteome and lipidome. In turn, reduced HDL-C levels and impaired HDL functionality impact the performance of key organs related to glucose homeostasis, such as pancreas and skeletal muscles. Interestingly, different structural alterations in HDL correlate with distinct metabolic abnormalities, as indicated by recent data evaluating the role of apolipoprotein A1 and lecithin-cholesterol acyltransferase deficiency in glucose homeostasis. While it is becoming evident that not all HDL disturbances are causatively associated with the development and progression of type 2 diabetes, a bidirectional correlation between these two conditions exists, leading to a perpetual self-feeding cycle.

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Impact of apolipoprotein A1- or lecithin:cholesterol acyltransferase-deficiency on white adipose tissue metabolic activity and glucose homeostasis in mice

Cited by 19 publications

References 49 publications

High Density Lipoproteins and Diabetes

High Density Lipoproteins and Diabetes

Identification of Long Non-Coding RNAs Involved in Fat Deposition in Pigs Using Two High-Throughput Sequencing Methods

HDL and type 2 diabetes: the chicken or the egg?

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