Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes

Qu, Jie; Ko, Chih‐Wei; Tso, Patrick; Bhargava, Aditi

doi:10.3390/cells8040319

Cited by 107 publications

(88 citation statements)

References 123 publications

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“…ApoA-I has a regulatory role in the complement system in various species [78][79][80]. ApoA-IV is a lipid binding protein, primarily synthesized in the small intestine and involved in a range of physiological proteins including lipid absorption and metabolism, glucose homeostasis, platelet aggregation and thrombosis [81]. ApoB-100 is synthesised by the liver, plays a part in innate immune responses [82] (Peterson et al, 2008), and is associated with endoplasmic reticulum (ER) stress and insulin resistance [83], as well as lipid metabolism disorders [84].…”

Section: Discussionmentioning

confidence: 99%

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Phillips

Kraev

Lange

2020

Biology

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Pelagic seabirds are amongst the most threatened of all avian groups. They face a range of immunological challenges which seem destined to increase due to environmental changes in their breeding and foraging habitats, affecting prey resources and exposure to pollution and pathogens. Therefore, the identification of biomarkers for the assessment of their health status is of considerable importance. Peptidylarginine deiminases (PADs) post-translationally convert arginine into citrulline in target proteins in an irreversible manner. PAD-mediated deimination can cause structural and functional changes in target proteins, allowing for protein moonlighting in physiological and pathophysiological processes. PADs furthermore contribute to the release of extracellular vesicles (EVs), which play important roles in cellular communication. In the present study, post-translationally deiminated protein and EV profiles of plasma were assessed in eight seabird species from the Antarctic, representing two avian orders: Procellariiformes (albatrosses and petrels) and Charadriiformes (waders, auks, gulls and skuas). We report some differences between the species assessed, with the narrowest EV profiles of 50–200 nm in the northern giant petrel Macronectes halli, and the highest abundance of larger 250–500 nm EVs in the brown skua Stercorarius antarcticus. The seabird EVs were positive for phylogenetically conserved EV markers and showed characteristic EV morphology. Post-translational deimination was identified in a range of key plasma proteins critical for immune response and metabolic pathways in three of the bird species under study; the wandering albatross Diomedea exulans, south polar skua Stercorarius maccormicki and northern giant petrel. Some differences in Gene Ontology (GO) biological and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways for deiminated proteins were observed between these three species. This indicates that target proteins for deimination may differ, potentially contributing to a range of physiological functions relating to metabolism and immune response, as well as to key defence mechanisms. PAD protein homologues were identified in the seabird plasma by Western blotting via cross-reaction with human PAD antibodies, at an expected 75 kDa size. This is the first study to profile EVs and to identify deiminated proteins as putative novel plasma biomarkers in Antarctic seabirds. These biomarkers may be further refined to become useful indicators of physiological and immunological status in seabirds—many of which are globally threatened.

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Section: Discussionmentioning

confidence: 99%

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Phillips

Kraev

Lange

2020

Biology

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“…AGPAT1 and AGPAT2 play roles in converting lysophosphatidic acid (LPA) into phosphatidic acid (PA) (Takeuchi and Reue 2009). APOA1, APOA4, and APOB encode key apolipoproteins to carry fats and fat-like substances in the blood (Mangaraj et al 2016;Qu et al 2019). Remarkably, we found the positive selection of one gene, ABCG5, which encodes sterolin-1 and works together with sterolin-2, encoded by gene ABCG8, to form a protein called sterolin.…”

Section: Resultsmentioning

confidence: 86%

“…MTTP is involved in the transport of triglycerides, cholesteryl esters, and phospholipids (Hussain et al 2012). APOA4 and APOB encode two key apolipoproteins responsive to carrying fats and fat-like substances in the blood (Mangaraj et al 2016;Qu et al 2019). Unlike PDA and FDA, CDA showed the lowest number of PSGs, and only three PSGs (SI, HKDC1, and ATP1B4) were detected.…”

Section: Resultsmentioning

confidence: 99%

Trophic shift and the origin of birds

2020

Preprint

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Birds are characterized by evolutionary specializations of both locomotion (e.g., flapping flight) and digestive system (toothless, crop, and gizzard), while the potential selection pressures responsible for these evolutionary specializations remain unclear. Here we used a recently developed molecular phyloecological method to reconstruct the diets of the ancestral archosaur and of the common ancestor of living birds (CALB). Our results showed that the ancestral archosaur exhibited a predominant Darwinian selection of protein and fat digestion and absorption, whereas the CALB showed a marked enhanced selection of carbohydrate and fat digestion and absorption, suggesting a trophic shift from carnivory to herbivory (fruit, seed, and/or nut-eater) at the archosaur-to-bird transition. The evolutionary shift of the CALB to herbivory may have essentially made them become a low-level consumer and, consequently, subject to relatively high predation risk from potential predators such as gliding maniraptorans, from which birds descended. Under the relatively high predation pressure, ancestral birds with gliding capability may have then evolved not only flapping flight as a possible anti-predator strategy against gliding predatory maniraptorans but also the specialized digestive system as an evolutionary tradeoff of maximizing foraging efficiency and minimizing predation risk. Our results suggest that the powered flight and specialized digestive system of birds may have evolved as a result of their tropic shift-associated predation pressure.

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“…ApoAIV knockout mice secrete larger CMs into the lymph (12) and thus altered apoAIV production may influence the rate of delipidation through alterations in CM size as larger CMs are lipolyzed at a faster rate than smaller particles in animal models (61,62). The multitude of metabolic functions of apoAIV are an active area of research that may improve our understanding of the regulation of intestinal apoAIV production and its influence on lipoprotein clearance in metabolic disease (63).…”

Section: Dysregulation Of Intestinal Lipoprotein Metabolism In Type 2mentioning

confidence: 99%

Role of the Gut in Diabetic Dyslipidemia

et al. 2020

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Type 2 diabetes (T2D) is associated with increased risk of cardiovascular disease (CVD). In insulin resistant states such as the metabolic syndrome, overproduction and impaired clearance of liver-derived very-low-density lipoproteins and gut-derived chylomicrons (CMs) contribute to hypertriglyceridemia and elevated atherogenic remnant lipoproteins. Although ingested fat is the major stimulus of CM secretion, intestinal lipid handling and ultimately CM secretory rate is determined by numerous additional regulatory inputs including nutrients, hormones and neural signals that fine tune CM secretion during fasted and fed states. Insulin resistance and T2D represent perturbed metabolic states in which intestinal sensitivity to key regulatory hormones such as insulin, leptin and glucagon-like peptide-1 (GLP-1) may be altered, contributing to increased CM secretion. In this review, we describe the evidence from human and animal models demonstrating increased CM secretion in insulin resistance and T2D and discuss the molecular mechanisms underlying these effects. Several novel compounds are in various stages of preclinical and clinical investigation to modulate intestinal CM synthesis and secretion. Their efficacy, safety and therapeutic utility are discussed. Similarly, the effects of currently approved lipid modulating therapies such as statins, ezetimibe, fibrates, and PCSK9 inhibitors on intestinal CM production are discussed. The intricacies of intestinal CM production are an active area of research that may yield novel therapies to prevent atherosclerotic CVD in insulin resistance and T2D.

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Apolipoprotein A-IV: A Multifunctional Protein Involved in Protection against Atherosclerosis and Diabetes

Cited by 107 publications

References 123 publications

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Protein Deimination and Extracellular Vesicle Profiles in Antarctic Seabirds

Trophic shift and the origin of birds

Role of the Gut in Diabetic Dyslipidemia

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