Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Adiels, Martin; Taskinen, Marja‐Riitta; Andersson, Linda; Matikainen, Niina; Söderlund, Sanni; Kahri, Juhani; Hakkarainen, Antti; Lundbom, Nina; Sihlbom, Carina; Thorsell, Annika; Zhou, Haihong; Pietiläinen, Kirsi H.; Borén, Jan

doi:10.1111/dom.13744

Cited by 47 publications

(45 citation statements)

References 64 publications

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“…It has been proposed that glucose-mediated regulation of APOC3 expression promotes a shift in the energy source for peripheral tissues from fatty acids released by lipolysis of TRLs to increased utilization of blood glucose ( 28 , 31 , 41 , 42 ). APOC3 expression is therefore upregulated in states of insulin resistance (characterized by insulin resistance and hyperglycemia), and recent results demonstrate that glycaemic control is a major determinant of apoC-III secretion rate in vivo (as measured by stable isotope technology) and thus plasma apoC-III levels ( 43 ). In these studies it was reported also that apoC-III metabolism is significantly perturbed in subjects with type 2 diabetes; the apoC-III secretion rate was markedly higher than that seen in BMI-matched non-diabetic controls.…”

Section: Structure and Regulation Of Apoc-iiimentioning

confidence: 99%

“…In these studies it was reported also that apoC-III metabolism is significantly perturbed in subjects with type 2 diabetes; the apoC-III secretion rate was markedly higher than that seen in BMI-matched non-diabetic controls. Improved glycaemic control with the glucagon-like peptide (GLP)−1 analog liraglutide for 16 weeks reduced the apoC-III secretion rate and as a consequence plasma apoC-III levels ( 43 ). These findings demonstrate that glucose homeostasis is an important regulator of apoC-III metabolism, and that the secretion rate of apoC-III is an important driver for the elevation of TRLs in subjects with type 2 diabetes ( 43 ).…”

Section: Structure and Regulation Of Apoc-iiimentioning

confidence: 99%

“…Fructose induced not only increased expression of APOC3 ( 111 , 113 ), but also increased hepatic de novo lipogenesis of fatty acids that is an important initiator of NAFLD and overproduction of triglyceride-rich VLDL 1 particles ( 43 , 61 , 118 – 122 ). The relative importance of increased liver fat vs. increased secretion of apoC-III for fructose-induced hypertriglyceridemia, remains to clarified.…”

Section: Can Diets Modulate Plasma Apoc-iii Levels?mentioning

confidence: 99%

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The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans

2020

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Cardiovascular disease (CVD) is the leading cause of death globally. It is well-established based on evidence accrued during the last three decades that high plasma concentrations of cholesterol-rich atherogenic lipoproteins are causatively linked to CVD, and that lowering these reduces atherosclerotic cardiovascular events in humans (1-9). Historically, most attention has been on low-density lipoproteins (LDL) since these are the most abundant atherogenic lipoproteins in the circulation, and thus the main carrier of cholesterol into the artery wall. However, with the rise of obesity and insulin resistance in many populations, there is increasing interest in the role of triglyceride-rich lipoproteins (TRLs) and their metabolic remnants, with accumulating evidence showing they too are causatively linked to CVD. Plasma triglyceride, measured either in the fasting or non-fasting state, is a useful index of the abundance of TRLs and recent research into the biology and genetics of triglyceride heritability has provided new insight into the causal relationship of TRLs with CVD. Of the genetic factors known to influence plasma triglyceride levels variation in APOC3-the gene for apolipoprotein (apo) C-III-has emerged as being particularly important as a regulator of triglyceride transport and a novel therapeutic target to reduce dyslipidaemia and CVD risk (10).

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Section: Structure and Regulation Of Apoc-iiimentioning

confidence: 99%

Section: Structure and Regulation Of Apoc-iiimentioning

confidence: 99%

Section: Can Diets Modulate Plasma Apoc-iii Levels?mentioning

confidence: 99%

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The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans

2020

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“…It is noteworthy that our results show the association between the apolipoprotein C and T2DM. Since there are limited studies in this area [51,52], we will pay more attention to the changes in apolipoprotein C during the progress of T2DM in the future.…”

Section: Discussionmentioning

confidence: 99%

Metalloproteins and apolipoprotein C: candidate plasma biomarkers of T2DM screened by comparative proteomics and lipidomics in ZDF rats

Wang

et al. 2020

Preprint

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Background Early diagnosis of type 2 diabetes mellitus (T2DM) is still difficult. Screening of plasma biomarkers has great significance of optimizing diagnosis and predicting the complications of T2DM. Methods We used a special diet, Purina #5C08, to induce diabetes in Zucker leptin receptor gene-deficient rats (fa/fa) to establish Zucker diabetic fatty (ZDF) rats, simulating the early stage of T2DM. The differentially expressed proteins (DEP) and lipids (DEL), as potential biomarkers, were screened to compare the plasma expression levels in ZDF rats and their basic diet-fed wild-type controls (fa/+) by Tandem Mass Tags (TMT) and liquid chromatography-tandem mass spectrometry. Results These two groups had different plasma proteins and lipids profiles consisting of 84 DEPs and, 179 DELs identified in the positive ion mode and 178 DELs in the negative ion mode, respectively. Enrichment analysis of these different indicators showed that oxidative stress, insulin resistance and metabolic disorders of glycan and lipid played an important role in generating the difference. Some markers can be used as candidate biomarkers, such as ceruloplasmin, apolipoprotein C-I, apolipoprotein C-II, apolipoprotein C-IV, etc., in prediction and treatments of T2DM. Conclusion These plasma differences help to optimize the diagnosis and predict the complications of T2DM, although this remains to be verified in the crowd. Trace elements related-metalloproteins, such as ceruloplasmin, and lipid metabolism and transport-related apolipoprotein C are expected to be candidate biomarkers of T2DM and should be given more attention.

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“…The HTG is thought to be due to TGL overproduction in type 2 diabetes as a result of increased release of free fatty acids from adipose tissue, enhanced hepatic lipogenesis and increased secretion of large TRL particles by the liver as well as the intestine as a consequence of insulin resistance and hyperglycemia (39). Although LPL activity is known to be decreased in insulin deficient states (40), recent developments in the understanding of LPL regulation have also shown that insulin resistance leads to increased APOC3 and ANGPTL4, which reduce LPL activity and TGR remnant particle clearance (41)(42)(43).…”

Section: Diabetesmentioning

confidence: 99%

A Comprehensive Update on the Chylomicronemia Syndrome

Goldberg

Chait

2020

Front. Endocrinol.

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The chylomicronemia syndrome is characterized by severe hypertriglyceridemia and fasting chylomicronemia and predisposes affected individuals to acute pancreatitis. When due to very rare monogenic mutations in the genes encoding the enzyme, lipoprotein lipase, or its regulators, APOC2, APOA5, GPIHBP1, and LMF1, it is referred to as the familial chylomicronemia syndrome. Much more frequently, the chylomicronemia syndrome results from a cluster of minor genetic variants causing polygenic hypertriglyceridemia, which is exacerbated by conditions or medications which increase triglyceride levels beyond the saturation point of triglyceride removal systems. This situation is termed the multifactorial chylomicronemia syndrome. These aggravating factors include common conditions such as uncontrolled diabetes, overweight and obesity, alcohol excess, chronic kidney disease and pregnancy and several medications, including diuretics, non-selective beta blockers, estrogenic compounds, corticosteroids, protease inhibitors, immunosuppressives, antipsychotics, antidepressants, retinoids, L-asparaginase, and propofol. A third uncommon cause of the chylomicronemia syndrome is familial forms of partial lipodystrophy. Development of pancreatitis is the most feared complication of the chylomicronemia syndrome, but the risk of cardiovascular disease as well as non-alcoholic steatohepatitis is also increased. Treatment consists of dietary fat restriction and weight reduction combined with the use of triglyceride lowering medications such as fibrates, omega 3 fatty acids and niacin. Effective management of aggravating factors such as improving diabetes control, discontinuing alcohol and replacing or reducing the dose of medications that raise triglyceride levels is essential. Importantly, many if not most cases of the chylomicronemia syndrome can be prevented by effective identification of polygenic hypertriglyceridemia in people with conditions that increase its likelihood or before starting medications that may increase triglyceride levels. Several new pharmacotherapeutic agents are being tested that are likely to considerably improve treatment of hypertriglyceridemia in people at risk.

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Role of apolipoprotein C‐III overproduction in diabetic dyslipidaemia

Cited by 47 publications

References 64 publications

The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans

The Roles of ApoC-III on the Metabolism of Triglyceride-Rich Lipoproteins in Humans

Metalloproteins and apolipoprotein C: candidate plasma biomarkers of T2DM screened by comparative proteomics and lipidomics in ZDF rats

A Comprehensive Update on the Chylomicronemia Syndrome

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