Lipoprotein Lipase Deficiency (R243H) in a Type 2 Diabetes Patient with Multiple Arterial Aneurysms

Suzuki, Toru; Sawada, Shojiro; Ishigaki, Yasushi; Tsukita, Sohei; Kodama, Shohei; Sugisawa, Takashi; Imai, Junta; Yamada, Tetsuya; Yamaguchi, Takashi; Murano, Takeyoshi; Katagiri, Hideki

doi:10.2169/internalmedicine.55.5239

Cited by 9 publications

(7 citation statements)

References 24 publications

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“…Lipoprotein lipase (LPL) is the key enzyme responsible for the modulation of circulating lipid levels, and a decrease in LPL activity was shown to be responsible for many cases of hyperlipidemia. 16 We then tested the levels of LPL by Western blot analyses, and observed a significant increase of LPL protein levels in the liver tissues of ApoE À/À /Tollip À/À as compared with ApoE À/ À mice fed with an HFD ( Figure 4D).…”

Section: Tollip Deficiency Exacerbates Liver Steatosismentioning

confidence: 98%

Tollip Deficiency Alters Atherosclerosis and Steatosis by Disrupting Lipophagy

Chen

Yuan

Zhang

et al. 2017

JAHA

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BackgroundCompromised lipophagy with unknown mechanisms may be critically involved in the intracellular accumulation of lipids, contributing to elevated atherosclerosis and liver steatosis. We hypothesize that toll‐interacting protein (Tollip), a key innate immune molecule involved in the fusion of autolysosome, may play a significant role in lipophagy and modulate lipid accumulation during the pathogenesis of atherosclerosis and liver steatosis.Methods and ResultsBy comparing mice fed with either a Western high‐fat diet or a regular chow diet, we observed that both atherosclerosis and liver steatosis were aggravated in apolipoprotein E–deficient (ApoE−/−)/Tollip−/− mice as compared with ApoE−/− mice. Through electron microscopy analyses, we observed compromised fusion of lipid droplets with lysosomes within aortic macrophages as well as liver hepatocytes from ApoE−/−/Tollip−/− mice as compared with ApoE−/− mice. As a molecular indicator for disrupted lysosome fusion, the levels of p62 were significantly elevated in aortic and liver tissues from ApoE−/−/Tollip−/− mice. Molecules involved in facilitating lipophagy completion such as Ras‐related protein 7 and gamma‐aminobutyric acid receptor‐associated protein were reduced in ApoE−/−/Tollip−/− mice as compared with ApoE−/− mice. Intriguingly, ApoE−/−/Tollip−/− mice had reduced circulating levels of inflammatory cytokines such as tumor necrosis factor‐α and increased levels of transforming growth factor‐β. The reduced inflammation due to Tollip deficiency is consistent with a stable atherosclerotic plaque phenotype with increased levels of plaque collagen and smooth muscle cells in ApoE−/−/Tollip−/− mice.ConclusionsTollip deficiency selectively leads to enlarged yet stable atherosclerotic plaques, increased circulating lipids, liver steatosis, and reduced inflammation. Compromised lipophagy and reduced expression of inflammatory mediators due to Tollip deficiency may be the underlying causes. Our data suggest that lipid accumulation and inflammation may be intertwined yet independent processes during the progression of atherosclerosis and steatosis.

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Section: Tollip Deficiency Exacerbates Liver Steatosismentioning

confidence: 98%

Tollip Deficiency Alters Atherosclerosis and Steatosis by Disrupting Lipophagy

Chen

Yuan

Zhang

et al. 2017

JAHA

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“…LPL hydrolyzes and removes triglyceride-rich lipoprotein from the circulation [24]. Type 2 diabetes patients with insulin resistance have lower LPL activity in plasma and impaired clearance of triglyceride-rich lipoprotein, leading to retention of chylomicrons and VLDL in blood [25]. In our patient, the plasma LPL activity measured after intravenous heparin injection was normal on day 9 after admission, when the triglyceride level was 421 mg/dL.…”

Section: Discussionmentioning

confidence: 73%

Eruptive xanthomas in a patient with soft-drink diabetic ketosis and apolipoprotein E4/2

et al. 2019

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Soft-drink diabetic ketosis, characterized by acute onset ketosis induced by excessive ingestion of sugar-containing drinks, is often seen in obese, young patients, even with undiagnosed type 2 diabetes. We herein report a 15-year-old obese patient with the apolipoprotein E4/2 phenotype, in whom eruptive xanthomas lead to a diagnosis of soft-drink diabetic ketosis. He developed multiple asymptomatic yellowish papules on the auricles, back, buttocks and the extensor surfaces of the elbows and knees. He initially visited a dermatology clinic and his blood triglyceride and HbA1c levels were found to be 6,490 mg/dL and 16.5%, respectively. He was referred to our hospital for treatment of hyperglycemia and hypertyriglyceridemia. On admission, he had ketonuria and increased blood levels of 3-hydroxybutylate and acetoacetate. He habitually drank 1-3 litters of sweet beverages daily to quench his thirst. Therefore, "soft-drink diabetic ketosis" was diagnosed. Severe hypertriglyceridemia was considered to have been a consequence of impaired insulin action and his apolipoprotein E4/2 phenotype. We treated the diabetic ketosis and hypertriglyceridemia with intensive insulin therapy and a fat-restricted diet. At discharge, he no longer required insulin therapy and his blood glucose levels were controlled with metformin and voglibose. Along with amelioration of the hyperglycemia, triglyceride levels decreased to 247 mg/dL without administration of anti-hyperlipidemia agents. The eruptive xanthoma lesions gradually diminished in size and number and eventually disappeared by 12 months. This case provides an instructive example of eruptive xanthomas serving as a sign of severe dysregulation, not only of lipid, but also glucose, metabolism.

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“…Hypertriglyceridemia is a common finding in diabetic patients and is responsible for vascular complications. Lipid accumulation in hepatic tissue is mediated through a variety of derangements in metabolic and regulatory processes leading to hypercholesterolemia and hypertriglyceridemia [17].In the diabetic state, insulin deficiency increases mobilization of fatty acids from adipose tissue which are channelized to liver and esterified resulting in hypertriglyceridemia [18]. monoacylglycerol for tissue utilisation.…”

Section: Discussionmentioning

confidence: 99%

Isopulegol Ameliorates Dyslipidemia by Modulating Adipokine Secretion in High Fat Diet / Streptozotocin Induced Diabetic Rats

Kalaivani¹,

Sankaranarayanan²

2019

J. Drug Delivery Ther.

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The present study investigates the effect of isopulegol on adipokine secretion and dyslipidemia in high fat diet and streptozotocin (HFD/STZ) induced diabetic rats. Animals were made diabetic by feeding HFD for 4 wks followed by single intraperitoneal injection of STZ (35mg/kg b.w; 0.1M citrate buffer; pH 4.0). Diabetic rats showed increased levels of total cholesterol, triglycerides, free fatty acids, phospholipids, low density lipoprotein-C (LDL-C), very low density lipoprotein -C (VLDL-C) and decreased high density lipoprotein-C levels (HDL-C). Similarly, the activity of HMG-CoA reductase, was increased while lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) activities were significantly decreased. Furthermore, the expression of sterol regulatory element binding protein-1C (SREBP-1C), adiponectin, peroxisome proliferator activated receptor gamma (PPARγ) were significantly down regulated, whereas leptin expression was upregulated in diabetic rats. Administration of isopulegol (100 mg/kg b.w) for 28 days signiﬁcantly restored lipid levels in plasma and liver tissue by modulating adipokine secretion in diabetic treated rats. From this we conclude that isopulegol exhibited significant antihyperlipidemic effect in HFD/STZ induced diabetic rats. Keywords: Dyslipidemia, Diabetes mellitus, Adiponectin, Leptin, PPARγ, SREBP-1C

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Lipoprotein Lipase Deficiency (R243H) in a Type 2 Diabetes Patient with Multiple Arterial Aneurysms

Cited by 9 publications

References 24 publications

Tollip Deficiency Alters Atherosclerosis and Steatosis by Disrupting Lipophagy

Tollip Deficiency Alters Atherosclerosis and Steatosis by Disrupting Lipophagy

Eruptive xanthomas in a patient with soft-drink diabetic ketosis and apolipoprotein E4/2

Isopulegol Ameliorates Dyslipidemia by Modulating Adipokine Secretion in High Fat Diet / Streptozotocin Induced Diabetic Rats

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