Studies of association of AGPAT6variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

Snogdal, Lena Sønder; Grarup, Niels; Banasik, Karina; Wod, Mette; Jørgensen, Torben; Witte, Daniel R.; Lauritzen, Torsten; Nielsen, Aneta Aleksandra; Brandslund, Ivan; Christensen, Cramer; Pedersen, Oluf; Yderstræde, Knud Bonnet; Beck‐Nielsen, Henning; Henriksen, Jan Erik; Hansen, Torben; Højlund, Kurt

doi:10.1186/1471-2350-14-113

Cited by 2 publications

(1 citation statement)

References 35 publications

(44 reference statements)

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“…Liver plays a central role in lipid metabolism . Usually, insulin resistance is hallmarked by the excessive lipid accumulation in liver, further the lipid deposition will give rise to the morphological and functional perturbations of liver. , Raised levels of triglyceride and cholesterol were common in insulin resistance, and have become two focused problems . Currently, looking for a suitable entry point is the linchpin to resolve above matters.…”

Section: Introductionmentioning

confidence: 99%

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid–FXR–SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice

Tian

Cai

et al. 2021

J. Agric. Food Chem.

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ι-Carrageenan tetrasaccharide (ιCTs), a novel oligosaccharide, was hydrolyzed from ι-carrageenan with targeting marine tool-enzyme Cgi82A. Previously, we have found ιCTs exhibited a hypoglycemic effect, whether it could regulate lipid metabolism remains unknown. In this study, the insulin-resistant mice induced by high-fat−high-sucrose diet were orally administrated with ιCTs (30 mg/kg•bw) for 20 weeks. The results showed that the contents of triglyceride and cholesterol in both serum and liver were reduced by ιCTs, and their excretion in feces were promoted, suggesting lipid accumulation was inhibited. Intriguingly, the overall levels of bile acid in serum, liver, and feces were all raised by ιCTs. Given that bile acids are the essential signal factors for regulating lipid metabolism via the farnesoid-X-receptor (FXR), we conducted serum bile acid profile analysis and found that the levels of high-affinity agonists deoxycholic acid and lithocholic acid were decreased in the ιCTs group, showing that ιCTs failed to activate FXR. Western blot analysis showed that ιCTs downregulated hepatic FXR and small heterodimer partner (SHP) expression and increased downstream CYP7A1 expression via regulating the FXR−SHP signal to accelerate liver cholesterol conversion. Meanwhile, ιCTs decreased the expression of PXR and SREBP1c and elevated the expression of PPARα and CPT1α via regulating the FXR-PXR-SREBP1c/PPARα signal to inhibit fatty acid synthesis and promote fatty acid β-oxidation. To the best of our knowledge, this study for the first time reported that ιCTs alleviated liver lipid accumulation via the bile acid−FXR−SHP/PXR signal to regulate cholesterol conversion and fatty acid metabolism, which highlighted a new idea for ameliorating insulin resistance.

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Section: Introductionmentioning

confidence: 99%

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid–FXR–SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice

Tian

Cai

et al. 2021

J. Agric. Food Chem.

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Vejle Diabetes Biobank – a resource for studies of the etiologies of diabetes and its comorbidities

Petersen¹,

Nielsen²,

Christensen³

et al. 2016

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AimsCarefully designed and established biobanks are considered one of the most essential resources to foster biomedical research as they provide cost-effective and rapid access to a vast variety of biological materials and related anthropometrics allowing for testing of various biomarkers as well as numerous original and pertinent bioclinical hypotheses related to human disease etiology and prognosis. The objective of the present study was to present the baseline data, design, and methods used for the establishment of the Vejle Diabetes Biobank. Further aims included assessment of the prevalence of diabetes and quality of diabetes treatment in a specified Danish region.MethodsThe Vejle Diabetes Biobank was established from 2007 to 2010 as a regional Biobank containing blood, DNA, and urine samples from patients with diabetes and a gender- and age-matched control population aged 25–75 years. Anthropometrics were obtained by physical examination, questionnaires, and interviews at the time of inclusion into the Biobank. The cohort was linked to the Danish Civil Registration System, the Danish National Patient Registry, and the Danish National Prescription Registry.ResultsIn total, 4,255 nondiabetic individuals and 3,320 patients with diabetes were included. Type 2 diabetes (T2D) patients had a higher body mass index (30 kg/m2) than type 1 diabetes (T1D) patients (25 and 26 kg/m2 in women and men, respectively) and control subjects (25 and 27 kg/m2 in women and men, respectively). Fasting levels of plasma triglycerides and blood pressure were higher in T2D patients (1.5 mmol/L and 148/85 mmHg, respectively) compared with T1D patients (0.9 mmol/L and 139/81 mmHg, respectively), whereas glycated hemoglobin (HbA1c), plasma high density lipoprotein, low density lipoprotein, and total cholesterol were lower in T2D patients (51 mmol/mol, 1.2 mmol/L, 2.2 mmol/L, and 4.2 mmol/L, respectively) compared with findings in T1D patients (61 mmol/mol, 1.6 mmol/L, 2.3 mmol/L, and 4.4 mmol/L, respectively). At the time of inclusion into the Biobank, 56% of the T2D patients and 25% of T1D patients had an HbA1c <7% (53 mmol/mol). Only 28% and 34% of the T2D patients, respectively, reached treatment target for blood pressure and lipids.ConclusionThe Vejle Diabetes Biobank represents one of the largest open diabetes case-control cohorts in Denmark. The Biobank invites collaborative investigations of diabetes and diabetes complication etiologies as well as studies of prognostic or predictive biomarkers.

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Studies of association of AGPAT6variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

Cited by 2 publications

References 35 publications

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid–FXR–SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid–FXR–SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice

Vejle Diabetes Biobank – a resource for studies of the etiologies of diabetes and its comorbidities

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Studies of association of AGPAT6variants with type 2 diabetes and related metabolic phenotypes in 12,068 Danes

Cited by 2 publications

References 35 publications

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid–FXR–SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice

Novel ι-Carrageenan Tetrasaccharide Alleviates Liver Lipid Accumulation via the Bile Acid–FXR–SHP/PXR Pathway to Regulate Cholesterol Conversion and Fatty Acid Metabolism in Insulin-Resistant Mice

Vejle Diabetes Biobank &ndash; a resource for studies of the etiologies of diabetes and its comorbidities

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Product

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Vejle Diabetes Biobank – a resource for studies of the etiologies of diabetes and its comorbidities