The role of abnormalities of lipoproteins and HDL functionality in small fibre dysfunction in people with severe obesity

AbstractObesity and associated dyslipidemia may contribute to increased cardiovascular disease. Obesity has also been associated with neuropathy. We have investigated presence of peripheral nerve damage in patients with severe obesity without type 2 diabetes and the status of metabolic syndrome and lipoprotein abnormalities. 47participants with severe obesity and 30 age-matched healthy controls underwent detailed phenotyping of neuropathy and an assessment of lipoproteins and HDL-functionality. Participants with severe obesity had a higher neuropathy symptom profile, lower sural and peroneal nerve amplitudes, abnormal thermal thresholds, heart rate variability with deep breathing and corneal nerve parameters compared to healthy controls. Circulating apolipoprotein A1 (P = 0.009), HDL cholesterol (HDL-C) (P < 0.0001), cholesterol efflux (P = 0.002) and paroxonase-1 (PON-1) activity (P < 0.0001) were lower, and serum amyloid A (SAA) (P < 0.0001) was higher in participants with obesity compared to controls. Obese participants with small nerve fibre damage had higher serum triglycerides (P = 0.02), lower PON-1 activity (P = 0.002) and higher prevalence of metabolic syndrome (58% vs. 23%, P = 0.02) compared to those without. However, HDL-C (P = 0.8), cholesterol efflux (P = 0.08), apoA1 (P = 0.8) and SAA (P = 0.8) did not differ significantly between obese participants with and without small nerve fibre damage. Small nerve fibre damage occurs in people with severe obesity. Patients with obesity have deranged lipoproteins and compromised HDL functionality compared to controls. Obese patients with evidence of small nerve fibre damage, compared to those without, had significantly higher serum triglycerides, lower PON-1 activity and a higher prevalence of metabolic syndrome.

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Measurement of Plasma Resistin Concentrations in Horses with Metabolic and Inflammatory Disorders

Animals ◽

10.3390/ani12010077 ◽

2021 ◽

Vol 12 (1) ◽

pp. 77

Author(s):

Beatriz Fuentes-Romero ◽

Alberto Muñoz-Prieto ◽

José J. Cerón ◽

María Martín-Cuervo ◽

Manuel Iglesias-García ◽

...

Keyword(s):

Metabolic Syndrome ◽

Basal Insulin ◽

Serum Amyloid A ◽

Expression Patterns ◽

Inflammatory Cells ◽

Healthy Controls ◽

Amyloid A ◽

Inflammatory Conditions ◽

Inflammatory Status ◽

Developed World

Obesity and its associated complications, such as metabolic syndrome, are an increasing problem in both humans and horses in the developed world. The expression patterns of resistin differ considerably between species. In rodents, resistin is expressed by adipocytes and is related to obesity and ID. In humans, resistin is predominantly produced by inflammatory cells, and resistin concentrations do not reflect the degree of obesity, although they may predict cardiovascular outcomes. The aim of this study was to investigate the usefulness of resistin and its relationship with ID and selected indicators of inflammation in horses. Seventy-two horses, included in one of the four following groups, were studied: healthy controls (C, n = 14), horses with inflammatory conditions (I, n = 21), horses with mild ID (ID1, n = 18), and horses with severe ID (ID2, n = 19). Plasma resistin concentrations were significantly different between groups and the higher values were recorded in the I and ID2 groups (C: 2.38 ± 1.69 ng/mL; I: 6.85 ± 8.38 ng/mL; ID1: 2.41 ± 2.70 ng/mL; ID2: 4.49 ± 3.08 ng/mL). Plasma resistin was not correlated with basal insulin concentrations. A significant (r = 0.336, p = 0.002) correlation was found between resistin and serum amyloid A. Our results show that, as is the case in humans, plasma resistin concentrations in horses are predominantly related to inflammatory conditions and not to ID. Horses with severe ID showed an elevation in resistin that may be secondary to the inflammatory status associated with metabolic syndrome.

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Early Detection of Diabetic Peripheral Neuropathy: A Focus on Small Nerve Fibres

Diagnostics ◽

10.3390/diagnostics11020165 ◽

2021 ◽

Vol 11 (2) ◽

pp. 165

Author(s):

Jamie Burgess ◽

Bernhard Frank ◽

Andrew Marshall ◽

Rashaad S. Khalil ◽

Georgios Ponirakis ◽

...

Keyword(s):

Peripheral Neuropathy ◽

Nerve Fibre ◽

Diabetic Peripheral Neuropathy ◽

Point Of Care ◽

Unmet Need ◽

Screening Tools ◽

Nerve Fibres ◽

Diagnostic Laboratory ◽

Corneal Confocal Microscopy ◽

Small Nerve

Diabetic peripheral neuropathy (DPN) is the most common complication of both type 1 and 2 diabetes. As a result, neuropathic pain, diabetic foot ulcers and lower-limb amputations impact drastically on quality of life, contributing to the individual, societal, financial and healthcare burden of diabetes. DPN is diagnosed at a late, often pre-ulcerative stage due to a lack of early systematic screening and the endorsement of monofilament testing which identifies advanced neuropathy only. Compared to the success of the diabetic eye and kidney screening programmes there is clearly an unmet need for an objective reliable biomarker for the detection of early DPN. This article critically appraises research and clinical methods for the diagnosis or screening of early DPN. In brief, functional measures are subjective and are difficult to implement due to technical complexity. Moreover, skin biopsy is invasive, expensive and lacks diagnostic laboratory capacity. Indeed, point-of-care nerve conduction tests are convenient and easy to implement however questions are raised regarding their suitability for use in screening due to the lack of small nerve fibre evaluation. Corneal confocal microscopy (CCM) is a rapid, non-invasive, and reproducible technique to quantify small nerve fibre damage and repair which can be conducted alongside retinopathy screening. CCM identifies early sub-clinical DPN, predicts the development and allows staging of DPN severity. Automated quantification of CCM with AI has enabled enhanced unbiased quantification of small nerve fibres and potentially early diagnosis of DPN. Improved screening tools will prevent and reduce the burden of foot ulceration and amputations with the primary aim of reducing the prevalence of this common microvascular complication.

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Bariatric surgery leads to an improvement in small nerve fibre damage in subjects with obesity

International Journal of Obesity ◽

10.1038/s41366-020-00727-9 ◽

2021 ◽

Vol 45 (3) ◽

pp. 631-638

Author(s):

Shazli Azmi ◽

Maryam Ferdousi ◽

Yifen Liu ◽

Safwaan Adam ◽

Zohaib Iqbal ◽

...

Keyword(s):

Bariatric Surgery ◽

Nerve Fibre ◽

Small Nerve

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Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma

Scientific Reports ◽

10.1038/s41598-021-85089-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sophie Jacques ◽

Arash Arjomand ◽

Hélène Perée ◽

Patrick Collins ◽

Alice Mayer ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Insulin Resistance ◽

Metabolic Syndrome ◽

Liver Damage ◽

Chow Diet ◽

Serum Triglycerides ◽

Alcoholic Fatty Liver ◽

Alcoholic Steatohepatitis ◽

Dual Specificity ◽

Dual Specificity Protein Phosphatase

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.

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Raised TSH is associated with endothelial dysfunction in Metabolic Syndrome: A case control study

Romanian Journal of Internal Medicine ◽

10.1515/rjim-2017-0023 ◽

2017 ◽

Vol 55 (4) ◽

pp. 212-221 ◽

Cited By ~ 2

Author(s):

Ashok Kumar Ahirwar ◽

Archana Singh ◽

Anju Jain ◽

Surajeet Kumar Patra ◽

Binita Goswami ◽

...

Keyword(s):

Metabolic Syndrome ◽

Endothelial Dysfunction ◽

Subclinical Hypothyroidism ◽

Serum Insulin ◽

Binary Logistic Regression ◽

Binary Logistic Regression Analysis ◽

Healthy Controls ◽

Healthy Control ◽

Study Population ◽

Serum Tsh

AbstractIntroduction. Endothelial dysfunction has been considered as one of the important factors in pathogenesis of Metabolic Syndrome (Met S). Subclinical hypothyroidism (SCH) has also been reported to be associated with Met S. The aim of our study is to evaluate the association of raised TSH with mediators of endothelial dysfunction in Met S with Subclinical hypothyroidism as compared to healthy controls.Methods. Study population consisted of 100 subjects, out of which 50 were cases of Met S and 50 were healthy controls. Met S group were further divided into two, based on the presence & absence of SCH. Serum insulin, T3, T4, TSH were measured by chemiluminescence based immunoassay (CLIA). Serum nitric oxide (NO) levels were measured by Modified Griess’s method and serum endothelin-1 (ET-1) levels were measured by ELISA.Results. Out of 50 cases of Met S, SCH was diagnosed in 22. The mean serum TSH levels were significantly higher in Met S cases as compared to healthy controls (5.7 ± 1.2 μIU/mL vs. 2.3 ± 1.6 μIU/mL, P <0.0001). Mean serum NO levels were significantly lower in Met S cases as compared to healthy control (15.4 ± 10 μM vs. 21 ± 10 μM, p = 0.009). Mean serum ET-1 levels were significantly higher in Met S cases as compared to healthy controls (2.68 ± 1.7 fmol/mL vs. 2.1 ± 0.84 fmol/mL, p = 0.011). On Pearson’s correlation analysis, TSH showed positive correlation with ET-1 (r = 0.341, p = 0.001) and negative correlation with NO (r = −0.331, p = 0.001). Binary logistic regression analysis showed that TSH, NO and ET-1 has significant odd’s ratio for predicting Met S.Conclusion. Met S cases were screened for thyroid abnormalities and found to have 44% of SCH along with co-existing endothelial dysfunction. Raised TSH in SCH could cause endothelial dysfunction which may lead to Met S and associated co-morbidities. Present study gives new insight in linking endothelial dysfunction and raised TSH in Met S. Therefore, Met S cases should be screened for SCH and treated appropriately to attenuate endothelial dysfunction and associated comorbidities in Met S.

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ASSOCIATION BETWEEN SERUM URIC ACID AND METABOLIC SYNDROME

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2018.v11i10.27233 ◽

2018 ◽

Vol 11 (10) ◽

pp. 400 ◽

Cited By ~ 1

Author(s):

Thaslima Nandhini Js ◽

Savitha Basker G ◽

Vishnupriya V

Keyword(s):

Metabolic Syndrome ◽

Uric Acid ◽

Venous Blood ◽

Fasting Blood Glucose ◽

Control Group ◽

Serum Triglycerides ◽

Significant Difference ◽

Disease Condition ◽

Student’S T ◽

Student’S T Test

Objective: Metabolic syndrome is a cluster of disease condition characterized by truncal obesity, hypertriglyceridemia, elevated blood pressure, and insulin resistance. An excessive circulating uric acid (UA) level even within normal range is always comorbid with metabolic syndrome and its components. The aim of the current study was to investigate the association between metabolic syndrome and serum UA level.Methods: A total of 60 subjects were divided into two groups of healthy (30 individuals) and metabolic syndrome patients (30 individuals) from dental outpatient department of Saveetha Dental College and Hospitals. 5 ml of fasting venous blood was collected in the plain collection tubes and centrifuged, and then serum was separated. Then, the serum was used to analyze the fasting blood glucose, serum triglycerides (TGLs), and serum UA by GOD-POD, enzymatic colorimetric, and uricase method, respectively. A statistical analysis was performed using Student’s t-test. p<0.05 was considered to be statistically significant.Result: Mean body mass index (BMI), fasting blood sugar (FBS), TGL, and UA level of control group were 23.36±1.81, 84.45±13.1, 110.9±22.6, and 3.48±1.21 respectively. Mean BMI, FBS, TGL, and UA level of study group were 35.24±3.04, 122.85±23.3, 212.1±39.6 and 9.08±2.63 respectively. There is a significant difference between these two groups with p<0.0001.Conclusion: This study showed that those individuals with metabolic syndrome have higher UA level that indicates hyperuricemia which is a significant predictor of metabolic syndrome.

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Serum Amyloid A Promotes Cholesterol Efflux Mediated by Scavenger Receptor B-I

Journal of Biological Chemistry ◽

10.1074/jbc.m505685200 ◽

2005 ◽

Vol 280 (43) ◽

pp. 35890-35895 ◽

Cited By ~ 101

Author(s):

Deneys R. van der Westhuyzen ◽

Lei Cai ◽

Maria C. de Beer ◽

Frederick C. de Beer

Keyword(s):

Acute Phase ◽

Cholesterol Efflux ◽

Serum Amyloid A ◽

Acute Phase Protein ◽

Scavenger Receptor ◽

Dependent Manner ◽

Cellular Cholesterol ◽

Amyloid A ◽

Phase Protein ◽

Cellular Cholesterol Efflux

Serum amyloid A (SAA) is an acute phase protein whose expression is markedly up-regulated during inflammation and infection. The physiological function of SAA is unclear. In this study, we reported that SAA promotes cellular cholesterol efflux mediated by scavenger receptor B-I (SR-BI). In Chinese hamster ovary cells, SAA promoted cellular cholesterol efflux in an SR-BI-dependent manner, whereas apoA-I did not. Similarly, SAA, but not apoA-I, promoted cholesterol efflux from HepG2 cells in an SR-BI-dependent manner as shown by using the SR-BI inhibitor BLT-1. When SAA was overexpressed in HepG2 cells using adenovirus-mediated gene transfer, the endogenously expressed SAA promoted SR-BI-dependent efflux. To assess the effect of SAA on SR-BI-mediated efflux to high density lipoprotein (HDL), we compared normal HDL, acute phase HDL (AP-HDL, prepared from mice injected with lipopolysaccharide), and AdSAA-HDL (HDL prepared from mice overexpressing SAA). Both AP-HDL and AdSAA-HDL promoted 2-fold greater cholesterol efflux than normal HDL. Lipid-free SAA was shown to also stimulate ABCA1-dependent cholesterol efflux in fibroblasts, in line with an earlier report (Stonik, J. A., Remaley, A. T., Demosky, S. J., Neufeld, E. B., Bocharov, A., and Brewer, H. B. (2004) Biochem. Biophys. Res. Commun. 321, 936–941). When added to cells together, SAA and HDL exerted a synergistic effect in promoting ABCA1-dependent efflux, suggesting that SAA may remodel HDL in a manner that releases apoA-I or other efficient ABCA1 ligands from HDL. SAA also facilitated efflux by a process that was independent of SR-BI and ABCA1. We conclude that the acute phase protein SAA plays an important role in HDL cholesterol metabolism by promoting cellular cholesterol efflux through a number of different efflux pathways.

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Serum triglycerides and cancer risk in the metabolic syndrome and cancer (Me-Can) collaborative study

Cancer Causes & Control ◽

10.1007/s10552-010-9697-0 ◽

2010 ◽

Vol 22 (2) ◽

pp. 291-299 ◽

Cited By ~ 59

Author(s):

Wegene Borena ◽

Tanja Stocks ◽

Håkan Jonsson ◽

Susanne Strohmaier ◽

Gabriele Nagel ◽

...

Keyword(s):

Metabolic Syndrome ◽

Cancer Risk ◽

Collaborative Study ◽

Serum Triglycerides ◽

The Metabolic Syndrome

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Kaempferol ameliorates symptoms of metabolic syndrome by improving blood lipid profile and glucose tolerance

Bioscience Biotechnology and Biochemistry ◽

10.1093/bbb/zbab132 ◽

2021 ◽

Author(s):

Ayasa Ochiai ◽

Mahmoud Ben Othman ◽

Kazuichi Sakamoto

Keyword(s):

Metabolic Syndrome ◽

Glucose Tolerance ◽

Molecular Mechanisms ◽

Ldl Receptor ◽

Blood Lipid ◽

Apolipoprotein A1 ◽

High Density Lipoproteins ◽

Blood Lipid Profile ◽

Beneficial Effects ◽

Apoa1 Gene

Abstract Kaempferol (KPF) is a dietary polyphenol reported to have various beneficial effects on human health. However, its molecular mechanisms in regulating lipid and glucose metabolism are not fully understood. This study examined the effects of KPF on obesity, dyslipidemia, and diabetes in Tsumura, Suzuki, Obese Diabetes (TSOD) mice. The six-week administration of KPF decreased fat weight, serum total cholesterol, and low-density lipoproteins (LDLs); increased high-density lipoproteins (HDLs); and improved glucose tolerance. Additionally, KPF increased LDL receptor (LDLR) and apolipoprotein A1 (ApoA1) gene expression and decreased serum resistin levels. These findings suggest that the decrease in LDL and the increase in HDL caused by KPF may be due to increases in hepatic LDLR and ApoA1 expression, respectively. Furthermore, it is possible that the improvement in glucose tolerance by KPF may occur via resistin reduction. These mechanisms may be parts of complex mechanism by which KPF improves metabolic syndrome.

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Abstract 226: Serum Amyloid A Isoforms and the Capacity to Mediate Cholesterol Efflux

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.34.suppl_1.226 ◽

2014 ◽

Vol 34 (suppl_1) ◽

Author(s):

Hussein Yassine ◽

Olgica Trenchevska ◽

Chad Borges ◽

Dobrin Nedelkov ◽

Randall W Nelson ◽

...

Keyword(s):

Cholesterol Efflux ◽

Serum Amyloid A ◽

Hdl Cholesterol ◽

Acute Phase Reactant ◽

Serum Amyloid ◽

Amyloid A ◽

Cholesterol Levels ◽

Acute Phase Reactant Protein

Serum Amyloid A (SAA) is an acute phase reactant protein that exists in multiple isoforms, can form HDL, and participates in cholesterol efflux. In vitro studies suggest that the SAA 2.1 isoform has an increased capacity to mediate cholesterol efflux compared to the other isoforms. We examined SAA isoforms using a novel mass spectrometric immunoassay (MSIA) and HDL’s cholesterol efflux capacity (via ABCA-1 and SR-BI) in samples from 59 subjects with (n=33) and without type 2 diabetes (n=26). SAA 1.1 levels were detectable in 58, SAA 2.1 in 14 and SAA 2.2 in 36 of the 59 subjects. SAA 2.1 levels significantly correlated with SR-BI cholesterol efflux (r=0.71, p=0.01, n=14), but not ABCA-1 mediated efflux (r=0.1, P=0.1). This correlation was not explained by changes in HDL phospholipids, Apo A-I or HDL cholesterol levels. In contrast, SAA 2.2 or 1.1 levels did not correlate with changes in SR-BI or ABCA-1 mediated efflux. Although the SAA 2.1 isoform is less frequently detected in plasma, our data confirm that it is closely linked with HDL mediated cholesterol efflux, particularly that is SR-BI mediated.

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