Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors

Pereira, Maria J.; Skrtic, Stanko; Katsogiannos, Petros; Abrahamsson, Niclas; Sidibeh, Cherno O.; Dahgam, Santosh; Månsson, Marianne; Risérus, Ulf; Kullberg, Joel; Eriksson, Jan W.

doi:10.1016/j.metabol.2016.09.008

Cited by 57 publications

(55 citation statements)

References 54 publications

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“…The use of linseed oil led to significant lipid changes after four weeks of supplementation. There was a decrease in TC, LDL-C and non-HDL-C, and TG, as well as an increase in HDL-C and HDL 3 -C. The positive linear relationship between TG and NEFAs, as well as between BMI and NEFAs, shown in the study are not unexpected because NEFAs are TG-released molecules due to lipase action, whereas NEFA regulation factors include obesity [25]. In the current study, the BMI in most patients was in the overweight/obesity range.…”

Section: Discussionsupporting

confidence: 53%

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

et al. 2018

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A b s t r a c tBackground: Linseed oil has cardio-protective effects. However, its antihypertensive action has not yet been well characterised. Aim:The primary purpose of the study was to evaluate the effect of short-term dietary supplementation with linseed oil on blood pressure (BP) and lipid metabolism in patients with mild hypercholesterolaemia. The secondary aim was to assess the effect of linseed oil on nitric oxide pathway and selected serum trace metals.Methods: 150 volunteers: 43 men (49.9 ± 11.5 years) and 107 women (53.2 ± 10.3 years), diagnosed with mild hypercholesterolaemia, were assessed prospectively for BP and lipid levels, before and after lipid-lowering diet plus linseed oil supplementation at a dose of 15 mL daily for four weeks (study groups) or four-weekly lipid-lowering diet (control group). Multivariate logistic regression analysis was used to determine the effect of linseed oil on BP after adjustment for age, sex, height, body weight, body mass index, smoking status, and alcohol consumption.Results: Supplementation with linseed oil significantly decreased low-density lipoprotein (LDL)-and non-high-density lipoprotein (HDL) cholesterol, and increased HDL-and HDL 3 -cholesterol levels. Additionally, linseed oil decreased diastolic BP in men (95% confidence interval [CI]: -6.0 to -1.1, p < 0.006), whereas in women linseed oil reduced (p < 0.001) systolic BP (-3.6 mmHg; 95% CI: -5.8 to -1.5) as well as diastolic BP (-4 mmHg; 95% CI: -5.8 to -2.1). Women with higher BP displayed an increase in serum L-arginine level (p < 0.01). In the logistic regression model oil consumption was associated with a decrease in mean BP (adjusted odds ratio 3.85; 95% CI 1.32-11.33). Conclusions:Our findings confirm the benefit of short-term linseed oil use in mild hypercholesterolaemia, particularly in patients with increased blood pressure.

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Section: Discussionsupporting

confidence: 53%

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

et al. 2018

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“…We found no short term effect of isoproterenol or of isoproterenol with different concentrations of insulin on the re-esterification, which suggests that the regulation is mainly at a transcriptional level (paper III). In agreement with our results, a recent paper reported that during an oral glucose tolerance test there was no difference in glycerol but elevated FA release when comparing T2D and control subjects [147]. Also in this report, the release of glycerol from isolated adipocytes obtained from T2D patients did not differ from controls.…”

Section: Lipolysis In T2dsupporting

confidence: 93%

“…This discrepancy could be due to smaller difference in body mass index (BMI) between the groups and number of subjects in the study. However, the physiological significance of reduced levels of HSL in T2D is questionable, since we and others see no difference in glycerol release from adipocytes between nondiabetic and diabetic individuals (paper III) [147].…”

Section: Atgl and Hslmentioning

confidence: 68%

“…Also in this report, the release of glycerol from isolated adipocytes obtained from T2D patients did not differ from controls. There were no difference in transcripts of genes associated with lipolysis like ATGL or HSL, but reduced levels of lipogenic genes like acylglycerol-3-P acyltransferase (AGPAT), diacylglycerol acyltransferase (DGAT) and fatty acid synthase in fat cells from T2D patients [147]. Also microdialysis measurements of basal and isoproterenol induced glycerol release from abdominal subcutaneous adipose tissue has shown no difference between T2D and control subjects [183].…”

Section: Lipolysis In T2dmentioning

confidence: 92%

“…There are reports of decreased or unaffected lipolysis in response to adrenergic stimulation in diabetes [147,181]. Likewise, insulin-mediated antilipolysis has been variously reported as, normal, increased or decreased in diabetes [147,181,182]. In paper III we measure the release of glycerol and FA from adipocytes obtained from obese patients diagnosed with T2D and with a BMI >28 and from control patients with BMI < 28.…”

Section: Lipolysis In T2dmentioning

confidence: 99%

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Insulin Signalling in Human Adipocytes and its Interplay with beta-Adrenergic Control of Lipolysis

Karlsson¹

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Cover: Fluorescence microscopic image demonstrating the association of caveolin-1 and IQGAP1 (paper II). In a proximity ligation assay each red dot represents a single IQGAP1 -caveolin-1 complex stained with Hoechst, nucleus is stained with DAPI. © Cecilia Jönsson 2018Published articles in this thesis have been reprinted with the permission of respective copyright holders. Printed by LiU-Tryck, Linköping 2018 During the course of the research underlying this thesis, Cecilia Jönsson was enrolled in Forum Scientium, a multidisciplinary doctoral program at Linköping University, Sweden AbstractThe prevalence of obesity has over the last 40 years nearly tripled and obesity is one of the major risk factors of developing type 2 diabetes. Type 2 diabetes was formerly called adultonset diabetes but today, probably due to the rise in childhood obesity, it is also seen in children and adolescents. Type 2 diabetes is diagnosed when the body no longer can control the glucose levels in the blood. This is due to an insulin resistant state in the insulin responding tissues, liver, adipose and muscle and insufficient production of insulin in the pancreas. However, in spite of extensive research the mechanisms behind insulin resistance is still not known.The adipose tissue is believed to play a major role in the development of whole body insulin resistance. Adipocytes are the most important sites for storage of the high energy containing triacylglycerols. Insulin stimulation causes the adipocyte to increase the uptake of glucose and to reduce lipolysis: the hydrolysis of triacylglycerol and release of glycerol and fatty acids. The insulin signalling network is complex with numerous proteins involved. These signalling proteins not only transmit the insulin signal but also create negative and positive feedbackloops and induce cross talk between different parts of the network and with the signalling of other hormones. One important positive feedback in insulin signalling is the mTORC1 mediated feedback to phosphorylation of IRS1 at serine 307. In paper I we found that in human adipocytes this feedback is not likely catalysed by the assumed kinase S6K1. However we find an immunoprecipitate of mTOR to contain a ser307 phosphorylating kinase.Scaffolding proteins serve as docking sites for several proteins to promote protein-protein interactions that facilitate signal transduction. In paper II we demonstrate the existence of the scaffolding protein IQGAP1 in human adipocytes and that the expression of IQGAP1 is downregulated in type 2 diabetes. We reveal that IQGAP1 co-localises with caveolae, invaginations of the plasma membrane where the insulin receptor is situated, and that this interaction is increased upon insulin stimulation.In paper III we focus on the control of lipolysis, and sought to understand the interplay between insulin and beta-adrenergic stimulation. We demonstrated that the re-esterification of fatty acids is downregulated in type 2 diabetes causing an increased release of fatty acids from the cells. We showed th...

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Positional and compositional analysis of saturated, monounsaturated, and polyunsaturated fatty acids in human adipose tissue triglyceride by ¹³C nuclear magnetic resonance

et al. 2021

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The synthesis and turnover of triglyceride in adipose tissue involves enzymes with preferences for specific fatty acid classes and/or regioselectivity regarding the fatty acid position within the glycerol moiety. The focus of the current study was to characterize both the composition of fatty acids and their positional distribution in triglycerides of biopsied human subcutaneous adipose tissue, from subjects with wide ranges of body mass index (BMI) and insulin sensitivity, using 13C nuclear magnetic resonance (NMR) spectroscopy. The triglyceride sn2 position was significantly more enriched with monounsaturated fatty acids compared with that of sn1,3, while the abundance of saturated fatty acids was significantly lower in the sn2 position compared with that of sn1,3. Furthermore, the analysis revealed significant positive correlations between the total fraction of palmitoleic acid with both BMI and insulin sensitivity scores (homeostatic model assessment of insulin resistance index). Additionally, we established that 13C NMR chemical shifts for ω‐3 signals, centered at 31.9 ppm, provided superior resolution of the most abundant fatty acid species, including palmitoleate, compared with the ω‐2 signals that were used previously. 13C NMR spectroscopy reveals for the first time a highly nonhomogenous distribution of fatty acids in the glycerol sites of human adipose tissue triglyceride, and that these distributions are correlated with different phenotypes, such as BMI and insulin sensitivity.

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Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors

Cited by 57 publications

References 54 publications

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

Insulin Signalling in Human Adipocytes and its Interplay with beta-Adrenergic Control of Lipolysis

Positional and compositional analysis of saturated, monounsaturated, and polyunsaturated fatty acids in human adipose tissue triglyceride by ¹³C nuclear magnetic resonance

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Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors

Cited by 57 publications

References 54 publications

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

Linseed oil increases HDL3 cholesterol and decreases blood pressure in patients diagnosed with mild hypercholesterolaemia

Insulin Signalling in Human Adipocytes and its Interplay with beta-Adrenergic Control of Lipolysis

Positional and compositional analysis of saturated, monounsaturated, and polyunsaturated fatty acids in human adipose tissue triglyceride by 13C nuclear magnetic resonance

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Product

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Positional and compositional analysis of saturated, monounsaturated, and polyunsaturated fatty acids in human adipose tissue triglyceride by ¹³C nuclear magnetic resonance