Determinants and correlates of adipose tissue insulin resistance index in Japanese women without diabetes and obesity

IntroductionDeterminants and correlates of a novel index of adipose tissue insulin resistance (AT-IR) (the product of fasting insulin and free fatty acid concentrations) were investigated in Japanese women without diabetes and obesity.Research design and methodsCross-sectional associations of AT-IR with fat mass and distribution, and IR-related cardiometabolic variables were examined in 210 young and 148 middle-aged women whose average body mass index (BMI) was <23 kg/m2 and waist was <80 cm. Multivariate linear regression analyses were used to identify most important determinants of AT-IR.ResultsYoung and middle-aged women did not differ in AT-IR (3.5±2.7 and 3.2±2.1, respectively). In both young and middle-aged women, AT-IR was positively associated with trunk/leg fat ratio, a sophisticated measure of abdominal fat accumulation, fasting plasma glucose (FPG), fasting triglycerides (FTG), serum alanine aminotransferase and γ-glutamyl-transpeptidase (all p<0.05). Furthermore, in middle-aged but not in young women, AT-IR showed positive associations with BMI, waist, fat mass index, low-density lipoprotein cholesterol, apolipoprotein B and systolic and diastolic blood pressure (BP) (all p<0.05). AT-IR showed no association with hemoglobin A1c, high-density lipoprotein (HDL) cholesterol and apolipoprotein A1 in two groups of women. On multivariate analysis including waist, FPG, FTG, HDL cholesterol and systolic BP as independent variables, FPG, FTG and HDL cholesterol emerged as independent determinants of AT-IR in young women (cumulative R2=0.141) and waist in middle-aged women (cumulative R2=0.056). In a model which included trunk/leg fat ratio instead of waist, trunk/leg fat ratio and systolic BP were determinants of AT-IR in middle-aged women (cumulative R2=0.093). Results did not alter in young women.ConclusionsAT-IR may be a simple and useful surrogate index of adipose tissue insulin resistance even in populations without diabetes and obesity.

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Contributions of total and regional fat mass to risk for cardiovascular disease in older women

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00467.2001 ◽

2002 ◽

Vol 282 (5) ◽

pp. E1023-E1028 ◽

Cited By ~ 167

Author(s):

R. E. Van Pelt ◽

E. M. Evans ◽

K. B. Schechtman ◽

A. A. Ehsani ◽

W. M. Kohrt

Keyword(s):

Insulin Resistance ◽

Postmenopausal Women ◽

Fat Mass ◽

Independent Predictor ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Oral Glucose ◽

Protective Effects ◽

Serum Triglycerides ◽

Regional Body Composition

The aim of this study was to determine whether trunk fat mass, measured by dual-energy X-ray absorptiometry (DEXA), is predictive of insulin resistance and dyslipidemia, independently of arm and leg fat mass, in postmenopausal women. Total and regional body composition was measured by DEXA in 166 healthy, postmenopausal women (66 ± 4 yr). Four primary markers of insulin resistance and dyslipidemia were assessed: 1) area under the curve for the insulin (INSAUC) response to an oral glucose tolerance test (OGTT), 2) product of the OGTT glucose and insulin areas (INSAUC×GLUAUC), 3) serum triglycerides (TG), and 4) high-density lipoprotein (HDL)-cholesterol. Trunk fat mass was the strongest independent predictor of each of the primary dependent variables. In multivariate regression models, trunk fat mass was associated with unfavorable levels of INSAUC, INSAUC×GLUAUC, TG, and HDL-C, whereas leg fat mass was favorably associated with each of these variables. Thus trunk fat is a strong independent predictor of insulin resistance and dyslipidemia in postmenopausal women, whereas leg fat appears to confer protective effects against metabolic dysfunction.

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Effect of Dietary Carbohydrate Type on Serum Cardiometabolic Risk Indicators and Adipose Tissue Inflammatory Markers

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2018-00667 ◽

2018 ◽

Vol 103 (9) ◽

pp. 3430-3438 ◽

Cited By ~ 4

Author(s):

Huicui Meng ◽

Nirupa R Matthan ◽

Susan K Fried ◽

Silvia Berciano ◽

Maura E Walker ◽

...

Keyword(s):

Adipose Tissue ◽

Cholesterol Efflux ◽

Cardiometabolic Risk ◽

Ex Vivo ◽

Inflammatory Marker ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Risk Indicators ◽

Dietary Carbohydrate ◽

Fasting Serum

Abstract Context and Objective Direct comparisons between types of dietary carbohydrate in terms of cardiometabolic risk indicators are limited. This study was designed to compare the effects of an isocaloric exchange of simple, refined, and unrefined carbohydrates on serum cardiometabolic risk indicators, adipose tissue inflammatory markers, and peripheral blood mononuclear cell (PBMC) fractional cholesterol efflux. Design, Participants, and Measures Participants [postmenopausal women and men (N = 11), 65 ± 8 years, body mass index 29.8 ± 3.2 kg/m2, low-density lipoprotein (LDL) cholesterol ≥2.6 mmol/L] were provided with diets (60% energy from total carbohydrate, 15% from protein, 25% from fat) for 4.5 weeks in a randomized crossover design, with 2-week washout periods. The variable component was an isocaloric exchange of simple, refined, or unrefined carbohydrate–containing foods. Serum lipoprotein, glucose, insulin, and inflammatory marker concentrations were measured. Abdominal subcutaneous adipose tissue was aspirated to assess macrophage and inflammatory marker gene expression and ex vivo cytokine secretion, and PBMCs were isolated to assess ex vivo fractional cholesterol efflux. Results Fasting serum LDL and non–high-density lipoprotein (HDL) cholesterol concentrations were higher after the refined compared with simple or unrefined carbohydrate–enriched diets (P < 0.01). Other serum measures, ex vivo fractional cholesterol efflux and adipose tissue gene expression and ex vivo cytokine secretion, were similar between diets. Conclusions Diets enriched in refined compared with simple or unrefined carbohydrate resulted in higher fasting serum LDL and non-HDL cholesterol concentrations but had little effect on other cardiometabolic risk indicators. This small study raises the intriguing possibility that refined carbohydrate may have unique adverse effects on cardiometabolic risk indicators distinct from simple and unrefined carbohydrate.

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Impaired postprandial clearance of triacylglycerol-rich lipoproteins in adipose tissue in obese subjects

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1995.268.4.e588 ◽

1995 ◽

Vol 268 (4) ◽

pp. E588-E594 ◽

Cited By ~ 8

Author(s):

J. L. Potts ◽

S. W. Coppack ◽

R. M. Fisher ◽

S. M. Humphreys ◽

G. F. Gibbons ◽

...

Keyword(s):

Adipose Tissue ◽

Low Density Lipoprotein ◽

Postprandial Lipemia ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Control Group ◽

Postprandial Period ◽

Before And After ◽

Obese Subjects ◽

Subcutaneous Adipose

Adipose tissue is an important site of clearance of circulating triacylglycerol (TAG), especially in the postprandial period. Postprandial lipemia is usually increased in obesity. We studied the extraction of TAG from plasma and TAG-rich lipoproteins (TRLs) in subcutaneous adipose tissue in 11 control and 8 obese subjects before and after a mixed meal. Clearance of plasma TAG and very low-density lipoprotein (VLDL)-TAG was decreased in the obese subjects after an overnight fast. After the meal, chylomicron-TAG extraction increased in the control group whereas VLDL-TAG clearance decreased; these changes were not seen in the obese group, in whom the VLDL particles appeared to be better able to compete with the chylomicrons for clearance by lipoprotein lipase. In the control subjects, removal of TAG from the TRL in the postprandial period was accompanied by a shift toward addition of cholesterol to the high-density lipoprotein (HDL) fraction; this was not observed in the obese subjects. We conclude that disturbed TRL-TAG clearance in adipose tissue is related both to the elevated plasma TAG concentrations and the depressed HDL-cholesterol concentrations typical of obesity.

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Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

Genes ◽

10.3390/genes9080410 ◽

2018 ◽

Vol 9 (8) ◽

pp. 410 ◽

Cited By ~ 7

Author(s):

Daniel Castellano-Castillo ◽

Isabel Moreno-Indias ◽

Jose Carlos Fernandez-Garcia ◽

Mercedes Clemente-Postigo ◽

Manuel Castro-Cabezas ◽

...

Keyword(s):

Insulin Resistance ◽

Dna Methylation ◽

Adipose Tissue ◽

Messenger Rna ◽

Density Lipoprotein ◽

Complement Factor ◽

Mrna Levels ◽

Model Assessment ◽

Tissue Samples ◽

Obese Class

Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns out to be an important protein in metabolic disorders, via either inflammation or the C3 subproduct acylation stimulating protein (ASP) which directly stimulates lipid storage. In this study, we analyze C3 DNA methylation in adipose tissue from subjects with a different grade of obesity. Adipose tissue samples were collected from subjects with a different degree of obesity determined by their body mass index (BMI) as: Overweight subjects (BMI ≥ 25 and <30), obese class 1/2 subjects (BMI ≥ 30 and <40) and obese class 3 subjects (BMI ≥ 40). C3 DNA methylation was measured for 7 CpGs by pyrosequencition using the Pyromark technology (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre-designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was measured using a ELISA kit. The data were analyzed using the statistic package SPSS. C3 DNA methylation levels were lower in the morbid obese group. Accordingly, C3 methylation correlated negatively with BMI and leptin. However, C3 mRNA levels were more associated with insulin resistance, and positive correlations with insulin, glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity variables, such as BMI and leptin, while the C3 mRNA levels were associated to glucose metabolism.

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Discordance Between Apolipoprotein B or Non-HDL-Cholesterol and LDL-Cholesterol in Middle-aged and Elderly Chinese Patients Predicts Arterial Stiffness

10.21203/rs.3.rs-561158/v1 ◽

2021 ◽

Author(s):

Geyue Qu ◽

Zhongying Zhang ◽

Hong Zhu

Keyword(s):

Arterial Stiffness ◽

Apolipoprotein B ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Lipoprotein Cholesterol ◽

Chinese Patients ◽

Middle Aged ◽

Residual Cardiovascular Risk ◽

Elderly Chinese ◽

The Mean

Abstract Background: Discordance of lipid parameters is closely associated with residual cardiovascular risk. This study investigated the discordance between non-high-density lipoprotein cholesterol (non-HDL-C), or apolipoprotein B (apoB), and low-density lipoprotein cholesterol (LDL-C) and assessed arterial stiffness risk.Methods: This study included a total of 402 middle-aged and elderly Northern Chinese individuals, whose brachial-ankle pulse wave conduction velocity(baPWV), as well as clinical and biochemical data, were measured. Arterial stiffness was defined as the upper quartile of the baPWV. All participants were divided into four mutually exclusive concordance/discordance groups based on the lipid goal for very high-risk populations, according to the 2016 European Society of Cardiology / European Atherosclerosis Society guidelines. Discordance was defined as an LDL-C≥ 1.81mmol/L with non-HDL-C< 2.59mmol/L, or apoB <0.80mmol/L, or vice versa.Results: The mean age of the participants was 65.9±13.0 years, and 59.5% were male. The mean LDL-C was 2.41±0.81mmol/L, non-HDL-C 3.06±0.94mmol/L, and apoB 0.84±0.21mmol/L. LDL-C was observed to be discordant with non-HDL-C (20.1%) and apoB (30.8%). When stratified according to LDL-C levels, the baPWV was greater in those patients with higher non-HDL-C or apoB levels. The Spearman analysis showed a significant association between discordant lipid patterns and the presence of arterial stiffness(r= 0.131 and r=0.117, respectively). In the adjusted logistic regression model, low LDL-C and high non-HDL-C or apoB discordance were also associated with the risk of arterial stiffness (OR: 13.412 and OR: 13.054, respectively).Conclusions: There was discordance between the LDL-C and non-HDL-C, or apoB in middle-aged and elderly Chinese individuals, which was associated with a higher risk of arterial stiffness. The non-HDL-C or apoB levels could be used to identify individuals who could benefit from more intensive lipid modification.

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Elevated apolipoprotein A1 and HDL cholesterol associated with age-related macular degeneration: two population cohorts

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab095 ◽

2021 ◽

Author(s):

Liv Tybjærg Nordestgaard ◽

Anne Tybjærg-Hansen ◽

Ruth Frikke-Schmidt ◽

Børge Grønne Nordestgaard

Keyword(s):

Macular Degeneration ◽

Ldl Cholesterol ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Age Related Macular Degeneration ◽

Apolipoprotein A1 ◽

Age Related ◽

Hazard Ratios ◽

Increased Risk ◽

Plasma Apolipoprotein

Abstract Context To enable prevention and treatment of age-related macular degeneration(AMD), understanding risk factors for AMD is important. Objective We tested the hypotheses that elevated plasma apolipoprotein A1 and high-density lipoprotein(HDL) cholesterol, and low levels of low-density lipoprotein(LDL) cholesterol, are associated with increased risk of AMD. Design and Setting From the Danish general population, we studied 106,703 and 16,032 individuals in the Copenhagen General Population Study(CGPS) and the Copenhagen City Heart Study(CCHS) with median follow-up of respectively 9 and 32 years. Main Outcome Measures 1,787 AMD in CGPS and 206 in CCHS. Results Higher concentrations of plasma apolipoprotein A1 and HDL cholesterol, and lower concentrations of LDL cholesterol, were associated with higher risk of AMD in CGPS. After multifactorial adjustment, individuals in the highest versus lowest quartile of plasma apolipoprotein A1 and HDL cholesterol had hazard ratios for AMD of 1.40(95%CI:1.20-1.63) and 1.22(1.03-1.45). Corresponding hazard ratios for individuals in the lowest versus highest quartile of LDL cholesterol were 1.18(1.02-1.37). Per 100 mg/dL higher plasma apolipoprotein A1, 1 mmol/L(39 mg/dL) higher HDL, and 1 mmol/L(39mmol/L) lower LDL cholesterol, the hazard ratios for AMD were 1.53(1.31-1.80), 1.19(1.07-1.32), and 1.05(1.00-1.11), respectively, with similar results across strata of different risk factors. Higher concentrations of HDL cholesterol were also associated with higher risk of AMD in the CCHS. Conclusion Elevated plasma apolipoprotein A1 and HDL cholesterol, and lower LDL cholesterol, are associated with increased risk of age-related macular degeneration.

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Circulating Apolipoprotein L1 is associated with insulin resistance-induced abnormal lipid metabolism

Scientific Reports ◽

10.1038/s41598-019-51367-7 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 1

Author(s):

Kenji Nishimura ◽

Taichi Murakami ◽

Toshihiro Sakurai ◽

Masashi Miyoshi ◽

Kiyoe Kurahashi ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Insulin Resistant ◽

Cell Dysfunction ◽

Fractionation Analysis ◽

Abnormal Lipid Metabolism ◽

Hdl Metabolism ◽

Relationship Of

Abstract Circulating ApolipoproteinL1 (ApoL1) is a component of pre-β-high-density lipoprotein (HDL), however little is known about the relationship of ApoL1 with cardiometabolic factors. Considering previous studies reporting the correlation of ApoL1 to triglyceride, we have hypothesized that ApoL1 associates with insulin-related metabolism. The current study examined their associations in 126 non-diabetic subjects and 36 patients with type 2 diabetes (T2DM). Non-diabetic subjects demonstrated triglyceride (standardized coefficients [s.c.] = 0.204, p < 0.05), body mass index (s.c. =0.232, p < 0.05) and HDL cholesterol (s.c. = −0.203, p < 0.05) as independent determinant of ApoL1 levels, and the significant elevation of ApoL1 in metabolic syndrome. Lipoprotein fractionation analysis revealed the predominant distribution of ApoL1 in large HDL fraction, and the significant increase of ApoL1 in large LDL fraction in high ApoL1 samples with insulin resistance. In T2DM, ApoL1 was higher in T2DM with metabolic syndrome, however ApoL1 was lower with β cell dysfunction. Insulin significantly promotes ApoL1 synthesis and secretion in HepG2 cells. In conclusion, circulating ApoL1 may be associated with abnormal HDL metabolism in insulin resistant status. This may suggest a regulation of insulin signal on the ApoL1 level, leading to offer a novel insight to the ApoL1 biology.

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Interaction between adipocytes and high-density lipoprotein:new insights into the mechanism of obesity-induced dyslipidemia and atherosclerosis

Lipids in Health and Disease ◽

10.1186/s12944-019-1170-9 ◽

2019 ◽

Vol 18 (1) ◽

Cited By ~ 2

Author(s):

Tianhua Zhang ◽

Jin Chen ◽

Xiaoyu Tang ◽

Qin Luo ◽

Danyan Xu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Adipose Tissue ◽

Hormone Secretion ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

High Density ◽

Atherosclerotic Cardiovascular Disease ◽

Nutritional Disorder ◽

Hdl Function ◽

And Function

AbstractObesity is the most common nutritional disorder worldwide and is associated with dyslipidemia and atherosclerotic cardiovascular disease. The hallmark of dyslipidemia in obesity is low high density lipoprotein (HDL) cholesterol (HDL-C) levels. Moreover, the quality of HDL is also changed in the obese setting. However, there are still some disputes on the explanations for this phenomenon. There is increasing evidence that adipose tissue, as an energy storage tissue, participates in several metabolism activities, such as hormone secretion and cholesterol efflux. It can influence overall reverse cholesterol transport and plasma HDL-C level. In obesity individuals, the changes in morphology and function of adipose tissue affect plasma HDL-C levels and HDL function, thus, adipose tissue should be the main target for the treatment of HDL metabolism in obesity. In this review, we will summarize the cross-talk between adipocytes and HDL related to cardiovascular disease and focus on the new insights of the potential mechanism underlying obesity and HDL dysfunction.

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Loss of hepatic PPARα promotes inflammation and serum hyperlipidemia in diet-induced obesity

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00153.2019 ◽

2019 ◽

Vol 317 (5) ◽

pp. R733-R745 ◽

Cited By ~ 16

Author(s):

David E. Stec ◽

Darren M. Gordon ◽

Jennifer A. Hipp ◽

Stephen Hong ◽

Zachary L. Mitchell ◽

...

Keyword(s):

Fat Mass ◽

Lean Mass ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Significant Shift ◽

Peroxisome Proliferator ◽

Peroxisome Proliferator Activated Receptor ◽

Triglyceride Accumulation ◽

M1 Macrophage ◽

Significant Difference

Agonists for PPARα are used clinically to reduce triglycerides and improve high-density lipoprotein (HDL) cholesterol levels in patients with hyperlipidemia. Whether the mechanism of PPARα activation to lower serum lipids occurs in the liver or other tissues is unknown. To determine the function of hepatic PPARα on lipid profiles in diet-induced obese mice, we placed hepatocyte-specific peroxisome proliferator-activated receptor-α (PPARα) knockout ( PparaHepKO) and wild-type ( Pparafl/fl) mice on high-fat diet (HFD) or normal fat diet (NFD) for 12 wk. There was no significant difference in weight gain, percent body fat mass, or percent body lean mass between the groups of mice in response to HFD or NFD. Interestingly, the PparaHepKO mice on HFD had worsened hepatic inflammation and a significant shift in the proinflammatory M1 macrophage population. These changes were associated with higher hepatic fat mass and decreased hepatic lean mass in the PparαHepKO on HFD but not in NFD as measured by Oil Red O and noninvasive EchoMRI analysis (31.1 ± 2.8 vs. 20.2 ± 1.5, 66.6 ± 2.5 vs. 76.4 ± 1.5%, P < 0.05). We did find that this was related to significantly reduced peroxisomal gene function and lower plasma β-hydroxybutyrate in the PparaHepKO on HFD, indicative of reduced metabolism of fats in the liver. Together, these provoked higher plasma triglyceride and apolipoprotein B100 levels in the PparaHepKO mice compared with Pparafl/fl on HFD. These data indicate that hepatic PPARα functions to control inflammation and liver triglyceride accumulation that prevent hyperlipidemia.

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