scholarly journals Diet-Induced Abdominal Obesity, Metabolic Changes, and Atherosclerosis in Hypercholesterolemic Minipigs

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ahmed Ludvigsen Al-Mashhadi ◽  
Christian Bo Poulsen ◽  
Karin von Wachenfeldt ◽  
Anna-Karin Robertson ◽  
Jacob Fog Bentzon ◽  
...  

Background. Obesity and metabolic syndrome (MetS) are major risk factors for atherosclerotic diseases; however, a causal link remains elusive. Animal models resembling human MetS and its complications, while important, are scarce. We aimed at developing a porcine model of human MetS. Methods. Forty pigs with familial hypercholesterolemia were fed a high fat + fructose diet for 30 weeks. Metabolic assessments and subcutaneous fat biopsies were obtained at 18 and 30 weeks, and fat distribution was assessed by CT-scans. Postmortem, macrophage density, and phenotype in fat tissues were quantified along with atherosclerotic burden. Results. During the experiment, we observed a >4-fold in body weight, a significant but small increase in fasting glucose (4.1 mmol/L), insulin (3.1 mU/L), triglycerides (0.5 mmol/L), and HDL cholesterol (2.6 mmol/L). Subcutaneous fat correlated with insulin resistance, but intra-abdominal fat correlated inversely with insulin resistance and LDL cholesterol. More inflammatory macrophages were found in visceral versus subcutaneous fat, and inflammation decreased in subcutaneous fat over time. Conclusions. MetS based on human criteria was not achieved. Surprisingly, visceral fat seemed part of a healthier metabolic and inflammatory profile. These results differ from human findings, and further research is needed to understand the relationship between obesity and MetS in porcine models.

2014 ◽  
Vol 62 (2) ◽  
pp. 169-179 ◽  
Author(s):  
Linda Müller ◽  
Eszter Kollár ◽  
Lajos Balogh ◽  
Zita Pöstényi ◽  
Teréz Márián ◽  
...  

The relationship between metabolic disorders and the distribution of fat in different body regions is not clearly understood in humans. The aim of this study was to develop a suitable method for assessing the regional distribution of fat deposits and their metabolic effects in dogs. Twenty-five dogs were subjected to computed tomographic (CT) imaging and blood sampling in order to characterise their metabolic status. The different fat areas were measured on a cross-sectional scan, and the animals’ metabolic status was evaluated by measuring fasting glucose, insulin and leptin levels. The volume of visceral adipose tissue is the main determinant of leptin levels. The correlation of visceral fat volume and leptin concentration was found to be independent of insulin levels or the degree of insulin resistance. There was a positive correlation between the visceral to subcutaneous fat volume ratio and serum insulin concentration, and a similar trend was observed in the relationship of fat ratio and insulin resistance. The distribution of body fat essentially influences the metabolic parameters in dogs, but the effects of adiposity differ between humans and dogs. The findings can facilitate a possible extrapolation of results from animal studies to humans with regard to the metabolic consequences of different obesity types.


2020 ◽  
Vol 8 (1) ◽  
pp. e001126
Author(s):  
Catherine E Cioffi ◽  
K M Venkat Narayan ◽  
Ken Liu ◽  
Karan Uppal ◽  
Dean P Jones ◽  
...  

IntroductionBody fat distribution is strongly associated with cardiometabolic disease (CMD), but the relative importance of hepatic fat as an underlying driver remains unclear. Here, we applied a systems biology approach to compare the clinical and molecular subnetworks that correlate with hepatic fat, visceral fat, and abdominal subcutaneous fat distribution.Research design and methodsThis was a cross-sectional sub-study of 283 children/adolescents (7–19 years) from the Yale Pediatric NAFLD Cohort. Untargeted, high-resolution metabolomics (HRM) was performed on plasma and combined with existing clinical variables including hepatic and abdominal fat measured by MRI. Integrative network analysis was coupled with pathway enrichment analysis and multivariable linear regression (MLR) to examine which metabolites and clinical variables associated with each fat depot.ResultsThe data divided into four communities of correlated variables (|r|>0.15, p<0.05) after integrative network analysis. In the largest community, hepatic fat was associated with eight clinical biomarkers, including measures of insulin resistance and dyslipidemia, and 878 metabolite features that were enriched predominantly in amino acid (AA) and lipid pathways in pathway enrichment analysis (p<0.05). Key metabolites associated with hepatic fat included branched-chain AAs (valine and isoleucine/leucine), aromatic AAs (tyrosine and tryptophan), serine, glycine, alanine, and pyruvate, as well as several acylcarnitines and glycerophospholipids (all q<0.05 in MLR adjusted for covariates). The other communities detected in integrative network analysis consisted of abdominal visceral, superficial subcutaneous, and deep subcutaneous fats, but no clinical variables, fewer metabolite features (280, 312, and 74, respectively), and limited findings in pathway analysis.ConclusionsThese data-driven findings show a stronger association of hepatic fat with key CMD risk factors compared with abdominal fats. The molecular network identified using HRM that associated with hepatic fat provides insight into potential mechanisms underlying the hepatic fat–insulin resistance interface in youth.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Chikako Fujii ◽  
Toshihide Kawai ◽  
Koichiro Azuma ◽  
Yuko Oguma ◽  
Fuminori Katsukawa ◽  
...  

Objective. The aim of this study was to evaluate the relationships between the composition of free fatty acids (FFAs) and metabolic parameters, including body fat distribution, in Japanese.Methods. The study subjects were 111 Japanese patients (54 males, 57 females). Metabolic parameters and visceral and subcutaneous fat areas as determined by CT scanning at the umbilical level were measured. Glucose tolerance test (GTT) was performed by administering 75 g glucose orally.Results. The percentage of linoleic acid (C18:2), the greatest constituent among FFAs, was negatively correlated with visceral fat area (r=−0.411,p<0.0001), fasting glucose (r=−0.330,p<0.0001), HbA1c (r=−0.231,p=0.0146), and systolic blood pressure (r=−0.224,p=0.0184). Linoleic acid percentage was also significantly negatively correlated with HOMA-IR (r=−0.416,p<0.0001) by simple correlation. Based on the findings of OGTT, the 111 subjects were classified into three groups: 33 with normal glucose tolerance, 71 with impaired glucose tolerance (IGT), and 7 diabetic subjects. The percentage of serum linoleic acid in diabetic subjects was significantly lower than that in normal subjects.Conclusion. We conclude that serum linoleic acid level is negatively correlated with the accumulation of visceral fat in relation to a reduction of insulin resistance in Japanese subjects.


2014 ◽  
Vol 32 (1) ◽  
pp. 55-59 ◽  
Author(s):  
Amanda Oliva Gobato ◽  
Ana Carolina J. Vasques ◽  
Mariana Porto Zambon ◽  
Antonio de Azevedo Barros Filho ◽  
Gabriel Hessel

Objective: To verify the prevalence of metabolic syndrome and insulin resistance in obese adolescents and its relationship with different body composition indicators. Methods: A cross-sectional study comprising 79 adolescents aged ten to 18 years old. The assessed body composition indicators were: body mass index (BMI), body fat percentage, abdominal circumference, and subcutaneous fat. The metabolic syndrome was diagnosed according to the criteria proposed by Cook et al. The insulin resistance was determined by the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) index for values above 3.16. The analysis of ROC curves was used to assess the BMI and the abdominal circumference, aiming to identify the subjects with metabolic syndrome and insulin resistance. The cutoff point corresponded to the percentage above the reference value used to diagnose obesity. Results: The metabolic syndrome was diagnosed in 45.5% of the patients and insulin resistance, in 29.1%. Insulin resistance showed association with HDL-cholesterol (p=0.032) and with metabolic syndrome (p=0.006). All body composition indicators were correlated with insulin resistance (p<0.01). In relation to the cutoff point evaluation, the values of 23.5 and 36.3% above the BMI reference point allowed the identification of insulin resistance and metabolic syndrome. The best cutoff point for abdominal circumference to identify insulin resistance was 40%. Conclusions: All body composition indicators, HDL-cholesterol and metabolic syndrome showed correlation with insulin resistance. The BMI was the most effective anthropometric indicator to identify insulin resistance.


2002 ◽  
Vol 2 (1_suppl) ◽  
pp. S12-S17 ◽  
Author(s):  
François Berthezène

Dyslipidaemia is likely to play a leading role in the cardiovascular risk associated with diabetes. Diabetic dyslipidaemia is characterised by hypertriglyceridaemia, a shift from large low-density lipoprotein (LDL) to smaller denser particles, and reduced high-density lipoprotein (HDL) cholesterol. Dyslipidaemia is closely associated with insulin resistance. Patients with diabetic dyslipidaemia should receive lipid lowering therapy with statins or fibrates, as appropriate. Due to the relationship between dyslipidaemia and insulin resistance, treatment of insulin resistance should be included in multifactorial risk factor modification. Thiazolidinediones such as pioglitazone may provide a useful treatment approach.


2018 ◽  
Vol 314 (5) ◽  
pp. E448-E456 ◽  
Author(s):  
Geneviève B. Marchand ◽  
Anne-Marie Carreau ◽  
S. John Weisnagel ◽  
Jean Bergeron ◽  
Fernand Labrie ◽  
...  

The relationship between circulating estrogen levels and cardiometabolic risk factors such as insulin resistance is unclear in postmenopausal women. High estradiol (E2) levels have been reported to predict increased risk of type 2 diabetes in this population. We aimed to examine associations among estrogen levels, adiposity measurements, and cardiometabolic risk variables including insulin resistance in postmenopausal women. One hundred-one healthy participants (mean ± SD: age 57 ± 4 yr, BMI 27.9 ± 4.8 kg/m2) were included in the analysis. Fifteen plasma steroids or metabolites were measured by liquid chromatography-tandem mass spectrometry. Insulin sensitivity was assessed with a hyperinsulinemic-euglycemic clamp. Body composition and fat distribution were determined with hydrostatic weighing and computed tomography, respectively. Blood lipids and circulating cytokines were also measured. Circulating E2 was positively correlated with all adiposity indexes ( r = 0.62 to 0.42, P < 0.0001) except waist-to-hip ratio. E2 was positively correlated with VLDL-cholesterol, plasma-, VLDL-, and HDL-triglyceride levels ( r = 0.31 to 0.24, P < 0.02) as well as with hs-CRP and IL-6 ( r = 0.52 and 0.29, P < 0.005) and negatively with HDL-cholesterol, adiponectin, and insulin sensitivity ( r = −0.36 to −0.20, P < 0.02). With adjustments for percent body fat, correlations between E2 and metabolic risk variables were no longer significant. Similar results were observed for circulating estrone (E1) and estrone-sulfate (E1-S) levels. In conclusion, circulating estrogen concentrations are proportional to adipose mass in postmenopausal women, although they remain in the low range. Insulin resistance as well as altered blood lipids and cytokines are observed when circulating estrogen levels are high within that range, but these differences are explained by concomitant variation in total adiposity.


PLoS ONE ◽  
2015 ◽  
Vol 10 (6) ◽  
pp. e0129764 ◽  
Author(s):  
Francisco J. A. de Paula ◽  
Iana M. de Araújo ◽  
Adriana L. Carvalho ◽  
Jorge Elias ◽  
Carlos E. G. Salmon ◽  
...  

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Takeshi Iida ◽  
Satoshi Morimoto ◽  
Hidenobu Okuda ◽  
Yoshifumi Amari ◽  
Takatomi Yurugi ◽  
...  

Abstract Background Hemodialysis patients have a greater risk of cardiovascular disease, their major cause of death. Obesity is a risk factor for arteriosclerosis, cardiovascular disease, and mortality in the general population. Conversely, an increased body mass index (BMI) is known to be associated with better survival of hemodialysis patients. However, the influences of changes in parameters associated with obesity on arteriosclerosis in these patients have not been evaluated. Here, we evaluated the relationship between changes in parameters associated with obesity and brachial-ankle pulse wave velocity (baPWV), as an index of arteriosclerosis, in hemodialysis patients. Methods Two hundred and fifty-eight subjects were selected from patients undergoing stable hemodialysis. BMI, abdominal circumference (AC), visceral fat area (VFA) and subcutaneous fat areas (SFA), and baPWV were assessed at baseline and 4 years later. Ankle-brachial index and baPWV were measured on a non-dialysis day using volume-plethysmographic apparatus. Abdominal circumference was measured at the level of umbilicus by computed tomography (CT). Body fat distribution was determined using CT. All CT scans were performed on a non-dialysis day with the subject in a supine position. Results Sixty-one patients died during the 4-year period. Abdominal circumference, BMI, VFA, and SFA were higher, and baPWV was lower in patients who survived than in those who died. During the study period, baPWV increased and was positively correlated with the change in visceral plus subcutaneous fat area in patients whose initial VFA was > 100 cm2. There were negative correlations between the change in baPWV and changes in AC, and SFA in individuals whose VFA was < 100 cm2. Conclusions These data suggest that patients with a large VFA should adopt strategies aimed at reducing body weight, while patients with a small VFA should avoid undernutrition.


2000 ◽  
Vol 83 (S1) ◽  
pp. S71-S77 ◽  
Author(s):  
Keith N. Frayn

The association between abdominal fat accumulation and risk of chronic diseases, including type II diabetes and coronary heart disease, has long been recognized. Insulin resistance may be a key factor in this link. Many studies have pointed to an association between insulin resistance and intra-abdominal fat accumulation (visceral obesity). However there is no clear proof of a causal link between visceral fat accumulation and insulin resistance. In assessing the probability of a causal link, it is useful to consider potential mechanisms. One such potential causal link is the release of non-esterified fatty acids from visceral fat into the portal vein, so that they have direct effects on hepatic metabolism. Visceral fat has been shown in many studies to exhibit a high rate of lipolysis compared with subcutaneous fat depots. However, if the idea that visceral fat releases fatty acids into the portal vein at a high rate is examined critically, a number of difficulties appear. Not least of these is the fact that continued high rates of lipolysis should lead to the disappearance of the visceral fat depot, unless these high rates of fat mobilization are matched by high rates of fat deposition. There is far less evidence for high rates of fat deposition in visceral adipose tissue, and some contrary evidence. Evidence for high rates of visceral lipolysis in vivo from studies involving catheterization of the portal vein is not strong. If this potential link is discounted, then other reasons for the relationship between visceral fat and insulin resistance must be considered. One is that there is no direct causal link, but both co-correlate with some other variable. A possibility is that this other variable is subcutaneous abdominal fat, which usually outweighs intra-abdominal fat several-fold. Subcutaneous fat probably plays the major role in determining systemic plasma non-esterified fatty acid concentrations, which are relevant in determining insulin resistance. In conclusion, there is at present no proof of a causal link between visceral fat accumulation and insulin resistance, or the associated metabolic syndrome. The possibility of co-correlation with some other factor, such as subcutaneous abdominal fat accumulation, must not be forgotten.


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