scholarly journals The Plasma Metabolomic Profile is Differently Associated with Liver Fat, Visceral Adipose Tissue, and Pancreatic Fat

2020 ◽  
Vol 106 (1) ◽  
pp. e118-e129
Author(s):  
Lars Lind ◽  
Samira Salihovic ◽  
Ulf Risérus ◽  
Joel Kullberg ◽  
Lars Johansson ◽  
...  

Abstract Context Metabolic differences between ectopic fat depots may provide novel insights to obesity-related diseases. Objective To investigate the plasma metabolomic profiles in relation to visceral adipose tissue (VAT) volume and liver and pancreas fat percentages. Design Cross-sectional. Setting Multicenter at academic research laboratories. Patients Magnetic resonance imaging (MRI) was used to assess VAT volume, the percentage of fat in the liver and pancreas (proton density fat fraction [PDFF]) at baseline in 310 individuals with a body mass index ≥ 25 kg/m2 and with serum triglycerides ≥ 1.7 mmol/l and/or type 2 diabetes screened for inclusion in the 2 effect of omega-3 carboxylic acid on liver fat content studies. Intervention None. Main Outcome Measure Metabolomic profiling with mass spectroscopy enabled the determination of 1063 plasma metabolites. Results Thirty metabolites were associated with VAT volume, 31 with liver PDFF, and 2 with pancreas PDFF when adjusting for age, sex, total body fat mass, and fasting glucose. Liver PDFF and VAT shared 4 metabolites, while the 2 metabolites related to pancreas PDFF were unique. The top metabolites associated with liver PDFF were palmitoyl-palmitoleoyl-GPC (16:0/16:1), dihydrosphingomyelin (d18:0/22:0), and betaine. The addition of these metabolites to the Liver Fat Score improved C-statistics significantly (from 0.776 to 0.861, P = 0.0004), regarding discrimination of liver steatosis. Conclusion Liver PDFF and VAT adipose tissue shared several metabolic associations, while those were not shared with pancreatic PDFF, indicating partly distinct metabolic profiles associated with different ectopic fat depots. The addition of 3 metabolites to the Liver Fat Score improved the prediction of liver steatosis.

2020 ◽  
Vol 112 (4) ◽  
pp. 979-990
Author(s):  
Anish Zacharia ◽  
Daniel Saidemberg ◽  
Chanchal Thomas Mannully ◽  
Natalya M Kogan ◽  
Alaa Shehadeh ◽  
...  

ABSTRACT Background Adipose tissue plays important roles in health and disease. Given the unique association of visceral adipose tissue with obesity-related metabolic diseases, the distribution of lipids between the major fat depots located in subcutaneous and visceral regions may shed new light on adipose tissue–specific roles in systemic metabolic perturbations. Objective We sought to characterize the lipid networks and unveil differences in the metabolic infrastructure of the 2 adipose tissues that may have functional and nutritional implications. Methods Paired visceral and subcutaneous adipose tissue samples were obtained from 17 overweight patients undergoing elective abdominal surgery. Ultra-performance LC-MS was used to measure 18,640 adipose-derived features; 520 were putatively identified. A stem cell model for adipogenesis was used to study the functional implications of the differences found. Results Our analyses resulted in detailed lipid metabolic maps of the 2 major adipose tissues. They point to a higher accumulation of phosphatidylcholines, triacylglycerols, and diacylglycerols, although lower ceramide concentrations, in subcutaneous tissue. The degree of unsaturation was lower in visceral adipose tissue (VAT) phospholipids, indicating lower unsaturated fatty acid incorporation into adipose tissue. The differential abundance of phosphatidylcholines we found can be attributed at least partially to higher expression of phosphatidylethanolamine methyl transferase (PEMT). PEMT-deficient embryonic stem cells showed a dramatic decrease in adipogenesis, and the resulting adipocytes exhibited lower accumulation of lipid droplets, in line with the lower concentrations of glycerolipids in VAT. Ceramides may inhibit the expression of PEMT by increased insulin resistance, thus potentially suggesting a functional pathway that integrates ceramide, PEMT, and glycerolipid biosynthetic pathways. Conclusions Our work unveils differential infrastructure of the lipid networks in visceral and subcutaneous adipose tissues and suggests an integrative pathway, with a discriminative flux between adipose tissues.


2020 ◽  
Vol 112 (2) ◽  
pp. 354-363
Author(s):  
Ilka Ratjen ◽  
Jakub Morze ◽  
Janna Enderle ◽  
Marcus Both ◽  
Jan Borggrefe ◽  
...  

ABSTRACT Background Better adherence to plant-based diets has been linked to lower risk of metabolic diseases but the effect on abdominal fat distribution and liver fat content is unclear. Objectives We aimed to examine the association between different plant-based diet indices and measures of abdominal fat distribution and liver fat content. Methods In a population-based sample of 578 individuals from Northern Germany (57% male, median age 62 y), diet was assessed with a validated FFQ and an overall, a healthy, and an unhealthy plant-based diet index were derived. Participants underwent MRI to assess volumes of visceral and subcutaneous abdominal adipose tissue and liver signal intensity (LSI), a measure of liver fat content. Fatty liver disease (FLD) was defined as log LSI ≥3.0. Cross-sectional associations of the plant-based diet indices with visceral and subcutaneous abdominal fat volumes, LSI, and FLD were assessed in linear and logistic regression analyses. The most comprehensive model adjusted for age, sex, education, smoking, alcohol, physical activity, energy intake, diabetes, hyperlipidemia, and BMI. Results Higher overall and healthy plant-based diet indices both revealed statistically significant associations with lower visceral and subcutaneous abdominal adipose tissue volumes and with lower odds of FLD in multivariable-adjusted models without BMI. Upon additional adjustment for BMI, only the association of the healthy plant-based diet with visceral adipose tissue remained statistically significant (per 10-point higher healthy plant-based diet index, percentage change in visceral adipose tissue: −4.9%, 95% CI: −8.6%, −2.0%). None of the plant-based diet indices was associated with LSI. The unhealthy plant-based diet index was unrelated to any of the abdominal or liver fat parameters. Conclusions Adherence to healthy plant-based diets was associated with lower visceral adipose tissue. None of the other examined associations remained statistically significant after adjustment for BMI.


2020 ◽  

The accumulation of visceral adipose tissue (VAT) and ectopic liver fat (ELF) generally parallel each other, but a proportion of individuals have discordant fat deposition. The cardiometabolic profile of individuals with a discordant phenotype is unknown.


2020 ◽  
Vol 8 (2) ◽  
pp. e001860
Author(s):  
Maria Apostolopoulou ◽  
Ruth Gordillo ◽  
Sofiya Gancheva ◽  
Klaus Strassburger ◽  
Christian Herder ◽  
...  

IntroductionSphingolipid accumulation has been linked to obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). A recent study showed that depletion of dihydroceramide desaturase-1 (DES-1) in adipose and/or liver tissue decreases ceramide-to-dihydroceramide ratios (ceramide/dihydroceramide) in several tissues and improves the metabolic profile in mice. We tested the hypothesis that ceramide/dihydroceramide would also be elevated and relate positively to liver fat content and insulin resistance in humans.Research design and methodsThus, we assessed total and specific ceramide/dihydroceramide in various biosamples of 7 lean and 21 obese volunteers without or with different NAFLD stages, who were eligible for abdominal or bariatric surgery, respectively. Biosamples were obtained from serum, liver, rectus abdominis muscle as well as subcutaneous abdominal and visceral adipose tissue during surgery.ResultsSurprisingly, certain serum and liver ceramide/dihydroceramide ratios were reduced in both obesity and non-alcoholic steatohepatitis (NASH) and related inversely to liver fat content. Specifically, hepatic ceramide/dihydroceramide (species 16:0) related negatively to hepatic mitochondrial capacity and lipid peroxidation. In visceral adipose tissue, ceramide/dihydroceramide (species 16:0) associated positively with markers of inflammation.ConclusionThese results failed to confirm the relationships of ceramide/dihydroceramide in humans with different degree of insulin resistance. However, the low hepatic ceramide/dihydroceramide favor a role for dihydroceramide accumulation in NASH, while a specific ceramide/dihydroceramide ratio in visceral adipose tissue suggests a role of ceramides in obesity-associated low-grade inflammation.


2012 ◽  
Vol 112 (1) ◽  
pp. 79-85 ◽  
Author(s):  
Joan C. Murphy ◽  
Jennifer L. McDaniel ◽  
Katherine Mora ◽  
Dennis T. Villareal ◽  
Luigi Fontana ◽  
...  

Intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) are associated with insulin resistance. We sought to determine whether exercise-induced weight loss (EX) results in greater reductions in IMAT and VAT compared with similar weight loss induced by calorie restriction (CR) and whether these changes are associated with improvements in glucoregulation. Sedentary men and women (50–60 yr; body mass index of 23.5–29.9 kg/m2) were randomized to 1 yr of CR ( n = 17), EX ( n = 16), or a control group (CON; n = 6). Bilateral thigh IMAT and VAT volumes were quantified using multi-slice magnetic resonance imaging. Insulin sensitivity index (ISI) was determined from oral glucose tolerance test glucose and insulin levels. Weight loss was comparable ( P = 0.25) in the CR (−10.8 ± 1.4%) and EX groups (−8.3 ± 1.5%) and greater than in the control group (−2.0 ± 2.4%; P < 0.05). IMAT and VAT reductions were larger in the CR and EX groups than in the CON group ( P ≤ 0.05). After controlling for differences in total fat mass change between the CR and EX groups, IMAT and VAT reductions were nearly twofold greater ( P ≤ 0.05) in the EX group than in the CR group (IMAT: −45 ±5 vs. −25 ± 5 ml; VAT: −490 ± 64 vs. −267 ± 61 ml). In the EX group, the reductions in IMAT were correlated with increases in ISI ( r = −0.71; P = 0.003), whereas in the CR group, VAT reductions were correlated with increases in ISI ( r = −0.64; P = 0.006). In conclusion, calorie restriction and exercise-induced weight loss both decrease IMAT and VAT volumes. However, exercise appears to result in preferential reductions in these fat depots.


2007 ◽  
Vol 32 (2) ◽  
pp. 265-272 ◽  
Author(s):  
Kathleen P. McMillan ◽  
Jennifer L. Kuk ◽  
Timothy S. Church ◽  
Steven N. Blair ◽  
Robert Ross

The independent associations between liver fat, visceral adipose tissue (AT), and metabolic risk factors are unclear. Although it has been reported that visceral AT is the strongest predictor of metabolic risk, liver fat has also been reported as a strong independent associate of a deleterious metabolic profile. We examined the independent associations between liver fat, visceral AT, and metabolic risk factors in a sample of 293 men varying widely in adiposity. Liver fat and abdominal AT were measured by computed tomography (CT). Univariate analysis revealed that liver fat was associated (p < 0.05) with triglycerides (TG), systolic blood pressure (SBP), and total cholesterol (TC), but not with glucose or high-density lipoprotein cholesterol (HDLC). Liver fat remained a significant correlate (p < 0.05) of TG and TC after control for age and subcutaneous AT or cardiorespiratory fitness (CRF), but not after adjustment for visceral AT alone. Conversely, visceral AT remained significantly associated with TG, SBP, glucose, HDLC (p < 0.01), and TC (p = 0.05) independent of liver fat, subcutaneous AT, CRF, and age. Both liver fat and visceral AT were associated with metabolic risk in men. However, when controlled for each other, visceral AT was the only independent associate of metabolic risk.


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