Subcutaneous Adipose Tissue Fat Research Articles

The relationship between body composition and left ventricular performance in women with breast, lymphoma, or sarcoma cancer

BackgroundTo understand how body composition in those with elevated body mass index impacts left ventricular function decline during cancer treatment, we determined the association between baseline body mass index (BMI), intra-abdominal adipose tissue (IAT) and subcutaneous adipose tissue (SAT) with baseline to 3-month left ventricular ejection fraction (LVEF) change among women receiving potentially cardiotoxic chemotherapy for breast cancer, lymphoma, or sarcoma.MethodsWomen underwent potentially cardiotoxic chemotherapy, such as doxorubicin, cyclophosphamide, paclitaxel, and trastuzumab, for treatment of breast cancer, lymphoma, or sarcoma. We obtained magnetic resonance images (MRIs) of body composition and cardiac function prior to treatment, and then a repeat MRI for cardiac function assessment at three months into treatment. Analyses and assessment of abdominal adipose tissue volumes and LVEF outcomes were conducted by independent reviewers blinded to all patient identifiers. A general linear model was created to examine associations between adipose tissue depots, BMI, and 3-month LVEF change.ResultsWomen (n = 210) aged 56 ± 11 years with breast cancer, lymphoma, and sarcoma were enrolled (n = 195, 14, 1 respectively). Baseline BMI, IAT, and SAT fat were independently associated with 3-month LVEF declines (p = 0.001 to 0.025 for all). After adjusting for baseline cardiovascular disease risk factors, BMI, IAT, and SAT, BMI remained the only variable associated with 3-month LVEF decline (p = 0.047).ConclusionsThese results suggest that factors other than abdominal adipose tissue or traditional cardiovascular risk factors may contribute to 3-month declines in LVEF among women with elevated BMI receiving potentially cardiotoxic chemotherapy. Further investigation should be conducted on psychosocial stress, physical activity, sleep, or diet.Trial registrationDETECTIV_NCT01719562, WF99112, & WF97415—NCT02791581.

Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders.

Metabolically healthy obesity refers to obese individuals who do not develop metabolic disorders. These people store fat in subcutaneous adipose tissue (SAT) rather than in visceral adipose tissue (VAT). However, the molecules participating in this specific scenario remain elusive. Rab18, a lipid droplet (LD)-associated protein, mediates the contact between the endoplasmic reticulum (ER) and LDs to facilitate LD growth and maturation. In the present study, we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and mice. Rab18 adipocyte-specific knockout (Rab18 AKO) mice had a decreased volume ratio of SAT to VAT compared with wildtype mice. When subjected to high-fat diet (HFD), Rab18 AKO mice had increased ER stress and inflammation, reduced adiponectin, and decreased triacylglycerol (TAG) accumulation in SAT. In contrast, TAG accumulation in VAT, brown adipose tissue (BAT) or liver of Rab18 AKO mice had a moderate increase without ER stress stimulation. Rab18 AKO mice developed insulin resistance and systematic inflammation. Rab18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT, similar to the counterpart mice. Furthermore, Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress, indicating the involvement of Rab18 in alleviating lipid toxicity. Rab18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired SAT. In conclusion, our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

Determination of lower radiation dose limit for automatic measurement of adipose tissue.

The purpose of this study was to determine the lower limit of radiation dose required to measure visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) volumes when a fat quantification and noise reduction techniques (NRTs) are combined. For this purpose, we utilized CT colonography (CTC) images taken at low doses and manually segmented VAT and SAT fat volumes as ground truth. In order to derive the acceptable precision of the measurements needed to estimate the lower limit of radiation dose, we estimated the effect of different positioning during CT scanning on fat measurements using manually segmented VAT and SAT against normal dose. As a result, the acceptable accuracy of SAT and VAT was found to be 94.5% and 85.2%, respectively. Using these thresholds, the lower radiation dose limit required to accurately measure SAT using 5.25-mm slice-thick images was 1.5mGy of size-specific dose estimates (SSDE), while the lower radiation dose limit required to accurately measure VAT was 0.4mGy of SSDE. The lower dose limit for SAT and VAT combined was 1.5mGy, which was equivalent to an estimated effective dose of 0.38mSv. Alternatively, without noise reduction, SAT could not achieve acceptable accuracy even for images with a slice thickness of 5.25mm, while VAT required noise reduction for images with a slice thickness of 1.25mm, but could achieve acceptable accuracy without noise reduction for images with a slice thickness of 5.25mm.

Genetic Parameters and Genome-Wide Association Studies of Quality Traits Characterised Using Imaging Technologies in Rainbow Trout, Oncorhynchus mykiss.

One of the top priorities of the aquaculture industry is the genetic improvement of economically important traits in fish, such as those related to processing and quality. However, the accuracy of genetic evaluations has been hindered by a lack of data on such traits from a sufficiently large population of animals. The objectives of this study were thus threefold: (i) to estimate genetic parameters of growth-, yield-, and quality-related traits in rainbow trout (Oncorhynchus mykiss) using three different phenotyping technologies [invasive and non-invasive: microwave-based, digital image analysis, and magnetic resonance imaging (MRI)], (ii) to detect quantitative trait loci (QTLs) associated with these traits, and (iii) to identify candidate genes present within these QTL regions. Our study collected data from 1,379 fish on growth, yield-related traits (body weight, condition coefficient, head yield, carcass yield, headless gutted carcass yield), and quality-related traits (total fat, percentage of fat in subcutaneous adipose tissue, percentage of fat in flesh, flesh colour); genotypic data were then obtained for all fish using the 57K SNP Axiom® Trout Genotyping array. Heritability estimates for most of the 14 traits examined were moderate to strong, varying from 0.12 to 0.67. Most traits were clearly polygenic, but our genome-wide association studies (GWASs) identified two genomic regions on chromosome 8 that explained up to 10% of the genetic variance (cumulative effects of two QTLs) for several traits (weight, condition coefficient, subcutaneous and total fat content, carcass and headless gutted carcass yields). For flesh colour traits, six QTLs explained 1–4% of the genetic variance. Within these regions, we identified several genes (htr1, gnpat, ephx1, bcmo1, and cyp2x) that have been implicated in adipogenesis or carotenoid metabolism, and thus represent good candidates for further functional validation. Finally, of the three techniques used for phenotyping, MRI demonstrated particular promise for measurements of fat content and distribution, while the digital image analysis-based approach was very useful in quantifying colour-related traits. This work provides new insights that may aid the development of commercial breeding programmes in rainbow trout, specifically with regard to the genetic improvement of yield and flesh-quality traits as well as the use of invasive and/or non-invasive technologies to predict such traits.

Human Brown Adipose Tissue Estimated With Magnetic Resonance Imaging Undergoes Changes in Composition After Cold Exposure: An in vivo MRI Study in Healthy Volunteers.

Aim: Magnetic resonance imaging (MRI) is increasingly being used to evaluate brown adipose tissue (BAT) function. Reports on the extent and direction of cold-induced changes in MRI fat fraction and estimated BAT volume vary between studies. Here, we aimed to explore the effect of different fat fraction threshold ranges on outcomes measured by MRI. Moreover, we aimed to investigate the effect of cold exposure on estimated BAT mass and energy content.Methods: The effects of cold exposure at different fat fraction thresholding levels were analyzed in the supraclavicular adipose depot of nine adult males. MRI data were reconstructed, co-registered and analyzed in two ways. First, we analyzed cold-induced changes in fat fraction, T2* relaxation time, volume, mass, and energy of the entire supraclavicular adipose depot at different fat fraction threshold levels. As a control, we assessed fat fraction differences of deltoid subcutaneous adipose tissue (SAT). Second, a local analysis was performed to study changes in fat fraction and T2* on a voxel-level. Thermoneutral and post-cooling data were compared using paired-sample t-tests (p < 0.05).Results: Global analysis unveiled that the largest cold-induced change in fat fraction occurred within a thermoneutral fat fraction range of 30–100% (−3.5 ± 1.9%), without changing the estimated BAT volume. However, the largest cold-induced changes in estimated BAT volume were observed when applying a thermoneutral fat fraction range of 70–100% (−3.8 ± 2.6%). No changes were observed for the deltoid SAT fat fractions. Tissue energy content was reduced from 126 ± 33 to 121 ± 30 kcal, when using a 30–100% fat fraction range, and also depended on different fat fraction thresholds. Voxel-wise analysis showed that while cold exposure changed the fat fraction across nearly all thermoneutral fat fractions, decreases were most pronounced at high thermoneutral fat fractions.Conclusion: Cold-induced changes in fat fraction occurred over the entire range of thermoneutral fat fractions, and were especially found in lipid-rich regions of the supraclavicular adipose depot. Due to the variability in response between lipid-rich and lipid-poor regions, care should be taken when applying fat fraction thresholds for MRI BAT analysis.

Gain of Metabolic Benefit with Ablation of miR-149-3p from Subcutaneous Adipose Tissue in Diet-Induced Obese Mice

The global rise in obesity has become a public health crisis. During the onset of obesity, disrupted catecholamine signals have been described to contribute to excess fat accumulation, however, the molecular and metabolic change of subcutaneous adipose tissue (SAT) upon chronic high-fat feeding has rarely been investigated. Here, we show that chronic high-fat feeding caused a significant decrease in the expression of thermogenic genes and acquisition of partial deleterious features of visceral fat in SAT. Upregulated miR-149-3p was involved in this obesity-induced “visceralization” of SAT via inhibiting PRDM16, a master regulator that promoted SAT thermogenesis. Reduction of miR-149-3p significantly increased PRDM16 expression in SAT, with improved whole-body insulin sensitivity, decreased SAT inflammation, and liver steatosis in high-fat fed mice. These findings provided direct evidence of the anti-obese and anti-diabetic effect of PRDM16 in the obese background for the first time and identified that miR-149-3p could serve as a therapeutic target to protect against diet-induced obesity and metabolic dysfunctions.

OR25-3 Toward a Circulating Marker of Hepato-Visceral Fat Excess: S100A4 in Adolescent Girls with Polycystic Ovary Syndrome

S100A4 has recently been identified as an adipokine that can serve as a marker of "pernicious" subcutaneous adipose tissue (Arner et al, Int J Ob 2018). However, S100A4 can also be released by an inflammatory subset of macrophages in the liver (Osterreicher et al, Proc Natl Acad Sci USA 2011). Development of polycystic ovary syndrome (PCOS) in adolescent girls is often driven by an early excess of fat in subcutaneous adipose tissue, accompanied by an excess of fat in ectopic locations, notably in viscera and liver (Cree-Green et al, Obesity 2016; de Zegher et al, Trends Endocrinol Metab 2018). Adolescent PCOS phenotypes are normalized more by preferential reduction of hepato-visceral adiposity with a low-dose combination of spironolactone, pioglitazone and metformin (SPIOMET) than by treatment with an oral contraceptive (OC) (Ibanez et al, J Adolesc Health 2017). Nowadays, the assessment of hepato-visceral adiposity (by magnetic resonance imaging) is rather cumbersome. In an attempt to identify a circulating marker of hepato-visceral fat excess, we studied whether S100A4 concentrations are elevated in adolescent girls with PCOS and, if so, whether they tend to normalize with OC or SPIOMET treatment. In 12 healthy controls and in 51 adolescent girls with PCOS (by International Consortium Update criteria; Ibanez et al, Horm Res Pediatr 2017), we assessed circulating S100A4 along with endocrine markers (including fasting insulin, SHBG, testosterone [by LC-MS/MS], high-molecular-weight adiponectin), body composition (by dual X-ray absorptiometry), and abdominal fat partitioning (by magnetic resonance imaging). Girls with PCOS were randomized for treatment with an OC (n=27) or SPIOMET (n=24) for 1 year, and the changes in their study endpoints were analysed. S100A4 concentrations were on average 71% (or 2.1 Z-score) higher in girls with PCOS than in controls (P<0.001), and they associated with hepato-visceral adiposity (r=0.47; p=0.001). Treatment with OC failed to lower the elevated S100A4 concentrations, whereas treatment with SPIOMET lowered circulating S100A4 toward normal (P<0.001 for within-group changes, and P<0.01 for between-group changes); on-treatment reduction of circulating S100A4 associated closely with reduction of hepato-visceral adiposity (r=0.50; p<0.0001). If the present findings are corroborated in other study cohorts with PCOS, then S100A4 is a first candidate-member of a future set of circulating markers that may simplify the diagnosis and follow-up of patients with PCOS, and perhaps also of patients with other phenotypes of central obesity.

Visceral fat mass: is it the link between uric acid and diabetes risk?

BackgroundUric acid (UA) has been suggested as a novel risk factor for diabetes. However, its definite role in this prevalent disease is still the subject of much discussion because it is always accompanied with other major risk factors such as obesity and high visceral adiposity. In order to clarify the role of UA in diabetes, this study aimed to investigate the associations between plasma UA and fasting plasma glucose, HbA1c, lipid profile and inflammatory markers after accounting for the contribution of other diabetes risk factors such as BMI and VAT fat mass.MethodsIn the present cross-sectional study, 100 non-diabetic middle-aged males (n = 48) and females (n = 52) were recruited. Central fat distribution measures including android to gynoid fat ratio, VAT and subcutaneous adipose tissue (SAT) fat mass were determined using dual-energy X-ray absorptiometry (DXA). Biochemical analysis was done using methods well established for clinical and research laboratories. Multiple linear regression analysis was performed to analyse the association between plasma UA and the biochemical and central fat distribution measures.ResultsUA was positivly associated with body mass index (BMI) (r (98) = 0.42, P ≤ 0.001), android to gynoid fat ratio (r (98) = 0.62, P ≤ 0.001) and VAT fat mass (r (96) = 0.55, P ≤ 0.001). UA was also positively associated with plasma glucose (r (98) = 0.33, P ≤ 0.001), hemoglobin A1c (r (93) = 0.25, P = 0.014), plasma triglyceride (rs (95) = 0.40, P ≤ 0.001), HDL cholesterol (r (98) = − 0.61, P ≤ 0.001) and CRP (rs (98) = 0.23, P = 0.026). However, these associations were no longer significant after accounting for BMI or/and VAT fat mass. No significant association was observed between UA and SAT fat mass (r (97) = 0.02, P ≥ 0.05), Total cholesterol (r (98) = 0.03, P ≥ 0.05), LDL cholesterol (r (98) = 0.13, P ≥ 0.05), TNF-α (r (97) = 0.12, P ≥ 0.05) and IL-6 (r (96) = −0.02, P ≥ 0.05).ConclusionResults from this study suggest, for the first time, that the association between plasma UA and glucose in a non-diabetic population is not direct but rather dependent on VAT fat mass.

Adipose tissue and liver.

Adipose tissue and liver are central tissues in whole body energy metabolism. Their composition, structure, and function can be noninvasively imaged using a variety of measurement techniques that provide a safe alternative to an invasive biopsy. Imaging of adipose tissue is focused on quantitating the distribution of adipose tissue in subcutaneous and intra-abdominal (visceral) adipose tissue depots. Also, detailed subdivisions of adipose tissue can be distinguished with modern imaging techniques. Adipose tissue (or adipocyte) accumulation or infiltration of other organs can also be imaged, with intramuscular adipose tissue a common example. Although liver fat content is now accurately imaged using standard magnetic resonance imaging (MRI) techniques, inflammation and fibrosis are more difficult to determine noninvasively. Liver imaging efforts are therefore concerted on developing accurate imaging markers of liver fibrosis and inflammatory status. Magnetic resonance elastography (MRE) is presently the most reliable imaging technique for measuring liver fibrosis but requires an external device for introduction of shear waves to the liver. Methods using multiparametric diffusion, perfusion, relaxometry, and hepatocyte-specific MRI contrast agents may prove to be more easily implemented by clinicians, provided they reach similar accuracy as MRE. Adipose tissue imaging is experiencing a revolution with renewed interest in characterizing and identifying distinct adipose depots, among them brown adipose tissue. Magnetic resonance spectroscopy provides an interesting yet underutilized way of imaging adipose tissue metabolism through its fatty acid composition. Further studies may shed light on the role of fatty acid composition in different depots and why saturated fat in subcutaneous adipose tissue is a marker of high insulin sensitivity.

Central obesity as a clinical marker of adiposopathy; increased visceral adiposity as a surrogate marker for global fat dysfunction.

Purpose of reviewSubcutaneous adipose tissue (SAT) is often described as ‘protective’. Visceral adipose tissue (VAT) is often described as ‘pathologic’. However, both SAT and VAT have protective and pathologic potential, with interdependent biologic functions.Recent findingsMost of the body's (excess) energy is stored as fat in SAT. If during positive caloric balance, SAT does not undergo adequate adipogenesis, then excess energy may result in adipocyte hypertrophy, leading to hypoxia, immunopathies, and endocrinopathies. Energy overflow may promote accumulation of pericardial fat, perivascular fat, and myocardial fat, which may directly contribute to atherosclerotic cardiovascular disease (CVD). Lipotoxic free fatty acid delivery to nonadipose body organs (e.g. liver, muscle, and pancreas) may indirectly contribute to CVD by promoting the most common metabolic disorders encountered in clinical practice (e.g. high blood sugars, high blood pressure, and dyslipidaemia), all major CVD risk factors. Finally, SAT energy overflow may increase VAT accumulation, which is also associated with increased risk of metabolic diseases and CVD.SummaryIncreased VAT is a surrogate marker for SAT dysfunction which increases waist circumference, reflecting a shared pathologic process leading to the pathogenic fat accumulation of other fat depots and fatty infiltration of nonadipose body organs. Central obesity is a clinical marker for adiposopathy.

Combined effects of dietary arginine, leucine and protein levels on fatty acid composition and gene expression in the muscle and subcutaneous adipose tissue of crossbred pigs

The cumulative effects of dietary arginine, leucine and protein levels on fat content, fatty acid composition and mRNA levels of genes controlling lipid metabolism in pig longissimus lumborum muscle and subcutaneous adipose tissue (SAT) were investigated. The experiment was performed on fifty-four intact male pigs (Duroc × Pietrain × Large White × Landrace crossbred), with a live weight ranging from 59 to 92 kg. The pigs were randomly assigned to one of six experimental treatments (n 9). The treatments followed a 2 × 3 factorial arrangement, with two levels of arginine supplementation (0 v. 1 %) and three levels of a basal diet (normal protein diet, NPD; reduced protein diet, RPD; reduced protein diet to achieve 2 % of leucine, RPDL). The results showed that dietary arginine supplementation did not affect the intramuscular fat (IMF) content and back fat thickness, but increased the total fat in SAT. This effect was associated with an increase in fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) mRNA levels in SAT, which suggests that arginine might be involved in the differential regulation of some key lipogenic genes in pig muscle and SAT. The increase in IMF content under the RPD, with or without leucine supplementation, was accompanied by increased FASN and SCD mRNA levels. Arginine supplementation did not influence the percentage of main fatty acids, while the RPD had a significant effect on fatty acid composition in both tissues. Leucine supplementation of RPD did not change IMF, total fat of SAT and back fat thickness, but increased 16 : 0 and 18 : 1cis-9 and decreased 18 : 2n-6 in muscle.

Contrasting cellularity on fat deposition in the subcutaneous adipose tissue and longissimus lumborum muscle from lean and fat pigs under dietary protein reduction

The production of pork with high amounts of intramuscular fat (IMF) without an increase in subcutaneous fat is highly desirable for the pig industry and consumers. Herein, we question the impact of dietary protein reduction (18% v. 13%) on fat deposition in the subcutaneous adipose tissue (SAT) and longissimus lumborum (LL) muscle using genetically diverse pigs for body fatness (lean v. fat). A clear effect of genotype was observed on plasma insulin (P=0.004) and leptin (P<0.001), as well as on backfat thickness (P<0.001), with the fat pigs having higher values. Accordingly, IMF was higher in the fat pigs, when compared with their lean counterparts (P=0.003), which was supported by enlarged adipocytes (P<0.001). The area of lipid droplets within the LL fibres (P=0.039) and extramyocellular lipids number (P=0.017) were increased in pigs fed reduced protein diets, regardless of genotype, which is consistent with higher levels of plasma triacylglycerols (P=0.002). The gene-expression pattern of lipogenic factors in the SAT was distinct from the LL muscle. In the SAT, PPARG expression was similar among genotypes (P>0.05), whereas in the LL muscle it was higher in the lean pigs (P=0.023), especially when fed on low protein diet (P=0.057). The CEBPA and FABP4 mRNA levels were increased in the SAT of fat pigs (P<0.001), without changes in the LL muscle (P>0.05). The influence of diet on FABP4 expression in the SAT was dependent on pig’s genetic background (P=0.005). In conclusion, fat deposition was clearly influenced by genotype and, to a lesser extent, by dietary protein level, the SAT being more sensitive than the LL muscle. One can speculate that the pathways involved in lipid metabolism are downregulated in intramuscular adipocytes when compared with SAT fat cells. This result might be a direct consequence of the relatively low proportion of adipocytes found in the LL muscle.

Increased nocturnal fat oxidation in young healthy men with low birth weight: Results from 24-h whole-body respiratory chamber measurements

ObjectiveLow birth weight (LBW), a marker of disturbed fetal growth, is associated with adiposity and increased risk of type 2 diabetes (T2D). The aim of the study was to investigate whether LBW is associated with changes in 24-h energy expenditure (EE) and/or substrate utilization rates, potentially contributing to the development of adiposity and/or T2D compared to matched control subjects. Materials/MethodsForty-six young, healthy men were included in the study; 20 with LBW (≤ 10th percentile) and 26 control subjects with normal birth weight (NBW) (50th–90th percentile). The subjects were fed a weight maintenance diet and 24-h energy expenditure (EE), respiratory quotient (RQ), and substrate oxidation were assessed in a respiratory chamber. ResultsNo differences in 24-h EE, RQ or substrate oxidation were observed between LBW and controls. Interestingly, the LBW group exhibited lower nocturnal RQ compared to controls (0.81 ± 0.01 vs. 0.85 ± 0.01 (mean ± SE), P = 0.01), and hence higher nocturnal fat oxidation (2.55 ± 0.13 vs. 2.09 ± 0.12 kJ/min (mean ± SE), P = 0.02). ConclusionsYoung LBW men do not exhibit reductions in 24-h EE. However, LBW subjects display increased nocturnal fat oxidation at the expense of reduced glucose oxidation. We speculate that this may be associated with insufficient capability to retain fat in subcutaneous adipose tissue after meals during day time, with an increased rate of nocturnal and morning lipolysis, and potentially with subtle elevations of gluconeogenesis and of fasting glucose levels in the LBW subjects.

Resistant starch and exercise independently attenuate weight regain on a high fat diet in a rat model of obesity.

BackgroundLong-term weight reduction remains elusive for many obese individuals. Resistant starch (RS) and exercise may be useful for weight maintenance. The effects of RS, with or without exercise, on weight regain was examined during relapse to obesity on a high carbohydrate, high fat (HC/HF) diet.MethodsObesity-prone rats were fed ad libitum for 16 weeks then weight reduced on a low fat diet to induce a 17% body weight loss (weight reduced rats). Weight reduced rats were maintained on an energy-restricted low fat diet for 18 weeks, with or without a daily bout of treadmill exercise. Rats were then allowed free access to HC/HF diet containing low (0.3%) or high (5.9%) levels of RS. Weight regain, energy balance, body composition, adipocyte cellularity, and fuel utilization were monitored as rats relapsed to obesity and surpassed their original, obese weight.ResultsBoth RS and exercise independently attenuated weight regain by reducing the energy gap between the drive to eat and suppressed energy requirements. Exercise attenuated the deposition of lean mass during relapse, whereas its combination with RS sustained lean mass accrual as body weight returned. Early in relapse, RS lowered insulin levels and reduced the deposition of fat in subcutaneous adipose tissue. Exercise cessation at five weeks of relapse led to increased weight gain, body fat, subcutaneous adipocytes, and decreased lean mass; all detrimental consequences to overall metabolic health.ConclusionsThese data are the first to show the complimentary effects of dietary RS and regular exercise in countering the metabolic drive to regain weight following weight loss and suggest that exercise cessation, in the context of relapse on a HC/HF diet, may have dire metabolic consequences.

VAT fat is bad for the liver, SAT fat is not!

VAT fat is bad for the liver, SAT fat is not!