PTRF acts as an adipokine contributing to adipocyte dysfunctionality and ectopic lipid deposition.

Adipose tissue (AT) expands under obesogenic conditions. Yet, when the growth exceeds a certain limit, AT becomes dysfunctional and surplus lipids start depositing ectopically. Polymerase I and transcription release factor (PTRF) has been proposed as a mechanism leading to a dysfunctional AT by decreasing the adipogenic potential of human adipocyte precursors. However, whether or not PTRF can be secreted by the adipocytes into the bloodstream is not yet known. For this work, PTRF presence was investigated in plasma. We also produced a recombinant PTRF (rPTRF) and examined its impact on the functional interactions between the adipocyte and the hepatocyte in vitro. We demonstrated that PTRF can be found in human plasma, and is at least in part, carried by exosomes. In vitro treatment with rPTRF increased the hypertrophy and senescence of 3T3-L1 adipocytes. In turn, those rPTRF-treated adipocytes increased lipid accumulation in hepatocytes. Lastly, we found a positive correlation between circulating PTRF and the concentration of PTRF in the visceral fat depot. All these findings point toward the presence of an enlarged and dysfunctional visceral adipose tissue which secretes PTRF. This circulating PTRF behaves as an adipokine and may partially contribute to the well-known detrimental effects of visceral fat accumulation.

Investigation of biomechanical response of Hoffa's fat pad and comparative characterization.

The infrapatellar adipose body (Hoffa's fat pad, IFP) is situated between the patellar tendon, the femoral condyle and the tibial plateau. The IFP consists of lobules of white adipose tissue delimited by thin connective septa. The actual structural functionality of the IFP is debated and should pertain to a cushioning role in the knee joint, providing to distribute and to damp mechanical stresses during articular activity. The present study is aimed to analyze the correlation between histological configuration and mechanical properties of the IFP, compared to other adipose tissues, partially differentiated by composition and conformation. Histological and ultrastructural methods were exploited to analyze the microscopic anatomies of IFP, knee (KSF) and abdominal (ASF) subcutaneous fat tissues. Numerical micro-models of the different tissues were developed by using histo-morphometric data, as the size of adipose lobules, the thickness of the septa and their composition. Numerical analyses made it possible to evaluate the mechanical functionality of the different fat tissues considering the characteristic loading conditions, as compressive and shear actions. The results pointed out the actual mechanical relevance of IFP and KSF, while ASF exhibited different mechanical properties. Furthermore, the contribution of connective septa and adipose lobules to compressive and shear mechanical behavior was elucidated. This preliminary investigation represents the basis for biomechanical interpretation and the definition of more refined model to be developed on the acquisition of additional histological and morphometric data.

Active individuals have high mitochondrial content and oxidative markers in their abdominal subcutaneous adipose tissue.

OBJECTIVE: Exercise training (training) effects on white adipose tissue (WAT) thermogenic and oxidative capacities in humans are inconclusive. This study aimed to investigate whether an active lifestyle is characterized by thermogenic and/or oxidative transcriptional markers in human WAT. METHODS: In vivo maximal muscle ATP synthetic rates (ATPmax) were measured by 31 P-MRS, body composition by DXA, and peak oxygen uptake (VO2 peak) by cycle ergometry in active (n = 7) and sedentary (SED) individuals before and after 3 weeks of training (n = 9, SED only). mRNA expressions of brown adipose and ß-oxidation markers, as well as mitochondrial DNA content (mtDNA), were measured by qRT-PCR and qPCR, respectively, in WAT. RESULTS: ATPmax and VO2 peak were higher in active versus SED individuals. Following training in SED individuals, ATPmax and VO2 peak increased. Proliferator-activated receptor gamma coactivator-1α and carnitine palmitoyltransferase-1ß gene expressions and mtDNA content were significantly higher in WAT of active versus SED individuals before training. mRNA contents of brown and beige-specific markers were not different between cohorts. Training effectively increased ATPmax and VO2 peak but had no effect on mtDNA content or expressions of genes that regulate thermogenic and oxidative capacities in WAT. CONCLUSIONS: Results indicate that an active lifestyle is characterized by elevated mitochondrial content and oxidative, not thermogenic, markers of WAT.

Mitochondrial respiration in subcutaneous and visceral adipose tissue from patients with morbid obesity.

Adipose tissue exerts important endocrine and metabolic functions in health and disease. Yet the bioenergetics of this tissue is not characterized in humans and possible regional differences are not elucidated. Using high resolution respirometry, mitochondrial respiration was quantified in human abdominal subcutaneous and intra-abdominal visceral (omentum majus) adipose tissue from biopsies obtained in 20 obese patients undergoing bariatric surgery. Mitochondrial DNA (mtDNA) and genomic DNA (gDNA) were determined by the PCR technique for estimation of mitochondrial density. Adipose tissue samples were permeabilized and respirometric measurements were performed in duplicate at 37 degrees C. Substrates (glutamate (G) + malate (M) + octanoyl carnitine (O) + succinate (S)) were added sequentially to provide electrons to complex I + II. ADP ((D)) for state 3 respiration was added after GM. Uncoupled respiration was measured after addition of FCCP. Visceral fat contained more mitochondria per milligram of tissue than subcutaneous fat, but the cells were smaller. Robust, stable oxygen fluxes were found in both tissues, and coupled state 3 (GMOS(D)) and uncoupled respiration were significantly (P < 0.05) higher in visceral (0.95 +/- 0.05 and 1.15 +/- 0.06 pmol O(2) s(1) mg(1), respectively) compared with subcutaneous (0.76 +/- 0.04 and 0.98 +/- 0.05 pmol O(2) s(1) mg(1), respectively) adipose tissue. Expressed per mtDNA, visceral adipose tissue had significantly (P < 0.05) lower mitochondrial respiration. Substrate control ratios were higher and uncoupling control ratio lower (P < 0.05) in visceral compared with subcutaneous adipose tissue. We conclude that visceral fat is bioenergetically more active and more sensitive to mitochondrial substrate supply than subcutaneous fat. Oxidative phosphorylation has a higher relative activity in visceral compared with subcutaneous adipose tissue.

Comparison of anthropometric, area- and volume-based assessment of abdominal subcutaneous and visceral adipose tissue volumes using multi-detector computed tomography.

PURPOSE: Cross-sectional imaging may enable accurate localization and quantification of subcutaneous and visceral adipose tissue. The reproducibility of multi-detector computed tomography (MDCT)-based volumetric quantification of abdominal adipose tissue and the ability to depict age- and gender-related characteristics of adipose tissue deposition have not been reported. METHODS: We evaluated a random subset of 100 Caucasian subjects (age range: 37-83 years; 49% women) of the Framingham Heart Study offspring cohort who underwent MDCT scanning. Two readers measured subcutaneous and visceral adipose tissue volumes (SAV and VAV; cm(3)) and areas (SAA and VAA; cm(2)) as well as abdominal sagital diameter (SD) and waist circumference (WC). RESULTS: Inter-reader reproducibility was excellent (relative difference: -0.34+/-0.52% for SAV and 0.59+/-0.93% for VAV, intra-class correlation (ICC)=0.99 each). The mean SAA/VAA ratio was significantly different from the mean SAV/VAV ratio (2.0+/-1.2 vs 1.7+/-0.9; P<0.001). The ratio of SAV/VAV was only weakly inversely associated with SD (ICC=-0.32, P=0.01) and not significantly associated with WC (ICC=-0.14, P=0.14) or body mass index (ICC=-0.17, P=0.09). The mean SAV/VAV ratio was significantly different between participants <60 vs >60 years (1.9+/-1.0 vs 1.5+/-0.7; P<0.001) and between men and women (1.2+/-0.5 vs 2.2+/-0.9; P<0.001). CONCLUSION: This study demonstrates that MDCT-based volumetric quantification of abdominal adipose tissue is highly reproducible. In addition, our results suggest that volumetric measurements can depict age- and gender-related differences of visceral and subcutaneous abdominal adipose tissue deposition. Further research is warranted to assess whether volumetric measurements may substantially improve the predictive value of obesity measures for insulin resistance, type 2 diabetes mellitus and other diseases.