Perirenal Adipose Tissue Inflammation: Novel Insights Linking Metabolic Dysfunction to Renal Diseases

A healthy adipose tissue (AT) is indispensable to human wellbeing. Among other roles, it contributes to energy homeostasis and provides insulation for internal organs. Adipocytes were previously thought to be a passive store of excess calories, however this view evolved to include an endocrine role. Adipose tissue was shown to synthesize and secrete adipokines that are pertinent to glucose and lipid homeostasis, as well as inflammation. Importantly, the obesity-induced adipose tissue expansion stimulates a plethora of signals capable of triggering an inflammatory response. These inflammatory manifestations of obese AT have been linked to insulin resistance, metabolic syndrome, and type 2 diabetes, and proposed to evoke obesity-induced comorbidities including cardiovascular diseases (CVDs). A growing body of evidence suggests that metabolic disorders, characterized by AT inflammation and accumulation around organs may eventually induce organ dysfunction through a direct local mechanism. Interestingly, perirenal adipose tissue (PRAT), surrounding the kidney, influences renal function and metabolism. In this regard, PRAT emerged as an independent risk factor for chronic kidney disease (CKD) and is even correlated with CVD. Here, we review the available evidence on the impact of PRAT alteration in different metabolic states on the renal and cardiovascular function. We present a broad overview of novel insights linking cardiovascular derangements and CKD with a focus on metabolic disorders affecting PRAT. We also argue that the confluence among these pathways may open several perspectives for future pharmacological therapies against CKD and CVD possibly by modulating PRAT immunometabolism.

Tamarind Multifunctional Protein: Safety and Anti-Inflammatory Potential in Intestinal Mucosa and Adipose Tissue in a Preclinical Model of Diet-Induced Obesity

<b><i>Introduction:</i></b> Obesity has emerged as one of the main public health problems. This condition triggers a series of hormonal and metabolic changes related to a low-grade chronic inflammatory condition. The trypsin inhibitor purified from tamarind (TTIp) seeds is a promising anti-inflammatory molecule, but its safety needs to be evaluated. This study aimed to evaluate TTIp bioactive dose effects on organs involved in its metabolism (liver and pancreas) and affected tissues (small intestine and perirenal adipose tissue) in an obesity model. <b><i>Methods:</i></b> Three groups of adult male Wistar rats were used (n = 5). Two of these groups had diet-induced obesity, and a third group was eutrophic. TTIp was administered by gavage in one of the obese groups for 10 days, while the remaining groups received a vehicle. The chromatographic profile and the inhibition assay corroded the purification of the inhibitor. Physical and behavioral changes, liver enzymes, and stereological and histopathological analyses of tissues were evaluated. <b><i>Results:</i></b> TTIp did not cause visible signs of toxicity, nor caused changes in liver enzymes, the liver, and pancreatic tissues. TTIp did not cause changes in the intestinal mucosa, showing improvement in the villi’s histopathological characteristics compared to the group of animals with obesity without treatment with TTIp (<i>p</i> = 0.004). The analysis of perirenal adipose tissue showed that the average sectional area of animals with obesity that received TTIp did not differ from the control. There was a difference between the high glycemic load diet group and the group treated with the inhibitor (351.8 ± 55.5) (<i>p</i> = 0.016). In addition, the group that received TTIp had no inflammatory infiltrates. <b><i>Conclusion:</i></b> Based on histological and stereological analysis, the use of TTIp is potentially safe and anti-inflammatory in the evaluated obesity model and can be investigated as a possible adjuvant in obesity therapy.

Untargeted Metabolomics Analysis Revealed Lipometabolic Disorders in Perirenal Adipose Tissue of Rabbits Subject to a High-fat Diet

Backgroud：High-fat diet (HFD) has been widely recognized as a significant modifiable risk for insulin resistance, inflammation, type 2-diabetes (T2D), atherosclerosis and other metabolic diseases. The biological mechanisms responsible for disturbances in perirenal adipose tissue (PAT) and other tissues in rodents fed a HFD are well understood. However, the biological mechanism responsible for key metabolic disorders in PAT of rabbits subject to HFD remains unclear. Methods: Here, untargeted metabolomics (LC-MS/MS) combined with liquid chromatography (LC) and high resolution mass spectrometry (MS) were used to evaluate PAT metabolic changes. Histological observations showed that the adipocytes cells and density of PAT was significantly increased in HFD rabbits. Principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) showed noticeable changes in PAT metabolites between the HFD and standard normal diet (SND) rabbit groups. Results: Our study revealed 206 differential metabolites (21 up-regulated and 185 down-regulated), and then the 47 differential metabolites (13 up-regulated and 34 down-regulated), mainly phospholipids, fatty acids, steroid hormones and amino acids, chosen as potential biomarkers to help explain metabolic disorders caused by HFD. These metabolites were mainly associated with biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a HFD caused significant metabolic disorders in rabbit PAT. Conclusion: High levels of phospholipids, fatty acids, steroid hormones and l-methionine may inhibit oxygen respiration by increasing the adipocytes cells and density cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thus increasing the risk of T2D , atherosclerosis, and other metabolic syndromes.

Perirenal Adipose Tissue—Current Knowledge and Future Opportunities

The perirenal adipose tissue (PRAT), a component of visceral adipose tissue, has been recently recognized as an important factor that contributes to the maintenance of the cardiovascular system and kidney homeostasis. PRAT is a complex microenvironment consisting of a mixture of white adipocytes and dormant and active brown adipocytes, associated with predipocytes, sympathetic nerve endings, vascular structures, and different types of inflammatory cells. In this review, we summarize the current knowledge about PRAT and discuss its role as a major contributing factor in the pathogenesis of hypertension, obesity, chronic renal diseases, and involvement in tumor progression. The new perspectives of PRAT as an endocrine organ and recent knowledge regarding the possible activation of dormant brown adipocytes are nowadays considered as new areas of research in obesity, in close correlation with renal and cardiovascular pathology. Supplementary PRAT complex intervention in tumor progression may reveal new pathways involved in carcinogenesis and, implicitly, may identify additional targets for tailored cancer therapy.

Peripheral nerve sheath malignancy with multiple metastasis: a rare clinical case

Background. Tumours of peripheral nervous system are represented by benign and malignant neoplasms with different clinical and biological traits. Malignant peripheral nerve sheath tumours of paraspinal localisation with the involvement of nerve structures are extremely rare and may occur isolated or comorbid with congenital neurofibromatosis. Current literature contains a few bioptic and selected autopsy clinical reports. Herewith, we present an own sectional observation of a rare malignant peripheral nerve sheath tumour with multiple metastasis supplemented with morphological and immunohistochemical descriptions.Clinical Case Description. An autopsy was performed on a 30-yo man’s cadaver. A tumour infiltrate was observed along Th5—Th9 of the spinal column intimately associated with thoracic vertebral bodies. Metastases were detected in the right lung, myocardium, peripancreatic and perirenal adipose tissue. Histological tumour examination revealed heterogeneous solid and rosette-like structures. Tumour immunophenotype: vimentin+, pancytokeratin-, CD45-, S-100+, NSE+, GFAP-, proliferative activity index (Ki-67 = 75-80%). This profile is descriptive of peripheral nerve sheath malignancy of high grade with multiple organic metastases.Conclusion. The sectional observation presented illustrates the difficulty to in vivo diagnose rare peripheral nerve sheath malignancies due to their infiltrative growth into spinal bone marrow and metastasis to organs (lungs, myocardium, peripancreatic and perirenal adipose tissue).

Quality changes of frozen Longissimus dorsi and Semimembranosus muscles and perirenal adipose tissue during storage in lambs fed dihydroquercetin or dry distilled rose petals supplemented diet.

The aim of the study was to determine the quality changes of frozen muscles of Longissimus dorsi and Semimembranosus and perirenal adipose tissue from lambs fed a diet supplemented by 7.5 mg dihydroquercetin/kg/d, or 545 mg dry distilled rose petals (DDRP)/kg/d. Three groups of 10 male lambs aged 65 days were fed 50 days ad libitum: a control (ground alfalfa + granular compound feed) and two experimental groups (the same diet but with the addition of phytonutrients). Samples were collected 1 d post mortem. A half of them were analyzed immediately and another one was vacuum-packed, frozen at -40°C and stored for 365 d at -18°C. It has been found that supplementing the lamb's diet with polyphenol-rich phytonutrients contributes to certain reduction in aerobic plate count, α-aminoacidic nitrogen, protein carbonyls, TBARS and the content of saturated fatty acids, but with small amplitudes, more pronounced in the m. Longissimus dorsi from lambs fed with 545 mg DDRP/kg/d. Further studies are needed to answer the question of whether the use of higher doses of DDRP or dihydroquercetin as supplements in the small ruminant's diet will be able to provide a more pronounced inhibitory effect on oxidation processes in frozen lamb.

Optimization of extracellular matrix extraction from human perirenal adipose tissue

Human adipose tissue includes useful substrates for regenerative medicine such as the extracellular matrix (ECM), but most perirenal fat tissue is wasted after kidney surgery. Since a lot of adipose tissue can be procured after a kidney, we extracted ECM from human perirenal adipose tissue and optimized the extraction process. To verify the efficacy for ECM extraction, we compared the products in several steps. Perirenal adipose tissue was either finely homogenized or underwent crude manual dissection. The amount of extracted ECM was quantified with ELISA for verification of the initial tissue downsizing effect. To validate the drying effect for fast and complete delipidation, tissues were prepared in a dry or wet phase, and residual lipids were visualized with Oil-Red-O staining. The extracted lipid was assayed at each time point to quantify the appropriate delipidation time. To select the optimal decellularization method, tissues were treated with physical, chemical, or enzymatic method, and the residual cell debris were identified with histological staining. The biochemical properties of the ECM extracted by the above methods were analyzed. The ECM extracted by fine homogenization showed a significantly enhanced amount of collagen, laminin and fibronectin compared to the crude dissection method. The dried tissue showed fast and complete lipid elimination compared to the wet tissue. Complete delipidation was achieved at 45 min after acetone treatment. Additionally, 1% triton X-100 chemical treatment showed complete decellularization with well-preserved collagen fibers. Biochemical analysis revealed preserved ECM proteins, a high cell proliferation rate and normal cell morphology without cell debris or lipids. The established process of homogenization, drying, delipidation with acetone, and decellularization with Triton X-100 treatment can be an optimal method for ECM extraction from human perirenal adipose tissue. Using this technique, human perirenal adipose tissue may be a valuable source for tissue engineering and regenerative medicine.