Perirenal Adipose Tissue Research Articles

Effects of Pig Dietary n-6/n-3 Polyunsaturated Fatty Acids Ratio and Gender on Carcass Traits, Fatty Acid Profiles, Nutritional Indices of Lipid Depots and Oxidative Stability of Meat in Medium-Heavy Pigs.

The effects of different dietary n-6/n-3 polyunsaturated fatty acids (PUFA) ratios and gender on key carcass traits, as well as the nutritional and technological quality of lipids in medium-heavy pig tissues have been poorly studied. To investigate the subject, 24 Large White, barrows and gilts, evenly divided into two groups of 12, were fed from 80 kg of live-weight (LW) until slaughter at 150 kg LW, either a high (9.7:1) (HPR) or low (1.4:1) (LPR) dietary n-6/n-3 PUFA ratio. On individual samples of longissimus thoracis muscle (LTM), subcutaneous (SF) and perirenal (PF) adipose tissues (ATs), the fatty acid (FA) composition was determined by gas chromatography, and lipid nutritional indices (LNIs) were calculated. The oxidative stability of meat was evaluated by determining the malondialdehyde content on raw and cooked (24 h postmortem) and refrigerated (8 days postmortem) LTM samples. The carcass traits did not vary between genders and diets. The LPR group showed a higher n-3 PUFA level and a lower n-6/n-3 PUFA ratio in all the tissues examined and better LNI, especially in the ATs. Diet did not affect the oxidative stability of meat. Gender did not influence the n-6/n-3 PUFA ratio, while barrows showed improvements in some LNI in ATs. Reducing the n-6/n-3 ratio in the diet of growing-finishing medium-heavy pigs improved the FA profile in all tissues and most LNI in ATs without impairing the oxidative stability of meat.

Morphological characteristics of SETD2-mutated locally advanced clear cell renal cell carcinoma: Comparison with BAP1-mutated clear cell renal cell carcinoma

SET-domain containing 2 (SETD2) and BRCA1-associated protein 1 (BAP1), both chromatin remodeling genes, are frequently mutated in clear cell renal cell carcinoma (ccRCC) and involved in tumor progression and metastasis. Herein, we studied clinicopathologic features of 7 cases of locally advanced ccRCC with single SETD2 mutation, and compared to 7 cases of locally advanced ccRCC with single BAP1 mutation. SETD2-mutated ccRCC showed high-grade transformation, comprising of enlarged tumor cells with voluminous clear cytoplasm, enlarged irregular nuclei with prominent nucleoli, eosinophilic cytoplasmic granules, arranged in various architectural patterns such as large nested, tubular, tubulopapillary and solid. 71 % (5 of 7 cases) of SETD2-mutated ccRCC showed a rhabdoid morphology. SETD2-mutated ccRCC have striking propensity for invasive growth; all cases have vascular invasion and perirenal (extracapsular) adipose tissue invasion. After nephrectomy, distant metastasis was found in 67 % (4 of 7 cases) of patients with SETD2-mutated ccRCC. The most common metastatic site was the lung (3 cases), followed by precaval lymph nodes (1 case). BAP1-mutated ccRCC also showed a similar high-grade morphology, with rhabdoid and/or sarcomatoid features. Their high-grade features mostly overlapped with those of SETD2-mutated ccRCC, which makes difficult to predict the presence of BAP1 or SETD2 mutation solely from morphology. These findings justify the use of molecular testing to detect these mutations, especially when we encounter high-grade ccRCC. Detecting SETD2 and BAP1 mutation in ccRCC is useful for risk stratification and proper therapeutic strategy.

The Dietary Inclusion of Ensiled Olive Cake Increases Unsaturated Lipids in Milk and Alters the Expression of Lipogenic Genes in Mammary and Adipose Tissue in Goats.

This study aimed to evaluate the effect of the dietary inclusion of ensiled OC on milk yield, composition, fatty acid (FA) profile, and the expression of selected genes involved in lipid metabolism in the udder and adipose tissue of goats. Seventy-two Damascus dairy goats in mid-lactation were assigned randomly to three iso-nitrogenous and iso-energetic diets containing 0, 10, and 20% of ensiled OC as a replacement of forage (OC0, OC10, and OC20, respectively) for 42 days. During weeks 5 and 6 of the trial, dry matter intake, milk yield, milk composition, and FA profiles were recorded, while mammary and perirenal adipose tissue samples were also collected from six animals per treatment from the OC0 and OC20 groups for gene expression analysis. No significant differences were observed among groups concerning milk yield, 4% fat-corrected milk, fat, or protein yield (kg/d). In contrast, the milk fat percentage was gradually increased with increasing OC inclusion rates in the diets, while milk protein percentages were elevated in both OC groups but significantly only in the milk of the OC20 group. The content of FA between C4:0 to C16:0 was reduced, while mono-unsaturated FA (MUFA) concentration was enhanced in the goat milk of OC groups. The OC feeding treatment was associated with the increased mammary expression of SLC2A1 (p < 0.05), VLDLR (p < 0.01), FABP3 (p < 0.01), and elevated SLC2A1 (p < 0.05) and FASN (p < 0.01) gene expression in the adipose tissue of goats fed the OC20 diet. Overall, OC can be used in goats' diets as a forage replacement, at least in the inclusion rate of 20% DM, since this could increase the milk protein and fat percentage and enrich its content with beneficial for human health lipids without adversely affecting milk production traits.

Glycolytic enzyme PFKFB3 regulates sphingosine 1-phosphate receptor 1 in proangiogenic glomerular endothelial cells under diabetic condition.

Glomerular angiogenesis is a characteristic feature of diabetic nephropathy (DN). Enhanced glycolysis plays a crucial role in angiogenesis. The present study was designed to investigate the role of glycolysis in glomerular endothelial cells (GECs) in a mouse model of DN. Mouse renal cortex and isolated glomerular cells were collected for single-cell and RNA sequencing. Cultured GECs were exposed to high glucose in the presence (proangiogenic) and absence of a vascular sprouting regimen. MicroRNA-590-3p was delivered by lipofectamine in vivo and in vitro. In the present study, a subgroup of GECs with proangiogenic features was identified in diabetic kidneys by using sequencing analyses. In cultured proangiogenic GECs, high glucose increased glycolysis and phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) protein expression, which were inhibited by overexpressing miRNA-590-3p. Mimics of miRNA-590-3p also increased receptor for sphingosine 1-phosphate (S1pR1) expression, an angiogenesis regulator, in proangiogenic GECs challenged with high glucose. Inhibition of PFKFB3 by pharmacological and genetic approaches upregulated S1pR1 protein in vitro. Mimics of miRNA-590-3p significantly reduced migration and angiogenic potential in proangiogenic GECs challenged with high glucose. Ten-week-old type 2 diabetic mice had elevated urinary albumin levels, reduced renal cortex miRNA-590-3p expression, and disarrangement of glomerular endothelial cell fenestration. Overexpressing miRNA-590-3p via perirenal adipose tissue injection restored endothelial cell fenestration and reduced urinary albumin levels in diabetic mice. Therefore, the present study identifies a subgroup of GECs with proangiogenic features in mice with DN. Local administration of miRNA-590-3p mimics reduces glycolytic rate and upregulates S1pR1 protein expression in proangiogenic GECs. The protective effects of miRNA-590-3p provide therapeutic potential in DN treatment.NEW & NOTEWORTHY Proangiogenetic glomerular endothelial cells (GECs) are activated in diabetic nephropathy. High glucose upregulates glycolytic enzyme phosphofructokinase/fructose bisphosphatase 3 (PFKFB3) in proangiogenetic cells. PFKFB3 protects the glomerular filtration barrier by targeting endothelial S1pR1. MiRNA-590-3p restores endothelial cell function and mitigates diabetic nephropathy.

Perirenal fat thickness as a superior obesity-related marker of subclinical carotid atherosclerosis in type 2 diabetes mellitus.

Emerging evidence highlighted that perirenal adipose tissue might regulate the cardiovascular and metabolism system through several pathways. This study aimed to assess the association between perirenal fat thickness (PrFT) and subclinical carotid atherosclerosis (SCCA) in type 2 diabetes mellitus (T2DM). A total of 670 participants with complete data were included in this study. The trained reviewer collected demographic and anthropometric information. Laboratory assessments were determined by standard methods. PrFT and SCCA were evaluated by computed tomography and ultrasound. Binomial logistic regression analysis was conducted to assess the association between PrFT and SCCA. Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the identifying value of PrFT for SCCA. Overall, the prevalence of SCCA was 61.8% in T2DM. PrFT was significantly increased in the SCCA group. Growing trends were observed in the prevalence of hypertension, carotid intima-media thickness (cIMT) > 1, plaque, and SCCA across the PrFT quartiles. Spearman correlation analysis revealed that PrFT was positively associated with cIMT (r = 0.401, p < 0.001). This correlation remained significant after adjustment for visceral fat area (VFA), subcutaneous fat area (SFA), and traditional metabolic risk factors (β = 0.184, p < 0.001). Meanwhile, PrFT was independently correlated with plaque, cIMT > 1 mm, and SCCA. The ORs (95% CI) were 1.072 (1.014-1.135), 1.319 (1.195-1.455), and 1.216 (1.119-1.322). Furthermore, PrFT remained correlated considerably with SCCA in subgroup analysis after stratification for age, sex, smoking, hypertension, and body mass index. From the ROC curve analysis, the AUCs (95% CI) of PrFT, VFA, and SFA identifying SCCA were 0.794 (0.760-0.828), 0.760 (0.724-0.796), and 0.697 (0.656-0.737), respectively. The AUC of PrFT was significantly higher than VFA (p = 0.028) and SFA (p < 0.001). The optimal cutoff values of PrFT were 14.0 mm, with a sensitivity of 66.7% and a specificity of 76.2%. PrFT was independently associated with cIMT, plaque, cIMT > 1 mm, and SCCA as a superior obesity-related marker of SCCA in T2DM. Clinical Trials.Gov, identifier ChiCTR2100052032.

Abdominal adipose tissue and type 2 diabetic kidney disease: adipose radiology assessment, impact, and mechanisms.

Diabetic kidney disease (DKD) is a significant healthcare burden worldwide that substantially increases the risk of kidney failure and cardiovascular events. To reduce the prevalence of DKD, extensive research is being conducted to determine the risk factors and consequently implement early interventions. Patients with type 2 diabetes mellitus (T2DM) are more likely to be obese. Abdominal adiposity is associated with a greater risk of kidney damage than general obesity. Abdominal adipose tissue can be divided into different fat depots according to the location and function, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), perirenal adipose tissue (PAT), and renal sinus adipose tissue (RSAT), which can be accurately measured by radiology techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI). Abdominal fat depots may affect the development of DKD through different mechanisms, and radiologic abdominal adipose characteristics may serve as imaging indicators of DKD risk. This review will first describe the CT/MRI-based assessment of abdominal adipose depots and subsequently describe the current studies on abdominal adipose tissue and DKD development, as well as the underlying mechanisms in patients of T2DM with DKD.

Finerenone protects against progression of kidney and cardiovascular damage in a model of type 1 diabetes through modulation of proinflammatory and osteogenic factors

The non-steroidal mineralocorticoid receptor antagonist (MRA) finerenone (FIN) improves kidney and cardiovascular outcomes in patients with chronic kidney disease (CKD) in type 2 diabetes (T2D). We explored the effect of FIN in a novel model of type 1 diabetic Munich Wistar Frömter (MWF) rat (D) induced by injection of streptozotocin (15 mg/kg) and additional exposure to a high-fat/high-sucrose diet. Oral treatment with FIN (10 mg/kg/day in rat chow) in diabetic animals (D-FIN) was compared to a group of D rats receiving no treatment and a group of non-diabetic untreated MWF rats (C) (n = 7–10 animals per group). After 6 weeks, D and D-FIN exhibited significantly elevated blood glucose levels (271.7 ± 67.1 mg/dl and 266.3 ± 46.8 mg/dl) as compared to C (110.3 ± 4.4 mg/dl; p < 0.05). D showed a 10-fold increase of kidney damage markers Kim-1 and Ngal which was significantly suppressed in D-FIN. Blood pressure, pulse wave velocity (PWV) and arterial collagen deposition were lower in D-FIN, associated to an improvement in endothelial function due to a reduction in pro-contractile prostaglandins, as well as reactive oxygen species (ROS) and inflammatory cytokines (IL-1, IL-6, TNFα and TGFβ) in perivascular and perirenal adipose tissue (PVAT and PRAT, respectively). In addition, FIN restored the imbalance observed in CKD between the procalcifying BMP-2 and the nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. Our data show that treatment with FIN improves kidney and vascular damage in a new rat model of DKD with T1D associated with a reduction in inflammation, fibrosis and osteogenic factors independently from changes in glucose homeostasis.

Retroperitoneal capillary arteriovenous malformation mimicking a malignant neoplasm

IntroductionRetroperitoneal tumors account for 0.2% of all neoplasms. Among these tumors, retroperitoneal vascular malformations are particularly rare, with most previously reported cases being venous malformations.Case presentationA 72‐year‐old woman was diagnosed with a retroperitoneal tumor on abdominal computed tomography. The 27‐mm diameter tumor was located away from the right kidney and major vessels in the right perirenal adipose tissue. Contrast‐enhanced computed tomography revealed a heterogeneously enhanced tumor with well‐defined borders. Dynamic contrast‐enhanced magnetic resonance imaging revealed rapid enhancement in the arterial phase and a progressive filling‐in pattern in the delayed phase. Although vascular malformation was suspected, a definitive diagnosis could not be established. The retroperitoneal tumor was excised laparoscopically for therapeutic and diagnostic purposes, and the histopathological diagnosis confirmed it as a capillary arteriovenous malformation.ConclusionHerein, we presented a rare case of retroperitoneal capillary arteriovenous malformation that was difficult to definitively diagnose preoperatively.

Cellular Evidence for Telocytes Mediating Electroacupuncture to Ameliorate Obesity in Mice.

Electroacupuncture has been generally applied to target obesity, the principle of which is based on the meridian in traditional Chinese medicine. Although Telocytes (TCs) have been reported as the potential essence of meridians, their specific role in the electroacupuncture treatment of obesity remains unclear. Thus, we investigated the cellular evidence for TC-mediated electroacupuncture to alleviate obesity. Mice were divided into three groups as follows: electroacupuncture group (EA), control group (CG), and normal group (NG). The present study showed that the weight of perirenal white adipose tissue (rWAT), the serum level of total cholesterol, and the low-density lipoprotein cholesterol were all significantly decreased after electroacupuncture. Ultrastructurally, the prolongations (telopodes, Tps) of TCs were in direct contact with adipocytes, and lipid droplets were distributed on the surface of Tps. The proportions of double-positive fluorescent areas of TCs (CD34 and PDGFRα) were significantly elevated with concomitant elongated Tps in EA mice, as compared to those in CG mice. The expression of Cx43 and CD63 (gap junction and exosome markers) was significantly enhanced. These characteristics facilitated the transmission of electroacupuncture stimulation from skin to rWAT. We conclude that electroacupuncture relieved obesity by activating TCs morphologically, upregulating the gap junctions between TCs, and increasing the exosomes around TCs.

Thermogenic Modulation of Adipose Depots: A Perspective on Possible Therapeutic Intervention with Early Cardiorenal Complications of Metabolic Impairment.

Cardiovascular complications of diabetes and obesity remain a major cause for morbidity and mortality worldwide. Despite significant advances in the pharmacotherapy of metabolic disease, the available approaches do not prevent or slow the progression of complications. Moreover, a majority of patients present with significant vascular involvement at early stages of dysfunction prior to overt metabolic changes. The lack of disease-modifying therapies affects millions of patients globally, causing a massive economic burden due to these complications. Significantly, adipose tissue inflammation was implicated in the pathogenesis of metabolic syndrome, diabetes, and obesity. Specifically, perivascular adipose tissue (PVAT) and perirenal adipose tissue (PRAT) depots influence cardiovascular and renal structure and function. Accumulating evidence implicates localized PVAT/PRAT inflammation as the earliest response to metabolic impairment leading to cardiorenal dysfunction. Increased mitochondrial uncoupling protein 1 (UCP1) expression and function lead to PVAT/PRAT hypoxia and inflammation as well as vascular, cardiac, and renal dysfunction. As UCP1 function remains an undruggable target so far, modulation of the augmented UCP1-mediated PVAT/PRAT thermogenesis constitutes a lucrative target for drug development to mitigate early cardiorenal involvement. This can be achieved either by subtle targeted reduction in UCP-1 expression using innovative proteolysis activating chimeric molecules (PROTACs) or by supplementation with cyclocreatine phosphate, which augments the mitochondrial futile creatine cycling and thus decreases UCP1 activity, enhances the efficiency of oxygen use, and reduces hypoxia. Once developed, these molecules will be first-in-class therapeutic tools to directly interfere with and reverse the earliest pathology underlying cardiac, vascular, and renal dysfunction accompanying the early metabolic deterioration. SIGNIFICANCE STATEMENT: Adipose tissue dysfunction plays a major role in the pathogenesis of metabolic diseases and their complications. Although mitochondrial alterations are common in metabolic impairment, it was only recently shown that the early stages of metabolic challenge involve inflammatory changes in select adipose depots associated with increased uncoupling protein 1 thermogenesis and hypoxia. Manipulating this mode of thermogenesis can help mitigate the early inflammation and the consequent cardiorenal complications.

Sexual dimorphic gene expression profile of perirenal adipose tissue in ovine fetuses with growth restriction.

Worldwide, fetal growth restriction (FGR) affects 7%-10% of pregnancies, or roughly 20.5 million infants, each year. FGR increases not only neonatal mortality and morbidity but also the risk of obesity in later life. Currently, the molecular mechanisms by which FGR "programs" an obese phenotype are not well understood. Studies demonstrate that FGR females are more prone to obesity compared to males; however, the molecular mechanisms that lead to the sexually dimorphic programming of FGR are not known. Thus, we hypothesized that FGR leads to the sexually dimorphic programming of preadipocytes and reduces their ability to differentiate into mature adipocytes. To test the hypothesis, we utilized a maternal hyperthermia-induced placental insufficiency to restrict fetal growth in sheep. We collected perirenal adipose tissue from near-term (∼140days gestation) male and female FGR and normal-weight fetal lambs (N = 4 to 5 in each group), examined the preadipocytes' differentiation potential, and identified differential mRNA transcript expression in perirenal adipose tissue. Male FGR fetuses have a lower cellular density (nuclei number/unit area) compared to control male fetuses. However, no difference was observed in female FGR fetuses compared to control female fetuses. In addition, the ability of preadipocytes to differentiate into mature adipocytes with fat accumulation was impaired in male FGR fetuses, but this was not observed in female FGR fetuses. Finally, we examined the genes and pathways involved in the sexually dimorphic programming of obesity by FGR. On enrichment of differentially expressed genes in males compared to females, the Thermogenesis KEGG Pathway was downregulated, and the Metabolic and Steroid Biosynthesis KEGG pathways were upregulated. On enrichment of differentially expressed genes in male FGR compared to male control, the Steroid Biosynthesis KEGG Pathway was downregulated, and the PPAR Signaling KEGG pathway was upregulated. No pathways were altered in females in response to growth restriction in perirenal adipose tissue. Thus, the present study demonstrates a sexually dimorphic program in response to growth restriction in sheep fetal perirenal adipose tissue.

Effect of simultaneous intake of rare sugars allitol and D-allulose on intra-abdominal fat accumulation in rats

Allitol, one of the sugar alcohols, is a rare sugar produced by reducing d-allulose contained in Itea, a deciduous shrub belonging to the Saxifrageaceae family. We previously found that the long-term feeding of rats with a diet supplemented with Itea powder suppressed obesity. The present study aimed to further investigate whether this effect on body fat accumulation may be attributed to the simultaneous intake of allitol and d-allulose in Itea. Thirty-two male 3-week-old Wistar rats were randomly divided into four groups of eight. The rats had ad libitum access to the control (C), 3% allitol (A), 3% d-allulose (P), or 3% allitol + 3% d-allulose (AP) diet for 8 weeks, after which the rats were euthanized. d-Allulose significantly lowered the final body weight, weight gain, and quantities of perirenal, mesenteric, and total abdominal adipose tissue. Allitol significantly decreased the mesenteric adipose tissue weight. However, we found no combined effect between d-allulose and allitol on all abdominal fat. The liver glucose-6-phosphate dehydrogenase activity was significantly higher in the d-allulose-supplemented groups. Cecal weight, surface area, and content weight were found to be significantly higher in Groups A and AP than those in Groups C and P, suggesting a higher intestinal fermentability of allitol. Our results suggest that allitol and d-allulose have anti-obesity properties that are affected through different mechanisms but are non-synergistic.

Gene co-expression network analysis reveals perirenal adipose tissue as an important target of prenatal malnutrition in sheep.

We have previously demonstrated that pre- and early postnatal malnutrition in sheep induced depot- and sex-specific changes in adipose morphological features, metabolic outcomes, and transcriptome in adulthood, with perirenal (PER) as the major target followed by subcutaneous (SUB) adipose tissue. We aimed to identify co-expressed and hub genes in SUB and PER to identify the underlying molecular mechanisms contributing to the early nutritional programming of adipose-related phenotypic outcomes. Transcriptomes of SUB and PER of male and female adult sheep with different pre- and early postnatal nutrition histories were used to construct networks of co-expressed genes likely to be functionally associated with pre-and early postnatal nutrition histories, and phenotypic traits using Weighted Gene Co-expression Network Analysis. The modules from PER showed enrichment of cell cycle regulation, gene expression, transmembrane transport, and metabolic processes associated with both sexes' prenatal nutrition. In SUB (only males), a module of enriched adenosine diphosphate metabolism and development correlated with prenatal nutrition. Sex-specific module enrichments were found in PER, such as chromatin modification in the male network, but histone modification and mitochondria- and oxidative phosphorylation-related functions in the female network. These sex-specific modules correlated with prenatal nutrition and adipocyte size distribution patterns. Our results point to PER as a primary target of prenatal malnutrition compared to SUB, which played only a minor role. The prenatal programming of gene expression and cell cycle, potentially through epigenetic modifications, might be underlying mechanisms responsible for observed changes in PER expandability and adipocyte-size distribution patterns in adulthood in both sexes.

Neonatal hyperoxia leads to white adipose tissue remodeling and susceptibility to hypercaloric diet

AbstractIndividuals born preterm are at higher risk of cardiovascular and metabolic diseases in adulthood, through mechanisms not completely understood. White adipose tissue in humans and rodents is a dynamic endocrine organ and a critical player in the regulation of metabolic homeostasis. However, the impact of preterm birth on white adipose tissue remains unknown. Using a well‐established rodent model of preterm birth‐related conditions in which newborn rats are exposed during postnatal days 3–10 to 80% of oxygen, we evaluated the impact of transient neonatal hyperoxia on adult perirenal white adipose tissue (pWAT) and liver. We further assessed the effect of a second hit with a high‐fat high‐fructose hypercaloric diet (HFFD). We evaluated 4‐month‐old adult male rats after 2 months of HFFD. Neonatal hyperoxia led to pWAT fibrosis and macrophage infiltration without modification in body weight, pWAT weight, or adipocyte size. In animals exposed to neonatal hyperoxia vs. room air control, HFFD resulted in adipocyte hypertrophy, lipid accumulation in the liver, and increased circulating triglycerides. Overall, preterm birth‐related conditions had long‐lasting effects on the composition and morphology of pWAT, along with a higher susceptibility to the deleterious impact of a hypercaloric diet. These changes suggest a developmental pathway to long‐term metabolic risk factors observed clinically in adults born preterm through programming of white adipose tissue.

Effects and action mechanisms of lotus leaf (Nelumbo nucifera) ethanol extract on gut microbes and obesity in high-fat diet-fed rats.

The present study aimed to clarify the effect of the lotus leaf ethanol extract (LLEE) on the mechanism of antiobesity and the intestinal microbiota of obese rats. A total of 40 specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were split into the blank control group, the model control group, the Orlistat capsule control group, and the LLEE group. All the groups were intervened and fed specific diets for 5 months. During the experiment, we evaluated the rats' body weight, length, serum biochemical indicators, and inflammatory factor levels. After dissection, the liver; epididymal and perirenal white adipose tissue (WAT); and the contents of the cecum were collected for pathological evaluation and intestinal flora analysis. Lotus leaf alcohol extract can significantly reduce the serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. It also decreases the accumulation of fatty deposits in the liver of rats and the levels of serum inflammatory factors IL-6 and TNF-α and increases the level of IL-10. Lotus leaf alcohol extracts significantly increased the abundance of Muribaculaceae in the intestinal flora of rats, reduced the abundance of pro-inflammatory bacteria Firmicutes, and relieved fatty liver and other inflammation and diseases caused by a high-fat diet. Besides, the ethanol extract of the lotus leaf significantly regulated the abundance of Ruminococcus, suggesting that the ethanol extract of the lotus leaf may prevent hyperlipidemia. We elucidated the effects and action mechanisms of LLEE on obesity in high-fat diet-fed rats to provide suggestions for regulating intestinal flora through dietary intervention and thus improving blood lipid metabolism.

Discovery, characterization, and adipocyte differentiation regulation in perirenal adipose tissue of large yellow croaker (Larimichthys crocea).

Adipose tissue is an essential tissue for lipid deposition in fish and is associated with excess lipid accumulation in aquaculture. However, the knowledge of the distribution and characterization of adipose tissue in fish still needs further investigation. This study for the first time discovered perirenal adipose tissue (PAT) in large yellow croaker by MRI and CT technologies. Then, the morphological and cytological characteristics of PAT were observed, showing a typical characteristic of white adipose tissue. Meanwhile, the mRNA expression of marker genes of white adipose tissue was highly expressed in PAT compared with the liver and muscle in large yellow croaker. Moreover, based on the discovery of PAT, preadipocytes from PAT were isolated, and the differentiation system of preadipocytes was established. The lipid droplet and TG content of cell were gradually increased during adipocyte differentiation. In addition, mRNA expressions of lipoprotein lipase, adipose triglyceride lipase, and transcription factors related to adipogenesis (cebpα, srebp1, pparα, and pparγ) were quantified to explain the regulation mechanism during the differentiation process. In summary, the present study first discovered perirenal adipose tissue in fish, then explored the characterization of PAT, and revealed the regulation of adipocyte differentiation. These results could advance the understanding of adipose tissue in fish and provide a novel idea for the study of the mechanism of lipid accumulation.

211-OR: Dual Amylin and Calcitonin Receptor Agonists Increase Mitochondrial Respiratory Capacity in Adipose Tissues of Obese Rat

Dual amylin and calcitonin receptor agonists (DACRAs) are potential therapeutic candidates for treatment of obesity. Preclinical studies have shown favorable effects of DACRAs on appetite regulation contributing to a reduction in body weight. Interestingly, the DACRA-induced effects on weight loss are superior to the effects of a suppressed food intake, suggesting an effect on energy expenditure potentially by targeting the mitochondria. We investigated the effects of long-term treatment with a class of DACRAs, namely KBPs, on body weight, food intake and mitochondrial respiratory capacity (MRC) in Sprague-Dawley rats fed a high-fat diet and treated s.c. with KBPs for 8 weeks. Moreover, a pair-fed (PF) group was used to examine food intake-independent effects of KBPs on MRC. At study end, MRC was analyzed in perirenal (pAT) and inguinal (iAT) adipose tissue using high resolution respirometry. Expectedly, KBP treatment significantly reduced body weight compared to PF and vehicle. PF was successfully KBP-matched in terms of accumulated food intake and the food intake was significantly lower than that of vehicle-treated rats. Coupled and uncoupled MRC supported by complex I+II substrates and fatty acids were significantly greater in iAT and pAT after KBP treatment indicating effects on both carbohydrate and lipid metabolism. Additionally, an increased oligomycin-induced leak-respiration was found to be independent of food intake in iAT. Further analysis will shed light on whether these changes in MRC are a result of an increased mitochondrial content or of the respiratory capacity of each mitochondrion. In conclusion, treatment with KBPs in obese rats is associated with an increased MRC in pAT and iAT and elicits effects additional to those obtained by diet-induced weight loss. This highlights DACRAs’ potential as anti-obesity agents with possible benefits on energy expenditure as a contributing cause to the DACRA-induced weight loss. Disclosure E.A.Petersen: Employee; Nordic Bioscience A/S. I.Blom: None. S.A.Melander: None. M.A.Karsdal: Speaker's Bureau; Pfizer Inc. S.Larsen: None. K.Henriksen: Employee; Nordic Bioscience A/S, Stock/Shareholder; Nordic Bioscience A/S. A.T.Larsen: Employee; Nordic Bioscience A/S. Funding Innovation Fund Denmark

Effects of Exogenous Glucocorticoid Infusion on Appetitic Center Development in Postnatal Dairy Bull Calves.

The objective of this study was to determine the effects of exogenous glucocorticoid administration on leptin concentrations and brain development markers, such as protein and hypothalamic gene expression, in dairy bull calves. Within 4 h of parturition, Holstein bulls were intravenously infused with either a low cortisol dose (LC; n = 9, 3.5 µg/kg of body weight (BW)), high cortisol dose (HC; n = 9, 7.0 µg/kg BW), or control (CON; n = 9, saline) dose, with a 2nd infusion 24 h postpartum. Jugular blood was collected prior to infusion and daily until the calves were euthanized (day 5). Cerebrospinal fluid (CSF) from the third ventricle and adipose (omental, perirenal, and mesenteric) and hypothalamic tissue were collected. The blood and CSF samples were analyzed for leptin concentrations. The data were analyzed using SAS. Serum (p = 0.013) and CSF (p = 0.005) leptin concentrations in HC- and LC-treated calves were decreased compared with CON-treated calves. Leptin protein expression was decreased (p < 0.044) in perirenal and omental adipose tissue of LC-treated calves compared with CON-treated calves. Gene abundance of brain-derived neurotrophic factor and fibroblast growth factors 1 and 2 were decreased (p < 0.006) in HC- and LC-treated calves compared with CON-treated calves. In summary, cortisol administered to dairy bull calves reduced leptin concentrations, decreased leptin protein expression in perirenal and omental adipose tissue, and altered gene expression in hypothalamic tissue.

#6056 NEPHROLOGIC INVOLVEMENT IN A SURGICAL COMPLICATION: WHEN TO SUSPECT A PYELO-DUODENAL FISTULA

Abstract Background and Aims Spontaneous pyeloduodenal fistula is a rare condition occurring primarily after urologic events, in most cases infected kidney stones, pyonephrosis, xanthogranulomatous pyelonephritis, renal tumors, and infected renal cysts, with nowadays 80 cases described. The close relationship between the kidney and the duodenum is a facilitating condition. Method We describe the case of a 78 yo woman admitted in April 2022 for Acute Kidney Injury associated with fever, vomiting, oliguria and metabolic alkalosis. Over the last two years the patient reported recurrent febrile episodes associated with abdominal tenderness and weight loss. Urine cultures showed recurrent bacterial growth and she received antibiotics for recurrent episodes of pyelonephritis and lower urinary tract infections (K. Pneumonie ESBL +, E. Faecalis, P. Mirabilis). She was under nephrologic follow-up with a renal function demonstrating eGFR CKD-EPI of 35-30 ml/min/1.73 m2. In past medical history she reported atrial fibrillation in DOAC, heart failure with preserved ejection fraction, hypertension, previous left occipito-parietal ischemic stroke and right parotid adenoma. On physical examination of the abdomen there was no tenderness, mild pain in the right hypochondrium, Giordano's maneuver mild positive on the right side. Because of the evidence of lithiasis in the right kidney on ultrasound with grade III hydroureteronephrosis, we performed a CT scan with contrast, finding imaging compatible with right pyelonephritis with associated grade IV hydronephrosis, in particular lithiasic formation localized at the level of the right pyelo-ureteral junction (2 × 1cm), with partial involvement of the proximal portion of the ureter, severe calico-pyelic dilatation with overall reduction of the cortico-medullary thickness; diffuse inhomogeneity of the middle and lower thirds of the renal parenchyma, with evidence of some bubbles in contextual areas and inhomogeneity of the perirenal adipose tissue. Reduced nephrographic effect in the post-contrastographic phases and lack of elimination of the contrast in the urographic phase (12 min) were reported. She was started on antibiotics piperacillin-tazobactam and underwent right percutaneous nephrostomy placement. During the procedure we evidenced a communication between the calyx of the right upper calyceal group and an intestinal loop, probably the duodenum (Fig. 1). Results The patient underwent elective laparotomic surgery for right nephrectomy (Fig. 2) and closure of the intestinal fistula with duodenoraffia and omental patch. She was admitted to a post-operative intensive care unit, given comorbidities and the complexity of the operation. She was discharged in 9 days without post-operative complications, with stable renal function. One month after discharge the patient died of pneumonia. Conclusion Pyeloduodenal fistula is an infrequent condition causing occasional or continuous passing of materials between the alimentary canal and urinary tract. The presence of gastrointestinal symptoms and urinary tract alterations may be misinterpreted when occurring. Management of this case required collaboration between several specialists, with particular skills on AKI and CKD, infective complications, interventional radiology and surgical procedures. The outcome was strongly affected by the patient's general condition and comorbidities, with a good short-term outcome but complications on the long-term follow-up. The occurrence of air in the urinary tract is strongly suggestive of communications across the renal pelvis and the gastrointestinal tract. In particular if occurring in the setting of recurrent infections and nephrolithiasis, the diagnosis of pyelo-intestinal fistula should be considered.

THE HIGH-ENERGY DIET/STREPTOZOTOCIN TREATED MUNICH WISTAR FRÖMTER RATS: A NEW EXPERIMENTAL MODEL OF DIABETES INDUCTION IN ESTABLISHED KIDNEY DISEASE

Objective: Chronic kidney disease (CKD) is especially prevalent in patients with diabetes mellitus (DM). We aim to induce diabetes in the Munich Wistar Frömter (MWF) rat, a genetic model of established CKD. Design and method: 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF) or a high fat/high-sucrose diet for 6 weeks together with streptozotocin administration (STZ; 15mg/Kg i.p.) at the start of dietary exposure (MWF-D). Results: Water intake, urine excretion, GTT and HOMA-IR index evidenced the development of diabetes in MWF-D rats. Albuminuria was higher in MWF with no further effect of diabetes. However, renal expression of Kim-1 and Ngal, markers of renal damage, AT1R, AT2R and Collagen 1A1 were significantly higher in MWF-D rats. Perirenal adipose tissue (PRAT) amount was significantly higher in MWF-D rats and exhibited an upregulation of TNF-alpha and profibrotic factors (TGF-beta and Collagen 1A1), together with a downregulation of IL-10. Although blood pressure was not further increased by the induction of diabetes, heart weight and left ventricular wall thickness were higher in MWF-D, coincident with a reduction in systolic volume, but without a change in the ejection fraction. Conclusions: We propose the MWF-D rat as an experimental model of NDKD and suggest a strong relation between alterations in PRAT and increased renal damage.