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Abstract The drastic change in global climate has led to in-depth studies of the geneticresources of native cattle adapted to challenging environments. Native cattle breeds may harbor unique genetic mechanisms that have enabled them adapt to their given environmental conditions. Adipose tissues are key factors in the regulation of metabolism and energy balance and are crucial for the molecular switches needed to adapt to rapid environmental and nutritional changes. The transcriptome landscape of four adipose tissues was used in this study to investigate the differential gene expression profiles in three local breeds, Yakutian cattle (Sakha Republic), Northern Finncattle (Finland), Mirandesa cattle (Portugal) and commercial Holstein cattle. A total of 26 animals (12 cows, 14 bulls) yielded 81 samples of perirenal adipose tissue (n = 26), metacarpal adipose tissue (n = 26), tailhead adipose tissue (n = 26) and prescapular adipose tissue (n = 3). More than 17,000 genes were expressed in our dataset. Principal component analysis of the normalized expression profiles revealed a differential expression profile of the metacarpal adipose tissue. We found that the genes upregulated in the metacarpal adipose tissue of Yakutian cattle, such as NR4A3, TEKT3, and FGGY, were associated with energy metabolism and response to cold temperatures. In Mirandesa cattle, the upregulated genes in perirenal adipose tissue were related to immune response and inflammation (AVPR2, CCN1, and IL6), while in Northern Finncattle, the upregulated genes appeared to be involved in various physiological processes, including energy metabolism (IGFBP2). According to the sex-based comparisons, the most interesting result was the upregulation of the TPRG1 gene in three tissues of Yakutian cattle females, suggesting that adaptation is related to feed efficiency. The highest number of differentially expressed genes was found between Yakutian cattle and Holstein, several of which were associated with immunity in Yakutian cattle, indicating potential differences in disease resistance and immunity between the two breeds. This study highlights the vast difference in gene expression profiles in adipose tissues among breeds from different climatic environments, most likely highlighting selective pressure and the potential significance of the uniquely important regulatory functions of metacarpal adipose tissue.

The drastic change in global climate has led to in-depth studies of the geneticresources of native cattle adapted to challenging environments. Native cattle breeds may harbor unique genetic mechanisms that have enabled them adapt to their given environmental conditions. Adipose tissues are key factors in the regulation of metabolism and energy balance and are crucial for the molecular switches needed to adapt to rapid environmental and nutritional changes. The transcriptome landscape of four adipose tissues was used in this study to investigate the differential gene expression profiles in three local breeds, Yakutian cattle (Sakha Republic), Northern Finncattle (Finland), Mirandesa cattle (Portugal) and commercial Holstein cattle. A total of 26 animals (12 cows, 14 bulls) yielded 81 samples of perirenal adipose tissue (n = 26), metacarpal adipose tissue (n = 26), tailhead adipose tissue (n = 26) and prescapular adipose tissue (n = 3). More than 17,000 genes were expressed in our dataset. Principal component analysis of the normalized expression profiles revealed a differential expression profile of the metacarpal adipose tissue. We found that the genes upregulated in the metacarpal adipose tissue of Yakutian cattle, such as NR4A3, TEKT3, and FGGY, were associated with energy metabolism and response to cold temperatures. In Mirandesa cattle, the upregulated genes in perirenal adipose tissue were related to immune response and inflammation (AVPR2, CCN1, and IL6), while in Northern Finncattle, the upregulated genes appeared to be involved in various physiological processes, including energy metabolism (IGFBP2). According to the sex-based comparisons, the most interesting result was the upregulation of the TPRG1 gene in three tissues of Yakutian cattle females, suggesting that adaptation is related to feed efficiency. The highest number of differentially expressed genes was found between Yakutian cattle and Holstein, several of which were associated with immunity in Yakutian cattle, indicating potential differences in disease resistance and immunity between the two breeds. This study highlights the vast difference in gene expression profiles in adipose tissues among breeds from different climatic environments, most likely highlighting selective pressure and the potential significance of the uniquely important regulatory functions of metacarpal adipose tissue. [ABSTRACT FROM AUTHOR]

Objective: Perirenal adipose tissue (PAT) has emerged as a potential therapeutic target for cardiovascular disease (CVD). However, the relationship between increased perirenal fat thickness (PrFT) and CVD risks in individuals with type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to evaluate the association between PrFT and the estimated 10-year risk of CVD and atherosclerotic cardiovascular disease (ASCVD) in T2DM. Method: The final analysis included 704 participants. PrFT was quantified using non-enhanced computed tomography scans, while the estimated 10-year CVD and ASCVD risk assessments were based on the Framingham and China-PAR equation risk scores, respectively. Multiple regression analysis was employed to analyze the correlation between PrFT and these risk scores. Results: Higher quartiles of PrFT displayed elevated Framingham and China-PAR equation risk scores (P<0.001). After adjusting for cardiometabolic risk factors and visceral fat area, PrFT remained significantly correlated with Framingham equation risk scores in men (β=0.098, P=0.036) and women (β=0.099, P=0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men (β=0.106, P=0.009) and women (β=0.108, P=0.007). Moreover, PrFT emerged as an independent variable associated with a high estimated 10-year risk of CVD and ASCVD, with odds ratios (ORs) of 1.14 (95% CI: 1.04-1.25, P=0.016) in men and 1.20 (95% CI: 1.11-1.31, P<0.001) in women for high estimated CVD risk, and ORs of 1.22 (95% CI: 1.08-1.41, P=0.009) inmen and 1.34 (95% CI: 1.12-1.60, P<0.001) in women for high estimated 10-year ASCVD risk. Furthermore, restricted cubic spline analyses confirmed a nonlinear relationship between PrFT and high estimated CVD and ASCVD risk in both genders (P for nonlinearity and overall < 0.05). Conclusions: PrFT contributed as an independent variable to the estimated 10-year risk of CVD and ASCVD in T2DM. [ABSTRACT FROM AUTHOR]

Copyright of Pamukkale Medical Journal is the property of Pamukkale Journal of Medicine and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here, we studied the effect of 12 weeks of drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined, as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males, with slightly higher adipocyte area values in both males and females under clozapine treatment. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol-medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine treatment. IR-ß expression changed sex-specifically in the clozapine-medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-treated females. Taken together, clozapine and haloperidol had a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined, and probably in their effect on liver metabolism. [ABSTRACT FROM AUTHOR]

Perirenal adipose tissue (PRAT) is a unique visceral depot that contains a mixture of brown and white adipocytes. The origin and plasticity of such cellular heterogeneity remains unknown. Here, we combine single-nucleus RNA sequencing with genetic lineage tracing to reveal the existence of a distinct subpopulation of Ucp1-&Cidea+ adipocytes that arises from brown-to-white conversion during postnatal life in the periureter region of mouse PRAT. Cold exposure restores Ucp1 expression and a thermogenic phenotype in this subpopulation. These cells have a transcriptome that is distinct from subcutaneous beige adipocytes and may represent a unique type of cold-recruitable adipocytes. These results pave the way for studies of PRAT physiology and mechanisms controlling the plasticity of brown/white adipocyte phenotypes.

Perirenal adipose tissue (PRAT) surrounding the kidney is emerging as a player and novel independent risk factor in diabetic kidney disease (DKD); DKD is a complication of diabetes and is a major cause of increased cardiovascular (CV) risk and CV mortality in affected patients. We determined the effect of diabetes induction on (i) kidney and CV damage and (ii) on the expression of proinflammatory and profibrotic factors in both the PRAT and the mesenteric adipose tissue (MAT) of Munich Wistar Frömter (MWF) rats. The 16-week-old male MWF rats (n = 10 rats/group) were fed standard chow (MWF-C) or a high-fat/high-sucrose diet for 6 weeks together with low-dose streptozotocin (15 mg/kg i.p.) at the start of dietary exposure (MWF-D). Phenotyping was performed at the end of treatment through determining water intake, urine excretion, and oral glucose tolerance; use of the homeostatic model assessment–insulin resistance index (HOMA-IR) evidenced the development of overt diabetes manifestation in MWF-D rats. The kidney damage markers Kim-1 and Ngal were significantly higher in MWF-D rats, as were the amounts of PRAT and MAT. A diabetes-induced upregulation in IL-1, IL-6, Tnf-α, and Tgf-β was observed in both the PRAT and the MAT. Col1A1 was increased in the PRAT but not in the MAT of MWF-D, whereas IL-10 was lower and higher in the PRAT and the MAT, respectively. Urinary albumin excretion and blood pressure were not further increased by diabetes induction, while heart weight was higher in the MWF-D. In conclusion, our results show a proinflammatory and profibrotic in vivo environment in PRAT induced by diabetes which might be associated with kidney damage progression in the MWF strain. [ABSTRACT FROM AUTHOR]

Copyright of Revista Mexicana de Endocrinología, Metabolismo y Nutrición is the property of Publicidad Permanyer SLU and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Metabolic disease is a complex disorder defined by a group with interrelated factors. There is growing evidence that obesity can lead to a variety of metabolic diseases, including diabetes and cardiovascular disease. Excessive adipose tissue (AT) deposition and ectopic accumulation can lead to increased peri-organ AT thickness. Dysregulation of peri-organ (perivascular, perirenal, and epicardial) AT is strongly associated with metabolic disease and its complications. The mechanisms include secretion of cytokines, activation of immunocytes, infiltration of inflammatory cells, involvement of stromal cells, and abnormal miRNA expression. This review discusses the associations and mechanisms by which various types of peri-organ AT affect metabolic diseases while addressing it as a potential future treatment strategy. • Obesity can cause various metabolic diseases. • Dysregulated peri-organ AT is linked to metabolic disease and complications. • Peri-organ AT is a valuable drug target for metabolic disease treatment. [ABSTRACT FROM AUTHOR]

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 coexpressed 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 coexpressed genes likely to be functionally associated with pre- and early postnatal nutrition histories and phenotypic traits using weighted gene coexpression 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Perirenal adipose tissue（PRAT) is a special visceral fat deposit, which is located between renal fibrous membrane and renal fascia. Compared with other connective tissues, PRAT exhibits a unique anatomical structure in the distribution of blood vessels, lymphatic vessels and nerves.Excessive PRAT deposition will increase the risk of hypertension, atherosclerosis and heart disease.Therefore, this paper reviewed the research progress on the origin, anatomical structure of PRAT and its relationship with cardiovascular diseases, in order to provide evidence for the treatment and prevention of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Increased adiposity is related to oxidative stress, inflammation and metabolic disorders. Our group has shown that melatonin totally or partially prevents the alterations that obesity causes in some neuroendocrine and inflammatory parameters indicative of oxidative stress. This study analyzes the effects of HFD on the relative gene expression of several redox balance enzymes on adult male Wistar rats subcutaneous (SAT) and perirenal adipose tissue (PRAT) and the possible preventive role of melatonin. Three experimental groups were established: control, high fat diet (HFD) and HFD plus 25 μg/mL melatonin in tap water. After 11 weeks, animals were sacrificed at 09:00 a.m. and 01:00 a.m. and PRAT and SAT were collected for selected redox enzymes qRT-PCR. Differential expression of redox enzyme genes, except for SODMn, GPx and catalase, was observed in the control group as a function of fat depot. HFD causes the disappearance of the temporal changes in the expression of the genes studied in the two fat depots analyzed. PRAT seems to be more sensitive than SAT to increased oxidative stress induced by obesity. Melatonin combined with a HFD intake, partially prevents the effects of the HFD on the gene expression of the redox enzymes. According to our results, melatonin selectively prevents changes in the relative gene expression of redox enzymes in PRAT and SAT of animals fed an HFD. [ABSTRACT FROM AUTHOR]

Perirenal adipose tissue (PRAT) has been identified as an important factor in local and general homeostasis of the human body and is especially important in regulating renal and cardiovascular functions. It has also been identified as a crucial risk factor to consider in cardiovascular and renal disorders, malignancies, and various other diseases. Having a concrete idea of the effects of therapeutic interventions on the size and metabolism of the PRAT could prove highly beneficial. This review summarizes what is known about the PRAT and provides a collection of studies on the effects of therapeutic interventions on PRAT and its related diseases. We used papers written on a variety of subjects, mainly concerning adipose tissue and the effects of therapeutic procedures on it. Our main challenge was to excerpt the information specifically related to the PRAT in these papers. These effects vary greatly, from an increase or decrease in mass or size of the PRAT to changes in metabolism and drug residue accumulation. The current studies often fail to consider PRAT as an individual subject of research and only examine the adipose tissue of the entire body as a whole. This leads us to believe this field could benefit greatly from further research., Competing Interests: There are no conflicts of interest., (© 2024 Indian Journal of Nephrology | Published by Scientific Scholar.)

Flammulina velutipes (FV) is edible mushroom that has nutritional and medicinal values. FV mycorrhizae, the by-products of FV, are an abundant source and receive less attention. The objective of this study was to investigate the composition of FV mycorrhizae, and its effects on high fat diet (HFD)-induced lipid disorder, oxidative stress, and inflammatory cytokines, both in the liver and perirenal adipose tissue (PAT) of mice. The results showed that FV mycorrhizae contain abundant trace elements, polysaccharide, amino acids and derivatives, and organic compounds. It was found that 4% FV mycorrhizae (HFDFV) supplementation decreased HFD-induced liver weight and triglyceride (TG) in the plasma, liver and PAT, altered plasma and hepatic fatty acids profiles, promoted gene expression involved in lipid hydrolysis, fatty acid transportation and β-oxidation in the liver and reduced lipid synthesis in the liver and PAT. HFDFV attenuated HFD-induced oxidative stress and pro-inflammatory cytokine by increasing GSH/GSSG, and decreasing levels of MDA and IL6 both in the liver and PAT, while it differentially regulated gene expression of IL1β, IL6, and CCL2 in liver and PAT. The results indicated that FV mycorrhizae are effective to attenuate HFD-induced lipid disorder, oxidative stress and inflammation in the liver and PAT, indicating their promising constituents for functional foods and herbal medicine. [ABSTRACT FROM AUTHOR]

Abstract Background Early life malnutrition is known to target adipose tissue with varying impact depending on timing of the insult. This study aimed to identify differentially expressed genes in subcutaneous (SUB) and perirenal (PER) adipose tissue of 2.5-years old sheep to elucidate the biology underlying differential impacts of late gestation versus early postnatal malnutrition on functional development of adipose tissues. Adipose tissues were obtained from 37 adult sheep born as twins to dams fed either NORM (fulfilling energy and protein requirements), LOW (50% of NORM) or HIGH (110% of protein and 150% of energy requirements) diets in the last 6-weeks of gestation. From day 3 to 6 months of age, lambs were fed high-carbohydrate-high-fat (HCHF) or moderate low-fat (CONV) diets, and thereafter the same moderate low-fat diet. Results The gene expression profile of SUB in the adult sheep was not affected by the pre- or early postnatal nutrition history. In PER, 993 and 186 differentially expressed genes (DEGs) were identified in LOW versus HIGH and NORM, respectively, but no DEG was found between HIGH and NORM. DEGs identified in the mismatched pre- and postnatal nutrition groups LOW-HCHF (101) and HIGH-HCHF (192) were largely downregulated compared to NORM-CONV. Out of 831 DEGs, 595 and 236 were up- and downregulated in HCHF versus CONV, respectively. The functional enrichment analyses revealed that transmembrane (ion) transport activities, motor activities related to cytoskeletal and spermatozoa function (microtubules and the cytoskeletal motor protein, dynein), and responsiveness to the (micro) environmental extracellular conditions, including endocrine and nervous stimuli were enriched in the DEGs of LOW versus HIGH and NORM. We confirmed that mismatched pre- and postnatal feeding was associated with long-term programming of adipose tissue remodeling and immunity-related pathways. In agreement with phenotypic measurements, early postnatal HCHF feeding targeted pathways involved in kidney cell differentiation, and mismatched LOW-HCHF sheep had specific impairments in cholesterol metabolism pathways. Conclusions Both pre- and postnatal malnutrition differentially programmed (patho-) physiological pathways with implications for adipose functional development associated with metabolic dysfunctions, and PER was a major target.

Chronic kidney disease (CKD) represents a significant and escalating global health challenge, with morbidity and mortality rates rising steadily. Evidence increasingly implicates perirenal adipose tissue (PRAT) deposition as a contributing factor in the pathogenesis of CKD. This review explores how PRAT deposition may exert deleterious effects on renal structure and function. The anatomical proximity of PRAT to the kidneys not only potentially causes mechanical compression but also leads to the dysregulated secretion of adipokines and inflammatory mediators, such as adiponectin, leptin, visfatin, tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and exosomes. Additionally, PRAT deposition may contribute to renal lipotoxicity through elevated levels of free fatty acids (FFA), triglycerides (TAG), diacylglycerol (DAG), and ceramides (Cer). PRAT deposition is also linked to the hyperactivation of the renin-angiotensin-aldosterone system (RAAS), which further exacerbates CKD progression. Recognizing PRAT deposition as an independent risk factor for CKD underscores the potential of targeting PRAT as a novel strategy for the prevention and management of CKD. This review further discusses interventions that could include measuring PRAT thickness to establish a baseline, managing metabolic risk factors that promote its deposition, and inhibiting key PRAT-induced signaling pathways. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: Perirenal adipose tissue (PAT) has emerged as a potential therapeutic target for cardiovascular disease (CVD). However, the relationship between increased perirenal fat thickness (PrFT) and CVD risks in individuals with type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to evaluate the association between PrFT and the estimated 10-year risk of CVD and atherosclerotic cardiovascular disease (ASCVD) in T2DM., Method: The final analysis included 704 participants. PrFT was quantified using non-enhanced computed tomography scans, while the estimated 10-year CVD and ASCVD risk assessments were based on the Framingham and China-PAR equation risk scores, respectively. Multiple regression analysis was employed to analyze the correlation between PrFT and these risk scores., Results: Higher quartiles of PrFT displayed elevated Framingham and China-PAR equation risk scores ( P <0.001). After adjusting for cardiometabolic risk factors and visceral fat area, PrFT remained significantly correlated with Framingham equation risk scores in men ( β =0.098, P =0.036) and women ( β =0.099, P =0.032). Similar correlations were observed between PrFT and China-PAR equation risk scores in men ( β =0.106, P =0.009) and women ( β =0.108, P =0.007). Moreover, PrFT emerged as an independent variable associated with a high estimated 10-year risk of CVD and ASCVD, with odds ratios (ORs) of 1.14 (95% CI: 1.04-1.25, P =0.016) in men and 1.20 (95% CI: 1.11-1.31, P <0.001) in women for high estimated CVD risk, and ORs of 1.22 (95% CI: 1.08-1.41, P =0.009) in men and 1.34 (95% CI: 1.12-1.60, P <0.001) in women for high estimated 10-year ASCVD risk. Furthermore, restricted cubic spline analyses confirmed a nonlinear relationship between PrFT and high estimated CVD and ASCVD risk in both genders ( P for nonlinearity and overall < 0.05)., Conclusions: PrFT contributed as an independent variable to the estimated 10-year risk of CVD and ASCVD in T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wang, Lv, Tu and Guo.)

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.

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. [ABSTRACT FROM AUTHOR]

Hypertension, a prevalent global cardiovascular disease, affects approximately 45.4 % of adults worldwide. Despite advances in therapy, hypertension continues to pose a significant health risk due to inadequate management. It has been established that excessive adiposity contributes majorly to hypertension, accounting for 65 to 75 % of primary cases. Fat depots can be categorised into subcutaneous and visceral adipose tissue based on anatomical and physiological characteristics. The metabolic impact and the risk of hypertension are determined more significantly by visceral fat. Perirenal adipose tissue (PRAT), a viscera enveloping the kidney, is known for its superior vascularisation and abundant innervation. Although traditionally deemed as a mechanical support tissue, recent studies have indicated its contributing potential to hypertension. Hypertensive patients tend to have increased PRAT thickness compared to those without, and there is a positive correlation between PRAT thickness and elevated systolic blood pressure. This review encapsulates the anatomical characteristics and biogenesis of PRAT. We provide an overview of the potential mechanisms where PRAT may modulate blood pressure, including physical compression, paracrine effects, and neurogenic regulation. PRAT has become a promising target for hypertension management, and continuous effort is required to further explore the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Background: Early life malnutrition is known to target adipose tissue with varying impact depending on timing of the insult. This study aimed to identify differentially expressed genes in subcutaneous (SUB) and perirenal (PER) adipose tissue of 2.5-years old sheep to elucidate the biology underlying differential impacts of late gestation versus early postnatal malnutrition on functional development of adipose tissues. Adipose tissues were obtained from 37 adult sheep born as twins to dams fed either NORM (fulfilling energy and protein requirements), LOW (50% of NORM) or HIGH (110% of protein and 150% of energy requirements) diets in the last 6-weeks of gestation. From day 3 to 6 months of age, lambs were fed high-carbohydrate-high-fat (HCHF) or moderate low-fat (CONV) diets, and thereafter the same moderate low-fat diet. Results: The gene expression profile of SUB in the adult sheep was not affected by the pre- or early postnatal nutrition history. In PER, 993 and 186 differentially expressed genes (DEGs) were identified in LOW versus HIGH and NORM, respectively, but no DEG was found between HIGH and NORM. DEGs identified in the mismatched pre- and postnatal nutrition groups LOW-HCHF (101) and HIGH-HCHF (192) were largely downregulated compared to NORM-CONV. Out of 831 DEGs, 595 and 236 were up- and downregulated in HCHF versus CONV, respectively. The functional enrichment analyses revealed that transmembrane (ion) transport activities, motor activities related to cytoskeletal and spermatozoa function (microtubules and the cytoskeletal motor protein, dynein), and responsiveness to the (micro) environmental extracellular conditions, including endocrine and nervous stimuli were enriched in the DEGs of LOW versus HIGH and NORM. We confirmed that mismatched pre- and postnatal feeding was associated with long-term programming of adipose tissue remodeling and immunity-related pathways. In agreement with phenotypic measurements, early postnatal HCHF feeding targeted pathways involved in kidney cell differentiation, and mismatched LOW-HCHF sheep had specific impairments in cholesterol metabolism pathways. Conclusions: Both pre- and postnatal malnutrition differentially programmed (patho-) physiological pathways with implications for adipose functional development associated with metabolic dysfunctions, and PER was a major target. [ABSTRACT FROM AUTHOR]

Abstract The aim was to investigate long‐term, tissue and sex‐specific impacts of pre and postnatal malnutrition on expandability and functional traits of different adipose tissues. Twin‐pregnant ewes were fed NORM (~requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein) diets the last 6 weeks prepartum (term ~147‐days). Lambs received moderate, low‐fat (CONV) or high‐carbohydrate‐high‐fat (HCHF) diets from 3 days until 6 months of age, and thereafter CONV diet. At 2½ years of age (adulthood), histomorphometric and gene expression patterns were characterized in subcutaneous (SUB), perirenal (PER), mesenteric (MES), and epicardial (EPI) adipose tissues. SUB had sex‐specific (♂

Background: Better understanding of the contribution of donor aging and comorbidity factors of expanded criteria donors (ECD) to the clinical outcome of a transplant is a challenge in kidney transplantation. We investigated whether the features of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF) could be indicative of the deleterious impact of the ECD microenvironment on a renal transplant.Methods: A comparative analysis of cellular components, transcriptomic and vasculogenic profiles was performed in PRAT-SVF obtained from 22 optimal donors and 31 ECD deceased donors. We then investigated whether these parameters could be associated with donor aging and early allograft dysfunction.Results: When compared with the PRAT-SVF of non-ECD donors, ECD PRAT-SVF displayed a lower proportion of stromal cells, a higher proportion of inflammatory NK cells. The global RNA sequencing approach indicated a differential molecular signature in the PRAT-SVF of ECD donors characterized by the over-expression of CXCL1 and IL1-β inflammatory transcripts. The vasculogenic activity of PRAT-SVF was highly variable but was not significantly affected in marginal donors. Periorgan recruitment of monocytes/macrophages and NK cells in PRAT-SVF was associated with donor aging. The presence of NK cell infiltrates was associated with lower PRAT-SVF angiogenic activity and with early allograft dysfunction evaluated on day 7 and at 1 month post-transplant.Conclusions: Our results indicate that human NK cell subsets are differentially recruited in the periorgan environment of aging kidney transplants. We provide novel evidence that PRAT-SVF represents a non-invasive and timely source of donor material with potential value to assess inflammatory features that impact organ quality and function.

The aim was to investigate long‐term, tissue and sex‐specific impacts of pre and postnatal malnutrition on expandability and functional traits of different adipose tissues. Twin‐pregnant ewes were fed NORM (~requirements), LOW (50% of NORM) or HIGH (150%/110% of energy/protein) diets the last 6 weeks prepartum (term ~147‐days). Lambs received moderate, low‐fat (CONV) or high‐carbohydrate‐high‐fat (HCHF) diets from 3 days until 6 months of age, and thereafter CONV diet. At 2½ years of age (adulthood), histomorphometric and gene expression patterns were characterized in subcutaneous (SUB), perirenal (PER), mesenteric (MES), and epicardial (EPI) adipose tissues. SUB had sex‐specific (♂<♀) upper‐limits for adipocyte size and cell‐number indices, irrespective of early life nutrition. PER mass and contents of adipocytes were highest in females and HIGH♂, whereas adipocyte cross‐sectional area was lowest in LOW♂. Pre/postnatal nutrition affected gene expression sex‐specifically in SUB + PER, but unrelated to morphological changes. In PER, LOW/LOW♂ were specific targets of gene expression changes. EPI was affected by postnatal nutrition, and HCHF sheep had enlarged adipocytes and upregulated expressions for adipogenic and lipogenic genes. Conclusion: upper‐limits for SUB expandability were markedly lower in males. Major targets for prenatal malnutrition were PER and males. LOW♂ had the lowest PER expandability, whereas HIGH♂ had an adaptive advantage due to increased hypertrophic ability equivalent to females. Fixed expandability in SUB meant PER became a determining factor for MES and ectopic fat deposition, rendering LOW♂ particularly predisposed for obesity‐associated metabolic risks. EPI, in contrast to other tissues, was targeted particularly by early postnatal obesity, resulting in adipocyte hypertrophy in adulthood. [ABSTRACT FROM AUTHOR]

Background: Better understanding of the contribution of donor aging and comorbidity factors of expanded criteria donors (ECD) to the clinical outcome of a transplant is a challenge in kidney transplantation. We investigated whether the features of donor-derived stromal vascular fraction of perirenal adipose tissue (PRAT-SVF) could be indicative of the deleterious impact of the ECD microenvironment on a renal transplant. Methods: A comparative analysis of cellular components, transcriptomic and vasculogenic profiles was performed in PRAT-SVF obtained from 22 optimal donors and 31 ECD deceased donors. We then investigated whether these parameters could be associated with donor aging and early allograft dysfunction. Results: When compared with the PRAT-SVF of non-ECD donors, ECD PRAT-SVF displayed a lower proportion of stromal cells, a higher proportion of inflammatory NK cells. The global RNA sequencing approach indicated a differential molecular signature in the PRAT-SVF of ECD donors characterized by the over-expression of CXCL1 and IL1-β inflammatory transcripts. The vasculogenic activity of PRAT-SVF was highly variable but was not significantly affected in marginal donors. Periorgan recruitment of monocytes/macrophages and NK cells in PRAT-SVF was associated with donor aging. The presence of NK cell infiltrates was associated with lower PRAT-SVF angiogenic activity and with early allograft dysfunction evaluated on day 7 and at 1 month post-transplant. Conclusions: Our results indicate that human NK cell subsets are differentially recruited in the periorgan environment of aging kidney transplants. We provide novel evidence that PRAT-SVF represents a non-invasive and timely source of donor material with potential value to assess inflammatory features that impact organ quality and function. [ABSTRACT FROM AUTHOR]

Perirenal adipose tissue (PrAT) is a visceral adipose tissue involved in the pathogenesis of obesity and cardiovascular diseases via neural pathways. However, the origins, morphological characterization, and resiniferatoxin (RTX)-susceptibility of sensory neurons that innervate rat PrAT are yet unclear. Using neural tracing, an injection of DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate) into PrAT revealed that sensory neurons that innervate PrAT reside in T9-L3 dorsal root ganglia (DRG). Peak labeling occurred in T13 and L1 DRGs. Two distinct peaks were observed in cross-sectional areas of the labeled soma, and the mean cross-sectional area was 717.1 ± 27.7 μm2. Immunofluorescence staining for transient receptor potential cation channel subfamily V member 1 (TRPV1) separated DiI-positive neurons into three subpopulations: small TRPV1-negative, small TRPV1-positive, and large TRPV1-negative. Furthermore, the injection of RTX into PrAT reduced labeled cells by 36.7% where TRPV1-positive cells were the main target of RTX denervation. These novel findings provide a structural basis for future TRPV1-dependent and TRPV1-independent studies on the sensory innervation of PrAT, which may be of interest for future therapeutic obesity treatment and intervention.

Perirenal adipose tissue (PRAT) is a unique visceral depot that contains a mixture of brown and white adipocytes. The origin and plasticity of such cellular heterogeneity remains unknown. Here, we combine single-nucleus RNA sequencing with genetic lineage tracing to reveal the existence of a distinct subpopulation of Ucp1 - & Cidea + adipocytes that arises from brown-to-white conversion during postnatal life in the periureter region of mouse PRAT. Cold exposure restores Ucp1 expression and a thermogenic phenotype in this subpopulation. These cells have a transcriptome that is distinct from subcutaneous beige adipocytes and may represent a unique type of cold-recruitable adipocytes. These results pave the way for studies of PRAT physiology and mechanisms controlling the plasticity of brown/white adipocyte phenotypes., Competing Interests: HZ, YL, CI, MX No competing interests declared, (© 2024, Zhang et al.)

Background: Obesity is a major worldwide health problem and can be related to cellular senescence. Along with the rise in obesity, the comorbidity of renal ischemia-reperfusion (IR) injury is increasing. Whether obesity accelerates the severity of IR injury and whether senescence contributes to these conditions remain unclear. We studied the degree of injury and cellular senescence in the IR kidneys and perirenal adipose tissues of high-fat-diet-induced obese mice., Methods: C57BL/6 mice fed standard chow or a high-fat diet for 16 weeks were randomized to renal IR or sham group (n = 6-10 each). Renal IR was performed by unilateral clamping of the right renal pedicle for 30 minutes. Six weeks after surgery, renal function, perirenal fat/renal senescence, and histology were evaluated ex vivo., Results: Obese mice showed more renal tubular damage and fibrosis in IR injury than control mice, even though the degree of ischemic insult was comparable. Renal expression of senescence and its secretory phenotype was upregulated in either IR injury or with a high-fat diet and was further increased in the IR kidneys of obese mice. Fat senescence and the expression of tumor necrosis factor alpha were also increased, especially in the perirenal depot of the IR kidneys, with a high-fat diet., Conclusion: A high-fat diet aggravates IR injury in murine kidneys, which is associated, at least in part, with perirenal fat senescence and inflammation. These observations support the exploration of therapeutic targets of the adipo-renal axis in injured obese kidneys.

Increasing the amounts of functionally competent brown adipose tissue (BAT) in adult humans has the potential to restore dysfunctional metabolism and counteract obesity. In this study, we aimed to characterize the human perirenal fat depot, and we hypothesized that there would be regional, within-depot differences in the adipose signature depending on local sympathetic activity. We characterized fat specimens from four different perirenal regions of adult kidney donors, through a combination of qPCR mapping, immunohistochemical staining, RNA-sequencing, and pre-adipocyte isolation. Candidate gene signatures, separated by adipocyte morphology, were recapitulated in a murine model of unilocular brown fat induced by thermoneutrality and high fat diet. We identified widespread amounts of dormant brown adipose tissue throughout the perirenal depot, which was contrasted by multilocular BAT, primarily found near the adrenal gland. Dormant BAT was characterized by a unilocular morphology and a distinct gene expression profile, which partly overlapped with that of subcutaneous white adipose tissue (WAT). Brown fat precursor cells, which differentiated into functional brown adipocytes were present in the entire perirenal fat depot, regardless of state. We identified SPARC as a candidate adipokine contributing to a dormant BAT state, and CLSTN3 as a novel marker for multilocular BAT. We propose that perirenal adipose tissue in adult humans consists mainly of dormant BAT and provide a data set for future research on factors which can reactivate dormant BAT into active BAT, a potential strategy for combatting obesity and metabolic disease. Image 1 • Dormant brown adipose tissue (BAT) dominates the perirenal adipose depot of adult humans. • Multilocular BAT accumulates adjacent to local sympathetic sources. • Dormant BAT displays a transcriptomic signature distinct from multilocular BAT and white adipose tissue. • Brown fat precursor cells are present in human dormant perirenal BAT. • SPARC is associated with a dormant BAT phenotype. [ABSTRACT FROM AUTHOR]

Perirenal adipose tissue (PrAT) is a visceral adipose tissue involved in the pathogenesis of obesity and cardiovascular diseases via neural pathways. However, the origins, morphological characterization, and resiniferatoxin (RTX)-susceptibility of sensory neurons that innervate rat PrAT are yet unclear. Using neural tracing, an injection of DiI (1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate) into PrAT revealed that sensory neurons that innervate PrAT reside in T9-L3 dorsal root ganglia (DRG). Peak labeling occurred in T13 and L1 DRGs. Two distinct peaks were observed in cross-sectional areas of the labeled soma, and the mean cross-sectional area was 717.1 ± 27.7 μm2. Immunofluorescence staining for transient receptor potential cation channel subfamily V member 1 (TRPV1) separated DiI-positive neurons into three subpopulations: small TRPV1-negative, small TRPV1-positive, and large TRPV1-negative. Furthermore, the injection of RTX into PrAT reduced labeled cells by 36.7% where TRPV1-positive cells were the main target of RTX denervation. These novel findings provide a structural basis for future TRPV1-dependent and TRPV1-independent studies on the sensory innervation of PrAT, which may be of interest for future therapeutic obesity treatment and intervention. [ABSTRACT FROM AUTHOR]

Objective: We evaluated adipose tissue distribution in different anatomical localizations by comparing with epidural fat tissue. Methods: Sixty patients' (28 female and 32 male) included in our study had abdominal computerized tomography and lumbar magnetic resonance images evaluated retrospectively. Subcutaneous and intraabdominal fat tissue thickness was compared with perirenal and epidural fat. The relationship with demographic characteristics of patients was investigated. Results: Mean value of subcutaneous fat thicknesses were higher in females (29.9±24.2 mm in females and 16.2±24.5 mm in males), while perirenal fat tissue area was higher in males than females (2118.4±2327.1 mm2 and 1204.1±851.3 mm2 respectively). There was no significant difference in intraabdominal and perirenal fat tissue measurements according to gender (p=0.407, p=0.390; respectively). Also subcutaneous, intraabdominal and perirenal fat tissue measurements showed increments in association with gender (r=0.33, p=0.010; r=0.37, p=0.004; r=0.51, p=<0,001; respectively); however no relationship was detected with epidural fat area (p=0.519). Subcutaneous and intraabdominal fat thicknesses were not related with epidural fat (p values 0.434 and 0.271, respectively); and there was a statistical relationship between perirenal and epidural fat (p=0.010). Conclusions: Increases in subcutaneous and intraabdominal fat tissue thickness with waist circumference was an expected finding, but no correlation was detected with epidural fat. Thus, we think that the amount of epidural fat does not change with obesity. Also, we concluded that while perirenal fat measurements were higher in the male group and correlated with epidural fat, androgenic effects can play a role in changing the amount of perirenal and epidural fat tissue. This result may be helpful in management of epidural pathologies, though there is a need for supportive studies. [ABSTRACT FROM AUTHOR]

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. [Display omitted] • FIN has a protective effect on kidney and cardiovascular damage progression in a new model of T1DM in established CKD. • FIN reduces kidney damage markers, blood pressure, vascular prostanoids, ROS and collagen content, PWV and heart weight. • FIN prevents diabetes-induced upregulation of proinflammatory, profibrotic, and osteogenic factors in PVAT and PRAT. • FIN restores the imbalance between procalcifying BMP-2 and nephroprotective BMP-7 in plasma, kidney, PVAT, and PRAT. • All beneficial effects of FIN are observed despite no change in glycaemia or other characteristic symptoms of diabetes. • These results support further studies exploring the therapeutic potential of FIN on kidney and vascular damage in T1DM. [ABSTRACT FROM AUTHOR]

Background: Inflammation and oxidative stress play critical roles in the pathogenesis of inhaled air pollutantmediated metabolic disease. Inflammation in the adipose tissues niches are widely believed to exert important effects on organ dysfunction. Recent data from both human and animal models suggest a role for inflammation and oxidative stress in epicardial adipose tissue (EAT) as a risk factor for the development of cardiovascular disease. We hypothesized that inhalational exposure to concentrated ambient fine particulates (CAPs) and ozone (O3) exaggerates inflammation and oxidative stress in EAT and perirenal adipose tissue (PAT). Methods: Eight- week-old Male Sprague–Dawley rats were fed a normal diet (ND) or high fructose diet (HFr) for 8 weeks, and then exposed to ambient AIR, CAPs at a mean of 356 μg/m3, O3 at 0.485 ppm, or CAPs (441 μg/m3) + O3 (0.497 ppm) in Dearborn, MI, 8 hours/day, 5 days/week, for 9 days over 2 weeks. Results: EAT and PAT showed whitish color in gross, and less mitochondria, higher mRNA expression of white adipose specific and lower brown adipose specific genes than in brown adipose tissues. Exposure to CAPs and O3 resulted in the increase of macrophage infiltration in both EAT and PAT of HFr groups. Proinflammatory genes of Tnf-α, Mcp-1 and leptin were significantly upregulated while IL-10 and adiponectin, known as antiinflammatory genes, were reduced after the exposures. CAPs and O3 exposures also induced an increase in inducible nitric oxide synthase (iNOS) protein expression, and decrease in mitochondrial area in EAT and PAT. We also found significant increases in macrophages of HFr-O3 rats. The synergetic interaction of HFr and dirty air exposure on the inflammation was found in most of the experiments. Surprisingly, exposure to CAPs or O3 induced more significant inflammation and oxidative stress than co-exposure of CAPs and O3 in EAT and PAT. Conclusion: EAT and PAT are both white adipose tissues. Short-term exposure to CAPs and O3, especially with high fructose diet, induced inflammation and oxidative stress in EAT and PAT in rats. These findings may provide a link between air-pollution exposure and accelerated susceptibility to cardiovascular disease and metabolic complications. [ABSTRACT FROM AUTHOR]

Morphogenesis of MDCK cells in a collagen gel matrix culture under stromal adipocyte-epithelial cell interaction. Background. The stromal-epithelial cell interaction is essential for epithelial morphogenesis. Recently, the specific stromal cell type adipocytes, which abundantly exist in perirenal adipose tissue, have been suggested to affect the biological behavior of some epithelial cell types. However, adipocyte-renal epithelial cell interaction remains unclear. We thus examined the effects of adipocytes on the morphogenesis of renal epithelial cells. Methods. The renal epithelial cell line, Madin-Darby canine kidney (MDCK), cells were cultured in three-dimensional collagen gel matrix with or without mature unilocular adipocytes. Cultures cells were examined by histochemistry, immunohistochemistry, and electron microscopy. Results. Adipocytes extensively promoted the tubule formation of MDCK cells in two different manners. In the first type, after approximately 20% of MDCK cells actively adhered to adipocytes; they organized double-cell structured tubules between the adipocytes and the gel, contacting directly with the entire surface of the adipocytes. In the second type, approximately 70% of MDCK cells apart from adipocytes also formed tubules that had no contact with adipocytes. The component cells of both tubule types at the apical side showed microvilli and peanut agglutinin lectin-positive stain. These cells at the basal side had the basal lamina and type IV collagen-positive stain. Conclusions. These results indicate that the specific stromal cell type adipocytes cause MDCK cells to organize the well-polarized tubular structures in two different manners according to their direct and indirect interactions, suggesting that adipocytes may be involved in the regulatory mechanism of renal epithelial morphogenesis. [ABSTRACT FROM AUTHOR]