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Purpose: The vascular blood flow in brown adipose tissue (BAT) is important for handling triglyceride clearance, increased blood flow and oxygenation. We used dynamic contrast‐enhanced (DCE)‐MRI and fat fraction (FF) imaging for investigating vascular perfusion kinetics in brown and beige adipose tissues with cold exposure or treatment with β3‐adrenergic agonist. Methods: FF imaging and DCE‐MRI using gadolinium‐diethylenetriaminepentaacetic acid were performed in interscapular BAT (iBAT) and beige tissues using male Wister rats (n = 38). Imaging was performed at thermoneutral condition and with either cold exposure, treatment with pharmacological agent CL‐316,243, or saline. DCE‐MRI and FF data were co‐registered to enhance the understanding of metabolic activity. Results: Uptake of contrast agent in activated iBAT and beige tissues were significantly (P <.05) higher than nonactivated iBAT. The Ktrans and kep increased significantly in iBAT and beige tissues after treatment with either cold exposure or β3‐adrenergic agonist. The FF decreased in activated iBAT and beige tissues. The Ktrans and FF from iBAT and beige tissues were inversely correlated (r = 0.97; r = 0.94). Significant increase in vascular endothelial growth factor expression and Ktrans in activated iBAT and beige tissues were in agreement with the increased vasculature and vascular perfusion kinetics. The iBAT and beige tissues were validated by measuring molecular markers. Conclusion: Increased Ktrans and decreased FF in iBAT and beige tissues were in agreement with the vascular perfusion kinetics facilitating the clearance of free fatty acids. The methodology can be extended for the screening of browning agents. [ABSTRACT FROM AUTHOR]

Objective: The aim was to auto-segment and characterize brown adipose, white adipose and muscle tissues in rats by multi-parametric magnetic resonance imaging with validation by histology and UCP1. Materials and methods: Male Wistar rats were randomized into two groups for thermoneutral ( n = 8) and cold exposure ( n = 8) interventions, and quantitative MRI was performed longitudinally at 7 and 11 weeks. Prior to imaging, rats were maintained at either thermoneutral body temperature (36 ± 0.5 °C), or short term cold exposure (26 ± 0.5 °C). Neural network based automatic segmentation was performed on multi-parametric images including fat fraction, T and T* maps. Isolated tissues were subjected to histology and UCP1 analysis. Results: Multi-parametric approach showed precise delineation of the interscapular brown adipose tissue (iBAT), white adipose tissue (WAT) and muscle regions. Neural network based segmentation results were compared with manually drawn regions of interest, and showed 96.6 and 97.1 % accuracy for WAT and BAT respectively. Longitudinal assessment of the iBAT volumes showed a reduction at 11 weeks of age compared to 7 weeks. The cold exposed group showed increased iBAT volume compared to thermoneutral group at both 7 and 11 weeks. Histology and UCP1 expression analysis supported our imaging results. Conclusion: Multi-parametric MR based neural network auto-segmentation provides accurate separation of BAT, WAT and muscle tissues in the interscapular region. The cold exposure improves the classification and quantification of heterogeneous BAT. [ABSTRACT FROM AUTHOR]

Background & Aims: Dietary saturated fatty acids contribute to the development of fatty liver and have pathogenic link to systemic inflammation. We investigated the effects of dietary fat towards the pathogenesis of non-alcoholic fatty liver disease by longitudinal in vivo magnetic resonance spectroscopy (MRS) and in vitro liquid chromatography coupled with mass spectrometry (LC-MS). Methods: All measurements were performed on rats fed with high fat diet (HFD) and chow diet for twenty four weeks. Longitudinal MRS measurements were performed at the 12th, 18th and 24th weeks. Liver tissues were analyzed by LC-MS, histology and gene transcription studies after terminal in vivo experiments. Results: Liver fat content of HFD rats for all ages was significantly (P<0.05) higher compared to their respective chow diet fed rats. Unsaturation indices estimated from MRS and LC-MS data of chow diet fed rats were significantly higher (P<0.05) than HFD fed rats. The concentration of triglycerides 48∶1, 48∶2, 50∶1, 50∶2, 50∶3, 52∶1, 52∶2, 52∶3, 54∶3 and 54∶2 was significantly higher (P<0.05) in HFD rats. The concentration for some polyunsaturated triglycerides 54∶7, 56∶8, 56∶7, 58∶11, 58∶10, 58∶9, 58∶8 and 60∶10 was significantly higher (P<0.05) in chow diet fed rats compared to HFD rats. Lysophospholipid concentrations including LPC and LPE were higher in HFD rats at 24 weeks indicating the increased risk of diabetes. The expression of CD36, PPARα, SCD1, SREBF1 and UCP2 were significantly upregulated in HFD rats. Conclusions: We demonstrated the early changes in saturated and unsaturated lipid composition in fatty liver by in vivo MRS and ex vivo LC-MS. The higher LPC concentration in HFD rats indicated a higher risk of developing diabetes. Early metabolic perturbations causing changes in lipid composition can be evaluated by the unsaturation index and correlated to the non alcoholic fatty liver disease. [ABSTRACT FROM AUTHOR]

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents an impending global health challenge. Current management strategies often face setbacks, emphasizing the need for preclinical models that faithfully mimic the human disease and its comorbidities. The liver disease progression aggravation diet (LIDPAD), a diet-induced murine model, extensively characterized under thermoneutral conditions and refined diets is introduced to ensure reproducibility and minimize species differences. LIDPAD recapitulates key phenotypic, genetic, and metabolic hallmarks of human MASLD, including multiorgan communications, and disease progression within 4 to 16 weeks. These findings reveal gut-liver dysregulation as an early event and compensatory pancreatic islet hyperplasia, underscoring the gut-pancreas axis in MASLD pathogenesis. A robust computational pipeline is also detailed for transcriptomic-guided disease staging, validated against multiple harmonized human hepatic transcriptomic datasets, thereby enabling comparative studies between human and mouse models. This approach underscores the remarkable similarity of the LIDPAD model to human MASLD. The LIDPAD model fidelity to human MASLD is further confirmed by its responsiveness to dietary interventions, with improvements in metabolic profiles, liver histopathology, hepatic transcriptomes, and gut microbial diversity. These results, alongside the closely aligned changing disease-associated molecular signatures between the human MASLD and LIDPAD model, affirm the model's relevance and potential for driving therapeutic development., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)