Optimized Analysis of &lt;em&gt;In Vivo&lt;/em&gt; and &lt;em&gt;In Vitro&lt;/em&gt; Hepatic Steatosis

Cui, Aoyuan; Hu, Zhimin; Han, Yamei; Yang, Yi Ching; Liu, Yu

doi:10.3791/55178

Cited by 21 publications

(15 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some methodological considerations are important. While TD-NMR seems to detect any sort of lipids in the samples [22], the colorimetric method used in the present work assesses TAG [23]. Although TAG is the most common form of lipids found in the organs [24], the differences in the compounds detected by these methods may decrease their correlation coefficient.…”

Section: Discussionmentioning

confidence: 94%

Evaluation of Hepatic Steatosis in Rodents by Time-Domain Nuclear Magnetic Resonance

et al. 2019

View full text Add to dashboard Cite

Devices that analyze body composition of rodents by time-domain nuclear magnetic resonance (TD-NMR) are becoming popular in research centers that study metabolism. Theoretically, TD-NMR devices can also evaluate lipid content in isolated tissues. However, the accuracy of TD-NMR to determine hepatic steatosis in the liver of small laboratory animals has not been evaluated in detail. We observed that TD-NMR was able to detect increased lipid content in the liver of rats consuming high-fat diet (HFD) for 12 weeks and in genetically obese (Lepob/ob and Leprdb/db) mice. The lipid content determined by TD-NMR showed a positive correlation with triglyceride content measured by colorimetric assays. In contrast, TD-NMR did not detect hepatic steatosis in C57BL/6 mice consuming HFD for 4 or 12 weeks, despite their obesity and increased liver triglyceride content. These findings indicate that tissue mass and the severity of hepatic steatosis affect the sensitivity of TD-NMR to detect liver lipid content.

show abstract

Section: Discussionmentioning

confidence: 94%

Evaluation of Hepatic Steatosis in Rodents by Time-Domain Nuclear Magnetic Resonance

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Using hepatic tissue from overnight-fasted control and DHT mice, lipid content was assessed in hematoxylin and eosin (H&E)-stained and oil red O-stained 5 μM sections following a previously established protocol ( Cui et al 2017 ). The stained slides were assessed via light microscopy and digital image analysis (ImageJ).…”

Section: Methodsmentioning

confidence: 99%

DHT causes liver steatosis via transcriptional regulation of SCAP in normal weight female mice

Seidu

McWhorter

Myer

et al. 2021

Journal of Endocrinology

View full text Add to dashboard Cite

Hyperandrogenemia (HA) is a hallmark of polycystic ovary syndrome (PCOS) and is an integral element of nonalcoholic fatty liver disease (NALFD) in females. Administering low dose dihydrotestosterone (DHT) induced a normal weight PCOS-like female mouse model displaying NAFLD. The molecular mechanism of HA-induced NAFLD has not been fully determined. We hypothesized that DHT would regulate hepatic lipid metabolism via increased SREBP1 expression leading to NAFLD. We extracted liver from control and low dose DHT female mice; and performed histological and biochemical lipid pro-files, Western blot, immunoprecipitation, chromatin immunoprecipitation, and real-time quantitative PCR analyses. DHT lowered the 65 kD form of cytosolic SREBP1 in the liver compared to controls. However, DHT did not alter the levels of SREBP2 in the liver. DHT mice displayed increased SCAP protein expression and SCAP-SREBP1 binding compared to controls. DHT mice exhibited increased AR binding to intron-8 of SCAP leading to increased SCAP mRNA compared to controls. FAS mRNA and protein expression was increased in liver of DHT mice compared to controls. p-ACC levels were unaltered in liver. Other lipid metabolism pathways were examined in liver, but no changes were observed. Our findings support evidence that DHT increased de novo lipogenic proteins resulting in increased hepatic lipid content via regulation of SREBP1 in liver. We show that in the presence of DHT the SCAP-SREBP1 interaction was elevated leading to increased nuclear SREBP1 resulting in increased de novo lipogenesis. We propose that the mechanism of action may be increased AR binding to an ARE in SCAP intron-8.

show abstract

“…We obtained 8-μm-thick sections with a CM1860 cryostat (Leica) and applied them to poly-lysine coated slides. Liver sections were stained with Oil red O as described elsewhere [ 26 ]. Images were taken with Nikon Eclipse E600 fluorescence microscope and collected with Olympus CellˆD software v3.4.…”

Section: Methodsmentioning

confidence: 99%

BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet

Díaz-Catalán

Alcarraz-Vizán

Castaño

et al. 2021

Molecular Metabolism

View full text Add to dashboard Cite

Objective Pancreatic β-cell dysfunction is a central feature in the pathogenesis of type 2 diabetes (T2D). Accumulating evidence indicates that β-site APP-cleaving enzyme 2 (BACE2) inhibition exerts a beneficial effect on β-cells in different models of T2D. Thus, targeting BACE2 may represent a potential therapeutic strategy for the treatment of this disease. Here, we aimed to investigate the effects of BACE2 suppression on glucose homeostasis in a model of diet-induced obesity. Methods BACE2 knock-out (BKO) and wild-type (WT) mice were fed with a high-fat diet (HFD) for 2 or 16 weeks. Body weight, food intake, respiratory exchange ratio, locomotor activity, and energy expenditure were determined. Glucose homeostasis was evaluated by glucose and insulin tolerance tests. β-cell proliferation was assessed by Ki67-positive nuclei, and β-cell function was determined by measuring glucose-stimulated insulin secretion. Leptin sensitivity was evaluated by quantifying food intake and body weight after an intraperitoneal leptin injection. Neuropeptide gene expression and insulin signaling in the mediobasal hypothalamus were determined by qPCR and Akt phosphorylation, respectively. Results After 16 weeks of HFD feeding, BKO mice exhibited an exacerbated body weight gain and hyperphagia, in comparison to WT littermates. Glucose tolerance was similar in both groups, whereas HFD-induced hyperinsulinemia, insulin resistance, and β-cell expansion were more pronounced in BKO mice. In turn, leptin-induced food intake inhibition and hypothalamic insulin signaling were impaired in BKO mice, regardless of the diet, in accordance with deregulation of the expression of hypothalamic neuropeptide genes. Importantly, BKO mice already showed increased β-cell proliferation and glucose-stimulated insulin secretion with respect to WT littermates after two weeks of HFD feeding, before the onset of obesity. Conclusions Collectively, these results reveal that BACE2 suppression in an obesogenic setting leads to exacerbated body weight gain, hyperinsulinemia, and insulin resistance. Thus, we conclude that inhibition of BACE2 may aggravate the adverse metabolic effects associated with obesity.

show abstract

Optimized Analysis of <em>In Vivo</em> and <em>In Vitro</em> Hepatic Steatosis

Cited by 21 publications

References 11 publications

Evaluation of Hepatic Steatosis in Rodents by Time-Domain Nuclear Magnetic Resonance

Evaluation of Hepatic Steatosis in Rodents by Time-Domain Nuclear Magnetic Resonance

DHT causes liver steatosis via transcriptional regulation of SCAP in normal weight female mice

BACE2 suppression in mice aggravates the adverse metabolic consequences of an obesogenic diet

Contact Info

Product

Resources

About