scholarly journals Metabolic consequences for mice lacking Endosialin: LC–MS/MS-based metabolic phenotyping of serum from C56Bl/6J Control and CD248 knock‐out mice

Metabolomics ◽  
2021 ◽  
Vol 17 (2) ◽  
Author(s):  
Emily G. Armitage ◽  
Alan Barnes ◽  
Kieran Patrick ◽  
Janak Bechar ◽  
Matthew J. Harrison ◽  
...  
Keyword(s):  
High Fat Diet ◽  
High Performance ◽  
Normal Diet ◽  
High Fat ◽  
Metabolic Phenotyping ◽  
Knock Out ◽  
Flight Mass Spectrometry ◽  
Lipid Species ◽  
Metabolic Consequence ◽  
Knock Out Mice

Abstract Introduction The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet. Objectives We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls. Methods From 10 weeks old, CD248−/− and +/+ mice were fed either chow (normal) diet or a high fat diet for 13 weeks. After 13 weeks the metabolic profiles and relative quantities of circulating lipid species were assessed using ultra high performance liquid chromatography-quadrupole time-of flight mass spectrometry (UHPLC–MS) with high resolution accurate mass (HRAM) capability. Results We demonstrate a specific reduction in the size of the perirenal fat pad in CD248−/− mice compared to CD248+/+, despite similar food intake. More strikingly, we identify significant, diet-dependent differences in the serum metabolic phenotypes of CD248 null compared to age and sex-matched wildtype control mice. Generalised protection from HFD-induced lipid accumulation was observed in CD248 null mice compared to wildtype, with particular reduction noted in the lysophosphatidylcholines, phosphatidylcholines, cholesterol and carnitine. Conclusions Overall these results show a clear and protective metabolic consequence of CD248 deletion in mice, implicating CD248 in lipid metabolism or trafficking and opening new avenues for further investigation using anti-CD248 targeting agents.

scholarly journals Tpcn2 Knock‐Out Mice Have Improved Insulin Sensitivity and Are Protected Against High‐Fat Diet Induced Weight Gain.

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Leah Solberg Woods ◽  
Katie Holl ◽  
Hong He ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
...  
Keyword(s):  
Weight Gain ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals Cholesterol Regulates Exosome Release in Cultured Astrocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Mohammad Abdullah ◽  
Tomohisa Nakamura ◽  
Taslima Ferdous ◽  
Yuan Gao ◽  
Yuxin Chen ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Normal Diet ◽  
Cellular Cholesterol ◽  
Knock Out ◽  
Pi3k Inhibitor Ly294002 ◽  
Akt Phosphorylation ◽  
Cholesterol Levels ◽  
Cultured Astrocytes ◽  
Knock Out Mice

Exosomes are vesicles secreted by various kinds of cells, and they are rich in cholesterol, sphingomyelin (SM), phosphatidylcholine, and phosphatidylserine. Although cellular sphingolipid-mediated exosome release has been reported, the involvement of other lipid components of cell membranes in the regulation of exosome release is poorly understood. Here, we show that the level of exosome release into conditioned media is significantly reduced in cultured astrocytes prepared from apolipoprotein E (ApoE) knock-out mice when compared to those prepared from wild-type (WT) mice. The reduced level of exosome release was accompanied by elevated levels of cellular cholesterol. The addition of cholesterol to WT astrocytes significantly increased the cellular cholesterol levels and reduced exosome release. PI3K/Akt phosphorylation was enhanced in ApoE-deficient and cholesterol-treated WT astrocytes. In contrast, the depletion of cholesterol in ApoE-deficient astrocytes due to treatment with β-cyclodextrin recovered the exosome release level to a level similar to that in WT astrocytes. In addition, the reduced levels of exosome release due to the addition of cholesterol recovered to the control levels after treatment with a PI3K inhibitor (LY294002). The cholesterol-dependent regulation of exosome release was also confirmed by in vivo experiments; that is, exosome levels were significantly reduced in the CSF and blood serum of WT mice that were fed a high-fat diet and had increased cholesterol levels when compared to those in WT mice that were fed a normal diet. These results suggest that exosome release is regulated by cellular cholesterol via stimulation of the PI3K/Akt signal pathway.

scholarly journals Mice lacking PLAP-1/asporin counteracts high fat diet-induced metabolic disorder and alveolar bone loss by controlling adipose tissue expansion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hiromi Sakashita ◽  
Satoru Yamada ◽  
Masaki Kinoshita ◽  
Tetsuhiro Kajikawa ◽  
Tomoaki Iwayama ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Periodontal Disease ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Periodontal Ligament ◽  
Metabolic Disorders ◽  
Alveolar Bone ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

AbstractAdipose tissue fibrosis with chronic inflammation is a hallmark of obesity-related metabolic disorders, and the role of proteoglycans in developing adipose tissue fibrosis is of interest. Periodontal disease is associated with obesity; however, the underlying molecular mechanisms remain unclear. Here we investigated the roles of periodontal ligament associated protein-1 (PLAP-1)/asporin, a proteoglycan preferentially and highly expressed in the periodontal ligament, in obesity-related adipose tissue dysfunction and adipocyte differentiation. It was found that PLAP-1 is also highly expressed in white adipose tissues. Plap-1 knock-out mice counteracted obesity and alveolar bone resorption induced by a high-fat diet. Plap-1 knock-down in 3T3-L1 cells resulted in less lipid accumulation, and recombinant PLAP-1 enhanced lipid accumulation in 3T3-L1 cells. In addition, it was found that primary preadipocytes isolated from Plap-1 knock-out mice showed lesser lipid accumulation than the wild-type (WT) mice. Furthermore, the stromal vascular fraction of Plap-1 knock-out mice showed different extracellular matrix gene expression patterns compared to WT. These findings demonstrate that PLAP-1 enhances adipogenesis and could be a key molecule in understanding the association between periodontal disease and obesity-related metabolic disorders.

scholarly journals MicroRNA-1 prevents high-fat diet-induced endothelial permeability in apoE knock-out mice

2013 ◽  
Vol 378 (1-2) ◽  
pp. 153-159 ◽  
Author(s):  
Hua Wang ◽  
Hua-Qing Zhu ◽  
Feng Wang ◽  
Qing Zhou ◽  
Shu-Yu Gui ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Endothelial Permeability ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

scholarly journals Effect of BI-1 on insulin resistance through regulation of CYP2E1

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Geum-Hwa Lee ◽  
Kyoung-Jin Oh ◽  
Hyung-Ryong Kim ◽  
Hye-Sook Han ◽  
Hwa-Young Lee ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Er Stress ◽  
Insulin Signaling ◽  
High Fat Diet ◽  
Stable Expression ◽  
Hepatic Insulin Resistance ◽  
Ros Production ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

Abstract Diet-induced obesity is a major contributing factor to the progression of hepatic insulin resistance. Increased free fatty acids in liver enhances endoplasmic reticulum (ER) stress and production of reactive oxygen species (ROS), both are directly responsible for dysregulation of hepatic insulin signaling. BI-1, a recently studied ER stress regulator, was examined to investigate its association with ER stress and ROS in insulin resistance models. To induce obesity and insulin resistance, BI-1 wild type and BI-1 knock-out mice were fed a high-fat diet for 8 weeks. The BI-1 knock-out mice had hyperglycemia, was associated with impaired glucose and insulin tolerance under high-fat diet conditions. Increased activity of NADPH-dependent CYP reductase-associated cytochrome p450 2E1 (CYP2E1) and exacerbation of ER stress in the livers of BI-1 knock-out mice was also observed. Conversely, stable expression of BI-1 in HepG2 hepatocytes was shown to reduce palmitate-induced ER stress and CYP2E1-dependent ROS production, resulting in the preservation of intact insulin signaling. Stable expression of CYP2E1 led to increased ROS production and dysregulation of insulin signaling in hepatic cells, mimicking palmitate-mediated hepatic insulin resistance. We propose that BI-1 protects against obesity-induced hepatic insulin resistance by regulating CYP2E1 activity and ROS production.

scholarly journals Accumulation of Oxidized LDL in the Tendon Tissues of C57BL/6 or Apolipoprotein E Knock-Out Mice That Consume a High Fat Diet: Potential Impact on Tendon Health

PLoS ONE ◽  
2014 ◽  
Vol 9 (12) ◽  
pp. e114214 ◽  
Author(s):  
Navdeep Grewal ◽  
Gail M. Thornton ◽  
Hayedeh Behzad ◽  
Aishwariya Sharma ◽  
Alex Lu ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
High Fat Diet ◽  
Oxidized Ldl ◽  
High Fat ◽  
Knock Out ◽  
Potential Impact ◽  
Knock Out Mice

Consumption of a high-fat diet alters the seminal fluid and gut microbiomes in male mice

2017 ◽  
Vol 29 (8) ◽  
pp. 1602 ◽  
Author(s):  
Angela B. Javurek ◽  
William G. Spollen ◽  
Sarah A. Johnson ◽  
Nathan J. Bivens ◽  
Karen H. Bromert ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Seminal Fluid ◽  
Bifidobacterium Longum ◽  
Male Mice ◽  
High Fat ◽  
Fecal Samples ◽  
Knock Out ◽  
Important Health ◽  
Bacillus Spp ◽  
Knock Out Mice

Our prior work showed that a novel microbiome resides in the seminal vesicles of wild-type and oestrogen receptor α (Esr1) knock-out mice and is impacted by the presence of functional Esr1 genes. The seminal fluid microbiome (SFM) may influence the health and reproductive status of the male, along with that of his partner and offspring. A high-fat diet (HFD) alters metabolites and other factors within seminal fluid and might affect the SFM. Adult (~15 weeks old) male mice were placed for 4 weeks on a control or high-fat diet and seminal fluid and fecal samples were collected, bacterial DNA isolated and subjected to 16s rRNA sequencing. Corynebacterium spp. were elevated in the seminal fluid of HFD males; however, Acinetobacter johnsonii, Streptophyta, Ammoniphilus spp., Bacillus spp. and Propionibacterium acnes were increased in control males. Rikenellaceae was more abundant in the fecal samples from HFD males. However, Bacteroides ovatus and another Bacteroides species, Bilophila, Sutterella spp., Parabacteroides, Bifidobacterium longum, Akkermansia muciniphila and Desulfovibrio spp. were greater in control males. Thus, short-term consumption of a HFD influences the seminal fluid and fecal microbiomes, which may have important health consequence for males and developmental origins of health and disease effects in resulting offspring.

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