Acute Fasting Induces Expression of Acylglycerophosphate Acyltransferase (AGPAT) Enzymes in Murine Liver, Heart, and Brain

Bradley, Ryan M.; Mardian, Emily B.; Moes, Katherine A.; Duncan, Robin E.

doi:10.1007/s11745-017-4251-4

Cited by 11 publications

(7 citation statements)

References 36 publications

(34 reference statements)

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“…At the time of submission, however, Lpar6 −/− mice were not available to our laboratory for examination. In agreement with prior studies (Bradley et al, ; Mardian et al, ), this work highlights the molecular heterogeneity of the various WAT depots, and suggests that significant variation in the predominant expression of Lpar homologues could be important in determining differences in the metabolic characteristics of these depots and the groups ( e.g . visceral, subcutaneous) that they belong to.…”

Section: Resultssupporting

confidence: 92%

“…We subjected mice to an overnight fast initiated at the beginning of the light cycle. Because mice are nocturnal and exhibit most of their feeding and activity in the dark cycle, this paradigm is analogous to overnight fasting in humans (Bradley et al, ). Fasting rats for 12–24 h has been shown to significantly decrease total plasma circulating lysoPtdOH concentrations by more than half, with changes occurring in specific lysoPtdOH species (Ino et al, ).…”

Section: Resultsmentioning

confidence: 99%

“…Total RNA was isolated and reverse transcription (RT)‐real‐time quantitative PCR (qPCR) was performed as we have previously described (Bradley et al, ). Taqman™ gene expression assays (Life Technologies, Burlington, ON, Canada) were used with PerfeCTA qPCR FastMix (Quanta Biosciences, Gaithersburg, MD, USA) to analyze expression of Lpar ( Lpar1 : Mm01346925_m1, Lpar2 : Mm00469562_m1, Lpar3 : Mm00469694_m1, Lpar4 : Mm02620784_s1, Lpar5 : Mm02621109_s1, Lpar6 : Mm00613058_s1).…”

Section: Methodsmentioning

confidence: 99%

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Relative expression and regulation by short‐term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

M’Hiri

Silva

Duncan

2020

Lipids

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Lysophosphatidic acid (lysoPtdOH) levels have previously been reported to decrease in rodents with shortterm fasting. We investigated whether a 16 h fast would change expression of autotaxin, the predominant phospholipase D responsible for adipose-derived lysoPtdOH synthesis, or any of the lysophosphatidic acid receptors (1-6) in four white adipose tissue (WAT) depots and interscapular brown adipose tissue (BAT) in male C57Bl/6J mice fed ad libitum, or fasted for 16 h. Aside from small inductions of Lpar1 in epididymal WAT and Lpar2 in epididymal and inguinal WAT, no significant changes were observed in expression of the Lpar family members, or autotaxin in perirenal, retroperitoneal, epididymal, or inguinal WAT or BAT with fasting. Comparison of the relative expression of Lpar1-6 in various depots showed that Lpar6 was the predominant Lpar in both WAT and BAT, and suggests that further work on the adipose-specific role of Lpar6 is warranted.

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Relative expression and regulation by short‐term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

M’Hiri

Silva

Duncan

2020

Lipids

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“…The glycerophosphate pathway is an important pathway for de novo synthesis of triglycerides, and AGPAT2 plays a key role in the synthesis of glycerolipid and triglyceride. As a precursor of de novo synthesis of major glycerides (Bradley et al, 2017), it is highly expressed in adipose tissue and liver and can catalyze the formation of triglycerides (Fernandez-Galilea et al, 2015). AGPAT2 mutation can lead to congenital systemic adipotrophic diabetes (GCL), which is characterized by adipose tissue deficiency, insulin resistance, diabetes, and hyperlipidemia (Oswiecimska et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

The Effect of Silibinin on Protein Expression Profile in White Adipose Tissue of Obese Mice

et al. 2020

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Objective: To investigate the effect of silibinin on the protein expression profile of white adipose tissue (WAT) in obese mice by using Tandem Mass Tag (TMT) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods: According to experimental requirements, 36 C57BL/6JC mice were randomly divided into normal diet group (WC group), high fat diet group (WF group), and high fat diet + silibinin group (WS group). WS group was intragastrically administered with 54 mg/ kg body weight of silibinin, and the WC group and the WF group were intragastrically administered with equal volume of normal saline. Serum samples were collected to detect fasting blood glucose and blood lipids. IPGTT was used to measure the blood glucose value at each time point and calculate the area under the glucose curve. TMT combined with LC-MS/MS were used to study the expression of WAT, and its cellular processes, biological processes, corresponding molecular functions, and related network molecular mechanisms were analyzed by bioinformatics. Finally, RT-PCR and LC-MS/MS were used to detect the mRNA and protein expressions of FABP5, Plin4, GPD1, and AGPAT2, respectively. Results: Although silibinin did not reduce the mice's weight, it did improve glucose metabolism. In addition, silibinin decreased the concentration of TC, TG, and LDL-C and increased the concentration of HDL-C in the serum of mice. In the WF/WS group, 182 differentially expressed proteins were up-regulated and 159 were down-regulated. While in the WS/WF group, 362 differentially expressed proteins were up-regulated and 176 were down-regulated. Further analysis found that these differential proteins are mainly distributed in the peroxisome proliferation-activated receptor (PPAR), lipolysis of fat cells, metabolism of glycerides, oxidative phosphorylation, and other signaling pathways, and participate in cell processes and lipid metabolism through catalysis and integration functions. Specifically, silibinin reduced the expression of several key factors such as FABP5, Plin4, GPD1, and AGPTA2.

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“…To date, 11 AGPATs have been identified in mice and humans, although only AGPAT1 to -5 preferentially utilize lysophosphatidic acid (LPA) as an acyl donor, while AGPAT6 to -11 have been reclassified based on alternate lysophospholipid substrate preferences, or preference for glycerol-3-phosphate. Thus, of the 11 known AGPAT family members, only AGPAT1 to -5 function as true LPAATs (3,4).…”

mentioning

confidence: 99%

Mice Deficient inlysophosphatidic acid acyltransferase delta(Lpaatδ)/acylglycerophosphate acyltransferase 4(Agpat4) Have Impaired Learning and Memory

Bradley

Mardian

Bloemberg

et al. 2017

Molecular and Cellular Biology

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We previously characterized LPAATδ/AGPAT4 as a mitochondrial lysophosphatidic acid acyltransferase that regulates brain levels of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylinositol (PI). Here, we report that δ mice display impaired spatial learning and memory compared to wild-type littermates in the Morris water maze and our investigation of potential mechanisms associated with brain phospholipid changes. Marker protein immunoblotting suggested that the relative brain content of neurons, glia, and oligodendrocytes was unchanged. Relative abundance of the important brain fatty acid docosahexaenoic acid was also unchanged in phosphatidylserine, phosphatidylglycerol, and cardiolipin, in agreement with prior data on PC, PE and PI. In phosphatidic acid, it was increased. Specific decreases in ethanolamine-containing phospholipids were detected in mitochondrial lipids, but the function of brain mitochondria in δ mice was unchanged. Importantly, we found that δ mice have a significantly and drastically lower brain content of the -methyl-d-asparate (NMDA) receptor subunits NR1, NR2A, and NR2B, as well as the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1, compared to wild-type mice. However, general dysregulation of PI-mediated signaling is not likely responsible, since phospho-AKT and phospho-mTOR pathway regulation was unaffected. Our findings indicate thatδ deficiency causes deficits in learning and memory associated with reduced NMDA and AMPA receptors.

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Acute Fasting Induces Expression of Acylglycerophosphate Acyltransferase (AGPAT) Enzymes in Murine Liver, Heart, and Brain

Cited by 11 publications

References 36 publications

Relative expression and regulation by short‐term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

Relative expression and regulation by short‐term fasting of lysophosphatidic acid receptors and autotaxin in white and brown adipose tissue depots

The Effect of Silibinin on Protein Expression Profile in White Adipose Tissue of Obese Mice

Mice Deficient inlysophosphatidic acid acyltransferase delta(Lpaatδ)/acylglycerophosphate acyltransferase 4(Agpat4) Have Impaired Learning and Memory

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