Agpat4/Lpaatδ deficiency highlights the molecular heterogeneity of epididymal and perirenal white adipose depots

Abstract

Acylglycerophosphate acyltransferase 4 (AGPAT4)/lysophosphatidic acid acyltransferase delta catalyzes the formation of phosphatidic acid (PA), a precursor of triacyl-glycerol (TAG). We investigated the effect of gene ablation on white adipose tissue (WAT) after finding consistent expression across depots. Epididymal WAT mass was 40% larger in male mice than littermates, but unchanged in perirenal, retroperitoneal, and inguinal WAT and subscapular brown adipose tissue. Metabolic changes were identified in epididymal WAT that were not evident in perirenal WAT, which was analyzed for comparison. The total epididymal TAG content doubled, increasing adipocyte cell size without changing markers of differentiation. Enzymes involved in de novo lipogenesis and complex lipid synthesis downstream of phosphatidic acid production were also unchanged. However, total epididymal TAG hydrolase activity was reduced, and there were significant decreases in total ATGL and reduced phosphorylation of hormone-sensitive lipase at the S563 and S660 PKA-activation sites. Analysis of, and , as well as 1, 2, 3, and 4, demonstrated compensatory upregulation in perirenal WAT that did not occur in epididymal WAT. Our findings therefore indicate depot-specific differences in the redundancy of Agpat4 and highlight the molecular and metabolic heterogeneity of individual visceral depots.

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

“…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.…”

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

“…Although the MWM is generally regarded as a gold standard in assessing spatial learning and memory (77,78), other confounding factors could affect the performance of Lpaat␦ Ϫ/Ϫ mice in this testing paradigm, such as a greater level of anxiety than their wild-type littermates. In this regard, we tested Lpaat␦ Ϫ/Ϫ mice using a computerized comprehensive laboratory animal modeling system and found no significant differences from wild-type littermates in total or directional activity when the mice were introduced to their new environment (79). This suggests that differences in anxiety or exploratory behavior are not responsible for impaired performance in the MWM.…”

Methylation and Acetylation Enhanced the Antidiabetic Activity of Some Selected Flavonoids: In Vitro, Molecular Modelling and Structure Activity Relationship-Based Study

“…The membranes were then incubated with primary antibodies 1:1000 (GLUT-4, C/EBP-α and β-actin goat anti-mouse as the loading reference) in 5% non-fat dried milk in TBS-Tween buffer for 24 h, then washed several times with TBS-tween buffer. The secondary antibody used for all membranes was horseradish peroxidase (HRP)-conjugated goat anti-rabbit IgG (GeneTex, Irvine, CA, USA) at a dilution of 1:1000, 5% non-fat dried milk in TBS-Tween buffer for 1 h, followed by several washes as above at a dilution of 1:500 [24]. The membranes were then developed with chemiluminescence, Chemi-Lumi One L (Nacalai-Tesque, Kyoto, Japan).…”