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.

No abstract

Delta-6-desaturase (D6D) activity is deficient in MCF-7 and other cancer cell lines, but it is not explained by FADS2 gene mutations. This deficient activity was not ameliorated by induction of the FADS2 gene; therefore, we hypothesized that some of the induced FADS2 transcript variants (tv) may play a negative regulatory role. FADS2_tv1 is the reference FADS2 tv, coding for full-length D6D isoform 1 (D6D-iso1), and alternative transcriptional start sites result in FADS2_tv2 and FADS2_tv3 variants encoding D6D-iso2 and D6D-iso3 isoforms, respectively, which lack the catalytically critical N-terminal domain. In MCF-7 cells, FADS2_tv2 and FADS2_tv3 were expressed at significantly higher levels than FADS2_tv1. Overexpression of FADS2_tv2 in HEK293 cells confirmed that D6D-iso2 is non-functional, and co-transfection demonstrated a dominant-negative role for D6D-iso2 in D6D-iso1 activity regulation. FADS2_tv2 was expressed at higher levels than FADS2_tv1 in HeLa, MDA-MB-435, MCF-10 A, and HT-29 cells, but at lower levels in A549, MDA-MB-231, and LNCaP cells. Overexpression studies indicated roles for FADS2 variants in proliferation and apoptosis regulation, which were also cell-line specific. Increased FADS2_tv2 expression provides a new mechanism to help explain deficient D6D activity in MCF-7 and other cancer cell lines, but it is not a hallmark of malignant cells.