Choline supplementation restores substrate balance and alleviates complications of Pcyt2 deficiency

Long non-coding RNA Gm12664 up-regulates CAV1 expression to promote hepatocellular lipid accumulation by sponging miR-295-5p

“…Fatty acid and fat synthesis in the liver is a highly regulated metabolic pathway, and several lipogenic genes are simultaneously regulated at the transcription level [6][7][8] . The lipolytic enzymes (HSL and ATGL) and lipogenic enzymes (FAS and DGAT2) are well acknowledged to act as vital roles in the regulation of triglyceride metabolism.…”

“…Evidence has shown that triglyceride (TG) de novo lipogenesis is a prominent abnormality in NAFLD and the key event that leads to massive steatosis [5] . Some lipolytic enzymes, including hormone sensitive lipase (HSL) and triglyceride lipase (ATGL), and lipogenic enzymes, including fatty acid synthase (FAS) and diacylglycerol O-acyltransferase 2 (DGAT2) play vital roles in the regulation of triglyceride metabolism [6][7][8] . In addition, caveolin-1 (CAV1), a structural protein of caveolae, has been found to facilitate the efficient progression of liver regeneration and accumulation of triacylglycerols in hepatocytes [9][10][11] .…”

Adaptations to excess choline in insulin resistant andPcyt2deficient skeletal muscle

“…(Funai et al 2016) was on the other hand protected from high-fat diet IR but was exercise intolerant, which has been attributed to PE dependent regulation of endoplasmic reticulum calcium handling. We have generated a heterozygous Pcyt2 mouse (Pcyt2 +/-) which D r a f t D r a f t (5 ml/day/mouse), and mouse weight (Schenkel et al 2015). Thus, in addition to 17 mg/day obtained from diet, the Pcyt2 +/-CHO group obtained additional 10 mg choline/day from water, which was a 59% increase in total choline intake.…”

“…The analysis of muscle phospholipids and cholesterol was performed by HPLC (Agilent Technologies, Santa Clara, CA, USA) as before (Schenkel et al 2015). Briefly, 1 mg of skeletal muscle homogenates from Pcyt2 +/-CHO, Pcyt2 +/and Pcyt2 +/+ mice (n = 3) was extracted in the presence of an internal standard (50 mg dipalmitoyl-phosphatidyl dimethyl ethanolamine) using a method of Folch et al (1957).…”

“…Glyceraldehyde-3-phosphate dehydrogenase (Gapdh) mRNA was used as a control. The primers and PCR conditions are in Table 1 and as described (Basu et al 2015, Schenkel et al 2015, Schenkel and Bakovic 2014.…”