TY - JOUR
T1 - Essential fatty acid deficiency in mice is associated with hepatic steatosis and secretion of large VLDL particles
AU - Werner, A
AU - Havinga, R
AU - Bos, T
AU - Bloks, VW
AU - Kuipers, F
AU - Verkade, HJ
PY - 2005/6
Y1 - 2005/6
N2 - Essential fatty acid (EFA) deficiency in mice decreases plasma triglyceride (TG) concentrations and increases hepatic TG content. We evaluated in vivo and in vitro whether decreased hepatic secretion of TG-rich very low-density lipoprotein (VLDL) contributes to this consequence of EFA deficiency. EFA deficiency was induced in mice by feeding an EFAdeficient (EFAD) diet for 8 wk. Hepatic VLDL secretion was quantified in fasted EFAD and EFA- sufficient (EFAS) mice using the Triton WR-1339 method. In cultured hepatocytes from EFAD and EFAS mice, VLDL secretion into medium was measured by quantifying [H-3]-labeled glycerol incorporation into TG and phospholipids. Hepatic expression of genes involved in VLDL synthesis and clearance was measured, as were plasma activities of lipolytic enzymes. TG secretion rates were quantitatively similar in EFAD and EFAS mice in vivo and in primary hepatocytes from EFAD and EFAS mice in vitro. However, EFA deficiency increased the size of secreted VLDL particles, as determined by calculation of particle diameter, particle sizing by light scattering, and evaluation of the TG-to-apoB ratio. EFA deficiency did not inhibit hepatic lipase and lipoprotein lipase activities in plasma, but increased hepatic mRNA levels of apoAV and apoCII, both involved in control of lipolytic degradation of TG-rich lipoproteins. EFA deficiency does not affect hepatic TG secretion rate in mice, but increases the size of secreted VLDL particles. Present data suggest that hypotriglyceridemia during EFA deficiency is related to enhanced clearance of altered VLDL particles.
AB - Essential fatty acid (EFA) deficiency in mice decreases plasma triglyceride (TG) concentrations and increases hepatic TG content. We evaluated in vivo and in vitro whether decreased hepatic secretion of TG-rich very low-density lipoprotein (VLDL) contributes to this consequence of EFA deficiency. EFA deficiency was induced in mice by feeding an EFAdeficient (EFAD) diet for 8 wk. Hepatic VLDL secretion was quantified in fasted EFAD and EFA- sufficient (EFAS) mice using the Triton WR-1339 method. In cultured hepatocytes from EFAD and EFAS mice, VLDL secretion into medium was measured by quantifying [H-3]-labeled glycerol incorporation into TG and phospholipids. Hepatic expression of genes involved in VLDL synthesis and clearance was measured, as were plasma activities of lipolytic enzymes. TG secretion rates were quantitatively similar in EFAD and EFAS mice in vivo and in primary hepatocytes from EFAD and EFAS mice in vitro. However, EFA deficiency increased the size of secreted VLDL particles, as determined by calculation of particle diameter, particle sizing by light scattering, and evaluation of the TG-to-apoB ratio. EFA deficiency did not inhibit hepatic lipase and lipoprotein lipase activities in plasma, but increased hepatic mRNA levels of apoAV and apoCII, both involved in control of lipolytic degradation of TG-rich lipoproteins. EFA deficiency does not affect hepatic TG secretion rate in mice, but increases the size of secreted VLDL particles. Present data suggest that hypotriglyceridemia during EFA deficiency is related to enhanced clearance of altered VLDL particles.
KW - hepatic lipoprotein secretion
KW - lipoprotein clearance
KW - hypotriglyceridemia
KW - DENSITY LIPOPROTEIN PARTICLES
KW - ELEMENT-BINDING PROTEIN-1
KW - LIPOGENIC GENE-EXPRESSION
KW - LIVER-X-RECEPTOR
KW - EFA DEFICIENCY
KW - TRIACYLGLYCEROL SECRETION
KW - RICH LIPOPROTEINS
KW - PLASMA-CLEARANCE
KW - CYSTIC-FIBROSIS
KW - TISSUE LIPIDS
U2 - 10.1152/ajpgi.00456.2004
DO - 10.1152/ajpgi.00456.2004
M3 - Article
SN - 0193-1857
VL - 288
SP - G1150-G1158
JO - American Journal of Physiology-Gastrointestinal and Liver Physiology
JF - American Journal of Physiology-Gastrointestinal and Liver Physiology
IS - 6
ER -