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Plasma lipoproteins, tissue cholesterol overload, and skeletal muscle apolipoprotein A-I synthesis in the developing
P Tarugi1, D Reggiani, E Ottaviani
1Dipartimento di Biologia Animale, Università di Modena, Italy.
Insights
Newly hatched chicks exhibit hypercholesterolemia, with skeletal muscle producing apolipoprotein A-I (apoA-I) to clear cholesterol overload. This process is linked to high-density lipoprotein (HDL) rise post-hatching.
Area of Science:
- Lipid metabolism
- Developmental biology
- Biochemistry
Background:
- Chicks hatch with hypercholesterolemia, characterized by elevated cholesterol-rich very-low-density lipoprotein + intermediate-density lipoprotein (VLDL + IDL).
- Lipoprotein profiles and tissue lipid composition undergo significant changes during late embryonic and early postnatal development.
Purpose of the Study:
- To investigate changes in plasma and tissue lipids, and lipoproteins during chick development.
- To elucidate the role of skeletal muscle in cholesterol homeostasis and apolipoprotein A-I (apoA-I) synthesis.
Main Methods:
- Analysis of plasma lipids and lipoproteins using density gradient ultracentrifugation.
- Measurement of cholesterol and cholesteryl esters in liver and skeletal muscle.
- Immunological methods and apoA-I mRNA quantification to assess apoA-I synthesis in skeletal muscle.
- In vitro studies using skeletal muscle explants.
Main Results:
- Plasma VLDL + IDL and LDL decreased post-hatching, while high-density lipoprotein (HDL) increased sharply.
- Newborn chicks showed cholesterol accumulation in liver and skeletal muscle, which depleted within 7 days.
- Skeletal muscle exhibited increased apoA-I synthesis and secretion of apoA-I-containing HDL, preceding cholesterol depletion.
Conclusions:
- The rise in plasma HDL and apoA-I post-hatching is likely due to skeletal muscle production.
- Skeletal muscle cholesterol overload may stimulate apoA-I synthesis, facilitating cholesterol removal.
- Metabolic stimuli appear to influence apoA-I synthesis in skeletal muscle during chick development.
Abstract:
In the present study we investigated the changes of plasma lipids, lipoproteins, and tissue lipids that occur during the late embryonic life (5 days before hatching) and the postnatal period (0, 2, 7, 14, and 30 days after hatching) of the chick. The chick emerges from the egg with extreme hypercholesterolemia associated with a high level of cholesterol-rich VLDL + IDL. The density gradient profile of plasma lipoproteins showed that the concentrations of VLDL + IDL and LDL decreased during the first week of postnatal life, whereas HDL concentration increased sharply around hatching and remained stable afterwards. All plasma lipoprotein classes of the newborn chick (2 days from hatching) were enriched in cholesterol and cholesteryl esters; 2 weeks after hatching, the relative amount of cholesterol and cholesteryl esters decreased. In the newborn chick, plasma VLDL + IDL consisted of two populations of cholesteryl ester-rich lipoproteins: the main one (designated apoB-VLDL) contained apoB and no apoA-I; the other (designated apoA-I-VLDL) contained predominantly apoA-I. In the newborn chick there was an accumulation of free and esterified cholesterol in the liver and, to a lesser extent, in the skeletal muscle. These cholesterol deposits were depleted 2 to 7 days after hatching. The depletion in skeletal muscle was preceded by and associated with a striking increase in the synthesis of apoA-I in this tissue, as demonstrated by immunological methods and apoA-I mRNA measurements. In addition, apoA-I-containing HDL were secreted in vitro by explants of skeletal muscle of the newborn chick. The synthesis of apoA-I in the skeletal muscle decreased to the level found in the adult animal 1 week after hatching. It is likely that the rise of HDL and apoA-I in plasma observed 1-2 days after hatching reflects the production of apoA-I-containing HDL by skeletal muscle. We suggest that the cholesterol overload in skeletal muscle might stimulate the production of apoA-I which, in turn, would promote the removal of cholesterol from this tissue. The hypothesis that metabolic stimuli play a role in inducing apoA-I synthesis in skeletal muscle is supported by the observation that feeding the newborn chick a diet rich in proteins and lipids and free of carbohydrates delays the fall of apoA-I mRNA which normally occurs 1 week after hatching.