Long-term growth hormone excess induces marked alterations in lipoprotein metabolism in mice

The effects of long-term chronic growth hormone (GH) excess on lipid and li poprotein metabolism were investigated in 8-mo-old bovine GH (bGH)-transgen ic mice. Total body weight, serum cholesterol, insulin-like growth factor-I , and insulin levels were higher, whereas serum levels of glucose, free fat ty acids, and triglycerides were lower in transgenic mice. Very low-density lipoprotein (VLDL) cholesterol levels were lower, and low-density lipoprot ein (LDL) cholesterol levels were higher, in transgenic mice irrespective o f gender, whereas only transgenic male mice had higher high-density lipopro tein cholesterol levels. Total serum apolipoprotein B (apoB) levels were no t affected, but the amount of apoB in the LDL fraction was higher in transg enic mice. Hepatic LDL receptor expression was unchanged, whereas apoB mRNA editing and hepatic triglyceride secretion rate were reduced in bGH-transg enic male mice. Both lipoprotein lipase activity in adipose and heart tissu e and beta -adrenergic-stimulated lipolysis were increased in transgenic ma le mice. The relative weight of adipose tissue was lower in transgenic mice , whereas hepatic triglyceride content was unchanged. Fat feeding of the mi ce equalized serum triglycerides and free fatty acids in bGH-transgenic and control mice. In summary, longterm GH excess is associated with marked alt erations in lipid and lipoprotein metabolism, indicating decreased producti on and increased degradation of VLDL and preferential flux of fatty acids t o muscle tissues.