Regulation of lipoprotein lipase and hormone-sensitive lipase activity andgene espression in adipose and muscle tissue by growth hormone treatment during weight loss in obese patients

It is well known that growth hormone (GH) treatment reduces fat mass (FM), which presumably is mediated through stimulation of triglyceride breakdown and inhibition of adipose tissue lipoprotein lipase activity (AT-LPL). Howe ver, it is unknown which of the 2 GH-regulated pathways are of most importa nce for the reduction in FM. We investigated the effect of weight loss toge ther with GH treatment an the activity and gene expression of LPL and hormo ne-sensitive lipase (HSL) in AT and muscle tissue. A very-law-calorie diet ([VLCD] 740 kcal/d) was given to 18 obese women (body mass index [BMI] > 35 kg/m(2)) and half of them were treated with GH (0.04 IU/kg) for 4 weeks in a randomized double-blind placebo controlled study. Subcutaneous fat and m uscle biopsies were taken before and after 4 weeks. Weight loss after 4 wee ks was similar in the 2 groups, with a reduction of 4.5% (placebo) and 4.6% (GH) and a reduction of FM by 7.4% and 9.0% ([NS] nonsignificant). The wei ght loss resulted in a small and NS reduction of AT-LPL activity by 20% +/- 12% in the placebo group, but in the GH group, AT-LPL was significantly re duced by 65% +/- 8% (P < .01). Muscle LPL (M-LPL) activity was not affected by the weight loss alone, but a significant reduction was observed in the GH group (20.4% +/- 10%, P < .05). AT-HSL activity was significantly enhanc ed after weight loss, but GH had no additional effect on this minor increme nt. This is in accordance with the finding that the increment in free fatty acid (FFA) after weight loss was similar in the 2 groups. GH treatment was associated with a significant reduction of high-density lipoprotein (HDL) cholesterol (P < .05). In conclusion, GH significantly inhibited AT-LPL act ivity but had no additional effect on the hypocaloric-induced loss of FM, i ndicating that under such circumstances, AT-LPL does not directly regulate adipose tissue mass. GH was not found to have apposite effects on the activ ity of LPL in adipose tissue and muscle, since GH treatment reduced them bo th (by 65% and 20%, respectively). The VLCD-induced weight loss was associa ted with a minor enhanced activity of AT-HSL with no independent effect of GH. Thus, concerning body weight, FM, and lipolytic activity, treatment wit h GH offers no extra benefits during a VLCD for 4 weeks. Copyright (C) 2000 by W.B. Saunders Company.