The antilipolytic, insulin-like effect of growth hormone is caused by a net decrease of hormone-sensitive lipase...

Area of Science:

• Endocrinology
• Metabolic Regulation
• Adipocyte Biology

Background:

• Growth hormone (GH) exhibits an antilipolytic effect, counteracting fat breakdown.
• The precise mechanism and the development of cellular refractoriness to GH action remain incompletely understood.
• Insulin shares antilipolytic properties, suggesting potential overlapping signaling pathways.

Purpose of the Study:

• To elucidate the mechanism underlying the antilipolytic effect of GH in isolated rat adipocytes.
• To investigate the cause of cellular refractoriness to GH's own action.
• To compare the effects of GH and insulin on lipolysis and hormone-sensitive lipase phosphorylation.

Main Methods:

• Isolated rat adipocytes were utilized to study lipolysis and hormone-sensitive lipase phosphorylation.
• Catecholamine-stimulated lipolysis was measured using a pH-stat titration technique.
• The extent of hormone-sensitive lipase phosphorylation was determined in parallel with lipolysis rates.

Main Results:

• GH rapidly inhibited catecholamine-stimulated lipolysis, with half-maximal inhibition at 100 ng/ml.
• GH reversed the noradrenaline-induced phosphorylation of hormone-sensitive lipase, paralleling decreased lipolysis.
• These effects mimicked insulin's action, indicating a shared mechanism of lipase dephosphorylation.

Conclusions:

• Both GH and insulin exert their antilipolytic effects through net dephosphorylation of hormone-sensitive lipase.
• GH refractoriness in adipocytes may arise from functional inhibition upstream of lipase activation.
• Hypophysectomy-induced changes in adipocytes facilitate immediate GH responsiveness, supporting a pre-activation inhibitory mechanism.