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Hormone-sensitive lipase-independent adipocyte lipolysis during -adrenergic stimulation, fasting, and dietary fat loading

Divisions of ¹Medical Genetics and ²Gastroenterology, Research Centre, Hôpital Ste.-Justine, Montreal, Quebec H3T 1C5; ³Division de Kinésiologie, Département de Médecine Sociale et Préventive, Université Laval, and ⁴Centre de Recherche de l'Hôpital Laval and Centre de Recherche sur le Métabolisme Énergétique de l'Université Laval, Département d'Anatomie et de Physiologie, Faculté de Médecine, Université Laval, Quebec, Canada G1K 7P4

Submitted 23 April 2003 ; accepted in final form 2 March 2004

In white adipose tissue, lipolysis can occur by hormone-sensitive lipase (HSL)-dependent or HSL-independent pathways. To study HSL-independent lipolysis, we placed HSL-deficient mice in conditions of increased fatty acid flux: -adrenergic stimulation, fasting, and dietary fat loading. Intraperitoneal administration of the ₃-adrenergic agonist CL-316243 caused a greater increase in nonesterified fatty acid level in controls (0.33 ± 0.05 mmol/l) than in HSL^–/– mice (0.12 ± 0.01 mmol/l, P < 0.01). Similarly, in isolated adipocytes, lipolytic response to CL-316243 was greatly reduced in HSL^–/– mice compared with controls. Fasting for 48 h produced normal mobilization and oxidation of fatty acids in HSL^–/– mice, as judged by similar values of respiratory quotient and oxygen consumption as in HSL^+/+ controls. In isolated adipocytes, lipolysis in the absence of -adrenergic stimulation was 1.9-fold greater in HSL^–/– than in HSL^+/+ cells (P < 0.05), increasing to 6.5-fold after fasting (P < 0.01). After 6 wk of a fat-rich diet containing 31.5% of energy as lipid, weight gain of HSL^–/– mice was 4.4-fold less than in HSL^+/+ mice (P < 0.01), and total abdominal fat mass was 5.2-fold lower in HSL^–/– than in HSL^+/+ mice (P < 0.01). In white adipose tissue, HSL is essential for normal acute -adrenergic-stimulated lipolysis and permits normal triglyceride storage capacity in response to dietary fat loading. However, HSL-independent lipolysis can markedly increase during fasting, both in isolated adipocytes and in intact mice, and can mediate a normal flux of fatty acids during fasting.

lipid energy metabolism

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