Hormone-sensitive lipase-independent adipocyte lipolysis during beta-adrenergic stimulation, fasting, and dietary fat loading.
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: beta-adrenergic stimulation, fasting, and dietary fat loading. Intraperitoneal administration of the beta(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 <or=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 beta-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 beta-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.
Division of Medical Genetics, Research Centre, Hôpital Ste.-Justine, Montreal, Quebec H3T 1C5, Canada.
Mélanie
M
Fortier
Shu Pei
SP
Wang
Pascale
P
Mauriège
Meriem
M
Semache
Léandra
L
Mfuma
Hong
H
Li
Emile
E
Levy
Denis
D
Richard
Grant A
GA
Mitchell
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects / Q000235:genetics; D005215:Fasting / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006706:Homeostasis / Q000187:drug effects / Q000235:genetics; D008066:Lipolysis / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D002787:Sterol Esterase / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D004041:Dietary Fats; D004149:Dioxoles; D005227:Fatty Acids; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D002787:Sterol Esterase