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: β-adrenergic stimulation, fasting, and dietary fat loading. Intraperitoneal administration of the β3-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 β-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 β-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.
Free Fatty Acids Are Involved in the Inverse Relationship between Hormone-Sensitive Lipase (HSL) Activity and Expression in Adipose Tissue after High-Fat Feeding or β3-Adrenergic Stimulation
