Regulation of hormone-sensitive lipase during fasting

Abstract

Hormone-sensitive lipase (HSL) is the rate-limiting enzyme in lipolysis. The activity of HSL is thought to be primarily regulated by phosphorylation-dephosphorylation reactions. Although FFA levels are elevated during fasting, it has been difficult to demonstrate an increase in HSL activity with fasting. The current studies were undertaken to explore directly the regulation of HSL expression in adipose tissue in the rat during fasting. Rats were fasted for periods up to 5 days and HSL activity, HSL immunoreactive protein, and HSL mRNA levels were measured both in intact epididymal adipose tissue and in isolated adipose cells. Fasting caused a progressive decline in total body weight and the weight of epididymal fat pads, whereas adipose cell size decreased approximately 50% after 2 days of fasting. Serum FFA levels approximately doubled within 1 day of fasting and remained elevated thereafter. Basal lipolysis, measured as glycerol release, did not increase until 2 days of fasting. HSL activity remained relatively unchanged until 3 days of fasting when it was increased twofold after 3-5 days of fasting. Likewise, HSL immunoreactive protein and HSL mRNA levels increased twofold after 3-5 days of fasting. Thus HSL activity appears to be regulated by pretranslational mechanisms during prolonged fasting. However, increases in FFA flux during short-term fasting appear to involve either post-translational control of HSL or the regulation of other enzymes.

Integrative physiology of human adipose tissue

“…Stimulation of fat mobilisation requires activation of HSL by phosphorylation, 3 and involves increased gene transcription in the longer term. 19 Phosphorylation of HSL by protein kinase A is accompanied by translocation of HSL from the adipocyte cytosol to the surface of the lipid droplet 20 and also by phosphorylation of perilipin, a protein that appears to coat the lipid droplet and to move away upon stimulation, to allow HSL access. 20 Acute activation of lipolysis, via perilipin and HSL phosphorylation, may be brought about by catecholamines acting through b-adrenergic receptors, although in the situation of overnight fasting, when lipolysis increases steadily, b-adrenergic stimulation appears not to be involved; 21 progressive removal of insulin inhibition may be more important.…”

Messenger RNAs encoding lipoprotein lipase, fatty acid synthase and hormone-sensitive lipase in the adipose tissue of underfed-refed ewes and cows

“…In contrast, underfeeding and refeeding have a stimulatory and an inhibitory effect, respectively, on lipolytic enzymes [43]. In monogastric species, the responses of AT lipogenic and lipolytic enzymes to underfeeding and/or refeeding are due either to changes in mRNA levels [7,10,22,28,43] or to changes in post-translational events [9,30] Adult non-lactating non-pregnant Holstein cows (n = 4, 4-to 9-year-old) and Lacaune ewes (n = 4, 2-to 6-year-old) were used. They received a restricted diet (that provided approximately 20 % of the estimated maintenance energy requirement (MER), Inra [19]) of straw (1 kg/day) and hay (1.5 kg/day) for cows, and straw only (400-500 g/day) for ewes, for 10 or 8 days, respectively.…”

“…Les [3,8,18,41]. In contrast, underfeeding and refeeding have a stimulatory and an inhibitory effect, respectively, on lipolytic enzymes [43]. In monogastric species, the responses of AT lipogenic and lipolytic enzymes to underfeeding and/or refeeding are due either to changes in mRNA levels [7,10,22,28,43] or to changes in post-translational events [9,30] Adult non-lactating non-pregnant Holstein cows (n = 4, 4-to 9-year-old) and Lacaune ewes (n = 4, 2-to 6-year-old) were used.…”

“…The [7] and Ladu et al [9] who reported increases in LPL mRNAs in refed guinea pig, chicken and rat AT, respectively. However, Doolittle et al [22] reported (3)(4)(5) days) of fasting [43] suggesting that the short-term regulation of HSL activity occurs primarily via post-translational mechanisms [25]. Ruminant …”

Lipase-selective Functional Domains of Perilipin A Differentially Regulate Constitutive and Protein Kinase A-stimulated Lipolysis

“…Hydrolysis of triacylglycerol (TAG) 1 (lipolysis) in adipocytes is a key event that supplies the primary source of energy, free fatty acids, for other tissues. In times of energy need such as fasting (1)(2)(3) and exercise (4,5), adipocyte lipolysis is regulated by hormones such as catecholamines, which activate cAMP-dependent protein kinase (PKA) (6,7).…”