| 1. |
- Alsted, Thomas J., et al.
(författare)
-
Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle
- 2013
-
Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 591:20, s. 5141-5155
-
Tidskriftsartikel (refereegranskat)abstract
- In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride lipase (ATGL) and HSL collectively account for approximate to 98% of the TG hydrolase activity in mouse skeletal muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.
|
|
| 2. |
- Malmlöf, Kjell, et al.
(författare)
-
The anorectic response to growth hormone in obese rats is associated with an increased rate of lipid oxidation and decreased hypothalamic galanin
- 2011
-
Ingår i: PHYSIOLOGY and BEHAVIOR. - : Elsevier Science B.V., Amsterdam.. - 0031-9384 .- 1873-507X. ; 102:5, s. 459-465
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to demonstrate differential effects of growth hormone (CH) on food intake in lean and obese rats and to investigate whether an anticipated anorectic response in obese rats might be associated with increased lipid oxidation and altered hypothalamic neuropeptide levels. GH (4 mg/kg/day) was administered during 5-21 days to non-obese and obese rats. Whereas GH stimulated food intake in the non-obese rats, the obese animals responded with a significantly (p andlt; 0.05) suppressed food intake for 4-5 days. On day 4, the obese rats injected with GH and those injected with vehicle consumed 9.2 +/- 0.66 g and 12.7 +/- 1.05 g, respectively. The suppression of food intake was associated with significantly (pandlt;0.05) increased lipid oxidation. A similar, but statistically not verified, trend was seen in pair-fed rats not exposed to GH. However, while these animals appeared to economize their energy expenditure, the GH-exposed animals did not, thus creating a significant (p andlt; 0.05) difference between these two groups. The increased lipid oxidation and energy expenditure observed in the rats exposed to GH were associated with significantly (p andlt; 0.05) decreased levels of hypothalamic galanin (111 +/- 33.2 pmol/g vs. those of the pair-fed controls: 228.5 +/- 49.4 pmol/g). This difference was, however, not sustained. Thus, on day 21 both hypothalamic galanin and the food intake in the GH group were back to normal. Hypothalamic NPY remained unchanged by GH at all times. In conclusion, the present study suggests that increased lipid oxidation and decreased hypothalamic galanin are components in the mechanism by which GH inhibits food intake in an obese phenotype.
|
|
| 3. |
- Schweiger, Martina, et al.
(författare)
-
Adipose triglyceride lipase and hormone-sensitive lipase are the major enzymes in adipose tissue triacylglycerol catabolism
- 2006
-
Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 281:52, s. 40236-40241
-
Tidskriftsartikel (refereegranskat)abstract
- The mobilization of free fatty acids from adipose triacylglycerol (TG) stores requires the activities of triacylglycerol lipases. In this study, we demonstrate that adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major enzymes contributing to TG breakdown in in vitro assays and in organ cultures of murine white adipose tissue (WAT). To differentiate between ATGL- and HSL-specific activities in cytosolic preparations of WAT and to determine the relative contribution of these TG hydrolases to the lipolytic catabolism of fat, mutant mouse models lacking ATGL or HSL and a mono-specific, small molecule inhibitor for HSL (76-0079) were used. We show that 76-0079 had no effect on TG catabolism in HSL-deficient WAT but, in contrast, essentially abolished free fatty acid mobilization in ATGL- deficient fat. CGI-58, a recently identified coactivator of ATGL, stimulates TG hydrolase activity in wild-type and HSL-deficient WAT but not in ATGL- deficient WAT, suggesting that ATGL is the sole target for CGI-58-mediated activation of adipose lipolysis. Together, ATGL and HSL are responsible for more than 95% of the TG hydrolase activity present in murine WAT. Additional known or unknown lipases appear to play only a quantitatively minor role in fat cell lipolysis.
|
|
