Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects : effect of beta-adrenergic stimulation. / Jocken, Johan We; Roepstorff, Carsten; Goossens, Gijs H.; van der Baan, Paula; van Baak, Marleen; Saris, Wim H. M.; Kiens, Bente; Blaak, Ellen E.
In: Diabetes, Vol. 57, No. 7, 2008, p. 1834-1841.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects
T2 - effect of beta-adrenergic stimulation
AU - Jocken, Johan We
AU - Roepstorff, Carsten
AU - Goossens, Gijs H.
AU - van der Baan, Paula
AU - van Baak, Marleen
AU - Saris, Wim H. M.
AU - Kiens, Bente
AU - Blaak, Ellen E
N1 - CURIS 2008 5200 047
PY - 2008
Y1 - 2008
N2 - Objective: Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity. Research design and Methods: Forearm skeletal muscle (SM) lipolysis was investigated in thirteen lean and ten obese men using [(2)H(5)]-glycerol combined with the measurement of arterio-venous differences before and during beta-adrenergic stimulation using the non-selective beta-agonist isoprenaline (ISO). Muscle biopsies were taken from the vastus lateralis muscle before and during ISO to investigate hormone-sensitive lipase (HSL) protein expression and serine phosphorylation. Results: Baseline total glycerol release across the forearm was significantly blunted in obese compared with lean subjects (P=0.045). This was accompanied by lower HSL protein expression (P=0.004), and HSL phosphorylation on PKA sites Ser(563) (P=0.041) and Ser(659) (P=0.09) and on the AMPK site Ser(565) (P=0.007), suggesting a blunted skeletal muscle lipolysis in obesity. Total forearm glycerol uptake during baseline did not differ significantly between groups while higher net fatty acid uptake across the forearm was observed in the obese (P=0.064). ISO induced an increase in total glycerol release from SM, which was not significantly different between groups. Interestingly, this was accompanied by an increase in HSL Ser(659) phosphorylation in obese subjects during ISO compared with baseline (P=0.008). Conclusions: Obesity is accompanied by impaired fasting glycerol release, lower HSL protein expression and serine phosphorylation. It remains to be determined whether this is a primary factor or an adaptation to the obese insulin resistant state.
AB - Objective: Increased intramuscular triacylglycerol (IMTG) storage is a characteristic of the obese insulin resistant state. We aimed to investigate whether a blunted fasting or beta-adrenergically mediated lipolysis contributes to this increased IMTG storage in obesity. Research design and Methods: Forearm skeletal muscle (SM) lipolysis was investigated in thirteen lean and ten obese men using [(2)H(5)]-glycerol combined with the measurement of arterio-venous differences before and during beta-adrenergic stimulation using the non-selective beta-agonist isoprenaline (ISO). Muscle biopsies were taken from the vastus lateralis muscle before and during ISO to investigate hormone-sensitive lipase (HSL) protein expression and serine phosphorylation. Results: Baseline total glycerol release across the forearm was significantly blunted in obese compared with lean subjects (P=0.045). This was accompanied by lower HSL protein expression (P=0.004), and HSL phosphorylation on PKA sites Ser(563) (P=0.041) and Ser(659) (P=0.09) and on the AMPK site Ser(565) (P=0.007), suggesting a blunted skeletal muscle lipolysis in obesity. Total forearm glycerol uptake during baseline did not differ significantly between groups while higher net fatty acid uptake across the forearm was observed in the obese (P=0.064). ISO induced an increase in total glycerol release from SM, which was not significantly different between groups. Interestingly, this was accompanied by an increase in HSL Ser(659) phosphorylation in obese subjects during ISO compared with baseline (P=0.008). Conclusions: Obesity is accompanied by impaired fasting glycerol release, lower HSL protein expression and serine phosphorylation. It remains to be determined whether this is a primary factor or an adaptation to the obese insulin resistant state.
U2 - 10.2337/db07-0857
DO - 10.2337/db07-0857
M3 - Journal article
C2 - 18398140
VL - 57
SP - 1834
EP - 1841
JO - Diabetes
JF - Diabetes
SN - 0012-1797
IS - 7
ER -
ID: 4261877