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 -