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Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Johan We Jocken
  • Carsten Roepstorff
  • Gijs H. Goossens
  • Paula van der Baan
  • Marleen van Baak
  • Wim H. M. Saris
  • Kiens, Bente
  • Ellen E Blaak
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.
OriginalsprogEngelsk
TidsskriftDiabetes
Vol/bind57
Udgave nummer7
Sider (fra-til)1834-1841
Antal sider8
ISSN0012-1797
DOI
StatusUdgivet - 2008

Bibliografisk note

CURIS 2008 5200 047

ID: 4261877